In treatment resistant OCD patients, who had failed two to six SRI trials, doubleblind addition of once-weekly morphine resulted in a significant reduction of OCD symptoms at week two versus placebo, while lorazepam as another control condition was

undistinguishable from placebo.102 Augmentation with the opoid antagonist naltrexone did not Inhibitors,research,lifescience,medical show efficacy for OCD symptoms in a double-blind placebo-controlled study in SSRI or clomipramine refractory patients.103 For several other drugs preliminary interesting findings mostly from AZD2281 mouse short-term open studies or case reports exist. Addition of gabapentin seems to shorten the time of onset of fluoxetine’s antiobsessive effect.104 Restarting of previously untolerated serotonergic antidepressants after valproate pretreatment Inhibitors,research,lifescience,medical was reported to lead to better tolerance and reduction of OCD symptoms in a case series.105 Valproate monotherapy was successful in an SRI-intolerant OCD patient.106 The 5-HT3 receptor antagonist

Inhibitors,research,lifescience,medical ondansetrone may have promise both as monotherapy107 and as an augmentation strategy for some OCD patients.108 Amelioration of refractory OCD on treatment with clozapine was described in a few case reports.109-111 Antiandrogenic treatment with cyproterone acetate112 and the long-acting gonadotropin-releasing hormone analogue triptorelin113 was reported to result in Inhibitors,research,lifescience,medical considerable improvement of symptoms of OCD. Marked decreases of symptoms were observed shortly after single-dose exposures to the psychedelic drug psilocybin in patients with OCD.114 Nicotine treatment was reported to display a

favorable response, both in monotherapy as well as for augmentation,115-117 while inositol augmentation of SSRIs led to a clinically significant response in some OCD patients in an open study118; in a small Inhibitors,research,lifescience,medical double-blind crossover study no significant improvement by this second messenger precursor was seen.119 Acute significant antiobsessional effects for a single dose of dextroamphetamine were reported in a double-blind crossover study in patients with severe OCD120 Improvement of OCD was seen in treatment-resistant patients to serotonergic antidepressants after augmentation with both first dextroamphetamine and caffeine in a double-blind study without placebo arm.121 Future prospects Despite the considerable current knowledge that has been accumulated about evidence-based drug treatment of adults with OCD, as given account of above, and as summarized in Table I, several important clinical issues are still unresolved and need further research. There is still a paucity of long-term trials (especially for treatment with SRIs for more than 1 year and for augmentation with antipsychotics).