David Baxter PhD
Late Founder
Diabetes and Depression
Norman Sussman, MD **
Primary Psychiatry, 2007;14(6):13-14
This month, the American Diabetes Association (ADA) holds its 67th Annual Scientific Sessions in Chicago. Papers presented at this meeting have received increased media coverage as diabetes mellitus has become a major public health concern. Physicians in all specialties are seeing more patients diagnosed with diabetes. However, psychiatrists are in a unique position because many medications currently used to treat mental disorders potentially induce or worsen glycemic control, with atypical antipsychotics being the most clearly demonstrated to adversely affect glucose regulation and cause weight gain. As this issue of Primary Psychiatry focuses on depression and response to treatment, it is appropriate to address some recent research findings about the possible relationship between depression, antidepressants, and diabetes.
Type 2 diabetes has long been thought of as a disease of advancing age, although this characterization is unfortunately changing as more adolescents are diagnosed with this disorder. Nevertheless, approximately 15% of people >65 years of age have diabetes. A recently published study suggests that, among older adults, major depressive disorder (MDD) is associated with an increased risk for diabetes, even in people who have no other risk factors for the disease.1 This study followed 4,681 men and women >65 years of age over a 10-year period. Researchers excluded patients with diabetes at baseline. MDD symptoms were measured each year, and blood sugar was tested at 2?4-year intervals. Researchers also calculated body mass index (BMI) and recorded alcohol intake, smoking status, and antidepressant use. Accounting for these factors, a single report of high depressive symptoms was associated with an increase in diabetes incidence. In addition, increases in symptoms over time and persistently high symptoms of MDD were associated with the disease. Overall, patients with the highest severity of MDD were approximately 50% more likely to develop diabetes than those with the lowest scores. No difference in result was uncovered when findings were adjusted for race, gender, smoking status, alcohol intake, and BMI.
These findings do not prove that improvements in depressive symptoms result in better control of glucose levels. A new study that investigated how changes in mood symptoms may be affected by cognitive-behavioral therapy (CBT) found that improvement in depressive symptoms were not associated with changes in HbA1c or fasting glucose levels over a 1-year period in patients with either Type 1 or Type 2 diabetes.2 Even among a small subgroup of patients who met criteria for MDD, there was no evidence of an improvement in HbA1c level as depression improved.
Another new study3 was designed to evaluate the effects of the norepinephrine and dopamine reuptake inhibitor bupropion in depressed patients with diabetes. Unlike selective serotonin reuptake inhibitors (SSRIs), which can cause significant weight gain over time, bupropion rarely causes weight gain and is capable of weight reduction. Theoretically, the combined antidepressant and weight effects of bupropion should improve glycemic control in diabetic patients. Utilizing an acute and maintenance phase, researchers found that bupropion treatment was associated with symptom remission in 68% of patients beginning bupropion treatment and in 84% of those who completed the acute phase. Of patients whose depression remitted and continued to receive bupropion, 87% completed the subsequent 6-month study interval and none had a recurrence. Significant improvement in A1C was observed among patients achieving MDD remission during the acute phase. Reductions in weight observed in the subset showing remission over the acute (1.5 kg) and maintenance (2.1 kg) phases were modest. It is encouraging that clinically important improvements in A1C can occur in the absence of large changes in body mass.
Reduction in depression was also accompanied by improvements in some diabetes self-care behaviors and glycemic control. According to the authors, this is the first study to demonstrate a broad improvement in diabetes self-care during depression treatment. There is the possibility that better compliance with lifestyle and diet regimens contributed to the improvement in diabetes parameters.
Nevertheless, I have certain reservations about the robust findings of this study; it was not a randomized, controlled trial?which may explain the inordinately high rate of depression remission (87%) and the absence of depression recurrence in patients who completed acute and maintenance phases. Yet, any improvement in glycemic control is welcome and, in the case of diabetic patients with depression, there is a special need for accurate diagnosis and treatment.
