User login
Single dose of psilocybin for major depression tied to short-term remission
, new research shows.
In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.
Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.
The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.
The response rate was high for those receiving the 25-mg dose, lead investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.
“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.
Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.
Based on the results of the trial it was announced that a phase 3 trial will launch in December.
The study was published online in the New England Journal of Medicine.
Further research planned
Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.
In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.
The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.
Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.
There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.
On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.
The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.
MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.
Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.
Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).
The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.
Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.
Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.
Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.
The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
Intriguing, sobering
In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”
Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.
“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”
Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.
Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.
The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.
The response rate was high for those receiving the 25-mg dose, lead investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.
“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.
Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.
Based on the results of the trial it was announced that a phase 3 trial will launch in December.
The study was published online in the New England Journal of Medicine.
Further research planned
Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.
In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.
The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.
Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.
There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.
On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.
The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.
MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.
Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.
Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).
The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.
Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.
Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.
Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.
The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
Intriguing, sobering
In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”
Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.
“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”
Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.
Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.
The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.
The response rate was high for those receiving the 25-mg dose, lead investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.
“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.
Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.
Based on the results of the trial it was announced that a phase 3 trial will launch in December.
The study was published online in the New England Journal of Medicine.
Further research planned
Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.
In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.
The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.
Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.
There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.
On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.
The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.
MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.
Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.
Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).
The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.
Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.
Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.
Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.
The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
Intriguing, sobering
In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”
Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.
“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”
Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Major depression treatments boost brain connectivity
VIENNA – , new research suggests.
In a “repeat” MRI study, adult participants with MDD had significantly lower brain connectivity compared with their healthy peers at baseline – but showed significant improvement at the 6-week follow-up. These improvements were associated with decreases in symptom severity, independent of whether they received electroconvulsive therapy (ECT) or other treatment modalities.
“This means that the brain structure of patients with serious clinical depression is not as fixed as we thought, and we can improve brain structure within a short time frame [of] around 6 weeks,” lead author Jonathan Repple, MD, now professor of predictive psychiatry at the University of Frankfurt, Germany, said in a release.
“This gives hope to patients who believe nothing can change and they have to live with a disease forever because it is ‘set in stone’ in their brain,” he added.
The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
‘Easily understandable picture’
Dr. Repple said in an interview that the investigators “were surprised to see how plastic” the brain could be.
“I’ve done a lot of imaging studies in the past where we looked at differences in depression vs. healthy controls, and then maybe had tiny effects. But we’ve never seen such a clear and easily understandable picture, where we see a deficit at the beginning and then a significant increase in whatever biomarker we were looking at, that even correlated with how successful the treatment was,” he said.
Dr. Repple noted that “this is the thing everyone is looking for when we’re talking about a biomarker: That we see this exact pattern” – and it is why they are so excited about the results.
However, he cautioned that the study included a “small sample” and the results need to be independently replicated.
“If this can be replicated, this might be a very good target for future intervention studies,” Dr. Repple said.
The investigators noted that altered brain structural connectivity has been implicated before in the pathophysiology of MDD.
However, it is not clear whether these changes are stable over time and indicate a biological predisposition, or are markers of current disease severity and can be altered by effective treatment.
To investigate further, the researchers used gray matter T1-weighted MRI to define nodes in the brain and diffusion-weighted imaging (DWI)-based tractography to determine connections between the nodes, to create a structural connectome or white matter network.
They performed assessments at baseline and at 6 weeks’ follow-up in 123 participants diagnosed with current MDD and receiving inpatient treatment, and 55 participants who acted as the healthy controls group.
Among the patients with MDD, 56 were treated with ECT and 67 received other antidepressant care, including psychological therapy or medications. Some patients had received all three treatment modalities.
Significant interactions
Results showed a significant interaction by group and time between the baseline and 6-week follow-up assessments (P < .05).
This was partly driven by the MDD group having a significantly lower connectivity strength at baseline than the healthy controls group (P < .05).
It was also partly driven by patients showing a significant improvement in connectivity strength between the baseline and follow-up assessments (P < .05), a pattern that was not seen in the nonpatients.
This increase in connectivity strength was associated with a significant decrease in depression symptom severity (P < .05). This was independent of the treatment modality, indicating that it was not linked to the use of ECT.
Dr. Repple acknowledged the relatively short follow-up period of the study, and added that he is not aware of longitudinal studies of the structural connectome with a longer follow-up.
He pointed out that the structural connectivity of the brain decreases with age, but there have been no studies that have assessed patients with depression and “measured the same person again after 2, 4, 6, or 8 years.”
Dr. Repple reported that the investigators will be following up with their participants, “so hopefully in a few years we’ll have more information on that.
“One thing I also need to stress is that, when we’re looking at the MRI brain scans, we see an increase in connectivity strength, but we really can’t say what the molecular mechanisms behind it are,” he said. “This is a black box for us.”
Several unanswered questions
Commenting in the release, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said this was a “very interesting and difficult study to perform.”
However, Dr. Ruhe, who was not involved in the research, told this news organization that it is “very difficult to connect the lack of brain connectivity to the patient symptomatology because there is a huge gap between them.”
The problem is that, despite “lots of evidence” that they are effective, “we currently don’t know how antidepressant therapies work” in terms of their underlying mechanisms of action, he said.
“We think that these types of therapies all modulate the plasticity of the brain,” said Dr. Ruhe. “What this study showed is there are changes that you can detect even in 6 weeks,” although they may have been observed even sooner with a shorter follow-up.
He noted that big questions are whether the change is specific to the treatment given, and “can you modulate different brain network dysfunctions with different treatments?”
Moreover, he wondered if a brain scan could indicate which type of treatment should be used. “This is, of course, very new and very challenging, and we don’t know yet, but we should be pursuing this,” Dr. Ruhe said.
Another question is whether or not the brain connectivity changes shown in the study represent a persistent change – “and whether this is a persistent change that is associated with a consistent and persistent relief of depression.
“Again, this is something that needs to be followed up,” said Dr. Ruhe.
No funding was declared. The study authors and Dr. Ruhe report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VIENNA – , new research suggests.
In a “repeat” MRI study, adult participants with MDD had significantly lower brain connectivity compared with their healthy peers at baseline – but showed significant improvement at the 6-week follow-up. These improvements were associated with decreases in symptom severity, independent of whether they received electroconvulsive therapy (ECT) or other treatment modalities.
“This means that the brain structure of patients with serious clinical depression is not as fixed as we thought, and we can improve brain structure within a short time frame [of] around 6 weeks,” lead author Jonathan Repple, MD, now professor of predictive psychiatry at the University of Frankfurt, Germany, said in a release.
“This gives hope to patients who believe nothing can change and they have to live with a disease forever because it is ‘set in stone’ in their brain,” he added.
The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
‘Easily understandable picture’
Dr. Repple said in an interview that the investigators “were surprised to see how plastic” the brain could be.
“I’ve done a lot of imaging studies in the past where we looked at differences in depression vs. healthy controls, and then maybe had tiny effects. But we’ve never seen such a clear and easily understandable picture, where we see a deficit at the beginning and then a significant increase in whatever biomarker we were looking at, that even correlated with how successful the treatment was,” he said.
Dr. Repple noted that “this is the thing everyone is looking for when we’re talking about a biomarker: That we see this exact pattern” – and it is why they are so excited about the results.
However, he cautioned that the study included a “small sample” and the results need to be independently replicated.
“If this can be replicated, this might be a very good target for future intervention studies,” Dr. Repple said.
The investigators noted that altered brain structural connectivity has been implicated before in the pathophysiology of MDD.
However, it is not clear whether these changes are stable over time and indicate a biological predisposition, or are markers of current disease severity and can be altered by effective treatment.
To investigate further, the researchers used gray matter T1-weighted MRI to define nodes in the brain and diffusion-weighted imaging (DWI)-based tractography to determine connections between the nodes, to create a structural connectome or white matter network.
They performed assessments at baseline and at 6 weeks’ follow-up in 123 participants diagnosed with current MDD and receiving inpatient treatment, and 55 participants who acted as the healthy controls group.
Among the patients with MDD, 56 were treated with ECT and 67 received other antidepressant care, including psychological therapy or medications. Some patients had received all three treatment modalities.
Significant interactions
Results showed a significant interaction by group and time between the baseline and 6-week follow-up assessments (P < .05).
This was partly driven by the MDD group having a significantly lower connectivity strength at baseline than the healthy controls group (P < .05).
It was also partly driven by patients showing a significant improvement in connectivity strength between the baseline and follow-up assessments (P < .05), a pattern that was not seen in the nonpatients.
This increase in connectivity strength was associated with a significant decrease in depression symptom severity (P < .05). This was independent of the treatment modality, indicating that it was not linked to the use of ECT.
Dr. Repple acknowledged the relatively short follow-up period of the study, and added that he is not aware of longitudinal studies of the structural connectome with a longer follow-up.
He pointed out that the structural connectivity of the brain decreases with age, but there have been no studies that have assessed patients with depression and “measured the same person again after 2, 4, 6, or 8 years.”
Dr. Repple reported that the investigators will be following up with their participants, “so hopefully in a few years we’ll have more information on that.
“One thing I also need to stress is that, when we’re looking at the MRI brain scans, we see an increase in connectivity strength, but we really can’t say what the molecular mechanisms behind it are,” he said. “This is a black box for us.”
Several unanswered questions
Commenting in the release, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said this was a “very interesting and difficult study to perform.”
However, Dr. Ruhe, who was not involved in the research, told this news organization that it is “very difficult to connect the lack of brain connectivity to the patient symptomatology because there is a huge gap between them.”
The problem is that, despite “lots of evidence” that they are effective, “we currently don’t know how antidepressant therapies work” in terms of their underlying mechanisms of action, he said.
“We think that these types of therapies all modulate the plasticity of the brain,” said Dr. Ruhe. “What this study showed is there are changes that you can detect even in 6 weeks,” although they may have been observed even sooner with a shorter follow-up.
He noted that big questions are whether the change is specific to the treatment given, and “can you modulate different brain network dysfunctions with different treatments?”
Moreover, he wondered if a brain scan could indicate which type of treatment should be used. “This is, of course, very new and very challenging, and we don’t know yet, but we should be pursuing this,” Dr. Ruhe said.
Another question is whether or not the brain connectivity changes shown in the study represent a persistent change – “and whether this is a persistent change that is associated with a consistent and persistent relief of depression.
“Again, this is something that needs to be followed up,” said Dr. Ruhe.
No funding was declared. The study authors and Dr. Ruhe report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VIENNA – , new research suggests.
In a “repeat” MRI study, adult participants with MDD had significantly lower brain connectivity compared with their healthy peers at baseline – but showed significant improvement at the 6-week follow-up. These improvements were associated with decreases in symptom severity, independent of whether they received electroconvulsive therapy (ECT) or other treatment modalities.
“This means that the brain structure of patients with serious clinical depression is not as fixed as we thought, and we can improve brain structure within a short time frame [of] around 6 weeks,” lead author Jonathan Repple, MD, now professor of predictive psychiatry at the University of Frankfurt, Germany, said in a release.
“This gives hope to patients who believe nothing can change and they have to live with a disease forever because it is ‘set in stone’ in their brain,” he added.
The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
‘Easily understandable picture’
Dr. Repple said in an interview that the investigators “were surprised to see how plastic” the brain could be.
“I’ve done a lot of imaging studies in the past where we looked at differences in depression vs. healthy controls, and then maybe had tiny effects. But we’ve never seen such a clear and easily understandable picture, where we see a deficit at the beginning and then a significant increase in whatever biomarker we were looking at, that even correlated with how successful the treatment was,” he said.
Dr. Repple noted that “this is the thing everyone is looking for when we’re talking about a biomarker: That we see this exact pattern” – and it is why they are so excited about the results.
However, he cautioned that the study included a “small sample” and the results need to be independently replicated.
“If this can be replicated, this might be a very good target for future intervention studies,” Dr. Repple said.
The investigators noted that altered brain structural connectivity has been implicated before in the pathophysiology of MDD.
However, it is not clear whether these changes are stable over time and indicate a biological predisposition, or are markers of current disease severity and can be altered by effective treatment.
To investigate further, the researchers used gray matter T1-weighted MRI to define nodes in the brain and diffusion-weighted imaging (DWI)-based tractography to determine connections between the nodes, to create a structural connectome or white matter network.
They performed assessments at baseline and at 6 weeks’ follow-up in 123 participants diagnosed with current MDD and receiving inpatient treatment, and 55 participants who acted as the healthy controls group.
Among the patients with MDD, 56 were treated with ECT and 67 received other antidepressant care, including psychological therapy or medications. Some patients had received all three treatment modalities.
Significant interactions
Results showed a significant interaction by group and time between the baseline and 6-week follow-up assessments (P < .05).
This was partly driven by the MDD group having a significantly lower connectivity strength at baseline than the healthy controls group (P < .05).
It was also partly driven by patients showing a significant improvement in connectivity strength between the baseline and follow-up assessments (P < .05), a pattern that was not seen in the nonpatients.
This increase in connectivity strength was associated with a significant decrease in depression symptom severity (P < .05). This was independent of the treatment modality, indicating that it was not linked to the use of ECT.
Dr. Repple acknowledged the relatively short follow-up period of the study, and added that he is not aware of longitudinal studies of the structural connectome with a longer follow-up.
He pointed out that the structural connectivity of the brain decreases with age, but there have been no studies that have assessed patients with depression and “measured the same person again after 2, 4, 6, or 8 years.”
