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FDA approves first oral treatment for spinal muscular atrophy
This marks the first approval of an oral therapy for the rare and devastating condition.
Risdiplam, marketed by Roche and PTC Therapeutics, provides “an important treatment option for patients with SMA, following the approval of the first treatment for this devastating disease less than 4 years ago,” Billy Dunn, MD, director of the Office of Neuroscience in the Center for Drug Evaluation and Research at the FDA, said in a release from the agency.
The approval was based on the results from two trials. In the open-label FIREFISH study of infantile-onset SMA, 7 (41%) of the 17 participants (mean baseline age, 6.7 months) were able to sit independently for more than 5 seconds after 12 months of treatment with risdiplam. This was a “meaningful difference from the natural progression of the disease because all untreated infants with infantile-onset SMA cannot sit independently,” the FDA noted. In addition, 81% of the participants were alive after 23 or more months of treatment – and without need of permanent ventilation.
The second study was the randomized controlled trial known as SUNFISH and included 180 patients with SMA between the ages of 2 and 25 years. Those who received the study drug had an average 1.36 increase from baseline on a motor function measure versus a 0.19 decrease in function for those who received placebo.
The FDA noted that the most common treatment-related adverse events (AEs) include fever, diarrhea, rash, ulcers of the mouth, arthralgia, and urinary tract infections. Additional AEs reported in some patients with infantile-onset SMA included upper respiratory tract infection, pneumonia, constipation, and vomiting.
The drug received fast track designation and priority review from the FDA, as well as orphan drug designation.
‘Eagerly awaited’
“Today marks an incredibly important moment for the broader SMA patient community that had been in dire need of safe and effective treatment options,” Stuart W. Peltz, PhD, chief executive officer of PTC Therapeutics, said in a company statement.
“Given [that] the majority of people with SMA in the U.S. remain untreated, we believe Evrysdi, with its favorable clinical profile and oral administration, may offer meaningful benefits for many living with this rare neurological disease,” Levi Garraway, MD, PhD, chief medical officer and head of global product development for Genentech, added in the company’s press release. Genentech is a member of the Roche Group.
The drug is continuing to be studied in more than 450 individuals as part of a “large and robust clinical trial program in SMA,” the company reports. These participants are between the ages of 2 months and 60 years.
“The approval of Evrysdi is an eagerly awaited milestone for our community. We appreciate Genentech’s commitment to … developing a treatment that can be administered at home,” Kenneth Hobby, president of the nonprofit Cure SMA, said in the same release.
In May 2019, the FDA approved the first gene therapy for SMA – the infusion drug onasemnogene abeparvovec-xioi (Zolgensma, AveXis Inc).
Genentech announced that the new oral drug will be available in the United States within 2 weeks “for direct delivery to patients’ homes.”
A version of this article originally appeared on Medscape.com.
This marks the first approval of an oral therapy for the rare and devastating condition.
Risdiplam, marketed by Roche and PTC Therapeutics, provides “an important treatment option for patients with SMA, following the approval of the first treatment for this devastating disease less than 4 years ago,” Billy Dunn, MD, director of the Office of Neuroscience in the Center for Drug Evaluation and Research at the FDA, said in a release from the agency.
The approval was based on the results from two trials. In the open-label FIREFISH study of infantile-onset SMA, 7 (41%) of the 17 participants (mean baseline age, 6.7 months) were able to sit independently for more than 5 seconds after 12 months of treatment with risdiplam. This was a “meaningful difference from the natural progression of the disease because all untreated infants with infantile-onset SMA cannot sit independently,” the FDA noted. In addition, 81% of the participants were alive after 23 or more months of treatment – and without need of permanent ventilation.
The second study was the randomized controlled trial known as SUNFISH and included 180 patients with SMA between the ages of 2 and 25 years. Those who received the study drug had an average 1.36 increase from baseline on a motor function measure versus a 0.19 decrease in function for those who received placebo.
The FDA noted that the most common treatment-related adverse events (AEs) include fever, diarrhea, rash, ulcers of the mouth, arthralgia, and urinary tract infections. Additional AEs reported in some patients with infantile-onset SMA included upper respiratory tract infection, pneumonia, constipation, and vomiting.
The drug received fast track designation and priority review from the FDA, as well as orphan drug designation.
‘Eagerly awaited’
“Today marks an incredibly important moment for the broader SMA patient community that had been in dire need of safe and effective treatment options,” Stuart W. Peltz, PhD, chief executive officer of PTC Therapeutics, said in a company statement.
“Given [that] the majority of people with SMA in the U.S. remain untreated, we believe Evrysdi, with its favorable clinical profile and oral administration, may offer meaningful benefits for many living with this rare neurological disease,” Levi Garraway, MD, PhD, chief medical officer and head of global product development for Genentech, added in the company’s press release. Genentech is a member of the Roche Group.
The drug is continuing to be studied in more than 450 individuals as part of a “large and robust clinical trial program in SMA,” the company reports. These participants are between the ages of 2 months and 60 years.
“The approval of Evrysdi is an eagerly awaited milestone for our community. We appreciate Genentech’s commitment to … developing a treatment that can be administered at home,” Kenneth Hobby, president of the nonprofit Cure SMA, said in the same release.
In May 2019, the FDA approved the first gene therapy for SMA – the infusion drug onasemnogene abeparvovec-xioi (Zolgensma, AveXis Inc).
Genentech announced that the new oral drug will be available in the United States within 2 weeks “for direct delivery to patients’ homes.”
A version of this article originally appeared on Medscape.com.
This marks the first approval of an oral therapy for the rare and devastating condition.
Risdiplam, marketed by Roche and PTC Therapeutics, provides “an important treatment option for patients with SMA, following the approval of the first treatment for this devastating disease less than 4 years ago,” Billy Dunn, MD, director of the Office of Neuroscience in the Center for Drug Evaluation and Research at the FDA, said in a release from the agency.
The approval was based on the results from two trials. In the open-label FIREFISH study of infantile-onset SMA, 7 (41%) of the 17 participants (mean baseline age, 6.7 months) were able to sit independently for more than 5 seconds after 12 months of treatment with risdiplam. This was a “meaningful difference from the natural progression of the disease because all untreated infants with infantile-onset SMA cannot sit independently,” the FDA noted. In addition, 81% of the participants were alive after 23 or more months of treatment – and without need of permanent ventilation.
The second study was the randomized controlled trial known as SUNFISH and included 180 patients with SMA between the ages of 2 and 25 years. Those who received the study drug had an average 1.36 increase from baseline on a motor function measure versus a 0.19 decrease in function for those who received placebo.
The FDA noted that the most common treatment-related adverse events (AEs) include fever, diarrhea, rash, ulcers of the mouth, arthralgia, and urinary tract infections. Additional AEs reported in some patients with infantile-onset SMA included upper respiratory tract infection, pneumonia, constipation, and vomiting.
The drug received fast track designation and priority review from the FDA, as well as orphan drug designation.
‘Eagerly awaited’
“Today marks an incredibly important moment for the broader SMA patient community that had been in dire need of safe and effective treatment options,” Stuart W. Peltz, PhD, chief executive officer of PTC Therapeutics, said in a company statement.
“Given [that] the majority of people with SMA in the U.S. remain untreated, we believe Evrysdi, with its favorable clinical profile and oral administration, may offer meaningful benefits for many living with this rare neurological disease,” Levi Garraway, MD, PhD, chief medical officer and head of global product development for Genentech, added in the company’s press release. Genentech is a member of the Roche Group.
The drug is continuing to be studied in more than 450 individuals as part of a “large and robust clinical trial program in SMA,” the company reports. These participants are between the ages of 2 months and 60 years.
“The approval of Evrysdi is an eagerly awaited milestone for our community. We appreciate Genentech’s commitment to … developing a treatment that can be administered at home,” Kenneth Hobby, president of the nonprofit Cure SMA, said in the same release.
In May 2019, the FDA approved the first gene therapy for SMA – the infusion drug onasemnogene abeparvovec-xioi (Zolgensma, AveXis Inc).
Genentech announced that the new oral drug will be available in the United States within 2 weeks “for direct delivery to patients’ homes.”
A version of this article originally appeared on Medscape.com.
Topline results for novel intranasal med to treat opioid overdose
Topline results show positive results for the experimental intranasal nalmefene product OX125 for opioid overdose reversal, Orexo, the drug’s manufacturer, announced on June 30.
A crossover, comparative bioavailability study was conducted in healthy volunteers to assess nalmefene absorption of three development formulations of OX125. Preliminary results showed “extensive and rapid absorption” across all three formulations versus an intramuscular injection of nalmefene, Orexo reported.
“As the U.S. heroin crisis has developed to a fentanyl crisis, the medical need for novel and more powerful opioid rescue medications is vast,” Nikolaj Sørensen, president and CEO of Orexo, said in a press release.
“The need has also escalated due to the COVID-19 pandemic as the consequences of social distancing and economic weakness are expected to lead to a significant increase in mental health issues and substance use disorders,” Mr. Sørensen added.
Robert Rönn, vice president and head of research and development at Orexo, noted in the same release that the company will now be working with the Food and Drug Administration “to identify the optimal route to market.”
There were more than 31,000 fatalities from highly potent synthetic opioids in the United States in 2018, the manufacturer reported. “Like naloxone, nalmefene is an opioid antagonist that acts by blocking the effects of opioids at the opioid receptors.”
However, nalmefene has a longer half-life than naloxone. These longer-acting properties may be “of particular value to protect against renarcotization (second overdose), as the antagonist wears off,” according to an Orexo press release.
In addition to showing rapid absorption across all formulations studied, study results showed “good tolerability, supporting the viability” of the treatment as an opioid overdose rescue medication, the company said.
“This is not only a proof of concept for our wholly owned OX125 product, but also a demonstration of the value of our novel nasal technology platform,” Mr. Rönn said.
“Alongside OX124, our naloxone rescue project, OX125 will be an important lifesaving addition in our commitment to helping patients suffering from opioid addiction in all phases,” Mr. Sørensen added.
A version of this article originally appeared on Medscape.com.
Topline results show positive results for the experimental intranasal nalmefene product OX125 for opioid overdose reversal, Orexo, the drug’s manufacturer, announced on June 30.
A crossover, comparative bioavailability study was conducted in healthy volunteers to assess nalmefene absorption of three development formulations of OX125. Preliminary results showed “extensive and rapid absorption” across all three formulations versus an intramuscular injection of nalmefene, Orexo reported.
“As the U.S. heroin crisis has developed to a fentanyl crisis, the medical need for novel and more powerful opioid rescue medications is vast,” Nikolaj Sørensen, president and CEO of Orexo, said in a press release.
“The need has also escalated due to the COVID-19 pandemic as the consequences of social distancing and economic weakness are expected to lead to a significant increase in mental health issues and substance use disorders,” Mr. Sørensen added.
Robert Rönn, vice president and head of research and development at Orexo, noted in the same release that the company will now be working with the Food and Drug Administration “to identify the optimal route to market.”
There were more than 31,000 fatalities from highly potent synthetic opioids in the United States in 2018, the manufacturer reported. “Like naloxone, nalmefene is an opioid antagonist that acts by blocking the effects of opioids at the opioid receptors.”
However, nalmefene has a longer half-life than naloxone. These longer-acting properties may be “of particular value to protect against renarcotization (second overdose), as the antagonist wears off,” according to an Orexo press release.
In addition to showing rapid absorption across all formulations studied, study results showed “good tolerability, supporting the viability” of the treatment as an opioid overdose rescue medication, the company said.
“This is not only a proof of concept for our wholly owned OX125 product, but also a demonstration of the value of our novel nasal technology platform,” Mr. Rönn said.
“Alongside OX124, our naloxone rescue project, OX125 will be an important lifesaving addition in our commitment to helping patients suffering from opioid addiction in all phases,” Mr. Sørensen added.
A version of this article originally appeared on Medscape.com.
Topline results show positive results for the experimental intranasal nalmefene product OX125 for opioid overdose reversal, Orexo, the drug’s manufacturer, announced on June 30.
A crossover, comparative bioavailability study was conducted in healthy volunteers to assess nalmefene absorption of three development formulations of OX125. Preliminary results showed “extensive and rapid absorption” across all three formulations versus an intramuscular injection of nalmefene, Orexo reported.
“As the U.S. heroin crisis has developed to a fentanyl crisis, the medical need for novel and more powerful opioid rescue medications is vast,” Nikolaj Sørensen, president and CEO of Orexo, said in a press release.
“The need has also escalated due to the COVID-19 pandemic as the consequences of social distancing and economic weakness are expected to lead to a significant increase in mental health issues and substance use disorders,” Mr. Sørensen added.
Robert Rönn, vice president and head of research and development at Orexo, noted in the same release that the company will now be working with the Food and Drug Administration “to identify the optimal route to market.”
There were more than 31,000 fatalities from highly potent synthetic opioids in the United States in 2018, the manufacturer reported. “Like naloxone, nalmefene is an opioid antagonist that acts by blocking the effects of opioids at the opioid receptors.”
However, nalmefene has a longer half-life than naloxone. These longer-acting properties may be “of particular value to protect against renarcotization (second overdose), as the antagonist wears off,” according to an Orexo press release.
In addition to showing rapid absorption across all formulations studied, study results showed “good tolerability, supporting the viability” of the treatment as an opioid overdose rescue medication, the company said.
“This is not only a proof of concept for our wholly owned OX125 product, but also a demonstration of the value of our novel nasal technology platform,” Mr. Rönn said.
“Alongside OX124, our naloxone rescue project, OX125 will be an important lifesaving addition in our commitment to helping patients suffering from opioid addiction in all phases,” Mr. Sørensen added.
A version of this article originally appeared on Medscape.com.
