Risk of Death and Suicide on Vilazodone
Vilazodone carries a black box warning for increased suicidal thoughts and behaviors, particularly in adolescents and young adults, but post-hoc analyses of clinical trials show that vilazodone does not increase treatment-emergent suicidal ideation or behavior compared to placebo in adults with major depressive disorder. 1, 2
FDA Black Box Warning
- All antidepressants, including vilazodone, carry an FDA black box warning for suicidal thoughts and behaviors in adolescents and young adults under age 25. 1
- This warning applies to the class effect of antidepressants rather than specific evidence unique to vilazodone. 1
Clinical Trial Evidence on Suicide Risk
- In pooled analyses of four randomized controlled trials in major depressive disorder (n=2,233), suicide-related adverse events occurred in less than 1% of both vilazodone-treated and placebo-treated patients. 2
- Treatment-emergent suicidal ideation measured by Columbia-Suicide Severity Rating Scale (C-SSRS) occurred in 19.9% of vilazodone patients versus 24.7% of placebo patients in MDD trials. 2
- Shifts from no suicidal ideation at baseline to suicidal ideation during treatment occurred in 9.4% of vilazodone patients versus 10.3% of placebo patients. 2
- These data indicate little or no risk of treatment-emergent suicidal ideation or behavior with vilazodone in adults with MDD. 2
Context: Underlying Disease Risk
- Patients with major depressive disorder face an 8.62-fold increased risk of death by suicide compared to the general population, independent of medication treatment. 3, 4, 5
- The first year following diagnosis or treatment initiation carries the greatest suicide risk, requiring vigilant monitoring. 4, 5
- Women with MDD face 9.40 times higher odds of death by suicide compared to the general population. 4, 5
Monitoring Requirements
- Implement weekly monitoring within 1-2 weeks of treatment initiation for worsening suicidality, regardless of which antidepressant is prescribed. 4, 5
- Continue structured surveillance throughout the first year of treatment, as this represents the period of greatest risk. 4, 5
- Monitor for activation of mania or hypomania, particularly in patients with undiagnosed bipolar disorder. 1
Overdose and Toxicity Concerns
- Vilazodone may cause serotonin syndrome in single-substance overdoses, unlike typical SSRIs. 6
- Children are at particularly high risk and may become critically ill after ingesting as little as 10 mg (the minimum daily dose). 6
- Overdose may require ICU admission, endotracheal intubation, and parenteral benzodiazepines. 6
Therapeutic Efficacy and Safety Profile
- Vilazodone demonstrated significant improvement in Montgomery-Åsberg Depression Rating Scale scores compared to placebo in randomized controlled trials. 7
- The most common adverse effects are diarrhea, nausea, vomiting, and insomnia, with potentially lower rates of sexual dysfunction compared to traditional SSRIs. 8, 7, 9
- Improvement in depressive symptoms is typically noted within 1 week of initiating therapy, with increased remission rates at 6 weeks. 8
Common Pitfalls to Avoid
- Do not prematurely discontinue or switch antidepressants before completing adequate 6-8 week trials, as inadequate treatment duration is a modifiable risk factor for persistent suicidality. 4
- Do not prescribe vilazodone without screening for bipolar disorder first, as antidepressant monotherapy can trigger manic episodes. 1
- Do not assume the black box warning indicates vilazodone-specific increased suicide risk; the warning applies to all antidepressants as a class effect, while actual trial data shows no increased risk compared to placebo in adults. 1, 2