Antidepressant use and new‐onset diabetes: a systematic review and meta‐analysis

Abstract

Summary Antidepressant use has been linked to new-onset diabetes. However, the existing literature on this relationship has yielded inconsistent findings. The primary objective of this study was to systematically synthesize the literature on the relationship between antidepressant use and new-onset diabetes using meta-analysis. A systematic literature search was conducted to identify relevant studies in seven electronic databases. Two independent reviewers identified the final list of studies to be included in the meta-analysis using a priori selection criteria. Results for the primary outcome of interest, that is, odds and hazards of developing new-onset diabetes, were pooled using a random-effects model. Egger’s regression test and the Trim and Fill method were utilized to detect the presence of any potential publication bias. Sensitivity analysis was conducted using the leave-one-out method as well as individual categories of antidepressant drugs. Eight studies met the inclusion criteria. Random effects models revealed that adults with any use of antidepressants were more likely to develop new-onset diabetes compared with those without any use of antidepressants [odd ratios = 1.50, 95% confidence interval (CI), 1.08–2.10; hazards ratio = 1.19, 95% CI, 1.08–1.32]. Sensitivity analyses revealed fair robustness; selective serotonin reuptake inhibitors and tricyclic antidepressants were more likely to be associated with the development of new-onset diabetes. Results from the Egger’s regression test and Trim and Fill method revealed no evidence of publication bias. Among adults, antidepressant use was associated with higher chances of new-onset diabetes. However, because a cause-and-effect relationship cannot be established by observational studies, future randomized controlled studies are needed to confirm this association.

The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature

“…The association between antidepressant use and incident diabetes mellitus (DM) remains inconclusive [62]. Some reports point to a higher risk of DM [63,64,65] whereas others do not [66,67]; however, a recent systematic review and meta-analysis found that antidepressants (mainly SSRIs and TCAs) increase the risk of DM (OR = 1.5, 95% CI 1.08-2.10; HR = 1.19, 95% CI 1.08-1.32) [68]. As the included studies were observational, this association may not be causal [69].…”

Schizophrenia and type 2 diabetes mellitus

“…[74][75][76] A meta-analysis, though included only observational studies, reported increase in diabetes onset likelihood (OR 51.50, 95% CI 1.08-2.10, HR 51.19, 95% CI: 1.08-1.32). 77 However, most studies 78,79 provide evidence for elevated diabetes risk with the concurrent use of tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) (OR=1.89), 80 the long-term use of both tricyclic antidepressants (incidence rate ratio, IRR=1.77) and SSRIs (IRR=2.06) in at least moderate daily doses, 81 as well as the use of antidepressants medication in high-risk patients. 82 Further, amitriptyline, imipramide and mirtazapine are associated substantially with weight gain, nortriptyline and paroxetine appear to have intermediate effect, whereas bupropion and fluoxetine are linked with weight loss.…”

Cardiovascular risk factors in elderly : With special emphasis on atrial fibrillation, hypertension and diabetes

“…Antidepressants have been reported to affect glycaemic control and to trigger the onset of type 2 DM [115][116][117][118][119]. It is difficult to differentiate between the possible diabetogenic side effects of antidepressants per se (such as weight gain), from the effects associated with the depressive disorder [116,119]. SSRIs have been reported to confer a glucose lowering effect [117,120] and animal model studies have reported glucose increment from TCAs [121].…”

“…Treatment decisions are therefore often based on data from younger adults [112]. Antidepressants have been reported to affect glycaemic control and to trigger the onset of type 2 DM [115][116][117][118][119]. It is difficult to differentiate between the possible diabetogenic side effects of antidepressants per se (such as weight gain), from the effects associated with the depressive disorder [116,119].…”