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Clinical briefing: Polypharmacy, antidepressants and diabetes

When it comes to antidepressants and type 2 diabetes, polypharmacy does not necessarily undermine adherence. As with so much in medicine and prescribing, the devil is in the detail says Mark Greener

Sixty-four per cent of older people with diabetes receive at least four to six medicines a day, according to a recent meta-analysis of eight studies.

Based on four of the studies that defined polypharmacy as at least five medicines a day, 50 per cent of older people with diabetes received polypharmacy.

Polypharmacy, in turn, seems to increase the risk of poor outcomes relating to quality of life, diabetes (poor glycaemic control and hypoglycaemia) and generally (falls, syncope, hospitalisation and death).

Indeed, a recent study hypothesised that polypharmacy would be associated with higher rates of antidepressant discontinuation in people with type 2 diabetes mellitus – but the opposite was actually found to be the case.2 


Depression and diabetes are intertwined. A meta-analysis of 44 studies reported, for instance, that the likelihood of depression was doubled in people with type 1 diabetes (22 and 13 per cent respectively) or type 2 diabetes (19 and 11 per cent respectively) compared to those without diabetes.3 Despite this mental health burden, a new study in the British Journal of General Practice reports that many people with type 2 diabetes discontinue antidepressants early.

Researchers identified 73,808 individuals with comorbid depression and type 2 diabetes who started antidepressants for the first time in UK primary care between 2000 and 2018.2 

The median age was 63 years and 52 per cent were female. Of these, 12.3 per cent had early diabetes and did not receive pharmacological treatment for type 2 diabetes. Another 14.4 per cent needed insulin.2

NICE suggests that treatment with antidepressants should be reviewed regularly, but, in general, should last at least six months after symptoms resolve. However, many people discontinue antidepressants early because of ineffectiveness or side-effects.2 In this study, treatment with the first antidepressant prescribed to people with type 2 diabetes lasted a median of just 4.57 months.2 Within 32 weeks of starting treatment, 44.3 per cent had discontinued antidepressants and 11.8 per cent had switched antidepressant medication.2

Inverse relationship

An inverse relationship emerged between the number of concurrent medications and the likelihood of discontinuing antidepressants. The relationship began to emerge at two concurrent medications. 

The rate of discontinuing antidepressants decreased for each additional medication prescribed.2 For example, the median number of seven concurrent medications (excluding the antidepressant) was associated with a 55 per cent decrease in the likelihood of discontinuing antidepressants within 32 weeks of starting treatment.2

In other words, people with higher levels of polypharmacy may actually be more adherent to treatment than those taking fewer drugs because they may have worse physical or mental health, or both, such as more severe depression.2 The authors were unable to account for depression severity in the analysis.2 

The number of concurrent medications did not seem to influence the likelihood of switching antidepressants.2 The authors say that the association between concurrent medications and discontinuing, but not switching, antidepressants may suggest that type 2 diabetes patients with higher levels of polypharmacy may be more adherent to medication overall.2

Sensitivity analysis

A sensitivity analysis that included repeat prescriptions only found that seven concurrent medications was associated with a 38 per cent decrease in the likelihood of discontinuing antidepressants within 32 weeks. The authors comment that the smaller inverse association with discontinuing antidepressants in the sensitivity analysis compared with the main results may suggest that experiencing acute events or new or worsened issues (such as more severe depression) when starting antidepressants may be associated with improved antidepressant adherence.2

Further research needs to explore why people with depression and type 2 diabetes receiving polypharmacy are less likely to discontinue antidepressants early. In the meantime, the authors comment that people with fewer concurrent medications may have less complex type 2 diabetes, fewer comorbidities, less contact with services or be less adherent. Depression may be under-treated in these individuals, which could lead to worse type 2 diabetes outcomes, so these patients may benefit from increased monitoring and adherence support.2


  1. Aging Clinical and Experimental Research 2022; 34:1969-1983
  2. British Journal of General Practice 2022; DOI:10.3399/bjgp.2022.0295
  3. Primary Care Diabetes 2022; 16:1-10
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