Efficacy of Brexpiprazole Combination Therapy on Anhedonia in a Case of Treatment Resistant Bipolar II Depression

Abstract

B ipolar disorder (BPD) is a lifelong, episodic illness 1 that affects nearly 50 million persons globally. 2 Depressive episodes are responsible for the major amount of disability, 2 especially in terms of anhedonia and circadian rhythm disturbance. 3 Nevertheless, there is only a limited number of approved drugs for bipolar depression: quetiapine, fluoxetine/ olanzapine combination, cariprazine, and lurasidone are the only medications currently approved by the US Food and Drug Administration (FDA). 4 Antidepressants have limited evidence of efficacy. 5 Brexpiprazole is a dopamine 2 (D 2 ) and serotonin 5HT 1A receptor partial agonist antipsychotic 6 ; it is approved for schizophrenia (FDA, 2015; EMA, 2018), as adjunctive treatment to antidepressants in major depressive disorder (FDA, 2015), and recently, it was investigated as monotherapy in acute mania of BPD I. 7 To the best of our knowledge, 2 single-arm studies have evaluated the efficacy of brexpiprazole in bipolar depression (ClinicalTrials.gov Identifier: NCT03427892 and NCT04569448), the former was completed with positive results on depressive symptoms, the latter is still recruiting. However, possible benefits on anhedonia, anxiety, irritability, and insomnia were not assessed, and follow-up was limited to 8 weeks, in the open label trial with published results. 8 In addition, this study did not include patients with treatment-resistant depression.In this regard, we present the case of a woman with treatment-resistant bipolar II depression who showed rapid and sustained amelioration not only in overall depressive symptoms, but in the hedonic drive, after brexpiprazole augmentation therapy, during a 16-week period of observation. Written informed consent was obtained from the patient for publication of the case report.