Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis

Mechanisms of action of atypical antipsychotic drugs. Implications for novel therapeutic strategies for schizophrenia.

BACKGROUND 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.

METHOD 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.

RESULTS 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.

CONCLUSIONS A subgroup of patients with chronic schizophrenia may substantially benefit from sulpiride addition to clozapine.

Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study.

Multiple dopamine receptors and behavior.

To evaluate the clinical potential of sulpiride for the treatment of schizophrenic patients, a double-blind study was performed comparing fixed doses of sulpiride (800 mg daily) and chlorpromazine (400 mg daily). Twentyfive schizophrenic (RDC) patients participated in each treatment group. Antipsychotic effects were evaluated by CPRS and NOSIE ratings before and after 1, 2, 4 and 8 weeks of treatment. Interrater reliabilities for CPRS items and subscales were satisfactory.



Treatment with sulpiride or chlorpromazine resulted in a significant reduction of psychotic morbidity as estimated by CPRS and global ratings. CPRS scores reflecting autism were significantly reduced in all ratings of sulpiride-treated patients, but only after four weeks in the chlorpromazine group. Total NOSIE scores indicated improvement in both treatment groups. A significant difference in favour of sulpiride was obtained for the NOSIE subscale “retardation”.



Extrapyramidal side effects occurred at a similar frequency in both treatment groups. Autonomic side effects occurred to a greater extent in chlorpromazine-treated patients. Lactation was reported only in four sulpiride-treated patients. Liver transaminase enzymes in serum were markedly elevated only in chlorpromazine-treated patients.



The results indicate that sulpiride has a marked antipsychotic effect which is at least not inferior to that of chlorpromazine. A better effect on autistic components of behaviour was demonstrated for sulpiride. The results indicate a higher risk of lactation but a lower risk of anticholinergic side effects and liver toxicity for treatment with sulpiride than with chlorpromazine.

Clinical Evaluation of Sulpiride in Schizophrenic Patients - A Double-blind Comparison with Chlorpromazine

In a material of 71 patients admitted because of acute or chronic psychoses, 32 were treated with sulpiride (up to 1,800 mg per day) and 39 with chlorpromazine (up to 675 mg). Duration of treatment was from 4 to 8 weeks. The effect of the two preparations was very similar as were the type and frequency of side effects, except that sulpiride did not cause sunrash.

O. Bratfos

Papers

Comparison of sulpiride and chlorpromazine in psychoses. A double-blind multicentre study.