Aripiprazole and Cariprazine for Bipolar Disorder?

In this article, the present author, a research psychologist and measurement expert, evaluates the major clinical trials used to support the use of aripiprazole and the chemically almost identical cariprazine for treating bipolar disorder. The main problem with the trials is that they were conducted mainly with outpatients, who on average were only moderately manic in the mania studies and only moderately depressed in the depression studies. The effectiveness of aripiprazole and cariprazine in treating moderate mania, most likely hypomania, and moderate depression, was far from encouraging. Aripiprazole produced just 7% greater reduction of mania symptoms than did placebo treatment, and just 1% greater reduction of depression symptoms than did placebo treatment when administered, as is common practice, with an SSRI or SNRI antidepressant. Cariprazine proved to be not much better because at the high dosage level of 3.0 mg/day to 12.0 mg/day, cariprazine produced only 9% greater reduction of mania symptoms than did placebo treatment, and at the typical low dosage of 1.5 to 3.0 mg/day produced just 4% greater reduction of depression symptoms than did placebo treatment. Moreover, as the pharmaceutical industry has long suspected, there is a massive placebo effect associated with these two drugs, especially for depression. These findings imply that government regulatory authorities’ approval of aripiprazole and cariprazine as mood stabilizers for treating bipolar disorder is dubious. Nevertheless, the possibility remains that the purported mood-stabilizing mechanism of these two medicines is activated only with patients presently experiencing severe mania or severe depression, a possibility that requires an in-hospital clinical trial or, at the very least, a longitudinal analysis of bipolar patients’ treatment records. Furthermore, an appendix to the present article demonstrates that the measures used in the trials, the Young Mania Rating Scale and the Montgomery-Asberg Depression Rating Scale, are deficient and that a briefer combination measure focusing only on the core symptoms of bipolar disorder should be used.