FDA approves apomorphine sublingual film for ‘off’ episodes in Parkinson’s disease
, the manufacturer has announced. This marks the first approval for a sublingual therapy for this indication, which is defined as the re-emergence or worsening of Parkinson’s disease symptoms that have otherwise been controlled with standard care of levodopa/carbidopa, Sunovion reports. Almost 60% of patients with Parkinson’s disease experience off episodes.
The approval “affords healthcare providers with a needed option that can be added to their patients’ medication regimen to adequately address off episodes as their Parkinson’s disease progresses,” Stewart Factor, DO, professor of neurology and director of the Movement Disorders Program at Emory University School of Medicine, Atlanta, Georgia, said in a press release from the manufacturer.
“We know from our research and discussion with the Parkinson’s community that off episodes can significantly disrupt a patient’s daily life,” Todd Sherer, PhD, CEO of the Michael J. Fox Foundation for Parkinson’s Research, said in the same release. He added that the Fox Foundation “supported early clinical development of sublingual apomorphine.”
The treatment is expected to be available in US pharmacies in September.
Disruptive symptoms
Off episodes can include periods of tremor, slowed movement, and stiffness and occur during daytime hours.
“Several years after a person is diagnosed with [Parkinson’s disease] they may notice problems such as having trouble getting out of bed in the morning or having difficulty getting out of a chair, or that they feel frozen while trying to walk as the effect of their maintenance medication diminishes,” Dr. Factor noted.
Subcutaneous infusion of the dopamine agonist apomorphine previously has shown benefit in treating persistent motor fluctuations in patients with Parkinson’s disease.
Apomorphine hydrochloride sublingual film is a novel formulation of apomorphine. It dissolves under the tongue to help improve off episode symptoms as needed up to five times per day.
A phase 3 study of 109 patients that was published in December in Lancet Neurology showed that those who received the sublingual film therapy had a mean reduction of 11.1 points on the Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III 30 minutes after dosing at the 12-week assessment. This was a significant improvement in motor symptoms versus those who received placebo (mean difference, -7.6 points; P = .0002).
In addition, initial clinical improvement was found 15 minutes after dosing.
The most frequently reported treatment-emergent adverse events in the study population were oropharyngeal reactions, followed by nausea, somnolence, and dizziness.
Long-term safety?
“The availability of this new apomorphine sublingual formulation, along with an inhaled formulation under development, will broaden the treatment options for off periods,” Angelo Antonini, MD, PhD, from University of Padua, Italy, wrote in an accompanying editorial in The Lancet Neurology.
Although the results were encouraging, he noted some caution should be heeded.
Because of “the high rate of oropharyngeal adverse events, long-term safety needs to be monitored once the product is registered and available for chronic use in patients with Parkinson’s disease,” Dr. Antonini wrote.
Other safety information issued by the manufacturer includes a warning that patients who take the 5HT3 antagonists ondansetron, dolasetron, palonosetron, granisetron, or alosetron for nausea should not also use apomorphine hydrochloride sublingual film.
“People taking ondansetron together with apomorphine, the active ingredient in Kynmobi, have had very low blood pressure and lost consciousness or ‘blacked out,’ “ the warning notes.
It also should not be taken by individuals who are allergic to the ingredients in the medication, including sodium metabisulfite.
This article first appeared on Medscape.com.
, the manufacturer has announced. This marks the first approval for a sublingual therapy for this indication, which is defined as the re-emergence or worsening of Parkinson’s disease symptoms that have otherwise been controlled with standard care of levodopa/carbidopa, Sunovion reports. Almost 60% of patients with Parkinson’s disease experience off episodes.
The approval “affords healthcare providers with a needed option that can be added to their patients’ medication regimen to adequately address off episodes as their Parkinson’s disease progresses,” Stewart Factor, DO, professor of neurology and director of the Movement Disorders Program at Emory University School of Medicine, Atlanta, Georgia, said in a press release from the manufacturer.
“We know from our research and discussion with the Parkinson’s community that off episodes can significantly disrupt a patient’s daily life,” Todd Sherer, PhD, CEO of the Michael J. Fox Foundation for Parkinson’s Research, said in the same release. He added that the Fox Foundation “supported early clinical development of sublingual apomorphine.”
The treatment is expected to be available in US pharmacies in September.
Disruptive symptoms
Off episodes can include periods of tremor, slowed movement, and stiffness and occur during daytime hours.
“Several years after a person is diagnosed with [Parkinson’s disease] they may notice problems such as having trouble getting out of bed in the morning or having difficulty getting out of a chair, or that they feel frozen while trying to walk as the effect of their maintenance medication diminishes,” Dr. Factor noted.
Subcutaneous infusion of the dopamine agonist apomorphine previously has shown benefit in treating persistent motor fluctuations in patients with Parkinson’s disease.
Apomorphine hydrochloride sublingual film is a novel formulation of apomorphine. It dissolves under the tongue to help improve off episode symptoms as needed up to five times per day.
A phase 3 study of 109 patients that was published in December in Lancet Neurology showed that those who received the sublingual film therapy had a mean reduction of 11.1 points on the Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III 30 minutes after dosing at the 12-week assessment. This was a significant improvement in motor symptoms versus those who received placebo (mean difference, -7.6 points; P = .0002).
In addition, initial clinical improvement was found 15 minutes after dosing.
The most frequently reported treatment-emergent adverse events in the study population were oropharyngeal reactions, followed by nausea, somnolence, and dizziness.
Long-term safety?
“The availability of this new apomorphine sublingual formulation, along with an inhaled formulation under development, will broaden the treatment options for off periods,” Angelo Antonini, MD, PhD, from University of Padua, Italy, wrote in an accompanying editorial in The Lancet Neurology.
Although the results were encouraging, he noted some caution should be heeded.
Because of “the high rate of oropharyngeal adverse events, long-term safety needs to be monitored once the product is registered and available for chronic use in patients with Parkinson’s disease,” Dr. Antonini wrote.
Other safety information issued by the manufacturer includes a warning that patients who take the 5HT3 antagonists ondansetron, dolasetron, palonosetron, granisetron, or alosetron for nausea should not also use apomorphine hydrochloride sublingual film.
“People taking ondansetron together with apomorphine, the active ingredient in Kynmobi, have had very low blood pressure and lost consciousness or ‘blacked out,’ “ the warning notes.
It also should not be taken by individuals who are allergic to the ingredients in the medication, including sodium metabisulfite.
This article first appeared on Medscape.com.
, the manufacturer has announced. This marks the first approval for a sublingual therapy for this indication, which is defined as the re-emergence or worsening of Parkinson’s disease symptoms that have otherwise been controlled with standard care of levodopa/carbidopa, Sunovion reports. Almost 60% of patients with Parkinson’s disease experience off episodes.
The approval “affords healthcare providers with a needed option that can be added to their patients’ medication regimen to adequately address off episodes as their Parkinson’s disease progresses,” Stewart Factor, DO, professor of neurology and director of the Movement Disorders Program at Emory University School of Medicine, Atlanta, Georgia, said in a press release from the manufacturer.
“We know from our research and discussion with the Parkinson’s community that off episodes can significantly disrupt a patient’s daily life,” Todd Sherer, PhD, CEO of the Michael J. Fox Foundation for Parkinson’s Research, said in the same release. He added that the Fox Foundation “supported early clinical development of sublingual apomorphine.”
The treatment is expected to be available in US pharmacies in September.
Disruptive symptoms
Off episodes can include periods of tremor, slowed movement, and stiffness and occur during daytime hours.
“Several years after a person is diagnosed with [Parkinson’s disease] they may notice problems such as having trouble getting out of bed in the morning or having difficulty getting out of a chair, or that they feel frozen while trying to walk as the effect of their maintenance medication diminishes,” Dr. Factor noted.
Subcutaneous infusion of the dopamine agonist apomorphine previously has shown benefit in treating persistent motor fluctuations in patients with Parkinson’s disease.
Apomorphine hydrochloride sublingual film is a novel formulation of apomorphine. It dissolves under the tongue to help improve off episode symptoms as needed up to five times per day.
A phase 3 study of 109 patients that was published in December in Lancet Neurology showed that those who received the sublingual film therapy had a mean reduction of 11.1 points on the Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part III 30 minutes after dosing at the 12-week assessment. This was a significant improvement in motor symptoms versus those who received placebo (mean difference, -7.6 points; P = .0002).
In addition, initial clinical improvement was found 15 minutes after dosing.
The most frequently reported treatment-emergent adverse events in the study population were oropharyngeal reactions, followed by nausea, somnolence, and dizziness.
Long-term safety?
“The availability of this new apomorphine sublingual formulation, along with an inhaled formulation under development, will broaden the treatment options for off periods,” Angelo Antonini, MD, PhD, from University of Padua, Italy, wrote in an accompanying editorial in The Lancet Neurology.
Although the results were encouraging, he noted some caution should be heeded.
Because of “the high rate of oropharyngeal adverse events, long-term safety needs to be monitored once the product is registered and available for chronic use in patients with Parkinson’s disease,” Dr. Antonini wrote.
Other safety information issued by the manufacturer includes a warning that patients who take the 5HT3 antagonists ondansetron, dolasetron, palonosetron, granisetron, or alosetron for nausea should not also use apomorphine hydrochloride sublingual film.
“People taking ondansetron together with apomorphine, the active ingredient in Kynmobi, have had very low blood pressure and lost consciousness or ‘blacked out,’ “ the warning notes.
It also should not be taken by individuals who are allergic to the ingredients in the medication, including sodium metabisulfite.
This article first appeared on Medscape.com.
Depression linked to neuro dysfunction, brain lesions in MS
Depression is associated with decreased neurologic function and new brain lesions in patients with multiple sclerosis (MS), new research suggests.
In an observational study of more than 2500 patients with relapsing-remitting MS (RRMS), participants with self-reported depression were more likely to have worse scores on neuroperformance measures, such as processing speed tests, than their peers without depression.
At baseline, the group with depression also had greater odds of having at least one new contrast-enhancing lesion on MRI.
“Our results suggest that depression is not merely a reactive symptom but indicates increased risk of future MS disease activity,” the investigators note.
Lead author Jenny Feng, MD, clinical associate at the Mellen Center for MS Treatment and Research at Cleveland Clinic, added that depression should be routinely screened for in all patients with MS, something done routinely at her center.
“Every single patient that comes through the door with newly diagnosed MS, we refer to neuropsychology to screen for depression; and if there is depression, then we actively manage it because it does have an effect” on patients, she told Medscape Medical News.
“Depression isn’t just a neuropsychiatric disease,” Feng added. As shown in their study, “it may have effects on MS, especially with regards to performance in neurological function testing.”
The research is presented on AAN.com as part of the American Academy of Neurology 2020 Science Highlights. Because of the COVID-19 pandemic, the AAN had to cancel its 2020 annual meeting.
Associations Have Been “Unclear”
Although inflammatory, psychosocial, and neurodegenerative factors “have been hypothesized as etiologies” for why depression is commonly found in patients with MS,
For the current study, they assessed data from the Partners Advancing Technology and Health Solutions (MS-PATHS) database, an ongoing collaborative network of seven MS centers in the United States and three in Europe.
MS disease history and MRI data were examined, as well as 12-month scores on neuroperformance tests measuring processing speed (Symbol Digit Modalities Test), walking speed (Timed 25-Foot Walk), and manual dexterity (Nine-Hole Peg Test).
Patient-reported outcomes (PROs), as measured with the Quality of Life in Neurological Disorders (Neuro-QoL) and patient-determined disease steps, were also assessed. Depression was defined as a depression T score at baseline greater than “the 50th percentile” on the Neuro-QoL.
In the patient sample, 1333 of the participants with RRMS were classified as “not depressed” (73.7% women; mean age, 45.6 years; disease duration, 13.7 years) while 1172 were “depressed” (78.4% women; mean age, 45.9 years; disease duration, 14.3 years).
“To balance for baseline variances in the observational cohort between group with depression and group without depression, propensity score analysis was used to adjust for potential confounding factors,” the investigators report.
Worse Performance
After adjustment for baseline covariates, results showed that the depressed patients performed worse on the walking speed test (0.48; 95% confidence interval, 0.038-0.918) and processing speed test (–1.899; 95% CI, –3.548 to –0.250).
The depressed group also had increased odds at baseline of having new contrast-enhancing lesions (odds ratio, 5.89; 95% CI, 2.236-15.517). This demonstrated an “association of depression and neuroinflammatory activity” in the central nervous system, the investigators note.
At 12 months, processing speed continued to be worse in the depressed group (–1.68; 95% CI, –3.254 to –0.105).
There were trends, albeit insignificant, for decreased walking speed scores at 12 months and for decreased manual dexterity scores at both baseline and at 12 months for the participants who were depressed.
Interestingly, there were “no significant differences in PROs at month 12, despite worsening neuroperformance,” the investigators report.
“This means that patients themselves may not even realize that they were getting worse,” Feng said.
Underpowered Study?
Further results showed nonsignificant trends for increased T2 lesion volume and white matter fraction and decreased brain volume, gray matter fraction, and cortical gray matter volume at baseline and at 12 months in the depressed group.
The researchers note that study limitations include the unavailability of information on treatment compliance for depression or date of depression onset.
Feng added that because this was an observational study, other missing data included depression status for some patients at year 1 and some MRI metrics.
“So this may have been underpowered to detect some of the results. The power may have been inadequate to detect all changes,” she said.
The investigators write that future research should assess larger sample sizes with longer follow-ups and should use more advanced MRI measures, such as diffusion tensor imaging or functional MRI.
In addition, they will continue examining data from MS-PATHS. “With the newest data cut, we have new patients that we can analyze. So perhaps that can provide sufficient power to detect [more MRI] changes,” Feng said.
