The effect of antidepressants on glucose homeostasis and insulin sensitivity: synthesis and mechanisms

McIntyre, Roger S.; Soczynska, Joanna K.; Konarski, Jakub Z.; Kennedy, Sidney H.

doi:10.1517/14740338.5.1.157

Cited by 172 publications

(116 citation statements)

References 64 publications

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“…Indeed, several previous longitudinal studies have shown that depression increased the risk of developing diabetes [2][3][4]. Second, antidepressants themselves might be a risk factor for diabetes, as the literature indicates that antidepressant use can disturb glucose levels and glycaemic control [23]. However, the short time period we observed between the increased incidence of antidepressant and benzodiazepine use and the initiation of diabetes treatment makes it unlikely that depression, psychosocial complaints or anti- Table 2 Incidence rates, and crude and adjusted incidence rate ratios (95% CIs), in non-diabetic individuals and diabetic patients (per 1,000 person-years) for antidepressant and benzodiazepine use in the 3 months before and after the index date depressants are causal risk factors for diabetes.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant use before and after initiation of diabetes mellitus treatment

et al. 2009

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Aims/hypothesis Although current literature suggests an association between diabetes and depression, the direction of the association is unclear. We examined the temporal association between diabetes and depression by studying antidepressant and benzodiazepine use around the initiation of diabetes treatment. Methods From a pharmacy registry database we selected 49,593 diabetic patients and a random sample of non-diabetic individuals (n=154,441), all >40 years old. Antidepressant and benzodiazepine use was calculated for the 7 years before and 7 years after the index date. The index date in diabetes patients was defined as the date of initiation of diabetes medication. A random index date was assigned to nondiabetic individuals. Time-specific incidence rate ratios of antidepressant and benzodiazepine use were calculated for intervals of 1 year, 3 months and 1 month. Results Antidepressant and benzodiazepine use was increased 2 months before and 3 months after the initiation of diabetes treatment compared with non-diabetic individuals.The strongest increase in incidence of antidepressant and benzodiazepine use was seen in the month after initiation of diabetes treatment with incidence rate ratios of 2.4 (95% CI 2.0-3.0) and 3.4 (95% CI 3.0-3.8) respectively, after adjustment for age, sex and Chronic Disease Score. Conclusions/interpretation The increased incidence of antidepressant and benzodiazepine use may be a consequence of the burden of disease, of starting with diabetes medication or of being diagnosed with diabetes. Our findings could also reflect earlier detection by their physician.

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Section: Discussionmentioning

confidence: 99%

Antidepressant use before and after initiation of diabetes mellitus treatment

et al. 2009

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“…Jacobson et al (2002) proposed that DM, especially type 1 DM, may place patients at risk for a depressive disorder through a biological mechanism related to the metabolic changes of DM on the structure and function of the brain. McIntyre et al (2006) showed that the treatment of depression with the use of serotonergic antidepressants (e.g., fluoxetine) may reduce hyperglycemia, normalize blood glucose level, and increase insulin sensitivity in diabetic patients. Elevated depression scores increase the risk of having carotid plaques at the 10-year follow-up in a prospective study (Haas et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Association between Depression and Anxiety Symptoms and Major Atherosclerosis Risk Factors in Patients with Chest Pain

Vural¹,

Şatıroğlu²,

Akbas

et al. 2007

Tohoku J. Exp. Med.

