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 well as little or no effect on prolactin elevation. These advantages constitute a major improvement in the treatment of patients with schizophrenia. The exact mechanisms that make these drugs atypical is not clear. However, a preferential action on serotonin 5-HT2 or D4 receptors, or a more rapid dissociation from the dopamine D2 receptor, may account for atypicality. Although the atypical antipsychotics have overcome EPS, other side effects such as weight gain and impaired glucose tolerance/lipid abnormalities have come to the fore. Thus, the challenges are far from over. The current atypicals are much more effective against the psychosis of schizophrenia than against the other, more enduring aspects of this disorder, e.g. negative symptoms and cognitive dysfunction. At present, the atypicals use a "pharmacological shotgun" strategy to treat aspects of the disease in all patients. A more 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 selective drugs that can be combined and individually titrated to the needs of each patient.
Kapur
S
S
Schizophrenia Program, PET Centre, CAMH, Toronto, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5T 1R8. skapur@camhpet.on.ca
Remington
G
G
D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001569:Benzodiazepines; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use*; D003987:Dibenzothiazepines / Q000494:pharmacology / Q000627:therapeutic use; D003988:Dibenzothiepins / Q000494:pharmacology / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D016903:Drug Monitoring; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050638:Receptors, Dopamine D4; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D014150:Antipsychotic Agents; C493599:DRD4 protein, human; D003987:Dibenzothiazepines; D003988:Dibenzothiepins; D018492:Dopamine Antagonists; D007093:Imidazoles; D007211:Indoles; D010879:Piperazines; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D013844:Thiazoles; D001569:Benzodiazepines; D050638:Receptors, Dopamine D4; D000069348:Quetiapine Fumarate; D010890:Pirenzepine; C092292:ziprasidone; D013469:Sulpiride; D000077582:Amisulpride; C066304:sertindole; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine; C022172:zotepine