MedicalResearch.com Interview with:
Dr. Stephen Stahl MD PhD
Professor of Psychiatry
University of California San Diego
MedicalResearch.com: What is the background for this study? How does cariprazine differ from other medications for bipolar depression?
MedicalResearch.com: It is important to note that cariprazine, a dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, is approved for the treatment of schizophrenia (1.5-6 mg/d) and bipolar mania (3-6 mg/d) in adults. It is not yet approved for depressive episodes related to bipolar I disorder (bipolar depression).
In these data that focus on the investigational use for the treatment of bipolar depression, cariprazine has demonstrated efficacy vs placebo (PBO) in 3 phase 2/3 studies of patients with bipolar depression (NCT01396447, NCT02670538, NCT02670551). These analyses investigated the efficacy of cariprazine in patients with bipolar depression and concurrent manic symptoms (mixed features).
Response: What are the main findings?
- A total of 808 (58.4%) of 1383 patients had bipolar depression and concurrent manic symptoms. For MADRS score change, the LS mean difference (LSMD) vs PBO was statistically significant in favor of cariprazine 1.5 mg (-2.5, P=.0033) and 3 mg (-2.9, P=.0010) in patients with manic symptoms and for cariprazine 1.5 mg (-3.3, P=.0008) in patients without manic symptoms.
- Similarly, the LSMD vs PBO for HAMD17 total score change was significant for cariprazine 1.5 and 3 mg (-1.9 and -1.5; P<.05 both) in patients with manic symptoms and for cariprazine 1.5 mg (-2.2, P=.0042) in patients without manic symptoms.
- On CGI-S score change, the LSMD vs PBO was significantly greater for cariprazine 1.5 and 3 mg, respectively, in patients with manic symptoms (-0.24 and -0.25; P<.05 both) and in patients without manic symptoms (-0.40 and -0.26; P<.05 both). Rates of MADRS response and remission, respectively, were significantly greater for cariprazine 1.5 mg (46.6% and 31.3%; P<.05 both) and 3 mg (49.8% and 31.4%; P<.01 both) than PBO (37.8% and 21.0%) in patients with manic symptoms and for cariprazine 1.5 mg (45.2% and 32.3%; P<.05 both) vs PBO (33.3% and 20.7%) in patients without manic symptoms.
- Rates of CGI-S remission were significantly greater than PBO for all cariprazine doses in both patient subgroups (P<.05 all).
MedicalResearch.com: What should readers take away from your report?
- Cariprazine demonstrated efficacy versus placebo in patients with mixed features in both the bipolar depression and bipolar mania populations, suggesting that cariprazine may be an appropriate treatment option for patients with bipolar depression with or without mixed features.
- Significant improvement for cariprazine versus placebo in most MADRS single items and all YMRS individual items suggests broad efficacy in depressive and manic symptoms, respectively; therefore, cariprazine appears be effective across the range of symptoms that affect patients with bipolar disorder.
- Cariprazine was generally well tolerated in the proposed dose range for bipolar depression (1.5–3 mg/d) and the FDA-recommended dose range (3–6 mg/d) for bipolar mania; slower titration and lower cariprazine doses in the bipolar depression studies relative to the bipolar mania studies resulted in a better tolerability profile.
Disclosures: I am a paid consultant for Allergan.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Dr. Willlie Earley, Associate Vice President of Clinical Development at Allergan:
Response: Allergan is conducting a few interesting studies to build on what we’ve learned. We are currently investigating cariprazine as an adjunct to antidepressants in the treatment of major depressive disorder (MDD) as well as plans to study cariprazine in pediatric patients for the treatment of schizophrenia and bipolar disorder.
APA 2019 abstract:
Cariprazine Efficacy in Patients With Bipolar Depression and Concurrent Manic Symptoms: Post Hoc Analysis of 3 Randomized, Placebo-Controlled Studies
- #P8-080: Cariprazine Efficacy in Patients With Bipolar Depression and Concurrent Manic Symptoms: Post Hoc Analysis of 3 Randomized, Placebo-Controlled Studies (Tuesday, May 21; 2:00 p.m. – 4:00 p.m. PT, Moscone South, Exhibition Level, Room 3-4; Presented by: Stahl, S.
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