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Although research into the synergistic mechanism by which depression and DM causes increased mortality is ongoing, large scale controlled studies have already conclusively proven a common mechanism. Prolonged low level inflammation influenced by HPA axis activation, increased sympathetic tone, obesity, and damaging behavioural patterns all result in a chronic affront to the vascular systems of diabetic depressed individuals. The body of evidence that this leads to the greatly increased mortality and morbidities in such populations is significant.
Pharmacotherapy
Antidepressant therapy in patients with DM who suffer from depression is an effective way of reducing depressive symptoms. This has been proven for SSRIs such as fluoxetine and citalopram (47), sertraline (48) and paroxetine (49); and tricyclic antidepressants such as nortriptyline (7). However, the evidence as to whether antidepressant therapy is useful in improving glycaemic control is fairly inconclusive. Certainly, remission of depression is beneficial for glycaemic control, as the presence of psychiatric illness in diabetic patients is associated with poorer glucose homeostasis, health behaviours and adherence to medication (50). However, it is important that the potential benefits of treating depression for metabolic control are not cancelled out by adverse effects of antidepressant drugs.
Some drug classes, such as tricyclic antidepressants (TCAs), have been shown to have deteriorative effects on glycaemic control – this was the case with nortriptyline, which was found to cause hyperglycaemia. This hyperglycaemia was not attributable to weight gain; however, weight gain is a well-documented side effect of tricyclic antidepressants (7), and as a result they should be avoided in diabetic patients. Another tricyclic antidepressant, imipramine, may also have a negative impact on glycaemic control by increasing fasting blood glucose levels (51). Although no longer widely prescribed due to its adverse effects and the development of newer and safer drugs, it is especially important that MAOIs are not prescribed for depression in diabetic patients, as they increase sensitivity to insulin and can directly induce hypoglycaemia (52).
SSRIs may be a preferable option for the treatment of depression in diabetic patients, as evidence suggests that drugs such as citalopram and fluoxetine may improve parameters such as fasting blood glucose and HbA1c (47). Fluoxetine in particular was found to have a favourable impact on glycaemic control (53, 54), as was sertraline (55). However, the evidence on this is still somewhat lacking, as several studies found that there was no significant change in glucose control when patients were prescribed SSRIs. This has been found with sertraline (56) and citalopram (57). Despite the conflicting information, it is likely that SSRIs are a better choice for depression in diabetic patients than drugs such as TCAs and MAOIs, given the evidence available to date.
Several studies have shown that an integrated approach to the care of patients with comorbid depression and DM could be very useful in improving clinical outcomes (58). Collaborative care is highly likely to improve recovery from depression as a direct outcome (59), thereby enabling diabetic patients to achieve better glycaemic control due to absence or lessened severity of psychiatric comorbidities (60). Patients who are given a personalised care plan, involving education about their comorbidity and the importance of managing depression in order to keep DM under control, may be more likely to achieve desired HbA1c levels, remission of depression, and satisfactory medication adherence (61).
Pharmacotherapy - Implications for Diabetes Development
It is important to consider how the treatment of mental illness may affect the risk of developing DM; particularly with respect to antidepressants and antipsychotics.
Being overweight or obese strongly influences the likelihood of developing DM. If none of the population had a BMI of over 25, then 64% of males and 74% of females could have been prevented from developing non-insulin dependent DM (62). A major concern for physicians now is the prescription of antidepressants and antipsychotics, as a variety of these are known to induce weight gain (6).
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