Dr. Repple reported that the investigators will be following up with their participants, “so hopefully in a few years we’ll have more information on that.
“One thing I also need to stress is that, when we’re looking at the MRI brain scans, we see an increase in connectivity strength, but we really can’t say what the molecular mechanisms behind it are,” he said. “This is a black box for us.”
Several unanswered questions
Commenting in the release, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said this was a “very interesting and difficult study to perform.”
However, Dr. Ruhe, who was not involved in the research, told this news organization that it is “very difficult to connect the lack of brain connectivity to the patient symptomatology because there is a huge gap between them.”
The problem is that, despite “lots of evidence” that they are effective, “we currently don’t know how antidepressant therapies work” in terms of their underlying mechanisms of action, he said.
“We think that these types of therapies all modulate the plasticity of the brain,” said Dr. Ruhe. “What this study showed is there are changes that you can detect even in 6 weeks,” although they may have been observed even sooner with a shorter follow-up.
He noted that big questions are whether the change is specific to the treatment given, and “can you modulate different brain network dysfunctions with different treatments?”
Moreover, he wondered if a brain scan could indicate which type of treatment should be used. “This is, of course, very new and very challenging, and we don’t know yet, but we should be pursuing this,” Dr. Ruhe said.
Another question is whether or not the brain connectivity changes shown in the study represent a persistent change – “and whether this is a persistent change that is associated with a consistent and persistent relief of depression.
“Again, this is something that needs to be followed up,” said Dr. Ruhe.
No funding was declared. The study authors and Dr. Ruhe report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ECNP 2022
Hormone therapy–depression link may depend on mode of administration
An analysis of more than 800,000 women in Denmark offers more insight into the murky links between female hormones and midlife mental illness in women: It hints that hormone therapy (HT) may boost the risk of depression, have no effect, or lower it – all depending on how it’s administered and when.
Women who took systemic HT had a higher risk of depression from age 48 to 50 (adjusted hazard ratio, 1.50; 95% confidence interval, 1.24-1.81), researchers reported in JAMA Network Open. However, there was no overall link between depression and locally administered HT (aHR, 1.15; 95% CI, 0.70-1.87) – except when HT was begun between ages 54 and 60, when there were signs of a protective effect (aHR, 0.80; 95% CI, 0.70-0.91).
“Women in menopause who initiate systemically administered HT should be aware of depression as a potential adverse effect,” epidemiologist and study corresponding author Merete Osler, MD, PhD, DMSc, of Bispebjerg and Frederiksberg (Denmark) Hospitals and the University of Copenhagen, said in an interview. ”Further, women and clinicians alike should be aware of any misinterpretation of symptoms of depression as menopausal disturbances.”
Dr. Osler said the researchers launched the study to better understand potential hormone-depression links in light of suspicions that lower levels of estrogen in menopause may contribute to depression.
Several randomized clinical trials and cohort and cross-sectional studies have explored whether systemic HT affects depression during menopause, Dr. Osler said, “but the results from these studies have been inconsistent, and few have explored the role of the route of administration.”
For the new registry-based study, researchers retrospectively tracked all women in Denmark who were aged 45 between 1995 and 2017 without prior oophorectomy, certain kinds of cancer, prior use of HT, or ongoing depression.
During follow-up to a mean age of 56, 23% of the women began HT (at a median age of 55), and 1.6% were hospitalized for depression. Of those on HT, 65.8% received locally administered HT.
Researchers adjusted hazard ratios for a long list of factors such as educational level, marital status, number of still births or live births, prior use of hormonal contraceptives, several medical conditions, and prior depression.
“We were surprised by our findings, which to some degree contradicted our prior hypothesis that systemic HT with estrogen would not be associated with first-time depression diagnosis in women aged 45 and above, while HT with progesterone would be associated with a slightly increased risk,” Dr. Osler said. “In our study, systemically administered HT was associated with an increased risk of depression with no difference between estrogen alone or in combination with progestin. As findings from previous studies have been inconsistent, our findings fit with some but not all previous studies.”
Why might the mode of administration make a difference? It’s possible that local administration may contribute less to the systemic circulation, Dr. Osler said, “or that menopausal symptoms including depression are more likely to be treated with systemic HT.”
As for age differences, Dr. Osler said “it is possible that women are more sensitive to the influence of HT on mood around menopause than at later ages. However, it should be noted that in the present study it was not possible to calculate precise risk estimates for use of systemic HT in menopausal women above age 54 because less than 1% initiated treatment with systemic HT after age 54 years.”
In an interview, psychiatrist Natalie Rasgon, MD, PhD, of Stanford (Calif.) University, who’s studied hormones and depression, said the study is “remarkably large and consistently executed.”
She cautioned, however, that the findings don’t prove any causality. “Saying that estrogen therapy or hormone therapy causes depression is patently incorrect.”
How can the findings be useful for medical professionals? “Women and physicians alike need to be very mindful of pre-existing mood disorders,” Dr. Rasgon said. “Women who in the past had anxiety disorders, mood swings, PTSD, or prior episodes of depression might have a differential response to hormone therapy in menopause.”
Also keep in mind, she said, that the transition from menopause to post menopause is “very volatile,” and depression may break through even in women undergoing treatment for the condition.
For her part, Dr. Osler said this study and others “emphasize the need for clinical guidelines to further consider the psychological side effects of systemic HT.”
Funding information was not provided. The study authors and Dr. Rasgon have no disclosures.
An analysis of more than 800,000 women in Denmark offers more insight into the murky links between female hormones and midlife mental illness in women: It hints that hormone therapy (HT) may boost the risk of depression, have no effect, or lower it – all depending on how it’s administered and when.
Women who took systemic HT had a higher risk of depression from age 48 to 50 (adjusted hazard ratio, 1.50; 95% confidence interval, 1.24-1.81), researchers reported in JAMA Network Open. However, there was no overall link between depression and locally administered HT (aHR, 1.15; 95% CI, 0.70-1.87) – except when HT was begun between ages 54 and 60, when there were signs of a protective effect (aHR, 0.80; 95% CI, 0.70-0.91).
“Women in menopause who initiate systemically administered HT should be aware of depression as a potential adverse effect,” epidemiologist and study corresponding author Merete Osler, MD, PhD, DMSc, of Bispebjerg and Frederiksberg (Denmark) Hospitals and the University of Copenhagen, said in an interview. ”Further, women and clinicians alike should be aware of any misinterpretation of symptoms of depression as menopausal disturbances.”
Dr. Osler said the researchers launched the study to better understand potential hormone-depression links in light of suspicions that lower levels of estrogen in menopause may contribute to depression.
Several randomized clinical trials and cohort and cross-sectional studies have explored whether systemic HT affects depression during menopause, Dr. Osler said, “but the results from these studies have been inconsistent, and few have explored the role of the route of administration.”
For the new registry-based study, researchers retrospectively tracked all women in Denmark who were aged 45 between 1995 and 2017 without prior oophorectomy, certain kinds of cancer, prior use of HT, or ongoing depression.
During follow-up to a mean age of 56, 23% of the women began HT (at a median age of 55), and 1.6% were hospitalized for depression. Of those on HT, 65.8% received locally administered HT.
Researchers adjusted hazard ratios for a long list of factors such as educational level, marital status, number of still births or live births, prior use of hormonal contraceptives, several medical conditions, and prior depression.
“We were surprised by our findings, which to some degree contradicted our prior hypothesis that systemic HT with estrogen would not be associated with first-time depression diagnosis in women aged 45 and above, while HT with progesterone would be associated with a slightly increased risk,” Dr. Osler said. “In our study, systemically administered HT was associated with an increased risk of depression with no difference between estrogen alone or in combination with progestin. As findings from previous studies have been inconsistent, our findings fit with some but not all previous studies.”
Why might the mode of administration make a difference? It’s possible that local administration may contribute less to the systemic circulation, Dr. Osler said, “or that menopausal symptoms including depression are more likely to be treated with systemic HT.”
As for age differences, Dr. Osler said “it is possible that women are more sensitive to the influence of HT on mood around menopause than at later ages. However, it should be noted that in the present study it was not possible to calculate precise risk estimates for use of systemic HT in menopausal women above age 54 because less than 1% initiated treatment with systemic HT after age 54 years.”
In an interview, psychiatrist Natalie Rasgon, MD, PhD, of Stanford (Calif.) University, who’s studied hormones and depression, said the study is “remarkably large and consistently executed.”
She cautioned, however, that the findings don’t prove any causality. “Saying that estrogen therapy or hormone therapy causes depression is patently incorrect.”
How can the findings be useful for medical professionals? “Women and physicians alike need to be very mindful of pre-existing mood disorders,” Dr. Rasgon said. “Women who in the past had anxiety disorders, mood swings, PTSD, or prior episodes of depression might have a differential response to hormone therapy in menopause.”
Also keep in mind, she said, that the transition from menopause to post menopause is “very volatile,” and depression may break through even in women undergoing treatment for the condition.
For her part, Dr. Osler said this study and others “emphasize the need for clinical guidelines to further consider the psychological side effects of systemic HT.”
Funding information was not provided. The study authors and Dr. Rasgon have no disclosures.
An analysis of more than 800,000 women in Denmark offers more insight into the murky links between female hormones and midlife mental illness in women: It hints that hormone therapy (HT) may boost the risk of depression, have no effect, or lower it – all depending on how it’s administered and when.
Women who took systemic HT had a higher risk of depression from age 48 to 50 (adjusted hazard ratio, 1.50; 95% confidence interval, 1.24-1.81), researchers reported in JAMA Network Open. However, there was no overall link between depression and locally administered HT (aHR, 1.15; 95% CI, 0.70-1.87) – except when HT was begun between ages 54 and 60, when there were signs of a protective effect (aHR, 0.80; 95% CI, 0.70-0.91).
“Women in menopause who initiate systemically administered HT should be aware of depression as a potential adverse effect,” epidemiologist and study corresponding author Merete Osler, MD, PhD, DMSc, of Bispebjerg and Frederiksberg (Denmark) Hospitals and the University of Copenhagen, said in an interview. ”Further, women and clinicians alike should be aware of any misinterpretation of symptoms of depression as menopausal disturbances.”
Dr. Osler said the researchers launched the study to better understand potential hormone-depression links in light of suspicions that lower levels of estrogen in menopause may contribute to depression.
Several randomized clinical trials and cohort and cross-sectional studies have explored whether systemic HT affects depression during menopause, Dr. Osler said, “but the results from these studies have been inconsistent, and few have explored the role of the route of administration.”
For the new registry-based study, researchers retrospectively tracked all women in Denmark who were aged 45 between 1995 and 2017 without prior oophorectomy, certain kinds of cancer, prior use of HT, or ongoing depression.
During follow-up to a mean age of 56, 23% of the women began HT (at a median age of 55), and 1.6% were hospitalized for depression. Of those on HT, 65.8% received locally administered HT.
Researchers adjusted hazard ratios for a long list of factors such as educational level, marital status, number of still births or live births, prior use of hormonal contraceptives, several medical conditions, and prior depression.
“We were surprised by our findings, which to some degree contradicted our prior hypothesis that systemic HT with estrogen would not be associated with first-time depression diagnosis in women aged 45 and above, while HT with progesterone would be associated with a slightly increased risk,” Dr. Osler said. “In our study, systemically administered HT was associated with an increased risk of depression with no difference between estrogen alone or in combination with progestin. As findings from previous studies have been inconsistent, our findings fit with some but not all previous studies.”
Why might the mode of administration make a difference? It’s possible that local administration may contribute less to the systemic circulation, Dr. Osler said, “or that menopausal symptoms including depression are more likely to be treated with systemic HT.”
As for age differences, Dr. Osler said “it is possible that women are more sensitive to the influence of HT on mood around menopause than at later ages. However, it should be noted that in the present study it was not possible to calculate precise risk estimates for use of systemic HT in menopausal women above age 54 because less than 1% initiated treatment with systemic HT after age 54 years.”
In an interview, psychiatrist Natalie Rasgon, MD, PhD, of Stanford (Calif.) University, who’s studied hormones and depression, said the study is “remarkably large and consistently executed.”
She cautioned, however, that the findings don’t prove any causality. “Saying that estrogen therapy or hormone therapy causes depression is patently incorrect.”
How can the findings be useful for medical professionals? “Women and physicians alike need to be very mindful of pre-existing mood disorders,” Dr. Rasgon said. “Women who in the past had anxiety disorders, mood swings, PTSD, or prior episodes of depression might have a differential response to hormone therapy in menopause.”
Also keep in mind, she said, that the transition from menopause to post menopause is “very volatile,” and depression may break through even in women undergoing treatment for the condition.
For her part, Dr. Osler said this study and others “emphasize the need for clinical guidelines to further consider the psychological side effects of systemic HT.”
Funding information was not provided. The study authors and Dr. Rasgon have no disclosures.
FROM JAMA NETWORK OPEN
Sexual assault–related visits to the ED are on the rise
Data from the Federal Bureau of Investigation show an increase in reported rapes and sexual assaults (SAs) since 2006, and studies of victims show an increased risk of conditions such as suicidal ideation, PTSD, depression, substance use, and chronic conditions, write Emily L. Vogt of the University of Michigan, Ann Arbor, and colleagues.
However, trends and disparities in ED use by adults seeking care following SA have not been explored, they said.
