Treatment-resistant schizophrenia (TRS) is a critical public health concern. Short-term treatment with electroconvulsive therapy (ECT), combined with neuroleptics, may increase the response rate in patients with TRS, when compared with either treatment alone. We conducted an open-trial study in 59 patients with TRS with acute exacerbations, by using bilateral ECT combined with flupenthixol (dose range, 12–24 mg/day). After the first sign of clinical improvement, all patients had to pass a 3-week stabilization period during which their clinical improvement had to be sustained. The patients had to receive at least 20 ECT treatments before being considered unresponsive to ECT. Thirty-one patients were ECT responders by our criteria, 19 were non-responders, and nine were dropouts. The responder group had more male patients, paranoid type, of younger age, shorter duration of illness and duration of the current episode, less family history of schizophrenia, and higher pretreatment GAF scores. They received a lesser number of ECT treatments, a less electrical charge used, and lower doses of flupenthixol (p < 0.05). Both positive and negative symptoms improved (p < 0.05), but positive symptoms responded to a greater extent. This study supports the therapeutic efficacy of combined treatment with ECT and neuroleptic drugs. A consensus in the definition of TRS is urgently required.