These researchers also evaluated effects of maintenance treatment with the SSRI sertraline in MDD patients with diabetes.4 This randomized, double-blind, placebo-controlled, maintenance treatment trial involved patients who recovered from MDD during 16 weeks of open-label sertraline treatment. Of patients initially assigned to the sertraline group, 43.3% recovered from MDD. This group then continued to receive sertraline or placebo and were followed for up to 52 weeks, or until depression recurred. The primary outcome was length of time to MDD recurrence. The secondary outcome was glycemic control, which was assessed via serial determinations of A1C levels. The study demonstrated that, in patients with diabetes, maintenance therapy with sertraline prolonged the depression-free interval following recovery from MDD.
At last year?s ADA meeting, a study suggested that antidepressants actually increase the risk of developing Type 2 diabetes.5 Researchers from the Diabetes Prevention Program, sponsored by the National Institutes of Health, reported that depression alone did not predict progression to diabetes in patients at risk for the disease. In fact, antidepressants were associated with a 2?3-fold increase in risk. The increase was not found in patients at high risk for diabetes who were taking both antidepressants and metformin. The study was based on a partial re-analysis of the Diabetes Prevention Program. A large-scale study, the program found that patients at higher risk for Type 2 diabetes who lost excess weight and exercised were often able to prevent diabetes onset. This was the first large study to examine antidepressant effect on patients at high risk for Type 2 diabetes. At baseline, 5.7% of patients were already taking antidepressants. During the study, approximately 13.5% of patients used antidepressants at some point. Researchers found that being on any kind of antidepressant increased diabetes risk. In addition, the type of antidepressant taken (tricyclic antidepressant or SSRI) did not change the result in the placebo or lifestyle arm of the study. The protective effect of metformin could not be explained. Of patients who developed diabetes, causes included weight gain, less physical activity, or increased insulin resistance.
Many experts have speculated that depression leads to elevated levels of the stress hormone cortisol, which increases blood glucose levels and causes more fat to collect around the abdominal area. Mid-section fat, as opposed to fat on the hip and thigh area, tends to be more metabolically active and causes damage to organs including the heart, liver, and pancreas. This process could also explain the link between depression, heart disease, and stroke. Thus, antidepressants would appear to help in this situation. Studies suggest that effects of depression treatment are determined by multiple factors. Improved self-care, dietary control, and compliance with diabetes medications are important. Weight-independent physiological mechanisms involved could include changes to the limbic-hypothalamic and hypothalamic-pituitary-adrenal axes, hippocampal glucocorticoid receptors, the autonomic nervous system, and immune or inflammatory processes. However, other research suggests that depression predisposes patients to diabetes. There has also been speculation that corticosteroids, which are elevated in depression, may have an impact on glucose homeostasis, and thus cause diabetes.
Based on available evidence, the cause and effect between depression, antidepressants, and diabetes remains poorly understood, and the association between antidepressants and diabetes risk remains uncertain. No compelling evidence exists showing that treating depression reduces the risk of developing diabetes; but the effects of depression are reason enough to opt for treatment.
References
1 Carnethon MR, Biggs ML, Barzilay JI, et al. Longitudinal association between depressive symptoms and incident type 2 diabetes mellitus in older adults: the cardiovascular health study. Arch Intern Med. 2007;167(8):802-807.
2 Georgiades A, Zucker N, Friedman KE, et al. Changes in depressive symptoms and glycemic control in diabetes mellitus. Psychosom Med. 2007;69(3):235-241.
3 Lustman PJ, Williams MM, Sayuk GS, Nix BD, Clouse RE. Factors influencing glycemic control in type 2 diabetes during acute- and maintenance-phase treatment of major depressive disorder with bupropion. Diabetes Care. 2007;30(3):459-466.
4 Lustman PJ, Clouse RE, Nix BD, et al. Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2006;63(5):521-529.
5 Diabetes Prevention Program Research Group. Depression symptoms, antidepressant medicine use and risk of developing diabetes in Diabetes Prevention Program participants. Paper presented at: 66th Annual Scientific Sessions of the American Diabetes Association; June 9?13, 2006; Washington, DC.
