New directions in psychiatric drug development: promising therapeutics in the pipeline

ABSTRACT

Introduction

Psychiatric disorders are a leading cause of disability worldwide, calling for an urgent need for new treatments, early detection, early intervention, and precision medicine. Drug discovery and development in psychiatry continues to expand in new and exciting areas, with several new medications approved for psychiatric indications by the U.S. Food and Drug Administration (FDA) in the last 5 years.

Areas covered

In this review, the authors summarize recent new drug approvals and new molecular mechanisms in Phase 1–3 clinical development for psychiatric disorders. Advances in human genetics-driven target identification, emergent technologies such as artificial intelligence-enabled drug discovery, digital health technologies, and biomarker tools and strategies for testing novel mechanisms are highlighted.

Expert opinion

There continues to be a need for research focused on understanding the natural history, developmental trajectory, and pathophysiology of psychiatric disorders to identify new molecular and circuit-based targets. Looking to the future, a vision of precision psychiatry is emerging, taking advantage of advances in genetics, digital technology, and multimodal biomarkers to accelerate the development of next-generation therapies for individuals living with mental illnesses.

KEYWORDS:

• biomarkers
• bipolar disorder
• major depressive disorder
• post-traumatic stress disorder
• precision psychiatry
• psychiatric genetics
• public–private partnerships
• schizophrenia
• treatment-resistant depression

Article highlights

• Drug discovery and development in psychiatry continues to expand in new and exciting areas, with 15 new medications approved for psychiatric indications by the U.S. Food and Drug Administration (FDA) in the last 5 years.

• Six New Drug Applications have been submitted and are under review by the FDA for major depressive disorder, postpartum depression, schizophrenia, and post-traumatic stress disorder.

• The psychiatric drug development pipeline contains 118 potential new medicines with novel mechanisms in Phase 1–3 development by pharmaceutical companies, including 44 for depression, 29 for schizophrenia, 23 for anxiety disorders, 9 for bipolar disorder, 6 for attention deficit hyperactivity disorder, and 7 for other neuropsychiatric disorder indications.

• Advances in human genetic association studies have identified hundreds of genes and protein-coding variants involved in fundamental processes of neuronal synaptic biology, differentiation, and transmission which can be leveraged to discover new therapeutic targets.

• Emergent technologies, including artificial intelligence-enabled drug discovery, digital health technologies to enable testing of novel mechanism, and biomarker tools and strategies for disease phenotyping, stratification, and staging are enabling the discovery and development of novel mechanisms.

• A vision of precision psychiatry is emerging, engaging genetics, digital technology, and multimodal biomarkers to spur the development of next-generation therapies for early intervention, maximal clinical benefit, and reduction of disease burden in individuals living with mental illnesses.

Declaration of interest

All authors are employees of the National Institute of Mental Health (NIMH). SH Lisanby additionally is an inventor of patents and has patent applications on electrical and magnetic brain stimulation therapy systems held by the National Institutes of Health and Columbia University and does not receive royalties. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This manuscript has not been funded.