Psychiatric outcomes and long-term school and work-related disability in offspring of parents with depression and treatment-resistant depression.

Purpose: To investigate the risk for adverse outcomes among offspring of parents with depression and with treatment-resistant depression (TRD), compared with matched offspring in the general population.

Methods: Parents diagnosed with depression in specialized psychiatric care in 2006-2018 were identified in nation-wide Swedish registers. Those starting a third sequential antidepressant trial were defined as treatment-resistant. Parents and their 2,359 first-born offspring, aged 6-15 years when parents were defined with TRD, were closely matched 1:1 with parent-offspring pairs with other parental depression as well as with parent-offspring pairs from the general population. Offspring cohorts were followed prospectively for psychiatric outcomes and school- and work-related disability.

Results: Offspring of parents with both TRD and other depression had substantially elevated risks for all outcomes compared to general population offspring. Adjusted hazard ratios for offspring of parents with TRD were: depression 4.6 (95%CI 3.2-6.5); contact with psychiatry 3.3 (2.8-4.0); psychiatric medication 3.6 (3.0-4.2); suicide attempt 3.2 (1.9-5.5); sick leave for mental health reasons 2.3 (1.1-4.6); and disability pension 4.2 (2.2-8.1). The adjusted odds ratio for non-completion of secondary school when expected was 2.1 (1.5-2.9). In direct comparisons between offspring of parents with TRD vs. other depression, relative risks for all outcomes were similar, with no statistically significant differences.

Conclusion: Offspring of parents with TRD and other depression are at similarly elevated risks of adverse clinical, educational, and work-related outcomes. Parental TRD, as defined in administrative health care data, may not serve as a risk indicator for long-term offspring burden in parental depression.