Lamotrigine for OCD Augmentation
Yes, lamotrigine (Lamictal) has been tried and shows evidence of efficacy as an augmentation agent for treatment-resistant obsessive-compulsive disorder, though it is not a first-line option.
Evidence-Based Positioning
According to the 2019 Nature Reviews Disease Primers guideline, lamotrigine is classified among the glutamatergic medications that have been evaluated as augmentation agents in treatment-resistant OCD and have "demonstrated some evidence of efficacy" 1. However, the guideline explicitly states that N-acetylcysteine has the largest evidence base (3 out of 5 positive RCTs), and memantine can also be considered in clinical practice based on several efficacy trials 1.
Clinical Trial Evidence
Lamotrigine has been studied in at least two randomized controlled trials with positive results:
A 2012 double-blind RCT (n=33) showed lamotrigine 100 mg/day added to SRIs significantly improved Y-BOCS obsessions (p<0.0001), compulsions (p<0.0001), and total scores (p<0.0001) over 16 weeks 2
A 2016 RCT (n=53) demonstrated that lamotrigine 100 mg/day augmentation produced mean Y-BOCS reductions of 8.73 points versus 5.07 for placebo (p=0.007), with an effect size (Cohen's d) of 0.54 3
Comparative Effectiveness
A 2023 network meta-analysis of 59 trials ranked augmentation agents by efficacy 4. The most effective agents with moderate certainty of evidence were:
- Memantine (MD: -6.2; 95% CrI: -9.9, -2.3)
- Lamotrigine (MD: -6.0; 95% CrI: -12, -0.47)
- Ondansetron and granisetron
A separate 2023 systematic review concluded that lamotrigine, memantine, and aripiprazole are the augmentation agents most supported by evidence for partial SRI responders 5.
Practical Considerations
Dosing: The studied dose is lamotrigine 100 mg/day as augmentation 3, 2. Standard titration protocols should be followed to minimize risk of serious rash, particularly Stevens-Johnson syndrome - this requires slow dose escalation over several weeks per FDA labeling 6.
Timeline: Response was observed by 8-12 weeks in clinical trials 3, though some case reports suggest earlier improvement is possible 7.
Position in treatment algorithm: Lamotrigine should be considered after:
- Adequate SSRI trials (8-12 weeks at therapeutic doses)
- CBT augmentation if available
- Consideration of first-line augmentation with antipsychotics (aripiprazole, risperidone) or clomipramine 1
Important Caveats
The guideline notes that only one-third of SSRI-resistant OCD patients show clinically meaningful response to any augmentation strategy 1. The effect sizes for glutamatergic agents like lamotrigine are modest, and individual response varies considerably.
The major safety concern with lamotrigine is the risk of serious rash, which requires careful dose titration and patient education about early warning signs 6. This risk-benefit calculation becomes particularly important given that lamotrigine is not the strongest evidence-based option.
Bottom line: Lamotrigine is a reasonable third- or fourth-line augmentation option for treatment-resistant OCD, particularly when first-line augmentation strategies (antipsychotics, memantine, N-acetylcysteine) have failed or are not tolerated. Use 100 mg/day with proper titration protocols.