Ziprasidone in the treatment of mania in bipolar disorder

Ziprasidone is an atypical antipsychotic with a unique receptor-binding profile. Currently, ziprasidone is approved by the US Food and Drug Administration for the acute treatment of psychosis in schizophrenia and mania in bipolar disorder. When compared to certain other atypical antipsychotics, ziprasidone appears to have a relatively benign side effect profile, especially as regards metabolic effects eg, weight gain, serum lipid elevations and glucose dysregulation. Taken together, these data suggest that ziprasidone may be a first line treatment for patients with bipolar mania. However, ziprasidone is a relatively new medication for which adverse events after long-term use and/or in vulnerable patient populations must be studied. Unstudied areas of particular importance include the efficacy and safety of ziprasidone in the treatment of bipolar depression and relapse prevention of mania as, well as in the subpopulations of pregnant women, the elderly and pediatric patients. The emergence of mania in patients taking ziprasidone is another topic for further study.     

A magnetic resonance imaging study of putamen nuclei in major depression.

The basal ganglia are recognized as putative mediators of certain cognitive and behavioral symptoms of major depression. Moreover, patients with basal ganglia lesions have repeatedly exhibited significant affective symptomatology, including apathy, depressive mood, and psychosis. Using high resolution, axial T2 intermediate magnetic resonance images, and a systematic sampling stereologic method, we assessed putamen nuclei volumes in 41 patients with major depression (DSM-III) and 44 healthy volunteer controls of similar age. Depressed patients had significantly smaller putamen nuclei compared with controls. Age was negatively correlated with putamen size in both groups. These results are the first demonstration of diminished putamen volumes in depression and further support a role for basal ganglia structures in the etiopathogenesis of depression.     

Cerebrospinal fluid neuropeptides in dementia.

Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) were measured in 77 female inpatients with moderate to extreme dementia and in 17 elderly female controls. Both multi-infarct (MID) and Alzheimer-type (SDAT) demented patients had equally elevated CSF CRH and TRH but not SRIF levels as compared with the controls. This elevation was, however, not seen in patients with simple dementia while it was most prominent in those exhibiting marked depressive symptoms. It is concluded that depression rather than dementia itself may be associated with CSF CRH and TRH elevation in elderly patients with cognitive impairment.     

Pharmacological specificity of the increase in neurotensin concentrations after antipsychotic drug treatment.

Neurotensin is an endogenous neuropeptide that produces many CNS effects that are similar to the behavioral and physiological alterations seen after administration of antipsychotic drugs to laboratory animals. As previously reported, sub-chronic (3 week) and acute (single injection) treatment with haloperidol (1 mg/kg), a clinically effective antipsychotic drug increases neurotensin concentrations in the nucleus accumbens and the caudate nucleus. In contrast, a tricyclic antidepressant (desipramine, 10 mg/kg), an anxiolytic (chlordiazepoxide, 25 mg/kg) and a histamine H1 receptor antagonist (diphenhydramine, 20 mg/kg) did not alter neurotensin concentrations in these brain regions after sub-chronic or acute treatment. These data demonstrate pharmacologic specificity to the antipsychotic drug-induced increases in regional brain neurotensin concentrations, and support the hypothesis that these changes may contribute to the clinical efficacy of these drugs.