Neurobiology and clinical pharmacology of obsessive-compulsive disorder.
Obsessive-compulsive disorder (OCD) is a brain disorder with recognizable periods of onset, course, familial occurrence, epidemiology, phenomenology, and treatment response. Several manifestations of pathophysiology are beginning to be defined, although they may represent intermediate pathophysiology rather than primary etiology. Positron emission tomography studies have consistently identified hypermetabolism in the orbitofrontal cortex, caudate nucleus, and, sometimes, anterior cingulate cortex. Neuropsychologic testing frequently identifies abnormalities in visuospatial function. Abnormal levels of cerebrospinal fluid neurotransmitters and neuromodulators are identifiable in untreated patients with OCD and return toward normal levels after effective treatment. The most consistent pathophysiologic finding in OCD points toward an abnormality in serotonin neurotransmission. Therapeutic response to selective serotonin reuptake inhibitors and the absence of improvement with norepinephrine reuptake inhibitors and dopamine antagonists argue strongly for a role of serotonin in the pathophysiology and treatment of OCD. Despite this clear indication from treatment trials, probes and manipulations of the serotonin system and its specific receptors have not provided a useful understanding of specific abnormalities. Clomipramine or potent selective serotonin reuptake inhibitors are the pharmacotherapy of choice for OCD, with a more limited role reserved for monoamine oxidase inhibitors. If one selective serotonin reuptake inhibitor is ineffective, others may be beneficial, in addition to the different proserotonergic and nonserotonergic augmentation strategies that could be useful in treatment of resistant OCD patients. Nondrug therapies are also important in OCD: behavioral therapy is frequently helpful and neurosurgery is sometimes helpful when other treatments fail.
Micallef
J
J
Centre de Pharmacologie et d'Evaluations Therapeutiques and Department of Clinical Pharmacology, Université de la Méditerranée, Développement et Pathologie du Mouvement, Timone University Hospital, Marseille, France.
Blin
O
O
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D002997:Clomipramine / Q000627:therapeutic use; D006801:Humans; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology; D009771:Obsessive-Compulsive Disorder / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
D015306:Biogenic Monoamines; D002997:Clomipramine; D017367:Selective Serotonin Reuptake Inhibitors