Difficult-to-Treat Depression: First-Line Antidepressant Selection, Switch vs. Augment, and Augmentation Strategies

<jats:p>Consider switching when the current medication is poorly tolerated or provides no benefit, and augmenting when there is a partial response and tolerability is acceptable. Bupropion is preferred when the patient wants to avoid sexual side effects, has low energy or motivation as primary symptoms, and has no significant insomnia or anxiety. Mirtazapine addresses poor sleep and appetite suppression and also carries a lower risk of sexual dysfunction. SGA efficacy differences are modest. Choose augmentation based on tolerability profile: weight gain, metabolic risk, sedation, and akathisia potential.</jats:p>