Vilazodone May Be Safer Option to Treat Adult MDD

Vilazodone appears to pose little or no risk of treatment-emergent suicidal ideation or behavior in adults with major depressive disorder (MDD) or generalized anxiety disorder (GAD), according to a study in the journal International Clinical Psychopharmacology.

Data pooled from four double-blind, placebo-controlled vilazodone trials for MDD (including 2,233 patients) and three for GAD (including 1,475 patients) revealed that suicide-related adverse events occurred in less than 1 percent of patients treated with vilazodone and placebo. Vilazodone, which is approved for the treatment of MDD in adults, has also been evaluated as a possible treatment for adults with GAD.

“We found this result reassuring, and it might steer us to picking this drug more often,” said lead author Michael Thase, M.D., a professor of psychiatry at Perelman School of Medicine at the University of Pennsylvania. For other types of antidepressants, the risk of suicide ideation may be as high as 4 percent compared with 2 percent for placebo, he said.

The Food and Drug Administration (FDA) requires clinical trials of new psychotropic drugs to include a prospective assessment of suicidal ideation and behavior.

“The FDA’s duty is to warn when there is evidence of some risk of initiating treatment,” Thase said. “In the previous decade, comprehensive reviews suggested a small, but real increase—not due to chance—in suicidal thoughts compared with placebo.”

For the vilazodone meta-analysis, Thase and colleagues evaluated treatment-emergent suicidal ideation using adverse event reporting and Columbia Suicide Severity Rating Scale (C-SSRS) monitoring. They analyzed treatment-emergent suicide by C-SSRS category shift from no suicidal ideation (C-SSRS=0) at baseline to suicidal ideation (C-SSRS=1-5).

Studies in the meta-analysis included MDD patients with 17-item Hamilton Depression Rating Scale (HAMD17) total score ≥22 and item 1 (depressed mood) score ≥2 or HAMD17 total score ≥18; and Montgomery-Åsberg Depression Rating Scale total score ≥26. Key eligibility criteria for GAD studies included patients with Hamilton Anxiety Rating Scale total score ≥20, item 1 (anxious mood) score ≥2, and item 2 (tension) score ≥2; Clinical Global Impressions-Severity of Illness score ≥4; and HAMD17 total score ≤17.

Incidences of suicidal ideation/behavior were as follows: MDD (vilazodone=19.9 percent, placebo=24.7 percent); GAD (vilazodone=7.7 percent, placebo=9.4 percent). Shifts from no suicidal ideation/behavior at baseline to suicidal ideation during treatment are as follows: MDD (vilazodone=9.4 percent, placebo=10.3 percent); GAD (vilazodone=4.4 percent, placebo=6.1 percent). The difference between any suicidal ideation during vilazodone treatment and any suicidal ideation during placebo treatment is statistically significant, Thase said.

Among patients who entered these studies with no recent suicidal ideation or behavior at baseline, more than 85 percent continued to have no suicidality during treatment.

“I think the Thase data showing a favorable profile with respect to treatment-emergent suicidal features in the manufacturer’s pooled trials are compelling, credible, and useful,” said Joseph Goldberg, M.D., a clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York.

Goldberg said he has prescribed the medication extensively with success for patients with major depression and depression with prominent anxiety.

Vilazodone, a serotonin partial agonist-reuptake inhibitor (SPARI), was introduced in the United States in 2011. SPARI medications have the potential for faster onset of action, greater efficacy, and better tolerability, according to a 2014 study.

This medication also could have benefits for subgroups of people with depression, including those with anxiety disorders, and might have fewer sexual side effects than selective serotonin reuptake inhibitors (SSRIs), according to a 2015 study on vilazodone.

Thase told Psychiatric News that treatment-emergent suicidal ideation and behavior remain ongoing concerns with antidepressants. He cautioned that all patients be monitored for suicidal thoughts and behaviors during antidepressant treatment.

The study was funded by Forest Research Institute Inc., an Allergan affiliate, makers of vilazodone (Viibryd). Thase reported a potential conflict of interest in his role as an advisor or consultant for Allergan and Forest Laboratories. The other authors on the study acknowledged a potential conflict of interest as full-time employees of Allergan or Forest Research Institute at time of study. ■