Objectives To investigate if exposure to adverse psychological job characteristics predicts incident use of antidepressants, taking into account differential misclassification and residual confounding.

Methods A prospective cohort study with a 3.5-year follow-up of 4661 Danish employees, aged 40 and 50 years, drawn from a 10% random sample of the Danish population was carried out. Job characteristics were the predictor variables and use of antidepressants was the outcome variable. Survey data on psychosocial work environment were linked with register data on dispensing of antidepressant medicine between June 2000 and December 2003. Respondents with major depression at baseline, with antidepressant use in the 5 years preceding baseline, or not employed at baseline were excluded.

Results Among men, the OR for antidepressant use was significantly increased for high quantitative demands (OR 2.12, 95% CI 1.29 to 3.48) and low social support from colleagues (OR 2.28, 95% 1.36 to 3.82) after adjustment for lifestyle factors, socio-demographic factors, co-morbidity, other work factors and depressive symptoms at baseline. Both effects were dose dependent. An interaction effect with high demands was found for high anticipated private social support and living with children. Among women, no effect of job characteristics on antidepressant use was found.

Conclusion Among men, but not among women, high quantitative demands and low social support from colleagues were predictive of incident use of antidepressants, indicating incident depressive episodes, even after taking into account differential misclassification and residual confounding. The effects were buffered for those with high anticipated private social support and for those having children.