Background The prescribing of antidepressant and antipsychotic drugs is increasing worldwide for a range of indications including mental ill-health. Numerous side effects have been associated with these drugs, including increased risk of cardiovascular complications. People with diabetes are more likely to be prescribed these drugs but few studies have investigated the effect of these drugs in this specific population. We therefore conducted a systematic review of studies that investigated the association between antidepressant and/or antipsychotic drug prescribing and vascular complications or mortality in people with diabetes.

Methods We systematically searched PubMed, EMBASE, and PsycINFO for observational studies examining the association between use of antidepressant and/or antipsychotic drug use and vascular disease (including cardiovascular disease and microvascular complications) and all-cause and cause-specific mortality among adults with type 1 or 2 diabetes. Secondary outcomes of interest included cardiometabolic risk factors. Data extraction was performed independently by two reviewers using standardised data collection forms.

Results Our search retrieved 9,833 articles, of which 13 were included in the review. Studies were heterogenous in design, population, and outcomes. Six studies were cohort design, two were case control, and five were cross-sectional. Some studies included an unselected population and others included only people with particular mental illnesses or excluded people with mental illness. Six studies reported on vascular complications, six studies reported on cardiometabolic risk factors (including glycaemic control), and one study reported on both vascular complications and cardiometabolic risk factors. Study population size ranged from 265 to 241,787. Whilst study heterogeneity makes comparability difficult and findings were mixed, there was some evidence that antidepressant and antipsychotic drugs may lead to a reduced risk of cardiovascular morbidity, possibly more so among women than men. There was also evidence that antidepressant use may lead to a reduced risk of diabetic retinopathy in women. There was evidence that antidepressants can lead to improved glycaemic control among people with depression, but there may be an increased risk of hospitalisation for hyperglycaemia in people using antipsychotics.

Conclusion Few studies have examined the effect of antidepressant and antipsychotic drugs on complications of diabetes, with mixed findings reported. These drugs may have a protective effect potentially mediated by their therapeutic effects on mental health and adherence to lifestyle advice and other treatment. It is also possible that there is effect modification by sex, with some protective effects observed in women but not in men. More research on this topic is required.