For a study that was published in JAMA Network Open, researchers reviewed data from the Nationwide Emergency Department Sample (NEDS), a large, nationally representative database managed by the Agency for Healthcare Research and Quality. The dataset consisted of 120 million to 143 million weighted ED visits reported annually from 2006 through 2016. The study population included adults aged 18-65 years who had made an ED visit that was recorded in the NEDS and that was coded as an SA. SA was defined using ICD-9 codes until the fourth quarter of 2015, at which time ICD-10 codes came into use.
Overall, the number of SA-related ED visits increased by 1,533.0% during the study period, from 3,607 in 2006 to 55,296 in 2019. The average annual percentage change was 23.0% (P < .001). The greatest increase occurred from 2015 to 2016, when annual visits increased from 17,709 to 47,732. This increase likely reflected the updated ICD-10 codes, in which there are categories for suspected adult rape, confirmed adult rape, and adult forced sexual exploitation, the researchers note.
Patients presenting to the ED after an SA were mainly women (91.5%). Individuals aged 18-25 years accounted for nearly half of the presentations. Individuals in the lowest and second-lowest income quartiles also were overrepresented.
Despite the increased presentation to EDs, admission rates for SA decreased, from 12.6% to 4.3%, the researchers note. Patients who were older and were insured through Medicaid were more likely to be admitted than persons of other demographic groups.
The researchers also found that increases in ED presentations outpaced increases in SA reports to law enforcement. They compared the ED trends with FBI-reported rapes/SAs from 2015 to 2019 and found increases of 7% and 22% during the times of ICD-9 and ICD-10 codes, respectively. However, in 2019, the number of SA survivors who sought ED care remained below the number who reported to law enforcement (55,296 vs. 139,815, as determined on the basis of revised SA definitions).
“Although the association between increased coding specificity and documentation of SA is still unclear, ICD-10 likely contributed to increased ED documentation of SA,” but the data show steady increases that are independent of the coding change, the researchers write.
The study findings were limited by several factors, including the potential for multiple representations of patients, coding errors associated with the NEDS database, and the reliance on voluntary reports in the NEDS and FBI datasets, the researchers note. The results were strengthened by the large, diverse sample size and by the inclusion of hospital admissions and crime data for comparison, they say.
“As few as 21% of survivors seek medical care after SA, meaning that the survivors captured in this study represent a fraction of total SA-related care need,” the researchers write. “Our finding that most SA ED visits are by young, female, and low-income survivors can inform policy changes to better support these individuals,” which could include the development of outpatient and longitudinal care settings to better serve these populations, they conclude.
Better understanding not only of the trends underlying SA reporting but also of the demographics of survivors who seek treatment and evaluation after SA is vital, said Robert Glatter, MD, in an interview.
“Being able to better understand how social and societal movements affect a patient’s comfort in reporting an SA is vital in tracking the numbers of people who seek care in the ED,” said Dr. Glatter, an emergency medicine physician at Lenox Hill Hospital at Northwell Health, New York, and also of Hofstra University, Hempstead, N.Y.
Dr. Glatter said he was not surprised by the significant increase in sexual assault presentations, especially in light of increased awareness and the influence of the #MeToo movement and other social justice movements over the past decade.
“While I believe that victims of sexual violence may now feel more empowered to report an assault, the volume of SA that go unreported remains a serious public health issue and concern” in the United States and globally, he emphasized.
A key message from the current study is that there is a need for investment in “compassionate and comprehensive care for all survivors of SA,” Dr. Glatter said. “This includes recognition of the extensive mental health consequences of SA that can lead to not only depression, PTSD, and anxiety but also to suicidal ideation and suicide. The longer-term medical effects become life altering, permeating families and future generations,” he emphasized.
“As a society, we must also place a strong emphasis on caring for all SA survivors, but particularly those who come from economically or socially disadvantaged backgrounds who are uninsured or underinsured,” Dr. Glatter said. Issues of race, gender identity, and sexual identity among SA survivors also must be taken into consideration, he added.
“We need to better understand how our health care system can provide more nuanced follow-up care and reporting for survivors in outpatient settings. … Making access easier, while ensuring confidentiality, will allow more survivors of SA to seek treatment and care,” he said. “We also need to understand how using forensic nurses in this capacity, and beyond the ED, can better serve minority and racially diverse communities” and to increase the recruitment and training of such specialized nurses to care for SA victims, Dr. Glatter noted.
The study was supported by internal funding from the University of Michigan and the department of obstetrics and gynecology. Corresponding author Erica C. Marsh, MD, has received personal fees from Myovant Sciences and Pfizer unrelated to the current study. Dr. Glatter has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Data from the Federal Bureau of Investigation show an increase in reported rapes and sexual assaults (SAs) since 2006, and studies of victims show an increased risk of conditions such as suicidal ideation, PTSD, depression, substance use, and chronic conditions, write Emily L. Vogt of the University of Michigan, Ann Arbor, and colleagues.
However, trends and disparities in ED use by adults seeking care following SA have not been explored, they said.
For a study that was published in JAMA Network Open, researchers reviewed data from the Nationwide Emergency Department Sample (NEDS), a large, nationally representative database managed by the Agency for Healthcare Research and Quality. The dataset consisted of 120 million to 143 million weighted ED visits reported annually from 2006 through 2016. The study population included adults aged 18-65 years who had made an ED visit that was recorded in the NEDS and that was coded as an SA. SA was defined using ICD-9 codes until the fourth quarter of 2015, at which time ICD-10 codes came into use.
Overall, the number of SA-related ED visits increased by 1,533.0% during the study period, from 3,607 in 2006 to 55,296 in 2019. The average annual percentage change was 23.0% (P < .001). The greatest increase occurred from 2015 to 2016, when annual visits increased from 17,709 to 47,732. This increase likely reflected the updated ICD-10 codes, in which there are categories for suspected adult rape, confirmed adult rape, and adult forced sexual exploitation, the researchers note.
Patients presenting to the ED after an SA were mainly women (91.5%). Individuals aged 18-25 years accounted for nearly half of the presentations. Individuals in the lowest and second-lowest income quartiles also were overrepresented.
Despite the increased presentation to EDs, admission rates for SA decreased, from 12.6% to 4.3%, the researchers note. Patients who were older and were insured through Medicaid were more likely to be admitted than persons of other demographic groups.
The researchers also found that increases in ED presentations outpaced increases in SA reports to law enforcement. They compared the ED trends with FBI-reported rapes/SAs from 2015 to 2019 and found increases of 7% and 22% during the times of ICD-9 and ICD-10 codes, respectively. However, in 2019, the number of SA survivors who sought ED care remained below the number who reported to law enforcement (55,296 vs. 139,815, as determined on the basis of revised SA definitions).
“Although the association between increased coding specificity and documentation of SA is still unclear, ICD-10 likely contributed to increased ED documentation of SA,” but the data show steady increases that are independent of the coding change, the researchers write.
The study findings were limited by several factors, including the potential for multiple representations of patients, coding errors associated with the NEDS database, and the reliance on voluntary reports in the NEDS and FBI datasets, the researchers note. The results were strengthened by the large, diverse sample size and by the inclusion of hospital admissions and crime data for comparison, they say.
“As few as 21% of survivors seek medical care after SA, meaning that the survivors captured in this study represent a fraction of total SA-related care need,” the researchers write. “Our finding that most SA ED visits are by young, female, and low-income survivors can inform policy changes to better support these individuals,” which could include the development of outpatient and longitudinal care settings to better serve these populations, they conclude.
Better understanding not only of the trends underlying SA reporting but also of the demographics of survivors who seek treatment and evaluation after SA is vital, said Robert Glatter, MD, in an interview.
“Being able to better understand how social and societal movements affect a patient’s comfort in reporting an SA is vital in tracking the numbers of people who seek care in the ED,” said Dr. Glatter, an emergency medicine physician at Lenox Hill Hospital at Northwell Health, New York, and also of Hofstra University, Hempstead, N.Y.
Dr. Glatter said he was not surprised by the significant increase in sexual assault presentations, especially in light of increased awareness and the influence of the #MeToo movement and other social justice movements over the past decade.
“While I believe that victims of sexual violence may now feel more empowered to report an assault, the volume of SA that go unreported remains a serious public health issue and concern” in the United States and globally, he emphasized.
A key message from the current study is that there is a need for investment in “compassionate and comprehensive care for all survivors of SA,” Dr. Glatter said. “This includes recognition of the extensive mental health consequences of SA that can lead to not only depression, PTSD, and anxiety but also to suicidal ideation and suicide. The longer-term medical effects become life altering, permeating families and future generations,” he emphasized.
“As a society, we must also place a strong emphasis on caring for all SA survivors, but particularly those who come from economically or socially disadvantaged backgrounds who are uninsured or underinsured,” Dr. Glatter said. Issues of race, gender identity, and sexual identity among SA survivors also must be taken into consideration, he added.
“We need to better understand how our health care system can provide more nuanced follow-up care and reporting for survivors in outpatient settings. … Making access easier, while ensuring confidentiality, will allow more survivors of SA to seek treatment and care,” he said. “We also need to understand how using forensic nurses in this capacity, and beyond the ED, can better serve minority and racially diverse communities” and to increase the recruitment and training of such specialized nurses to care for SA victims, Dr. Glatter noted.
The study was supported by internal funding from the University of Michigan and the department of obstetrics and gynecology. Corresponding author Erica C. Marsh, MD, has received personal fees from Myovant Sciences and Pfizer unrelated to the current study. Dr. Glatter has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Data from the Federal Bureau of Investigation show an increase in reported rapes and sexual assaults (SAs) since 2006, and studies of victims show an increased risk of conditions such as suicidal ideation, PTSD, depression, substance use, and chronic conditions, write Emily L. Vogt of the University of Michigan, Ann Arbor, and colleagues.
However, trends and disparities in ED use by adults seeking care following SA have not been explored, they said.
For a study that was published in JAMA Network Open, researchers reviewed data from the Nationwide Emergency Department Sample (NEDS), a large, nationally representative database managed by the Agency for Healthcare Research and Quality. The dataset consisted of 120 million to 143 million weighted ED visits reported annually from 2006 through 2016. The study population included adults aged 18-65 years who had made an ED visit that was recorded in the NEDS and that was coded as an SA. SA was defined using ICD-9 codes until the fourth quarter of 2015, at which time ICD-10 codes came into use.
Overall, the number of SA-related ED visits increased by 1,533.0% during the study period, from 3,607 in 2006 to 55,296 in 2019. The average annual percentage change was 23.0% (P < .001). The greatest increase occurred from 2015 to 2016, when annual visits increased from 17,709 to 47,732. This increase likely reflected the updated ICD-10 codes, in which there are categories for suspected adult rape, confirmed adult rape, and adult forced sexual exploitation, the researchers note.
Patients presenting to the ED after an SA were mainly women (91.5%). Individuals aged 18-25 years accounted for nearly half of the presentations. Individuals in the lowest and second-lowest income quartiles also were overrepresented.
Despite the increased presentation to EDs, admission rates for SA decreased, from 12.6% to 4.3%, the researchers note. Patients who were older and were insured through Medicaid were more likely to be admitted than persons of other demographic groups.
The researchers also found that increases in ED presentations outpaced increases in SA reports to law enforcement. They compared the ED trends with FBI-reported rapes/SAs from 2015 to 2019 and found increases of 7% and 22% during the times of ICD-9 and ICD-10 codes, respectively. However, in 2019, the number of SA survivors who sought ED care remained below the number who reported to law enforcement (55,296 vs. 139,815, as determined on the basis of revised SA definitions).
“Although the association between increased coding specificity and documentation of SA is still unclear, ICD-10 likely contributed to increased ED documentation of SA,” but the data show steady increases that are independent of the coding change, the researchers write.
The study findings were limited by several factors, including the potential for multiple representations of patients, coding errors associated with the NEDS database, and the reliance on voluntary reports in the NEDS and FBI datasets, the researchers note. The results were strengthened by the large, diverse sample size and by the inclusion of hospital admissions and crime data for comparison, they say.
“As few as 21% of survivors seek medical care after SA, meaning that the survivors captured in this study represent a fraction of total SA-related care need,” the researchers write. “Our finding that most SA ED visits are by young, female, and low-income survivors can inform policy changes to better support these individuals,” which could include the development of outpatient and longitudinal care settings to better serve these populations, they conclude.
Better understanding not only of the trends underlying SA reporting but also of the demographics of survivors who seek treatment and evaluation after SA is vital, said Robert Glatter, MD, in an interview.
“Being able to better understand how social and societal movements affect a patient’s comfort in reporting an SA is vital in tracking the numbers of people who seek care in the ED,” said Dr. Glatter, an emergency medicine physician at Lenox Hill Hospital at Northwell Health, New York, and also of Hofstra University, Hempstead, N.Y.
Dr. Glatter said he was not surprised by the significant increase in sexual assault presentations, especially in light of increased awareness and the influence of the #MeToo movement and other social justice movements over the past decade.
“While I believe that victims of sexual violence may now feel more empowered to report an assault, the volume of SA that go unreported remains a serious public health issue and concern” in the United States and globally, he emphasized.
A key message from the current study is that there is a need for investment in “compassionate and comprehensive care for all survivors of SA,” Dr. Glatter said. “This includes recognition of the extensive mental health consequences of SA that can lead to not only depression, PTSD, and anxiety but also to suicidal ideation and suicide. The longer-term medical effects become life altering, permeating families and future generations,” he emphasized.
