Cariprazine for Mania Appears Safe and Well-Tolerated
At the 2014 meeting of the International College of Neuropsychopharmacology, researcher Lakshmi Latham presented a poster on three studies of the atypical atypical antipsychotic caripazine, a treatment that has not yet been approved by the Federal Drug Administration. We call it an atypical atypical because it is a partial agonist at dopamine D2 and D3 receptors, meaning it stimulates the receptors a little, but in the presence of high levels of dopamine it blocks excess activity by sitting on the receptor and preventing the actions of the excess dopamine. Aripiprazole is also a partial agonist at dopamine and serotonin 5HT1a receptors, but caripazine differs in that it has a particular affinity for the D3 receptor.
Previous analyses had revealed that cariprazine has good acute antimanic efficacy. All three studies described by Latham were randomized, double-blind, placebo-controlled three-week studies in patients with bipolar mania. In total the studies included 1065 patients, 442 of whom received placebo and 623 of whom received cariprazine.
Cariprazine doses from three studies were pooled, and ranged from 3-12 mg/day. Additional analyses evaluated the 3-6 and 9-12 mg/day groups specifically.
Approximately 70% of patients completed the study. The most common side effects included akathisia or restless legs (placebo, 5%; cariprazine, 20%), extrapyramidal disorder characterized by abnormal motor symptoms (5%, 13%), restlessness (2%, 6%) and vomiting (4%, 9%). The incidence of serious side effects was similar across the placebo and the treatment groups. Side effects that led to discontinuation of participation in the study occurred in 7% of placebo patients and 12% of cariprazine patients. Suicidal ideation was an infrequent side effect (placebo, 4; cariprazine, 2), and there were no suicide attempts.
Mean changes in weight were small (averaging 0.17kg in patients taking placebo and 0.54kg in those taking cariprazine), and the proportion of patients with 7% or higher increase in weight were similar across the two groups (both 2%). Mean changes in blood pressure and pulse were slightly greater with cariprazine and were related to dosage. Cariprazine was not associated with mean increases in electrocardiogram (EKG) parameters except for a slight increase in ventricular heart rate versus placebo (5.0 and 0.9 bpm, respectively). Mean changes in lipids and glucose were generally small and similar between groups. Levels of the hormone prolactin decreased in both groups.
Latham concluded that cariprazine treatment for three weeks was safe and well-tolerated.
