What add-on medications can be considered for a patient still depressed on ZOLOFT (sertraline) 50mg?

First, Optimize Sertraline Dose Before Adding Anything

Before considering add-on therapy, increase sertraline from 50mg to at least 100-150mg daily, as 50mg is merely the starting dose and most patients require higher doses for adequate antidepressant response. 1, 2

Dose Optimization Strategy

• Sertraline 50mg is the initial starting dose, not the therapeutic target dose 1
• The optimal therapeutic range is typically 100-200mg daily, with most patients responding to 100-150mg 1, 3
• Increase by 50mg increments at weekly intervals if tolerated, up to 200mg maximum 1
• Allow at least 2-4 weeks at each dose level to assess response before further titration 4
• Sertraline demonstrates dose-dependent efficacy, and inadequate dosing is a common reason for apparent treatment failure 1, 2

If Inadequate Response After Dose Optimization

Add-On Medication Options (in order of evidence strength):

1. Lithium Augmentation 4

• Dosage: 150-300mg daily targeting blood levels of 0.2-0.6 mEq/L 4
• Well-established augmentation strategy for antidepressant non-response 4
• Monitor for neurotoxicity, especially in elderly patients 4

2. Atypical Antipsychotic Augmentation 4

• Consider if depression includes psychotic features 4
• Requires concomitant use when psychosis is present 4

3. Bupropion Addition 4

• Start 37.5mg daily, increase by 37.5mg every 3 days to maximum 150mg twice daily 4
• Activating properties may improve energy and apathy 4
• Contraindicated in patients with seizure disorders or significant agitation 4
• Give second dose before 3 PM to minimize insomnia risk 4

4. Mirtazapine Addition 4

• Start 7.5mg at bedtime, maximum 30mg 4
• Particularly useful if patient has insomnia, poor appetite, or weight loss 4
• Well-tolerated augmentation option 4

Critical Safety Considerations

Avoid combining multiple serotonergic agents due to serotonin syndrome risk 4

• When adding a second serotonergic medication, start at low dose and increase slowly 4
• Monitor closely in first 24-48 hours after any dose change 4
• Never combine with MAOIs (contraindicated) 4

Common Pitfalls to Avoid

• Premature augmentation: Most "treatment failures" at 50mg sertraline are actually inadequate dosing 1, 2
• Insufficient trial duration: Allow 4-8 weeks at therapeutic doses before declaring treatment failure 1, 2
• Polypharmacy without optimization: Adding medications before maximizing sertraline dose increases side effect burden without addressing the primary issue 1

Non-Pharmacological Augmentation

Consider adding Cognitive Behavioral Therapy (CBT) 4

• Combination CBT plus SSRI shows superior outcomes compared to medication alone 4
• Particularly effective for anxiety comorbidities 4