What are the considerations for withdrawing Lamotrigine (an augmenting agent) in an adult patient with Obsessive-Compulsive Disorder (OCD) and Major Depressive Disorder (MDD) who has been taking Sertraline (Selective Serotonin Reuptake Inhibitor (SSRI)) 200mg with a partial response?

Withdrawing Lamotrigine Augmentation in Partial Response to Sertraline for OCD and MDD

Direct Recommendation

Lamotrigine should be gradually tapered and discontinued in this case, as it lacks robust evidence for augmentation in OCD and has only limited case report support, while evidence-based augmentation strategies (antipsychotics, CBT, or switching SSRIs) should be prioritized instead. 1

Rationale for Discontinuation

Limited Evidence Base for Lamotrigine in OCD

• Lamotrigine augmentation for treatment-resistant OCD is supported only by case reports and small case series, not by randomized controlled trials 2, 3, 4
• The strongest evidence-based augmentation strategies for SSRI-resistant OCD are risperidone and aripiprazole, with approximately one-third of patients showing clinically meaningful response 1
• N-acetylcysteine has the strongest evidence among glutamatergic agents (which includes lamotrigine), with only three out of five randomized controlled trials showing superiority to placebo 1

Risk of Lamotrigine-Induced OCD Symptoms

• A critical caveat: lamotrigine has been reported to induce de novo obsessions and compulsions in patients with bipolar disorder, with symptoms developing 2-8 months after initiation and resolving within one month of discontinuation 5
• This paradoxical effect makes lamotrigine a particularly questionable choice for OCD augmentation 5

Definition of Adequate Treatment Trial

• Before considering any augmentation strategy, ensure sertraline has been trialed at maximum tolerated doses (typically up to 200mg for OCD) for at least 8-12 weeks with confirmed adherence 1
• Treatment resistance in OCD requires failure of both adequate SSRI trials AND Cognitive Behavioral Therapy with Exposure and Response Prevention (ERP) 1

Safe Discontinuation Protocol

Tapering Strategy

• Taper lamotrigine gradually over 2-4 weeks to avoid withdrawal symptoms or rebound worsening of symptoms 6
• General clinical reasoning suggests removing augmenting agents first before adjusting the primary medication (sertraline) 6
• Monitor for 2-3 months after complete discontinuation, as mood and anxiety disorder symptoms may return weeks to months after the last dose 6

Monitoring During Discontinuation

• Assess for return or worsening of OCD symptoms using standardized measures (Y-BOCS scale) 1
• Monitor for depressive symptom changes given the comorbid MDD 6
• Watch for any paradoxical improvement in OCD symptoms, given the potential for lamotrigine to induce obsessionality 5

Evidence-Based Next Steps After Discontinuation

First-Line Augmentation Options

• Adding CBT with Exposure and Response Prevention has larger effect sizes compared to pharmacological augmentation alone and should be prioritized if not already implemented 1
• Augmentation with risperidone or aripiprazole has the strongest evidence, with approximately one-third of SSRI-resistant OCD patients showing clinically meaningful response 1

Alternative Pharmacological Strategies

• Consider switching to a different SSRI or venlafaxine (SNRI) if augmentation strategies fail 1
• Augmentation with bupropion for the comorbid MDD component showed decreased depression severity compared to buspirone in citalopram-treated patients 6
• N-acetylcysteine (1200-3000mg/day) represents a glutamatergic option with stronger evidence than lamotrigine 1

Treatment Duration Considerations

• Maintain any effective treatment for 12-24 months after achieving remission due to high relapse rates after discontinuation 1
• Approximately 50% of OCD patients fail to fully respond to first-line treatments, which can be even higher in real-world settings 1

Key Clinical Pitfalls to Avoid

• Do not discontinue lamotrigine abruptly, as this may cause withdrawal symptoms or rebound worsening 6
• Do not assume partial response to sertraline 200mg represents treatment resistance without confirming adequate trial duration (8-12 weeks) and adherence 1
• Do not pursue further augmentation strategies without ensuring CBT with ERP has been adequately trialed 1
• When monitoring metabolic side effects with antipsychotic augmentation (if chosen next), assess weight, blood glucose, and lipid profiles 1