New Data: Cariprazine Adjunctive to Antidepressant Therapy for Anhedonia Symptoms

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CONFERENCE REPORTER

Investigators presented promising data on the durability of treatment with cariprazine adjunctive to antidepressant therapy for symptoms of anhedonia at the 2025 American Society of Clinical Psychopharmacology Annual Meeting in Scottsdale, AZ. Long-term open-label treatment with adjunctive cariprazine was associated with improvements in anhedonia for up to 26 weeks and suggest that long-term treatment with adjunctive cariprazine is safe and well tolerated, with potentially durable effects on anhedonia in patients with major depressive disorder (MDD).¹

Evidence suggests that first-line antidepressants may not adequately address symptoms of anhedonia.² Cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist, is approved as an adjunctive treatment of MDD in adults and could lead to reduction in symptoms.³

In a 26-week, phase 3, multicenter, open-label, flexible-dose (1.5-4.5 mg/d) study (NCT01838876), investigators assessed the safety and tolerability of cariprazine treatment used adjunctively with antidepressant therapies in adult patients with MDD.⁴ In the lead-in study, participants completed an 8-week, prospective, open-label, antidepressant therapies + single-blind (SB) placebo (PBO) phase. Participants who did not adequately respond to antidepressant therapies + PBO were randomized to 8-week double-blind (DB) treatment with PBO + antidepressant therapies or cariprazine + antidepressant therapies. Patients who responded to PBO + ADT were not randomized for DB treatment but continued to receive SB placebo + antidepressant therapies for 8 more weeks. Anhedonia was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) anhedonia subscale, which consists of 5 item scores (item 1 [apparent sadness], item 2 [reported sadness], item 6 [concentration difficulties], item 7 [lassitude], and item 8 [inability to feel]). Outcomes included mean (SE) change from baseline at week 26. Additionally, the mean change from baseline at the end of the open-label treatment period was assessed using the last available observation for all patients. Analyses were based on the intent-to-treat (ITT) population, which included all patients who received 1 or more doses of cariprazine and had baseline and greater than or equal to 1 post-baseline efficacy assessments. Results were summarized using descriptive statistics.

The ITT population included 336 participants. Of these, 101, 91, and 86 were in the rollover DB PBO + antidepressant therapies, DB cariprazine + antidepressant therapies, and SB PBO + antidepressant therapies subgroups, respectively, and 58 were new patients in the open-label study. The overall mean daily dose of cariprazine during the treatment period was 2.71 mg/d. The most frequently taken dose was 3 mg/day (52%; n=182), followed by 1.5 mg/day (28%; n=99) and 4.5 mg/day (17%; n=59). In the overall ITT population, as well as all patient subgroups, treatment with cariprazine + antidepressant therapies was associated with reductions from baseline in anhedonia subscale scores as early as week 4 and at all study visits through week 26. When using the last available observation for all patients, the mean change from baseline in anhedonia subscale score was –5.42 (0.37), similar to that observed at week 26. Treatment with open-label cariprazine + antidepressant therapies was also associated with reductions from baseline in all 5 individual MADRS anhedonia item scores. Cariprazine was safe and generally well tolerated for up to 26 weeks of treatment. Study limitations included the open-label study design and lack of inferential statistics.

References

1. Cutler AJ, Chepke C, Wilson AC, et al. Effect of long-term treatment with adjunctive cariprazine on anhedonia in patients with major depressive disorder: post hoc analysis of a 26-week open-label study. Poster presented at: 2025 American Society of Clinical Psychopharmacology Annual Meeting; May 27-30, 2025; Scottsdale, AZ. Accessed May 29, 2025.

2. Serretti A. Anhedonia: current and future treatments. PCN Rep. 2025;4(1):e70088.

3. 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

4. Vieta E, Earley WR, Burgess MV, et al. Long-term safety and tolerability of cariprazine as adjunctive therapy in major depressive disorder. Int Clin Psychopharmacol. 2019;34(2):76-83.