Background: In treatment-resistant schizophrenia a combination of ECT with antipsychotics has been reported to have superior outcomes compared to other strategies, however the results were inconsistent. We investigated the long-term effects of the combination of unilateral, non-dominant hemisphere ECT with three antipsychotics. Subjects and methods: The clinical study was a naturalistic, prospective, openlabeled, active-controlled study in adult outpatients of both genders suffering from treatment-resistant schizophrenia with a follow up of 2 years. The patients received sulpiride (n=17, 100-400mg/day, PO), risperidone (n=26, 2-8mg/day, PO) or olanzapine (n=27, 5-10mg/day, PO). Unilateral ECT was applied in 1 unit (0.5A, 0.8 mS) in six single applications, once a week and further according to the clinical need, in fortnight steps. Clinical efficacy was established using the PANSS and CGI psychometric scales. Results: According to the results, the most effective treatment mode was olanzapine plus ECT, then risperidone plus ECT, while sulpiride plus ECT had lower clinical efficacy. Olanzapine plus ECT was significantly superior in all scale scores vs sulpiride plus ECT, as well as risperidone plus ECT except for PANSS-P (t=1.85, p>0.05). During the study, 38 of 70 patients were withdrawn due to treatment failure (n=21), side effects (n=6) and non-compliance (n=11). Conclusion: The combination of novel antipsychotics and ECT can be used safely and effectively in treatment-resistant schizophrenia.