Duloxetine proves beneficial in elderly GAD

HOLLYWOOD, FLA. – Duloxetine proved safe and effective for the treatment of generalized anxiety disorder in the elderly in a phase IV clinical trial restricted to patients aged 65 and up.

This study fills a major gap in the evidence base for duloxetine (Cymbalta). Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders in the elderly, with a prevalence estimated at up to 7%. Yet prior studies of duloxetine for GAD largely excluded the elderly. Indeed, the product labeling states prominently that premarketing studies did not include enough patients over age 65 to determine whether they respond differently than younger subjects.

With the new evidence provided by the phase IV study, the answer to that question is now in: Duloxetine proved significantly more effective than placebo in seniors. Moreover, the discontinuation rate because of adverse events did not differ significantly between the duloxetine and placebo groups, Karla J. Alaka reported at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

The study included 291 patients aged 65 or older (mean age, 72) who met DSM-IV-TR criteria for GAD. They were randomized to 10 weeks of double-blind treatment with duloxetine dosed at 30-120 mg/day or placebo. Throughout the study, roughly one-third of the duloxetine group remained on 30 mg/day, another third bumped up to 60 mg/day, one-quarter increased to 90 mg/day, and the remainder eventually received 120 mg/day.

Elderly patients with an additional Axis I diagnosis plus GAD were not eligible for the trial. However, patients with comorbid medical illnesses were not excluded from participation so long as those conditions were stable and not expected to result in hospitalization within the next 6 months. Fully 83% of subjects had one or more preexisting medical conditions for which they took concomitant medication during the study. Geriatricians and other physicians have become increasingly vocal about the absence of quality safety and efficacy data for many widely prescribed drugs in the elderly, where issues such as polypharmacy, drug-drug interactions, and slowed drug metabolism become key considerations.

The primary efficacy measure in the study was a change in the Hamilton Anxiety Scale (HAS) total score from baseline to week 10. From a mean baseline HAS score of 24.6, the duloxetine group averaged a 15.9-point decrease, significantly better than the 11.7-point drop with placebo, according to Ms. Alaka of Eli Lilly, Indianapolis.

The HAS response rate, defined by at least a 50% reduction in the HAS total score, was 75% in duloxetine-treated patients, compared with 56% in controls. The Hamilton Anxiety Scale remission rate, a more stringent endpoint requiring a week 10 total score of 10 or less, was achieved by 62% of the duloxetine group and 40% on placebo.

Duloxetine-treated patients also outperformed controls in terms of several other secondary endpoints. For example, the Sheehan Disability Scale global function impairment score in the duloxetine group improved by a mean of 7.6 points from a baseline score of 13.7, compared with a 4.3-point improvement with placebo.

Study discontinuation because of treatment-emergent adverse events occurred in 9.9% of elderly patients on duloxetine and 10.7% on placebo. The only adverse event that was significantly more common in the active treatment group was dry mouth, which occurred in 7% on duloxetine, compared with 1% of controls. Duloxetine was not associated with any clinically significant changes in laboratory findings, ECG parameters, or body weight.

The phase IV study was sponsored by Eli Lilly, which markets duloxetine. The presenter is a company employee.

bjancin@frontlinemedcom.com

HOLLYWOOD, FLA. – Duloxetine proved safe and effective for the treatment of generalized anxiety disorder in the elderly in a phase IV clinical trial restricted to patients aged 65 and up.

This study fills a major gap in the evidence base for duloxetine (Cymbalta). Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders in the elderly, with a prevalence estimated at up to 7%. Yet prior studies of duloxetine for GAD largely excluded the elderly. Indeed, the product labeling states prominently that premarketing studies did not include enough patients over age 65 to determine whether they respond differently than younger subjects.

With the new evidence provided by the phase IV study, the answer to that question is now in: Duloxetine proved significantly more effective than placebo in seniors. Moreover, the discontinuation rate because of adverse events did not differ significantly between the duloxetine and placebo groups, Karla J. Alaka reported at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

The study included 291 patients aged 65 or older (mean age, 72) who met DSM-IV-TR criteria for GAD. They were randomized to 10 weeks of double-blind treatment with duloxetine dosed at 30-120 mg/day or placebo. Throughout the study, roughly one-third of the duloxetine group remained on 30 mg/day, another third bumped up to 60 mg/day, one-quarter increased to 90 mg/day, and the remainder eventually received 120 mg/day.

Elderly patients with an additional Axis I diagnosis plus GAD were not eligible for the trial. However, patients with comorbid medical illnesses were not excluded from participation so long as those conditions were stable and not expected to result in hospitalization within the next 6 months. Fully 83% of subjects had one or more preexisting medical conditions for which they took concomitant medication during the study. Geriatricians and other physicians have become increasingly vocal about the absence of quality safety and efficacy data for many widely prescribed drugs in the elderly, where issues such as polypharmacy, drug-drug interactions, and slowed drug metabolism become key considerations.