Unusual, Intriguing Findings
Commenting on the study for Medscape Medical News, Mark Freedman, MD, professor of neurology at the University of Ottawa and director of the Multiple Sclerosis Research Clinic at the Ottawa Hospital Research Institute, noted that he wasn’t terribly surprised” by the overall findings.
“We’ve known for years that patients who are depressed don’t do as well on our performance methods,” said Freedman, who was not involved with the research.
However, the current investigators “took a huge number of patients in this multicenter study and started using some of the statistical methods we’ve seen in the use of real-world evidence,” he noted.
“So you’re looking at some outcome measures and you have to ask yourself, ‘Why would it influence that?’ and ‘Did it happen by chance or not?’ And you ask why it is that depressed people might actually have more lesions on their MRI, which is something that is unusual,” Freedman said.
“When you start to look at this, even when you’re trying to standardize things for the differences that we know of, there are some stuff that comes out as intriguing. In general, I think those depressed patients did worse on several outcome measures that one would say, ‘That’s somewhat surprising.’ That’s why this group was very careful to not conclude absolutely that depression drives this disease. But it was consistently trending in the direction that it looks like there was more inflammatory activity in these people,” he said.
He echoed the investigators’ note that drug adherence and which depression treatment was used wasn’t controlled for; and he added that depression in the study was not based on receiving a diagnosis of clinical depression but on self-report.
Still, the patients classified as depressed “did worse. They didn’t walk as fast, which was interesting; and we know that cognitive performance is often damped because of poor concentration. But how do you get worse MRIs? This study is raising a question and [the researchers] conclude that it may be that depression might be an independent factor” for that outcome, Freedman said.
“It might be that you could get more out of a particular [MS] medicine if you pay attention to depression; and if that’s the investigators’ conclusion, and I think it is, then I certainly agree with it.”
Freedman noted that, instead of a blanket recommendation that all patients with MS should be screened for depression, he thinks clinicians, especially those at smaller centers, should focus on what’s best for treating all aspects of an individual patient.
“Don’t try to manage them if you’re not going to manage the entire picture. Looking at depression and mood and other things is very important. And if you have the capacity for an official screening, I think it’s wonderful; but not everybody does,” he said.
Feng and Freedman have disclosed no relevant financial relationships. Freedman is currently a member of the Medscape Neurology Advisory Board.
This article appeared on Medscape.com.
Depression is associated with decreased neurologic function and new brain lesions in patients with multiple sclerosis (MS), new research suggests.
In an observational study of more than 2500 patients with relapsing-remitting MS (RRMS), participants with self-reported depression were more likely to have worse scores on neuroperformance measures, such as processing speed tests, than their peers without depression.
At baseline, the group with depression also had greater odds of having at least one new contrast-enhancing lesion on MRI.
“Our results suggest that depression is not merely a reactive symptom but indicates increased risk of future MS disease activity,” the investigators note.
Lead author Jenny Feng, MD, clinical associate at the Mellen Center for MS Treatment and Research at Cleveland Clinic, added that depression should be routinely screened for in all patients with MS, something done routinely at her center.
“Every single patient that comes through the door with newly diagnosed MS, we refer to neuropsychology to screen for depression; and if there is depression, then we actively manage it because it does have an effect” on patients, she told Medscape Medical News.
“Depression isn’t just a neuropsychiatric disease,” Feng added. As shown in their study, “it may have effects on MS, especially with regards to performance in neurological function testing.”
The research is presented on AAN.com as part of the American Academy of Neurology 2020 Science Highlights. Because of the COVID-19 pandemic, the AAN had to cancel its 2020 annual meeting.
Associations Have Been “Unclear”
Although inflammatory, psychosocial, and neurodegenerative factors “have been hypothesized as etiologies” for why depression is commonly found in patients with MS,
For the current study, they assessed data from the Partners Advancing Technology and Health Solutions (MS-PATHS) database, an ongoing collaborative network of seven MS centers in the United States and three in Europe.
MS disease history and MRI data were examined, as well as 12-month scores on neuroperformance tests measuring processing speed (Symbol Digit Modalities Test), walking speed (Timed 25-Foot Walk), and manual dexterity (Nine-Hole Peg Test).
Patient-reported outcomes (PROs), as measured with the Quality of Life in Neurological Disorders (Neuro-QoL) and patient-determined disease steps, were also assessed. Depression was defined as a depression T score at baseline greater than “the 50th percentile” on the Neuro-QoL.
In the patient sample, 1333 of the participants with RRMS were classified as “not depressed” (73.7% women; mean age, 45.6 years; disease duration, 13.7 years) while 1172 were “depressed” (78.4% women; mean age, 45.9 years; disease duration, 14.3 years).
“To balance for baseline variances in the observational cohort between group with depression and group without depression, propensity score analysis was used to adjust for potential confounding factors,” the investigators report.
Worse Performance
After adjustment for baseline covariates, results showed that the depressed patients performed worse on the walking speed test (0.48; 95% confidence interval, 0.038-0.918) and processing speed test (–1.899; 95% CI, –3.548 to –0.250).
The depressed group also had increased odds at baseline of having new contrast-enhancing lesions (odds ratio, 5.89; 95% CI, 2.236-15.517). This demonstrated an “association of depression and neuroinflammatory activity” in the central nervous system, the investigators note.
At 12 months, processing speed continued to be worse in the depressed group (–1.68; 95% CI, –3.254 to –0.105).
There were trends, albeit insignificant, for decreased walking speed scores at 12 months and for decreased manual dexterity scores at both baseline and at 12 months for the participants who were depressed.
Interestingly, there were “no significant differences in PROs at month 12, despite worsening neuroperformance,” the investigators report.
“This means that patients themselves may not even realize that they were getting worse,” Feng said.
Underpowered Study?
Further results showed nonsignificant trends for increased T2 lesion volume and white matter fraction and decreased brain volume, gray matter fraction, and cortical gray matter volume at baseline and at 12 months in the depressed group.
The researchers note that study limitations include the unavailability of information on treatment compliance for depression or date of depression onset.
Feng added that because this was an observational study, other missing data included depression status for some patients at year 1 and some MRI metrics.
“So this may have been underpowered to detect some of the results. The power may have been inadequate to detect all changes,” she said.
The investigators write that future research should assess larger sample sizes with longer follow-ups and should use more advanced MRI measures, such as diffusion tensor imaging or functional MRI.
In addition, they will continue examining data from MS-PATHS. “With the newest data cut, we have new patients that we can analyze. So perhaps that can provide sufficient power to detect [more MRI] changes,” Feng said.
Unusual, Intriguing Findings
Commenting on the study for Medscape Medical News, Mark Freedman, MD, professor of neurology at the University of Ottawa and director of the Multiple Sclerosis Research Clinic at the Ottawa Hospital Research Institute, noted that he wasn’t terribly surprised” by the overall findings.
“We’ve known for years that patients who are depressed don’t do as well on our performance methods,” said Freedman, who was not involved with the research.
However, the current investigators “took a huge number of patients in this multicenter study and started using some of the statistical methods we’ve seen in the use of real-world evidence,” he noted.
“So you’re looking at some outcome measures and you have to ask yourself, ‘Why would it influence that?’ and ‘Did it happen by chance or not?’ And you ask why it is that depressed people might actually have more lesions on their MRI, which is something that is unusual,” Freedman said.
“When you start to look at this, even when you’re trying to standardize things for the differences that we know of, there are some stuff that comes out as intriguing. In general, I think those depressed patients did worse on several outcome measures that one would say, ‘That’s somewhat surprising.’ That’s why this group was very careful to not conclude absolutely that depression drives this disease. But it was consistently trending in the direction that it looks like there was more inflammatory activity in these people,” he said.
He echoed the investigators’ note that drug adherence and which depression treatment was used wasn’t controlled for; and he added that depression in the study was not based on receiving a diagnosis of clinical depression but on self-report.
Still, the patients classified as depressed “did worse. They didn’t walk as fast, which was interesting; and we know that cognitive performance is often damped because of poor concentration. But how do you get worse MRIs? This study is raising a question and [the researchers] conclude that it may be that depression might be an independent factor” for that outcome, Freedman said.
“It might be that you could get more out of a particular [MS] medicine if you pay attention to depression; and if that’s the investigators’ conclusion, and I think it is, then I certainly agree with it.”
Freedman noted that, instead of a blanket recommendation that all patients with MS should be screened for depression, he thinks clinicians, especially those at smaller centers, should focus on what’s best for treating all aspects of an individual patient.
“Don’t try to manage them if you’re not going to manage the entire picture. Looking at depression and mood and other things is very important. And if you have the capacity for an official screening, I think it’s wonderful; but not everybody does,” he said.
Feng and Freedman have disclosed no relevant financial relationships. Freedman is currently a member of the Medscape Neurology Advisory Board.
This article appeared on Medscape.com.
Depression is associated with decreased neurologic function and new brain lesions in patients with multiple sclerosis (MS), new research suggests.
In an observational study of more than 2500 patients with relapsing-remitting MS (RRMS), participants with self-reported depression were more likely to have worse scores on neuroperformance measures, such as processing speed tests, than their peers without depression.
At baseline, the group with depression also had greater odds of having at least one new contrast-enhancing lesion on MRI.
“Our results suggest that depression is not merely a reactive symptom but indicates increased risk of future MS disease activity,” the investigators note.
Lead author Jenny Feng, MD, clinical associate at the Mellen Center for MS Treatment and Research at Cleveland Clinic, added that depression should be routinely screened for in all patients with MS, something done routinely at her center.
“Every single patient that comes through the door with newly diagnosed MS, we refer to neuropsychology to screen for depression; and if there is depression, then we actively manage it because it does have an effect” on patients, she told Medscape Medical News.
“Depression isn’t just a neuropsychiatric disease,” Feng added. As shown in their study, “it may have effects on MS, especially with regards to performance in neurological function testing.”
The research is presented on AAN.com as part of the American Academy of Neurology 2020 Science Highlights. Because of the COVID-19 pandemic, the AAN had to cancel its 2020 annual meeting.
Associations Have Been “Unclear”
Although inflammatory, psychosocial, and neurodegenerative factors “have been hypothesized as etiologies” for why depression is commonly found in patients with MS,
For the current study, they assessed data from the Partners Advancing Technology and Health Solutions (MS-PATHS) database, an ongoing collaborative network of seven MS centers in the United States and three in Europe.
MS disease history and MRI data were examined, as well as 12-month scores on neuroperformance tests measuring processing speed (Symbol Digit Modalities Test), walking speed (Timed 25-Foot Walk), and manual dexterity (Nine-Hole Peg Test).
Patient-reported outcomes (PROs), as measured with the Quality of Life in Neurological Disorders (Neuro-QoL) and patient-determined disease steps, were also assessed. Depression was defined as a depression T score at baseline greater than “the 50th percentile” on the Neuro-QoL.
In the patient sample, 1333 of the participants with RRMS were classified as “not depressed” (73.7% women; mean age, 45.6 years; disease duration, 13.7 years) while 1172 were “depressed” (78.4% women; mean age, 45.9 years; disease duration, 14.3 years).
“To balance for baseline variances in the observational cohort between group with depression and group without depression, propensity score analysis was used to adjust for potential confounding factors,” the investigators report.
Worse Performance
After adjustment for baseline covariates, results showed that the depressed patients performed worse on the walking speed test (0.48; 95% confidence interval, 0.038-0.918) and processing speed test (–1.899; 95% CI, –3.548 to –0.250).
The depressed group also had increased odds at baseline of having new contrast-enhancing lesions (odds ratio, 5.89; 95% CI, 2.236-15.517). This demonstrated an “association of depression and neuroinflammatory activity” in the central nervous system, the investigators note.
At 12 months, processing speed continued to be worse in the depressed group (–1.68; 95% CI, –3.254 to –0.105).
There were trends, albeit insignificant, for decreased walking speed scores at 12 months and for decreased manual dexterity scores at both baseline and at 12 months for the participants who were depressed.
Interestingly, there were “no significant differences in PROs at month 12, despite worsening neuroperformance,” the investigators report.
“This means that patients themselves may not even realize that they were getting worse,” Feng said.
Underpowered Study?
Further results showed nonsignificant trends for increased T2 lesion volume and white matter fraction and decreased brain volume, gray matter fraction, and cortical gray matter volume at baseline and at 12 months in the depressed group.
The researchers note that study limitations include the unavailability of information on treatment compliance for depression or date of depression onset.
Feng added that because this was an observational study, other missing data included depression status for some patients at year 1 and some MRI metrics.
“So this may have been underpowered to detect some of the results. The power may have been inadequate to detect all changes,” she said.
The investigators write that future research should assess larger sample sizes with longer follow-ups and should use more advanced MRI measures, such as diffusion tensor imaging or functional MRI.
In addition, they will continue examining data from MS-PATHS. “With the newest data cut, we have new patients that we can analyze. So perhaps that can provide sufficient power to detect [more MRI] changes,” Feng said.
Unusual, Intriguing Findings
Commenting on the study for Medscape Medical News, Mark Freedman, MD, professor of neurology at the University of Ottawa and director of the Multiple Sclerosis Research Clinic at the Ottawa Hospital Research Institute, noted that he wasn’t terribly surprised” by the overall findings.
“We’ve known for years that patients who are depressed don’t do as well on our performance methods,” said Freedman, who was not involved with the research.
However, the current investigators “took a huge number of patients in this multicenter study and started using some of the statistical methods we’ve seen in the use of real-world evidence,” he noted.
“So you’re looking at some outcome measures and you have to ask yourself, ‘Why would it influence that?’ and ‘Did it happen by chance or not?’ And you ask why it is that depressed people might actually have more lesions on their MRI, which is something that is unusual,” Freedman said.
“When you start to look at this, even when you’re trying to standardize things for the differences that we know of, there are some stuff that comes out as intriguing. In general, I think those depressed patients did worse on several outcome measures that one would say, ‘That’s somewhat surprising.’ That’s why this group was very careful to not conclude absolutely that depression drives this disease. But it was consistently trending in the direction that it looks like there was more inflammatory activity in these people,” he said.
