What is the first-line pharmacotherapy for post-traumatic stress disorder?

• A. SSRIs
• B. TCAs (e.g., imipramine)
• C. MAO inhibitors
• D. Atypical antipsychotics

Answer: (A)

SSRIs are chosen first for PTSD because they have the strongest and most consistent evidence showing real improvement in the core symptoms—intrusive memories, avoidance, negative mood, and hyperarousal—and they help with overall functioning. Sertraline and paroxetine are specifically approved for PTSD, and guidelines routinely list them as the initial pharmacologic option. Mechanistically, increasing serotonin helps normalize the overactive fear circuitry involving the amygdala and prefrontal areas, aiding extinction of fear responses and reducing reactivity to trauma cues.

Other antidepressants like TCAs (imipramine) and MAO inhibitors generally have less robust PTSD evidence and greater side-effect or safety concerns, making them less favorable as first-line choices. Atypical antipsychotics can be helpful for certain symptoms or as augmentation in more severe or treatment-resistant cases, but they carry metabolic and other risks and are not used as the primary monotherapy.