Diabetes and Depression Combo Poses Management Challenge

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Diabetes and Depression Combo Poses Management Challenge
DOC News June 1, 2007
Kurt Ullman
Volume 4 Number 6 p. 1

Both conditions show similar metabolic abnormalities
This is part one of a two-part series on the complex interplay between depression, diabetes, and related risk factors. In July we will examine CVD's role, as well as origins of the overlap.

Caring for patients with type 2 diabetes can be precarious at best, but when the disease is compounded by depression, treatment options become increasingly important so that one condition doesn't needlessly exacerbate the other.

"The depression-diabetes interaction is complex and probably bidirectional," says Wayne Katon, MD, professor and vice chair in the department of psychiatry and behavioral sciences at University of Washington Medical School in Seattle. "There is good evidence showing that, if you have depression earlier in your life, there's about a 35% increased risk of developing type 2 diabetes. On the other hand, when you compare those with diabetes to age-matched controls without [diabetes], studies have generally shown a twofold increase in the prevalence of depression among those with diabetes."

Why this happens is not yet well understood, although multiple reasons probably are at play. Both depression and type 2 diabetes show some similar metabolic abnormalities, including increased insulin resistance and lack of suppression in the dexamethasone suppression test.1 There are other suggestions that both conditions might be associated with white matter brain disease.2

"Where this gets interesting is whether there are some diabetes-specific factors that play a role in this association," notes Alan Jacobson, MD, senior vice president and director of behavior and mental health programs at Joslin Diabetes Center in Boston. "For example, some suggest depression's effect on the brain and neuronal control over beta-cells in the pancreas could lead to diabetes."

A growing body of research shows that chronic illnesses, including diabetes, can be involved in development of depression. Further, the more chronic conditions a person is battling, the greater the likelihood of the mood disorder. Thus, when diabetes results in complications such as nephropathy, neuropathies, or blindness, the stress adds up.

"Against the backdrop of chronic illness in general, I think it is fair to say that, when the illness is debilitating or painful, depression becomes more common," says Jacobson. "The more serious or the higher number of chronic illnesses seen in a patient, the more likely they are to suffer from depressive disorders. This may be especially true in patients with diabetes where lack of control can add neuropathies, nephropathies, or blindness to the baseline stressors of diet change, multiple medications, and blood testing."

Indeed, up to 15% of patients with type 1 or type 2 diabetes also meet the criteria for depression.3

Theoretically, depression can trigger diabetes in a number of ways. "Depression may lead to a more sedentary life, which may then result in obesity and other risk factors for diabetes," says Caroline Carney Doebbeling, MD, associate professor of medicine and psychiatry at Indiana University School of Medicine in Indianapolis. "Also, depressed people tend to exercise less, drink more alcohol, and eat higher-fat diets, all of which can contribute to the development of diabetes."

To further complicate matters, depression has been shown to have an adverse impact on diabetes outcomes. A meta-analysis of 27 studies published in 2001 found both type 1 and type 2 diabetes to be significantly associated with retinopathy, nephropathy, macrovascular complications, and sexual dysfunction.4 Some studies suggest that depression has an impact on control as measured by higher glycated hemoglobin (A1C) levels.5 Others have shown a relationship between mental illness and failure to receive appropriate diabetic care.6

"Diabetes by itself is a complex illness that requires a lot of self-care," says Jacobson. "Depression clearly makes all of those things tougher to do and therefore they may get more complications, which increases morbidity and mortality. Our research has shown depressed diabetics dying at a rate twice that of nondepressed [diabetes] patients over a 4-year period."

INTERVENTIONS FOR THE PRIMARY CARE PHYSICIAN
Because of the high levels of the depression-diabetes comorbidity, all three experts agree that screening for mood disorders is an important part of care. Currently, no formal guidelines exist for how often this should be completed. They suggest at least yearly screening along with regular testing for retinopathy and other complications.

Many depression assessment tools are available, however. The Patient Health Questionnaire-9 (www.pfizer.com/pfizer/download/do/phq-9.pdf) is one such tool often suggested. It has the advantages of being short and easy to use, and also involves assessment of other parameters of mental health at the same time.

"At the primary care level, an important caveat is that the physician must be willing to either do or arrange the necessary follow-on treatment," says Doebbeling. "To screen is not good enough; there has to be a program in place to address the problem. The primary care provider either should feel comfortable treating depression or should have a referral plan to a psychiatrist, psychologist, or other mental health professional."

DEPRESSION TREATMENT CONSIDERATIONS
Depression most likely is undertreated in those with both diseases. Only 30% of patients with depression and diabetes receive adequate antidepressant treatment and fewer than 20% complete four or more visits for psychotherapy.7

"The key for the primary care physician is to follow a patient closely enough to make sure they are adhering to the medication instructions," says Katon. "Giving your patient a prescription and telling them to come back in 4–6 weeks is a prescription for failure. About 40% of people will drop out of treatment during that time if they are not followed closely."

