Objective: Obsessive-compulsive disorder (OCD) is a mental disease commonly
associated with severe distress and impairment of social functioning. Serotonin reuptake inhibitors
and/or cognitive behavioural therapy are the therapy of choice, however up to 40% of patients do
not respond to treatment. Glutamatergic signalling has also been implicated in OCD. The aim of the
current study was to review the clinical evidence for therapeutic utility of glutamate-modulating
drugs as an augmentation or monotherapy in OCD patients.
Methods: We conducted a search of the MEDLINE database for clinical studies evaluating the
effect of glutamate-modulating drugs in OCD.
Results: Memantine is the compound most consistently showing a positive effect as an augmentation
therapy in OCD. Anti-convulsant drugs (lamotrigine, topiramate) and riluzole may also provide
therapeutic benefit to some OCD patients. Finally, ketamine may be of interest due to its potential
for a rapid onset of action.
Conclusion: Further randomized placebo-controlled trials in larger study populations are necessary
in order to draw definitive conclusions on the utility of glutamate-modulating drugs in OCD.
Furthermore, genetic and epigenetic factors, clinical symptoms and subtypes predicting treatment
response to glutamate-modulating drugs need to be investigated systematically.