SUMMARYThe aim of this study was to compare the shortterm clinical efficacy and safety of risperidone with haloperidol and placebo. A meta-analysis of seven published randomized double-blind controlled trials was carried out. Study quality was assessed. The proportion of patients failing to reach at least 20% improvement on the positive and negative syndrome scale (P ANSS) or brief psychiatric rating scale (BPRS), the proportion of patients discontinuing treatment because of adverse effects and the number of patients who needed antiparkinsonian medication were abstracted for use as outcome measures.Treatment failure was present in 50% of risperidone-treated patients compared to 66% in those treated with haloperidol and 83% in those treated with placebo. It would be necessary to treat 11 patients with risperidone to prevent one treatment failure in those patients treated with haloperidol (Odds ratio (0R)=0·74, 95% CI of 0·58-0·94, P=0·02). Pooling of the three multicentre trials which included placebo as a treatment arm, showed that one in three patients treated with risperidone 4-16 mg/day (OR=0·22, 95% CI of 0·13-o·39, P<0·00001) and one in six treated with haloperidol 1o-20 mg/day (OR=0·44, 95% CI of 0·22-o·84, P=0·02) would derive significant benefit. Moreover, there was a highly significant greater need for anticholinergic medication due

No abstract

SUMMARY Haloperidol, the most studied antipsychotic drug, is the only one about which reliable statements on the relationship between blood levels and clinical outcome can be made. A systematic overview was undertaken to determine whether there was an optimum blood concentration range for clinical efficacy. Eighteen published studies which provided individual patient data in tables or graphs were reviewed. Clinical benefits tended to decline when the haloperidol blood concentration was increased above 26 ng/ml. Our data support the existence of a therapeutic window between 4 and 26 ng/ml for haloperidol in the treatment of schizophrenic, schizoaffective and schizophreniform disorders.

In the present study, we investigated the effect of central serotonergic pathway activation achieved through third ventricle injections of quipazine, a serotonergic agonist, on plasma glucose levels of fasted and fed adult Wistar male rats, whose third ventricles were canulated 7 days before the experiments. Central quipazine administration induced a significant increase in plasma glucose levels in fasted animals, but was unable to modify plasma glucose concentrations in fed rats. Pretreatment with alpha-helical CRH, a CRH antagonist, significantly attenuated quipazine-induced hyperglycemia. Pretreatment with two different 5-HT3 receptor antagonists, LY-278,584 and ondansetron, was also able to produce a significant reduction in the hyperglycemic response evoked by central administration of quipazine. None of the antagonists used was capable of modifying plasma glucose concentrations when injected alone into the third ventricle. Quipazine-treated, hyperglycemic animals did not show any increase in plasma insulin levels. We conclude that acute pharmacological serotonergic stimulation by quipazine produces hyperglycemia by mechanisms that require the functional integrity of both CRH and 5-HT3 receptors, and that impairment in insulin secretion and/or activity may explain hyperglycemia induced by third ventricle injections of quipazine.

The aim of the present study was to investigate the role of central 5-HT3 receptors on the control of blood glucose in stressed and non-stressed rats in both fasted and fed states. Adult Wistar male rats had each their third ventricle cannulated 7 days before the experiments. Injections of m-CPBG, a selective 5-HT3 receptor agonist, induced a significant increase in blood glucose in non-stressed rats in both fasted and in fed states. The same procedure was unable to modify stress-induced hyperglycemia. The hyperglycemic effect of m-CPBG central administration was blocked by pretreatment with ondansetron, a specific 5-HT3 receptor antagonist, indicating that the effects here obtained with m-CPBG were a result of its interaction with 5-HT3 receptors. Third ventricle injections of ondansetron alone were not able to modify blood glucose in non-stressed animals and did not change the hyperglycemic responses observed after immobilization stress. We conclude that pharmacological activation of the central 5-HT3 receptor induces a hyperglycemic effect in non-stressed animals.