Pharmacological Treatment of Bipolar Depression: What are the Current and Emerging Options?

Depression accounts for the predominant burden associated with bipolar disorder. The identification and management of bipolar depression are challenging, since bipolar depression differs from unipolar depression, responding poorly to traditional antidepressants, which may also induce a switch to hypomania/mania, mixed states and/or cause rapid cycling. Current treatment options for bipolar depression are limited and guidelines vary greatly in their recommendations, reflecting gaps and inconsistencies in the current evidence base. Moreover, some treatment options, such as quetiapine and olanzapine-fluoxetine, although clearly efficacious, may be associated with adverse cardiometabolic side effects, which can be detrimental to the long-term physical health and well-being of patients, increasing the likelihood of treatment non-adherence and relapse. Evidence for some more recent therapeutic options, including lurasidone and cariprazine, suggests that patients' symptoms can be effectively managed without compromising their physical health. In addition, novel agents targeting alternative neurotransmitter pathways and inflammatory processes (such as ketamine and N-acetyl cysteine) are emerging as promising potential options for the treatment of bipolar depression in the future.

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© 2020 Yalin and Young.

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Nefize Yalin is employed by the Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, UK. She has worked as a researcher in clinical studies conducted together with Jannsen Cliag, Corcept Therapeutics and COMPASS Pathways. She also reports non-financial support from mXm Medical Communications and grants from Sunovion Pharmaceuticals, during the conduct of the study. Allan Young is employed by the Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, UK, and is an Honorary Consultant at the Maudsley Hospital, London, UK (UK NHS). He has conducted paid lectures and advisory boards for Allergan, AstraZeneca, Bionomics, BrainCells Inc., Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, Novartis, Otsuka Pharmaceutical Co., Pharmaceutica, Pfizer, Roche, Sanofi-Aventis, Servier Laboratories, Sunovion and Wyeth. He has no shareholdings in pharmaceutical companies. He was lead Investigator for the EMBOLDEN Study (AstraZeneca), BCI Neuroplasticity Study and Aripiprazole Mania Study, and has been involved in investigator-initiated studies for AstraZeneca, Eli Lilly and Wyeth. He was also the Principal Investigator in the Restore-Life VNS registry study funded by LivaNova. Principal Investigator on ESKETINTRD3004: “An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression” For Janssen/Johnson & Johnson; Principal Investigator on “The Effects of Psilocybin on Cognitive Function in Healthy Participants” for Compass; Principal Investigator on “The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)” for Livanova. He has received grant funding (past and present) from: NIMH (USA); NIHR (UK); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); VGH & UBC Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); and MSFHR (Canada). The authors report no other conflicts of interest in this work.