Adjunctive Cariprazine in Treating Major Depressive Disorder

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CONFERENCE REPORTER

Augmenting antidepressant with a second-generation antipsychotic is a well-supported option in a clinician’s arsenal when treating a patient with major depressive disorder (MDD).

The poster, “Long-Term Efficacy of Adjunctive Cariprazine in Patients With MDD: Results From an Open-Label 26-Week Safety Study,” presented at the American College of Neuropsychopharmacology 2023 Annual Meeting, demonstrated the efficacy of cariprazine as such an adjunctive treatment.

In a phase 3, 26-week, flexible dose (1.5 to 4.5 mg/d), safety study, investigators evaluated cariprazine combined with an antidepressant in adult participants with MDD who had completed an initial study (n=311). Participants received placebo or cariprazine and antidepressant therapy (double-blind placebo, n=109; double-blind cariprazine, n=108; single-blind placebo, n=94), and were then assessed via the Montgomery-Åsberg Depression Rating Scale (MADRS) total score and Clinical Global Impressions-Severity (CGI-S) score in changes from baseline.

Baseline mean (SD) MADRS and CGI-S scores were 22.8 (9.0) and 3.8 (1.0). MADRS response rates from baseline are as follows: week 4, 34.8%; week 12, 43.8%; week 18, 44.0%; and week 26, 47.6%. MADRS remission rates from baseline are: week 4, 11%; week 12, 34.8%; week 18, 42.6%; and week 26, 45.8%.

The study found that cariprazine 1.5–4.5 mg/day was generally safe and well tolerated when used as a long-term adjunctive therapy for MDD. Investigators noted via follow-up that MADRS and CGI-S scores continued to decrease in the 6 months following treatment. These data suggest that long-term treatment with adjunctive cariprazine was associated with a durable antidepressant effect in patients with MDD.

It is important to note that this study was not placebo-controlled, but investigators believe this simulated long-term treatment as it would occur in real practice.

Previous research indicates that cariprazine binds with higher affinity to D₃ receptors than D₂ receptors.^1,2 This is critical, as preclinical and clinical data suggest that enhanced D₃ activity may play a role in neuroadaptive changes related to antidepressant activity.³

Cariprazine was approved by the US Food and Drug Administration in December 2022 as an adjunctive therapy to antidepressants for the treatment of MDD in adults, but it is also FDA-approved to treat adults with depressive, acute manic and mixed episodes associated with bipolar I disorder (1.5 or 3 mg/day), as well as schizophrenia (1.5 to 6 mg/day). More than 8000 patients worldwide have been treated with cariprazine across more than 20 clinical trials evaluating the efficacy and safety of cariprazine for a broad range of psychiatric disorders.⁴

References

1. Kiss B, Horvath A, Némethy Z, et al. Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther. 2010;333(1):328-340.

2. Girgis RR, Slifstein M, D’souza D, et al. Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [(11)C]-(+)-PHNO. Psychopharmacology (Berl). 2016;233(19-20):3503-3512.

3. Leggio GM, Salomone S, Bucolo C, et al. Dopamine D(3) receptor as a new pharmacological target for the treatment of depression. Eur J Pharmacol. 2013;719(1-3):25-33.

4. Kuntz L. Cariprazine FDA-approved as adjunctive therapy to antidepressants. Psychiatric Times. December 20, 2022. https://www.psychiatrictimes.com/view/cariprazine-fda-approved-as-adjunctive-therapy-to-antidepressants