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Context: Most previous studies have examined suicide risk in relation to a single physical disease.

Objectives: To estimate relative risk across a range of physical diseases, to assess the confounding effect of clinical depression and effect modification by sex and age, and to examine physical illness multimorbidity.

Design: Nested case-control study.

Setting: Family practices (n = 593) registered with the General Practice Research Database from January 1, 2001, through December 31, 2008. The case-control data were drawn from approximately 10.6 million complete patient records, pertaining to approximately 8% of the total population of the United Kingdom, with complete linkage to national mortality records.

Participants: A total of 873 adult suicide cases and 17 460 living controls matched on age and sex were studied. The reference group for relative risk estimation consisted of people without any of the specific physical illnesses examined.

Main Outcome Measures: Suicide and open verdicts.

Results: Among all patients, coronary heart disease, stroke, chronic obstructive pulmonary disease, and osteoporosis were linked with elevated suicide risk, and, with the exception of osteoporosis, the increase was explained by clinical depression. The only significantly elevated risk in men was with osteoporosis. Female effect sizes were greater, with 2- or 3-fold higher risk found among women diagnosed as having cancer, coronary heart disease, stroke, chronic obstructive pulmonary disease, and osteoporosis. In women with cancer and coronary heart disease, a significant elevation persisted after adjustment for depression. Overall, heightened risk was confined to physically ill women younger than 50 years and to older women with multiple physical diseases.

Conclusions: Our findings indicate that clinical depression is a strong confounder of increased suicide risk among physically ill people. They also demonstrate an independent elevation in risk linked with certain diagnoses, particularly among women. Health care professionals working across all medical specialties should be vigilant for signs of undetected psychological symptoms.

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