The use of sequential pharmacotherapy for the treatment of acute major depression: a scoping review

ABSTRACT

Introduction

Major Depressive Disorder (MDD) is a chronic, relapsing, and remitting disorder affecting over 250 million persons each year worldwide. More than 50% of the patients do not respond to their initial antidepressant treatment and may benefit from sequential pharmacotherapy for the acute treatment of their MDD. Although guidelines outline options for next-step treatments, there is a paucity of evidence to select specific second- or third-step treatments.

Areas Covered

This scoping review synthesizes and discusses available evidence for sequential pharmacotherapy for MDD. MEDLINE was searched from inception to 7 July 2020; 4490 studies were identified. We selected meta-analyses and reports on clinical trials that were judged to inform the sequential selection of pharmacotherapy for MDD.

Expert opinion

Most relevant published trials are focused on, and support, the use of augmentation pharmacotherapy. There is also some support for other strategies such as combining or switching antidepressants. In the future, more studies need to directly compare these sequential options. To provide more personalized treatment within the framework of precision psychiatry, these studies should include an assessment of moderators and mediators (‘mechanism’) of antidepressant response.

KEYWORDS:

• Major depressive disorder
• outcomes
• pharmacotherapy
• augmentation
• combination
• switch
• treatment algorithm
• sequential treatment
• antidepressant

Article highlights

• A large proportion of patients requires sequential pharmacotherapy for treatment of MDD.

• Common practices in sequential pharmacotherapy include increasing the antidepressant dosage, switching the antidepressant, combining antidepressants, or augmenting the antidepressant with another psychotropic agents.

• Currently, there is only limited evidence to support switching antidepressants either between or within class.

• Results of high-quality RCTs support augmenting antidepressants with second-generation antipsychotics; however, very few RCTs compare this specific augmentation strategy to either switching or combining antidepressants.

• Larger RCTs comparing multiple treatment options with mechanistic (‘biomarkers’) evaluation are needed.

• Treatment of MDD in clinical practice should use measurement-based care to guide clinical decisions regarding the selection and sequencing of treatment options.

This box summarizes key points contained in the article.

Declaration of interest

MI Husain is the principal investigator for a trial sponsored by COMPASS Pathways Limited. BH Mulsant currently receives personal support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto and research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study funded by CAMH Foundation) and HAPPYneuron (software used in a study founded by Brain Canada). Within the past 5 years, he has also received research support (medications for NIH-funded clinical trials) from Bristol-Myers, Eli Lilly and Company and Pfizer. He directly owns stocks of General Electric (less than C$5000). None of the companies have a financial interest in this research. 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

The completion of this review was supported in part by an Academic Scholars Award from the Department of Psychiatry, University of Toronto (MI Husain) and by the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto (to BH Mulsant)