R.A. is a 58-year-old married man seen by his primary physician for scheduled care of diabetes. Diagnosed 4 years ago with type 2 diabetes, he is mildly obese (5 feet, 11 inches, 218 lb, body mass index 30.4 kg/m2) and hypertensive (blood pressure 165/92 mmHg), but otherwise has no evidence of coronary heart disease or other complications of diabetes. He uses insulin and has insufficient control of hyperglycemia (recent hemoglobin A1c [A1C] concentrations range from 10 to 11.5%). He does not perform blood glucose testing.

Six months ago, the patient started having difficulty falling and staying asleep. As a result, he felt tired and fatigued most of the time. He became less physically active, stopped exercising, and gained 12 lb. Then he gradually stopped socializing and eventually lost interest in most things, including sexual activity. During this time, he earnestly denied feeling sad or depressed. He has continued to work but has trouble concentrating, frequently forgets things, and feels impatient, irritable, and frustrated. For the past month, the constellation of symptoms has been persistent and interfering.

Physical examination was remarkable only for mild obesity. Routine laboratory and CT scan of the head were normal. R.A. was treated with alprazolam (Xanax), 0.25 mg at bedtime, which relieved the insomnia but had no effect on his other symptoms.

  1. Can a diagnosis of depression be established?

  2. Which treatment would be effective for R.A.?

  3. What are the potential benefits of depression treatment?

Can a diagnosis of depression be established?

The diagnosis of depression, or major depressive disorder, can be established even though, as in the case of R.A., the patient does not feel depressed, sad, or blue. Loss of interest or pleasure can serve as the major criterion for a depression diagnosis as long as at least four other defining symptoms are present (significant weight loss or gain, hypersomnia or insomnia, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or guilt, impaired concentration or indecisiveness, and recurrent thoughts of death or suicide). The symptoms must occur together, be severe, and persist daily over a period of at least 2 weeks. Applying these criteria, R.A. qualifies for a diagnosis of depression.

Depression without sadness, or nondysphoric depression (NDD), occurs more often in men than women and more often in those who are medically ill than in those who are not. Irritability, social withdrawal, and indecisiveness often figure prominently in the clinical presentation. While patients are likely to acknowledge these symptoms, they may resist considering the possibility of being depressed given the absence of sadness. In these situations, it can be useful to include the spouse, other family members, or significant others in the clinical interview to help identify existing affective symptoms and the degree of their interference with patients’ usual functioning.

The link between diabetes and depression has been extensively studied. Diabetes doubles the likelihood of co-morbid depression, making it present in ∼20% of patients with type 1 or type 2 diabetes. This psychiatric illness is associated with hyperglycemia and an increased risk for all complications of the metabolic disorder. The risk for coronary heart disease is three times greater in depressed than in nondepressed diabetic women. The subset of depressed diabetic patients with NDD has not been systematically studied, but irritability, a seminal feature of NDD, is associated with abnormalities in glucose metabolism. Of interest, many of the adverse effects of affective illness on the course of diabetes, including poor treatment compliance and hyperglycemia, were evident in R.A.

Which treatment would be effective for R.A.?

Evidence from recent controlled trials indicates that depression in diabetic patients can be treated effectively with conventional antidepressant medications or with cognitive behavior therapy (CBT). Improvement in depression by either approach often produces reductions in A1C test results of 0.5–1.2%. CBT is a particularly potent approach and is recommended for patients who are receptive to counseling and have adequate insurance or find it affordable. Counseling can be especially useful in helping patients impaired by diabetes complications develop effective coping strategies.

Conventional tricyclic antidepressants (TCAs; e.g., amitriptyline [Elavil] and nortriptyline [Pamelor]) and newer antidepressants such as the serotonin reuptake inhibitors (SSRIs; paroxetine [Paxil], fluoxetine [Prozac], and sertraline [Zoloft]) have equivalent efficacy, relieving depression in 50–60% of patients who complete 8–16 weeks of therapy. Antidepressant selection is based on such factors as presenting symptoms, concomitant medical conditions, drug interactions, and side effects. The potential for direct drug effects on glucose should also be considered and monitored. The available data suggest that the TCAs may induce mild hyperglycemia, whereas the SSRIs have an opposite effect. Consequently, the SSRIs and other contemporary antidepressants (such as nefazodone [Serzone] and venlafaxine [Effexor]) comprise the first-line pharmacotherapy for depression in diabetic patients. The TCAs, alone or in combination with a newer agent, may be favored when pain is a predominant complaint.

In all cases, it is important to set reasonable goals. Depression is rarely cured. Without specific antidepressant treatment, individual episodes do not rapidly remit and are not responsive to efforts focused solely on improving glycemic control. And although depression is acutely responsive to treatment, the disorder is highly recurrent. Afflicted patients suffer on average one episode annually throughout their lifetimes.

What are the potential benefits of depression treatment?

The benefits of depression management go beyond improved mood. Successful treatment produces a number of ancillary benefits, including restoration of normal sleep, pain relief and improved pain tolerance, decreased somatic preoccupation, enhanced sexual function, and improved illness coping and general functioning. Finally, relief of depression is associated with behavioral activation (increased social, occupational, and physical activity), improved compliance with diabetes treatment, and clinically significant improvements in glycemic control.

  1. Diabetes doubles the risk for depression, a psychiatric disorder that can be diagnosed in the absence of sadness. Loss of interest (including social withdrawal) and irritability are prominent features of this nondysphoric presentation of depression.

  2. Pharmacotherapy and counseling are viable treatment options. Depression in diabetes is a chronic condition; recurrent episodes requiring treatment are the norm, not the exception.

  3. Restoring mental health improves glycemic control and has ancillary beneficial effects on sleep, appetite, mentation, and physical, social, and sexual functioning.

Patrick J. Lustman, PhD, is a professor of medical psychology in the Department of Psychiatry; Marty L. Caudle, BS, PA-C, is a clinical research supervisor in the Department of Psychiatry; and Ray E. Clouse, MD, is a professor of medicine and psychiatry in the Department of Medicine, Division of Gastroenterology, at Washington University School of Medicine in St. Louis, Mo. Dr. Lustman is also a counseling psychologist at the Department of Veterans Affairs Medical Center in St. Louis.

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