Antidepressants and electroconvulsive therapy may reduce all-cause mortality in depression

In patients with depression, antidepressant use may lower all-cause mortality risk, while electroconvulsive therapy (ECT) is associated with reduced risks of all-cause, natural-cause, and suicide-related death, researchers from the University of Hong Kong (HKU) have reported.

In a large-scale systematic review and meta-analysis, the HKU researchers searched EMBASE, MEDLINE, and PsycINFO databases for studies published up to January 2025, and pooled data from 268 studies involving 10,842,094 patients with depression and 2,837,933,536 controls. The primary outcome was all-cause mortality. [World Psychiatry 2025;24:404-421]

All-cause death doubles in depression

All-cause mortality risk showed a doubling in patients with depression (relative risk [RR], 2.10; 95 percent confidence interval [CI], 1.87–2.35; I²=99.9 percent) vs those without depression or general population controls. After matching for comorbid conditions, the risk of all-cause mortality remained significantly elevated in patients with depression (RR, 1.29; 95 percent CI, 1.21–1.37; I²=99.9 percent).

Notably, mortality risk was highest for suicide (RR, 9.89; 95 percent CI, 7.59–12.88; I²=99.6 percent), but was also increased for natural causes (RR, 1.63; 95 percent CI, 1.51–1.75; I²=99.6 percent).

Psychotic depression and TRD at high mortality risk

The presence of psychotic symptoms was associated with a 61 percent higher risk of all-cause mortality (RR, 1.61; 95 percent CI, 1.45–1.78; I²=6.3 percent) vs absence of psychotic symptoms. “As psychotic symptoms might not be readily identified in depression, careful evaluation is required to facilitate their early detection and effective management,” noted the researchers.

Treatment-resistant depression (TRD) was associated with a 27 percent higher risk of all-cause mortality (RR, 1.27; 95 percent CI: 1.16–1.39; I²=85.3 percent) vs non-TRD. “Previous research suggested that this increased mortality risk is driven largely by suicide and other external causes. However, common chronic comorbidities such as cardiovascular diseases and diabetes mellitus are also over-represented among patients with TRD,” pointed out the researchers.

Mortality-reducing effect of antidepressants and ECT

“To our knowledge, this is the first meta-analysis comprehensively assessing mortality risk associated with antidepressant treatment in patients with depression,” wrote the researchers.

Antidepressant use was associated with significantly lower all-cause mortality in patients with depression (RR, 0.79; 95 percent CI, 0.68–0.93; I²=99.2 percent) vs no antidepressant use.

All-cause mortality risk was generally comparable between antidepressant drug classes. However, serotonin and noradrenaline reuptake inhibitor (SNRI) use was associated with a higher suicide risk (RR, 1.55; 95 percent CI, 1.08–2.22; I²=5.9 percent) vs selective serotonin reuptake inhibitor (SSRI) use.

ECT use was associated with lower risks of all-cause mortality (RR, 0.73; 95 percent CI, 0.66–0.82; I²=0 percent), natural-cause mortality (RR, 0.76, 95 percent CI, 0.59–0.97; I²=12.0 percent), and suicide-related mortality (RR, 0.67; 95 percent CI, 0.53–0.85; I²=32.3 percent) vs no ECT use. These results further support its crucial role as an effective treatment for severe depression.

“A multifaceted approach that focuses on improving physical health, reducing suicide risk, optimizing antidepressant treatment, as well as promoting early detection and effective interventions for psychosis and TRD may close this mortality gap,” suggested the researchers.