Why is electroconvulsive therapy for depression more effective in older age? A causal mediation analysis

Older people with depression exhibit better response to electroconvulsive therapy (ECT). We aimed to measure the total effect of age on ECT response and investigate whether this effect is mediated by psychotic features, psychomotor retardation, psychomotor agitation, age of onset, and episode duration.

We pooled data from four prospective Irish studies where ECT was administered for a major depressive episode (unipolar or bipolar) with baseline score ≥21 on the 24-item Hamilton Depression Rating Scale (HAM-D). The primary outcome was change in HAM-D between baseline and end of treatment. The estimands were total effect of age, estimated using linear regression, and the indirect effects for each putative mediator, estimated using causal mediation analyses.

A total of 256 patients (mean age 57.8 [SD = 14.6], 60.2% female) were included. For every additional 10 years of age, HAM-D was estimated to decrease by a further 1.74 points over the ECT period (p < 0.001). Age acted on all putative mediators. Mechanistic theories, whereby a mediator drives treatment response, were confirmed for all putative mediators except age of onset. Consequently, mediation of the effect of age on change in HAM-D could be demonstrated for psychotic features, psychomotor retardation, psychomotor agitation, and episode duration but not for age of onset.

A total of 43.1% of the effect of older age on increased ECT response was explained by the mediators. Treatment planning could be improved by preferentially offering ECT to older adults, especially if presenting with psychotic features, greater severity of psychomotor disturbance, and earlier in the episode.