Novel experimental and early investigational drugs for the treatment of bipolar disorder

ABSTRACT

Introduction

The quest toward more effective treatments for bipolar disorder (BD) solicits novel drugs and further research on the underpinning neurobiology. The present review aims to critically appraise the existing evidence about the pharmacological treatment of BD toward the development of novel treatment avenues.

Areas covered

The present review appraises animal and human studies concerning both the currently available psychotropic drugs, and the general medicine drugs which may represent a path toward the development of novel drugs for BD. PubMed and Scopus were last accessed on February 20^th, 2021 for records indexed upon inception relevant to the pharmacological treatment of BD. Immune-modulating agents, anti-inflammatory agents, and glutamate antagonists represent the most intriguing potential targets for the development of new drugs for BD, thus receiving critical appraisal in the present text.

Expert Opinion

Regardless of the neurobiological pathways worthy of investigation toward the development of experimental drugs for BD, several unmet needs need to be addressed first. In particular, several biomarkers are altered in BD. However, it is the opinion herein expressed by the authors that it remains uncertain what comes first, that is peripheral changes or the disease.

KEYWORDS:

• Bipolar disorder
• experimental drugs
• minocycline
• esketamine
• tamoxifen
• ebselen

Article highlights

• Established treatments for bipolar disorder (BD), such as lithium, still represent a path towards a better understanding of the neurobiology of BD.

• Novel treatment options for BD will arise from a deeper understanding of the molecular mechanisms involved in BD.

• The preliminary results fetched by several animal studies on novel drugs for BD require replication by controlled trials in humans.

• Human studies warrant controlled replication for TNF-alpha inhibitors and memantine, for bipolar depression and acute mania, respectively.

• Animal studies are in their infancy concerning arketamine for depression, and ebselen for mania.

Acknowledgments

Goce Kalcev (M.D.) participated in writing this paper in the framework of the International Ph.D. in Innovation Sciences and Technologies at the University of Cagliari, Italy.

Authors’ contributions

GK has prepared the first draft; MGC, MF, and AEN revised it. All authors approved the final version of the paper.

Declaration of Interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.