AMISULPRIDE VERSUS FLUPENTIXOL IN SCHIZOPHRENIA WITH PREDOMINANTLY POSITIVE SYMPTOMATOLOGY - A DOUBLE-BLIND CONTROLLED-STUDY COMPARING A SELECTIVE D-2-LIKE ANTAGONIST TO A MIXED D-1- D-2-LIKE ANTAGONIST/

The benzamide amisulpride (ASP) is a selective D-2-like dopamine antag onist, while flupentixol (FPX), a thioxanthene, blocks D-2-like, D-1-l ike and 5-HT2 receptors, To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for an tipsychotic effects and extrapyramidal tolerability, a randomized doub le-blind multi- center study versus FPX as reference drug was performe d for 6 weeks in 132 patients suffering from acute schizophrenia (DSM- III-R) with predominant positive symptomatology. Doses were initially fixed (ASP, 1000 mg/day; FPX: 25 mg/day) but could be reduced by 40% i n case of side effects (mean daily doses: ASP, 956 mg; FPX: 22.6 mg). Intention-to-treat evaluation demonstrated significant improvement und er both medications. The difference between the mean BPRS decreases of both treatment groups was 5.6 points (95% CI, 0.55,10.65) in favour o f ASP. According to CGI, 62% of patients in either drug group were tre atment responders. ANCOVA analysis showed that reductions of BPRS (ASP : -42%; FPX, -32%) and SAPS (ASP, - 78 %; FPX: - 65 %) were more prono unced under ASP Due to adverse events, significantly fewer ASP patient s (6%) were withdrawn from the study (FPX: 18%). Extrapyramidal tolera bility was better in the ASP group, as demonstrated by smaller increas es in the Simpson-Angus Scale, the AIMS, and the Barnes Akathisia Scal e in ANCOVA analyses with dosage as covariate. ASP appears to be as ef fective as FPX with regard to antipsychotic effects on positive schizo phrenic symptomatology, while extrapyramidal tolerability is better. T hese conclusions have to be drawn cautiously, as dosage effects on out come parameters cannot be entirely ruled out. The present results ques tion the notion that additional blockade of D1-like receptors may be n ecessary to achieve sufficient antipsychotic effects or to improve ext rapyramidal tolerability.