A patient on escitalopram (Lexapro) 5 mg daily for 14 days initially improved but now has worsening sadness, anxiety, and fatigue; what is the next step in management?

Increase Escitalopram to 10 mg Daily and Continue for 4–6 More Weeks

The patient requires dose escalation to 10 mg daily and continued treatment for at least 4–6 additional weeks before declaring treatment failure, as 5 mg is a subtherapeutic dose and 14 days is insufficient to assess antidepressant response. 1, 2

Why the Current Regimen Is Inadequate

• Escitalopram 5 mg is below the therapeutic range for major depressive disorder and anxiety disorders; the recommended starting dose is 10 mg daily, with 20 mg as the optimal therapeutic dose. 1, 3, 4
• Two weeks of treatment is too brief to evaluate antidepressant efficacy; full response typically requires 6–8 weeks at a therapeutic dose, and approximately 50% of patients who ultimately achieve remission do so between weeks 6 and 14. 5, 1, 2
• The initial improvement followed by worsening is consistent with early placebo response or transient symptom fluctuation, not treatment failure, and does not indicate the need to switch medications. 1

Recommended Dose Escalation Protocol

• Increase escitalopram from 5 mg to 10 mg daily immediately; this is the standard therapeutic starting dose for depression and anxiety. 1, 3, 4
• Maintain 10 mg daily for a minimum of 4 weeks to assess response; if inadequate improvement occurs, escalate to 20 mg daily (the maximum recommended dose). 1, 2, 4
• Do not exceed 20 mg daily without cardiac monitoring, as higher doses increase QT-interval prolongation risk without demonstrated additional benefit. 1, 2

Expected Timeline and Monitoring

• Symptom improvement may begin within 1–2 weeks of reaching therapeutic dosing, but maximal benefit typically requires 6–8 weeks at 10–20 mg daily. 3, 6, 4
• Reassess at week 4 after dose increase (approximately 6 weeks total treatment); if partial response is present, continue the same dose for another 4 weeks before considering augmentation or switching. 5, 1
• Monitor closely for suicidal ideation during the first 1–2 months of treatment and after any dose change, as this period carries the highest risk for treatment-emergent suicidality. 1, 2

What to Avoid

• Do not switch to another SSRI prematurely; switching before completing an adequate trial (6–8 weeks at 10–20 mg) delays recovery and misses potential therapeutic response. 5, 1
• Do not add buspirone, bupropion, or other augmentation agents until the patient has completed at least 8 weeks at escitalopram 20 mg daily, as augmentation is indicated only after documented failure of optimized monotherapy. 1
• Do not combine escitalopram with other serotonergic agents (MAOIs, other SSRIs, SNRIs, triptans, tramadol, St. John's Wort) due to serotonin syndrome risk. 1, 2

If Dose Escalation Fails After 8 Weeks at 20 mg

• Add cognitive-behavioral therapy (CBT) to escitalopram, as combination therapy demonstrates superior efficacy compared to medication alone for both depression and anxiety. 1
• Consider augmentation with bupropion SR (150–400 mg daily), which has significantly lower discontinuation rates due to adverse events (12.5%) compared to buspirone (20.6%, p<0.001) and addresses residual low energy and motivation. 1
• Alternatively, switch to an SNRI (venlafaxine 150–225 mg or duloxetine 40–120 mg daily), which demonstrates statistically superior response and remission rates compared to SSRIs in treatment-resistant cases. 1

Common Pitfall: Misinterpreting Early Symptom Fluctuation

• Worsening symptoms at day 14 on a subtherapeutic dose (5 mg) does not represent treatment failure or indicate the need to switch medications; it reflects inadequate dosing and insufficient treatment duration. 1, 2
• The initial improvement likely represented placebo response or natural symptom variability, not true pharmacologic effect, as escitalopram 5 mg is below the therapeutic threshold. 1, 3