Weight Gain Low, Comparable to Placebo in Vilazodone Trial

PHOENIX – Vilazodone appears to be effective in patients with depression across severity subgroups and isn’t associated with meaningful weight gains, based on post hoc analyses of data from phase III studies.

The findings were based on data from 869 patients who were part of the two trials that examined the drug’s safety; 31% had moderate depression based on scores of less than 30 on the Montgomery-Asberg Depression Rating Scale, 49% had moderately severe depression (MADRS of 30-35), and 20% had severe depression (MADRS of 35 or greater). Patients on vilazodone had improvements that exceeded those of patients on placebo. The least squares mean differences for change were –2.9 (moderate depression), –2.3 (moderately severe depression), and –4.1 (severe depression), reported Dr. Donald S. Robinson of Worldwide Drug Development, Shelburne, Vt., and his colleagues in a poster presented at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Differences exceeded 2.0 in all three subgroups, representing clinically significant effects, according to the researchers.

In the treatment and placebo groups, the respective percent responses were 41% and 31% in those with moderate depression, 41% and 29% in those with moderately severe depression, and 44% and 26% those with severe depression. The adverse events profiles were similar for vilazodone and placebo across the severity groups.

In another poster, Dr. John Edwards of Forest Research Institute, Jersey City, N.J., and his colleagues reported an analysis of vilazodone effectiveness. He found that the number needed to treat (NNT) was 12 to achieve a MADRS of 10 or less and 8 for a MADRS of 12 or less. The number needed to harm was 26 to result in a discontinuation caused by adverse events.

A MADRS of 10 or less is generally considered to be evidence of clinical relevance in depression treatment, and the NNT for response in this analysis – using both MADRS and the Clinical Global Impression of Improvement (CGI-I) criteria – was "sufficient to regard improvement by vilazodone as clinically significant," the investigators said, noting also that the NNT values for remission were "well within the range of those observed for other antidepressants in clinical studies."

The analysis suggested a lower risk of discontinuation due to adverse events relative to clinically meaningful improvement for vilazodone, they concluded.

A third post hoc analysis of the pooled phase III trial data and the 52-week open-label trial indicated that vilazodone had little effect on body weight and clinical laboratory measures.

The mean baseline body weight of patients in the treatment and placebo groups was 86.0 kg and 86.5 kg, respectively, and the mean weight of treated patients in the open-label study was 89.6 kg. Mean baseline body mass index was 30.2 kg/m², 30.1 kg/m², and 31.6 kg/m² in those groups, respectively. The mean change in body weight from baseline to the end of treatment for vilazodone and placebo patients was 0.16 kg and 0.18 kg, respectively, overall, reported Dr. Michael E. Thase of the University of Pennsylvania, Philadelphia, and his colleagues in a poster.

There also was little difference between the treatment and placebo groups after stratification based on normal weight, overweight, and obese status, (mean change of 0.0 kg and 0.32 kg, respectively, for normal weight patients; 0.08 kg and 0.57 kg for overweight patients; and –0.39 kg and 0.18 kg for obese patients).

In the open-label study patients, the mean change in body weight from baseline to the end of treatment was 1.20 kg overall, and 1.13, 1.21, 1.50, and 1.06 kg for underweight, normal weight, overweight, and obese patients, respectively, they said. Clinically significant weight gain occurred in one patient each in the treatment and placebo groups in the phase III trials, and in 2%, 3%, and 5% of the normal, overweight, and obese patients, respectively, in the open-label trial population.

Additionally, no significant differences between the treatment and placebo groups with respect to changes in liver enzymes and blood glucose were seen in the phase III trials, the investigators said.

The studies were supported by funding from Forest Laboratories. Dr. Robinson and Dr. Thase reported receiving grant support and/or consulting fees from Forest Research Institute, a scientific division of Forest Labs. Dr. Robinson and several other study authors are employees of Forest Research Institute.

PHOENIX – Vilazodone appears to be effective in patients with depression across severity subgroups and isn’t associated with meaningful weight gains, based on post hoc analyses of data from phase III studies.

The findings were based on data from 869 patients who were part of the two trials that examined the drug’s safety; 31% had moderate depression based on scores of less than 30 on the Montgomery-Asberg Depression Rating Scale, 49% had moderately severe depression (MADRS of 30-35), and 20% had severe depression (MADRS of 35 or greater). Patients on vilazodone had improvements that exceeded those of patients on placebo. The least squares mean differences for change were –2.9 (moderate depression), –2.3 (moderately severe depression), and –4.1 (severe depression), reported Dr. Donald S. Robinson of Worldwide Drug Development, Shelburne, Vt., and his colleagues in a poster presented at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Differences exceeded 2.0 in all three subgroups, representing clinically significant effects, according to the researchers.

In the treatment and placebo groups, the respective percent responses were 41% and 31% in those with moderate depression, 41% and 29% in those with moderately severe depression, and 44% and 26% those with severe depression. The adverse events profiles were similar for vilazodone and placebo across the severity groups.

In another poster, Dr. John Edwards of Forest Research Institute, Jersey City, N.J., and his colleagues reported an analysis of vilazodone effectiveness. He found that the number needed to treat (NNT) was 12 to achieve a MADRS of 10 or less and 8 for a MADRS of 12 or less. The number needed to harm was 26 to result in a discontinuation caused by adverse events.

A MADRS of 10 or less is generally considered to be evidence of clinical relevance in depression treatment, and the NNT for response in this analysis – using both MADRS and the Clinical Global Impression of Improvement (CGI-I) criteria – was "sufficient to regard improvement by vilazodone as clinically significant," the investigators said, noting also that the NNT values for remission were "well within the range of those observed for other antidepressants in clinical studies."

