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Key Take Home Message – Don’t Panic

“I do think that the numbers suggest that depression carries an increased risk of stroke, but one substantially lower than the increased stroke risk associated with smoking, which is 2 to 3 times increased, high blood pressure, 5 to 6 times increased, diabetes, 2 to 4 times, and even high cholesterol,” he pointed out. “Pregnancy or use of hormone therapies also carries a somewhat higher risk of stroke, in the vicinity of a hazard ratio of 2.”

Depression Linked to Increased Stroke Risk in Women

Fran Lowry

From Medscape Medical News > Neurology

August 11, 2011 — Depression is associated with a moderately increased risk for future stroke, a new study shows.

Dr. An Pan (RIGHT)

After 6 years of follow-up, researchers found that among women in the Nurses’ Health Study (NHS), depression was associated with a 29% increased risk for total stroke, and that the risk increased to 39% if antidepressant medications, particularly selective serotonin reuptake inhibitors, were used.

“We know that depression is associated with an increased risk of cardiovascular disease, and we also know that poststroke depression is common,” An Pan, PhD, a research fellow at Harvard School of Public Health in Boston, Massachusetts, and the lead author of the study, told Medscape Medical News.

Depression can increase stroke risk through a variety of mechanisms, Dr. Pan explained. “Recognizing that depressed individuals may be at a higher risk of stroke could help the physician focus on not only treating the depression, but treating stroke risk factors such as hypertension, diabetes, and elevated cholesterol, as well as addressing lifestyle behaviors such as smoking and exercise.”

Their findings are published online August 11 in Stroke.

History of Depression

In their study, Dr. Pan and his colleagues sought to determine whether depression itself could increase the risk for future stroke.

From 2000 to 2006, they followed 80,574 women 54 to 79 years of age without a history of stroke in the NHS. Depressive symptoms were assessed with a Mental Health Index score in 1992, 1996, and 2000. Clinically significant depressive symptoms were defined as a score of 52 or less.

The women were asked about their use of antidepressant medication every 2 years, beginning in 1996. They also reported whether they had been diagnosed with depression by a physician every 2 years, beginning in 2000.

During the 6 years of follow-up, 1033 incident stroke cases were documented — 538 ischemic strokes, 124 hemorrhagic strokes, and 371 strokes of unknown origin.

After adjustment for age, the study showed that having a history of depression was associated with an increased risk for total stroke, with a hazard ratio (HR) of 1.49 (95% confidence interval [CI], 1.30 to 1.70).

The risk was lessened but remained significant after major comorbidities, including history of hypertension, hypercholesterolemia, diabetes, cancer, and heart disease (HR, 1.29; 95% CI, 1.13 to 1.48), were controlled for.

For women who used antidepressant medication, the HR was 1.39; (95% CI, 1.15 to 1.69) if they also had a Mental Health Index score of 52 or less or diagnosed depression, or if they had neither (HR, 1.31; 95% CI, 1.03 to 1.67).

Current depression was linked to a greater risk for stroke than a history of depression. Women who reported that they were currently depressed had a 41% increased risk for stroke (HR, 1.41; 95% CI, 1.18 to 1.67).

In comparison, women who only had a history of depression had a nonsignificantly elevated risk (HR, 1.23; 95% CI, 0.97 to 1.56), compared with women who reported no diagnosis of depression or antidepressant use.

He added that the decision to use antidepressant medication at this time should be up to the physician and patient. “Further studies are needed to investigate whether antidepressant medication itself can increase the risk or act as a marker for depression severity,” he said.

Active Depression

From these data it does appear that active depression is a risk factor for stroke, just as it is for myocardial infarction and sudden death, Howard Kirshner, MD, professor and vice chair of the Department of Neurology at Vanderbilt Medical Center in Nashville, Tennessee, told Medscape Medical News.

“I do think that the numbers suggest that depression carries an increased risk of stroke, but one substantially lower than the increased stroke risk associated with smoking, which is 2 to 3 times increased, high blood pressure, 5 to 6 times increased, diabetes, 2 to 4 times, and even high cholesterol,” he pointed out. “Pregnancy or use of hormone therapies also carries a somewhat higher risk of stroke, in the vicinity of a hazard ratio of 2.”

“It would have been helpful to know that treatment of depression reduced the risk of stroke,” Dr. Kirshner added. “That was not found in this study, however, in that nurses on antidepressants had a hazard ratio of 1.39, higher than those with a history of depression, almost equal to those with current depression. It is not clear from the discussion whether antidepressant use was just a marker for depression, or whether the drugs themselves could carry a risk of stroke.”

The study raises the question of what people with depression should do, he said. “It would be helpful to have a study showing what happens to the risk if depression is successfully treated, either with psychotherapy or with medications.”

The picture is likely to be complex. For example, results of the Fluoxetine in Motor Recovery of Patients with Acute Ischemic Stroke (FLAME) study, published recently in the Lancet Neurology (2011;10:123-30), showed that stroke patients treated with the antidepressant fluoxetine had better motor recovery after a stroke. Conversely, a recent study published in the American Journal of Psychiatry (2011;168:511-521) suggested that antidepressant use was associated with an increased risk for stroke.

This study was funded by the National Institutes of Health. Dr. Pan and Dr. Kirshner have disclosed no relevant financial relationships.

Stroke 2011; 42: Published online August 11, 2011.