He echoed the investigators’ note that drug adherence and which depression treatment was used wasn’t controlled for; and he added that depression in the study was not based on receiving a diagnosis of clinical depression but on self-report.
Still, the patients classified as depressed “did worse. They didn’t walk as fast, which was interesting; and we know that cognitive performance is often damped because of poor concentration. But how do you get worse MRIs? This study is raising a question and [the researchers] conclude that it may be that depression might be an independent factor” for that outcome, Freedman said.
“It might be that you could get more out of a particular [MS] medicine if you pay attention to depression; and if that’s the investigators’ conclusion, and I think it is, then I certainly agree with it.”
Freedman noted that, instead of a blanket recommendation that all patients with MS should be screened for depression, he thinks clinicians, especially those at smaller centers, should focus on what’s best for treating all aspects of an individual patient.
“Don’t try to manage them if you’re not going to manage the entire picture. Looking at depression and mood and other things is very important. And if you have the capacity for an official screening, I think it’s wonderful; but not everybody does,” he said.
Feng and Freedman have disclosed no relevant financial relationships. Freedman is currently a member of the Medscape Neurology Advisory Board.
This article appeared on Medscape.com.
COVID-19: Dramatic changes to telepsychiatry rules and regs
In the wake of the coronavirus pandemic,
Under the 1135 emergency waiver, Medicare has expanded telehealth services to include patients across the country – not just in rural areas or under other limited conditions, as was previously the case. In addition, there’s now a waiver to the Ryan Haight Act that allows the prescribing of controlled substances via telemedicine.
Peter Yellowlees, MD, from University of California, Davis, reported that outpatient service at his center was converted to an almost 100% telepsychiatry service from mid- to late March.
He and John Torous, MD, director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, led a free webinar late last month sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA).
During the hour-long event, they answered questions and offered tips on changes in licensure, patient safety, new prescribing rules, and equipment needed.
“Clinicians need to be aware of these changes so they can ensure they are reaching as many people as possible and taking advantage of the reduced barriers to offering safe and effective video visits,” Dr. Torous said in an interview.
‘This is huge’
The new 1135 waiver “basically says CMS will pay for any patient on Medicare who is seen by video by any provider who is correctly licensed in any state in this country,” Dr. Yellowlees told webinar attendees.
“You don’t need to be licensed in the state where the patient is if the patient is on Medicare. This opens up a huge number of patients we can now see on video,” he said. “And you can bill at normal Medicare rates for whatever you normally get for your in-person patients.”
Although this temporary rule only applies to Medicare and not to private insurers, or to patients on Medicaid, “these are really big changes. This is huge,” Dr. Torous said.
Previously, the “originating site” rule stated that, for the most part, clinicians had to be licensed in the state where the patient was located and not where the physician was stationed.
Asked about college students receiving mental health care who were in school in the psychiatrist’s area but are now back home in a state where the clinician doesn’t have a license, Dr. Yellowlees said that scenario could be a bit “tricky.”
“Most of those patients probably aren’t on Medicare. Legally, you [usually] can’t see them on video if they have private insurance or Medicaid. So, hopefully you can give them a 3-month supply of medication and then recommend they see a local provider,” he said.
Still, all states have their own rules, Dr. Yellowlees said. He and Dr. Torous noted that the Federation of State Medical Boards has a “very up-to-date” listing of policies at FSMB.org, all of which are organized by state. In addition, the American Psychiatric Association provides a telepsychiatry toolkit on its website.
Ryan Haight Act and prescribing
Physicians are now permitted to prescribe medication to patients assessed via telemedicine.
For those with substance use disorders, the U.S. Drug Enforcement Administration has announced a new waiver for the Ryan Haight Online Pharmacy Consumer Protection Act.
The waiver states that “practitioners in all areas of the United States may issue prescriptions for all schedule II-V controlled substances” – as long as it’s for a legitimate medical purpose; real-time, two-way interactive communication with patients has been used; and the clinician “is acting in accordance with applicable Federal and State laws.”
“It’s now possible to prescribe all the normal psychiatric drugs but also benzodiazepines, stimulants, and potentially narcotics over telepsychiatry,” even at a first visit via video, Dr. Yellowlees said.
However, he noted at this point the waiver is current for only 60 days. “This isn’t a permanent condition. It could be extended or even shortened at any given time.”
In addition, SAMHSA has relaxed some of its own regulations regarding telehealth and opioid treatment programs. An FAQ section on the organization’s website provides guidance for providing methadone and buprenorphine treatment.
“Some of the previous regulations will probably be put back in place later on, but the new changes are helpful now,” Dr. Yellowlees said.
Simple equipment needed
Regarding equipment, Dr. Yellowlees noted that the most important component is just a laptop, tablet, or smartphone – for the clinician and for the patient.
“You don’t need fancy new technology with a separate camera or microphone,” he said. However, it might be worth investing in a little better system down the line, he added.
Simple platforms that can be used to meet virtually with patients include FaceTime, Google Hangouts, and Skype.
Although some of these (such as FaceTime) are not HIPAA compliant, “that’s okay for now” under the new rules, Dr. Yellowlees said. While the health system/commercial version of Skype is compliant, the normal consumer-downloaded version is not, he noted.
“I would still strongly suggest using HIPAA-compliant video-conferencing programs in the long run,” he added.
Either way, it’s important for various safety practices to be put into place. For example, clinicians should be careful because the consumer version of Skype can show names of patients who were previously spoken with.
A business associate agreement (BAA) is something that HIPAA-compliant video systems will offer and which should be signed. It’s an agreement that “you’ll be, essentially, looking through a tunnel at the persona at the other end, and the company cannot get inside the tunnel and watch you while you’re having your interview,” said Dr. Yellowlees.
“There are multiple videoconferencing systems around that you can use,” he added. “The three major ones are from Zoom, Vidyo, and VSee, but there are probably 40 or 50 more.”
“There are a lot out there, and we’re certainly not endorsing any one of them,” Dr. Torous added.
When evaluating potential programs, Dr. Yellowlees suggested looking at Yelp-style reviews or telemedicine review sites, or talk with colleagues.
“Basically, you want systems that offer high-definition video quality and the ability to ‘lock’ and ‘unlock’ the rooms. And you want it to have an app so mobile devices can use it,” he said.
Phone vs. video
Some patients, especially older ones, may be resistant to the idea of video chats, preferring to talk via telephone instead.
“If you can use video, it’s better to do that if you can, especially when setting up the systems are relatively simple,” Dr. Yellowlees said, adding that it might just be an issue of patients needing help to get started.
However, “for some people, this is a barrier that we have to respect,” Dr. Torous said.
Either way, clinicians should check the American Medical Association’s website for information about coding for both video and phone visits.
Asked whether a clinician needs written consent from patients for conducting telepsychiatry visits, Dr. Yellowlees said it’s important to check state-by-state rules. For example, California allows a verbal consent.
In many cases, “simply jot down a note that consent was given and how” and write down the address where the patient is located at time of visit, such as for their home, he said.
If a patient wants to conduct a telehealth session while in their car, Dr. Yellowlees suggested getting the address of the parking lot. For safety, clinicians also are advised asking for the cell phone number of the patient as well as that of a loved one.
Vital signs
When it comes to checking vital signs, Dr. Yellowlees suggested asking patients to purchase an inexpensive blood pressure (BP) monitor, thermometer, etc, prior to an appointment.
“Ask them to do a BP test on video and show you the readings. For the AIMS [Abnormal Involuntary Movement Scale] test, or to check for tardive dyskinesia, instruct patients to come close to the camera to show movement.”
In addition, most psychiatric rating scales are available online, which patients can fill out before a telehealth visit. The Serious Mental Illness (SMI) Adviser mobile app also includes several of these scales, Dr. Torous noted.
Overall, “there have been dramatic changes in the rules and regulations governing [telepsychiatry] that, for the next 60 days, make it easier to offer telehealth to patients,” Dr. Torous said.
Therefore, all psychiatrists need to “get on board,” as soon as possible, Dr. Yellowlees added.
The webinar was funded in part by a grant from SAMHSA.
A version of this article originally appeared on Medscape.com.
In the wake of the coronavirus pandemic,
Under the 1135 emergency waiver, Medicare has expanded telehealth services to include patients across the country – not just in rural areas or under other limited conditions, as was previously the case. In addition, there’s now a waiver to the Ryan Haight Act that allows the prescribing of controlled substances via telemedicine.
Peter Yellowlees, MD, from University of California, Davis, reported that outpatient service at his center was converted to an almost 100% telepsychiatry service from mid- to late March.
He and John Torous, MD, director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, led a free webinar late last month sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA).
During the hour-long event, they answered questions and offered tips on changes in licensure, patient safety, new prescribing rules, and equipment needed.
“Clinicians need to be aware of these changes so they can ensure they are reaching as many people as possible and taking advantage of the reduced barriers to offering safe and effective video visits,” Dr. Torous said in an interview.
‘This is huge’
The new 1135 waiver “basically says CMS will pay for any patient on Medicare who is seen by video by any provider who is correctly licensed in any state in this country,” Dr. Yellowlees told webinar attendees.
“You don’t need to be licensed in the state where the patient is if the patient is on Medicare. This opens up a huge number of patients we can now see on video,” he said. “And you can bill at normal Medicare rates for whatever you normally get for your in-person patients.”
Although this temporary rule only applies to Medicare and not to private insurers, or to patients on Medicaid, “these are really big changes. This is huge,” Dr. Torous said.
Previously, the “originating site” rule stated that, for the most part, clinicians had to be licensed in the state where the patient was located and not where the physician was stationed.
Asked about college students receiving mental health care who were in school in the psychiatrist’s area but are now back home in a state where the clinician doesn’t have a license, Dr. Yellowlees said that scenario could be a bit “tricky.”
“Most of those patients probably aren’t on Medicare. Legally, you [usually] can’t see them on video if they have private insurance or Medicaid. So, hopefully you can give them a 3-month supply of medication and then recommend they see a local provider,” he said.
Still, all states have their own rules, Dr. Yellowlees said. He and Dr. Torous noted that the Federation of State Medical Boards has a “very up-to-date” listing of policies at FSMB.org, all of which are organized by state. In addition, the American Psychiatric Association provides a telepsychiatry toolkit on its website.
Ryan Haight Act and prescribing
Physicians are now permitted to prescribe medication to patients assessed via telemedicine.
For those with substance use disorders, the U.S. Drug Enforcement Administration has announced a new waiver for the Ryan Haight Online Pharmacy Consumer Protection Act.
The waiver states that “practitioners in all areas of the United States may issue prescriptions for all schedule II-V controlled substances” – as long as it’s for a legitimate medical purpose; real-time, two-way interactive communication with patients has been used; and the clinician “is acting in accordance with applicable Federal and State laws.”
“It’s now possible to prescribe all the normal psychiatric drugs but also benzodiazepines, stimulants, and potentially narcotics over telepsychiatry,” even at a first visit via video, Dr. Yellowlees said.
However, he noted at this point the waiver is current for only 60 days. “This isn’t a permanent condition. It could be extended or even shortened at any given time.”
In addition, SAMHSA has relaxed some of its own regulations regarding telehealth and opioid treatment programs. An FAQ section on the organization’s website provides guidance for providing methadone and buprenorphine treatment.
“Some of the previous regulations will probably be put back in place later on, but the new changes are helpful now,” Dr. Yellowlees said.
Simple equipment needed
Regarding equipment, Dr. Yellowlees noted that the most important component is just a laptop, tablet, or smartphone – for the clinician and for the patient.
“You don’t need fancy new technology with a separate camera or microphone,” he said. However, it might be worth investing in a little better system down the line, he added.
Simple platforms that can be used to meet virtually with patients include FaceTime, Google Hangouts, and Skype.
Although some of these (such as FaceTime) are not HIPAA compliant, “that’s okay for now” under the new rules, Dr. Yellowlees said. While the health system/commercial version of Skype is compliant, the normal consumer-downloaded version is not, he noted.
“I would still strongly suggest using HIPAA-compliant video-conferencing programs in the long run,” he added.
Either way, it’s important for various safety practices to be put into place. For example, clinicians should be careful because the consumer version of Skype can show names of patients who were previously spoken with.
A business associate agreement (BAA) is something that HIPAA-compliant video systems will offer and which should be signed. It’s an agreement that “you’ll be, essentially, looking through a tunnel at the persona at the other end, and the company cannot get inside the tunnel and watch you while you’re having your interview,” said Dr. Yellowlees.
“There are multiple videoconferencing systems around that you can use,” he added. “The three major ones are from Zoom, Vidyo, and VSee, but there are probably 40 or 50 more.”
“There are a lot out there, and we’re certainly not endorsing any one of them,” Dr. Torous added.
When evaluating potential programs, Dr. Yellowlees suggested looking at Yelp-style reviews or telemedicine review sites, or talk with colleagues.
“Basically, you want systems that offer high-definition video quality and the ability to ‘lock’ and ‘unlock’ the rooms. And you want it to have an app so mobile devices can use it,” he said.
Phone vs. video
Some patients, especially older ones, may be resistant to the idea of video chats, preferring to talk via telephone instead.
“If you can use video, it’s better to do that if you can, especially when setting up the systems are relatively simple,” Dr. Yellowlees said, adding that it might just be an issue of patients needing help to get started.
However, “for some people, this is a barrier that we have to respect,” Dr. Torous said.
Either way, clinicians should check the American Medical Association’s website for information about coding for both video and phone visits.
Asked whether a clinician needs written consent from patients for conducting telepsychiatry visits, Dr. Yellowlees said it’s important to check state-by-state rules. For example, California allows a verbal consent.
