Hypothalamic-pituitary-adrenal axis effects on plasma homovanillic acid in man.

BACKGROUND: Effects of the hypothalamic-pituitary-adrenal (HPA) axis on central dopaminergic systems have been proposed to underlie the development of psychotic symptoms in depression. This study examined HPA axis hormone effects on plasma levels of homovanillic acid (HVA), the dopamine metabolite, in healthy volunteers, using a placebo-controlled, double-blind, random-assignment, crossover design. On the basis of preliminary studies, we hypothesized that HPA axis hormones would produce delayed effects on plasma HVA levels measured in the afternoon. METHODS: Ten healthy subjects underwent a standard protocol on four occasions and each time received ovine corticotropin-releasing hormone, synthetic adrenocorticotropic hormone (ACTH), cortisol, or placebo. Plasma HVA was measured at 9 AM and 4 PM on Day 1, immediately prior to administration of the test substance at 7 PM, then at 30-60-min intervals until 11 PM. Plasma HVA levels were subsequently obtained at 9 AM and 4 PM on Days 2 and 3. RESULTS: As predicted, there were significant differences between test substances in delayed effects on afternoon HVA levels measured on Days 2 and 3, with cortisol and ACTH producing greater increases in HVA than placebo. Acute effects of HPA axis hormones on HVA were not found, while differences between test substances in delayed effects on morning HVA levels approached significance. CONCLUSIONS: HPA axis hormones exert delayed effects on plasma HVA levels in healthy humans.

Efficacy of the combination of fluoxetine and perphenazine in the treatment of psychotic depression.

BACKGROUND: The aim of this study was to examine the efficacy of the combination of fluoxetine plus perphenazine in the treatment of psychotic depression. METHOD: Thirty patients who met DSM-III-R criteria for major depression with psychotic features were treated with fluoxetine plus perphenazine for 5 weeks. Patients were assessed at baseline and weekly using the Hamilton Rating Scale for Depression (HAM-D), Brief Psychiatric Rating Scale (BPRS), and a side-effect checklist that included specific extrapyramidal and anticholinergic side effects. RESULTS: Twenty-two (73%) of the 30 patients had a 50% or greater reduction in total HAM-D by Week 5. There was a significant improvement in HAM-D and BPRS scores at each week compared with baseline scores. Side effects reported by the patients included dry mouth (40%), blurry vision (40%), constipation (40%), tremor or rigidity (40%), and orthostatic hypotension or dizziness (27%). CONCLUSION: Fluoxetine when used in combination with perphenazine for the treatment of patients with psychotic depression has a response rate similar to the reported rates of response for tricyclic antidepressants (TCAs) plus antipsychotics, amoxapine, and electroconvulsive therapy. The side effects produced by the fluoxetine plus perphenazine combination were less than what has been reported for TCA plus antipsychotic treatment of psychotic depression and similar to the side effects reported with amoxapine. These data suggest that the combination of fluoxetine and perphenazine is effective for the treatment of psychotic depression and may be easier for patients to tolerate than a TCA plus antipsychotic.