Norman Sussman, MD **
Primary Psychiatry, 2007;14(6):13-14
This month, the American Diabetes Association (ADA) holds its 67th Annual Scientific Sessions in Chicago. Papers presented at this meeting have received increased media coverage as diabetes mellitus has become a major public health concern. Physicians in all specialties are seeing more patients diagnosed with diabetes. However, psychiatrists are in a unique position because many medications currently used to treat mental disorders potentially induce or worsen glycemic control, with atypical antipsychotics being the most clearly demonstrated to adversely affect glucose regulation and cause weight gain. As this issue of Primary Psychiatry focuses on depression and response to treatment, it is appropriate to address some recent research findings about the possible relationship between depression, antidepressants, and diabetes.
Type 2 diabetes has long been thought of as a disease of advancing age, although this characterization is unfortunately changing as more adolescents are diagnosed with this disorder. Nevertheless, approximately 15% of people >65 years of age have diabetes. A recently published study suggests that, among older adults, major depressive disorder (MDD) is associated with an increased risk for diabetes, even in people who have no other risk factors for the disease.1 This study followed 4,681 men and women >65 years of age over a 10-year period. Researchers excluded patients with diabetes at baseline. MDD symptoms were measured each year, and blood sugar was tested at 2?4-year intervals. Researchers also calculated body mass index (BMI) and recorded alcohol intake, smoking status, and antidepressant use. Accounting for these factors, a single report of high depressive symptoms was associated with an increase in diabetes incidence. In addition, increases in symptoms over time and persistently high symptoms of MDD were associated with the disease. Overall, patients with the highest severity of MDD were approximately 50% more likely to develop diabetes than those with the lowest scores. No difference in result was uncovered when findings were adjusted for race, gender, smoking status, alcohol intake, and BMI.
These findings do not prove that improvements in depressive symptoms result in better control of glucose levels. A new study that investigated how changes in mood symptoms may be affected by cognitive-behavioral therapy (CBT) found that improvement in depressive symptoms were not associated with changes in HbA1c or fasting glucose levels over a 1-year period in patients with either Type 1 or Type 2 diabetes.2 Even among a small subgroup of patients who met criteria for MDD, there was no evidence of an improvement in HbA1c level as depression improved.
Another new study3 was designed to evaluate the effects of the norepinephrine and dopamine reuptake inhibitor bupropion in depressed patients with diabetes. Unlike selective serotonin reuptake inhibitors (SSRIs), which can cause significant weight gain over time, bupropion rarely causes weight gain and is capable of weight reduction. Theoretically, the combined antidepressant and weight effects of bupropion should improve glycemic control in diabetic patients. Utilizing an acute and maintenance phase, researchers found that bupropion treatment was associated with symptom remission in 68% of patients beginning bupropion treatment and in 84% of those who completed the acute phase. Of patients whose depression remitted and continued to receive bupropion, 87% completed the subsequent 6-month study interval and none had a recurrence. Significant improvement in A1C was observed among patients achieving MDD remission during the acute phase. Reductions in weight observed in the subset showing remission over the acute (1.5 kg) and maintenance (2.1 kg) phases were modest. It is encouraging that clinically important improvements in A1C can occur in the absence of large changes in body mass.
Reduction in depression was also accompanied by improvements in some diabetes self-care behaviors and glycemic control. According to the authors, this is the first study to demonstrate a broad improvement in diabetes self-care during depression treatment. There is the possibility that better compliance with lifestyle and diet regimens contributed to the improvement in diabetes parameters.
Nevertheless, I have certain reservations about the robust findings of this study; it was not a randomized, controlled trial?which may explain the inordinately high rate of depression remission (87%) and the absence of depression recurrence in patients who completed acute and maintenance phases. Yet, any improvement in glycemic control is welcome and, in the case of diabetic patients with depression, there is a special need for accurate diagnosis and treatment.
