Although D-cycloserine does not appear to be effective as an adjunctive treatment in schizophrenia, it has been successfully used to enhance learning and behavioral therapies in anxiety disorders [30]. Combining NMDA-based medication with a cognitive training program is supported by the strong relationship of NMDA receptors and learning; especially because NMDA dysfunction in schizophrenia is relative, rather than absolute, enhanced practice might be able to overcome reduced plasticity, as has recently been reported for sensory-based remediation training [31]. In a proof of concept study [32], an NMDA agonist dose of D-cycloserine was combined with a cognitive behavioral therapy (CBT) targeting delusions. A crossover design was used, so all individuals received a single dose of either D-cycloserine 50 mg or placebo in a randomized double-blind counterbalanced order over two consecutive weeks. Subsequent to study drug dose, individuals received a CBT intervention involving training in the generation of alternative beliefs. The main outcome was not significant, as there was no treatment effect on delusional distress or severity. There was, however, a significant order effect, as individuals who received D-cycloserine first had significantly
