Comparison of Acute Followed by Maintenance ECT vs Clozapine on Psychopathology and Regional Cerebral Blood Flow in Treatment-Resistant Schizophrenia: A Randomized Controlled Trial

Abstract

Background and hypothesis: In treatment-resistant schizophrenia (TRS), Clozapine is only approved treatment with undesirable side-effects, warranting better alternatives. Our hypothesis is acute followed by maintenance Electroconvulsive Therapy (M-ECT) will be comparable in efficacy and safety to Clozapine in TRS.

Study design: In this open-label trial, 60 TRS patients were randomized equally to M-ECT (following an acute-course) or Clozapine. Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Schizophrenia Scale (CGI-SCH), Montreal Cognitive Assessment (MoCA), and Global assessment of functioning (GAF) were measured and compared within and between the groups at baseline, 6 weeks, 12 weeks, and 24 weeks. SPECT-CT brain was done at baseline and 24 weeks to compare the changes in regional cerebral perfusion between the groups and correlate with the changes in the outcome-measures.

Study results: The PANSS-T scores changes from baseline over the observation-points were significant in both M-ECT and clozapine groups (P < .001), with comparatively better reduction with M-ECT (P < .001). Similar trends were observed in PANSS subscales, CGI-SCH and GAF in both groups, with significantly better improvement with M-ECT over the study-period. After 24 weeks, there was significantly better perfusion with M-ECT in bilateral prefrontal and temporal cortices (P < .05). With M-ECT, a positive correlation was found between changes in PANSS-P scores and left-lateral Temporal cortical perfusion (r = .465, P = .017).

Conclusions: Acute followed by M-ECT was more effective than clozapine over 6 months in reducing the positive and negative symptoms, general psychopathology, illness-severity, and improving the global functionality in TRS [clinicaltrials.gov: NCT03807882].

Keywords: M-ECT; PANSS; RCT; SPECT-CT brain; TRS; antipsychotic.

Fig. 1.

CONSORT flow diagram of the progress through the phases of the parallel randomized trial of the two groups.

Fig. 2.

Response trajectory of different outcome-measures over time. Group I: M-ECT, Group II: Clozapine treatment.

Fig. 3.

SPECT-CT 3-D stereotactic surface projection (3D-SSP) maps of the brain of single exemplar cases from the M-ECT and clozapine groups: (A) A patient in the M-ECT group, showing significant improvement in perfusion in the left prefrontal cortex and right temporal cortex in post treatment scan as compared to base-line scan. (B) A patient in the Clozapine group, showing improvement in perfusion in the left prefrontal cortex, partial improvement in right temporal cortex and no improvement in left temporal cortex in post treatment scan compared to base-line scan.