At baseline (), 10.3% of DPP participants had BDI scores indicating at least mild depression (≥11), and 5.7% were taking antidepressants. During the DPP (), intermittent antidepressant use was reported for 7.2% of total person-years and continuous antidepressant use for 3.2% of total person-years.
Depression symptoms and antidepressant use at baseline and during the DPP
At baseline the median BDI score for all three treatment arms was 3 (interquartile range 1–7). At follow-up the median BDI score was 2 (0–5) for the ILS arm and 2 (0–6) for the MET and PLB arms. Elevated BDI scores at baseline and during the study were associated with 1) female sex, 2) race/ethnicity other than non-Hispanic white, 3) less education, and 4) higher BMI, higher fasting insulin levels, and lower levels of physical activity. Elevated BDI scores were not related to age at baseline, but during the DPP older participants (aged ≥60 years) were less likely to have elevated BDI scores than younger participants.
Antidepressant use on entry to the study and use during the study () was associated with female sex, non-Hispanic white race/ethnicity, and (on entry to the study only) more education. In contrast to elevated depression symptoms, antidepressant use was not associated with fasting insulin levels or physical activity level on entry to the DPP. Antidepressant use was associated with BMI on entry to and during the study and with lower levels of physical activity during the study. Antidepressant use at baseline was not related to age, but during the DPP older participants (aged ≥60 years) were less likely to take these agents than younger participants.
At baseline, 7.4% of women, but only 2.0% (21 of 1,029) of men, took antidepressants. The associations between antidepressant use and age, race/ethnicity, and education were similar for male and female participants, but when analyzed separately these associations were no longer significant among men, possibly due to lack of statistical power. Higher BMI at randomization was significantly associated with antidepressant use at baseline and during the study for women only.
When other factors associated with an increased risk of developing diabetes (age, sex, fasting glucose, baseline weight, and weight change during the study) as well as race/ethnicity were controlled, neither elevated BDI scores at baseline nor during the study were significantly associated with diabetes risk in any treatment arm (see lines labeled HRa in ). Leisure activity was not controlled because it was not associated with diabetes risk. (Absolute BDI scores at baseline were significantly associated with diabetes risk in the ILS arm only [P = 0.04].)
Prediction of diabetes by depression symptoms and antidepressant drug exposure
Baseline antidepressant use, on the other hand, was strongly associated with diabetes risk for participants in the PLB (hazard ratio 2.25 [95% CI 1.38–3.66]) and ILS (3.48 [1.93–6.28]) arms. Continuous antidepressant use during the study (compared with no use) was also significantly associated with diabetes risk in the same arms (PLB hazard ratio 2.60 [95% CI 1.37–4.94]; ILS 3.39 [1.61–7.13]), as was intermittent antidepressant use during the study in the ILS arm (hazard ratio 2.07 [95% CI 1.18–3.62]). In the PLB arm, the association between intermittent antidepressant uses during the study and diabetes risk approached significance (1.50 [0.97–2.33]). In the MET arm, antidepressant use was not associated with diabetes risk. There was a significant difference between the ILS and MET arms in the association between antidepressant medication and diabetes risk.
We further analyzed baseline antidepressant use, comparing only participants who were taking SSRIs, selective serotonin and norepinepherine reuptake inhibitors, or serotonin modulators with those who did not take any antidepressant, since these agents were considered less likely to increase the risk of diabetes. The results for this subgroup, which included 78% of all those taking antidepressants at baseline, were similar to those for all antidepressant users; taking SSRIs or related agents at baseline was significantly associated with the risk of developing diabetes during the DPP in the PLB and ILS arms but not in the MET arm. For this reason, our analysis of the association between antidepressant use during the DPP and diabetes risk included all antidepressants.
Our findings suggest that antidepressant use might have increased diabetes risk in the PLB and ILS arms. Under this assumption, we calculated that treating 5.4 PLB participants (95% CI 3.1–24.8) or 5.2 ILS participants (3.2–15.5) with antidepressants would have caused one additional case of diabetes 3 years later (31
). We did not perform this calculation for the MET arm, in which it would not be meaningful because there was no association between antidepressant use and diabetes risk.