Adjunctive Cariprazine with Antidepressants Benefits Adult Major Depressive Disorder

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New phase 3 data presented at APA 2022 support the agent as an adjunctive in older patients without benefit from monotherapy antidepressant medication.

Cariprazine (VRAYLAR) provided statistically significant benefit versus placebo in Montgomery-Åsberg Depression Rating Scale (MADRS) total score change as an adjunctive therapy for adults with major depressive disorder (MDD), according to new findings.

In phase 3 data presented at the American Psychiatric Association (APA) 2022 Annual Meeting in New Orleans this week, a team of Abbie-supported investigators reported a 1.5 mg dose of the atypical antipsychotic therapy was effective in improving MADRS and anxiety per Hamilton Anxiety Rating Scale over 6 weeks among older patients without prior response to standard-care antidepressant therapy.

Cariprazine was also observed to be well-tolerated and safe as an adjunctive therapy to antidepressant medication in the patient population, further suggesting its potential utility as an MDD agent.

In an interview with HCPLive during APA 2022, study author Gary Sachs, MD, associate professor of psychiatry at Massachusetts General Hospital, discussed the impact of the phase 3 findings as they relate to complementing standard MDD care.

“Cariprazine is an interesting compound, because it now has been studied in schizophrenia, manic and mixed states of bipolar depression, and now finally, MDD,” Sachs said. “What’s happened as we as a field have learned how to use (standard antidepressants), we’ve gotten comfortable moving patients from one to another—even though, for instance, the STAR*D results show us that the law of diminishing returns happen almost immediately.”

Sachs discussed the observed MDD patient population in the phase 3 trial, whose mean age of 44.8 years old underscores the reality that they’ve likely been burdened with treatment-unresponsive depression for decades.

“To have some drugs now with proven efficacy added on to the standard drugs to take away that forced choice…now we have another kind of option, and I can say to a patient, ‘This has been proven to have efficacy for the diagnosis you have’,” he said.

In this role as an efficacious adjunctive therapy, cariprazine would also be a “fault-tolerant” option, Sachs said. A patient reliant on standard short-acting antidepressant regimens has more pressure to adhere to daily care.

Though 1.5 mg cariprazine fared better in efficacy outcomes than 3 mg doses, Sachs said more interpretation into dosing and long-term use is still under work. He also expressed interest in seeing the benefit of cariprazine in treating patients with anxious distress.

“In turns out the biggest predictor of who’s not going to respond (to antidepressants) are those subject to, in addition to low mood, symptoms of anxiety,” Sachs said. “That is clearly a more worrisome, less responsive group. And in this study…you see a benefit on the Hamilton Anxiety Rating Scale, which is intriguing, but we don’t really have all the breakout of data to know whether this is a beneficial drug for those who meet anxious distress.”

The study, “Cariprazine for the Adjunctive Treatment of Major Depressive Disorder: Results of a Randomized Phase 3 Placebo-Controlled Study (Study 301),” was presented at APA 2022.