What is the best antidepressant?

Best Antidepressant Selection

There is no single "best" antidepressant for all patients, as second-generation antidepressants have similar efficacy for treating depression, with differences primarily in side effect profiles and onset of action. 1, 2

Efficacy Considerations

• Evidence from 80 head-to-head RCTs shows no clinically significant differences in efficacy between SSRIs, SNRIs, and other second-generation antidepressants for treating major depressive disorder 1

• All classes demonstrate similar effectiveness for:

  • Acute phase treatment 1
  • Quality of life improvements 1
  • Maintenance of response/remission 1

• Mirtazapine shows a faster onset of action compared to other antidepressants, though response rates become similar after 4 weeks 1

Side Effect Profile-Based Selection Algorithm

First-Line Options:

1. SSRIs (Sertraline, Escitalopram, Citalopram)

   • Best overall tolerability profile 2
   • Sertraline: 25-50mg initial dose, up to 200mg daily 2
   • Escitalopram: 10mg initial dose, up to 20mg daily 2
   • Citalopram: 10-20mg daily (maximum 20mg in elderly due to QT prolongation risk) 2

2. Bupropion

   • Consider when sexual dysfunction or weight gain is a concern 2
   • Lower rate of sexual adverse events
   • Promotes weight loss rather than gain

3. SNRIs (Venlafaxine, Duloxetine)

   • Consider when depression is accompanied by pain symptoms
   • May have slightly higher efficacy in severe depression 3, 4

Special Considerations

For Treatment-Resistant Depression:

• STAR*D study showed that when initial therapy fails, switching to another antidepressant (bupropion, sertraline, or venlafaxine) results in approximately 25% of patients becoming symptom-free, with no difference among these three options 1

For Depression with Accompanying Symptoms:

• Anxiety symptoms: SSRIs and SNRIs show similar efficacy 1
• Insomnia: Mirtazapine may be beneficial due to sedating properties 1
• Pain symptoms: Duloxetine may be preferred 3

Monitoring and Follow-up

• Assess response within 1-2 weeks of initiation 2
• Full therapeutic effect may take 6-8 weeks 2
• If inadequate response after 6-8 weeks, consider:
  • Dose adjustment
  • Switching to another antidepressant
  • Augmentation strategies

Common Pitfalls to Avoid

1. Inadequate dosing: Ensure therapeutic doses are reached before concluding treatment failure
2. Insufficient duration: Allow 6-8 weeks for full therapeutic effect
3. Ignoring drug interactions: Consider CYP2D6 and CYP2C19 genetic variations that affect metabolism 2
4. Abrupt discontinuation: Always taper gradually to avoid withdrawal symptoms 2
5. Overlooking comorbidities: 50-60% of individuals with depression have comorbid anxiety disorders 2

Conclusion

The selection of an antidepressant should be guided primarily by anticipated side effects, patient comorbidities, and potential drug interactions rather than differences in efficacy. Recent evidence suggests novel agents may offer improved efficacy and tolerability 5, but established second-generation antidepressants remain the standard of care based on extensive clinical evidence.