Cariprazine in the Treatment of Bipolar Disorder: Within and Beyond Clinical Trials

Abstract

Bipolar disorder (BD) is chronic psychiatric disorder associated with significant impairment in psychosocial functioning and quality of life. Although current pharmacological treatments for BD have improved its clinical management, many patients do not achieve remission, particularly those suffering from bipolar depression. In addition, available treatments are associated with a myriad of potential adverse effects, which highlights the need for novel therapeutic agents that can be effective for both phases of the illness with a reduced side effect burden. Cariprazine is a novel antipsychotic that is a dopamine D2/D3 partial agonist with a preference for D3 receptors. In this review, we examine the pharmacological properties, clinical efficacy and tolerability profile of cariprazine in patients with BD, taking into account the latest clinical trials data. We also review post hoc analyses addressing clinically relevant subgroups and symptom domains in BD. Current evidence suggests efficacy for cariprazine 3–12 mg/day in the treatment of acute manic and mixed episodes; for bipolar depression, the efficacy of cariprazine appears to be dose-related, with doses of 1.5–3 mg/day beneficial as monotherapy. Cariprazine is overall well-tolerated by patients in both manic and depressive episodes. Its most common side effects relative to placebo include akathisia, extrapyramidal symptoms and nausea. There are no metabolic concerns reported with cariprazine use. In summary, the latest evidence suggests that cariprazine is an effective and safe treatment option for BD.

Cariprazine: An Antipsychotic Medication with High Therapeutic Potential

“…Akathisia was the main adverse event leading to discontinuation in cariprazine treatment. However, it can be effectively managed by using a beta-blocker, such as propranolol [26]. Cariprazine was not associated with clinically meaningful changes in body weight, glycemic or prolactin levels [4,33].…”

A review on the pharmacology of cariprazine and its role in the treatment of negative symptoms of schizophrenia

“…This differs from two other TGAs like aripiprazole and brexpiprazole, by its distinct receptor-binding characteristics not only at dopamine D2/D3 receptors, but also at serotonin 5HT1A, 5HT2B, 5HT2A, 5HT2C, and histamine H1 receptors ( 62 ). Cariprazine acts as an antagonist when dopamine activity is normal and as partial agonist when the activity is low, depending on the available dopamine ( 63 ). This feature of cariprazine is proven effective for treatment of predominant primary negative symptoms of schizophrenia ( 24 , 64 ).…”

“…Its strong affinity towards 5-HT 1B receptor is the reason for reduced EPS and akathisia; however, the clinical relevance of antagonism to serotonin 5-HT 2B receptors is unknown. Partial agonism of cariprazine to 5-HT 1A receptors lowers depressant effects of schizophrenia, and weak antagonism to 5-HT 2C and H1 receptors reduces risk of weight gain, metabolic abnormalities and sedation than olanzapine and quetiapine ( 63 ). Additionally, cariprazine has a lower or negligible affinity for noradrenergic, histaminergic, and cholinergic receptors ( 65 ).…”

“…Additionally, cariprazine has a lower or negligible affinity for noradrenergic, histaminergic, and cholinergic receptors ( 65 ). Because of its lower inhibition of dopaminergic neurotransmission in the striatum, cariprazine has lower risk of developing EPS than other atypical antipsychotics ( 63 ). The receptor binding affinities of different anti-psychotics in comparison with cariprazine is shown in Table 2 ( 5 , 36 , 66 – 69 ).…”

New treatment strategies for bipolar disorder in the elderly

“…In contrast, in the case of depression in the course of bipolar disorder, the efficacy of cariprazine seems to be effective in monotherapy at a dose of 1.5-3 mg / day. Cariprazine gives high hopes because it is well tolerated by patients in both manic and depressive episodes [18].…”