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To test the effect of prophylactic use of benzhexol in schizophrenia patients after risperidone treatment. Sixty-nine drug naïve schizophrenia patients were recruited. All patients were administered risperidone. Patients in the benzhexol group were given a benzhexol tablet of 2 mg bid daily. The controls received a placebo tablet of 2 mg bid daily. The primary outcome measured using the Extrapyramidal Symptoms Rating Scale (ESRS). The Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) measured secondary outcome. There were significant time and group effects on the ESRS scores of the two groups. The post hoc analysis yielded significant differences at 1, 2, 4, and 8 weeks between the two groups. There was a significant time effect on the PANSS scores of the two groups. No significant group and interaction effects on the PANSS scores of the two groups. There was a significant time effect on the BPRS scores of the two groups. No serious adverse events were found in this study. Prophylactic use of benzhexol reduced extrapyramidal symptom in schizophrenia patients after risperidone treatment and did not affect the antipsychotic action of risperidone., Competing Interests: The authors declare no competing interests., (© 2023 Published by Elsevier Ltd.)