In an adult without contraindications, how should sertraline be initiated (starting dose, titration schedule, maximum dose), what are its contraindications and common adverse effects, what monitoring is required, and what alternatives are available if it is ineffective?

Sertraline Initiation and Management in Adults

Starting Dose and Titration

Begin sertraline at 50 mg once daily, taken in the morning or evening; this is the standard therapeutic starting dose for major depressive disorder and most anxiety disorders. 1, 2, 3

• For panic disorder specifically, some clinicians may start at 25 mg daily for the first week to minimize early activation symptoms, then increase to 50 mg daily. 2
• The therapeutic dose range is 50–200 mg daily, with most patients responding to 50–150 mg. 1, 4, 3
• Increase the dose by 25–50 mg increments at intervals of at least one week if inadequate response occurs after 4 weeks at the current dose. 1, 2
• Maximum dose is 200 mg daily; doses above this threshold have not demonstrated additional efficacy and increase adverse effect risk. 1, 3
• Allow 6–8 weeks at therapeutic dose (minimum 50 mg, optimally 100–200 mg) before declaring treatment failure, as approximately 50% of eventual responders achieve remission between weeks 6 and 14. 5

Contraindications

Absolute contraindications include:

• Concurrent use or within 14 days of monoamine oxidase inhibitors (MAOIs), due to risk of serotonin syndrome. 1, 5
• Concurrent use of pimozide, due to QT prolongation risk. 1

Relative contraindications and cautions:

• History of seizure disorders (sertraline lowers seizure threshold). 1
• Concurrent use of other serotonergic agents (triptans, other SSRIs, SNRIs, St. John's wort, tryptophan) increases serotonin syndrome risk. 1, 5
• Bleeding disorders or concurrent antiplatelet/NSAID use, as SSRIs increase gastrointestinal bleeding risk (OR = 1.2–1.5). 1
• Hyponatremia risk is elevated in older adults (0.5–12% incidence, OR = 3.3 for SSRIs). 1

Common Adverse Effects

The most frequent adverse effects are gastrointestinal and sexual dysfunction:

• Nausea and diarrhea/loose stools are the most common early side effects, typically mild and transient, decreasing with continued treatment. 4, 6
• Male sexual dysfunction, primarily ejaculatory delay/disturbance, occurs in approximately 40% of patients (weighted mean across observational studies). 1, 4
• Dry mouth, headache, insomnia, somnolence, dizziness, and sweating occur frequently. 4, 6
• Sertraline has minimal anticholinergic effects and is essentially devoid of cardiovascular effects, making it safer than tricyclic antidepressants in elderly patients and those with cardiac disease. 4, 6
• Behavioral activation (restlessness, agitation, insomnia) may occur early in treatment, particularly in younger patients; slow titration minimizes this risk. 5

Monitoring Requirements

Suicidality monitoring is the highest priority:

• Assess for suicidal thoughts and behaviors at every visit during the first 1–2 months of treatment or after any dose change, as suicide risk is greatest during this period (OR = 2.30 for adults 18–24 years; neutral for ages 25–64; protective for ≥65 years). 1, 5

Additional monitoring:

• Evaluate treatment response at week 4 of therapeutic dosing using standardized depression/anxiety scales (PHQ-9, HAM-D, GAD-7). 5
• Monitor for hyponatremia within the first month, especially in older adults; check serum sodium if symptoms of confusion, headache, or weakness develop. 1
• Screen for gastrointestinal bleeding symptoms if patient is on concurrent NSAIDs or antiplatelet agents. 1
• Assess for discontinuation syndrome (dizziness, anxiety, irritability, sensory disturbances) if doses are missed or reduced, though sertraline has lower risk than paroxetine. 5
• Monitor for serotonin syndrome (mental status changes, neuromuscular hyperactivity, autonomic instability) within 24–48 hours of dose changes or when combining with other serotonergic drugs. 1, 5

Alternatives if Ineffective

If sertraline fails after an adequate trial (6–8 weeks at 100–200 mg daily), the following evidence-based strategies are recommended:

Switching to Another Antidepressant:

• Switch to a different SSRI (escitalopram 10–20 mg, fluoxetine 20–40 mg) achieves remission in approximately 21–25% of non-responders. 5
• Switch to an SNRI (venlafaxine 150–225 mg or duloxetine 60–120 mg) demonstrates statistically significantly better response and remission rates than continuing SSRI therapy in treatment-resistant depression. 5
• Bupropion SR 150–400 mg daily is an alternative with distinct mechanism (norepinephrine-dopamine reuptake inhibition) and significantly lower sexual dysfunction rates. 1, 5

Augmentation Strategies:

• Add bupropion SR 150–400 mg daily to sertraline; this achieves remission rates of approximately 50% versus 30% with SSRI monotherapy alone, with lower discontinuation rates (12.5%) than buspirone augmentation (20.6%). 5
• Add cognitive-behavioral therapy (CBT) to sertraline; combination therapy demonstrates superior efficacy compared to medication alone for both depression and anxiety disorders. 1, 5
• Add buspirone 5 mg twice daily, titrating to 20 mg three times daily over 2–4 weeks, though this has higher discontinuation rates due to adverse events than bupropion. 5

Critical Decision Points:

• The American College of Physicians found no significant difference between switching versus augmenting strategies overall, so choice depends on whether partial benefit exists from sertraline (favor augmentation) or no benefit (favor switching). 5
• Do not switch to another SSRI before completing 6–8 weeks at therapeutic sertraline dose (100–200 mg), as premature switching delays recovery and misses potential response. 5
• Do not try multiple SSRIs sequentially after failing two SSRIs; switch to a different antidepressant class (SNRI or bupropion) instead. 5

Duration of Continuation Therapy

• Continue sertraline for 4–9 months after achieving remission for a first episode of major depressive disorder. 5
• For recurrent depression (≥2 episodes), continue for years to lifelong to prevent relapse. 5
• For anxiety disorders, continue for 6+ months after remission; relapse prevention studies show 23% relapse with sertraline versus 50–52% with placebo at 24 weeks. 5

Pharmacokinetic Considerations

• Sertraline has an elimination half-life of 22–36 hours, making once-daily dosing appropriate. 7
• Minimal inhibition of cytochrome P450 enzymes results in low potential for drug-drug interactions, an advantage over fluoxetine and paroxetine. 7, 6
• No dosage adjustment required for elderly patients based on age alone, though starting at lower doses may improve tolerability. 6
• Steady-state plasma concentrations vary widely (up to 15-fold) at standard doses, but therapeutic drug monitoring is not routinely indicated as concentration-effect relationships are poorly established. 7