What is the recommended sertraline dosing and titration schedule for adults (including elderly or frail patients), children (6‑12 years), adolescents (13‑17 years), and patients with moderate hepatic impairment, and how should it be tapered when discontinued?

Sertraline Titration: Dosing and Discontinuation Guidelines

Standard Adult Dosing and Titration

Start sertraline at 50 mg once daily—this is both the starting dose and the optimal therapeutic dose for most patients. 1, 2

• The therapeutic range is 50-200 mg/day across all approved indications. 1
• Sertraline can be administered at any time of day (morning or evening). 1
• Dose increases should occur only after 2-4 weeks at the current dose if therapeutic response is inadequate. 1
• When titrating, increase in 50 mg increments at intervals of no less than 1 week, up to a maximum of 200 mg/day. 2
• For shorter half-life SSRIs like sertraline, dose adjustments can be made at approximately 1-2 week intervals. 1

Response Timeline and Monitoring

• Statistically significant improvement may occur within 2 weeks, with clinically significant improvement typically by week 6, and maximal improvement by week 12 or later. 1
• An adequate trial requires 8 weeks of treatment on an optimal dose to identify response. 1
• Most adverse effects emerge within the first few weeks of treatment and are dose-related. 1
• Weekly monitoring during dose adjustments is recommended, with systematic assessment using standardized rating scales. 1

Special Population Dosing

Elderly Patients (≥60 years)

For elderly patients, start at 25-50 mg once daily, with a maximum dose of 200 mg daily—no age-based dose reduction is required beyond this initial consideration. 3, 4, 5, 6

• Sertraline is a preferred agent for elderly patients due to favorable tolerability, lack of anticholinergic effects, and minimal cytochrome P450 interactions. 3, 5, 6
• No dosage adjustments are warranted for elderly patients solely based on age once treatment is established. 5, 6, 2
• Avoid paroxetine and fluoxetine in elderly patients due to higher anticholinergic effects and longer half-life, respectively. 3

Patients with Alzheimer's Disease and Depression

• Initial dose is 25-50 mg per day, with a maximum dose of 200 mg per day. 1
• Sertraline is well tolerated and has less effect on metabolism of other medications compared to other SSRIs in this population. 1

Hepatic Impairment

Patients with liver disease should start at a lower dose (25 mg) and titrate more slowly, with the exact reduction determined by the severity of hepatic dysfunction. 3, 4

Renal Impairment

No dose adjustment is required for patients with renal impairment—the standard dosing range of 50-200 mg per day applies regardless of kidney function. 3, 4, 7

Pediatric and Adolescent Dosing

Children (6-12 years) and Adolescents (13-17 years)

• Consider starting with a subtherapeutic "test dose" (even lower than 25 mg) in patients prone to anxiety or agitation, as SSRIs can initially worsen these symptoms. 1
• Parental oversight of medication regimens is paramount in pediatric patients. 1
• At low doses (below 50 mg), some patients may require twice-daily dosing due to sertraline's shorter half-life compared to other SSRIs. 1
• Dose adjustments can be made at approximately 1-2 week intervals. 1

Critical Safety Monitoring

Suicidality Risk

Monitor closely for suicidal thinking and behavior, especially in the first months of treatment and following dosage adjustments. 1

• All SSRIs carry a boxed warning for suicidal thinking and behavior through age 24 years. 1
• The pooled absolute rate for suicidal ideation is 1% for antidepressants versus 0.2% for placebo (Number Needed to Harm = 143). 1

Other Safety Concerns

• Watch for behavioral activation/agitation, hypomania, mania, seizures, abnormal bleeding, and serotonin syndrome. 1
• Behavioral activation typically improves quickly after dose reduction, whereas true mania/hypomania may persist and require more active intervention. 1
• Monitor for serotonin syndrome especially in the first 24-48 hours after starting or dose increases, with symptoms including mental status changes, neuromuscular hyperactivity, and autonomic instability. 1

Drug Interactions and Contraindications

Absolute Contraindications

Sertraline is absolutely contraindicated with MAOIs due to the risk of serotonin syndrome—allow at least 14 days between discontinuing an MAOI and starting sertraline. 1

Important Drug Interactions

• Exercise caution when combining with other serotonergic agents (triptans, tramadol, fentanyl) due to serotonin syndrome risk. 1
• Monitor for abnormal bleeding when prescribed with anticoagulants or antiplatelet agents (warfarin, aspirin, NSAIDs), as SSRIs increase bleeding risk. 1
• Sertraline has minimal cytochrome P450 interactions compared to other SSRIs, making it safer in polypharmacy situations. 1, 3, 5, 6

Discontinuation and Tapering

When discontinuing sertraline, taper gradually over a minimum of 2-4 weeks for short-term therapy, or several weeks to months for long-term therapy—never stop abruptly. 1, 3

Tapering Protocol

• For patients on long-term therapy (4-12 months or longer), slower tapers extending over several weeks to months are more appropriate than rapid tapers. 1
• The taper rate is ultimately determined by the patient's ability to tolerate dose reductions, with some patients requiring 10% reductions of the current dose at each step. 1
• Extended tapers of several months may be necessary for patients on long-term treatment or those experiencing withdrawal symptoms. 1

Managing Withdrawal Symptoms

If moderate to severe withdrawal symptoms occur, reinstitute the previous dose and slow the rate of taper, holding at the current dose for an additional 1-2 weeks before attempting further reduction. 1

• Sertraline is associated with discontinuation syndrome characterized by dizziness, fatigue, myalgias, headaches, nausea, insomnia, and sensory disturbances. 1
• High-risk patients (history of severe withdrawal symptoms or comorbid anxiety) should receive especially slow tapers. 1

Patient Education Before Tapering

• Establish a collaborative plan that includes a clear explanation of why gradual tapering is necessary, discussion of potential withdrawal symptoms, and agreement on taper schedule. 1
• Monitor closely during taper for emergence of withdrawal symptoms, return of original psychiatric symptoms, and suicidal ideation, particularly in younger patients. 1

Treatment Duration

For patients with a first episode of major depressive disorder, continue treatment for 4-12 months after symptom remission. 1, 3

• For patients with recurrent depression, consider prolonged or indefinite treatment. 1, 3

Common Adverse Effects

• Common side effects include nausea, diarrhea, headache, insomnia, dizziness, sexual dysfunction, sweating, tremors, dry mouth, somnolence, and constipation. 1, 3, 5, 6
• Most adverse effects emerge within the first few weeks of treatment and are dose-related, improving with time. 1
• Sertraline lacks the marked anticholinergic effects that characterize tricyclic antidepressants. 5, 6, 8

Common Pitfalls to Avoid

• Never start at higher doses than recommended, as this increases the risk of adverse effects and poor tolerability. 1
• Do not increase the dose too quickly—allow adequate trial duration (2-4 weeks minimum) at each dose before increasing. 1
• Never abruptly discontinue sertraline—always taper gradually to avoid discontinuation syndrome. 1
• Do not misinterpret inadequate trials (short duration on each dose) as non-response. 1