Pharmacological Monotherapy for Depressive Disorders: Current and Future-A Narrative Review

Area of Science:

• Neuroscience
• Pharmacology
• Psychiatry

Background:

• Depressive disorders represent a significant global health burden, necessitating continuous research into effective therapeutic interventions.
• Current treatments primarily rely on monoamine-based antidepressants, but limitations in efficacy and side effect profiles drive the search for novel agents.

Purpose of the Study:

• To conduct a narrative review of existing and emerging antidepressant therapies for monotherapy treatment of depressive disorders.
• To evaluate the efficacy and potential of various antidepressant classes, including traditional and novel agents.

Main Methods:

• Review of established antidepressants (SSRIs, SNRIs, bupropion, TCAs, MAOIs) based on STAR*D study and systematic reviews.
• PubMed/Medline searches for other antidepressants, prioritizing systematic reviews.
• Database searches (PubMed, Google, ClinicalTrials.gov) for drugs in development for depressive disorders.

Main Results:

• STAR*D study indicated similar efficacy for sertraline, venlafaxine, and bupropion in treatment-resistant major depressive disorder (MDD).
• Network meta-analyses show comparable efficacy for SSRIs, SNRIs, bupropion, TCAs, mirtazapine, and agomelatine versus placebo, with varying acceptability.
• Novel agents like ketamine, esketamine, brexanolone, and zuranolone show potential, with psychedelics demonstrating rapid onset, large effect sizes, and durability.

Conclusions:

• Monoamine-based antidepressants are expected to remain the primary treatment for depressive disorders.
• NMDA receptor antagonists and neurosteroid antidepressants may increase in importance with improved accessibility.
• Psychedelics could revolutionize depression treatment if Phase III trials confirm their efficacy and safety.