In many cases, “simply jot down a note that consent was given and how” and write down the address where the patient is located at time of visit, such as for their home, he said.
If a patient wants to conduct a telehealth session while in their car, Dr. Yellowlees suggested getting the address of the parking lot. For safety, clinicians also are advised asking for the cell phone number of the patient as well as that of a loved one.
Vital signs
When it comes to checking vital signs, Dr. Yellowlees suggested asking patients to purchase an inexpensive blood pressure (BP) monitor, thermometer, etc, prior to an appointment.
“Ask them to do a BP test on video and show you the readings. For the AIMS [Abnormal Involuntary Movement Scale] test, or to check for tardive dyskinesia, instruct patients to come close to the camera to show movement.”
In addition, most psychiatric rating scales are available online, which patients can fill out before a telehealth visit. The Serious Mental Illness (SMI) Adviser mobile app also includes several of these scales, Dr. Torous noted.
Overall, “there have been dramatic changes in the rules and regulations governing [telepsychiatry] that, for the next 60 days, make it easier to offer telehealth to patients,” Dr. Torous said.
Therefore, all psychiatrists need to “get on board,” as soon as possible, Dr. Yellowlees added.
The webinar was funded in part by a grant from SAMHSA.
A version of this article originally appeared on Medscape.com.
In the wake of the coronavirus pandemic,
Under the 1135 emergency waiver, Medicare has expanded telehealth services to include patients across the country – not just in rural areas or under other limited conditions, as was previously the case. In addition, there’s now a waiver to the Ryan Haight Act that allows the prescribing of controlled substances via telemedicine.
Peter Yellowlees, MD, from University of California, Davis, reported that outpatient service at his center was converted to an almost 100% telepsychiatry service from mid- to late March.
He and John Torous, MD, director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, led a free webinar late last month sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA).
During the hour-long event, they answered questions and offered tips on changes in licensure, patient safety, new prescribing rules, and equipment needed.
“Clinicians need to be aware of these changes so they can ensure they are reaching as many people as possible and taking advantage of the reduced barriers to offering safe and effective video visits,” Dr. Torous said in an interview.
‘This is huge’
The new 1135 waiver “basically says CMS will pay for any patient on Medicare who is seen by video by any provider who is correctly licensed in any state in this country,” Dr. Yellowlees told webinar attendees.
“You don’t need to be licensed in the state where the patient is if the patient is on Medicare. This opens up a huge number of patients we can now see on video,” he said. “And you can bill at normal Medicare rates for whatever you normally get for your in-person patients.”
Although this temporary rule only applies to Medicare and not to private insurers, or to patients on Medicaid, “these are really big changes. This is huge,” Dr. Torous said.
Previously, the “originating site” rule stated that, for the most part, clinicians had to be licensed in the state where the patient was located and not where the physician was stationed.
Asked about college students receiving mental health care who were in school in the psychiatrist’s area but are now back home in a state where the clinician doesn’t have a license, Dr. Yellowlees said that scenario could be a bit “tricky.”
“Most of those patients probably aren’t on Medicare. Legally, you [usually] can’t see them on video if they have private insurance or Medicaid. So, hopefully you can give them a 3-month supply of medication and then recommend they see a local provider,” he said.
Still, all states have their own rules, Dr. Yellowlees said. He and Dr. Torous noted that the Federation of State Medical Boards has a “very up-to-date” listing of policies at FSMB.org, all of which are organized by state. In addition, the American Psychiatric Association provides a telepsychiatry toolkit on its website.
Ryan Haight Act and prescribing
Physicians are now permitted to prescribe medication to patients assessed via telemedicine.
For those with substance use disorders, the U.S. Drug Enforcement Administration has announced a new waiver for the Ryan Haight Online Pharmacy Consumer Protection Act.
The waiver states that “practitioners in all areas of the United States may issue prescriptions for all schedule II-V controlled substances” – as long as it’s for a legitimate medical purpose; real-time, two-way interactive communication with patients has been used; and the clinician “is acting in accordance with applicable Federal and State laws.”
“It’s now possible to prescribe all the normal psychiatric drugs but also benzodiazepines, stimulants, and potentially narcotics over telepsychiatry,” even at a first visit via video, Dr. Yellowlees said.
However, he noted at this point the waiver is current for only 60 days. “This isn’t a permanent condition. It could be extended or even shortened at any given time.”
In addition, SAMHSA has relaxed some of its own regulations regarding telehealth and opioid treatment programs. An FAQ section on the organization’s website provides guidance for providing methadone and buprenorphine treatment.
“Some of the previous regulations will probably be put back in place later on, but the new changes are helpful now,” Dr. Yellowlees said.
Simple equipment needed
Regarding equipment, Dr. Yellowlees noted that the most important component is just a laptop, tablet, or smartphone – for the clinician and for the patient.
“You don’t need fancy new technology with a separate camera or microphone,” he said. However, it might be worth investing in a little better system down the line, he added.
Simple platforms that can be used to meet virtually with patients include FaceTime, Google Hangouts, and Skype.
Although some of these (such as FaceTime) are not HIPAA compliant, “that’s okay for now” under the new rules, Dr. Yellowlees said. While the health system/commercial version of Skype is compliant, the normal consumer-downloaded version is not, he noted.
“I would still strongly suggest using HIPAA-compliant video-conferencing programs in the long run,” he added.
Either way, it’s important for various safety practices to be put into place. For example, clinicians should be careful because the consumer version of Skype can show names of patients who were previously spoken with.
A business associate agreement (BAA) is something that HIPAA-compliant video systems will offer and which should be signed. It’s an agreement that “you’ll be, essentially, looking through a tunnel at the persona at the other end, and the company cannot get inside the tunnel and watch you while you’re having your interview,” said Dr. Yellowlees.
“There are multiple videoconferencing systems around that you can use,” he added. “The three major ones are from Zoom, Vidyo, and VSee, but there are probably 40 or 50 more.”
“There are a lot out there, and we’re certainly not endorsing any one of them,” Dr. Torous added.
When evaluating potential programs, Dr. Yellowlees suggested looking at Yelp-style reviews or telemedicine review sites, or talk with colleagues.
“Basically, you want systems that offer high-definition video quality and the ability to ‘lock’ and ‘unlock’ the rooms. And you want it to have an app so mobile devices can use it,” he said.
Phone vs. video
Some patients, especially older ones, may be resistant to the idea of video chats, preferring to talk via telephone instead.
“If you can use video, it’s better to do that if you can, especially when setting up the systems are relatively simple,” Dr. Yellowlees said, adding that it might just be an issue of patients needing help to get started.
However, “for some people, this is a barrier that we have to respect,” Dr. Torous said.
Either way, clinicians should check the American Medical Association’s website for information about coding for both video and phone visits.
Asked whether a clinician needs written consent from patients for conducting telepsychiatry visits, Dr. Yellowlees said it’s important to check state-by-state rules. For example, California allows a verbal consent.
In many cases, “simply jot down a note that consent was given and how” and write down the address where the patient is located at time of visit, such as for their home, he said.
If a patient wants to conduct a telehealth session while in their car, Dr. Yellowlees suggested getting the address of the parking lot. For safety, clinicians also are advised asking for the cell phone number of the patient as well as that of a loved one.
Vital signs
When it comes to checking vital signs, Dr. Yellowlees suggested asking patients to purchase an inexpensive blood pressure (BP) monitor, thermometer, etc, prior to an appointment.
“Ask them to do a BP test on video and show you the readings. For the AIMS [Abnormal Involuntary Movement Scale] test, or to check for tardive dyskinesia, instruct patients to come close to the camera to show movement.”
In addition, most psychiatric rating scales are available online, which patients can fill out before a telehealth visit. The Serious Mental Illness (SMI) Adviser mobile app also includes several of these scales, Dr. Torous noted.
Overall, “there have been dramatic changes in the rules and regulations governing [telepsychiatry] that, for the next 60 days, make it easier to offer telehealth to patients,” Dr. Torous said.
Therefore, all psychiatrists need to “get on board,” as soon as possible, Dr. Yellowlees added.
The webinar was funded in part by a grant from SAMHSA.
A version of this article originally appeared on Medscape.com.
Another round of research shows ketamine may help alcoholism
More research suggests that a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
In a pilot study of 40 participants, those who were randomly assigned to receive intravenous ketamine plus outpatient motivational enhancement therapy (MET) showed greater abstinence rates, longer time to relapse, and fewer heavy drinking days than did those who received MET plus midazolam.
The findings support a U.K. study published late last year showing that a single dose of intravenous ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone (Nat Commun. 2019 Nov 26;10[1]:5187).
of the New York State Psychiatric Institute, Columbia University, New York, said in an interview.
“It’s an important area of research to understand in order to make behavioral treatments more effective, and ketamine appears to have the properties to address those vulnerabilities,” Dr. Dakwar said.
The study was published in the American Journal of Psychiatry (2019 Dec 2. doi: 10.1176/appi.ajp.2019.19070684).
Real-world approach
Pathologic alcohol use is responsible for an estimated 3.8% of all deaths globally, yet current interventions for alcohol use disorder have limited efficacy, the researchers noted.
New treatments with innovative mechanisms would be valuable, they added.
Ketamine is a high-affinity N-methyl-d-aspartate receptor (NMDAR) antagonist.
Previously, research offered “promising results” with the use of ketamine for cocaine use disorder, including increased motivation to quit and decreased craving, Dr. Dakwar noted.
“Those results led us to think about how ketamine might be helpful for other substance use disorders, especially given the overlap in clinical vulnerabilities and epidemiology,” he said.
The study from the U.K. researchers was conducted in 90 patients with harmful drinking behavior but who had not been diagnosed with alcohol use disorder.
Dr. Dakwar noted that this was “a nontreatment study. None of the people there had alcohol use disorder; they were heavy drinkers. Also, the effects there were fairly modest.
“My interest was how to integrate ketamine into a clinical, real-world framework that could be helpful for people,” he added.
The study included 40 participants (52.5% women; 70.3% white; mean age, 53 years) with alcohol dependence whose average consumption was five drinks per day.
All entered a 5-week outpatient program of MET, which involved engaging in strategies to promote motivation and self-directed change.
During the program’s second week, the participants were randomly assigned to received a 52-minute IV infusion of ketamine 0.71 mg/kg (n = 17) or the benzodiazepine midazolam 0.025 mg/kg (n = 23).
This ketamine dose was selected “because it was the highest dose tolerated by participants in preliminary studies,” the researchers reported.
“Midazolam was chosen as the active control because it alters consciousness without any known persistent ... effect on alcohol dependence,” they added.
The “timeline follow back method” was used to assess alcohol use after treatment. Abstinence was confirmed by measuring urine ethyl glucuronide levels with urine toxicology tests.
Other measures included use of a visual analogue scale, the Clinical Institute Withdrawal Assessment, and the modified Perceived Stress Scale.
Primary outcome met
Results showed that 47.1% of the ketamine group and 59.1% of the midazolam group used alcohol during the 21 days after treatment infusion; 17.6% and 40.9%, respectively, had a heavy drinking day.
For the primary outcome measure of alcohol abstinence, the “quadratic effect of time was significant” (P = .004), as was time-by-treatment interaction (P less than .001).
Although the model-estimated proportions of alcohol abstinence remained stable for the ketamine group for 21 days post infusion, the proportions decreased significantly for the control group.
The odds of having a heavy drinking day did not change significantly after treatment for the ketamine group (odds ratio, 0.98; P = .74) but increased significantly with each postinfusion day for the midazolam group (OR, 1.19; P less than .001).
For the ketamine group, time to relapse was also significantly longer (P = .04).
No significant differences were found between the groups in rates of withdrawal, craving, or stress sensitivity.
A new direction?
The most common adverse events after treatment were sedation, seen in 12 members of the midazolam group and in 8 members of the ketamine group, and headache, seen in four and six members, respectively.
Although two ketamine-group members experienced mild agitation for up to 1 hour post infusion, no incidents of persistent psychoactive effects were reported in either group.
No participants who received ketamine dropped out during the study period; among those who received midazolam, six dropped out.
“These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder,” the investigators wrote.
However, a larger patient population will be needed in future research in order to “replicate these promising results,” they added.
Dr. Dakwar noted that the time to first drink after treatment was comparable between the groups.
“But what was different in the ketamine group was that they didn’t continue drinking after that first drink. They didn’t initiate heavy drinking, they didn’t relapse, they were able to bounce back and stay with the program,” he said.
“It was surprising but still consistent with the central hypothesis that ketamine provides this opportunity for setting the foundation for the requisite commitment so that, once things become difficult, they’re still able to maintain recovery,” Dr. Dakwar said.
‘Provocative findings’
In an accompanying editorial, Sanjay J. Mathew, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine in Houston, and Rebecca B. Price, PhD, of the department of psychiatry at the University of Pittsburgh, noted that ketamine’s effects on abstinence “were robust” in this trial.
“It is also noteworthy that, in spite of recruiting from a population of patients with active and significant substance use history (a group that has routinely been excluded from ketamine trials in depression), no participant showed evidence of new drug-seeking behaviors,” Dr. Mathew and Dr. Price wrote.
“Overall, these findings are provocative and hypothesis generating but certainly not definitive because of the small sample size,” they add.
Other limitations cited include the short follow-up period and the fact that only half of the participants were available for a 6-month follow-up telephone interview. In addition, generalizability was limited because the population did not have additional medical or psychiatric illnesses or additional substance use disorders, the editorialists wrote.
Because of the limitations, the investigators “are appropriately circumspect about the immediate clinical implications of this small pilot study.”
Still, the results “affirm the potential of rational combinatorial approaches for a vexing medical and public health problem,” Dr. Mathew and Dr. Price concluded.
