A prospective multicenter assessor-blinded randomized controlled study to compare the efficacy of short versus long protocols of electroconvulsive therapy as an augmentation strategy to clozapine in patients with ultra-resistant schizophrenia (SURECT study)

Abstract

Background: Although clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia, it leads to a poor or partial response in 40 to 70% of patients. Augmentation of clozapine with electroconvulsive therapy (ECT) is a highly effective and relatively safe treatment for these clozapine-resistant patients. However, parameters are not yet well specified, such as the optimal number of sessions, their frequency, and the relevance of maintenance ECT. Our objective is to compare the efficacy and tolerance between two protocols of combined ECT and clozapine treatment in patients with ultra-resistant schizophrenia (URS): a 6-month protocol (short protocol with 20 ECT sessions) and a 12-month protocol (long protocol with 40 ECT sessions).

Methods: Sixty-four patients with schizophrenia with persistent psychotic symptoms despite clozapine treatment will be enrolled in a prospective multicentric assessor-blinded randomized controlled trial. Patients will be randomly assigned to the short or the long protocol. The main outcome is the response rate assessed by the Positive and Negative Symptoms Scale (PANSS) 3 months after the end of the treatment in patients following the long protocol compared to those following the short protocol. The response was defined as a 30% reduction on the PANSS baseline. Clinical assessments (PANSS, BPRS, HAMD-21, YMRS, CGI, GAF, Modified Overt Aggression Scale (MOAS), and Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS)) and plasma clozapine concentration will be performed at baseline and at 2, 4, 6, 9, 12, and 15 months. Neuropsychological measures (MMSE, RL/RI-16, Doors test, D2 Test of Attention, Copy of the Rey-Osterrieth complex figure) will be performed at baseline and at 6 and 15 months.

Discussion: The aims of this research are to optimize protocols of combined ECT with clozapine in patients with URS and to offer specific recommendations for these patients' care.

Trial registration: ClinicalTrials.gov NCT03542903 . Registered on May 31, 2018. Id RCB: 2017-A02657-46.

Keywords: Augmentation strategy; Clozapine; Electroconvulsive therapy; Randomized controlled trial; Ultra-resistant schizophrenia.

Fig. 1

Flow chart of the study design. The main objective was the comparison of the response rate 3 months after the end of each treatment (black circles surrounded)

Fig. 2

Schedule of enrollment, interventions, and assessments of the study. PANSS, Positive and Negative Symptoms Scale; BPRS, Brief Psychiatric Rating Scale-18 items; MOAS, Modified Overt Aggression Scale; CGI, Clinical Global Impression; GAF, Global Assessment Functioning; HAMD-21, Hamilton Rating Scale-21 items; YMRS, the Young Mania Rating Scale; SSTICS, Subjective Scale to Investigate Cognition in Schizophrenia; MMSE, Mini-Mental Status Examination