Title:Considering New and Emerging Treatment Strategies for Depression: Beyond STAR*D and the Monoamines
Volume: 21
Issue: 3
Author(s): L. Alison McInnes*Tobias F Marton
Affiliation:
- Department of Psychiatry, Osmind 3130 20th Street Suite 250, San Francisco CA, 94110, United
States
Keywords:
Treatment resistant depression, precision psychiatry, esketamine, transcranial magnetic stimulation, ketamine, electroconvulsive therapy.
Abstract: While the number of treatment options for major depressive disorder (MDD)
has grown in recent years, the lack of quality data to guide optimal modality selection has
lessened the potential impact of having a more diverse set of mechanistic approaches to
treatment. The last attempt to investigate treatment sequencing for MDD was the Sequenced
Treatment Alternatives for Relief of Depression Study (STAR*D), which gave
rise to the concept of treatment-resistant depression (TRD) as a failure to respond to two or
more monoaminergic antidepressants. However, a recent reanalysis of the STAR*D data
indicates that most patients do not remit even when treated with multiple traditional antidepressants.
Given these new results, labeling the majority of patients as treatmentresistant
is not appropriate or useful. If monoamine-based drugs are not that effective for
the majority of MDD patients, then it is necessary to consider the mechanistically distinct
pharmacological and non-pharmacological treatment options that have emerged recently,
including brain stimulation, glutamate receptor modulators, and psychedelic medicines.
While these new treatment modalities have the potential to enhance patient outcomes, clinicians
and patients currently lack a framework to guide their choices other than cost, feasibility,
personal preference, and certain medical contraindications. Here, we review alternative
treatment modalities for monoamine non-responders and consider the possibility
that there will be new first-line therapies for MDD. We will review how treatment decisions
for these patients are currently being made and how developments in precision psychiatry
may help guide rational treatment selection in the future.
