Is lamotrigine (anticonvulsant) evidence-based for treating Obsessive-Compulsive Disorder (OCD) and anxiety?

Lamotrigine for OCD and Anxiety: Evidence Assessment

Lamotrigine is not a first-line or well-established treatment for OCD or anxiety disorders, but has some limited evidence as an augmentation strategy only for treatment-resistant OCD cases that have failed multiple SSRI trials. 1

First-Line Evidence-Based Treatments for OCD

Psychotherapy

• Cognitive-Behavioral Therapy (CBT) with Exposure and Response Prevention (ERP) is the psychological treatment of choice for OCD, with larger effect sizes than pharmacological treatments (number needed to treat of 3 for CBT vs 5 for SSRIs) 1
• ERP involves gradual exposure to fear-provoking stimuli combined with instructions to abstain from compulsive behaviors 1
• Patient adherence to between-session homework is the strongest predictor of good outcomes 1

First-Line Pharmacotherapy

• SSRIs are the first-line pharmacological treatment for OCD based on established efficacy, tolerability, safety, and absence of abuse potential 1
• Higher doses of SSRIs are typically needed for OCD compared to depression or other anxiety disorders 1
• Clomipramine, a non-selective serotonin reuptake inhibitor, was the first medication shown to be effective for OCD but is generally considered second-line due to its side effect profile 1

Treatment-Resistant OCD Management

Evidence-Based Augmentation Strategies

• For patients who fail to respond to first-line treatments (approximately 50% of cases), several augmentation strategies exist 1
• Primary evidence-based augmentation strategies include:
  • Adding CBT to SSRI therapy 1
  • Antipsychotic augmentation (particularly risperidone and aripiprazole) 1
  • Clomipramine added to an SSRI (with careful monitoring for adverse effects) 1

Glutamatergic Agents Including Lamotrigine

• Glutamatergic medications have been evaluated as augmentation agents in treatment-resistant OCD with some evidence of efficacy 1
• Among glutamatergic agents, N-acetylcysteine has the largest evidence base (three out of five randomized controlled trials showed superiority to placebo) 1
• Memantine has several trials demonstrating efficacy as an SSRI augmentation strategy 1
• Lamotrigine has been evaluated as an augmentation agent for treatment-resistant OCD, but with limited evidence 1
• Case reports suggest potential benefit when adding lamotrigine to SSRIs or clomipramine in highly treatment-resistant OCD patients who have failed multiple previous treatments 2, 3

Important Caveats and Considerations

• Lamotrigine has paradoxically been reported to induce obsessive-compulsive symptoms in some patients with bipolar disorder 4
• Most studies of lamotrigine for unipolar depression and anxiety have methodological limitations including short treatment phases 5
• Lamotrigine is primarily approved for epilepsy and bipolar disorder maintenance, not for anxiety disorders or OCD 6
• When considering lamotrigine, clinicians should be aware of the risk of serious rash including Stevens-Johnson syndrome, requiring careful titration

Treatment Algorithm for OCD

1. First-line: CBT with ERP and/or SSRI medication 1
2. For partial response: Optimize SSRI dose and ensure adequate trial duration (8-12 weeks) 1
3. For inadequate response: Consider switching to another SSRI or to clomipramine 1
4. For treatment resistance:
   • Add CBT if patient is on medication only 1
   • Consider antipsychotic augmentation (risperidone or aripiprazole) 1
   • Consider glutamatergic agents with stronger evidence (N-acetylcysteine, memantine) 1
   • Consider lamotrigine augmentation only after multiple failed treatments 1, 2

In conclusion, while there are case reports suggesting potential benefit of lamotrigine augmentation in highly treatment-resistant OCD, it should not be considered before established first-line and second-line treatments have been adequately tried.