Rethinking the medication management of major depression

ABSTRACT

Introduction

Current treatment of major depressive disorder (MDD) warrants critical reexamination. Initial treatment response rates are modest and drop dramatically after 3 months. Meanwhile, MDD is emerging as the leading cause of disease burden worldwide.

Areas covered

We searched PubMed (up to June 2021) for randomized controlled trials comparing antidepressant combinations versus monotherapy. We discuss findings from these studies in light of current treatment guidelines for MDD. These recommend a sequence of single, six-week-long, medication trials, before trying antidepressant combinations. The result leaves one third of patients still depressed after six months of treatment.

Expert opinion

Optimizing the first three months of MDD treatment is crucial because response rates during this period are five times better than in the second three months. We propose a new, evidence-based algorithm of sequential antidepressant treatment steps, termed Accelerated Sequential Antidepressant Protocol (ASAP), that may offer better response rates than current guidelines. ASAP involves shorter duration medication trials (2–4 weeks) and earlier use of antidepressant combinations, seeking additive antidepressant effects without worsening side effects. Future research should compare ASAP to current treatment guidelines. Research is also needed on the role of rapidly acting antidepressants like ketamine for acutely ill and suicidal depressed patients.

KEYWORDS:

• Depression
• major depressive disorder
• antidepressant
• accelerated sequential antidepressant protocol
• ASAP

Article highlights

• Current treatment guidelines for MDD leaves one third of patients still depressed after six months of treatment.

• We propose an Accelerated Sequential Antidepressant Protocol (ASAP).

• ASAP proposes earlier use of antidepressant combinations and shorter medication trials

• ASAP is designed to provide additive antidepressant effects without increasing side effects, seeking better early remission rates.

• ASAP represents a proposed set of ideas that need to be tested as a composite.

Acknowledgments

J Mann and M Rizk planned, wrote and edited this review article, and take joint responsibility for its contents. We thank Angela Citrola for her contribution to this article by preparing and reviewing the supplementary tables.

Declaration of interest

J Mann receives royalties from the Research Foundation for Mental Hygiene for the commercial use of the Columbia Suicide Severity Rating Scale. 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

One peer reviewer declares: Consultant for Acadia, Abbvie, Intra-Cellular Therapies, Neumora Therapeutics, Neurocrine Biosciences, Sunovion; speaker’s bureau for Abbvie, Intra-Cellular Therapies, Sunovion (in the last 12 months). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

M Rizk was supported by a Paul Janssen Fellowship in Translational Neuroscience at Columbia University and a Young Investigator Award from the Brain and Behavior Research Foundation.