Should Lamotrigine Be Tapered in This Patient?
No, lamotrigine should not be tapered at this time—it should be maintained at 200mg while optimizing the sertraline regimen, as the patient has achieved only partial response and lamotrigine demonstrates specific efficacy in treatment-resistant depression that may be contributing to the current improvement.
Rationale for Maintaining Lamotrigine
Evidence Supporting Continuation
Lamotrigine has demonstrated significant efficacy as augmentation therapy in treatment-resistant depression, with studies showing rapid symptom reduction (as early as 2 weeks) when added to antidepressants, particularly for core depressive symptoms including depressed mood, loss of interest, and cognitive impairment 1, 2.
The patient's partial response to sertraline may represent the combined effect of both medications, not sertraline alone. Discontinuing lamotrigine risks losing any contribution it is making to the current improvement 2, 3.
Treatment-resistant depression requires sustained combination therapy until full remission is achieved. The American College of Physicians recommends modifying treatment only after 6-8 weeks if response is inadequate, not removing effective components prematurely 4.
Principles for Medication Discontinuation in Polypharmacy
The American Academy of Child and Adolescent Psychiatry provides clear guidance on which medication to remove first when patients are on multiple agents 4:
When two medications target the same disorder, remove the augmenting agent first—but only after achieving full remission, not partial response 4.
In this case, lamotrigine is the augmenting agent, but the patient has not achieved remission, making this the wrong time to taper 4.
Gradual tapering is prudent when it is unclear whether the current medication is having beneficial effect—however, lamotrigine's established efficacy in treatment-resistant depression suggests it likely is contributing 4.
Recommended Management Strategy
Optimize Current Regimen First
Increase sertraline to maximum therapeutic dose (200mg daily) before considering any medication removal, as the American College of Physicians recommends ensuring adequate dose and duration (6-8 weeks at therapeutic dose) before declaring treatment failure 4.
Maintain lamotrigine at 200mg throughout this optimization period, as this dose has demonstrated efficacy in controlled trials for bipolar depression and treatment-resistant unipolar depression 5, 1.
Reassess response after 6-8 weeks at optimized sertraline dosing using standardized depression rating scales (PHQ-9 or HAM-D) 4.
If Full Remission Is Achieved
Only after achieving full remission and maintaining it for 4-9 months should medication discontinuation be considered 4:
Taper lamotrigine first (as the augmenting agent) while maintaining sertraline, following the principle of removing the adjunctive medication before the primary agent 4.
Monitor closely for symptom return during and after tapering, as mood disorder symptoms may recur weeks to months after the last dose 4.
If Partial Response Persists After Optimization
Consider switching sertraline to an SNRI (venlafaxine or duloxetine), which demonstrates statistically significantly better response and remission rates than SSRIs in treatment-resistant depression, while maintaining lamotrigine 4.
Alternatively, add bupropion SR to the current regimen (sertraline + lamotrigine + bupropion), as combination therapy achieves remission rates of approximately 50% compared to 30% with monotherapy 6.
Critical Pitfalls to Avoid
Do not remove lamotrigine based solely on the assumption that sertraline is responsible for the partial response—treatment-resistant depression by definition requires multiple agents, and premature discontinuation risks relapse 1, 2.
Do not taper medications during partial response—this violates the principle of optimizing treatment before declaring success or failure 4.
Do not continue ineffective treatment beyond 8 weeks at therapeutic doses—but "partial response" is not treatment failure; it indicates the need for optimization, not medication removal 4.
Monitoring Protocol
Assess treatment response every 2-4 weeks using standardized depression rating scales 6.
Monitor specifically for suicidal ideation during any medication changes, as risk is highest during the first 1-2 months 4.
Watch for lamotrigine-specific adverse effects including rash (which requires immediate discontinuation), headache, dizziness, and somnolence 2, 3.