Efficacy and safety of cariprazine in the treatment of bipolar disorder

ABSTRACT

Introduction: Cariprazine, a D3-preferring, dopamine D2/D3 partial agonist, has efficacy in treating both acute phases of bipolar I disorder (BD-I). It has been approved by the FDA for treatment of acute manic, mixed and depressive episodes associated with BD-I.

Areas covered: In this review, the authors discuss the unique pharmacological properties and clinical efficacy profile of cariprazine, and their relevance in the context of routine clinical decision-making for BD-I. For the purpose of this review, the authors searched for clinical trials in BD published in the PubMed, Web of Science, Embase and PsychInfo databases as well as for studies registered in the ClinicalTrials.gov database.

Expert opinion: Based on evidence from RCTs in manic and mixed episodes, cariprazine in a dose-range of 3–12 mg is effective for treating acute mania and mixed states associated with BD-I. Importantly, evidence from placebo-controlled trials in bipolar depression suggests that cariprazine is also effective as a monotherapy in treating acute bipolar depression in doses of 1.5–3 mg/day. It is overall well tolerated; however, clinicians need to monitor patients for akathisia.

KEYWORDS:

• Cariprazine
• bipolar disorder
• mania
• bipolar depression
• atypical antipsychotic

Article Highlights

• Cariprazine is a D3 preferring, D2/D3 partial agonist. It is also a partial agonist at the serotonin 5HT_1A and antagonist at 5HT_2B and 5HT_2A receptors.

• It has been approved by the FDA for treating acute manic, mixed and depressive episodes associated with bipolar I disorder.

• Cariprazine is extensively broken down by CYP3A4 and CYP2D6 into desmethyl-cariprazine and didesmethyl-cariprazine.

• Because of its long half-life and long time taken to reach the steady state, doses should be increased later, rather than earlier in therapy.

• For acute manic and mixed episodes associated with bipolar I disorder, cariprazine is effective in a dose range of 3-12 mg/day.

• It is effective for treating bipolar depression in doses of 1.5-3 mg/day.

• The most common adverse effects are akathisia and extrapyramidal symptoms.

Box 1. Drug summary box

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Declaration of interest

LN Yatham has received research grants from, or is on speaking/advisory boards for Alkermes, AstraZeneca, Bristol-Myers Squibb, the Canadian Institutes of Health Research, (CIHR) the Canadian Network for Mood and Anxiety Treatments (CANMAT), Sumitomo Dainippon Pharma, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck, the Michael Smith Foundation for Health Research, Novartis, Otsuka, Pfizer, Ranbaxy, Servier, Sunovion, the Stanley Foundation and Valeant. JV Pinto has received a scholarship from the National Council for Scientific and Technological Development, the Ministry of Science and Technology, Brazil (CNPq). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

One referee is a consultant and serves on the speaker’s bureau for the manufacturer of cariprazine, as well as for the manufacturer of most of the available branded antipsychotics and antidepressants. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript has not been funded.