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Psychological variables, such as depression and anxiety, are known as independent risk factors for coronary artery disease (CAD), suggesting the interaction of psychological and physiological factors in the development of CAD. In the present study, we analyzed the possible association between depressive and anxiety symptoms and major atherosclerotic risk factors in patients with chest pain warranting coronary angiography. The patients without CAD (n = 159) and those with CAD (n = 155) were evaluated for the severity of depression and anxiety by the symptom scales; high scores indicate severe symptoms. Age, male/female ratio, prevalence of diabetes mellitus (DM), and depression level were significantly higher in the CAD group. Among a total of 314 patients with chest pain, the mean depression score was higher in patients with DM (16.01 ± 8.12 vs 13.01 ± 9.6, p = 0.01) and those with hypercholesterolemia (15.43 ± 9.61 vs 12.53 ± 9.61, p = 0.02). The mean anxiety score was also higher in patients with DM (20.81 ± 12.85 vs 16.51 ± 12.09, p = 0.008), hypercholesterolemia (20.67 ± 13.11 vs 15.29 ± 11.36, p = 0.002), or hypertension (20.74 ± 12.94 vs 14.1 ± 10.8, p = 0.001). Thus, DM and hypercholesterolemia are associated with depression and anxiety, while hypertension is only related to anxiety. In contrast, smoking and family history of atherosclerosis are not related to depression and anxiety scores. These results suggest depression and anxiety symptoms may contribute to the development and progression of CAD, especially in patients with DM or hypercholesterolemia.depression; anxiety; psychological tests; atherosclerosis risk factors; coronary artery disease

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“…It is unclear how duloxetine might affect glucose homeostasis, but some noradrenergic antidepressants (e.g., desipramine) have shown to modulate glucose homeostasis (21). It has been reported that increased noradrenergic effects may be associated with elevation of blood glucose in humans, since catecholamines can promote hyperglycemia through multiple mechanisms (e.g., inhibition of insulin secretion, stimulation of gluconeogenesis, and decrease in insulin sensitivity) (22).…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Impact of Disease Characteristics on the Efficacy of Duloxetine in Diabetic Peripheral Neuropathic Pain

et al. 2007

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OBJECTIVE -To evaluate the impact of baseline disease variables related to diabetes and diabetic neuropathy severity on efficacy and safety of duloxetine in the management of diabetic peripheral neuropathic pain.RESEARCH DESIGN AND METHODS -The impact of baseline conditions was evaluated using the data from three pooled placebo-controlled studies for combined duloxetine, doses of 60 mg q.d. and 60 mg b.i.d., versus placebo. The primary efficacy measure was the weekly mean of 24-h average pain severity, and night pain was the secondary measure. Safety and tolerability were assessed.RESULTS -There were no significant (P Ͼ 0.10) interactions of treatment by age (Ͻ65 or Ն65 years), type of diabetes (type 1 or type 2), duration of diabetes (median split Ͻ9.18 or Ն9.18 years), duration of diabetic neuropathy (Ͻ2, 2 to Ͻ6, or Ն6 years), severity of diabetic neuropathy (baseline Michigan Neuropathy Screening Instrument score Ͻ5 or Ն5), baseline A1C level (median split Ͻ7.6 or Ն7.6%), or baseline insulin use (yes/no). Significant interactions for both pain measures were observed in baseline pain subgroups (Brief Pain Inventory average pain, Ն6 and Ͻ6). Duloxetine was more effective in the subgroup with more pain. No significant association was found between any other subgroups (P Ͼ 0.10). Significant interactions (P Ͻ 0.1) occurred with treatment-emergent adverse events when stratified by subgroups.CONCLUSIONS -Pain severity but not variables related to diabetes or neuropathy may predict the effects of duloxetine in diabetic peripheral neuropathic pain. The efficacy of duloxetine is related to the initial pain severity and is generalizable across a broad spectrum of diabetic patients, including those with the highest severity of diabetes or neuropathy. Diabetes Care 30:664 -669, 2007

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The effect of antidepressants on glucose homeostasis and insulin sensitivity: synthesis and mechanisms

Abstract: Some antidepressants exert a clinically significant effect on metabolism relevant to both therapeutic outcome and adverse events.

Cited by 172 publications

References 64 publications

Antidepressant use before and after initiation of diabetes mellitus treatment

Antidepressant use before and after initiation of diabetes mellitus treatment

Association between Depression and Anxiety Symptoms and Major Atherosclerosis Risk Factors in Patients with Chest Pain

Impact of Disease Characteristics on the Efficacy of Duloxetine in Diabetic Peripheral Neuropathic Pain

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