When to start selective serotonin reuptake inhibitor (SSRI) treatment for major depressive disorder?

When to Start SSRI Treatment for Major Depressive Disorder

Start SSRI treatment immediately upon diagnosis of major depressive disorder in adults, beginning with low starting doses (fluoxetine 10 mg, sertraline 25-50 mg, escitalopram 10 mg, or citalopram 10 mg daily) and initiating close monitoring within 1-2 weeks. 1

Immediate Initiation Strategy

Starting Doses by Medication

• Fluoxetine: Start at 10 mg daily, increase by 10-20 mg increments to effective dose of 20 mg (maximum 60 mg) 1
• Sertraline: Start at 25 mg daily, increase by 12.5-25 mg increments to effective dose of 50 mg (maximum 200 mg) 1, 2
• Escitalopram: Start at 10 mg daily, increase by 5 mg increments to effective dose of 10 mg (maximum 20 mg) 1, 3
• Citalopram: Start at 10 mg daily, increase by 10 mg increments to effective dose of 20 mg (maximum 60 mg) 1

Critical principle: Always start at the lower end of the dosing range to minimize behavioral activation and adverse effects, particularly in younger patients. 1

Timeline for Treatment Response

Expected Response Pattern

• Week 2: Statistically (but not clinically) significant improvement may begin 1
• Week 6: Clinically significant improvement should be evident 1
• Week 6-8: If inadequate response, increase dose or modify treatment 1
• Week 12 or later: Maximal improvement expected 1

If no adequate response by 6-8 weeks at therapeutic doses, modify the treatment plan rather than continuing ineffective therapy. 1

Mandatory Monitoring Schedule

Initial Monitoring (Highest Risk Period)

• First contact: Within 1-2 weeks after starting SSRI 1
• Frequency: Close monitoring especially during first 1-2 months when suicide risk is highest 1
• Method: Either in-person or telephone contact is acceptable 1

What to Monitor

• Suicidal thinking and behavior (absolute risk increase 0.7%, NNH = 143) 1
• Behavioral activation/agitation (motor restlessness, insomnia, impulsiveness, disinhibited behavior) - more common in younger patients 1
• Treatment adherence and understanding of the treatment plan 1
• Adverse effects: nausea, diarrhea, headache, insomnia, sexual dysfunction 1

Critical Safety Warnings

Black Box Warning Considerations

All SSRIs carry FDA black box warnings for suicidal thinking and behavior through age 24 years, with pooled rates of 1% on antidepressants versus 0.2% on placebo. 1 However, the number needed to treat for response is only 3, vastly outweighing the NNH of 143. 1

Avoid These Pitfalls

• Never start at high doses: Deliberate self-harm and suicide risk increase when SSRIs are started at higher than recommended starting doses 1
• Never combine with MAOIs: All SSRIs are contraindicated with monoamine oxidase inhibitors 1
• Never abruptly discontinue: Always taper slowly to avoid withdrawal effects 1
• Watch for serotonin syndrome: Symptoms can arise within 24-48 hours when combining serotonergic medications (confusion, tremors, hyperreflexia, hypertension, tachycardia) 1

Treatment Duration After Response

Continue SSRI treatment for at least 4-9 months after achieving satisfactory response in a first episode, with longer duration recommended for patients with 2 or more episodes. 4, 5

Special Considerations for Adolescents

For adolescents with depression, only fluoxetine has FDA approval for use in children and adolescents, and only escitalopram is approved for adolescents aged 12 years and older. 1 The same low starting dose and close monitoring principles apply, with even greater vigilance for behavioral activation in younger children. 1