In an older adult allergic to fluoxetine (Prozac) and paroxetine (Paxil) who is tolerating escitalopram (Lexapro) 20 mg daily but remains depressed, what are the recommended next‑step pharmacologic and non‑pharmacologic treatment options?

Augment Escitalopram 20 mg to 30 mg Daily or Add Bupropion SR 150 mg

For a geriatric patient tolerating escitalopram 20 mg without side effects but experiencing persistent depression, the strongest evidence supports adding bupropion SR 150 mg daily rather than switching antidepressants. 1

Why Augmentation Over Switching

The STAR*D trial demonstrated that augmenting the current SSRI produces comparable efficacy to switching but results in fewer discontinuation symptoms (e.g., dizziness, anxiety), making augmentation the preferable strategy when partial response occurs. 1

• Approximately 38% of patients fail to achieve adequate response during initial SSRI treatment at 6-12 weeks, and 54% do not achieve remission—this patient falls into that category. 2, 1
• Switching antidepressants carries the burden of tapering, washout periods, and re-titration, along with potential withdrawal symptoms. 1

Primary Recommendation: Add Bupropion

Add bupropion SR 150 mg once daily in the morning to the current escitalopram 20 mg regimen. 1

• Bupropion is particularly valuable when cognitive symptoms are prominent, offering dopaminergic/noradrenergic activity with lower rates of sexual dysfunction compared to increasing SSRI doses. 1
• High-quality evidence from a large randomized trial supports bupropion augmentation as superior to buspirone augmentation for reducing depression severity. 2
• Start at approximately 50% of standard adult doses (75-150 mg daily) in geriatric patients, then adjust based on response and tolerability. 1

Alternative: Increase Escitalopram Dose

If bupropion is contraindicated (seizure history, eating disorder), consider increasing escitalopram to 30 mg daily, but never exceed this dose in patients over 60 years. 1

• The FDA and European Medicines Agency have established a maximum dose of 10 mg daily for escitalopram in patients > 60 years due to dose-dependent QTc prolongation and cardiac conduction risks. 1
• However, some guidelines reference 20 mg as the maximum safe dose in this age group. 1, 3
• Critical safety warning: Never exceed 20 mg daily of citalopram or 10 mg daily of escitalopram in patients > 60 years per the most conservative FDA guidance. 1

Given the conflicting evidence on maximum escitalopram dosing in elderly patients (10 mg vs 20 mg), and the fact that this patient is already at 20 mg, augmentation with bupropion is safer than further dose escalation.

Assessment Before Augmentation

• Confirm medication adherence—non-adherence is a common cause of apparent treatment failure. 1
• Assess for treatment-emergent side effects that may be limiting response (sexual dysfunction, emotional blunting, sedation). 1
• Evaluate for comorbid medical conditions that may be contributing to depression (hypothyroidism, vitamin B12 deficiency, anemia). 1
• Review concomitant medications for drug interactions or medications that may worsen depression (beta-blockers, benzodiazepines). 1

Monitoring After Augmentation

• Assess treatment response at week 4 and week 8 using standardized scales (PHQ-9, HAM-D). 1
• Monitor for suicidal ideation during the first 1-2 weeks after adding bupropion, though the risk is markedly lower in adults ≥ 65 years (OR 0.06). 1
• Check blood pressure at each visit, as bupropion can occasionally elevate blood pressure. 1
• Monitor for activation symptoms (restlessness, insomnia, agitation) during the first 2-4 weeks. 1

Treatment Duration After Response

• Continue combination therapy for a minimum of 4-12 months after achieving remission for first-episode depression. 2, 1
• For patients with recurrent depression (≥3 episodes), consider indefinite maintenance therapy at the lowest effective dose, as recurrence risk reaches ~90% after the third episode. 2, 1

Non-Pharmacologic Augmentation

• Add cognitive behavioral therapy (CBT) to pharmacotherapy—combination treatment is superior to either alone for depression and anxiety disorders. 1
• Implement aerobic exercise programs, which have a moderate antidepressant effect (standardized mean difference -0.82). 1
• Address social isolation through referral to local social assistance programs, optimize nutrition, and encourage social engagement. 1

Medications to Avoid in This Patient

• Do not switch to paroxetine—the patient has a documented allergy, and paroxetine should not be used in older adults due to highest anticholinergic effects, highest sexual dysfunction rates, and potent CYP2D6 inhibition. 1
• Do not switch to fluoxetine—the patient has a documented allergy, and fluoxetine should be avoided in older adults due to greater risk of agitation, long half-life, and drug interaction potential. 1
• Do not use tertiary-amine TCAs (amitriptyline, imipramine)—these are potentially inappropriate per Beers Criteria due to severe anticholinergic effects and cardiac toxicity (OR 1.69 for cardiac arrest). 2, 1

Common Pitfalls to Avoid

• Do not prematurely switch antidepressants before attempting augmentation—switching has comparable efficacy but more discontinuation symptoms. 1
• Do not exceed maximum safe doses of escitalopram in elderly patients (10-20 mg daily depending on guideline). 1, 3
• Do not combine escitalopram with NSAIDs without gastroprotection—the combination increases GI bleeding risk 15-fold (adjusted OR 15.6). 1
• Do not discontinue monitoring after initial titration—hyponatremia can occur at any time during SSRI treatment, with 0.5-12% of elderly patients affected. 1