[Comparison of higher-dose haloperidol therapy with perazine standard therapy in acute schizophrenic patients]. Initial improvement as a criterion for drug choice in acute schizophrenia. [Effectiveness and tolerance of zotepine in a double-blind comparison with perazine in schizophrenic patients]. Antipsychotic efficacy of the antidepressant trimipramine: a randomized, double-blind comparison with the phenothiazine perazine. [Zotepine versus perazine in patients with paranoid schizophrenia: a double-blind controlled trial of its effectiveness].
nan Several investigators have found that the initial improvement of acute schizophrenia after some days of neuroleptic treatment is correlated in a statistically significant way to the outcome after four weeks. In all these studies the question arises as to whether the correlation between early response and subsequent outcome is due to a specific response to a certain neuroleptic, or whether patients who respond early simply have a better prognosis. In order to isolate the specific drug effect from prognostic influences we performed a controlled double-blind study in 50 newly admitted schizophrenic inpatients. All patients were treated over three days with 15 mg haloperidol i.v., following which they were classified as 'early responders (ER)' (markedly improved or improved) or as 'early nonresponders (EN)' and then randomly assigned to group 1 (3 x 5 mg haloperidol p.o./d) or to group 2 (3 x 100 mg perazin p.o./d). If there was a specific drug effect on the correlation between early response and subsequent outcome a therapeutic superiority of perazin in EN and no superiority in ER was expected. Independently of the treatment condition the mean BPRS score had decreased from 61.2 (Sx = 12.1) to 38.1 (Sx = 13.9) at the end of the study. ER and EN were evenly distributed in the haloperidol and perazin group. The analysis of variance revealed no significant interactions of the factors 'treatment condition' x 'duration' x 'early response' (p = 0.27) and 'treatment condition' x 'early response' (p = 0.88) on the outcome (BPRS, CGI). This means that the initial hypothesis of this study has to be rejected.(ABSTRACT TRUNCATED AT 250 WORDS) 40 inpatients suffering from a schizophrenia (ICD-9) were treated with either zotepine or perazin. The study was continued for a period of 28 days. Assessment of clinical efficacy was effected via BPRS, AMDP, CGI and SANS; tolerance was assessed by means of Simpson's scale. In addition, EEG, ECG and laboratory controls were conducted. The overall therapeutic efficacy was good, and it was not possible to distinguish one group from the other, i.e. both substances were equally effective, judged by means of the psychopathometric tools that were at our disposal. In 11 patients of the zotepine group and in 9 patients of the perazin group, slight extrapyramidal symptoms were observed. No clinically relevant changes were seen in EEG, ECG and laboratory controls in both groups. The tricyclic antidepressant trimipramine exhibits several features (e. g., dopaminergic effect, molecular structure similar to a neuroleptic, receptor-binding profile similar to clozapine) that suggest its potential as an antipsychotic medication. The aim of the study was to investigate the antipsychotic potential of trimipramine in a controlled clinical trial comparing its antipsychotic efficacy with that of a neuroleptic.
                In a German multi-center, randomized, double-blind trial, the antipsychotic efficacy of trimipramine was compared with that of the phenothiazine neuroleptic perazine, using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impressions (CGI). Antidepressant efficacy of both agents was measured by use of the Bech-Rafaelsen Melancholia Scale (BRMES). Ninety-five patients with acute schizophrenia (DSM-III-R) and a BPRS total score > 40 at baseline were treated with either 300-400 mg trimipramine or 450-600 mg perazine for 5 weeks.
                Therapeutic equivalence of both treatments (in the dosages used) could not be demonstrated (change in BPRS total score, per-protocol [PP] analysis, one-sided equivalence testing). However, intention-to-treat (ITT) as well as PP analysis showed a statistically significant decrease in the BPRS total scores in both treatment groups (PP: trimipramine, 56.5 +/- 9.8 to 44.1 +/- 17.9; perazine, 56.4 +/- 10.8 to 37.9 +/- 12.9). Significant decreases in all BPRS and PANSS subscores as well as CGI results and response rate support the antipsychotic efficacy of trimipramine. The BRMES total scores significantly decreased in both treatment groups without showing a significant difference between the two agents. Trimipramine was better tolerated than perazine and did not elicit extrapyramidal symptoms.
                Trimipramine failed to exhibit therapeutic equivalence to perazine in the dosages used. However, there was evidence of a substantial antipsychotic effect of trimipramine. It may be a useful medication if depressive symptoms in psychotic patients require antidepressant treatment or if other antipsychotics cannot be administered. The dibenzothiepine zotepine is a new potential "atypical" neuroleptic exhibiting powerful antiserotonergic and antidopaminergic properties. The efficacy of zotepine was evaluated in a double-blind controlled trial versus the tricyclic neuroleptic perazine in 41 patients suffering mainly from the paranoid-hallucinatory type of schizophrenia. The key outcome variable was the extent of mental disturbance as defined by the total score of the BPRS. Additional outcome variables were GAS and CGI. In addition, adverse reactions and extrapyramidal side effects were assessed according to the FSUCL scale and the Gerlach and AIMS rating scale, respectively. Additional variables recorded were blood pressure, heart rate and routine laboratory parameters as well as electrocardiogram and electroencephalogram. In the first two days, standard equivalent doses of both drugs were administered. Thereafter, doses were administered as required. The efficacy of both substances was compared after 7, 14 and 28 days of treatment. Both drugs showed a similar antipsychotic efficacy. Under zotepine treatment a 55% improvement of the BPRS total score was observed while perazine led to a 41% BPRS score reduction. After 7 days the zotepine group was significantly more improved than the perazine group, possibly due to a dosing effect in the perazine group. In the zotepine group, fewer adverse reactions and a better benefit/risk index were observed although the differences between the two treatment groups did not reach levels of statistical significance. There were no drug-specific abnormal laboratory findings. Thus, in the present study there was no significant difference between zotepine and perazine with respect to antipsychotic efficacy and side-effect rates. However, zotepine showed a trend to a better benefit/risk index at the end of treatment.
The number, size and reporting of randomised controlled perazine trials is insufficient to present firm conclusions about the properties of this antipsychotic. It is possible that perazine is associated with a similar risk of extrapyramidal side-effects as some atypical antipsychotics, and this should be clarified in larger, well-designed trials.
[Note: the four citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]