What to add to Lamictal (lamotrigine) 25mg daily for ongoing depressive symptoms?

Lamotrigine Augmentation for Ongoing Depression

Continue titrating lamotrigine to a therapeutic dose of 200 mg daily over the next 5 weeks, then add an SSRI (such as sertraline 25-50 mg daily) or bupropion (37.5 mg daily, titrated by 37.5 mg every 3 days) if depressive symptoms persist after reaching the target lamotrigine dose. 1, 2, 3

Why 25 mg Daily is Insufficient

• Lamotrigine 25 mg daily is only the first week of a 6-week titration schedule required to reach the therapeutic dose of 200 mg/day 2, 3
• The slow titration is mandatory to minimize the risk of serious rash, including Stevens-Johnson syndrome (0.1% incidence), which occurs primarily when dosing is escalated too rapidly 2, 3, 4
• Therapeutic efficacy for bipolar depression typically requires 200 mg/day, and clinical response should not be assessed until this target dose is maintained for at least 2-4 weeks 2, 3, 5

Recommended Titration Algorithm

Standard lamotrigine titration schedule (when NOT on valproate): 2, 3

• Weeks 1-2: 25 mg daily
• Weeks 3-4: 50 mg daily
• Week 5: 100 mg daily
• Week 6 onward: 200 mg daily (therapeutic target)

Critical caveat: If the patient is taking valproate, the titration must be slower and the target dose reduced to 100 mg daily due to pharmacokinetic interactions 2, 3

What to Add After Reaching Therapeutic Lamotrigine Dose

First-Line Augmentation Options

If depressive symptoms persist after 2-4 weeks at lamotrigine 200 mg daily:

1. SSRI augmentation (preferred for anxiety + depression): 6

   • Sertraline 25-50 mg daily, titrated to 200 mg daily maximum
   • Citalopram 10 mg daily, titrated to 40 mg daily maximum
   • SSRIs are well-tolerated and have minimal drug interactions with lamotrigine 6

2. Bupropion augmentation (preferred for fatigue/low energy): 6

   • Start 37.5 mg every morning
   • Increase by 37.5 mg every 3 days
   • Target dose: 150 mg twice daily
   • Activating properties provide rapid improvement in energy levels 6
   • Give second dose before 3 PM to minimize insomnia risk 6
   • Contraindicated if seizure history or eating disorder present 6

3. Mirtazapine (if insomnia/poor appetite predominate): 6

   • Start 7.5 mg at bedtime
   • Target dose: 30 mg at bedtime
   • Promotes sleep, appetite, and weight gain 6

Critical Monitoring Requirements

• Assess treatment response every 1-2 weeks initially, then monthly once stable 6, 1
• Monitor weekly for any signs of rash, particularly during the first 8 weeks of lamotrigine titration 1, 2, 3
• If inadequate response after 6-8 weeks at therapeutic doses, modify treatment by switching or adding another agent 6
• Watch for treatment-emergent hypomania/mania when adding antidepressants, though lamotrigine itself has minimal antimanic effects 7

Important Clinical Considerations

Lamotrigine's specific efficacy profile: 1, 2, 3

• Highly effective for preventing depressive episodes in bipolar disorder
• Limited efficacy for preventing manic episodes (lithium superior for this)
• NOT effective for acute mania treatment
• Does not cause weight gain, unlike most mood stabilizers 2, 3

Risk of lamotrigine-induced mania: 7

• More likely in patients with bipolar I disorder, manic predominant polarity, or history of antidepressant-induced mania
• If bipolar disorder is suspected, ensure adequate mood stabilization before adding antidepressants
• Never use antidepressant monotherapy in bipolar disorder 1, 8

Common Pitfalls to Avoid

• Assessing efficacy before reaching therapeutic dose (200 mg daily for at least 2-4 weeks) 2, 3, 5
• Rapid titration increasing serious rash risk 2, 3, 4
• Restarting lamotrigine at previous dose after >5 days discontinuation—must restart full titration 1
• Adding antidepressants too early before adequate lamotrigine trial 6, 5
• Inadequate duration of maintenance therapy—continue for at least 12-24 months after response 1