NYMC Faculty Publications


Cariprazine for Bipolar Depression: What is the Number Needed to Treat, Number Needed to Harm and Likelihood to be Helped or Harmed?

First Page


Document Type


Publication Date

October 2019


Psychiatry and Behavioral Sciences


OBJECTIVE: Cariprazine is an oral antipsychotic approved in the US for the treatment of schizophrenia, acute bipolar mania, and most recently, bipolar depression. The aim of this systematic review is to describe the efficacy, tolerability, and safety of cariprazine for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults. DATA SOURCES: The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the search terms 'cariprazine' AND 'bipolar' AND 'depression', and by also querying the Web of Science commercial database for clinical poster abstracts, and by asking the manufacturer for copies of posters presented at congresses. Product labeling provided additional information. STUDY SELECTION: Double-blind placebo-controlled studies in adults with bipolar depression. DATA EXTRACTION: Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were calculated from the available study reports and other sources of information. DATA SYNTHESIS: Cariprazine differs from other antipsychotics in that it has a 10-fold higher affinity for dopamine D3 receptors than for D2 receptors. Cariprazine's principal active metabolite, didesmethyl-cariprazine (DDCAR), has a half-life of 1 to 3 weeks and at steady state DDCAR is the predominant circulating moiety. Four double-blind placebo-controlled studies of cariprazine for bipolar depression were found of which three were considered positive and provided data on efficacy; all four studies were used to assess tolerability. Rates of treatment response, defined by a >/=50% reduction from baseline on the Montgomery-Asburg Depression Ratting Scale (MADRS) total score at study endpoint, for the approved doses of 1.5 mg/d and 3.0 mg/d (pooled) vs. placebo were 46.3% vs. 35.9% (NNT 10, 95% CI 7-21). Corresponding rates for remission (defined as MADRS total score