“As a society, we must also place a strong emphasis on caring for all SA survivors, but particularly those who come from economically or socially disadvantaged backgrounds who are uninsured or underinsured,” Dr. Glatter said. Issues of race, gender identity, and sexual identity among SA survivors also must be taken into consideration, he added.
“We need to better understand how our health care system can provide more nuanced follow-up care and reporting for survivors in outpatient settings. … Making access easier, while ensuring confidentiality, will allow more survivors of SA to seek treatment and care,” he said. “We also need to understand how using forensic nurses in this capacity, and beyond the ED, can better serve minority and racially diverse communities” and to increase the recruitment and training of such specialized nurses to care for SA victims, Dr. Glatter noted.
The study was supported by internal funding from the University of Michigan and the department of obstetrics and gynecology. Corresponding author Erica C. Marsh, MD, has received personal fees from Myovant Sciences and Pfizer unrelated to the current study. Dr. Glatter has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Antibiotic may enhance noninvasive brain stimulation for depression
“The take-home message is that this proof-of-concept study opens up a new avenue of treatment research so that in the future, we may be able to provide our patients with safe and well-tolerated medications and enhance noninvasive brain stimulation treatments for depression,” senior author Alexander McGirr, MD, PhD, assistant professor of psychiatry, University of Calgary (Alta.), told this news organization.
“Once the safety and efficacy of this strategy have been confirmed with larger multisite studies, this could be deployed within existing health care infrastructure,” he said.
The study was published online in JAMA Psychiatry.
Synaptic plasticity
Repetitive transmagnetic stimulation (rTMS) and the more recently developed intermittent theta-burst stimulation (iTBS) are noninvasive brain stimulation modalities that have the largest evidence base in improving MDD. Although efficacious, an “unacceptable proportion of patients do not significantly improve” with these approaches, the authors write.
“We believe that iTBS improves depression through a process called synaptic plasticity, or how neurons adapt to stimulation, but we know that synaptic plasticity is impacted by the illness,” Dr. McGirr explained. This “could be the reason that only some patients benefit.”
One potential strategy to enhance neuroplasticity is to administer an adjunctive N-methyl D-aspartate (NMDA) receptor agonist during stimulation, since the NMDA receptor is a “key regulator of synaptic plasticity,” the authors state. In fact, synaptic plasticity with continuous and intermittent TBS is NMDA-receptor–dependent.
“DCS is an NMDA receptor partial agonist, and so at the low dose we used in our trial (100 mg), it can facilitate NMDA receptor signaling. The hypothesis was that pairing it with iTBS would enhance synaptic plasticity and clinical outcomes,” Dr. McGirr said.
The group’s previous research demonstrated that targeting the NMDA receptor with low-dose DCS “normalizes long-term motor cortex plasticity in individuals with MDD.” It also led to greater persistence of iTBS-induced changes compared to placebo.
However, “a demonstration that these physiological effects have an impact on treatment outcomes is lacking,” the authors note.
To address this gap, the researchers conducted a 4-week double-blind, placebo-controlled trial in which 50 participants (mean [standard deviation] age, 40.8 [13.4] years; 62% women) were randomly assigned on a 1:1 basis to receive either iTBS plus DCS or iTBS plus placebo (n = 25 per group) for the first 2 weeks of the trial, followed by iTBS without an adjunct for the third and fourth weeks.
Participants were required to be experiencing a major depressive episode and to have failed to respond to at least one adequate antidepressant trial or psychotherapy (but not more than four adequate antidepressant trials during the current episode).
Patients with acute suicidality, psychosis, recent substance use disorder, benzodiazepine use, seizures, unstable medical conditions, history of nonresponse to rTMS or electroconvulsive therapy, or comorbid psychiatric conditions, as well as those for whom psychotherapy was initiated within 3 months of enrollment or during the trial, were excluded.
Depression was measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) (changes in score constituted the primary outcome) and the 17-item Hamilton Depression Rating Scale (17-HDRS).
“Secondary outcomes included clinical response, clinical remission, and Clinical Global Impression (CGI) scores,” the authors state.
“Promising” findings
Most participants in the iTBS plus placebo group were White (80%); 12% were Asian, and 8% were classified as “other.” A smaller proportion of participants in the iTBS plus DCS group were White (68%); the next smallest group was Asian (16%), followed by Hispanic (12%), and “other” (4%).
Participants presented with moderate-severe depressive symptoms, as measured by both the HRDS-17 and the MADRS. The placebo and intervention groups had similar scores at baseline. Resting motor threshold did not differ significantly between the groups, either at baseline or between the weeks with and without adjunctive treatment.
Greater improvements in MADRS scores were found in the intervention group than in the placebo groups (mean difference, –6.15 [95% confidence interval, –2.43 to –9.88]; Hedges g, 0.99 [0.34-1.62]).
A larger treatment effect was found after 4 weeks of treatment than after 2 weeks, although the adjuvant was present for the first 2 weeks. “We speculate that, despite ongoing iTBS, this reflects an erosion of the placebo effect, as 15 of 25 participants (60%) in the iTBS plus placebo group plateaued or had a worsening MADRS score, compared with 9 of 25 participants (36%) in the iTBS plus DCS group,” the authors write.
The intervention group showed higher rates of clinical response compared to the placebo group (73.9% vs. 29.3%, respectively), as well as higher rates of clinical remission (39.1% vs. 4.2%, respectively), as reflected in lower CGI-severity ratings and greater CGI-improvement ratings.
There were no serious adverse events during the trial.
The authors note several limitations, including the small sample size and the fact that participants received the adjunctive treatment for only 2 weeks. Longer treatment courses “require dedicated study.” And the short length of the trial (only 4 weeks) meant the difference between “treatment acceleration” and “treatment enhancement” could not be determined.
Nevertheless, the results are “promising” and suggest additional investigation into “intersectional approaches with other dosing regimens and precision medicine targeting approaches,” the authors state.
Synergistic approach
Commenting on the study, Scott Aaronson, MD, chief science officer, Institute for Advanced Diagnostics and Therapeutics, Sheppard Pratt, Towson, Md., called the findings “heartening.” He noted that the study “demonstrates a creative approach of combining an FDA-approved antibiotic with NMDA partial agonist activity – D-cycloserine – with a brief course of iTBS with the aim of enhancing the neuronal plasticity iTBS creates.”
Dr. Aaronson, who is also an adjunct professor at the University of Maryland, Baltimore, and was not involved with the study, added, “This is an early demonstration of the ability to further exploit neuronal changes from neurostimulation by synergistic use of a pharmacologic intervention.”
The study was supported in part by a Young Investigator Award from the Brain and Behavior Research Foundation and the Campus Alberta Innovates Program Chair in Neurostimulation. Dr. McGirr has a patent for PCT/CA2022/050839 pending with MCGRx Corp and is a shareholder of MCGRx Corp. The other authors’ disclosures are listed on the original article. Dr. Aaronson is a consultant for Neuronetics.
A version of this article first appeared on Medscape.com.
“The take-home message is that this proof-of-concept study opens up a new avenue of treatment research so that in the future, we may be able to provide our patients with safe and well-tolerated medications and enhance noninvasive brain stimulation treatments for depression,” senior author Alexander McGirr, MD, PhD, assistant professor of psychiatry, University of Calgary (Alta.), told this news organization.
“Once the safety and efficacy of this strategy have been confirmed with larger multisite studies, this could be deployed within existing health care infrastructure,” he said.
The study was published online in JAMA Psychiatry.
Synaptic plasticity
Repetitive transmagnetic stimulation (rTMS) and the more recently developed intermittent theta-burst stimulation (iTBS) are noninvasive brain stimulation modalities that have the largest evidence base in improving MDD. Although efficacious, an “unacceptable proportion of patients do not significantly improve” with these approaches, the authors write.
“We believe that iTBS improves depression through a process called synaptic plasticity, or how neurons adapt to stimulation, but we know that synaptic plasticity is impacted by the illness,” Dr. McGirr explained. This “could be the reason that only some patients benefit.”
One potential strategy to enhance neuroplasticity is to administer an adjunctive N-methyl D-aspartate (NMDA) receptor agonist during stimulation, since the NMDA receptor is a “key regulator of synaptic plasticity,” the authors state. In fact, synaptic plasticity with continuous and intermittent TBS is NMDA-receptor–dependent.
“DCS is an NMDA receptor partial agonist, and so at the low dose we used in our trial (100 mg), it can facilitate NMDA receptor signaling. The hypothesis was that pairing it with iTBS would enhance synaptic plasticity and clinical outcomes,” Dr. McGirr said.
The group’s previous research demonstrated that targeting the NMDA receptor with low-dose DCS “normalizes long-term motor cortex plasticity in individuals with MDD.” It also led to greater persistence of iTBS-induced changes compared to placebo.
However, “a demonstration that these physiological effects have an impact on treatment outcomes is lacking,” the authors note.
To address this gap, the researchers conducted a 4-week double-blind, placebo-controlled trial in which 50 participants (mean [standard deviation] age, 40.8 [13.4] years; 62% women) were randomly assigned on a 1:1 basis to receive either iTBS plus DCS or iTBS plus placebo (n = 25 per group) for the first 2 weeks of the trial, followed by iTBS without an adjunct for the third and fourth weeks.
Participants were required to be experiencing a major depressive episode and to have failed to respond to at least one adequate antidepressant trial or psychotherapy (but not more than four adequate antidepressant trials during the current episode).
Patients with acute suicidality, psychosis, recent substance use disorder, benzodiazepine use, seizures, unstable medical conditions, history of nonresponse to rTMS or electroconvulsive therapy, or comorbid psychiatric conditions, as well as those for whom psychotherapy was initiated within 3 months of enrollment or during the trial, were excluded.
Depression was measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) (changes in score constituted the primary outcome) and the 17-item Hamilton Depression Rating Scale (17-HDRS).
“Secondary outcomes included clinical response, clinical remission, and Clinical Global Impression (CGI) scores,” the authors state.
“Promising” findings
Most participants in the iTBS plus placebo group were White (80%); 12% were Asian, and 8% were classified as “other.” A smaller proportion of participants in the iTBS plus DCS group were White (68%); the next smallest group was Asian (16%), followed by Hispanic (12%), and “other” (4%).
Participants presented with moderate-severe depressive symptoms, as measured by both the HRDS-17 and the MADRS. The placebo and intervention groups had similar scores at baseline. Resting motor threshold did not differ significantly between the groups, either at baseline or between the weeks with and without adjunctive treatment.
Greater improvements in MADRS scores were found in the intervention group than in the placebo groups (mean difference, –6.15 [95% confidence interval, –2.43 to –9.88]; Hedges g, 0.99 [0.34-1.62]).
A larger treatment effect was found after 4 weeks of treatment than after 2 weeks, although the adjuvant was present for the first 2 weeks. “We speculate that, despite ongoing iTBS, this reflects an erosion of the placebo effect, as 15 of 25 participants (60%) in the iTBS plus placebo group plateaued or had a worsening MADRS score, compared with 9 of 25 participants (36%) in the iTBS plus DCS group,” the authors write.
The intervention group showed higher rates of clinical response compared to the placebo group (73.9% vs. 29.3%, respectively), as well as higher rates of clinical remission (39.1% vs. 4.2%, respectively), as reflected in lower CGI-severity ratings and greater CGI-improvement ratings.
There were no serious adverse events during the trial.
The authors note several limitations, including the small sample size and the fact that participants received the adjunctive treatment for only 2 weeks. Longer treatment courses “require dedicated study.” And the short length of the trial (only 4 weeks) meant the difference between “treatment acceleration” and “treatment enhancement” could not be determined.
Nevertheless, the results are “promising” and suggest additional investigation into “intersectional approaches with other dosing regimens and precision medicine targeting approaches,” the authors state.
Synergistic approach
Commenting on the study, Scott Aaronson, MD, chief science officer, Institute for Advanced Diagnostics and Therapeutics, Sheppard Pratt, Towson, Md., called the findings “heartening.” He noted that the study “demonstrates a creative approach of combining an FDA-approved antibiotic with NMDA partial agonist activity – D-cycloserine – with a brief course of iTBS with the aim of enhancing the neuronal plasticity iTBS creates.”
Dr. Aaronson, who is also an adjunct professor at the University of Maryland, Baltimore, and was not involved with the study, added, “This is an early demonstration of the ability to further exploit neuronal changes from neurostimulation by synergistic use of a pharmacologic intervention.”
The study was supported in part by a Young Investigator Award from the Brain and Behavior Research Foundation and the Campus Alberta Innovates Program Chair in Neurostimulation. Dr. McGirr has a patent for PCT/CA2022/050839 pending with MCGRx Corp and is a shareholder of MCGRx Corp. The other authors’ disclosures are listed on the original article. Dr. Aaronson is a consultant for Neuronetics.
A version of this article first appeared on Medscape.com.
“The take-home message is that this proof-of-concept study opens up a new avenue of treatment research so that in the future, we may be able to provide our patients with safe and well-tolerated medications and enhance noninvasive brain stimulation treatments for depression,” senior author Alexander McGirr, MD, PhD, assistant professor of psychiatry, University of Calgary (Alta.), told this news organization.
“Once the safety and efficacy of this strategy have been confirmed with larger multisite studies, this could be deployed within existing health care infrastructure,” he said.
The study was published online in JAMA Psychiatry.
