The Food and Drug Administration (FDA) has approved Vraylar® (cariprazine) as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults.

The approval was based on data from 2 trials in adults who met DSM-IV-TR or DSM-5 criteria for MDD and had an inadequate response to 1 to 3 courses of prior antidepressant therapy. The primary endpoint was the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score, a 10-item clinician-rated scale that evaluates depressive symptomatology. Patients in both the treatment and placebo arms continued to receive antidepressant therapy.

Results from the 3111-301-001 study ( Identifier: NCT03738215) demonstrated that adjunctive treatment with cariprazine 1.5mg/day (n=250) was associated with an improved MADRS total score at week 6 compared with placebo (n=249) (placebo-subtracted difference, -2.5 [95% CI, -4.2, -0.9]; P =.005). The treatment effect in the cariprazine 3mg/day arm (n=252) was not found to be statistically significant.

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Findings from an 8-week, placebo-controlled study (RGH-MD-75; Identifier: NCT01469377) showed that adjunctive treatment with cariprazine 1-2mg/day demonstrated improvement in the MADRS total score at week 8 vs placebo but did not meet statistical significance.  Dosages of cariprazine between 2mg and 4.5mg per day were found to be statistically superior to placebo on the MADRS total score (placebo-subtracted difference, -2.2 [95% CI, -3.7, -0.6]).

The most common adverse reactions reported in the MDD trials included akathisia, restlessness, fatigue, constipation, nausea, insomnia, increased appetite, dizziness, and extrapyramidal symptoms.

“Patients with inadequate response to standard antidepressant medication are often frustrated by the experience of trying multiple medicines and still suffering from unresolved symptoms,” said Gary Sachs, MD, clinical vice president at Signant Health, associate clinical professor of psychiatry at Massachusetts General Hospital, and lead phase 3 clinical trial investigator. “Instead of starting over with another standard antidepressant, Vraylar works with an existing treatment and can help build on the progress already made.”

Vraylar, an atypical antipsychotic, is also indicated for the treatment of schizophrenia, for the acute treatment of manic or mixed episodes associated with bipolar I disorder, and for the treatment of depressive episodes associated with bipolar I disorder.


  1. US FDA approves Vraylar® (cariprazine) as an adjunctive treatment for major depressive disorder. News release. December 16, 2022. Accessed December 19, 2022.
  2. Vraylar. Package insert. AbbVie; 2022. Accessed December 19, 2022.

This article originally appeared on MPR