Concomitant benzodiazepine use and outcomes of electroconvulsive therapy in major depressive disorder: a nationwide register study

Introduction

Electroconvulsive therapy (ECT) is an effective treatment for major depressive disorder (MDD), and its effect relies on the induction of a generalized seizure. Benzodiazepines are frequently used in severe depression but may shorten seizure duration and potentially reduce ECT effectiveness. Evidence on their impact on treatment outcomes is inconsistent, with some studies suggesting poorer outcomes in unilateral ECT. We hypothesized that concomitant benzodiazepine use is associated with reduced treatment response to ECT in patients with MDD.

Methods

This nationwide register-based study included adult patients treated with ECT for MDD in Sweden between 2016 and 2019, identified through the National Quality Register for ECT (Q-ECT, ~95% coverage) and linked to national health registers.

Exposure was defined as concomitant benzodiazepine use recorded on the ECT prescription form at ECT initiation.

The primary outcome was treatment response, defined as Clinical Global Impressions-Improvement (CGI-I) score 1–2. Secondary outcomes included remission (MADRS-S <10), distinct response (CGI-I = 1), number of ECT sessions, cognitive side effects, and length of hospital stay.

The between-individual analysis was restricted to the first eligible treatment series per patient to ensure independent observations, and logistic and linear regression models were used for binary and continuous outcomes, adjusting for relevant demographic and clinical covariates. A within-individual analysis using conditional logistic regression was performed in patients with both exposed and unexposed treatment series.

Results

Among 4121 patients, 49.6% received concomitant benzodiazepines. Treatment response was observed in 77.9% of benzodiazepine users and 75.9% of non-users. In adjusted analyses, benzodiazepine use was not associated with treatment response (adjusted odds ratio (aOR) 0.93, 95% CI 0.79–1.09, p = 0.358). No significant association was observed for distinct response (aOR 1.00, 95% CI 0.87–1.16, p = 0.948) or remission (aOR 0.86, 95% CI 0.72–1.02, p = 0.085).

Benzodiazepine use was associated with a small increase in post-treatment depressive symptoms (β = 1.14, 95% CI 0.27–2.02, p = 0.011), a slightly higher number of ECT sessions (β = 0.23, 95% CI 0.01–0.44, p = 0.037), and shorter seizure duration (β = –1.98 seconds, 95% CI –3.46–0.50, p = 0.009), but not with cognitive side effects.

In the within-individual analysis (80 discordant pairs), no significant association was observed between benzodiazepine use and treatment response (OR 1.53, 95% CI 0.92–2.57, p = 0.103).

Conclusions

In this large nationwide cohort, concomitant benzodiazepine use was not associated with clinically meaningful differences in ECT response or remission in patients with MDD. While small differences were observed in secondary outcomes, these were unlikely to be of major clinical relevance. Although individual dosing strategies and choice of benzodiazepine were not validated in this study, the findings are consistent with current Swedish clinical guidelines recommending avoidance when possible and, if continuation is necessary, use of the lowest effective dose and short-acting agents. These findings support an individualised approach to benzodiazepine use during ECT, balancing seizure optimisation with the need to manage acute symptoms.

References

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