The study was funded by grants from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the New York State Psychiatric Institute. The study authors and Dr. Price reported no relevant financial relationships. Dr Mathew reported serving as a consultant to or having received research support from several companies, including Alkermes, Allergan, Clexio Biosciences, and Janssen. The original article includes a full list of his disclosures.
A version of this article first appeared on Medscape.com.
More research suggests that a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
In a pilot study of 40 participants, those who were randomly assigned to receive intravenous ketamine plus outpatient motivational enhancement therapy (MET) showed greater abstinence rates, longer time to relapse, and fewer heavy drinking days than did those who received MET plus midazolam.
The findings support a U.K. study published late last year showing that a single dose of intravenous ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone (Nat Commun. 2019 Nov 26;10[1]:5187).
of the New York State Psychiatric Institute, Columbia University, New York, said in an interview.
“It’s an important area of research to understand in order to make behavioral treatments more effective, and ketamine appears to have the properties to address those vulnerabilities,” Dr. Dakwar said.
The study was published in the American Journal of Psychiatry (2019 Dec 2. doi: 10.1176/appi.ajp.2019.19070684).
Real-world approach
Pathologic alcohol use is responsible for an estimated 3.8% of all deaths globally, yet current interventions for alcohol use disorder have limited efficacy, the researchers noted.
New treatments with innovative mechanisms would be valuable, they added.
Ketamine is a high-affinity N-methyl-d-aspartate receptor (NMDAR) antagonist.
Previously, research offered “promising results” with the use of ketamine for cocaine use disorder, including increased motivation to quit and decreased craving, Dr. Dakwar noted.
“Those results led us to think about how ketamine might be helpful for other substance use disorders, especially given the overlap in clinical vulnerabilities and epidemiology,” he said.
The study from the U.K. researchers was conducted in 90 patients with harmful drinking behavior but who had not been diagnosed with alcohol use disorder.
Dr. Dakwar noted that this was “a nontreatment study. None of the people there had alcohol use disorder; they were heavy drinkers. Also, the effects there were fairly modest.
“My interest was how to integrate ketamine into a clinical, real-world framework that could be helpful for people,” he added.
The study included 40 participants (52.5% women; 70.3% white; mean age, 53 years) with alcohol dependence whose average consumption was five drinks per day.
All entered a 5-week outpatient program of MET, which involved engaging in strategies to promote motivation and self-directed change.
During the program’s second week, the participants were randomly assigned to received a 52-minute IV infusion of ketamine 0.71 mg/kg (n = 17) or the benzodiazepine midazolam 0.025 mg/kg (n = 23).
This ketamine dose was selected “because it was the highest dose tolerated by participants in preliminary studies,” the researchers reported.
“Midazolam was chosen as the active control because it alters consciousness without any known persistent ... effect on alcohol dependence,” they added.
The “timeline follow back method” was used to assess alcohol use after treatment. Abstinence was confirmed by measuring urine ethyl glucuronide levels with urine toxicology tests.
Other measures included use of a visual analogue scale, the Clinical Institute Withdrawal Assessment, and the modified Perceived Stress Scale.
Primary outcome met
Results showed that 47.1% of the ketamine group and 59.1% of the midazolam group used alcohol during the 21 days after treatment infusion; 17.6% and 40.9%, respectively, had a heavy drinking day.
For the primary outcome measure of alcohol abstinence, the “quadratic effect of time was significant” (P = .004), as was time-by-treatment interaction (P less than .001).
Although the model-estimated proportions of alcohol abstinence remained stable for the ketamine group for 21 days post infusion, the proportions decreased significantly for the control group.
The odds of having a heavy drinking day did not change significantly after treatment for the ketamine group (odds ratio, 0.98; P = .74) but increased significantly with each postinfusion day for the midazolam group (OR, 1.19; P less than .001).
For the ketamine group, time to relapse was also significantly longer (P = .04).
No significant differences were found between the groups in rates of withdrawal, craving, or stress sensitivity.
A new direction?
The most common adverse events after treatment were sedation, seen in 12 members of the midazolam group and in 8 members of the ketamine group, and headache, seen in four and six members, respectively.
Although two ketamine-group members experienced mild agitation for up to 1 hour post infusion, no incidents of persistent psychoactive effects were reported in either group.
No participants who received ketamine dropped out during the study period; among those who received midazolam, six dropped out.
“These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder,” the investigators wrote.
However, a larger patient population will be needed in future research in order to “replicate these promising results,” they added.
Dr. Dakwar noted that the time to first drink after treatment was comparable between the groups.
“But what was different in the ketamine group was that they didn’t continue drinking after that first drink. They didn’t initiate heavy drinking, they didn’t relapse, they were able to bounce back and stay with the program,” he said.
“It was surprising but still consistent with the central hypothesis that ketamine provides this opportunity for setting the foundation for the requisite commitment so that, once things become difficult, they’re still able to maintain recovery,” Dr. Dakwar said.
‘Provocative findings’
In an accompanying editorial, Sanjay J. Mathew, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine in Houston, and Rebecca B. Price, PhD, of the department of psychiatry at the University of Pittsburgh, noted that ketamine’s effects on abstinence “were robust” in this trial.
“It is also noteworthy that, in spite of recruiting from a population of patients with active and significant substance use history (a group that has routinely been excluded from ketamine trials in depression), no participant showed evidence of new drug-seeking behaviors,” Dr. Mathew and Dr. Price wrote.
“Overall, these findings are provocative and hypothesis generating but certainly not definitive because of the small sample size,” they add.
Other limitations cited include the short follow-up period and the fact that only half of the participants were available for a 6-month follow-up telephone interview. In addition, generalizability was limited because the population did not have additional medical or psychiatric illnesses or additional substance use disorders, the editorialists wrote.
Because of the limitations, the investigators “are appropriately circumspect about the immediate clinical implications of this small pilot study.”
Still, the results “affirm the potential of rational combinatorial approaches for a vexing medical and public health problem,” Dr. Mathew and Dr. Price concluded.
The study was funded by grants from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the New York State Psychiatric Institute. The study authors and Dr. Price reported no relevant financial relationships. Dr Mathew reported serving as a consultant to or having received research support from several companies, including Alkermes, Allergan, Clexio Biosciences, and Janssen. The original article includes a full list of his disclosures.
A version of this article first appeared on Medscape.com.
More research suggests that a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
In a pilot study of 40 participants, those who were randomly assigned to receive intravenous ketamine plus outpatient motivational enhancement therapy (MET) showed greater abstinence rates, longer time to relapse, and fewer heavy drinking days than did those who received MET plus midazolam.
The findings support a U.K. study published late last year showing that a single dose of intravenous ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone (Nat Commun. 2019 Nov 26;10[1]:5187).
of the New York State Psychiatric Institute, Columbia University, New York, said in an interview.
“It’s an important area of research to understand in order to make behavioral treatments more effective, and ketamine appears to have the properties to address those vulnerabilities,” Dr. Dakwar said.
The study was published in the American Journal of Psychiatry (2019 Dec 2. doi: 10.1176/appi.ajp.2019.19070684).
Real-world approach
Pathologic alcohol use is responsible for an estimated 3.8% of all deaths globally, yet current interventions for alcohol use disorder have limited efficacy, the researchers noted.
New treatments with innovative mechanisms would be valuable, they added.
Ketamine is a high-affinity N-methyl-d-aspartate receptor (NMDAR) antagonist.
Previously, research offered “promising results” with the use of ketamine for cocaine use disorder, including increased motivation to quit and decreased craving, Dr. Dakwar noted.
“Those results led us to think about how ketamine might be helpful for other substance use disorders, especially given the overlap in clinical vulnerabilities and epidemiology,” he said.
The study from the U.K. researchers was conducted in 90 patients with harmful drinking behavior but who had not been diagnosed with alcohol use disorder.
Dr. Dakwar noted that this was “a nontreatment study. None of the people there had alcohol use disorder; they were heavy drinkers. Also, the effects there were fairly modest.
“My interest was how to integrate ketamine into a clinical, real-world framework that could be helpful for people,” he added.
The study included 40 participants (52.5% women; 70.3% white; mean age, 53 years) with alcohol dependence whose average consumption was five drinks per day.
All entered a 5-week outpatient program of MET, which involved engaging in strategies to promote motivation and self-directed change.
During the program’s second week, the participants were randomly assigned to received a 52-minute IV infusion of ketamine 0.71 mg/kg (n = 17) or the benzodiazepine midazolam 0.025 mg/kg (n = 23).
This ketamine dose was selected “because it was the highest dose tolerated by participants in preliminary studies,” the researchers reported.
“Midazolam was chosen as the active control because it alters consciousness without any known persistent ... effect on alcohol dependence,” they added.
The “timeline follow back method” was used to assess alcohol use after treatment. Abstinence was confirmed by measuring urine ethyl glucuronide levels with urine toxicology tests.
Other measures included use of a visual analogue scale, the Clinical Institute Withdrawal Assessment, and the modified Perceived Stress Scale.
Primary outcome met
Results showed that 47.1% of the ketamine group and 59.1% of the midazolam group used alcohol during the 21 days after treatment infusion; 17.6% and 40.9%, respectively, had a heavy drinking day.
For the primary outcome measure of alcohol abstinence, the “quadratic effect of time was significant” (P = .004), as was time-by-treatment interaction (P less than .001).
Although the model-estimated proportions of alcohol abstinence remained stable for the ketamine group for 21 days post infusion, the proportions decreased significantly for the control group.
The odds of having a heavy drinking day did not change significantly after treatment for the ketamine group (odds ratio, 0.98; P = .74) but increased significantly with each postinfusion day for the midazolam group (OR, 1.19; P less than .001).
For the ketamine group, time to relapse was also significantly longer (P = .04).
No significant differences were found between the groups in rates of withdrawal, craving, or stress sensitivity.
A new direction?
The most common adverse events after treatment were sedation, seen in 12 members of the midazolam group and in 8 members of the ketamine group, and headache, seen in four and six members, respectively.
Although two ketamine-group members experienced mild agitation for up to 1 hour post infusion, no incidents of persistent psychoactive effects were reported in either group.
No participants who received ketamine dropped out during the study period; among those who received midazolam, six dropped out.
“These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder,” the investigators wrote.
However, a larger patient population will be needed in future research in order to “replicate these promising results,” they added.
Dr. Dakwar noted that the time to first drink after treatment was comparable between the groups.
“But what was different in the ketamine group was that they didn’t continue drinking after that first drink. They didn’t initiate heavy drinking, they didn’t relapse, they were able to bounce back and stay with the program,” he said.
“It was surprising but still consistent with the central hypothesis that ketamine provides this opportunity for setting the foundation for the requisite commitment so that, once things become difficult, they’re still able to maintain recovery,” Dr. Dakwar said.
‘Provocative findings’
In an accompanying editorial, Sanjay J. Mathew, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine in Houston, and Rebecca B. Price, PhD, of the department of psychiatry at the University of Pittsburgh, noted that ketamine’s effects on abstinence “were robust” in this trial.
“It is also noteworthy that, in spite of recruiting from a population of patients with active and significant substance use history (a group that has routinely been excluded from ketamine trials in depression), no participant showed evidence of new drug-seeking behaviors,” Dr. Mathew and Dr. Price wrote.
“Overall, these findings are provocative and hypothesis generating but certainly not definitive because of the small sample size,” they add.
Other limitations cited include the short follow-up period and the fact that only half of the participants were available for a 6-month follow-up telephone interview. In addition, generalizability was limited because the population did not have additional medical or psychiatric illnesses or additional substance use disorders, the editorialists wrote.
Because of the limitations, the investigators “are appropriately circumspect about the immediate clinical implications of this small pilot study.”
Still, the results “affirm the potential of rational combinatorial approaches for a vexing medical and public health problem,” Dr. Mathew and Dr. Price concluded.
The study was funded by grants from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the New York State Psychiatric Institute. The study authors and Dr. Price reported no relevant financial relationships. Dr Mathew reported serving as a consultant to or having received research support from several companies, including Alkermes, Allergan, Clexio Biosciences, and Janssen. The original article includes a full list of his disclosures.
A version of this article first appeared on Medscape.com.
Seminal, highly anticipated Alzheimer’s trial falters
DIAN-TU top-line results negative
Top-line results from the seminal phase 2/3 Dominantly Inherited Alzheimer’s Network–Trials Unit (DIAN-TU) study show that the novel drugs gantenerumab (Roche) and solanezumab (Lilly) did not meet the primary endpoint in patients with early-stage, dominantly inherited Alzheimer’s disease (AD), investigators have announced.
In the international trial, which included almost 200 participants, the two experimental agents were evaluated separately. However, initial analyses showed that neither significantly slowed cognitive decline, the primary outcome measure, nor memory loss.
Still, the researchers noted that they will continue exploring data from DIAN-TU’s cognitive and clinical outcomes and are awaiting analyses of various biomarkers.
“Although the drugs we evaluated were not successful, the trial will move us forward in understanding Alzheimer’s,” principal investigator Randall J. Bateman, MD, of Washington University, St. Louis, said in a news release.
Funders for the trial included the National Institute on Aging and the Alzheimer’s Association.
“While the top-line data fell short, the Alzheimer’s Association looks forward to a more complete report at upcoming scientific conferences. We learn from every trial,” Maria Carrillo, PhD, chief scientific officer at the Alzheimer’s Association, noted in the organization’s own release.
Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, agreed with Dr. Carrillo that, although the results were disappointing, the data will be beneficial for the field.
“It’s always a difficult day when we get news like this,” Dr. Edelmayer said in an interview. However, “this research is going to absolutely provide valuable information once we can really pick through all of the data.”
Rare condition
Dominantly inherited AD, also known as familial AD or autosomal dominant AD, is rare but can affect memory and cognitive skills in individuals as young as age 30. It is caused by mutations on chromosomes 21, 14, and/or 1 that play a part in the breakdown of amyloid proteins and formation of amyloid plaques.
