JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
RESEARCH SUPPORT, NON-U.S. GOV'T
REVIEW
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Pharmacotherapies for Treatment-Resistant Depression: How Antipsychotics Fit in the Rapidly Evolving Therapeutic Landscape.

One in three adults with major depressive disorder (MDD) do not experience clinically significant improvement after multiple sequential courses of antidepressants and have treatment-resistant depression (TRD). The presence of TRD contributes to the morbidity and excess mortality associated with MDD and has been linked to significantly increased health care expenses. In the absence of a consensus definition of TRD, this report takes a broad approach by considering inadequate response to one or more courses of antidepressants and focuses on atypical antipsychotics that are approved by the U.S. Food and Drug Administration for treatment of depression (aripiprazole, brexpiprazole, cariprazine, extended-release quetiapine, and olanzapine-fluoxetine combination). While multiple acute-phase studies have demonstrated the efficacy of these medications in improving depressive symptoms, clinically meaningful improvement (i.e., remission) remains limited, with significant concerns about side effects (including weight gain, metabolic dysfunction, extrapyramidal symptoms, and tardive dyskinesia), especially with long-term use. With the rapidly evolving landscape of antidepressant treatments over the past few years, which has witnessed approval of rapid-acting antidepressants (e.g., esketamine nasal spray and dextromethorphan-bupropion combination) and several more in the late-stage pipeline (e.g., zuranolone and psilocybin), it remains to be seen whether the use of atypical antipsychotics will go the way of the older and rarely prescribed antidepressants (such as tricyclics and monoamine oxidase inhibitors). Pragmatic clinical trials are needed to compare the effectiveness of atypical antipsychotics with TRD-specific pharmacotherapies and neuromodulation treatments and to identify the optimal sequencing of these varied approaches for patients with MDD. When using atypical antipsychotics, clinicians and patients are encouraged to use a shared decision-making approach by personalizing treatment selection based on anticipated side effects, tolerability, cost, and feasibility.

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Ep12 - Antipsychotics and antidepressants: a winning combination for treatment-resistant depression?

Join us for the next episode of the Psychiatry Update Journal Club, where we examine the rapidly evolving therapeutic landscape for treatment-resistant depression (TRD). Dr. Leslie Citrome will be interviewing Dr. Manish Jha, author of a review on this topic that appeared in the March 2023 issue of the American Journal of Psychiatry. Explore the role of atypical antipsychotics in tackling TRD and gain insights into optimal sequencing for novel treatment options.

This event will go live at 10:00 AM EST on Wednesday, 20th of September 2023. To join us, simply register via the button below.

This episode will focus on the five atypical antipsychotics approved by the U.S. Food and Drug Administration for treatment resistant depression, discussing their efficacy, tolerability, and limitations. While these medications have demonstrated acute efficacy in improving depressive symptoms, the conversation will address the gap in evidence for clinically meaningful improvement and the considerations surrounding long-term use.

The landscape of antidepressant treatments continues to evolve rapidly, with emerging treatments such as rapid-acting antidepressants, neuromodulation and an innovative drug pipeline. The conversation will delve into the need for pragmatic clinical trials to compare the effectiveness of different approaches and identify optimal treatment strategies.c

Join Dr. Leslie Citrome and Dr. Manish Jha and gain a deeper understanding of the complex treatment landscape for TRD.

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