What are the recommended first-line treatments for depression, including dosage and potential alternatives?

First-Line Antidepressant Treatment for Depression

For treatment-naïve adults with major depressive disorder, select any second-generation antidepressant (SSRI, SNRI, or atypical agent) based on adverse effect profile, cost, and patient preference, as all are equally effective. 1

Recommended Starting Doses

SSRIs (Selective Serotonin Reuptake Inhibitors)

• Fluoxetine: Start 20 mg once daily in the morning 2
• Sertraline: Start 50 mg once daily (morning or evening) 3
• Citalopram/Escitalopram: Preferred for older adults 1

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Venlafaxine: Start 75 mg/day, may titrate to 75-225 mg/day 1, 4
• SNRIs show slightly greater symptom improvement than SSRIs but have higher rates of nausea and vomiting 1

Atypical Antidepressants

• Bupropion: Associated with lower rates of sexual dysfunction compared to fluoxetine or sertraline 1
• Mirtazapine: Faster onset of action than fluoxetine, paroxetine, or sertraline, with most patients responding within 4 weeks 1

Key Adverse Effect Considerations

Sexual dysfunction varies significantly between agents: Bupropion causes less sexual dysfunction than SSRIs, while paroxetine causes more sexual dysfunction than fluoxetine, fluvoxamine, or sertraline 1

SSRIs carry increased risk for suicide attempts compared to placebo, requiring close monitoring 1

Common adverse effects include constipation, diarrhea, dizziness, headache, insomnia, nausea, sexual dysfunction, and somnolence, with nausea/vomiting being the most common reason for discontinuation 1

Monitoring Protocol

Begin monitoring within 1-2 weeks of initiation for suicidal thoughts, agitation, irritability, or unusual behavioral changes, as suicide risk is greatest during the first 1-2 months 1

Assess therapeutic response at 6-8 weeks: If inadequate response, modify treatment by switching agents or adding other modalities 1

Treatment Duration

First episode: Continue for 4-9 months after satisfactory response 1

Recurrent depression (≥2 episodes): Consider years to lifelong treatment 1

Special Populations

Older adults: Prefer citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, or bupropion; avoid paroxetine and fluoxetine due to higher adverse effect rates 1

Pediatric patients (ages 6-17): Start fluoxetine 10-20 mg/day or sertraline 25-50 mg/day depending on age and weight 2, 3

Alternative First-Line Options

Cognitive behavioral therapy (CBT) is equally effective as antidepressants for major depressive disorder, with no difference in response or remission rates 1

Combination therapy (antidepressant + CBT) shows no clear advantage over monotherapy for most patients 1

Common Pitfalls

Do not expect full therapeutic effect before 4 weeks of treatment at adequate doses 1

38% of patients do not respond to initial antidepressant therapy within 6-12 weeks, and 54% do not achieve remission, necessitating treatment modification 1

Antidepressants are most effective in severe depression; efficacy is more modest in mild-to-moderate cases 1