A clinical control study of modified electroconvulsive therapy and sodium valproate as enhancement strategies for ultra-treatment-resistant schizophrenia.

Background: A substantial proportion of patients with schizophrenia show an inadequate response to clozapine, a condition termed ultra-treatment-resistant schizophrenia (UTRS). While modified electroconvulsive therapy (MECT) and sodium valproate are common augmentation strategies, head-to-head trials directly comparing their efficacy and safety are lacking. This study aimed to directly compare the short-term efficacy and safety of MECT versus sodium valproate as augmenting agents to clozapine in patients with UTRS. Methods: This was an 8-week, single-center, randomized controlled trial. Seventy inpatients meeting diagnostic criteria for UTRS were randomly assigned to receive either MECT augmentation (n = 35) or sodium valproate augmentation (n = 35), both in addition to their ongoing clozapine treatment. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes included changes in cognitive function assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and laboratory safety parameters. Results: At week 8, the MECT group demonstrated a significantly greater reduction in PANSS total score compared to the sodium valproate group (p < 0.01). The response rate, defined as a ≥ 25 % reduction in PANSS total score, was also significantly higher in the MECT group (48.6 %, 17/35) than in the valproate group (14.3 %, 5/35, p < 0.01). Regarding cognitive function, there was no statistically significant difference in the change of the RBANS total score between the two groups from baseline to endpoint (p = 0.24). Both treatments were generally well-tolerated, with no significant differences observed in key laboratory safety parameters, including leukocyte counts, liver function, and glucose levels, either within or between groups (all p > 0.05). Conclusion: In this cohort of inpatients with UTRS, 8 weeks of MECT augmentation appeared to be more effective than sodium valproate in reducing overall psychotic symptoms. These findings should be considered preliminary, and neither intervention demonstrated short-term benefits for cognitive function. Future studies with longer follow-up periods are warranted to assess the durability of response and should include a clozapine-only control arm to confirm the true value of these augmentation strategies.