Synaptic plasticity
Repetitive transmagnetic stimulation (rTMS) and the more recently developed intermittent theta-burst stimulation (iTBS) are noninvasive brain stimulation modalities that have the largest evidence base in improving MDD. Although efficacious, an “unacceptable proportion of patients do not significantly improve” with these approaches, the authors write.
“We believe that iTBS improves depression through a process called synaptic plasticity, or how neurons adapt to stimulation, but we know that synaptic plasticity is impacted by the illness,” Dr. McGirr explained. This “could be the reason that only some patients benefit.”
One potential strategy to enhance neuroplasticity is to administer an adjunctive N-methyl D-aspartate (NMDA) receptor agonist during stimulation, since the NMDA receptor is a “key regulator of synaptic plasticity,” the authors state. In fact, synaptic plasticity with continuous and intermittent TBS is NMDA-receptor–dependent.
“DCS is an NMDA receptor partial agonist, and so at the low dose we used in our trial (100 mg), it can facilitate NMDA receptor signaling. The hypothesis was that pairing it with iTBS would enhance synaptic plasticity and clinical outcomes,” Dr. McGirr said.
The group’s previous research demonstrated that targeting the NMDA receptor with low-dose DCS “normalizes long-term motor cortex plasticity in individuals with MDD.” It also led to greater persistence of iTBS-induced changes compared to placebo.
However, “a demonstration that these physiological effects have an impact on treatment outcomes is lacking,” the authors note.
To address this gap, the researchers conducted a 4-week double-blind, placebo-controlled trial in which 50 participants (mean [standard deviation] age, 40.8 [13.4] years; 62% women) were randomly assigned on a 1:1 basis to receive either iTBS plus DCS or iTBS plus placebo (n = 25 per group) for the first 2 weeks of the trial, followed by iTBS without an adjunct for the third and fourth weeks.
Participants were required to be experiencing a major depressive episode and to have failed to respond to at least one adequate antidepressant trial or psychotherapy (but not more than four adequate antidepressant trials during the current episode).
Patients with acute suicidality, psychosis, recent substance use disorder, benzodiazepine use, seizures, unstable medical conditions, history of nonresponse to rTMS or electroconvulsive therapy, or comorbid psychiatric conditions, as well as those for whom psychotherapy was initiated within 3 months of enrollment or during the trial, were excluded.
Depression was measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) (changes in score constituted the primary outcome) and the 17-item Hamilton Depression Rating Scale (17-HDRS).
“Secondary outcomes included clinical response, clinical remission, and Clinical Global Impression (CGI) scores,” the authors state.
“Promising” findings
Most participants in the iTBS plus placebo group were White (80%); 12% were Asian, and 8% were classified as “other.” A smaller proportion of participants in the iTBS plus DCS group were White (68%); the next smallest group was Asian (16%), followed by Hispanic (12%), and “other” (4%).
Participants presented with moderate-severe depressive symptoms, as measured by both the HRDS-17 and the MADRS. The placebo and intervention groups had similar scores at baseline. Resting motor threshold did not differ significantly between the groups, either at baseline or between the weeks with and without adjunctive treatment.
Greater improvements in MADRS scores were found in the intervention group than in the placebo groups (mean difference, –6.15 [95% confidence interval, –2.43 to –9.88]; Hedges g, 0.99 [0.34-1.62]).
A larger treatment effect was found after 4 weeks of treatment than after 2 weeks, although the adjuvant was present for the first 2 weeks. “We speculate that, despite ongoing iTBS, this reflects an erosion of the placebo effect, as 15 of 25 participants (60%) in the iTBS plus placebo group plateaued or had a worsening MADRS score, compared with 9 of 25 participants (36%) in the iTBS plus DCS group,” the authors write.
The intervention group showed higher rates of clinical response compared to the placebo group (73.9% vs. 29.3%, respectively), as well as higher rates of clinical remission (39.1% vs. 4.2%, respectively), as reflected in lower CGI-severity ratings and greater CGI-improvement ratings.
There were no serious adverse events during the trial.
The authors note several limitations, including the small sample size and the fact that participants received the adjunctive treatment for only 2 weeks. Longer treatment courses “require dedicated study.” And the short length of the trial (only 4 weeks) meant the difference between “treatment acceleration” and “treatment enhancement” could not be determined.
Nevertheless, the results are “promising” and suggest additional investigation into “intersectional approaches with other dosing regimens and precision medicine targeting approaches,” the authors state.
Synergistic approach
Commenting on the study, Scott Aaronson, MD, chief science officer, Institute for Advanced Diagnostics and Therapeutics, Sheppard Pratt, Towson, Md., called the findings “heartening.” He noted that the study “demonstrates a creative approach of combining an FDA-approved antibiotic with NMDA partial agonist activity – D-cycloserine – with a brief course of iTBS with the aim of enhancing the neuronal plasticity iTBS creates.”
Dr. Aaronson, who is also an adjunct professor at the University of Maryland, Baltimore, and was not involved with the study, added, “This is an early demonstration of the ability to further exploit neuronal changes from neurostimulation by synergistic use of a pharmacologic intervention.”
The study was supported in part by a Young Investigator Award from the Brain and Behavior Research Foundation and the Campus Alberta Innovates Program Chair in Neurostimulation. Dr. McGirr has a patent for PCT/CA2022/050839 pending with MCGRx Corp and is a shareholder of MCGRx Corp. The other authors’ disclosures are listed on the original article. Dr. Aaronson is a consultant for Neuronetics.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
Brussels terror attack victim euthanized in Belgium at age 23
This article was originally published on MediQuality.com, an online service for health care professionals in the Benelux and a member of the Medscape Professional Network.
Performing euthanasia for “mental suffering that cannot be alleviated” is still considered an extraordinary measure in Belgium. Indeed, fewer than 2% of the requests for euthanasia fall within that category, and few such requests are made by young patients.
to be applicable. It’s something that Belgian broadcaster RTBF brought up during a recent episode of #Investigation, which reported on the aftermath of the 2016 Brussels attacks.
On May 7, surrounded by her family, Ms. De Corte was euthanized. She was 23 years old. Six years earlier, on March 22, 2016, Ms. De Corte had been at Brussels Airport when terrorists set off bombs. She was in the departures area with 90 other students from Sint-Rita Campus College, located in the northern town of Kontich. Ms. De Corte was only a few meters away from the blast. Although she was not physically injured, the Flemish teen was traumatized by the attack. This was confirmed by the school psychologist who treated the students. “There were some students who reacted worse than others to these traumatic events. And having had two discussions with Shanti, I can tell you that she was one of these students who were more sensitive to the effects. To me, it’s quite clear. Even before the attacks, she’d experienced serious psychological issues. Therefore, I referred her for psychiatric care.”
Eleven antidepressants daily
A few weeks after that March day, Ms. De Corte was admitted to a psychiatric hospital in Antwerp. It was a place she knew well, having been an inpatient there several times before the attacks. Ms. De Corte was treated with antidepressants. She shared her thoughts about them on numerous occasions. “I get several drugs at breakfast and up to 11 antidepressants a day. I couldn’t do without them. With all the drugs I take, I feel like a ghost who doesn’t feel anything anymore. Perhaps there were solutions other than the drugs.”
It was a brief respite. In 2020, Ms. De Corte attempted suicide. Her spirits were at their lowest. She was heavily medicated, and her medication had been increased over time. She turned down therapeutic help that was offered by a therapist who specializes in treating the victims of the Brussels attacks. The student got in touch with the Life End Information Forum, an association that supports the right to die with dignity. In April 2022, Ms. De Corte submitted a new euthanasia request, stating that she was in a medically futile condition of mental suffering. Two psychiatrists granted their approval.
A small proportion
Last March, Belgium’s Federal Commission for the Control and Evaluation of Euthanasia reported on data from 2021. “There continues to be a very small number of euthanasia requests that cite mental and behavioral disorders (psychiatric conditions, such as personality disorders, and cognitive issues, like Alzheimer’s disease, are included in this group): 1.9% of all cases of euthanasia. Like all euthanasia files, these requests meet the legal conditions (the patient is legally competent, the request is in writing, the condition is medically futile, and the suffering – which is constant, unbearable, and cannot be alleviated – results from a serious and incurable disorder; the request is well-considered and repeated),” the report states.
This article was translated from MediQuality and appeared on Medscape.com.
This article was originally published on MediQuality.com, an online service for health care professionals in the Benelux and a member of the Medscape Professional Network.
Performing euthanasia for “mental suffering that cannot be alleviated” is still considered an extraordinary measure in Belgium. Indeed, fewer than 2% of the requests for euthanasia fall within that category, and few such requests are made by young patients.
to be applicable. It’s something that Belgian broadcaster RTBF brought up during a recent episode of #Investigation, which reported on the aftermath of the 2016 Brussels attacks.
On May 7, surrounded by her family, Ms. De Corte was euthanized. She was 23 years old. Six years earlier, on March 22, 2016, Ms. De Corte had been at Brussels Airport when terrorists set off bombs. She was in the departures area with 90 other students from Sint-Rita Campus College, located in the northern town of Kontich. Ms. De Corte was only a few meters away from the blast. Although she was not physically injured, the Flemish teen was traumatized by the attack. This was confirmed by the school psychologist who treated the students. “There were some students who reacted worse than others to these traumatic events. And having had two discussions with Shanti, I can tell you that she was one of these students who were more sensitive to the effects. To me, it’s quite clear. Even before the attacks, she’d experienced serious psychological issues. Therefore, I referred her for psychiatric care.”
Eleven antidepressants daily
A few weeks after that March day, Ms. De Corte was admitted to a psychiatric hospital in Antwerp. It was a place she knew well, having been an inpatient there several times before the attacks. Ms. De Corte was treated with antidepressants. She shared her thoughts about them on numerous occasions. “I get several drugs at breakfast and up to 11 antidepressants a day. I couldn’t do without them. With all the drugs I take, I feel like a ghost who doesn’t feel anything anymore. Perhaps there were solutions other than the drugs.”
It was a brief respite. In 2020, Ms. De Corte attempted suicide. Her spirits were at their lowest. She was heavily medicated, and her medication had been increased over time. She turned down therapeutic help that was offered by a therapist who specializes in treating the victims of the Brussels attacks. The student got in touch with the Life End Information Forum, an association that supports the right to die with dignity. In April 2022, Ms. De Corte submitted a new euthanasia request, stating that she was in a medically futile condition of mental suffering. Two psychiatrists granted their approval.
A small proportion
Last March, Belgium’s Federal Commission for the Control and Evaluation of Euthanasia reported on data from 2021. “There continues to be a very small number of euthanasia requests that cite mental and behavioral disorders (psychiatric conditions, such as personality disorders, and cognitive issues, like Alzheimer’s disease, are included in this group): 1.9% of all cases of euthanasia. Like all euthanasia files, these requests meet the legal conditions (the patient is legally competent, the request is in writing, the condition is medically futile, and the suffering – which is constant, unbearable, and cannot be alleviated – results from a serious and incurable disorder; the request is well-considered and repeated),” the report states.
This article was translated from MediQuality and appeared on Medscape.com.
This article was originally published on MediQuality.com, an online service for health care professionals in the Benelux and a member of the Medscape Professional Network.
Performing euthanasia for “mental suffering that cannot be alleviated” is still considered an extraordinary measure in Belgium. Indeed, fewer than 2% of the requests for euthanasia fall within that category, and few such requests are made by young patients.
to be applicable. It’s something that Belgian broadcaster RTBF brought up during a recent episode of #Investigation, which reported on the aftermath of the 2016 Brussels attacks.
On May 7, surrounded by her family, Ms. De Corte was euthanized. She was 23 years old. Six years earlier, on March 22, 2016, Ms. De Corte had been at Brussels Airport when terrorists set off bombs. She was in the departures area with 90 other students from Sint-Rita Campus College, located in the northern town of Kontich. Ms. De Corte was only a few meters away from the blast. Although she was not physically injured, the Flemish teen was traumatized by the attack. This was confirmed by the school psychologist who treated the students. “There were some students who reacted worse than others to these traumatic events. And having had two discussions with Shanti, I can tell you that she was one of these students who were more sensitive to the effects. To me, it’s quite clear. Even before the attacks, she’d experienced serious psychological issues. Therefore, I referred her for psychiatric care.”
Eleven antidepressants daily
A few weeks after that March day, Ms. De Corte was admitted to a psychiatric hospital in Antwerp. It was a place she knew well, having been an inpatient there several times before the attacks. Ms. De Corte was treated with antidepressants. She shared her thoughts about them on numerous occasions. “I get several drugs at breakfast and up to 11 antidepressants a day. I couldn’t do without them. With all the drugs I take, I feel like a ghost who doesn’t feel anything anymore. Perhaps there were solutions other than the drugs.”
It was a brief respite. In 2020, Ms. De Corte attempted suicide. Her spirits were at their lowest. She was heavily medicated, and her medication had been increased over time. She turned down therapeutic help that was offered by a therapist who specializes in treating the victims of the Brussels attacks. The student got in touch with the Life End Information Forum, an association that supports the right to die with dignity. In April 2022, Ms. De Corte submitted a new euthanasia request, stating that she was in a medically futile condition of mental suffering. Two psychiatrists granted their approval.
