Cost-effectiveness of vortioxetine compared with levomilnacipran and vilazodone in patients with major depressive disorder switching from an initial antidepressant.

Introduction: Many patients with major depressive disorder (MDD) do not achieve remission with their first antidepressant (AD), resulting in a high burden due to treatment failure. Vortioxetine is a valid treatment option for patients with MDD only partially responding to their first AD. Characterization of vortioxetine's potential benefits versus other approved treatments is important. Areas covered: The cost-effectiveness of vortioxetine, including cognitive outcomes, was modeled in comparison with levomilnacipran and vilazodone for patients switched to these medications after inadequate responses to a first AD. Expert opinion: Vortioxetine was associated with incremental quality-adjusted life-year (QALY) gains versus levomilnacipran (0.008) or vilazodone (0.009). Vortioxetine was dominant versus levomilnacipran and cost-effective versus vilazodone (incremental cost-effectiveness ratio [ICER],33,829 USD/QALY). In sensitivity analyses using residual cognitive dysfunction rates (vortioxetine, 49%; levomilnacipran, 58%, and vilazodone, 64%), incremental QALY gains for vortioxetine versus levomilnacipran (0.0085) or vilazodone (0.0109) were found. Vortioxetine remained dominant versus levomilnacipran and cost-effective versus vilazodone (ICER, 27,633 USD/QALY). ICER reduction was found with cognition outcomes inclusion. This model provides additional support for considering vortioxetine for patients requiring a switch of MDD treatments, although its conclusions are limited by the data available for inclusion. Additional research and real-world trials are needed to confirm the findings.

Measures of suicidality in phase 3 clinical trials of levomilnacipran ER in adults with major depressive disorder.

OBJECTIVE: To evaluate the effects of levomilnacipran extended-release (ER) on suicidal ideation and behavior in adults with major depressive disorder (MDD). METHODS: Post hoc analyses were conducted in patients from 4 randomized, double-blind, placebo-controlled trials and a long-term, open-label extension study of levomilnacipran ER (40-120 mg/d) in adults with MDD. Analyses included incidence of suicide-related treatment-emergent adverse events (TEAEs); incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation (score=1-5) and behavior (score=6-10); percent of patients who shifted from no C-SSRS suicidal ideation/behavior at baseline to suicidal ideation during treatment (worsened from score=0 to score=1-5), or vice-versa (improved from score=1-5 to score=0). RESULTS: Suicide-related TEAEs occurred in<1% of patients in the levomilnacipran ER studies. The incidence of C-SSRS suicidal ideation was 22.2%, 23.9%, and 21.7% for placebo, short-term levomilnacipran ER, and long-term levomilnacipran ER, respectively; C-SSRS suicidal behavior was<1% in all of these groups. In the short-term studies, the percentage of patients with C-SSRS shifts were as follows: worsening from score=0 to score=1-5 (placebo, 8.6%; levomilnacipran ER, 11.0%); improvement from score=1-5 to score=0 (placebo, 24.0%; levomilnacipran ER, 27.7%). CONCLUSION: In adult MDD patients, the incidence of suicidal ideation and behavior was similar between placebo and short-term levomilnacipran ER as indicated by TEAE reports and C-SSRS scores. Worsening in C-SSRS scores was also similar between placebo and levomilnacipran ER. There was no indication of increased suicidality during longer courses of continued therapy. Together, these findings suggest that this medication is not associated with increased risks of suicidal ideation or behavior.