Both gantenerumab and solanezumab were created to target and neutralize amyloid-beta, albeit through different mechanisms. Both are also being assessed in other trials as treatment for more common forms of AD.
As reported by Medscape Medical News, results of the phase 3 EXPEDITION3 trial of solanezumab in patients with mild AD were negative, as were two other phase 3 trials. The drug is now being evaluated in the ongoing solanezumab Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study.
Although the phase 3 SCARLET ROAD trial of gantenerumab for mild AD was stopped early for futility in 2014, it was continued as an open-label extension at the high dose for 2 years. During that period, follow-up analyses showed a dramatic decline in amyloid-beta deposition in the participants – leading to the launch of the phase 3 GRADUATE 1 and GRADUATE 2 trials.
Starting in 2012, DIAN-TU was conducted at 24 sites in the United States, the United Kingdom, Canada, Europe, and Australia. It followed 194 adult patients for up to 7 years (average duration, 5 years). Its original estimated completion date was December 2020, as stated on clinicaltrials.gov.
All participants had family members with a genetic mutation that causes early-onset Alzheimer’s disease. They already had very mild symptoms of cognitive decline and memory loss at the start of the trial or were expected to develop symptoms within 15 years of enrollment.
“People who inherit the mutation are all but guaranteed to develop symptoms at about the same age their parents did,” the release noted.
“While devastating for families, such mutations allow researchers to identify people in the early stages of the disease before their behavior and memory begin to change,” it added.
The Alzheimer’s Association noted in its release that a child of a parent with the mutation has a 50/50 chance of inheriting the disease. “This form affects less than 1% of the individuals living with Alzheimer’s disease today,” Dr. Edelmayer noted.
Detailed data coming soon
Trial participants were randomly assigned to receive either solanezumab, gantenerumab, or matching placebo. To act as a comparator group, family members without the AD mutation were also included.
The primary measure was change from baseline in the DIAN-TU cognitive composite score. Secondary measures included changes on the Mini-Mental State Examination, the Functional Assessment Scale, the Neuropsychiatric Inventory Questionnaire, the 12-item International Shopping List Test, the Memory Complaint Questionnaire, and the Wechsler Memory Scale Logical Memory/Paragraph Memory test.
The researchers also conducted imaging scans and collected samples of blood and cerebrospinal fluid.
Along with announcing the negative top-line results for the trial, the investigators noted that “a more detailed analysis of the trial’s data” will be presented at the Advances in Alzheimer’s and Parkinson’s Therapies in Vienna on April 2, 2020, and at the Alzheimer’s Association International Conference in Amsterdam in July.
The researchers will continue to explore all data gathered – but already new insights have been discovered into the development and progression of AD, Dr. Bateman noted.
Included among these discoveries is that brain changes that occur as the disease progresses are similar among those with the inherited, early-onset form of AD and the late-onset form.
“The trial’s innovative design ... will make advances for future Alzheimer’s trials. Ongoing and continued research and trials will bring us closer to our goal to stop Alzheimer’s,” Dr. Bateman said. “We will continue until we are successful.”
“These results reflect the difficult nature of treating [AD] and the great need for continued research,” said Daniel Skovronsky, MD, PhD, chief scientific officer and president of Lilly Research Labs.
“If we have learned one thing after more than 30 years of Alzheimer’s research, it is that even negative results propel the science forward,” he added.
Lilly noted in a statement that the DIAN-TU top-line results will not affect its ongoing A4 study of solanezumab. Roche noted in its own statement that the findings also will not affect the company’s ongoing GRADUATE studies of gantenerumab.
“The work doesn’t stop here”
Richard J. Hodes, MD, director of the National Institute on Aging, said that DIAN-TU will advance the field’s knowledge about a complex disease.
“We look forward to learning more through the published, peer-reviewed data, which will provide a broad range of scientists with crucial information and guidance for future research,” he said.
Howard Fillit, MD, founding executive director and chief science officer at the Alzheimer’s Drug Discovery Foundation (ADDF), agreed.
“While we are disappointed that patients in this study did not see a benefit, we need to keep in mind that Alzheimer’s is a complicated disease due to complex, multifactorial causes,” he said in a statement.
“ADDF has long supported a broader approach that moves past targeting beta-amyloid and advances a diverse pipeline of drugs addressing multiple targets” in AD, Dr. Fillit added. “We need multiple ‘shots on goals’ to discover effective drugs.”
Dr. Edelmayer said the results emphasize that “this story isn’t yet completely told” and that there is still a lot to learn from the data, especially regarding the biomarkers that were tested.
“With that information, we will gain valuable insight into the outcomes that have been released but will also probably better understand where we should be putting our energies and focus moving forward,” she said.
Going forward, “we will continue this fight until we have an effective treatment for all individuals living with Alzheimer’s, whether it’s dominantly inherited [AD] or the more common version, which is the late-onset or sporadic form of the disease,” said Dr. Edelmayer.
“We have to stay optimistic. The work doesn’t stop here.”
The trial was funded by Eli Lilly, Roche, the Alzheimer’s Association, the National Institute on Aging, the GHR Foundation, and FBRI.
This article first appeared on Medscape.com.
DIAN-TU top-line results negative
DIAN-TU top-line results negative
Top-line results from the seminal phase 2/3 Dominantly Inherited Alzheimer’s Network–Trials Unit (DIAN-TU) study show that the novel drugs gantenerumab (Roche) and solanezumab (Lilly) did not meet the primary endpoint in patients with early-stage, dominantly inherited Alzheimer’s disease (AD), investigators have announced.
In the international trial, which included almost 200 participants, the two experimental agents were evaluated separately. However, initial analyses showed that neither significantly slowed cognitive decline, the primary outcome measure, nor memory loss.
Still, the researchers noted that they will continue exploring data from DIAN-TU’s cognitive and clinical outcomes and are awaiting analyses of various biomarkers.
“Although the drugs we evaluated were not successful, the trial will move us forward in understanding Alzheimer’s,” principal investigator Randall J. Bateman, MD, of Washington University, St. Louis, said in a news release.
Funders for the trial included the National Institute on Aging and the Alzheimer’s Association.
“While the top-line data fell short, the Alzheimer’s Association looks forward to a more complete report at upcoming scientific conferences. We learn from every trial,” Maria Carrillo, PhD, chief scientific officer at the Alzheimer’s Association, noted in the organization’s own release.
Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, agreed with Dr. Carrillo that, although the results were disappointing, the data will be beneficial for the field.
“It’s always a difficult day when we get news like this,” Dr. Edelmayer said in an interview. However, “this research is going to absolutely provide valuable information once we can really pick through all of the data.”
Rare condition
Dominantly inherited AD, also known as familial AD or autosomal dominant AD, is rare but can affect memory and cognitive skills in individuals as young as age 30. It is caused by mutations on chromosomes 21, 14, and/or 1 that play a part in the breakdown of amyloid proteins and formation of amyloid plaques.
Both gantenerumab and solanezumab were created to target and neutralize amyloid-beta, albeit through different mechanisms. Both are also being assessed in other trials as treatment for more common forms of AD.
As reported by Medscape Medical News, results of the phase 3 EXPEDITION3 trial of solanezumab in patients with mild AD were negative, as were two other phase 3 trials. The drug is now being evaluated in the ongoing solanezumab Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study.
Although the phase 3 SCARLET ROAD trial of gantenerumab for mild AD was stopped early for futility in 2014, it was continued as an open-label extension at the high dose for 2 years. During that period, follow-up analyses showed a dramatic decline in amyloid-beta deposition in the participants – leading to the launch of the phase 3 GRADUATE 1 and GRADUATE 2 trials.
Starting in 2012, DIAN-TU was conducted at 24 sites in the United States, the United Kingdom, Canada, Europe, and Australia. It followed 194 adult patients for up to 7 years (average duration, 5 years). Its original estimated completion date was December 2020, as stated on clinicaltrials.gov.
All participants had family members with a genetic mutation that causes early-onset Alzheimer’s disease. They already had very mild symptoms of cognitive decline and memory loss at the start of the trial or were expected to develop symptoms within 15 years of enrollment.
“People who inherit the mutation are all but guaranteed to develop symptoms at about the same age their parents did,” the release noted.
“While devastating for families, such mutations allow researchers to identify people in the early stages of the disease before their behavior and memory begin to change,” it added.
The Alzheimer’s Association noted in its release that a child of a parent with the mutation has a 50/50 chance of inheriting the disease. “This form affects less than 1% of the individuals living with Alzheimer’s disease today,” Dr. Edelmayer noted.
Detailed data coming soon
Trial participants were randomly assigned to receive either solanezumab, gantenerumab, or matching placebo. To act as a comparator group, family members without the AD mutation were also included.
The primary measure was change from baseline in the DIAN-TU cognitive composite score. Secondary measures included changes on the Mini-Mental State Examination, the Functional Assessment Scale, the Neuropsychiatric Inventory Questionnaire, the 12-item International Shopping List Test, the Memory Complaint Questionnaire, and the Wechsler Memory Scale Logical Memory/Paragraph Memory test.
The researchers also conducted imaging scans and collected samples of blood and cerebrospinal fluid.
Along with announcing the negative top-line results for the trial, the investigators noted that “a more detailed analysis of the trial’s data” will be presented at the Advances in Alzheimer’s and Parkinson’s Therapies in Vienna on April 2, 2020, and at the Alzheimer’s Association International Conference in Amsterdam in July.
The researchers will continue to explore all data gathered – but already new insights have been discovered into the development and progression of AD, Dr. Bateman noted.
Included among these discoveries is that brain changes that occur as the disease progresses are similar among those with the inherited, early-onset form of AD and the late-onset form.
“The trial’s innovative design ... will make advances for future Alzheimer’s trials. Ongoing and continued research and trials will bring us closer to our goal to stop Alzheimer’s,” Dr. Bateman said. “We will continue until we are successful.”
“These results reflect the difficult nature of treating [AD] and the great need for continued research,” said Daniel Skovronsky, MD, PhD, chief scientific officer and president of Lilly Research Labs.
“If we have learned one thing after more than 30 years of Alzheimer’s research, it is that even negative results propel the science forward,” he added.
Lilly noted in a statement that the DIAN-TU top-line results will not affect its ongoing A4 study of solanezumab. Roche noted in its own statement that the findings also will not affect the company’s ongoing GRADUATE studies of gantenerumab.
“The work doesn’t stop here”
Richard J. Hodes, MD, director of the National Institute on Aging, said that DIAN-TU will advance the field’s knowledge about a complex disease.
“We look forward to learning more through the published, peer-reviewed data, which will provide a broad range of scientists with crucial information and guidance for future research,” he said.
Howard Fillit, MD, founding executive director and chief science officer at the Alzheimer’s Drug Discovery Foundation (ADDF), agreed.
“While we are disappointed that patients in this study did not see a benefit, we need to keep in mind that Alzheimer’s is a complicated disease due to complex, multifactorial causes,” he said in a statement.
“ADDF has long supported a broader approach that moves past targeting beta-amyloid and advances a diverse pipeline of drugs addressing multiple targets” in AD, Dr. Fillit added. “We need multiple ‘shots on goals’ to discover effective drugs.”
Dr. Edelmayer said the results emphasize that “this story isn’t yet completely told” and that there is still a lot to learn from the data, especially regarding the biomarkers that were tested.
“With that information, we will gain valuable insight into the outcomes that have been released but will also probably better understand where we should be putting our energies and focus moving forward,” she said.
Going forward, “we will continue this fight until we have an effective treatment for all individuals living with Alzheimer’s, whether it’s dominantly inherited [AD] or the more common version, which is the late-onset or sporadic form of the disease,” said Dr. Edelmayer.
“We have to stay optimistic. The work doesn’t stop here.”
The trial was funded by Eli Lilly, Roche, the Alzheimer’s Association, the National Institute on Aging, the GHR Foundation, and FBRI.
This article first appeared on Medscape.com.
Top-line results from the seminal phase 2/3 Dominantly Inherited Alzheimer’s Network–Trials Unit (DIAN-TU) study show that the novel drugs gantenerumab (Roche) and solanezumab (Lilly) did not meet the primary endpoint in patients with early-stage, dominantly inherited Alzheimer’s disease (AD), investigators have announced.
In the international trial, which included almost 200 participants, the two experimental agents were evaluated separately. However, initial analyses showed that neither significantly slowed cognitive decline, the primary outcome measure, nor memory loss.
Still, the researchers noted that they will continue exploring data from DIAN-TU’s cognitive and clinical outcomes and are awaiting analyses of various biomarkers.
“Although the drugs we evaluated were not successful, the trial will move us forward in understanding Alzheimer’s,” principal investigator Randall J. Bateman, MD, of Washington University, St. Louis, said in a news release.
Funders for the trial included the National Institute on Aging and the Alzheimer’s Association.
“While the top-line data fell short, the Alzheimer’s Association looks forward to a more complete report at upcoming scientific conferences. We learn from every trial,” Maria Carrillo, PhD, chief scientific officer at the Alzheimer’s Association, noted in the organization’s own release.
Rebecca M. Edelmayer, PhD, director of scientific engagement for the Alzheimer’s Association, agreed with Dr. Carrillo that, although the results were disappointing, the data will be beneficial for the field.
“It’s always a difficult day when we get news like this,” Dr. Edelmayer said in an interview. However, “this research is going to absolutely provide valuable information once we can really pick through all of the data.”
Rare condition
Dominantly inherited AD, also known as familial AD or autosomal dominant AD, is rare but can affect memory and cognitive skills in individuals as young as age 30. It is caused by mutations on chromosomes 21, 14, and/or 1 that play a part in the breakdown of amyloid proteins and formation of amyloid plaques.
Both gantenerumab and solanezumab were created to target and neutralize amyloid-beta, albeit through different mechanisms. Both are also being assessed in other trials as treatment for more common forms of AD.
