Evidence-Based Pharmacotherapies for Major Depressive Disorder: A Clinical Update

Major Depressive Disorder (MDD) represents the classically described episodic depression, with varying degrees of severity and recurrence. With a lifetime prevalence close to 20%, the condition represents a leading cause of disability worldwide. Pharmacotherapy is an option for initial treatment, especially in cases of higher severity. As over half of patients will not experience remission after first antidepressant trial, it is essential for clinicians to understand the vast number of medications available and their unique characteristics. This review provides a comprehensive clinical update on evidence-based pharmacotherapies for MDD, including both established and novel treatment options. Traditional monoaminergic antidepressants remain as important options with comparable efficacy but often distinct side-effect profile. Augmentation strategies are often employed with partial treatment response and are available with a wide range of mechanisms and unique clinical nuances. Fast-acting agents are now a reality in practice, including neuroactive steroids for postpartum depression and agents that target glutamatergic pathways. Relevant aspects for clinical practice are provided for over forty different medications, presenting dose ranges, adverse effects, monitoring requirements, and important patient characteristics to consider when prescribing. We also highlight concepts important for successful pharmacotherapy such as accurate diagnosis and treatment resistance. With the expanding therapeutic arsenal for MDD, ongoing comparative-effectiveness and real-world studies will be crucial for transforming today's advances into accurately personalized care.