What is the recommended starting dose of sertraline (Selective Serotonin Reuptake Inhibitor) for an adult patient with moderate to severe depression?

Starting Dose for Sertraline

For adults with moderate to severe depression, start sertraline at 50 mg once daily. 1

Standard Adult Dosing

• The FDA-approved starting dose for major depressive disorder is 50 mg once daily, which can be taken either in the morning or evening 1
• This 50 mg dose is both the starting dose and the optimal therapeutic dose for most patients when considering efficacy and tolerability 2
• The American Family Physicians guideline confirms the therapeutic range is 50-200 mg/day across all approved indications 3

Dose Titration Strategy

• Patients not responding to 50 mg after 2-4 weeks may benefit from dose increases up to a maximum of 200 mg/day 3, 1
• Dose changes should not occur at intervals of less than 1 week due to sertraline's 24-hour elimination half-life 1
• The American Academy of Child and Adolescent Psychiatry recommends dose adjustments at approximately 1-2 week intervals for shorter half-life SSRIs like sertraline 3
• Increase in 50 mg increments when titrating upward 2

Special Populations

Elderly Patients (≥60 years)

• No age-based dose adjustment is required for elderly patients - start at the standard 50 mg once daily 4, 5
• The American Geriatrics Society confirms standard dosing of 50-200 mg/day applies unless hepatic impairment is present 3
• Sertraline is preferred in elderly patients due to lack of anticholinergic effects and minimal cytochrome P450 interactions 4, 5

Patients with Hepatic Disease

• A reduced dose is recommended in patients with hepatic impairment 3

Patients with Renal Impairment

• No dose adjustment is needed 3

Alternative Starting Dose for Specific Indications

For panic disorder, PTSD, and social anxiety disorder, the FDA recommends starting at 25 mg once daily for one week, then increasing to 50 mg once daily 1. This lower initial dose helps minimize activation symptoms that can worsen anxiety in these populations.

Important Clinical Considerations

Timing of Response

• Statistically significant improvement may occur within 2 weeks, with clinically significant improvement typically by week 6, and maximal improvement by week 12 or later 3
• This timeline supports slow up-titration to avoid exceeding the optimal dose 3

Common Pitfalls to Avoid

• Do not increase the dose before 1 week due to sertraline's pharmacokinetics 1
• Do not start at 25 mg for depression unless the patient has panic disorder, PTSD, or social anxiety disorder - the 50 mg dose is both effective and well-tolerated for depression 1, 2
• Consider a subtherapeutic "test dose" approach (starting at 25 mg) only in patients particularly prone to anxiety or agitation, as SSRIs can initially worsen these symptoms 3

Monitoring Requirements

• Monitor closely for suicidal thinking and behavior, especially in the first months of treatment and following dosage adjustments (pooled absolute rate: 1% for antidepressants vs 0.2% for placebo) 3
• Watch for behavioral activation/agitation, hypomania, mania, seizures, abnormal bleeding, and serotonin syndrome 3
• Most adverse effects emerge within the first few weeks of treatment and are related to both dosage and dosing regimen 3

Drug Interactions and Safety

• Exercise caution when combining with other serotonergic agents (triptans, tramadol, fentanyl) due to serotonin syndrome risk 3
• Monitor for abnormal bleeding when prescribed with anticoagulants or antiplatelet agents (warfarin, aspirin, NSAIDs) 3
• Sertraline has minimal effects on cytochrome P450 enzymes, resulting in fewer drug-drug interactions compared to other SSRIs 3, 4

Cardiovascular Considerations

• Sertraline is the preferred SSRI in patients with cardiovascular disease due to lower QTc prolongation risk and minimal cardiovascular side effects 3
• The American College of Cardiology recommends sertraline as preferred in patients with coronary heart disease and heart failure 3