Obsessive-compulsive disorder The serendipitous discovery that clomipramine (CMI), a more serotonergic tricyclic, is effective for obsessive-compulsive disorder (OCD) was important in giving impetus to a serotonin hypothesis of OCD.47 Subsequent work found that the more selective SSRIs were not only efficacious but also well-tolerated.48 More recent psychobiological Inhibitors,research,lifescience,medical research has focused on

delineating the role of neurotransmitters other than serotonin; dopaminergic augmentation strategies have been used clinically for some time now,49 and a range of other molecular treatment targets are being pursued.50,51 Anecdotal reports of the efficacy of CMI in OCD were followed by rigorous randomized controlled trials. Such work demonstrated Inhibitors,research,lifescience,medical that clomipramine was more efficacious than both placebo and noradrenergic tricyclic agents such as desipramine, and that it was efficacious in both adults as well as in children and adolescents with OCD.52 Such work led to the first FDA approval for OCD pharmacotherapy.15 The use of intravenous (IV) CMI for refractory OCD has also been investigated,53,54 as this route of administration avoids first-pass hepatic metabolism which breaks CMI down to its less potent form, desmethyl-clomipramine. Inhibitors,research,lifescience,medical With the introduction of the SSRIs, several studies of these

agents were undertaken in OCD, and these generally showed efficacy and safety.55 Fluoxetine, fluvoxamine, paroxetine, and sertraline have all been FDA-approved for OCD.56 While several meta-analyses have suggested that CMI may be more effective Inhibitors,research,lifescience,medical than SSRIs (Table II),57 this finding may reflect the fact that earlystudies were characterized by a lower placebo response rate. Flead-to-head comparisons of CMI and SSRIs have shown equal efficacy and superior tolerability for the SSRIs.58 Thus, the SSRIs are now typically viewed as the first-line choice for OCD.8,9,11,56,59 Table II. Selected meta-analyses of obsessive-compulsive disorder treatment. CMI, clomipramine; SSRI, selective serotonin reuptake Inhibitors,research,lifescience,medical inhibitor;

OCD, obsessive-compulsive disorder A meta-analysis of medication dosage findings in OCD suggests that patients who fail to respond to low-dose therapy should be increased to a higher isothipendyl dose.60 An adequate trial in OCD should be at least 12 weeks in length.61 Although there is less published work on the ERK inhibitor concentration longer-term treatment of OCD, a number of studies have demonstrated that early discontinuation often leads to relapse.58 Guidelines therefore suggest that patients who respond to initial acute treatment should then be continued for at least 1 year, and withdrawn gradually.8,9,56,59 It has been suggested that efficacy can be maintained even after a reduction in dosage of long-term treatment, with the benefits of improved tolerability and adherence.