First-line antidepressants for major depressive disorder with favorable side effect profile?

• A. Monoamine oxidase inhibitors
• B. Tricyclic antidepressants
• C. Selective serotonin reuptake inhibitors
• D. Serotonin-norepinephrine reuptake inhibitors

Answer: (C)

In major depressive disorder, the best initial choice centers on balancing efficacy with safety and tolerability. An SSRI works by selectively blocking the serotonin transporter, increasing serotonin in the synapse, and they are chosen first because they have a relatively favorable side effect profile compared with older antidepressants. They lack the broad anticholinergic and cardiotoxic effects of tricyclic antidepressants and don’t require the dietary restrictions or potentially dangerous interactions associated with monoamine oxidase inhibitors, making them safer for outpatient use. While all antidepressants can cause side effects, SSRIs are generally better tolerated and safer in overdose, which is especially important in primary care or general psychiatry settings. Other options may be effective but tend to have more challenging side effects (like blood pressure effects with certain agents) or dietary restrictions, so SSRIs remain the preferred first-line choice for a favorable side effect profile.