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Tricyclic and SSRI usage influences the association between BMI and health risk factors

To determine if selective‐serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) influence the association between obesity and cardiovascular disease risk, participants from the Third National Health and Nutrition Examination Survey (NHANES III; 1988–1992) and continuous NHANES (1999–2009, n = 18 274) were used. For a given body mass index (BMI), individuals taking SSRIs (n = 219) tended to have significantly better health risk profiles with lower systolic blood pressure (P = 0.002) and higher high‐density lipoprotein (P = 0.003) compared with non‐users. Conversely, those who used TCAs (n = 116) had significantly worse health risk profiles with higher diastolic blood pressure (P ≤ 0.0001) and triglycerides (P = 0.023) as compared with non‐users for a given BMI. Insulin resistance (HOMA‐IR) was higher in TCA users and those with larger BMIs, whereby the differences in insulin resistance between TCA users and non‐users was greater with higher BMIs (interaction effect: P = 0.013). Furthermore, individuals taking SSRIs were less likely to have cardiovascular disease than non‐users (odds ratio, 95% confidence interval = 0.50, 0.33–0.75) for a given BMI, with no differences by TCA use (odds ratio = 0.74, 0.44–1.24). SSRI and TCA use may alter how body weight relates with cardiovascular risk. When prescribing antidepressant medications, it may be necessary to monitor and consider body weight and cardiovascular risk profile of individual patients.