Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study. A double blind trial of sulpiride in Huntington's disease and tardive dyskinesia. Prophylactic effects of neuroleptics in symptom-free schizophrenics: a comparative dose-response study of timiperone and sulpiride. [Clinical trial with Sulpiride and placebo in chronic schizophrenics (study of 89 patients using the Harris-Letemendía-Willems scale)]. Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. A single-blind study of clocapramine and sulpiride in hospitalized chronic schizophrenic patients. Comparative effectiveness of second-generation antipsychotics and haloperidol in acute schizophrenia. A randomized, placebo-controlled trial of the discontinuation of long-term antipsychotics in dementia. Sulpiride and perphenazine in schizophrenia. A double-blind clinical trial.
We hypothesised that a combined regimen of clozapine, a relatively weak D2-dopaminergic antagonist, and sulpiride, a selective D2 blocker, would demonstrate a greater antipsychotic efficacy by enhancing the D2 blockade of clozapine.
                Twenty-eight people with schizophrenia, previously unresponsive to typical antipsychotics and only partially responsive to current treatment with clozapine, received, double-blind, 600 mg/day sulpiride or placebo, in addition to an ongoing clozapine treatment. The clinical status was evaluated before, during, and at the end of 10 weeks of sulpiride addition using the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms, and Hamilton Rating Scale for Depression.
                The clozapine-sulpiride group exhibited substantially greater and significant improvements in positive and negative psychotic symptoms. About half of them, characterised by a younger age and lower baseline SAPS scores, had a mean reduction of 42.4 and 50.4% in their BPRS and SAPS scores, respectively.
                A subgroup of patients with chronic schizophrenia may substantially benefit from sulpiride addition to clozapine. Eleven patients with Huntington's disease and nine patients with tardive dyskinesia participated in a randomised double-blind crossover trial of sulpiride (as sole antidopaminergic therapy) versus placebo. Although functional improvement was not seen in Huntington's disease patients, sulpiride reduced movement count and total dyskinesia score in both conditions. Sulpiride differs pharmacologically in several respects from conventional neuroleptics, and has not been convincingly shown to cause tardive dyskinesia. Among currently available treatments, it may therefore be considered a drug of choice for treatment of tardive dyskinesia. Remitted schizophrenic outpatients were prophylactically treated to prevent relapse with three different doses of timiperone or sulpiride for a year in a double-blind controlled study employing a randomized design. Each drug's ability to prevent relapse was by counting the number of subjects with different outcomes (remission, relapse, adverse reactions) during the trial and/or the number of symptom-free days for each patient before any sign of relapse or adverse reactions appeared. Patients were randomly assigned to the following drugs, which were orally administered once every night: placebo; timiperone 1 mg, 3 mg, 6 mg; sulpiride 100 mg, 300 mg, 600 mg. Data from previous studies involving haloperidol and propericiazine were utilized as a retrospective placebo group to compare the characteristics of the four drugs for maintenance treatment of remitted schizophrenic outpatients. Both timiperone and sulpiride increased the number of patients in remission and decreased the number of patients who relapsed, compared with the placebo group. With timiperone, there was an especially marked increase in the number of patients who showed signs of adverse reactions compared with sulpiride. Sulpiride was the only drug that increased the number of dose-dependent symptom-free days. However, both of these drugs significantly increased the number of symptom-free days compared with placebo. By comparing the dose-response curves of four drugs tested in the same fashion, haloperidol and sulpiride were superior to propericiazine and timiperone because they displayed a wider dose range for the maintenance treatment of remitted schizophrenic outpatients. nan Evidence that the metabolism of phospholipids and polyunsaturated fatty acids (PUFA) is abnormal in schizophrenia provided the rationale for intervention studies using PUFA supplementation. An initial open label study indicating efficacy for n-3 PUFA in schizophrenia led to two small double-blind pilot studies. The first study was designed to distinguish between the possible effects of two different n-3 PUFA: eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA). Forty-five schizophrenic patients on stable antipsychotic medication who were still symptomatic were treated with either EPA, DHA or placebo for 3 months. Improvement on EPA measured by the Positive and Negative Syndrome Scale (PANSS) was statistically superior to both DHA and placebo using changes in percentage scores on the total PANSS. EPA was significantly superior to DHA for positive symptoms using ANOVA for repeated measures. In the second placebo-controlled study, EPA was used as a sole treatment, though the use of antipsychotic drugs was still permitted if this was clinically imperative. By the end of the study, all 12 patients on placebo, but only eight out of 14 patients on EPA, were taking antipsychotic drugs. Despite this, patients taking EPA had significantly lower scores on the PANSS rating scale by the end of the study. It is concluded that EPA may represent a new treatment approach to schizophrenia, and this requires investigation by large-scale placebo-controlled trials. The therapeutic effects, safety and side-effects of clocapramine and sulpiride were evaluated in 52 hospitalized chronic schizophrenic patients using a single-blind method during an 8-week trial period. While the final global improvement rating showed clocapramine to be superior to sulpiride, the differences were not statistically significant. The time course of the total psychiatric rating scales (PRS) showed a progressive decline during treatment for both drugs, and at the end of treatment clocapramine proved significantly lower in total PRS than did sulpiride. In the improvement of psychotic symptoms, clocapramine seemed to be superior to sulpiride with respect to motor retardation, delusion, hallucination or disturbance of self-consciousness, social isolation or withdrawal, and recreation or work. Side-effects appeared more frequently with clocapramine than with sulpiride, but abnormal laboratory-test results appeared less in clocapramine-treated patients than in sulpiride-treated ones. Neither side-effects nor abnormal laboratory-test results induced by the two drugs were severe enough to terminate administration. Clocapramine is concluded to have a more favourable effect on negative symptoms, as well as on some positive symptoms of chronic schizophrenia, than sulpiride. There is little information on the comparative effectiveness of second-generation antipsychotic agents.
