Memantine for OCD: Evidence-Based Recommendation
Memantine (Namenda) can be considered as an effective augmentation agent for treatment-resistant OCD when added to SSRIs, particularly in patients with moderate to severe symptoms who have failed first-line treatments. 1, 2
Clinical Context and Treatment Algorithm
Memantine is not a first-line treatment for OCD. The evidence-based treatment hierarchy is:
- First-line: SSRIs or CBT with Exposure and Response Prevention (ERP) 2, 3
- Second-line: Optimize SSRI dose, switch to another SSRI or clomipramine, or add CBT to medication 2
- Third-line (Treatment-Resistant): Augmentation strategies including memantine, N-acetylcysteine, or antipsychotics 1, 2
Evidence for Memantine Augmentation
The glutamatergic approach with memantine has demonstrated efficacy specifically for treatment-resistant OCD:
Meta-analysis findings: Memantine augmentation produced a mean reduction of 11.73 points on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), with patients 3.61 times more likely to respond compared to placebo 4
Guideline support: Multiple randomized controlled trials have demonstrated memantine's efficacy in SSRI augmentation for treatment-resistant OCD, earning it recognition in current treatment guidelines 1
Optimal dosing: 20 mg/day memantine added to ongoing SSRI therapy for at least 8 weeks is the evidence-based regimen 4
Specific Trial Results
The highest quality double-blind placebo-controlled trial showed:
- Response rates: 100% of memantine patients versus 32% of placebo patients met criteria for partial or complete response 5
- Remission rates: 89% in the memantine group achieved remission compared to 32% in placebo group 5
- Safety profile: Frequency of side effects was not significantly different between memantine and placebo groups 5
Clinical Application
When to consider memantine:
- Patients with Y-BOCS scores ≥21 (moderate to severe OCD) 5
- Inadequate response after 8-12 weeks of adequate-dose SSRI monotherapy 1
- Patients who cannot access or tolerate CBT with ERP 1
- Those with prominent intrusive obsessions may show particularly robust response 6
Dosing protocol:
- Start with 10 mg/day for the first week 5
- Increase to 20 mg/day (10 mg twice daily) for maintenance 5, 4
- Continue for minimum 8 weeks to assess response 4
Important Caveats
One recent trial (2022) showed memantine improved executive function on the Wisconsin Card Sorting Test but did not show superiority over placebo for OCD symptom reduction when added to sertraline 7. However, this contradicts the broader evidence base including the 2019 meta-analysis and multiple positive trials 5, 4. The weight of evidence, including the most recent systematic review, supports memantine's efficacy 4.
Memantine should be positioned after optimizing first-line treatments but before considering more invasive options like neuromodulation, which is reserved for less than 1% of treatment-seeking individuals with extremely intractable cases. 1