The primary efficacy measure in the study was a change in the Hamilton Anxiety Scale (HAS) total score from baseline to week 10. From a mean baseline HAS score of 24.6, the duloxetine group averaged a 15.9-point decrease, significantly better than the 11.7-point drop with placebo, according to Ms. Alaka of Eli Lilly, Indianapolis.

The HAS response rate, defined by at least a 50% reduction in the HAS total score, was 75% in duloxetine-treated patients, compared with 56% in controls. The Hamilton Anxiety Scale remission rate, a more stringent endpoint requiring a week 10 total score of 10 or less, was achieved by 62% of the duloxetine group and 40% on placebo.

Duloxetine-treated patients also outperformed controls in terms of several other secondary endpoints. For example, the Sheehan Disability Scale global function impairment score in the duloxetine group improved by a mean of 7.6 points from a baseline score of 13.7, compared with a 4.3-point improvement with placebo.

Study discontinuation because of treatment-emergent adverse events occurred in 9.9% of elderly patients on duloxetine and 10.7% on placebo. The only adverse event that was significantly more common in the active treatment group was dry mouth, which occurred in 7% on duloxetine, compared with 1% of controls. Duloxetine was not associated with any clinically significant changes in laboratory findings, ECG parameters, or body weight.

The phase IV study was sponsored by Eli Lilly, which markets duloxetine. The presenter is a company employee.

bjancin@frontlinemedcom.com

HOLLYWOOD, FLA. – Duloxetine proved safe and effective for the treatment of generalized anxiety disorder in the elderly in a phase IV clinical trial restricted to patients aged 65 and up.

This study fills a major gap in the evidence base for duloxetine (Cymbalta). Generalized anxiety disorder (GAD) is one of the most common psychiatric disorders in the elderly, with a prevalence estimated at up to 7%. Yet prior studies of duloxetine for GAD largely excluded the elderly. Indeed, the product labeling states prominently that premarketing studies did not include enough patients over age 65 to determine whether they respond differently than younger subjects.

With the new evidence provided by the phase IV study, the answer to that question is now in: Duloxetine proved significantly more effective than placebo in seniors. Moreover, the discontinuation rate because of adverse events did not differ significantly between the duloxetine and placebo groups, Karla J. Alaka reported at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

The study included 291 patients aged 65 or older (mean age, 72) who met DSM-IV-TR criteria for GAD. They were randomized to 10 weeks of double-blind treatment with duloxetine dosed at 30-120 mg/day or placebo. Throughout the study, roughly one-third of the duloxetine group remained on 30 mg/day, another third bumped up to 60 mg/day, one-quarter increased to 90 mg/day, and the remainder eventually received 120 mg/day.

Elderly patients with an additional Axis I diagnosis plus GAD were not eligible for the trial. However, patients with comorbid medical illnesses were not excluded from participation so long as those conditions were stable and not expected to result in hospitalization within the next 6 months. Fully 83% of subjects had one or more preexisting medical conditions for which they took concomitant medication during the study. Geriatricians and other physicians have become increasingly vocal about the absence of quality safety and efficacy data for many widely prescribed drugs in the elderly, where issues such as polypharmacy, drug-drug interactions, and slowed drug metabolism become key considerations.

The primary efficacy measure in the study was a change in the Hamilton Anxiety Scale (HAS) total score from baseline to week 10. From a mean baseline HAS score of 24.6, the duloxetine group averaged a 15.9-point decrease, significantly better than the 11.7-point drop with placebo, according to Ms. Alaka of Eli Lilly, Indianapolis.

The HAS response rate, defined by at least a 50% reduction in the HAS total score, was 75% in duloxetine-treated patients, compared with 56% in controls. The Hamilton Anxiety Scale remission rate, a more stringent endpoint requiring a week 10 total score of 10 or less, was achieved by 62% of the duloxetine group and 40% on placebo.

Duloxetine-treated patients also outperformed controls in terms of several other secondary endpoints. For example, the Sheehan Disability Scale global function impairment score in the duloxetine group improved by a mean of 7.6 points from a baseline score of 13.7, compared with a 4.3-point improvement with placebo.

Study discontinuation because of treatment-emergent adverse events occurred in 9.9% of elderly patients on duloxetine and 10.7% on placebo. The only adverse event that was significantly more common in the active treatment group was dry mouth, which occurred in 7% on duloxetine, compared with 1% of controls. Duloxetine was not associated with any clinically significant changes in laboratory findings, ECG parameters, or body weight.

The phase IV study was sponsored by Eli Lilly, which markets duloxetine. The presenter is a company employee.

bjancin@frontlinemedcom.com