For the most part, treating depression with newer antidepressive medications is safe and effective. However, some of the older drugs still in use can present challenges when prescribed to patients with diabetes. Monoamine oxidase inhibitors (Nardil, Pfizer; Parnate, GlaxoSmithKline) are linked to sudden hypoglycemia requiring emergency treatment.8 While they may be safer for those whose diabetes is controlled by diet alone, this effect is especially important for those taking insulin, sulfonylureas, and other medications that lower blood glucose.

Selective serotonin reuptake inhibitors, known collectively as SSRIs, are widely prescribed and appear to be safe and effective in treating depression in diabetes. The lead medication in the class, fluoxetine (Prozac, Sarafem), reduces depressive symptoms, and at least one study shows a trend toward improved glycemic control.

Other classes of drugs such as the serotonin-norepinephrine reuptake inhibitors venlafaxine (Effexor, Wyeth) and duloxetine (Cymbalta, Eli Lilly) and tetracyclic antidepressants mirtazapine (Remeron, Organon USA) have not yet been extensively studied in comorbid depression and diabetes. However, venlafaxine and buproprion are more effective than placebo in treating pain from diabetic neuropathy.9, 10 Duloxetine was the first of this class to have diabetic neuropathy included as a labeled indication.11

If the clinician feels comfortable treating depression, absent suicidal thought in the patient, there is probably no reason to refer the patient to a specialist initially. However, if the symptoms do not entirely resolve after a trial of one medication, transferring care is appropriate, according to those interviewed.

"I have a strong belief in a three-pronged treatment for depression," says Doebbeling. "I use an antidepressant and have the patient work with a coach such as a psychologist or nurse on supportive counseling. Finally, I urge patients to exercise, which improves mood and has well-documented positive effects on diabetes."

Clinicians also need to keep in mind that treatment may unmask or worsen preexisting problems. "For example, an antidepressant may reveal previously unknown orthostatic hypotension in somebody with autonomic neuropathy," says Jacobson. "These medications may make gastroperesis worse. Because of these confounds, it might be prudent to be more cautious, initiating treatment with lower initial dosing and longer ramp-ups."

Although comorbid diabetes and depression can be a treatment challenge, the bottom line is that they are treatable. "Depression in diabetes is just as treatable as it is in any other population," says Jacobson. "There are studies available that show standard depression treatments work in diabetic populations pretty much the way you would expect." {blacksquare}

Footnotes

FYI
A patient education brochure is available from the National Institute of Mental Health at www.nimh.nih.gov/publicat/NIMHdepdiabetes.pdf.

References

1. Talbot F, Nouwen A: A review of the relationship between depression and diabetes in adults: Is there a link? Diabetes Care 23: 1556–1562, 2000.[Abstract]

2. Lenze E, De Witte C, McKeel D, et al.: White matter hyperintensities and gray matter lesions in physically health depressed subjects. Am J Psychiatry 156:1602–1607, 1999.[Abstract/Free Full Text]

3. Katon W, Von Korff M, Ciechanowski P, et al.: Behavioral and clinical factors associated with depression among individuals with diabetes. Diabetes Care 24:1069–1078, 2004.

4. de Groot M, Anderson R, Freedland KE, et al.: Association of depression and diabetes complications: A meta-analysis. Psychosom Med 63:619–630, 2001.[Abstract/Free Full Text]

5. Lustman PJ, Anderson RJ, Freedland KE, et al.: Depression and poor glycemic control: A meta-analytic review of the literature. Diabetes Care 23:934–942, 2000.[Abstract]

6. Jones LE, Clarke W, Carney CP, et al.: Receipt of diabetes services by insured adults with and without claims for mental disorders. Med Care 42(12):1167 –1175, 2004.[Medline]

7. Katon WJ, Simon G, Russo J, et al.: Quality of depression care in a population-based sample of patients with diabetes and major depression. Med Care 42:1222–1229, 2004.[Medline]

8. Goodnick PJ: Diabetes mellitus and depression: Issues in theory and treatment. Psychiatr Ann 27:353–359, 1997.

9. Rowbotham MC, Goli V, Kunz NR, et al.: Venlafaxine extended release in the treatment of painful diabetic neuropathy: A double-blind, placebo-controlled study. Pain 110: 697–706, 2004.[Medline]

10. Semenchuk MR, Sherman S, Bennet D, et al.: Double-blind, randomized trial of buproprion SR for the treatment of neuropathic pain. Neurology 57:1583–1588, 2001.[Abstract/Free Full Text]

11. U.S. Food and Drug Administration: FDA approves drug for neuropathic pain associated with diabetes. September 7, 2004. Available online at http://www.fda.gov/bbs/topics/news/2004/NEW01113.html. Accessed April 20, 2007.


© 2007 American Diabetes Association