Antidepressant Medication and the link with T2D

Antidepressant Medication

Antidepressant medication use has risen sharply over recent years with 46.7 million prescriptions for antidepressants issued in the United Kingdom in 2011 compared with 20.1 million in 1999 [1].

Antidepressant Link with Type 2 Diabetes

Recently there have been concerns that antidepressants may adversely affect glucose metabolism, not least because some antidepressants induce significant weight gain, which may contribute to insulin resistance [2].

The Evidence

Case reports have found that certain antidepressants have been associated with the development of diabetes, which returns to normal after treatment stops. Cross sectional studies have not demonstrated an increase in diabetes prevalence, independent from depressive symptoms; however, there are changes in metabolic and body composition measurements that are associated with diabetes. Case-control studies have reported an approximate doubling of diabetes rates in those taking antidepressants, with higher rates seen with higher doses, longer duration or as combinations.

Some cohort studies have also found an increase in the incidence of diabetes in people taking antidepressants although the most recent larger studies have shown a much lower risk than in the first studies published in 2008. There is evidence of potential confounding variables as rates of undiagnosed diabetes were not increased in the one study that compared diagnosed and undiagnosed diabetes. Further research provides evidence of a dose response with a higher rate in those taking higher doses.

Is it all Antidepressants?

Different types of antidepressants may carry different risks and long-term prospective randomized control trials to look at the effects of individual tablets are needed.

The picture is confused with noradrenergic tricyclic antidepressants and nortriptyline reportedly linked to worsening glycaemic control [3] whereas selective serotonin re-uptake inhibitors are linked to both worsening [4] and improved [5] glycaemic control in people with diabetes, while tricyclic antidepressants induce hyperglycaemia in humans [6].

As antidepressants may be used in people at higher risk of developing diabetes per se, disentangling a drug effect from this complex relationship is challenging [7].

The Complexities

People with depression are at increased risk of diabetes, independent of treatment.

There is evidence that some antidepressants affect glucose metabolism and antidepressant use may be an independent risk factor for diabetes.

Depression is an important clinical problem and antidepressants are effective treatments for this debilitating condition. Clinicians need to be aware of the potential risk of diabetes, particularly when using antidepressants in higher doses or for longer duration.

When prescribing antidepressants, doctors should be aware of this risk and take steps to monitor for diabetes and reduce that risk of diabetes through lifestyle modification

What Does It Mean?

The evidence suggests a link between antidepressant use and diabetes but causality is not established. The strength of association in the larger most recent cohort studies is weak, which increases the chance that the finding occurs through residual confounding.

It is likely that most serious adverse drugs effects have a weak association only because a high risk of a serious side effect would have prevented a drug reaching the market. There is inconsistency amongst findings from different study types regarding increased diabetes risk, although more consistency is found within the cohort and experimental studies that provide the strongest evidence.

To conclude that diabetes is a consequence of antidepressant use, the drug must be prescribed before the onset of diabetes. While this occurs in the case histories, cohort and experimental studies, in other studies, diabetes preceded antidepressant use, with evidence of reverse causality. There is evidence of a biological gradient, i.e. increasing exposure associated with increasing diabetes risk, as several studies have shown that diabetes is more common in those using antidepressants in higher dose or for longer duration or both. This may, however, be confounded with worse severity of depression, rather than antidepressants, increasing diabetes risk.

There are several plausible reasons why antidepressants may be associated with an increased diabetes risk. Several antidepressants are associated with significant weight gain, which in turn increases insulin resistance and the risk of diabetes [8][9]. However, several studies still observed an increased risk of diabetes after adjustment for changes in body weight, implying that there are other mechanisms involved. This is consistent with previous findings that other psychiatric drugs, for example antipsychotics, may affect glucose metabolism by altering insulin resistance or secretion directly.

Increased antidepressant use is occurring concurrently with increasing diabetes prevalence, thus any cause and effect interpretation does not conflict with generally known facts of natural history and biology of the disease.

Conclusion

There may be a causative link between antidepressants and diabetes but this risk is probably low and the majority of patients receiving antidepressants will not develop diabetes as a result of their medication.

Further Information

Barnard, K.D., Peveler, R. and Holt, R.I.G. Antidepressant Medication as a Risk Factor for Type 2 Diabetes: Systematic Review. Diabetes Care 36:3337-3345, 2013

References

  1. ^ National Health Executive: www.nationalhealthexecutive.com/Health-Care-News/antidepressant

  2. ^ Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry 2010; 71(10): 1259-1272.

  3. ^ Isotani H, Kameoka K: Hypoglycemia associated with maprotiline in a patient with type 1 diabetes. Diabetes Care (1999) 22 (5/May): 862-3

  4. ^ Sansone, R.A. and Sansone, L.A. Driving on Antidepressants: Cruising for a Crash? Psychiatry (Edgmont). 2009 September; 6(9): 13–16.

  5. ^ van der Feltz-Cornelis CM., Nuyen J., Stoop C., Chan J., Jacobson AM., Katon W., Snoek F and Sartorius N. Effects of interventions for major depressive disorder and significant depressive symptoms in patients with diabetes mellitus: a systematic review and meta-analysis. General Health Psychiatry 32 (2010) 380-395

  6. ^ Khoza S, Barner JC. Glucose dysregulation associated with antidepressant agents: an analysis of 17 published case reports. Int J Clin Pharm 2011; 33(3): 484-492.

  7. ^ Barnard K.D., Skinner T.C., and Peveler R. “The Prevalence of Comorbid Depression in Adults with Type 1 Diabetes” Diabetic Medicine, Volume 23, Issue 4, Page 445-448, Apr 2006

  8. ^ Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry 2010; 71(10): 1259-1272

  9. ^ Holt RIG, Peveler, RC. Association between antipsychotic drugs and diabetes. Diabetes Obesity and Metabolism Mar;8(2): 125-35 Review

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