A small proportion
Last March, Belgium’s Federal Commission for the Control and Evaluation of Euthanasia reported on data from 2021. “There continues to be a very small number of euthanasia requests that cite mental and behavioral disorders (psychiatric conditions, such as personality disorders, and cognitive issues, like Alzheimer’s disease, are included in this group): 1.9% of all cases of euthanasia. Like all euthanasia files, these requests meet the legal conditions (the patient is legally competent, the request is in writing, the condition is medically futile, and the suffering – which is constant, unbearable, and cannot be alleviated – results from a serious and incurable disorder; the request is well-considered and repeated),” the report states.
This article was translated from MediQuality and appeared on Medscape.com.
Healthy diet, less news helped prevent anxiety, depression during COVID
VIENNA –
Results from a longitudinal Spanish survey study of more than 1,000 adults showed that being outside, relaxing, participating in physical activities, and drinking plenty of water were also beneficial. However, social contact with friends and relatives, following a routine, and pursuing hobbies had no significant impact.
“This was a little surprising,” lead author Joaquim Radua, MD, PhD, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, said in a release.
“Like many people, we had assumed that personal contact would play a bigger part in avoiding anxiety and depression during stressful times,” he added.
However, Dr. Radua said that because the study was conducted during the COVID-19 pandemic, “people who socialized may also have been anxious about getting infected.”
Consequently, “it may be that this specific behavior cannot be extrapolated to other times, when there is no pandemic,” he said.
The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
Correlational versus longitudinal studies
Dr. Radua emphasized that individuals “should socialize,” of course.
“We think it’s important that people continue to follow what works for them and that if you enjoy seeing friends or following a hobby, you continue to do so,” he said.
“Our work was centered on COVID, but we now need to see if these factors apply to other stressful circumstances. These simple behaviors may prevent anxiety and depression, and prevention is better than cure,” he added.
The researchers note that, in “times of uncertainty” such as the COVID-19 pandemic, many individuals experience increases in both anxiety and depressive symptoms.
Although a range of behaviors are recommended to help people cope, the investigators add that some of the recommendations are based on correlational studies.
Indeed, the researchers previously identified a correlation between following a healthy/balanced diet, among other measures, and lower anxiety and depressive symptoms during the pandemic.
However, it is unclear from cross-sectional studies whether the behavior alters the symptoms, in which case the behavior could be considered “helpful,” or conversely whether the symptoms alter an individual’s behavior, in which case the behaviors “may be useless,” the investigators note.
The investigative team therefore set out to provide more robust evidence for making recommendations and conducted a prospective longitudinal study.
They recruited 1,049 adults online via social networks, matching them to the regional, age and sex, and urbanicity distribution of the overall Spanish population.
Every 2 weeks for 12 months, the researchers administered the General Anxiety Disorder (GAD)-7, the Patient Health Questionnaire (PHQ)-9, and a two-item ecological momentary assessment to minimize recall bias, among other measures. They also asked about 10 self-report coping behaviors.
Significant coping behaviors
The study was completed by 942 individuals, indicating a retention of 90%.
Among both completers and non-completers there was an over-representation of individuals aged 18-34 years and women, compared with the general population, and fewer participants aged at least 65 years.
Pre-recruitment, the mean baseline GAD-7 score among completers was 7.4, falling to around 5.5 at the time of the first questionnaire. Scores on the PHQ-9 were 7.6 and 5.6, respectively.
Performing population-weighted autoregressive moving average models to analyze the relationship between the current frequency of the coping behaviors and future changes in anxiety and depressive symptoms, the investigators found that the greatest effect was from following a healthy, balanced diet, with an impact size of 0.95.
This was followed by avoiding too much stressful news (impact size, 0.91), staying outdoors or looking outside (0.40), doing relaxing activities (0.33), participating in physical exercise (0.32), and drinking water to hydrate (0.25).
Overall, these coping behaviors were associated with a significant reduction in anxiety and depressive symptoms (all, P < .001).
On the other hand, there was no impact on future symptoms from socializing with friends and relatives, whether or not they lived in the same household. There was also no effect from following a routine, pursuing hobbies, or performing home tasks.
The researchers note that similar results were obtained when excluding participants with hazardous alcohol consumption, defined as a score on the Alcohol Use Disorders Identification Test of 8 or higher.
However, they point out that despite its prospective design and large cohort, the study was not interventional. Therefore, they “cannot rule out the possibility that decreasing the frequency of a behavior is an early sign of some mechanism that later leads to increased anxiety and depression symptoms.”
Nevertheless, they believe that possibility “seems unlikely.”
Reflective of a unique time?
Commenting on the findings, Catherine Harmer, PhD, director of the Psychopharmacology and Emotional Research Lab, department of psychiatry, University of Oxford (England), said in the release this was an “interesting study” that “provides some important insights as to which behaviors may protect our mental health during times of significant stress.”
She said the finding that social contact was not beneficial was “surprising” but may reflect the fact that, during the pandemic, it was “stressful even to have those social contacts, even if we managed to meet a friend outside.”
The results of the study may therefore be “reflective of the unique experience” of the COVID-19 pandemic, said Dr. Harmer, who was not involved with the research.
“I wouldn’t think that reading too much news would generally be something that has a negative impact on depression and anxiety, but I think it was very much at the time,” she said.
With the pandemic overwhelming one country after another, “the more you read about it, the more frightening it was,” she added, noting that it is “easy to forget how frightened we were at the beginning.”
Dr. Harmer noted that “it would be interesting” if the study was repeated and the same factors came out – or if they were unique to that time.
This would be “useful to know, as these times may come again. And the more information we have to cope with a pandemic, the better,” she concluded.
The research was supported by the AXA Research Fund via an AXA Award granted to Dr. Radua from the call for projects “mitigating risk in the wake of the COVID-19 pandemic.” The investigators and Dr. Harmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VIENNA –
Results from a longitudinal Spanish survey study of more than 1,000 adults showed that being outside, relaxing, participating in physical activities, and drinking plenty of water were also beneficial. However, social contact with friends and relatives, following a routine, and pursuing hobbies had no significant impact.
“This was a little surprising,” lead author Joaquim Radua, MD, PhD, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, said in a release.
“Like many people, we had assumed that personal contact would play a bigger part in avoiding anxiety and depression during stressful times,” he added.
However, Dr. Radua said that because the study was conducted during the COVID-19 pandemic, “people who socialized may also have been anxious about getting infected.”
Consequently, “it may be that this specific behavior cannot be extrapolated to other times, when there is no pandemic,” he said.
The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
Correlational versus longitudinal studies
Dr. Radua emphasized that individuals “should socialize,” of course.
“We think it’s important that people continue to follow what works for them and that if you enjoy seeing friends or following a hobby, you continue to do so,” he said.
“Our work was centered on COVID, but we now need to see if these factors apply to other stressful circumstances. These simple behaviors may prevent anxiety and depression, and prevention is better than cure,” he added.
The researchers note that, in “times of uncertainty” such as the COVID-19 pandemic, many individuals experience increases in both anxiety and depressive symptoms.
Although a range of behaviors are recommended to help people cope, the investigators add that some of the recommendations are based on correlational studies.
Indeed, the researchers previously identified a correlation between following a healthy/balanced diet, among other measures, and lower anxiety and depressive symptoms during the pandemic.
However, it is unclear from cross-sectional studies whether the behavior alters the symptoms, in which case the behavior could be considered “helpful,” or conversely whether the symptoms alter an individual’s behavior, in which case the behaviors “may be useless,” the investigators note.
The investigative team therefore set out to provide more robust evidence for making recommendations and conducted a prospective longitudinal study.
They recruited 1,049 adults online via social networks, matching them to the regional, age and sex, and urbanicity distribution of the overall Spanish population.
Every 2 weeks for 12 months, the researchers administered the General Anxiety Disorder (GAD)-7, the Patient Health Questionnaire (PHQ)-9, and a two-item ecological momentary assessment to minimize recall bias, among other measures. They also asked about 10 self-report coping behaviors.
Significant coping behaviors
The study was completed by 942 individuals, indicating a retention of 90%.
Among both completers and non-completers there was an over-representation of individuals aged 18-34 years and women, compared with the general population, and fewer participants aged at least 65 years.
Pre-recruitment, the mean baseline GAD-7 score among completers was 7.4, falling to around 5.5 at the time of the first questionnaire. Scores on the PHQ-9 were 7.6 and 5.6, respectively.
Performing population-weighted autoregressive moving average models to analyze the relationship between the current frequency of the coping behaviors and future changes in anxiety and depressive symptoms, the investigators found that the greatest effect was from following a healthy, balanced diet, with an impact size of 0.95.
This was followed by avoiding too much stressful news (impact size, 0.91), staying outdoors or looking outside (0.40), doing relaxing activities (0.33), participating in physical exercise (0.32), and drinking water to hydrate (0.25).
Overall, these coping behaviors were associated with a significant reduction in anxiety and depressive symptoms (all, P < .001).
On the other hand, there was no impact on future symptoms from socializing with friends and relatives, whether or not they lived in the same household. There was also no effect from following a routine, pursuing hobbies, or performing home tasks.
The researchers note that similar results were obtained when excluding participants with hazardous alcohol consumption, defined as a score on the Alcohol Use Disorders Identification Test of 8 or higher.
However, they point out that despite its prospective design and large cohort, the study was not interventional. Therefore, they “cannot rule out the possibility that decreasing the frequency of a behavior is an early sign of some mechanism that later leads to increased anxiety and depression symptoms.”
Nevertheless, they believe that possibility “seems unlikely.”
Reflective of a unique time?
Commenting on the findings, Catherine Harmer, PhD, director of the Psychopharmacology and Emotional Research Lab, department of psychiatry, University of Oxford (England), said in the release this was an “interesting study” that “provides some important insights as to which behaviors may protect our mental health during times of significant stress.”
She said the finding that social contact was not beneficial was “surprising” but may reflect the fact that, during the pandemic, it was “stressful even to have those social contacts, even if we managed to meet a friend outside.”
The results of the study may therefore be “reflective of the unique experience” of the COVID-19 pandemic, said Dr. Harmer, who was not involved with the research.
“I wouldn’t think that reading too much news would generally be something that has a negative impact on depression and anxiety, but I think it was very much at the time,” she said.
With the pandemic overwhelming one country after another, “the more you read about it, the more frightening it was,” she added, noting that it is “easy to forget how frightened we were at the beginning.”
Dr. Harmer noted that “it would be interesting” if the study was repeated and the same factors came out – or if they were unique to that time.
This would be “useful to know, as these times may come again. And the more information we have to cope with a pandemic, the better,” she concluded.
The research was supported by the AXA Research Fund via an AXA Award granted to Dr. Radua from the call for projects “mitigating risk in the wake of the COVID-19 pandemic.” The investigators and Dr. Harmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VIENNA –
Results from a longitudinal Spanish survey study of more than 1,000 adults showed that being outside, relaxing, participating in physical activities, and drinking plenty of water were also beneficial. However, social contact with friends and relatives, following a routine, and pursuing hobbies had no significant impact.
“This was a little surprising,” lead author Joaquim Radua, MD, PhD, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, said in a release.
“Like many people, we had assumed that personal contact would play a bigger part in avoiding anxiety and depression during stressful times,” he added.
However, Dr. Radua said that because the study was conducted during the COVID-19 pandemic, “people who socialized may also have been anxious about getting infected.”
Consequently, “it may be that this specific behavior cannot be extrapolated to other times, when there is no pandemic,” he said.
The findings were presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress.
Correlational versus longitudinal studies
Dr. Radua emphasized that individuals “should socialize,” of course.
“We think it’s important that people continue to follow what works for them and that if you enjoy seeing friends or following a hobby, you continue to do so,” he said.
“Our work was centered on COVID, but we now need to see if these factors apply to other stressful circumstances. These simple behaviors may prevent anxiety and depression, and prevention is better than cure,” he added.
The researchers note that, in “times of uncertainty” such as the COVID-19 pandemic, many individuals experience increases in both anxiety and depressive symptoms.
Although a range of behaviors are recommended to help people cope, the investigators add that some of the recommendations are based on correlational studies.
Indeed, the researchers previously identified a correlation between following a healthy/balanced diet, among other measures, and lower anxiety and depressive symptoms during the pandemic.
However, it is unclear from cross-sectional studies whether the behavior alters the symptoms, in which case the behavior could be considered “helpful,” or conversely whether the symptoms alter an individual’s behavior, in which case the behaviors “may be useless,” the investigators note.
The investigative team therefore set out to provide more robust evidence for making recommendations and conducted a prospective longitudinal study.
They recruited 1,049 adults online via social networks, matching them to the regional, age and sex, and urbanicity distribution of the overall Spanish population.
Every 2 weeks for 12 months, the researchers administered the General Anxiety Disorder (GAD)-7, the Patient Health Questionnaire (PHQ)-9, and a two-item ecological momentary assessment to minimize recall bias, among other measures. They also asked about 10 self-report coping behaviors.
Significant coping behaviors
The study was completed by 942 individuals, indicating a retention of 90%.
Among both completers and non-completers there was an over-representation of individuals aged 18-34 years and women, compared with the general population, and fewer participants aged at least 65 years.
Pre-recruitment, the mean baseline GAD-7 score among completers was 7.4, falling to around 5.5 at the time of the first questionnaire. Scores on the PHQ-9 were 7.6 and 5.6, respectively.
Performing population-weighted autoregressive moving average models to analyze the relationship between the current frequency of the coping behaviors and future changes in anxiety and depressive symptoms, the investigators found that the greatest effect was from following a healthy, balanced diet, with an impact size of 0.95.
