Objective:An important challenge in schizophrenia therapeutics is to develop an efficacious treatment for cognitive impairment. Acetylcholinesterase inhibitors, such as rivastigmine, have been studied for improving cognitive performance in these patients.Materials and Methods:Rivastigmine (uptitrated to 6 mg/day) was given as an add-on therapy to risperidone-treated stable schizophrenia patients in a randomized, double-blind, placebo-controlled design. Of 67 patients who met eligibility criteria, 55 were recruited into the study. Twenty-eight were assigned to rivastigmine and 27 to placebo. These patients completed tests of attention, executive functioning, verbal skills, verbal and visuospatial working memory, and psychomotor speed on five occasions: at baseline, and at the end of the 1st, 3rd, 6th, and 12th months.Results:The groups were similar in terms of sociodemographic profile and baseline clinical characteristics (Positive and Negative Syndrome Scale and Clinical Global Impression-Severity). Contrary to expectations, rivastigmine patients showed poorer outcomes on several cognitive measures. Rivastigmine patients experienced also more psychological as well as neurological side effects. Core psychopathology ratings, however, did not differ between rivastigmine and placebo groups.Conclusions:Our study does not support the long-term use of rivastigmine as an augmentation agent in schizophrenia. Rivastigmine may be associated with higher incidence of psychological and neurological side effects in patients with schizophrenia.