Should lamotrigine be discontinued in a patient with treatment-resistant MDD and OCD, stabilized on max dose sertraline (200mg), with a history of failed combination therapy with lamotrigine and other SSRIs?

Should Lamotrigine Be Discontinued?

Yes, discontinue lamotrigine in this patient—the evidence strongly suggests that when only changing the SSRI provides benefit and lamotrigine has failed with multiple prior SSRIs, continuing it offers no meaningful therapeutic value and unnecessarily exposes the patient to medication burden and potential adverse effects.

Clinical Reasoning Based on Treatment Response Pattern

Your patient's clinical course reveals a critical pattern: sertraline succeeded where other SSRIs failed, and this improvement occurred despite lamotrigine augmentation being present throughout multiple failed trials. This strongly suggests:

• The therapeutic benefit derives from sertraline specifically, not from the lamotrigine augmentation 1
• When augmentation strategies fail across multiple SSRI trials but switching SSRIs succeeds, the augmenting agent has demonstrated inefficacy for that individual patient 2
• Lamotrigine augmentation appears in treatment algorithms for SSRI-resistant OCD only after adequate trials of first-line augmentation strategies (antipsychotics like risperidone or aripiprazole) have failed 1, 2

Evidence Hierarchy for OCD Augmentation

The treatment-resistant OCD literature establishes a clear hierarchy that your patient's history violates:

• First-line augmentation: Risperidone and aripiprazole have the strongest evidence, with approximately one-third of SSRI-resistant OCD patients achieving clinically meaningful response 1, 2
• Second-line augmentation: N-acetylcysteine has the strongest evidence among glutamatergic agents (three out of five RCTs showing superiority to placebo), followed by memantine 1, 2
• Lamotrigine appears only in case reports and small case series for treatment-resistant OCD, with evidence limited to patients who failed combinations of SSRIs with clomipramine and/or antipsychotics 3, 4, 5

Why Lamotrigine Failed in This Case

The case report evidence for lamotrigine reveals important context that doesn't apply to your patient:

• Published lamotrigine successes involved patients with 10-22 years of severe, treatment-refractory OCD who had failed multiple combinations including clomipramine plus SSRIs and antipsychotic augmentation 3, 4
• These were "last resort" scenarios where lamotrigine was added after exhausting evidence-based options 3, 4, 5
• Your patient achieved response by switching SSRIs, indicating they were not truly treatment-refractory to serotonergic mechanisms 1, 2

Practical Algorithm for Decision-Making

Step 1: Confirm sertraline optimization

• Ensure patient has been on sertraline 200mg for at least 8-12 weeks with confirmed adherence 1, 2
• Verify that Cognitive Behavioral Therapy with Exposure and Response Prevention (ERP) is implemented, as CBT produces larger effect sizes than pharmacological augmentation alone 1, 2

Step 2: Discontinue lamotrigine

• Taper lamotrigine gradually (reduce by 50mg every 1-2 weeks) to avoid withdrawal effects
• Monitor for any unexpected worsening, though this is unlikely given the failed augmentation history across multiple SSRIs 3, 4

Step 3: Optimize sertraline monotherapy

• Continue sertraline 200mg as monotherapy for 12-24 months after achieving remission, given high relapse rates after discontinuation 1, 2
• If partial response persists, consider evidence-based augmentation with aripiprazole (lower metabolic side effects than risperidone) or N-acetylcysteine before considering lamotrigine again 1, 2

Critical Pitfalls to Avoid

• Do not maintain ineffective augmentation "just in case"—this increases medication burden, potential drug interactions, and side effect risk without therapeutic benefit 2
• Do not assume lamotrigine contributed to sertraline's success when it failed with multiple other SSRIs—the most parsimonious explanation is that sertraline's unique pharmacological profile (potent SSRI with dopamine reuptake inhibition at higher doses) provided the benefit 6, 7
• Do not restart lamotrigine without first trying evidence-based augmentation strategies (antipsychotics, N-acetylcysteine, memantine) if sertraline monotherapy proves insufficient 1, 2

Monitoring After Discontinuation

• Assess OCD symptoms using standardized measures (Y-BOCS) at 2,4, and 8 weeks post-discontinuation 3, 4
• If symptoms worsen after lamotrigine discontinuation (unlikely but possible), this would represent the first evidence of efficacy for this patient and would warrant reconsideration 3
• Continue monitoring metabolic parameters if any antipsychotic augmentation is considered in the future 1, 2