This was followed by avoiding too much stressful news (impact size, 0.91), staying outdoors or looking outside (0.40), doing relaxing activities (0.33), participating in physical exercise (0.32), and drinking water to hydrate (0.25).
Overall, these coping behaviors were associated with a significant reduction in anxiety and depressive symptoms (all, P < .001).
On the other hand, there was no impact on future symptoms from socializing with friends and relatives, whether or not they lived in the same household. There was also no effect from following a routine, pursuing hobbies, or performing home tasks.
The researchers note that similar results were obtained when excluding participants with hazardous alcohol consumption, defined as a score on the Alcohol Use Disorders Identification Test of 8 or higher.
However, they point out that despite its prospective design and large cohort, the study was not interventional. Therefore, they “cannot rule out the possibility that decreasing the frequency of a behavior is an early sign of some mechanism that later leads to increased anxiety and depression symptoms.”
Nevertheless, they believe that possibility “seems unlikely.”
Reflective of a unique time?
Commenting on the findings, Catherine Harmer, PhD, director of the Psychopharmacology and Emotional Research Lab, department of psychiatry, University of Oxford (England), said in the release this was an “interesting study” that “provides some important insights as to which behaviors may protect our mental health during times of significant stress.”
She said the finding that social contact was not beneficial was “surprising” but may reflect the fact that, during the pandemic, it was “stressful even to have those social contacts, even if we managed to meet a friend outside.”
The results of the study may therefore be “reflective of the unique experience” of the COVID-19 pandemic, said Dr. Harmer, who was not involved with the research.
“I wouldn’t think that reading too much news would generally be something that has a negative impact on depression and anxiety, but I think it was very much at the time,” she said.
With the pandemic overwhelming one country after another, “the more you read about it, the more frightening it was,” she added, noting that it is “easy to forget how frightened we were at the beginning.”
Dr. Harmer noted that “it would be interesting” if the study was repeated and the same factors came out – or if they were unique to that time.
This would be “useful to know, as these times may come again. And the more information we have to cope with a pandemic, the better,” she concluded.
The research was supported by the AXA Research Fund via an AXA Award granted to Dr. Radua from the call for projects “mitigating risk in the wake of the COVID-19 pandemic.” The investigators and Dr. Harmer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ECNP 2022
Study finds systemic AD treatment relieves depressive symptoms along with skin symptoms
MONTREAL – presented at the annual meeting of the International Society of Atopic Dermatitis.
“Randomized, controlled, phase 3 studies have shown that systemic treatment of AD reduces depressive symptoms, but whether this holds true in real-world cohorts remains to be shown,” said study investigator Lina Ivert, MD, PhD, of the dermatology and venereology unit in the department of medicine at the Karolinska Institutet, Stockholm.
The study used data from SwedAD, a newly launched web-based Swedish national registry of patients with AD on systemic treatment between June 2017 and August 2021. Participants were followed at 6 and 12 months for the primary outcome of depressive symptoms using the Montgomery–Åsberg Depression Rating Scale–self-report (MADRS-S). Secondary outcomes included the Eczema Area and Severity Index (EASI) score, Patient-Oriented Eczema Measure (POEM), the Dermatology Life Quality Index (DLQI), and pruritus visual analog scale/numeric rating scale (VAS/NRS).
At baseline, 120 patients (median age, 39 years; 57.5% men) were started on dupilumab (n = 91), methotrexate (26), or cyclosporin (3). Although almost half had no depression at baseline, mild depression was present in 29.2%, with moderate and severe depression in 20% and 4.2%, respectively.
Among 59 patients with 6-month follow-up data (48 on dupilumab, 10 on methotrexate, 1 on cyclosporin), all nine depressive symptoms in MADRS-S improved significantly, with reduced sleep improving the most (from a median of 3 points to a median of 1 point). Similarly, overall MADRS-S scores improved (from a median of 14 points to a median of 5; P < .001), as did EASI scores (from a median of 20.5 to 2), POEM scores (from a median of 22 to 6), DLQI (from a median of 15 to 3), and pruritus scores (from a median of 7.1 to 1.8; all P < .001).
The analysis also found a strong correlation between the MADRS-S score and all of the secondary outcomes (P < .001 for all). All these improvements remained significant among the 36 patients with 12-month follow-up data.
“The median MADRS-S reduction also remained when we excluded eight patients who were on antidepressants during the study period, so these results cannot be explained by psychiatric medication,” noted Dr. Ivert, adding that three patients with severe suicide ideation at baseline improved their MADRS-S suicide item to less than 2 points. “So, this study taught us to look at the suicide item score and not only the total MADRS-S score,” she commented.
Comparing patients treated with dupilumab with those treated with methotrexate, the analysis showed that though baseline median MADRS-S scores did not differ significantly between them, there was a significant 6-month reduction in the dupilumab group but not in the methotrexate group.
Asked to comment on the findings, moderator Marissa Joseph, MD, a pediatric dermatologist at the University of Toronto, said that “the mental health effects of inflammatory skin conditions like atopic dermatitis are well known, but whether or not they are well explored in the patient-physician interaction is a whole other scenario.” There are time constraints, she said, adding, “it sometimes takes some deep-diving ... but exploring those types of symptoms is something we need to do more of, and the severity of the disease and reasons for treatment are not just what you can see.”
Dr. Joseph pointed out that taking the deep dive also involves being prepared for what comes up. “Once you’ve established there’s a mental health issue, what do you do then?” she said. “If you are a dermatologist, is that in your wheelhouse to address? There’s the education and connection piece for the physician, creating networks where – if you identify a patient who has an issue – who is a person I can send them to? We have these types of connections with infectious disease or with ophthalmologists if there are ocular symptoms, but mental health is one area where there may not be as much support for dermatologists.”
She noted that though all doctors learn how to screen for depression, “there’s the formulaic, yes/no answers, and then there’s the nuanced history-taking, creating a safe space, where the patient is going to answer you fulsomely ... and feel heard. Many of us know how to do that. The question is time.”
Dr. Ivert had no disclosures connected to this study. Dr. Joseph had no disclosures.
A version of this article first appeared on Medscape.com.
MONTREAL – presented at the annual meeting of the International Society of Atopic Dermatitis.
“Randomized, controlled, phase 3 studies have shown that systemic treatment of AD reduces depressive symptoms, but whether this holds true in real-world cohorts remains to be shown,” said study investigator Lina Ivert, MD, PhD, of the dermatology and venereology unit in the department of medicine at the Karolinska Institutet, Stockholm.
The study used data from SwedAD, a newly launched web-based Swedish national registry of patients with AD on systemic treatment between June 2017 and August 2021. Participants were followed at 6 and 12 months for the primary outcome of depressive symptoms using the Montgomery–Åsberg Depression Rating Scale–self-report (MADRS-S). Secondary outcomes included the Eczema Area and Severity Index (EASI) score, Patient-Oriented Eczema Measure (POEM), the Dermatology Life Quality Index (DLQI), and pruritus visual analog scale/numeric rating scale (VAS/NRS).
At baseline, 120 patients (median age, 39 years; 57.5% men) were started on dupilumab (n = 91), methotrexate (26), or cyclosporin (3). Although almost half had no depression at baseline, mild depression was present in 29.2%, with moderate and severe depression in 20% and 4.2%, respectively.
Among 59 patients with 6-month follow-up data (48 on dupilumab, 10 on methotrexate, 1 on cyclosporin), all nine depressive symptoms in MADRS-S improved significantly, with reduced sleep improving the most (from a median of 3 points to a median of 1 point). Similarly, overall MADRS-S scores improved (from a median of 14 points to a median of 5; P < .001), as did EASI scores (from a median of 20.5 to 2), POEM scores (from a median of 22 to 6), DLQI (from a median of 15 to 3), and pruritus scores (from a median of 7.1 to 1.8; all P < .001).
The analysis also found a strong correlation between the MADRS-S score and all of the secondary outcomes (P < .001 for all). All these improvements remained significant among the 36 patients with 12-month follow-up data.
“The median MADRS-S reduction also remained when we excluded eight patients who were on antidepressants during the study period, so these results cannot be explained by psychiatric medication,” noted Dr. Ivert, adding that three patients with severe suicide ideation at baseline improved their MADRS-S suicide item to less than 2 points. “So, this study taught us to look at the suicide item score and not only the total MADRS-S score,” she commented.
Comparing patients treated with dupilumab with those treated with methotrexate, the analysis showed that though baseline median MADRS-S scores did not differ significantly between them, there was a significant 6-month reduction in the dupilumab group but not in the methotrexate group.
Asked to comment on the findings, moderator Marissa Joseph, MD, a pediatric dermatologist at the University of Toronto, said that “the mental health effects of inflammatory skin conditions like atopic dermatitis are well known, but whether or not they are well explored in the patient-physician interaction is a whole other scenario.” There are time constraints, she said, adding, “it sometimes takes some deep-diving ... but exploring those types of symptoms is something we need to do more of, and the severity of the disease and reasons for treatment are not just what you can see.”
Dr. Joseph pointed out that taking the deep dive also involves being prepared for what comes up. “Once you’ve established there’s a mental health issue, what do you do then?” she said. “If you are a dermatologist, is that in your wheelhouse to address? There’s the education and connection piece for the physician, creating networks where – if you identify a patient who has an issue – who is a person I can send them to? We have these types of connections with infectious disease or with ophthalmologists if there are ocular symptoms, but mental health is one area where there may not be as much support for dermatologists.”
She noted that though all doctors learn how to screen for depression, “there’s the formulaic, yes/no answers, and then there’s the nuanced history-taking, creating a safe space, where the patient is going to answer you fulsomely ... and feel heard. Many of us know how to do that. The question is time.”
Dr. Ivert had no disclosures connected to this study. Dr. Joseph had no disclosures.
A version of this article first appeared on Medscape.com.
MONTREAL – presented at the annual meeting of the International Society of Atopic Dermatitis.
“Randomized, controlled, phase 3 studies have shown that systemic treatment of AD reduces depressive symptoms, but whether this holds true in real-world cohorts remains to be shown,” said study investigator Lina Ivert, MD, PhD, of the dermatology and venereology unit in the department of medicine at the Karolinska Institutet, Stockholm.
The study used data from SwedAD, a newly launched web-based Swedish national registry of patients with AD on systemic treatment between June 2017 and August 2021. Participants were followed at 6 and 12 months for the primary outcome of depressive symptoms using the Montgomery–Åsberg Depression Rating Scale–self-report (MADRS-S). Secondary outcomes included the Eczema Area and Severity Index (EASI) score, Patient-Oriented Eczema Measure (POEM), the Dermatology Life Quality Index (DLQI), and pruritus visual analog scale/numeric rating scale (VAS/NRS).
At baseline, 120 patients (median age, 39 years; 57.5% men) were started on dupilumab (n = 91), methotrexate (26), or cyclosporin (3). Although almost half had no depression at baseline, mild depression was present in 29.2%, with moderate and severe depression in 20% and 4.2%, respectively.
Among 59 patients with 6-month follow-up data (48 on dupilumab, 10 on methotrexate, 1 on cyclosporin), all nine depressive symptoms in MADRS-S improved significantly, with reduced sleep improving the most (from a median of 3 points to a median of 1 point). Similarly, overall MADRS-S scores improved (from a median of 14 points to a median of 5; P < .001), as did EASI scores (from a median of 20.5 to 2), POEM scores (from a median of 22 to 6), DLQI (from a median of 15 to 3), and pruritus scores (from a median of 7.1 to 1.8; all P < .001).
The analysis also found a strong correlation between the MADRS-S score and all of the secondary outcomes (P < .001 for all). All these improvements remained significant among the 36 patients with 12-month follow-up data.
“The median MADRS-S reduction also remained when we excluded eight patients who were on antidepressants during the study period, so these results cannot be explained by psychiatric medication,” noted Dr. Ivert, adding that three patients with severe suicide ideation at baseline improved their MADRS-S suicide item to less than 2 points. “So, this study taught us to look at the suicide item score and not only the total MADRS-S score,” she commented.
Comparing patients treated with dupilumab with those treated with methotrexate, the analysis showed that though baseline median MADRS-S scores did not differ significantly between them, there was a significant 6-month reduction in the dupilumab group but not in the methotrexate group.
Asked to comment on the findings, moderator Marissa Joseph, MD, a pediatric dermatologist at the University of Toronto, said that “the mental health effects of inflammatory skin conditions like atopic dermatitis are well known, but whether or not they are well explored in the patient-physician interaction is a whole other scenario.” There are time constraints, she said, adding, “it sometimes takes some deep-diving ... but exploring those types of symptoms is something we need to do more of, and the severity of the disease and reasons for treatment are not just what you can see.”
Dr. Joseph pointed out that taking the deep dive also involves being prepared for what comes up. “Once you’ve established there’s a mental health issue, what do you do then?” she said. “If you are a dermatologist, is that in your wheelhouse to address? There’s the education and connection piece for the physician, creating networks where – if you identify a patient who has an issue – who is a person I can send them to? We have these types of connections with infectious disease or with ophthalmologists if there are ocular symptoms, but mental health is one area where there may not be as much support for dermatologists.”
She noted that though all doctors learn how to screen for depression, “there’s the formulaic, yes/no answers, and then there’s the nuanced history-taking, creating a safe space, where the patient is going to answer you fulsomely ... and feel heard. Many of us know how to do that. The question is time.”
Dr. Ivert had no disclosures connected to this study. Dr. Joseph had no disclosures.
A version of this article first appeared on Medscape.com.
