Should lamotrigine (an anticonvulsant and mood stabilizer) be discontinued in a non-bipolar adult patient with a history of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) who has been taking it for 3 years as an augmenting agent to various selective serotonin reuptake inhibitors (SSRIs) and has recently responded well to sertraline (a selective serotonin reuptake inhibitor)?

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Should Lamotrigine Be Discontinued After Successful Sertraline Response?

Continue lamotrigine alongside sertraline 200mg rather than discontinuing it, as the patient has achieved a successful response with this combination and lamotrigine has demonstrated efficacy as an augmentation agent in treatment-resistant OCD and MDD. Discontinuing a medication that is part of a successful regimen risks relapse, particularly given the patient's three-year history of treatment resistance.

Rationale for Continuation

Evidence Supporting Lamotrigine Augmentation in Treatment-Resistant OCD

  • Lamotrigine has demonstrated efficacy as an augmentation agent specifically in severe, treatment-resistant OCD cases where patients failed multiple SSRI trials, with case reports showing 50% reductions in Yale-Brown Obsessive-Compulsive Scale scores when added to SSRIs 1, 2.

  • The National Institute of Mental Health recognizes lamotrigine among glutamatergic agents with evidence for treatment-resistant OCD, noting that glutamatergic modulation represents a distinct mechanism from serotonergic agents 3.

  • In documented cases, patients with over 10 years of treatment resistance (similar to your patient's profile) achieved significant improvement only after lamotrigine augmentation was added to their SSRI regimen 1.

Risk of Relapse After Discontinuation

  • Treatment duration should be maintained for at least 12-24 months after achieving remission due to high relapse rates after discontinuation in both OCD and MDD 3, 4.

  • The patient's current response represents the first successful treatment after three years of failed trials—this is a fragile therapeutic achievement that should not be disrupted prematurely 3.

  • Approximately 50% of OCD patients fail to fully respond to first-line treatments, and your patient falls into this treatment-resistant category, making maintenance of effective therapy critical 3.

Clinical Decision Algorithm

Step 1: Assess Duration of Current Response

  • Maintain the current regimen (sertraline 200mg + lamotrigine 200mg) for a minimum of 12-24 months after achieving stable remission before considering any medication discontinuation 3, 4.

  • Monitor symptom stability using standardized measures at regular intervals to confirm sustained response 4.

Step 2: If Considering Future Discontinuation

  • After 12-24 months of sustained remission, consider tapering lamotrigine first (rather than sertraline) as a trial, since sertraline is the agent that "responded well" most recently 3.

  • Taper slowly over 2-3 months while monitoring closely for symptom re-emergence 4.

  • If symptoms return during taper, resume the previous effective dose immediately 3.

Step 3: Long-Term Maintenance Strategy

  • Continue both medications indefinitely if the patient has severe, chronic symptoms or multiple prior treatment failures, as this profile predicts high relapse risk 3, 5.

  • The combination of sertraline (maximum FDA-approved dose for OCD at 200mg) plus lamotrigine augmentation represents an evidence-based approach for treatment-resistant cases 4, 1.

Important Caveats and Monitoring

Safety Considerations

  • Monitor for serotonin syndrome at every visit when combining serotonergic medications, watching for agitation, confusion, rapid heart rate, dilated pupils, muscle rigidity, or hyperthermia 3, 4.

  • Continue monitoring for any mood destabilization, though lamotrigine is generally well-tolerated in non-bipolar patients 4.

Common Pitfall to Avoid

  • Do not prematurely discontinue medications that are part of a successful regimen simply because the patient is "not bipolar"—lamotrigine's utility extends beyond mood stabilization to include glutamatergic modulation relevant for OCD treatment 3, 1, 2.

  • The fact that lamotrigine was initially prescribed for augmentation (not mood stabilization) means its therapeutic role is specifically tied to treating the patient's treatment-resistant OCD and MDD 1, 2.

Alternative Consideration Only If Discontinuation Is Mandatory

  • If there are compelling reasons to simplify the regimen (cost, side effects, patient preference), consider adding evidence-based CBT with Exposure and Response Prevention before discontinuing lamotrigine, as CBT shows larger effect sizes than pharmacological augmentation alone and may help maintain gains 3, 4.

  • However, this still carries relapse risk and should only be attempted after 12-24 months of stable remission 3, 4.

Bottom Line

The patient achieved success with sertraline 200mg + lamotrigine 200mg after three years of treatment failure—this combination should be maintained for at least 12-24 months of sustained remission before considering any changes. The evidence supports lamotrigine's role as an effective augmentation agent in treatment-resistant OCD, and discontinuing it now risks losing hard-won therapeutic gains 3, 4, 1, 2.

References

Guideline

Treatment of Treatment-Resistant OCD

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Treatment of Treatment-Resistant OCD with Comorbid Bipolar Features

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

A review of pharmacologic treatments for obsessive-compulsive disorder.

Psychiatric services (Washington, D.C.), 2003

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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