These researchers also evaluated effects of maintenance treatment with the SSRI sertraline in MDD patients with diabetes.4 This randomized, double-blind, placebo-controlled, maintenance treatment trial involved patients who recovered from MDD during 16 weeks of open-label sertraline treatment. Of patients initially assigned to the sertraline group, 43.3% recovered from MDD. This group then continued to receive sertraline or placebo and were followed for up to 52 weeks, or until depression recurred. The primary outcome was length of time to MDD recurrence. The secondary outcome was glycemic control, which was assessed via serial determinations of A1C levels. The study demonstrated that, in patients with diabetes, maintenance therapy with sertraline prolonged the depression-free interval following recovery from MDD.
At last year?s ADA meeting, a study suggested that antidepressants actually increase the risk of developing Type 2 diabetes.5 Researchers from the Diabetes Prevention Program, sponsored by the National Institutes of Health, reported that depression alone did not predict progression to diabetes in patients at risk for the disease. In fact, antidepressants were associated with a 2?3-fold increase in risk. The increase was not found in patients at high risk for diabetes who were taking both antidepressants and metformin. The study was based on a partial re-analysis of the Diabetes Prevention Program. A large-scale study, the program found that patients at higher risk for Type 2 diabetes who lost excess weight and exercised were often able to prevent diabetes onset. This was the first large study to examine antidepressant effect on patients at high risk for Type 2 diabetes. At baseline, 5.7% of patients were already taking antidepressants. During the study, approximately 13.5% of patients used antidepressants at some point. Researchers found that being on any kind of antidepressant increased diabetes risk. In addition, the type of antidepressant taken (tricyclic antidepressant or SSRI) did not change the result in the placebo or lifestyle arm of the study. The protective effect of metformin could not be explained. Of patients who developed diabetes, causes included weight gain, less physical activity, or increased insulin resistance.
Many experts have speculated that depression leads to elevated levels of the stress hormone cortisol, which increases blood glucose levels and causes more fat to collect around the abdominal area. Mid-section fat, as opposed to fat on the hip and thigh area, tends to be more metabolically active and causes damage to organs including the heart, liver, and pancreas. This process could also explain the link between depression, heart disease, and stroke. Thus, antidepressants would appear to help in this situation. Studies suggest that effects of depression treatment are determined by multiple factors. Improved self-care, dietary control, and compliance with diabetes medications are important. Weight-independent physiological mechanisms involved could include changes to the limbic-hypothalamic and hypothalamic-pituitary-adrenal axes, hippocampal glucocorticoid receptors, the autonomic nervous system, and immune or inflammatory processes. However, other research suggests that depression predisposes patients to diabetes. There has also been speculation that corticosteroids, which are elevated in depression, may have an impact on glucose homeostasis, and thus cause diabetes.
Based on available evidence, the cause and effect between depression, antidepressants, and diabetes remains poorly understood, and the association between antidepressants and diabetes risk remains uncertain. No compelling evidence exists showing that treating depression reduces the risk of developing diabetes; but the effects of depression are reason enough to opt for treatment.
References
1 Carnethon MR, Biggs ML, Barzilay JI, et al. Longitudinal association between depressive symptoms and incident type 2 diabetes mellitus in older adults: the cardiovascular health study. Arch Intern Med. 2007;167(8):802-807.
2 Georgiades A, Zucker N, Friedman KE, et al. Changes in depressive symptoms and glycemic control in diabetes mellitus. Psychosom Med. 2007;69(3):235-241.
3 Lustman PJ, Williams MM, Sayuk GS, Nix BD, Clouse RE. Factors influencing glycemic control in type 2 diabetes during acute- and maintenance-phase treatment of major depressive disorder with bupropion. Diabetes Care. 2007;30(3):459-466.
4 Lustman PJ, Clouse RE, Nix BD, et al. Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2006;63(5):521-529.
5 Diabetes Prevention Program Research Group. Depression symptoms, antidepressant medicine use and risk of developing diabetes in Diabetes Prevention Program participants. Paper presented at: 66th Annual Scientific Sessions of the American Diabetes Association; June 9?13, 2006; Washington, DC.
