Sulpiride augmentation of olanzapine in the management of treatment-resistant chronic schizophrenia: evidence for improvement of mood symptomatology

Abstract

Several recent studies, albeit limited in sample number, design and generalizability, have suggested that augmentation of atypical antipsychotic medication (such as clozapine and olanzapine) with sulpiride, a substituted benzamide antipsychotic medication, may play a role in the management of treatment-resistant psychotic conditions. The objective of this study was to investigate any change in clinical symptomatology or side-effect profile in treatment-resistant schizophrenia patients receiving sulpiride in addition to olanzapine. Seventeen patients with treatment-resistant chronic schizophrenia, who were receiving olanzapine monotherapy for at least 6 months before study commencement, were randomized in a 1:1 fashion to receive either adjunctive treatment with sulpiride (study group) or to continue their pre-study treatment with olanzapine with no medication augmentation (control group), each for a period of 8 weeks. Changes in measures of positive and negative symptoms, anxiety, depression and extrapyramidal symptoms were assessed at baseline and at 8 weeks. Study observations indicated no significant differences in the changes in positive or negative symptomatology between patients receiving a combined regimen of olanzapine with sulpiride (600 mg/ day) augmentation and controls. However, a significantly greater improvement of depressive symptomatology (P < 0.05; as assessed by the Hamilton Scale for Depression) was noted in the sulpiride augmentation group. These data indicate improvement in depressive symptomatology with sulpiride augmentation of olanzapine in treatment-resistant chronic schizophrenia patients.

Development and Delivery of a Quality Improvement Program to Reduce Antipsychotic Polytherapy

“…[4][5][6] In the majority of randomized controlled efficacy trials, antipsychotic polytherapy did not significantly differ from monotherapy on primary outcome measures. [7][8][9][10][11][12] Of the randomized controlled efficacy trials that found differences between groups on primary outcome measures, 2 studies reported antipsychotic polytherapy superior, 11,12 and 1 reported antipsychotic monotherapy more effective. 7 Effects on secondary outcome measures were mixed, but benefits gained with polytherapy were often, although not always, small.…”

Antipsychotic polypharmacy: review of mechanisms, mortality and management

“…One study published in 2004 compared olanzapine monotherapy to olanzapine combined with sulpiride and found no significant difference in positive or negative symptoms. 13 Interestingly, the patients receiving dual therapy showed improvement in terms of depressive symptoms as measured by the Hamilton Rating Scale for Depression. Other studies examining the combination of risperidone and clozapine showed no significant improvement in positive or negative symptoms, 14,15 but did show increased rates of sedation, akathisia, hyperprolactinaemia and elevated fasting blood glucose.…”

When Is Antipsychotic Polypharmacy Supported by Research Evidence? Implications for QI

“…[47][48][49][50][51][52] All studies were of patients with schizophrenia or schizoaffective disorder. Two studies found that patients on multiple antipsychotics, compared with patients on a single antipsychotic, experienced greater improvement in the primary clinical outcome (that is, symptoms or functioning).…”

“…50,52 Three trials found no difference in the primary clinical outcome between patients on single and multiple antipsychotics. 48,49,51 One trial reported better clinical outcomes for patients on a single antipsychotic. 47 Four of the six trials reported comparatively greater side effects for patients on multiple antipsychotics, whereas two found no differences in side effects.…”

“…The sixth trial compared the combination of olanzapine and sulpiride with olanzapine monotherapy. 51 We identified nine noncontrolled observational trials comparing antipsychotic polypharmacy to monotherapy in samples with established treatment resistance to trials of a single antipsychotic (Table 1). [53][54][55][56][57][58][59][60][61] All studies were of patients with schizophrenia or schizoaffective disorder.…”