Efficacy of Vortioxetine Monotherapy for Posttraumatic Stress Disorder

Abstract

Purpose/Background There are few efficacious pharmacological treatments for posttraumatic stress disorder (PTSD) and many patients fail to benefit from existing treatments. Vortioxetine, a recently developed antidepressant, acts as a serotonin modulator through inhibition of the serotonin transporter and actions at multiple types of serotonin receptors. Its unique pharmacodynamic profile suggests it may have efficacy for the treatment of PTSD. Methods/Procedures We conducted a 12-week placebo-controlled, randomized clinical trial of vortioxetine (flexibly dosed from 10 to 20 mg/d) versus placebo in adults with PTSD. The primary outcome was change from baseline in the past-month version of the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), analyzed using a mixed-model repeated-measures analysis of variance. Findings/Results Forty-one patients were randomized, and 32 (78%) completed the 12 weeks of treatment. The mean reduction in CAPS-5 scores at week 12 did not significantly differ between the 2 arms; the effect size for the difference in changes between vortioxetine and placebo on CAPS-5 total scores at week 12 was Cohen d = 0.29. However, at week 8, the drug-placebo difference was d = 0.78, which met the multivariate criteria for statistical significance, P = 0.014. Implications/Conclusions In this study of 41 patients, vortioxetine did not demonstrate superiority over placebo for adults with PTSD. Future PTSD trials may benefit from stratifying the randomization based on number of years since the index traumatic event and a history of failure to respond to treatment.

Effects of Vortioxetine Versus Placebo on Cognition and Functional Capacity in Adults With Posttraumatic Stress Disorder

“…8 Glutamate's role in hyperarousal symptom development is supported by association of elevated glutamate in the parieto-occipital cortex and insomnia symptoms in patients with posttraumatic stress disorder. 9 Riluzole is a glutamatergic modulator that reduces glutamate excitotoxicity by increasing neuronal and glial reuptake, decreasing presynaptic release, and inhibiting voltage-gated sodium channels. 10 In previous studies, it has demonstrated efficacy as augmentation for depression.…”

“…Vortioxetine is a serotonin-modulating pharmacotherapeutic approved by the US Food and Drug Administration for the treatment of major depressive disorder. In the previously published primary study, 9 vortioxetine separated from placebo at week 8 of the 12-week clinical trial (Cohen d = 0.78) and the end point effect size for vortioxetine versus placebo was d = 0.29.…”