First-Line Treatment for Major Depressive Disorder
Selective Serotonin Reuptake Inhibitors (SSRIs) are the first-line medication class for treating major depressive disorder, with the American College of Physicians explicitly recommending SSRIs (sertraline, escitalopram, fluoxetine, paroxetine, or citalopram) or SNRIs as initial pharmacotherapy. 1
Why SSRIs Are First-Line
The answer is b. Selective Serotonin Reuptake Inhibitors.
The American College of Physicians guidelines specifically limit first-line pharmacologic therapy to second-generation antidepressants, which include SSRIs and SNRIs, with SSRIs being the preferred initial choice. 2, 1
SSRIs have demonstrated equivalent efficacy to cognitive behavioral therapy for both response rates (relative risk 0.90) and remission rates (relative risk 0.98), with moderate-quality evidence supporting their use. 3
These medications have superior tolerability and lower toxicity in overdose compared to first-generation antidepressants like tricyclic antidepressants and monoamine oxidase inhibitors. 2, 4
Why Other Options Are Incorrect
Tricyclic Antidepressants (option d): While effective, these are considered first-generation antidepressants that are less commonly used due to higher toxicity in overdose and more significant side effects compared to SSRIs. 2, 4
Atypical Antipsychotics (option a): These are not first-line agents for MDD monotherapy; they may be used as augmentation strategies in treatment-resistant depression but not as initial treatment. 2
Stimulants (option c): These have no established role as first-line treatment for MDD and are not mentioned in any major depression treatment guidelines. 2, 1
Benzodiazepines (option e): These are anxiolytics without antidepressant efficacy and are not recommended for treating the core symptoms of MDD. 2
Clinical Implementation
Start with an SSRI from this list: sertraline, escitalopram, fluoxetine, paroxetine, or citalopram. 1
SSRIs are prescribed in 52.1% of MDD patients in real-world European practice, reflecting their guideline-concordant status as first-line agents. 5
The choice between specific SSRIs should be based on patient preference, previous treatment response, side effect profile (particularly sexual dysfunction risk), cost, and drug interaction potential. 1, 3
Important Caveats
All SSRIs carry risks of sexual dysfunction, potential suicidality (especially in younger patients), and higher discontinuation rates due to adverse events compared to psychotherapy. 3
Response to treatment is defined as ≥50% reduction in depression severity scores on validated tools like the Hamilton Depression Rating Scale or PHQ-9. 2, 1
Treatment should continue for 4-9 months after satisfactory response in first-episode MDD, with longer duration needed for patients with multiple prior episodes. 2