In a 21‑year‑old woman with major depressive disorder and suicidal ideation who was started on sertraline 25 mg daily and aripiprazole (Abilify) 5 mg daily, how frequently should the sertraline dose be increased?

Sertraline Dose Titration in Major Depressive Disorder with Suicidal Ideation

Increase sertraline by 25–50 mg every 1–2 weeks, targeting a therapeutic dose of 50–200 mg daily, with close monitoring for suicidal ideation especially during the first months and after each dose adjustment.

Initial Dosing and Titration Schedule

• The FDA-approved starting dose for panic disorder, PTSD, and social anxiety disorder is 25 mg daily for one week, then increase to 50 mg daily. For major depressive disorder, the standard starting dose is 50 mg daily, but given this patient's suicidal ideation and young age, the 25 mg starting dose is appropriate. 1

• Dose increases should occur at intervals of no less than 1 week, based on 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. 2

• Patients not responding to 50 mg may benefit from dose increases up to a maximum of 200 mg daily, with the therapeutic range being 50–200 mg/day across all approved indications. 2, 1

Critical Safety Monitoring Requirements

• Monitor closely for suicidal thinking and behavior, especially in the first months of treatment and following each dosage adjustment, as the pooled absolute rate for suicidal ideation is 1% for antidepressants versus 0.2% for placebo (Number Needed to Harm = 143). 2

• All SSRIs carry a boxed warning for suicidal thinking and behavior through age 24 years, making weekly monitoring during dose adjustments essential in this 21-year-old patient. 2

• Watch for behavioral activation/agitation, which can occur early in treatment or with dose increases, particularly in anxiety-prone patients—this typically improves quickly after dose reduction. 2

Response Timeline and Dose Optimization

• Statistically significant improvement may occur within 2 weeks, with clinically significant improvement typically by week 6, and maximal improvement by week 12 or later. 2

• Allow at least 2–4 weeks at each dose level before increasing, as inadequate trial duration at each dose can lead to misinterpretation of non-response. 2

• For an adequate trial, 8 weeks of treatment on an optimal dose (typically 100–200 mg daily) are required to identify response. 2

Practical Titration Algorithm

1. Week 1: Continue 25 mg daily (current dose)
2. Week 2–3: Increase to 50 mg daily
3. Week 4–5: If inadequate response, increase to 100 mg daily
4. Week 6–7: If inadequate response, increase to 150 mg daily
5. Week 8+: If inadequate response, increase to 200 mg daily (maximum dose)

2, 1

Special Considerations for This Patient

• The incidence of side effects is related to both dosage and dosage regimen—slower titration (2-week intervals) produces a very low incidence of side effects, with no single side effect occurring with frequency greater than 10%. 3

• At low doses (25 mg), some patients may require twice-daily dosing due to sertraline's shorter half-life compared to other SSRIs. 2

• Most adverse effects emerge within the first few weeks of treatment and include nausea, diarrhea, headache, insomnia, dizziness, sexual dysfunction, and sweating—these are dose-related and typically improve with time. 2, 3

Aripiprazole Augmentation Context

• The addition of aripiprazole 5 mg daily is appropriate for this patient with major depressive disorder, as adjunctive aripiprazole has been shown to decrease the rate of suicidality in patients with inadequate antidepressant response. 4

• In pooled trials, no treatment-emergent suicide-related adverse events occurred in the aripiprazole group, compared to 2 patients in the placebo group. 4

Common Pitfalls to Avoid

• Never increase doses more frequently than every 1 week, as this prevents adequate assessment of therapeutic response and increases destabilization risk. 2, 1

• Never abruptly discontinue sertraline—it is associated with discontinuation syndrome characterized by dizziness, fatigue, myalgias, headaches, nausea, insomnia, and sensory disturbances. 2

• Never combine with MAOIs due to serotonin syndrome risk—allow at least 14 days between discontinuing an MAOI and starting sertraline. 2

• Never exceed 200 mg daily without reassessing the diagnosis and considering alternative strategies. 1