Concerning the effects of depression on other major medical illnesses, Dr. Musselman reviewed some of the recent literature outlining how depression can influence the treatment of diabetes, stroke, and cancer. Current data indicate that the lifetime prevalence of depression in the general population may range from 2% to 15%, while it is much higher in patients with diabetes (9% to 27%), stroke (22% to 50%), or cancer (18% to 39%). Thus it is important to understand how depression may influence the treatment and long-term outcome of disease in these patients.
Depression is the most common psychological problem in the US. Minor Depression can be attributed to normal depressed feelings that arise because of a specific life situation, a side effect of medication, hormonal changes or physical illness, and does not usually require treatment. Major Depression (depressive illness) is a serious condition that result in extreme fatigue, sleep problems and eventually an inability to function. The exact cause is unknown, but it is thought to be a malfunction of brain neurotransmitters, which are chemicals that modulate moods. Major Depression is usually treated with a combination of psychotherapy and antidepressants which moderate or correct chemical imbalances in the brain. The group of antidepressants most frequently prescribed is the selective serotonin reuptake inhibitors (SSRIs) which regulate the neurotransmitter serotonin.
Several studies have now demonstrated that there is at least a 2-fold increased risk for developing depression in diabetic patients (type 1 or type 2); and among children and adolescents with type 1 diabetes. there is at least a 2- to 3-fold increase in the prevalence of depression. Women, minorities, and patients with lower socioeconomic status or physical disability are particularly at risk. Diagnosing depression in this population can also be difficult in that some of the key symptoms of both diseases overlap, including insomnia, fatigue, and changes in appetite. Fortunately, exclusive diagnostic criteria that eliminate somatic symptoms can be successfully employed in diabetes patients to discriminate depressed vs nondepressed patients.
Comorbid depression is known to increase the incidence of diabetic complications and is associated with poor adherence to diabetic medication, exercise, and diet, as well as poor glycemic control. Depression itself is also often associated with elevated glucocorticoids, which may further complicate diabetes. One study actually showed elevated glucose levels and insulin resistance in depressed patients following an oral glucose tolerance test. Indeed, depression may increase the risk for subsequently developing diabetes by nearly 2-fold.
It is clear that depression may further complicate diabetes, and it is important to ensure that the medications used to treat depression do not further worsen the condition. Monoamine oxidase inhibitors and TCAs in combination with sulfonylureas may induce hypoglycemia, and TCAs and mirtazapine may increase weight gain and HbA1c levels. However, SSRIs may be useful treatments in such patients. Fluoxetine, and presumably SSRIs in general, have been shown to produce an increase in insulin sensitivity, and sertraline has been shown to actually lower HbA1c levels. TCAs and SSRIs are also useful treatments for painful neuropathy, which is common in diabetics. The importance of treating depression in diabetic patients has also been shown, as treatment is associated with better quality of life and improved glycemic control.
Depression is also very common in stroke patients (approximately 15% to 25%) and is particularly common in females. One of the key questions is whether the stroke itself may directly affect the circuits involved in depression. A recent meta-analysis did not demonstrate that the location of stroke affected the incidence of poststroke depression , although it is possible that specific left-frontal cortical strokes may specifically increase the rate of depression.
Not surprisingly, poststroke depression is associated with a lack of recovery in daily activities. It is also associated with a reduced 10-year survival. In one study, approximately 60% of nondepressed patients were still alive 10 years after their initial stroke, compared to only about 30% of depressed patients. A 6-week study with citalopram demonstrated it was a safe and effective treatment in poststroke depression. A 52-week, double blind, randomized trial demonstrated sertraline significantly decreased the incidence of depression (all patients were not depressed when enrolled in the study) and was also associated with a decrease in adverse events. The rate of cardiovascular disease was particularly reduced in sertraline-treated patients, most likely due to the antiplatelet/anticlotting effects of SSRIs.
Depression is also very prevalent in cancer, with rates in some forms of cancer (pancreatic, oropharanygeal) as high as 40% to 50%. Chronic depression may also be a risk factor for developing cancer. The field of psychoneuroimmunology is particularly intriguing, and suggests possible mechanisms where the immune system and nervous system interact. One of the best demonstrations of the powerful interaction between these two systems is that immune activations resemble many of the cardinal symptoms (ie, “sickness behavior”). Cytokines, which are powerful modulators of the immune system and released after infection, can produce anhedonia, malaise, weakness, social withdrawal, anorexia, hypersomnia, and hyperalgesia, which are all reminiscent of the major symptoms in depression. Patients with major depression also have elevated serum concentrations of interleukin (IL)-6, a powerful proinflammatory cytokine.
Cytokines, particularly interferons, have also been used to treat a number of medical conditions, including severe viral infections (hepatitis) and certain cancers (particularly malignant melanoma). Although effective treatments, the use of interferons has been associated with a number of debilitating side effects including flu-like symptoms, fatigue, nausea, anorexia, vomiting, and, in some cases, mood changes, cognitive changes, and/or psychosis. As depressive symptoms are particularly common following long-term interferon treatment, Dr. Musselman’s group recently completed a study where they prophylactically treated nondepressed melanoma patients for 2 weeks with paroxetine (20-40 mg/day) prior to initiation of interferon treatment. After 12 weeks of interferon-alpha treatment, the rate of depression was approximately 50% in the placebo group, vs about 10% in the paroxetine group. Paroxetine was also associated with significantly higher compliance (fewer patients had to discontinue interferon-alpha treatment).
In conclusion, it is clear that depression hinders compliance, increases symptom burden, and also diminishes survival in both cancer and stroke. Chronic depression may also be an independent risk factor for diabetes and stroke. Although more work is needed, the existing evidence also suggests depression may exacerbate diabetes, stroke, and cancer. Dr. Musselman concluded by suggesting that prophylactic antidepressant administration may be reasonable in medical patients at high risk for depression.
Revision date: June 14, 2011
Last revised: by David A. Scott, M.D.