gov Identifiers: NCT00211744 and NCT00182520). Also for pregabalin, which can indirectly inhibit glutamate release via blockade of calcium channels, beneficial effects on OCD symptoms in combination with serotonergic antidepressants have been reported in case reports.69,70 A double-blind placebo-controlled study with pregablin in SSRI-refractory OCD is being conducted (ClinicalTrials.gov Identifier: NCT00994786). For augmentation of fluoxetine in a treatment refractory patient with glutamate modulator N-acetylcysteine, a marked decrease of OCD symptoms was observed.71 A doubleblind study

with this agent is currently recruiting patients with OCD (ClinicalTrials.gov Inhibitors,research,lifescience,medical Identifier: NCT00539513). Another interesting development with a glutamatergic agent involves D -cycloserine, a partial agonist at the NMDA receptor, which was found to facilitate fear extinction learning in preclinical and human studies when administered before or shortly after exposure to fearful cues.72

Inhibitors,research,lifescience,medical D-cycloserine augmentation of psychotherapy with exposure and A674563 response prevention in OCD has so far been investigated in three randomized, double-blind, placebo-controlled studies. A study with ten exposure sessions and drug intake 4 hours before each session failed to support the use of D-cycloserine Inhibitors,research,lifescience,medical (250 mg).73 In contrast, significantly greater decreases in obsession-related distress after four exposure sessions under D-cycloserine (125 mg, given 2 hours before each session) were reported.74

However, the placebo Inhibitors,research,lifescience,medical group tended to catch up after additional sessions. Both the number of therapy dropouts and the number of sessions needed to achieve “clinical milestones” were decreased by active treatment. In another study, OCD patients were reported to be significantly more improved under D-cycloserine at mid-treatment (ten behavior therapy sessions in total, dose of 100 mg 1 hour before each session), but not at later time points.75 Dosage and timing of D-cycloserine as well as the number of combined intervensions are critical parameters. So far, just a shortterm acceleration of response to exposure therapy under D-cycloserine was shown, Inhibitors,research,lifescience,medical but no significant differences in the further course due to floor effects of exposure therapy. Several antidepressants other than SSRIs or clomipramine have been 3-mercaptopyruvate sulfurtransferase tested, as mentioned for noradrenergic tricyclics above. For the alpha-2 receptor and serotonin (5-HT)2/3 receptor antagonist mirtazapine an open trial showed negative results.76 However, in a double -blind discontinuation period of 8 weeks (after an open trial) superiority of to placebo was demonstrated.77 Addition of mirtazapine to citalopram did not result in increased efficacy when compared with addition of placebo, but was associated with an accelerated onset of action in a single -blind study.78 Preclinical experiments suggest that blockade of 5-HT2C receptors may have an anticompulsive effect in OCD.