A Randomized, Double-Blind Comparison of Risperidone Versus Low-Dose Risperidone Plus Low-Dose Haloperidol in Treating Schizophrenia

Abstract

Monotherapy is recommended for schizophrenia treatment, but the risk-benefit issue of antipsychotic drug combination (except for clozapine) remains unclear. Risperidone, an atypical antipsychotic drug, has a lower incidence of extrapyramidal syndrome but higher risks of prolactinemia and metabolic syndrome than haloperidol, a typical agent. This study compared efficacy and safety of risperidone monotherapy versus low-dose risperidone plus low-dose haloperidol in schizophrenia. In this 6-week, double-blind study, patients were randomized to the combination group (2-mg/d risperidone plus 2-mg/d haloperidol, n = 46) or the monotherapy group (4-mg/d risperidone, n = 42). Efficacy assessments included Clinical Global Impression-Severity, Positive and Negative Syndrome Scale and subscales, Calgary Depression Scale, Global Assessment of Functioning, and Medical Outcomes Study Short-Form 36. Safety was rigorously monitored. Response was defined as 30% reduction in the Positive and Negative Syndrome Scale total score. The 2 treatment groups were similar in (1) demographic and clinical characteristics at baseline, (2) response rate, and (3) improvement in various psychopathological measures and quality of life at end point. The monotherapy group had a higher increase in prolactin levels (P = 0.04) and Simpson-Angus Scale scores (P = 0.04) and a higher percentage of biperiden use (P = 0.045). There were no significant between-group difference in changes in weight, vital signs, corrected QT interval, liver/renal function, fasting glucose level, and lipid profiles. The findings suggest that risperidone monotherapy may yield higher prolactin levels than a combination of low-dose risperidone plus low-dose haloperidol. The 2 treatment groups are similar in efficacy, life quality, and other safety profiles. Future long-term studies are warranted.

Safety and tolerability of antipsychotic polypharmacy

“…Other authors found similar results, by using data from Medicaid claims 20, 21 , pharmacy claims 15, 22, 23 , studying outpatients with non-affective psychosis 24 , studying patients admitted in a state hospital 25, 26 and studying patients in East Asia 27 and Europe 28–32 . By contrast, in a double-blind study 33 , the combination of low dose haloperidol and low dose risperidone was associated with lower scores in the Simpson-Angus Scale compared to risperidone alone in full doses. However, this APP regimen specifically attempted to avoid increased net dopamine blockage.…”

“…Another approach that was found to be helpful in reducing prolactin levels was the combination of antipsychotics in low doses. Lin 33 , in a 6-week, double-blind study, found that patients taking low dose risperidone plus low dose haloperidol had lower prolactin levels compared to patients taking full dose risperidone.…”

“…In contrast, some studies found either no difference or, with certain combinations and/or reported an improvement in side effects after addition of a second antipsychotic or when the dose of the first antipsychotic was lowered 33, 62 . In this regard, most studies reported that aripiprazole augmentation was associated with a decrease in certain side effects.…”

Polypharmacy and high-dose antipsychotics at the time of discharge from acute psychiatric wards

“…28 A review by Gö ren et al 30 observed that 'limited data' support the use of antipsychotic polypharmacy for patients with treatmentresistant illness. However, in a double-blind randomised study 31 a small group of patients with schizophrenia were randomised to receive either risperidone monotherapy or a combination of low-dose risperidone and low-dose haloperidol. Although no significant difference was observed between the two groups in symptom response, the result favoured the polypharmacy group in terms of the side-effect profile.…”

Fixed dose-combination products in psychiatry: Systematic review and meta-analysis

“…For example, in a recent study, Lin et al (2010) compared two groups: one receiving both risperidone (2 mg/d) and haloperidol (2 mg) and other on monotherapy (risperidone 4 mg/d). While the two treatments were similar in efficacy, the monotherapy group had higher prolactin levels and extrapyramidal side effects.…”