                To determine if any of five second-generation antipsychotics or haloperidol is more effective in treating acutely ill patients with schizophrenia, schizoaffective disorder or schizophreniform disorder.
                A sample of 327 newly admitted patients were randomised to open-label treatment with aripiprazole, haloperidol, olanzapine, quetiapine, risperidone or ziprasidone for a minimum of 3 weeks. Measures of effectiveness were improvement in mental status so that the patient no longer required acute in-patient care, and changes in Brief Psychiatric Rating Scale (BPRS) scores.
                By the first measure, haloperidol (89%), olanzapine (92%) and risperidone (88%) were significantly more effective than aripiprazole (64%), quetiapine (64%) and ziprasidone (64%). Changes in BPRS ratings were not significant among treatments.
                Haloperidol, olanzapine and risperidone are superior to aripiprazole, quetiapine and ziprasidone for the acute treatment of psychosis in hospitalised patients with schizophrenia, schizoaffective disorder or schizophreniform disorder. The objectives of this randomized clinical trial were to investigate the impact of the discontinuation of long-term antipsychotics in residents with dementia in chronic care institutions and to identify clinical predictors of safe discontinuation. Subjects included 34 residents with dementia who were on antipsychotics for more than 6 months and whose behavior was currently stable. Subjects were randomized to either continue receiving their regular dosage of antipsychotics or to receive placebo for 6 months. Early withdrawal from the study was not statistically different between the groups (relative risk [RR] = 1.57, 95% confidence interval [CI] 0.76-3.26), and though not significantly different, subjects in the placebo group were more likely to be withdrawn from the study because of worsening behavior (RR = 1.25, 95% Cl 0.33-4.76). Three subjects in the placebo group were withdrawn from the study due to worsening of extrapyramidal symptoms. The active treatment group had more behavioral problems (e.g., physical aggression towards others, p < .05) compared to the placebo group. The placebo group developed more apathy, but balancing this outcome was a relative improvement in cognitive functioning. Baseline antipsychotic dose was predictive of behavioral worsening upon discontinuation of long-term antipsychotic drugs. The primary limitation of the study was the small sample size. In conclusion, a trial of discontinuation of antipsychotics should be considered in this population. Seventeen patients with acute schizophrenia and 30 with chronic schizophrenia were included in a randomized, double-blind parallel-group trial comparing sulpiride and perphenazine. Patients were evaluated using the 16-item Brief Psychiatric Rating Scale (BPRS) prior to the onset of treatment and 1 and 2 weeks, and 1, 2, 3, and 4 months thereafter. In patients with acute schizophrenia, total BPRS scores declined significantly at the end of the trial compared with pretreatment values in sulpiride-treated patients but not in schizophrenics treated with perphenazine. Differences in response between the groups did not reach statistical significance, however. For patients suffering from chronic schizophrenia, a statistically significant decline was observed in total BPRS scores at 4 months compared with pretreatment scores in both sulpiride and perphenazine groups. There was no significant difference in the treatment response between the groups. Sulpiride appeared to be somewhat more effective than perphenazine for treatment of acute schizophrenia. Efficacy of both compounds was less marked in chronic forms of schizophrenia.
Sulpiride may be an effective antipsychotic drug but evidence of its superiority over placebo from randomised trials is very limited. Practice will have to use evidence from sources other than trials until better evidence is generated.