As reported by Medscape Medical News, results of the phase 3 EXPEDITION3 trial of solanezumab in patients with mild AD were negative, as were two other phase 3 trials. The drug is now being evaluated in the ongoing solanezumab Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study.
Although the phase 3 SCARLET ROAD trial of gantenerumab for mild AD was stopped early for futility in 2014, it was continued as an open-label extension at the high dose for 2 years. During that period, follow-up analyses showed a dramatic decline in amyloid-beta deposition in the participants – leading to the launch of the phase 3 GRADUATE 1 and GRADUATE 2 trials.
Starting in 2012, DIAN-TU was conducted at 24 sites in the United States, the United Kingdom, Canada, Europe, and Australia. It followed 194 adult patients for up to 7 years (average duration, 5 years). Its original estimated completion date was December 2020, as stated on clinicaltrials.gov.
All participants had family members with a genetic mutation that causes early-onset Alzheimer’s disease. They already had very mild symptoms of cognitive decline and memory loss at the start of the trial or were expected to develop symptoms within 15 years of enrollment.
“People who inherit the mutation are all but guaranteed to develop symptoms at about the same age their parents did,” the release noted.
“While devastating for families, such mutations allow researchers to identify people in the early stages of the disease before their behavior and memory begin to change,” it added.
The Alzheimer’s Association noted in its release that a child of a parent with the mutation has a 50/50 chance of inheriting the disease. “This form affects less than 1% of the individuals living with Alzheimer’s disease today,” Dr. Edelmayer noted.
Detailed data coming soon
Trial participants were randomly assigned to receive either solanezumab, gantenerumab, or matching placebo. To act as a comparator group, family members without the AD mutation were also included.
The primary measure was change from baseline in the DIAN-TU cognitive composite score. Secondary measures included changes on the Mini-Mental State Examination, the Functional Assessment Scale, the Neuropsychiatric Inventory Questionnaire, the 12-item International Shopping List Test, the Memory Complaint Questionnaire, and the Wechsler Memory Scale Logical Memory/Paragraph Memory test.
The researchers also conducted imaging scans and collected samples of blood and cerebrospinal fluid.
Along with announcing the negative top-line results for the trial, the investigators noted that “a more detailed analysis of the trial’s data” will be presented at the Advances in Alzheimer’s and Parkinson’s Therapies in Vienna on April 2, 2020, and at the Alzheimer’s Association International Conference in Amsterdam in July.
The researchers will continue to explore all data gathered – but already new insights have been discovered into the development and progression of AD, Dr. Bateman noted.
Included among these discoveries is that brain changes that occur as the disease progresses are similar among those with the inherited, early-onset form of AD and the late-onset form.
“The trial’s innovative design ... will make advances for future Alzheimer’s trials. Ongoing and continued research and trials will bring us closer to our goal to stop Alzheimer’s,” Dr. Bateman said. “We will continue until we are successful.”
“These results reflect the difficult nature of treating [AD] and the great need for continued research,” said Daniel Skovronsky, MD, PhD, chief scientific officer and president of Lilly Research Labs.
“If we have learned one thing after more than 30 years of Alzheimer’s research, it is that even negative results propel the science forward,” he added.
Lilly noted in a statement that the DIAN-TU top-line results will not affect its ongoing A4 study of solanezumab. Roche noted in its own statement that the findings also will not affect the company’s ongoing GRADUATE studies of gantenerumab.
“The work doesn’t stop here”
Richard J. Hodes, MD, director of the National Institute on Aging, said that DIAN-TU will advance the field’s knowledge about a complex disease.
“We look forward to learning more through the published, peer-reviewed data, which will provide a broad range of scientists with crucial information and guidance for future research,” he said.
Howard Fillit, MD, founding executive director and chief science officer at the Alzheimer’s Drug Discovery Foundation (ADDF), agreed.
“While we are disappointed that patients in this study did not see a benefit, we need to keep in mind that Alzheimer’s is a complicated disease due to complex, multifactorial causes,” he said in a statement.
“ADDF has long supported a broader approach that moves past targeting beta-amyloid and advances a diverse pipeline of drugs addressing multiple targets” in AD, Dr. Fillit added. “We need multiple ‘shots on goals’ to discover effective drugs.”
Dr. Edelmayer said the results emphasize that “this story isn’t yet completely told” and that there is still a lot to learn from the data, especially regarding the biomarkers that were tested.
“With that information, we will gain valuable insight into the outcomes that have been released but will also probably better understand where we should be putting our energies and focus moving forward,” she said.
Going forward, “we will continue this fight until we have an effective treatment for all individuals living with Alzheimer’s, whether it’s dominantly inherited [AD] or the more common version, which is the late-onset or sporadic form of the disease,” said Dr. Edelmayer.
“We have to stay optimistic. The work doesn’t stop here.”
The trial was funded by Eli Lilly, Roche, the Alzheimer’s Association, the National Institute on Aging, the GHR Foundation, and FBRI.
This article first appeared on Medscape.com.
FDA okays cenobamate (Xcopri) for focal epilepsy
The Food and Drug Administration has approved cenobamate (Xcopri) for the treatment of partial-onset seizures in adult patients with epilepsy.
The approval on Nov. 21 was based on results from two randomized controlled trials that included more than 600 patients, the agency said in a press release.
Together, the trials showed that the study drug at doses of 100, 200, and 400 mg significantly reduced the percentage of seizures, compared with placebo.
The FDA notes that, although the recommended maintenance dose of the drug is 200 mg/day after titration, some patients may need to be titrated up to 400 mg/day.
“Xcopri is a new option to treat adults with partial-onset seizures, which is an often difficult-to-control condition that can have a significant impact on patient quality of life,” Billy Dunn, MD, director of the Office of Neuroscience in the Center for Drug Evaluation and Research at the FDA, said in a statement.
Adverse events
As reported by Medscape Medical News, results from one of the studies upon which this approval was based were published online last week in Lancet Neurology. The findings showed that both primary endpoints were met.
Although most treatment-emergent adverse events (AEs) were reported to be mild to moderate in severity, one of these participants receiving the 200 mg dose had a drug reaction with eosinophilia and systemic symptoms (DRESS).
The FDA noted that one patient in the other trial also died when the active drug was titrated rapidly.
In an open-label safety trial of 1,339 participants that was also reviewed by the FDA, there were no cases of DRESS when patients started cenobamate at 12.5 mg/day and the dose was adjusted every 2 weeks.
Because more patients who took the drug than those taking placebo had a shortening of the QT interval greater than 20 milliseconds, cenobamate shouldn’t be used in those with hypersensitivity to the drug “or any of the inactive ingredients in Xcopri or Familial Short QT syndrome,” the agency wrote, adding that QT shortening can be associated with ventricular fibrillation, a serious heart rhythm problem.
The FDA also noted that any patient taking an antiepileptic drug should be monitored for the emergence or worsening of depressive symptoms, suicidal thoughts or behaviors, or any other changes in mood.
The most common AEs reported in the trials were somnolence, dizziness, fatigue, and diplopia (double vision).
‘Welcome option’
“The approval of Xcopri will provide clinicians with an effective medication for our patients who are continuing to have focal [partial-onset] seizures,” Michael Sperling, MD, professor of neurology and director of the Jefferson Comprehensive Epilepsy Center, Philadelphia, and an investigator in the drug’s clinical development program, said in a press release from SK Life Science.
“It is very encouraging to see that patients receiving Xcopri saw significant reductions in frequency of seizures, with some even achieving zero seizures,” Dr. Sperling added.
“There is an urgent need to advance research and introduce new treatment options. The FDA approval of Xcopri for the treatment of partial-onset seizures is a welcome option for the epilepsy community,” Beth Lewin Dean, chief executive officer of Citizens United for Research in Epilepsy, said in the same release.
SK Life Science noted in a statement that the drug is expected to be available in the United States in the second quarter of 2020 “following scheduling review” by the Drug Enforcement Administration.
This story first appeared on Medscape.com.
The Food and Drug Administration has approved cenobamate (Xcopri) for the treatment of partial-onset seizures in adult patients with epilepsy.
The approval on Nov. 21 was based on results from two randomized controlled trials that included more than 600 patients, the agency said in a press release.
Together, the trials showed that the study drug at doses of 100, 200, and 400 mg significantly reduced the percentage of seizures, compared with placebo.
The FDA notes that, although the recommended maintenance dose of the drug is 200 mg/day after titration, some patients may need to be titrated up to 400 mg/day.
“Xcopri is a new option to treat adults with partial-onset seizures, which is an often difficult-to-control condition that can have a significant impact on patient quality of life,” Billy Dunn, MD, director of the Office of Neuroscience in the Center for Drug Evaluation and Research at the FDA, said in a statement.
Adverse events
As reported by Medscape Medical News, results from one of the studies upon which this approval was based were published online last week in Lancet Neurology. The findings showed that both primary endpoints were met.
Although most treatment-emergent adverse events (AEs) were reported to be mild to moderate in severity, one of these participants receiving the 200 mg dose had a drug reaction with eosinophilia and systemic symptoms (DRESS).
The FDA noted that one patient in the other trial also died when the active drug was titrated rapidly.
In an open-label safety trial of 1,339 participants that was also reviewed by the FDA, there were no cases of DRESS when patients started cenobamate at 12.5 mg/day and the dose was adjusted every 2 weeks.
Because more patients who took the drug than those taking placebo had a shortening of the QT interval greater than 20 milliseconds, cenobamate shouldn’t be used in those with hypersensitivity to the drug “or any of the inactive ingredients in Xcopri or Familial Short QT syndrome,” the agency wrote, adding that QT shortening can be associated with ventricular fibrillation, a serious heart rhythm problem.
The FDA also noted that any patient taking an antiepileptic drug should be monitored for the emergence or worsening of depressive symptoms, suicidal thoughts or behaviors, or any other changes in mood.
The most common AEs reported in the trials were somnolence, dizziness, fatigue, and diplopia (double vision).
‘Welcome option’
“The approval of Xcopri will provide clinicians with an effective medication for our patients who are continuing to have focal [partial-onset] seizures,” Michael Sperling, MD, professor of neurology and director of the Jefferson Comprehensive Epilepsy Center, Philadelphia, and an investigator in the drug’s clinical development program, said in a press release from SK Life Science.
“It is very encouraging to see that patients receiving Xcopri saw significant reductions in frequency of seizures, with some even achieving zero seizures,” Dr. Sperling added.
“There is an urgent need to advance research and introduce new treatment options. The FDA approval of Xcopri for the treatment of partial-onset seizures is a welcome option for the epilepsy community,” Beth Lewin Dean, chief executive officer of Citizens United for Research in Epilepsy, said in the same release.
SK Life Science noted in a statement that the drug is expected to be available in the United States in the second quarter of 2020 “following scheduling review” by the Drug Enforcement Administration.
This story first appeared on Medscape.com.
The Food and Drug Administration has approved cenobamate (Xcopri) for the treatment of partial-onset seizures in adult patients with epilepsy.
The approval on Nov. 21 was based on results from two randomized controlled trials that included more than 600 patients, the agency said in a press release.
Together, the trials showed that the study drug at doses of 100, 200, and 400 mg significantly reduced the percentage of seizures, compared with placebo.
The FDA notes that, although the recommended maintenance dose of the drug is 200 mg/day after titration, some patients may need to be titrated up to 400 mg/day.
“Xcopri is a new option to treat adults with partial-onset seizures, which is an often difficult-to-control condition that can have a significant impact on patient quality of life,” Billy Dunn, MD, director of the Office of Neuroscience in the Center for Drug Evaluation and Research at the FDA, said in a statement.
Adverse events
As reported by Medscape Medical News, results from one of the studies upon which this approval was based were published online last week in Lancet Neurology. The findings showed that both primary endpoints were met.
Although most treatment-emergent adverse events (AEs) were reported to be mild to moderate in severity, one of these participants receiving the 200 mg dose had a drug reaction with eosinophilia and systemic symptoms (DRESS).
The FDA noted that one patient in the other trial also died when the active drug was titrated rapidly.
In an open-label safety trial of 1,339 participants that was also reviewed by the FDA, there were no cases of DRESS when patients started cenobamate at 12.5 mg/day and the dose was adjusted every 2 weeks.
Because more patients who took the drug than those taking placebo had a shortening of the QT interval greater than 20 milliseconds, cenobamate shouldn’t be used in those with hypersensitivity to the drug “or any of the inactive ingredients in Xcopri or Familial Short QT syndrome,” the agency wrote, adding that QT shortening can be associated with ventricular fibrillation, a serious heart rhythm problem.
The FDA also noted that any patient taking an antiepileptic drug should be monitored for the emergence or worsening of depressive symptoms, suicidal thoughts or behaviors, or any other changes in mood.
The most common AEs reported in the trials were somnolence, dizziness, fatigue, and diplopia (double vision).
‘Welcome option’
“The approval of Xcopri will provide clinicians with an effective medication for our patients who are continuing to have focal [partial-onset] seizures,” Michael Sperling, MD, professor of neurology and director of the Jefferson Comprehensive Epilepsy Center, Philadelphia, and an investigator in the drug’s clinical development program, said in a press release from SK Life Science.
“It is very encouraging to see that patients receiving Xcopri saw significant reductions in frequency of seizures, with some even achieving zero seizures,” Dr. Sperling added.
“There is an urgent need to advance research and introduce new treatment options. The FDA approval of Xcopri for the treatment of partial-onset seizures is a welcome option for the epilepsy community,” Beth Lewin Dean, chief executive officer of Citizens United for Research in Epilepsy, said in the same release.
SK Life Science noted in a statement that the drug is expected to be available in the United States in the second quarter of 2020 “following scheduling review” by the Drug Enforcement Administration.
This story first appeared on Medscape.com.