FROM ISAD 2022
Confirmed: ECT tops ketamine for major depression
in new findings that are in line with the KetECT study – the first head-to-head trial of ketamine and ECT.
The KetECT trial, which was published earlier this year, showed that ECT was more effective than IV ketamine for hospitalized patients with severe depression. ECT yielded higher remission rates and a greater reduction of symptoms.
Despite the apparent superiority of ECT over ketamine, the researchers of the current meta-analysis caution that treatment options for MDE “should still be individualized and patient-centered because ketamine’s faster antidepressant effects may still be desirable for certain patients with severe MDE who require quick recovery from the severity of depression.”
The study was published online in JAMA Psychiatry.
Confirmatory data
The review included six clinical trials with 340 patients with MDE. Of those patients, 162 were treated with ECT, and 178 were treated with ketamine. The mean age of the participants ranged from 37 to 52 years.
The primary efficacy outcome of interest was improvement of depressive symptoms.
ECT was superior to ketamine across different depressive symptom measures, reported Taeho Greg Rhee, PhD, of the University of Connecticut, Farmington, and colleagues.
The standardized mean difference (SMD) was –0.59 (95% confidence interval [CI], –0.85 to –0.33) on the Montgomery-Åsberg Depression Rating Scale.
The SMD was –0.83 (95% CI, –1.22 to –0.44] on the Hamilton Depression Rating Scale and –0.86 (95% CI, –1.50 to –0.22) on the Beck Depression Inventory.
The overall pooled SMD for ECT, when compared with ketamine, was –0.69 (95% CI, –0.89 to –0.48), indicating that ECT was more efficacious than ketamine.
The researchers did not find any moderating effects of various factors, including age, male sex, and presence of psychotic features.
For cognition and memory performance, one study reported that the ketamine group outperformed the ECT group in cognition, but the effect size was small to moderate.
A separate study that reported memory performance found no difference between ketamine and ECT, though this study was likely underpowered to detect such differences, with a total sample size of 32.
“Because of underpowered study designs, no firm conclusions regarding cognition and memory performance can be made in this meta-analysis. Future research should address this issue,” the investigators wrote.
Unique side effects
Ketamine and ECT had unique adverse effect profiles.
With ketamine, there was a lower risk of headache and muscle pain but a higher risk of transient dissociative or depersonalization symptoms. With ECT, there was a lower risk of blurred vision, vertigo, and diplopia/nystagmus.
Only one study reported suicide attempts and suicide deaths, for which there was no marked difference between ECT and ketamine.
A limitation of the meta-analysis is the low to moderate methodologic quality of the studies that were included, as well as the use of different ketamine and/or ECT treatment protocols, which could have influenced efficacy and safety outcomes.
The researchers noted that more research is needed to optimize long-term treatment outcomes for both ketamine and ECT to prevent relapse, “which is of key importance for clinical practice.”
The study had no specific funding. Dr. Rhee currently serves as a co–editor-in-chief of Mental Health Science and will receive honorarium payments annually from the publisher, John Wiley & Sons. A complete list of the authors’ relevant financial relationships is available with the original article.
A version of this article first appeared on Medscape.com.
in new findings that are in line with the KetECT study – the first head-to-head trial of ketamine and ECT.
The KetECT trial, which was published earlier this year, showed that ECT was more effective than IV ketamine for hospitalized patients with severe depression. ECT yielded higher remission rates and a greater reduction of symptoms.
Despite the apparent superiority of ECT over ketamine, the researchers of the current meta-analysis caution that treatment options for MDE “should still be individualized and patient-centered because ketamine’s faster antidepressant effects may still be desirable for certain patients with severe MDE who require quick recovery from the severity of depression.”
The study was published online in JAMA Psychiatry.
Confirmatory data
The review included six clinical trials with 340 patients with MDE. Of those patients, 162 were treated with ECT, and 178 were treated with ketamine. The mean age of the participants ranged from 37 to 52 years.
The primary efficacy outcome of interest was improvement of depressive symptoms.
ECT was superior to ketamine across different depressive symptom measures, reported Taeho Greg Rhee, PhD, of the University of Connecticut, Farmington, and colleagues.
The standardized mean difference (SMD) was –0.59 (95% confidence interval [CI], –0.85 to –0.33) on the Montgomery-Åsberg Depression Rating Scale.
The SMD was –0.83 (95% CI, –1.22 to –0.44] on the Hamilton Depression Rating Scale and –0.86 (95% CI, –1.50 to –0.22) on the Beck Depression Inventory.
The overall pooled SMD for ECT, when compared with ketamine, was –0.69 (95% CI, –0.89 to –0.48), indicating that ECT was more efficacious than ketamine.
The researchers did not find any moderating effects of various factors, including age, male sex, and presence of psychotic features.
For cognition and memory performance, one study reported that the ketamine group outperformed the ECT group in cognition, but the effect size was small to moderate.
A separate study that reported memory performance found no difference between ketamine and ECT, though this study was likely underpowered to detect such differences, with a total sample size of 32.
“Because of underpowered study designs, no firm conclusions regarding cognition and memory performance can be made in this meta-analysis. Future research should address this issue,” the investigators wrote.
Unique side effects
Ketamine and ECT had unique adverse effect profiles.
With ketamine, there was a lower risk of headache and muscle pain but a higher risk of transient dissociative or depersonalization symptoms. With ECT, there was a lower risk of blurred vision, vertigo, and diplopia/nystagmus.
Only one study reported suicide attempts and suicide deaths, for which there was no marked difference between ECT and ketamine.
A limitation of the meta-analysis is the low to moderate methodologic quality of the studies that were included, as well as the use of different ketamine and/or ECT treatment protocols, which could have influenced efficacy and safety outcomes.
The researchers noted that more research is needed to optimize long-term treatment outcomes for both ketamine and ECT to prevent relapse, “which is of key importance for clinical practice.”
The study had no specific funding. Dr. Rhee currently serves as a co–editor-in-chief of Mental Health Science and will receive honorarium payments annually from the publisher, John Wiley & Sons. A complete list of the authors’ relevant financial relationships is available with the original article.
A version of this article first appeared on Medscape.com.
in new findings that are in line with the KetECT study – the first head-to-head trial of ketamine and ECT.
The KetECT trial, which was published earlier this year, showed that ECT was more effective than IV ketamine for hospitalized patients with severe depression. ECT yielded higher remission rates and a greater reduction of symptoms.
Despite the apparent superiority of ECT over ketamine, the researchers of the current meta-analysis caution that treatment options for MDE “should still be individualized and patient-centered because ketamine’s faster antidepressant effects may still be desirable for certain patients with severe MDE who require quick recovery from the severity of depression.”
The study was published online in JAMA Psychiatry.
Confirmatory data
The review included six clinical trials with 340 patients with MDE. Of those patients, 162 were treated with ECT, and 178 were treated with ketamine. The mean age of the participants ranged from 37 to 52 years.
The primary efficacy outcome of interest was improvement of depressive symptoms.
ECT was superior to ketamine across different depressive symptom measures, reported Taeho Greg Rhee, PhD, of the University of Connecticut, Farmington, and colleagues.
The standardized mean difference (SMD) was –0.59 (95% confidence interval [CI], –0.85 to –0.33) on the Montgomery-Åsberg Depression Rating Scale.
The SMD was –0.83 (95% CI, –1.22 to –0.44] on the Hamilton Depression Rating Scale and –0.86 (95% CI, –1.50 to –0.22) on the Beck Depression Inventory.
The overall pooled SMD for ECT, when compared with ketamine, was –0.69 (95% CI, –0.89 to –0.48), indicating that ECT was more efficacious than ketamine.
The researchers did not find any moderating effects of various factors, including age, male sex, and presence of psychotic features.
For cognition and memory performance, one study reported that the ketamine group outperformed the ECT group in cognition, but the effect size was small to moderate.
A separate study that reported memory performance found no difference between ketamine and ECT, though this study was likely underpowered to detect such differences, with a total sample size of 32.
“Because of underpowered study designs, no firm conclusions regarding cognition and memory performance can be made in this meta-analysis. Future research should address this issue,” the investigators wrote.
Unique side effects
Ketamine and ECT had unique adverse effect profiles.
With ketamine, there was a lower risk of headache and muscle pain but a higher risk of transient dissociative or depersonalization symptoms. With ECT, there was a lower risk of blurred vision, vertigo, and diplopia/nystagmus.
Only one study reported suicide attempts and suicide deaths, for which there was no marked difference between ECT and ketamine.
A limitation of the meta-analysis is the low to moderate methodologic quality of the studies that were included, as well as the use of different ketamine and/or ECT treatment protocols, which could have influenced efficacy and safety outcomes.
The researchers noted that more research is needed to optimize long-term treatment outcomes for both ketamine and ECT to prevent relapse, “which is of key importance for clinical practice.”
The study had no specific funding. Dr. Rhee currently serves as a co–editor-in-chief of Mental Health Science and will receive honorarium payments annually from the publisher, John Wiley & Sons. A complete list of the authors’ relevant financial relationships is available with the original article.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
Phase 3 topline results ‘disappointing’ for novel antidepressant as monotherapy
The negative monotherapy data come on the heels of earlier phase 2 data showing a benefit of REL-1017 when used as add-on therapy for adults with major depressive disorder (MDD).
Despite the monotherapy results, Relmada reported in a release that it is continuing to enroll patients in two other phase 3 trials. However, RELIANCE I and RELIANCE II are assessing the drug only as adjunctive therapy.
“While these RELIANCE III results are disappointing for patients, the need for new, safe, and effective treatments for MDD continues to exist,” Maurizio Fava, MD, psychiatrist in chief at Massachusetts General Hospital, Boston, said in the release.
“We look forward to the data from the ongoing RELIANCE I and II trials of REL-1017, a potential new therapy for the adjunctive treatment of MDD,” Dr. Fava added.
REL-1017 is a novel N-methyl-D-aspartate receptor channel blocker that preferentially targets hyperactive channels while maintaining physiologic glutamatergic neurotransmission. RELIANCE III tested REL-1017 against placebo for 28 days in 232 adults with MDD.
The study did not achieve its primary endpoint, which was a statistically significant improvement in symptoms of depression compared with placebo, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) on day 28.
At that time point, the REL-1017 treatment group showed a reduction in MADRS scores of 14.8 points, vs. 13.9 points for the placebo arm.
The placebo response was “higher than expected” – placebo “dramatically” outperformed REL-1017 at some study sites, Relmada said in the release.
The company added that it is “investigating the nature of these results.”
A version of this article first appeared on Medscape.com.
The negative monotherapy data come on the heels of earlier phase 2 data showing a benefit of REL-1017 when used as add-on therapy for adults with major depressive disorder (MDD).
Despite the monotherapy results, Relmada reported in a release that it is continuing to enroll patients in two other phase 3 trials. However, RELIANCE I and RELIANCE II are assessing the drug only as adjunctive therapy.
“While these RELIANCE III results are disappointing for patients, the need for new, safe, and effective treatments for MDD continues to exist,” Maurizio Fava, MD, psychiatrist in chief at Massachusetts General Hospital, Boston, said in the release.
“We look forward to the data from the ongoing RELIANCE I and II trials of REL-1017, a potential new therapy for the adjunctive treatment of MDD,” Dr. Fava added.
REL-1017 is a novel N-methyl-D-aspartate receptor channel blocker that preferentially targets hyperactive channels while maintaining physiologic glutamatergic neurotransmission. RELIANCE III tested REL-1017 against placebo for 28 days in 232 adults with MDD.
The study did not achieve its primary endpoint, which was a statistically significant improvement in symptoms of depression compared with placebo, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) on day 28.
At that time point, the REL-1017 treatment group showed a reduction in MADRS scores of 14.8 points, vs. 13.9 points for the placebo arm.
The placebo response was “higher than expected” – placebo “dramatically” outperformed REL-1017 at some study sites, Relmada said in the release.
The company added that it is “investigating the nature of these results.”
A version of this article first appeared on Medscape.com.
The negative monotherapy data come on the heels of earlier phase 2 data showing a benefit of REL-1017 when used as add-on therapy for adults with major depressive disorder (MDD).
Despite the monotherapy results, Relmada reported in a release that it is continuing to enroll patients in two other phase 3 trials. However, RELIANCE I and RELIANCE II are assessing the drug only as adjunctive therapy.
“While these RELIANCE III results are disappointing for patients, the need for new, safe, and effective treatments for MDD continues to exist,” Maurizio Fava, MD, psychiatrist in chief at Massachusetts General Hospital, Boston, said in the release.
“We look forward to the data from the ongoing RELIANCE I and II trials of REL-1017, a potential new therapy for the adjunctive treatment of MDD,” Dr. Fava added.
REL-1017 is a novel N-methyl-D-aspartate receptor channel blocker that preferentially targets hyperactive channels while maintaining physiologic glutamatergic neurotransmission. RELIANCE III tested REL-1017 against placebo for 28 days in 232 adults with MDD.
The study did not achieve its primary endpoint, which was a statistically significant improvement in symptoms of depression compared with placebo, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) on day 28.
At that time point, the REL-1017 treatment group showed a reduction in MADRS scores of 14.8 points, vs. 13.9 points for the placebo arm.
The placebo response was “higher than expected” – placebo “dramatically” outperformed REL-1017 at some study sites, Relmada said in the release.
The company added that it is “investigating the nature of these results.”
A version of this article first appeared on Medscape.com.