Rethinking reserpine: Should it be revived?
Anti-hypertensive costs pennies a day
It’s cheap and effective but it’s disappeared from the therapeutic landscape. In the age of managed care, how did this dinosaur of antihypertensive therapy bite the dust? One physician says a series of bad media hits, coupled with a lack of a corporate defender for the drug, caused the rapid demise of reserpine in the late 1970s.
"That’s something I’ve seen before," says Frank Lederle, MD, of the Minnesota Veterans Affairs Medical Center in Minneapolis. That is, drug companies with a big stake in a product’s success may battle negative publicity with high-powered tactics. If a drug company can go to bat for a beleaguered product perhaps by sponsoring a study to refute bad publicity it can rescue its investment.
Unfortunately, generic drugs like reserpine, usually have no corporate sponsors, Lederle says, because nobody is making any money from them. "Niacin has some of the same problems," he adds. It’s an effective, inexpensive cholesterol treatment that frequently gets bad press about the intense flushing that it causes.
Reserpine came on the U.S. market in 1953, after Robert Wilkins, a Massachusetts General Hospital researcher, confirmed the drug’s antihypertensive effect. Originally derived from the Indian snakeroot plant, the active component was isolated and synthesized in 1956.
Reserpine entered a market desperate for a reasonable cure for hypertension and the drug became the first to enjoy wide clinical use. No wonder. In the early 1950s, surgeons not cardiologists commonly treated high blood pressure by severing sympathetic nerves. In 1953, after Stalin died, "a leading New York neurologist," commenting on the antihypertensive treatment given the Russian leader on his death bed, told The New York Times the Russian doctors used an antiquated method for lowering Stalin’s blood pressure leeches. "Here, of course, we would puncture the vein to draw blood instead of using leeches," he said.
In a word, reserpine revolutionized the treatment of hypertension. Unfortunately, it was chronically dosed too high. At doses nearing 1 mg, reserpine caused side effects most notably, depression and peptic ulcers. Reserpine’s reputation suffered further when, in the 1970s, it was linked to breast cancer. By the time the breast cancer link had been disproved, the beta-blockers were already on line, and the first ACE inhibitor would soon follow. Reserpine’s golden age had come to an end.
Low doses of reserpine well-tolerated
But now some doctors are arguing for the inclusion of reserpine in the nation’s antihypertensive arsenal. They say at small doses even as low as 0.1 mg reserpine used in combination with a diuretic can control hypertension and lower the risk of a serious cardiovascular event in many patients with mild to moderate high blood pressure. And all at a cost of only pennies a day. In fact, an entire year’s worth of reserpine therapy costs less than a week’s worth of some antihypertensive drugs.
William Applegate, MD, of the University of Tennessee Medical School in Memphis, uses reserpine as a second-line agent in combination with a diuretic usually chlorthalidone. "Reserpine is one of those drugs shown in combination with a diuretic and I stress in combination with a diuretic to lower the risk of a stroke or heart attack," he says. Applegate avoids using the drug in patients with a history of depression or suicide attempts, and in patients with seasonal allergic rhinitis. About 20% of patients on reserpine experience nasal stuffiness.
Lederle also avoids prescribing the drug for those with depression, but not because he thinks low doses of the drug cause it. "I’ve avoided it in patients with depression. Not that I’m concerned these doses cause depression, but patients who get depressed will blame reserpine." He adds that you could make the same argument that beta-blockers cause depression.
The captopril example
The key to a reserpine resurgence may be in getting the word out about its favorable efficacy vs. side effect profile when given at a low dose something only discovered late in the drug’s market life. Applegate notes that captopril suffered terrible publicity when it was first introduced because it, too, was given in high doses and caused a severe side effect renal proteinuria. But the drug company caught the problem early on, lowered the dose, and the rest, as they say, is history. "Had reserpine had the same kind of truncated realization" that low doses worked, Applegate says, it might still have a place on many formularies.
"I’ve found it to be as useful [a drug] as any," Lederle says. "It’s another choice. There’s reasonable data. This drug has a long track record."
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