If depression induces heart disease and magnifies the lethality of existing cardiac conditions, does treatment of depression curb heart disease?
The question was important enough to spawn a major international study known as SADHART, for Sertraline Antidepressant Heart Attack Randomized Trial. The goal was to recruit 400 depressed patients hospitalized for heart attack or angina. All received standard treatment for heart disease, and were then randomly assigned to receive medication for depression, either placebo or active treatment with sertraline (Zoloft, Pfizer).
Researchers in seven countries initially screened nearly 12,000 cardiac patients to find 600 who met all the criteria for major depression without having confounding medical or psychiatric conditions. Of the 600 patients, 369 signed consent forms, and 186 were randomized to receive sertraline while 183 received placebo for 24 weeks.
The initial goal was to determine whether antidepressant treatment was safe in cardiac patients. "No one had ever given antidepressants immediately after myocardial infarction before," Dr. Glassman explained. "It's a dangerous time for giving other drugs in the presence of unhealed tissue."
The presumed cardiac instability translated into difficulties getting the study funded. Drug companies did not leap to close the knowledge gap. Eventually, Pfizer funded the study.
And sertraline proved "unbelievably safe." There were no more cardiovascular incidents among those treated with the SSRI than among those who received the placebo.
As a group, 66% of those drug-treated were significantly improved after 24 weeks, versus 53% of those on placebo. That added up to a very suggestive difference in favor of active treatment of depression, but not to a definitive difference. The effects of treatment were more pronounced among patients with recurrent depression. "If a patient has no prior episode of depression, there was no difference between the drug and placebo," Glassman reported. But among patients with any prior episodes of depression, 75% of those treated after a heart attack responded to sertraline, compared to 51% of those getting placebo.
Among patients with two prior episodes of depression, active post-MI treatment was even more effective. Seventy-eight percent of those receiving sertraline experienced depression relief, versus 45% on placebo.
"These patients are on 11 other drugs," says Dr. Glassman by way of pointing out the potential for troublesome drug interactions in heart attack victims. "They're taking aspirin, beta blockers, cholesterol-lowering statins, and many other drugs. The antidepressants caused very little in the way of side effects."
They also reduced the occurrence of life-threatening cardiac events. The sertraline-treated were less likely to experience every type of cardiac catastrophe—less mortality, fewer heart attacks, less angina, less congestive heart failure.
They were 23% less likely to have any life-threatening event. While the numbers were suggestive, they did not reach statistical significance. "It's not proven yet," says Glassman, who orchestrated the multimillion-dollar study, "but I think it's real."
"The SSRIs are mediocre antidepressants," adds Glassman. "They are not as effective as tricyclic antidepressants—but they cause far fewer side effects. They are also good against anxiety. And they are the only drugs that are good against post-traumatic stress disorder." Many depressed patients are also afflicted with anxiety. As a result, Glassman says, he turns to SSRIs 60% of the time in treating new patients.
"The tricyclics double the risk of heart attacks. There is no difference with SSRIs; it looks as if they protect against heart attack in some way.
"Only one drug changes the risk of having a heart attack—the SSRIs." Further, he says, "it looks as if it's the same story with strokes," although there is not as much evidence yet as with heart attack.
Glassman contends that a vastly larger study is needed to test definitively whether treating depression reduces cardiac mortality. "It's unclear what the mechanism is. It's unclear if the drug is working via depression. I suspect it's working in multiple ways."
If the jury is still out on whether antidepressants save lives, it's rendered a verdict on improving lives. On measures of quality of life—how much illness impairs a patient's ability to function in life—the impact is "dramatic," insists Glassman. "The more chronic the depression, the more difference treatment with sertraline makes in the quality of life. Psychological factors have a huge impact on the quality of life. They are more important than physical measures, even in heart disease."
The resounding conclusion? "Depression in the presence of coronary syndromes should be treated," says Glassman.
While his group addressed the case for sertraline, he points out that "there is also lots of evidence for using omega-3 fatty acids to treat heart disease and depression."
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