The analysis suggested a lower risk of discontinuation due to adverse events relative to clinically meaningful improvement for vilazodone, they concluded.

A third post hoc analysis of the pooled phase III trial data and the 52-week open-label trial indicated that vilazodone had little effect on body weight and clinical laboratory measures.

The mean baseline body weight of patients in the treatment and placebo groups was 86.0 kg and 86.5 kg, respectively, and the mean weight of treated patients in the open-label study was 89.6 kg. Mean baseline body mass index was 30.2 kg/m², 30.1 kg/m², and 31.6 kg/m² in those groups, respectively. The mean change in body weight from baseline to the end of treatment for vilazodone and placebo patients was 0.16 kg and 0.18 kg, respectively, overall, reported Dr. Michael E. Thase of the University of Pennsylvania, Philadelphia, and his colleagues in a poster.

There also was little difference between the treatment and placebo groups after stratification based on normal weight, overweight, and obese status, (mean change of 0.0 kg and 0.32 kg, respectively, for normal weight patients; 0.08 kg and 0.57 kg for overweight patients; and –0.39 kg and 0.18 kg for obese patients).

In the open-label study patients, the mean change in body weight from baseline to the end of treatment was 1.20 kg overall, and 1.13, 1.21, 1.50, and 1.06 kg for underweight, normal weight, overweight, and obese patients, respectively, they said. Clinically significant weight gain occurred in one patient each in the treatment and placebo groups in the phase III trials, and in 2%, 3%, and 5% of the normal, overweight, and obese patients, respectively, in the open-label trial population.

Additionally, no significant differences between the treatment and placebo groups with respect to changes in liver enzymes and blood glucose were seen in the phase III trials, the investigators said.

The studies were supported by funding from Forest Laboratories. Dr. Robinson and Dr. Thase reported receiving grant support and/or consulting fees from Forest Research Institute, a scientific division of Forest Labs. Dr. Robinson and several other study authors are employees of Forest Research Institute.

PHOENIX – Vilazodone appears to be effective in patients with depression across severity subgroups and isn’t associated with meaningful weight gains, based on post hoc analyses of data from phase III studies.

The findings were based on data from 869 patients who were part of the two trials that examined the drug’s safety; 31% had moderate depression based on scores of less than 30 on the Montgomery-Asberg Depression Rating Scale, 49% had moderately severe depression (MADRS of 30-35), and 20% had severe depression (MADRS of 35 or greater). Patients on vilazodone had improvements that exceeded those of patients on placebo. The least squares mean differences for change were –2.9 (moderate depression), –2.3 (moderately severe depression), and –4.1 (severe depression), reported Dr. Donald S. Robinson of Worldwide Drug Development, Shelburne, Vt., and his colleagues in a poster presented at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

Differences exceeded 2.0 in all three subgroups, representing clinically significant effects, according to the researchers.

In the treatment and placebo groups, the respective percent responses were 41% and 31% in those with moderate depression, 41% and 29% in those with moderately severe depression, and 44% and 26% those with severe depression. The adverse events profiles were similar for vilazodone and placebo across the severity groups.

In another poster, Dr. John Edwards of Forest Research Institute, Jersey City, N.J., and his colleagues reported an analysis of vilazodone effectiveness. He found that the number needed to treat (NNT) was 12 to achieve a MADRS of 10 or less and 8 for a MADRS of 12 or less. The number needed to harm was 26 to result in a discontinuation caused by adverse events.

A MADRS of 10 or less is generally considered to be evidence of clinical relevance in depression treatment, and the NNT for response in this analysis – using both MADRS and the Clinical Global Impression of Improvement (CGI-I) criteria – was "sufficient to regard improvement by vilazodone as clinically significant," the investigators said, noting also that the NNT values for remission were "well within the range of those observed for other antidepressants in clinical studies."

The analysis suggested a lower risk of discontinuation due to adverse events relative to clinically meaningful improvement for vilazodone, they concluded.

A third post hoc analysis of the pooled phase III trial data and the 52-week open-label trial indicated that vilazodone had little effect on body weight and clinical laboratory measures.

The mean baseline body weight of patients in the treatment and placebo groups was 86.0 kg and 86.5 kg, respectively, and the mean weight of treated patients in the open-label study was 89.6 kg. Mean baseline body mass index was 30.2 kg/m², 30.1 kg/m², and 31.6 kg/m² in those groups, respectively. The mean change in body weight from baseline to the end of treatment for vilazodone and placebo patients was 0.16 kg and 0.18 kg, respectively, overall, reported Dr. Michael E. Thase of the University of Pennsylvania, Philadelphia, and his colleagues in a poster.

There also was little difference between the treatment and placebo groups after stratification based on normal weight, overweight, and obese status, (mean change of 0.0 kg and 0.32 kg, respectively, for normal weight patients; 0.08 kg and 0.57 kg for overweight patients; and –0.39 kg and 0.18 kg for obese patients).

In the open-label study patients, the mean change in body weight from baseline to the end of treatment was 1.20 kg overall, and 1.13, 1.21, 1.50, and 1.06 kg for underweight, normal weight, overweight, and obese patients, respectively, they said. Clinically significant weight gain occurred in one patient each in the treatment and placebo groups in the phase III trials, and in 2%, 3%, and 5% of the normal, overweight, and obese patients, respectively, in the open-label trial population.

Additionally, no significant differences between the treatment and placebo groups with respect to changes in liver enzymes and blood glucose were seen in the phase III trials, the investigators said.

The studies were supported by funding from Forest Laboratories. Dr. Robinson and Dr. Thase reported receiving grant support and/or consulting fees from Forest Research Institute, a scientific division of Forest Labs. Dr. Robinson and several other study authors are employees of Forest Research Institute.