hile only a few decades ago "obsessive neurosis" had been regarded as a psychiatric condition that was mostly treatment-refractory, several effective therapeutic strategies for obsessive-compulsive disorder (OCD)-both psychotherapeutic drugs and behavioral psychotherapeu-tic techniques-began to evolve during the last third of the 20th century. In terms of modern pharmacotherapy, the first hints of the efficacy of clomipramine, a tricyclic antidepressant (TCA), which inhibits serotonin reuptake,

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... date back about 40 years. 1-3 In the 1970s, research with more stringent designs in this area began, and soon placebo-controlled trials showed the antiobsessive and anticompul-sive action of clomipramine. 4-6 Interestingly, specific anti-OCD effects were even observed when comorbid depression was rigorously excluded. Treatment of OCD patients may require relatively high doses for an extended period of time, which may be accounted for by a greater delay of effect in the orbitofrontal cortex, which is thought to be implicated in OCD. 7 A possible role of serotonergic neurotransmission in the pathophysiology of OCD was surmised by the results of the studies with clomipramine, by later numerous investigations showing the therapeutic action of different selective serotonin reuptake inhibitors (SSRIs) in OCD, and by additional findings, such as the provocation of OCD symptoms by the serotonergic agent m-chlorophenylpiperazine. 8-10 Interestingly, predominantly noradrenergic drugs, such as the TCAs desipramine 11 and nortriptyline 4 were less Knowledge of pharmacotherapeutic treatment options in obsessive-compulsive disorder (OCD) has grown considerably over the past 40 years. Serotonergic antide-pressants, such as selective serotonin reuptake inhibitors (SSRIs) and clomipramine, are the established pharma-cologic first-line treatment of OCD. Medium to large dosages and acute treatment for at least 3 months are recommended until efficacy is assessed. In case of significant improvement, maintenance treatment is necessary. Unfortunately, about half of the patients do not respond sufficiently to oral serotonergic antidepressants; augmentation with atypical antipsychotics is an established second-line drug treatment strategy. Alternatives include intravenous serotonergic antidepressants and combination with or switch to cognitive behavioral psychotherapy. Remarkably, a considerable proportion of OCD patients still do not receive rational drug treatment. Novel research approaches, such as preliminary treatment studies with glutamatergic substances, and trials with further drugs, as well as needed aspects of future research, are reviewed.