Postdiagnostic Anxiety and Depression Increase Rupture Risk and Mortality in Unruptured Intracranial Aneurysms.

BACKGROUND

Postdiagnostic anxiety and depression's impact on management and outcomes in patients with unruptured intracranial aneurysms remains underexplored. We assessed associations with treatment patterns and outcomes using a large multi-institutional database.

METHODS

This retrospective cohort study used TriNetX Global Collaborative Network records (2015-2025; >130 million patients across ≈250 health care organizations), identifying 127 361 adults with unruptured intracranial aneurysms. Addressing immortal time bias, we used a 127-day landmark analysis (median time to psychiatric diagnosis), requiring event-free survival before cohort assignment. Of 119 211 patients surviving to the landmark, those with anxiety/depression diagnosed within 0 to 127 days (n=7250) were 1:1 propensity score matched to controls (n=111 961), yielding 6800 per cohort. Cox proportional hazards models evaluated outcomes from a landmark.

RESULTS

Matched cohorts (6800 each) had balanced characteristics (all standardized mean differences <0.10) and comparable follow-up (median, 1550 versus 1600 days). Anxiety/depression was associated with higher all-cause mortality (6.3% versus 4.5%; hazard ratio [HR], 1.28 [95% CI, 1.11-1.48]; P<0.001) and rupture (3.1% versus 2.2%; HR, 1.33 [95% CI, 1.08-1.64]; P=0.007). Five-year survival was 93.7% in the anxiety/depression cohort versus 95.5% in matched controls. Preventive treatment showed nonsignificant trends toward lower rates (odds ratio, 0.80 [95% CI, 0.62-1.03]; P=0.082). Sensitivity analysis using a 365-day landmark (n=10 200 per cohort) expanded eligibility by including diagnoses between days 128 and 365, and confirmed findings (mortality HR, 1.22 [95% CI, 1.08-1.38]; rupture HR, 1.28 [95% CI, 1.08-1.52]). Fine-Gray competing risk models yielded consistent results (mortality subdistribution HR, 1.27; rupture subdistribution HR, 1.31). Dose-response patterns emerged for psychiatric medication adherence: low (mortality HR, 1.50 [95% CI, 1.12-2.00]; P=0.006), moderate (HR, 1.29 [95% CI, 0.98-1.70]; P=0.071), and high (HR, 1.16 [95% CI, 0.89-1.51]; P=0.270). E values were 1.88 for mortality and 1.99 for rupture.

CONCLUSIONS

Postdiagnostic anxiety and depression are associated with increased rupture risk and mortality in patients with unruptured intracranial aneurysms. Residual confounding cannot be excluded. These findings require further investigation to establish causality and suggest that an integrated psychiatric assessment may be considered in unruptured intracranial aneurysm management.