What is the recommended initial treatment for a adult patient with a history of depression when starting a new antidepressant?

Initial Antidepressant Treatment for Adult Depression

Start with a second-generation antidepressant (SSRI or SNRI) at standard dosing, specifically sertraline 50 mg daily, escitalopram 10-20 mg daily, or citalopram 20-40 mg daily, as these agents are first-line therapy due to their superior tolerability profiles compared to older antidepressants. 1

Medication Selection Strategy

Choose sertraline, escitalopram, or citalopram as preferred first-line agents based on the following evidence:

• Second-generation antidepressants are recommended as first-line treatment because of their better adverse effect profile compared to tricyclic antidepressants and MAOIs 1
• The American Academy of Family Physicians specifically recommends sertraline, escitalopram, or citalopram as preferred agents due to favorable tolerability 2
• All second-generation antidepressants demonstrate equal efficacy for treatment-naive patients, so selection should prioritize adverse effect profiles, cost, and dosing frequency 2

Alternative First-Line Options

Consider bupropion if sexual side effects are a primary concern:

• Bupropion shows decreased risk of sexual dysfunction compared to SSRIs 1
• Escitalopram and paroxetine show a trend toward increased sexual side effects 1

Consider SNRIs (duloxetine or venlafaxine) if comorbid pain is present:

• SNRIs provide additional benefits for patients with comorbid pain disorders 1
• However, SNRIs have marginally superior remission rates (49% vs 42%) but higher discontinuation rates due to nausea and vomiting 1

Starting Dosages (FDA-Approved)

Sertraline: 50 mg once daily for major depressive disorder; may increase up to 200 mg/day at intervals of at least 1 week 3

Fluoxetine: 20 mg once daily in the morning; doses above 20 mg/day may be considered after several weeks if insufficient improvement 4

Escitalopram: 10-20 mg once daily 1

Citalopram: 20-40 mg once daily 1

Critical Monitoring Requirements

Monitor for suicidality within the first 1-2 months of treatment:

• Adults 18-24 years have slightly increased risk (OR = 2.30; 95% CI, 1.04 to 5.09) 1
• Adults 25-64 years show neutral risk 1
• Adults ≥65 years show protective effect (OR = 0.06; 95% CI, 0.01 to 0.58) 1

Assess treatment response within 1-2 weeks of initiation:

• Evaluate for therapeutic effects, adverse effects, and suicidality 5
• Full antidepressant effect may be delayed until 4 weeks of treatment or longer 4

If inadequate response by 6-8 weeks, modify treatment:

• Consider dose escalation, switching agents, or augmentation strategies 5
• If no improvement after 2-4 weeks at upper standard dose, response becomes less likely 6

Treatment Duration

Continue treatment for 4-9 months after satisfactory response for first episode:

• This duration prevents relapse in acute major depressive disorder 5, 3, 4

Consider prolonged treatment (≥1 year) for recurrent depression:

• Patients with 2 or more prior episodes benefit from longer maintenance therapy 5

Common Pitfalls to Avoid

Do not underdose or discontinue prematurely:

• Approximately 38% of patients do not achieve treatment response during 6-12 weeks, and 54% do not achieve remission with any single antidepressant 2
• Approximately 63% of patients experience at least one adverse effect, so set realistic expectations 2

Avoid paroxetine and fluoxetine in older adults (≥65 years):

• These agents have higher rates of adverse effects in elderly patients 2
• Preferred agents for older adults include citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, and bupropion 2

Do not combine with MAOIs or start MAOI without appropriate washout:

• This combination poses serious safety risks 2

Anticipate common adverse effects:

• Sexual dysfunction occurs in 40% of patients (95% CI, 28.3 to 52.6) across observational studies 1
• Nausea and vomiting are the most common reasons for antidepressant discontinuation 2
• Weight gain risk varies by agent, with initiation timing dependent on coexisting risk factors 1

Severity-Based Considerations

Antidepressants show greater benefit in severe depression:

• Patients with severe depression have more robust responses to antidepressants compared with placebo than those with mild to moderate depression 1
• For severe depression, consider combination therapy with cognitive behavioral therapy, which nearly doubles remission rates (57.5% vs 31.0%, P < 0.001) 7