Detecting potential adverse reactions of sulpiride in schizophrenic patients by prescription sequence symmetry analysis

Abstract

Purpose: Previous studies have demonstrated sulpiride to be significantly more effective than haloperidol, risperidone and olanzapine in schizophrenic treatment; however, only limited information is available on the potential risks associated with sulpiride treatment. This study attempts to provide information on the potential risks of sulpiride treatment of schizophrenia, especially with regard to unexpected adverse effects.

Materials and methods: Patients with schizophrenia aged 18 and older, newly prescribed with a single antipsychotic medication from the National Health Insurance Research Database of Taiwan in the period from 2003 to 2010 were included. A within-subject comparison method, prescription sequence symmetry analysis (PSSA) was employed to efficiently identify potential causal relationships while controlling for potential selection bias.

Results: A total of 5,750 patients, with a mean age of 39, approximately half of whom were male, constituted the study cohort. The PSSA found that sulpiride was associated with EPS (adjusted SR, 1.73; 95% CI, 1.46-2.06) and hyperprolactinemia (12.04; 1.59-91.2). In comparison, EPS caused by haloperidol has a magnitude of 1.99 when analyzed with PSSA, and hyperprolactinemia caused by amisulpride has a magnitude of 8.05, respectively. Another finding was the unexpected increase in the use of stomatological corticosteroids, emollient laxatives, dermatological preparations of corticosteroids, quinolone antibacterials, and topical products for joint and muscular pain, after initiation of sulpiride treatment.

Conclusions: We found sulpiride to be associated with an increased risk of EPS and hyperprolactinemia, and the potential risk could be as high as that induced by haloperidol and amisulpride, respectively. Additionally, our study provides grounds for future investigations into the associations between sulpiride and the increased use of additional drugs for managing adverse effects, including stomatological, dermatological, and musculoskeletal or joint side effects, constipation, and pneumonia.

Figure 1. Flowchart of study cohort selection.

Footnote of figure1: PSSA: Prescription Sequence Symmetry Analysis; NHI: national health insurance. *Include sulpiride, haloperidol, risperidone, olanzapine, quetiapine, and amisulpride.

Figure 2. The distribution of age of patients by antipsychotic drugs.

Figure 3. Confirmatory analyses on adverse events of sulpiride and other antipsychotics.

Footnote of figure 3: NA: Not applicable, *Statistical significant at alpha level at 0.05.