Atypical antipsychotics: New directions and new challenges in the treatment of schizophrenia

"Atypical" antipsychotics represent a new generation of antipsychotics with a significantly lower incidence of extrapyramidal side effects (EPS), as w ell as little or no effect on prolactin elevation. These advantages constit ute a major improvement in the treatment of patients with schizophrenia. Th e exact mechanisms that make these drugs atypical is not clear. However, a preferential action on serotonin 5-HT2 or Dq receptors, or a more rapid dis sociation from the dopamine D-2 receptor, may account for atypicality. Alth ough the atypical antipsychotics have overcome EPS, other side effects such as weight gain and impaired glucose tolerance/lipid abnormalities have com e to the fore. Thus, the challenges are far from over. The current atypical s are much more effective against the psychosis of schizophrenia than again st the other. more enduring aspects of this disorder, e.g. negative symptom s and cognitive dysfunction. At present, the atypicals use a "pharmacologic al shotgun" strategy to treat aspects of the disease in all patients. A mor e sophisticated and perhaps effective approach to schizophrenia may lie in independently targeting the pathophysiological mechanisms of each clinical dimension (i.e. positive, negative, cognitive, and affective) with more sel ective drugs that can be combined and individually titrated to the needs of each patient.