title: Clozapine in bipolar disorder: treatment implications for other atypical antipsychotics.
abstract: Traditional neuroleptics are often utilized clinically for the management of bipolar disorder. Although effective as antimanic agents, their mood stabilizing properties are less clear. Additionally, their acute clinical side effect profile and long term risk of tardive dyskinesia, particularly in mood disorder patients, portend significant liability. This review focuses on the use of atypical antipsychotics in the treatment of bipolar disorder focusing on clozapine as the prototypical agent. Although, preclinical research and clinical experience suggest that the atypical antipsychotics are distinctly different from typical antipsychotics, they themselves are heterogeneous in profiles of neuropharmacology, clinical efficacy, and tolerability. The early clinical experience of clozapine as a potential mood stabilizer suggests greater antimanic than antidepressant properties. Conversely, very preliminary clinical experience with risperidone suggests greater antidepressant than antimanic properties and some liability for triggering or exacerbating mania. Olanzapine and sertindole are under investigation in psychotic mood disorders. The foregoing agents and future drugs with atypical neuroleptic properties should come to play an increasingly important role, compared to the older classical neuroleptics, in the acute and long term management of bipolar disorder.
authors.affiliation: National Institute of Mental Health, Biological Psychiatry Branch, Bethesda, MD, USA. maf@helix.nih.gov
authors.forename: M A
authors.initials: MA
authors.lastname: Frye
authors.forename: T A
authors.initials: TA
authors.lastname: Ketter
authors.forename: L L
authors.initials: LL
authors.lastname: Altshuler
authors.forename: K
authors.initials: K
authors.lastname: Denicoff
authors.forename: R T
authors.initials: RT
authors.lastname: Dunn
authors.forename: T A
authors.initials: TA
authors.lastname: Kimbrell
authors.forename: G
authors.initials: G
authors.lastname: Corá-Locatelli
authors.forename: R M
authors.initials: RM
authors.lastname: Post
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology; D018692:Antimanic Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001569:Benzodiazepines; D001714:Bipolar Disorder / Q000188:drug therapy*; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D018967:Risperidone / Q000494:pharmacology; D014299:Trimipramine / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D001569:Benzodiazepines; D010890:Pirenzepine; D014299:Trimipramine; C066304:sertindole; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine