This Month in Psychopharmacology

Efficacy of Cariprazine in Patients with Bipolar Depression and Comorbid Anxiety

Patients with bipolar disorder and comorbid anxiety disorders can often be difficult to treat because they have more depressive and manic/hypomanic episodes, shorter periods of euthymia, shorter time to relapse, more suicidal behavior, increased substance use issues, greater risk of residual symptoms, and reduced quality of life and functioning. Because of this, patients are more likely to be treated with polypharmacy, which may be associated with increased clinical complexity and medication cost.


Unfortunately, the efficacy of first-line agents approved to treat anxiety cannot be generalized to managing anxiety in bipolar disorder. For example, serotonergic antidepressants are not recommended as bipolar disorder monotherapy because they have the potential to cause treatment-emergent mood instability. Benzodiazepines may be helpful, but there is no good evidence that benzodiazepines are the best option in the context of anxiety and bipolar disorder. Cariprazine (Figure.) is an atypical antipsychotic that targets dopamine D3 receptors as a partial agonist, serotonin 1A receptors as a partial agonist, and serotonin 2B receptors as an antagonist and has been shown to help decrease anxiety symptoms in patients with bipolar disorder.

In this post-hoc analysis by Jain and colleagues, data were pooled from two identically designed phase 3 randomized placebo-controlled, double blind, multicenter, parallel group, fixed-dose studies in adults with bipolar I disorder. In total, there were 952 patients data pooled for this study where 319 were in the placebo group, 316 taking 1.5 mg/day of cariprazine, and 317 taking 3 mg/day of cariprazine. These patients were further divided into low-anxiety and high-anxiety subgroups based on their HAM-A scores where HAM-A scores over 18 were designated as high-anxiety and those under 18 were designated low-anxiety.

Overall, this study found that low-dose 1.5 mg/day of cariprazine was more effective at treating individuals with high anxiety, while the higher dose of 3 mg/day of cariprazine was effective in treating the low-anxiety group. Rates of remission data also show that individuals with higher anxiety showed better results with 1.5 mg/day of cariprazine with an odds ratio of 1.81 and a number needed to treat (NNT) of 9 while the odds ratio for the 3 mg/day group was only 0.98. As for the lower anxiety group, 3 mg/day was more effective at helping patients reach remission with an odds ratio of 2.62 and an NNT of 6, while the 1.5 mg/day subgroups odds ratio was 1.32.

In conclusion, these data suggest that cariprazine is a viable treatment option for patients struggling with comorbid anxiety and bipolar disorder.


Jain R, McIntyre RS, Cutler AJ, et al. International Clinical Psychopharmacology. 2024;39(2):82-92. Abstract

Additional Education and Resources:


Encore Presentation
What’s In a Name? Using "Antipsychotics" to Treat Mood Disorders
CME/CE Credit: 1.0 | Expires: November 12, 2026


Stahl's Essential Videos
Stahl’s Essential Psychopharmacology, Chapter 7D: Treatments for Bipolar Spectrum Disorders
CME/CE Credit: 0.75 | Expires: February 10, 2025


Encore Presentation
BPI and BPII: Diagnosing and Treating Across the Spectrum
CME/CE Credit: 0.75 | Expires: November 12, 2026


Patient Education
Bipolar Neurobiology Coloring Page
Fun and educational patient handouts!


Video Snippet
Differential Diagnosis for Mood Disorders
CME/CE Credit: 0.50  |  Expires: November 27, 2026


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