Unapproved prescriptions draw increased attention
Fri May 19, 2006 10:28 AM ET
By Kim Dixon
CHICAGO, May 19 (Reuters) - One of the most widely-prescribed medications for sleeplessness was never actually sanctioned by U.S. regulators to treat insomnia.
The drug, a 25-year-old medication called trazodone approved for depression, illustrates the ubiquity of so-called off-label prescriptions.
One in five prescriptions [!] in the United States is written to treat a condition for which the drug was not approved by the U.S. Food and Drug Administration, according a study released earlier this month in the Archives of Internal Medicine, a medical journal.
The practice is drawing more attention these days as drugmakers aggressively market drugs to both doctors and patients, experts said. Because of this, the study's authors suggest that the FDA should consider a more active role in off-label regulation.
"You have colleagues and patients asking for these therapies," said Randall Stafford, a sleep researcher at Stanford University, internal care doctor and co-author of the study, the first major review of off-label use.
"But when you look at the evidence there is not nearly as much (research) as one might hope -- for drugs used by millions of people," he said.
Writing off-label prescriptions by doctors is legal, though drugmakers cannot market drugs for uses not approved by the FDA.
The off-label study reviewed roughly 200,000 doctor-patient interactions, in which 160 common drugs were prescribed. It found that a third of off-label use occurs without the support of major research.
The most widely prescribed drug for unapproved use is Pfizer Inc.'s (PFE.N: Quote, Profile, Research) epilepsy drug Neurontin, which is often prescribed for the treatment of bipolar disorder and chronic pain, the study said.
That's despite the fact that Pfizer, the world's biggest drugmaker, paid the government $430 million in 2004 to settle charges it illegally promoted the drug for unapproved uses.
PEOPLE KEPT SLEEPING
Though trazodone was sold originally under the Desyrel brand to treat depression, doctor experience led to its widespread use as an insomnia drug.
"It was marketed as an anti-depressant in the early 1980s but it never really caught on because people kept falling asleep," said Susan Esther, a sleep physician in North Carolina. "We don't have a lot of research data to hang our hats on."
She and other doctors said that off-label drug prescriptions illustrate the trial and error nature of medical practice, where clinical experience and word-of-mouth referrals drive many decisions.
With trazodone, "there are no guidelines, positive or negative" for doctors, leaving them to experiment, said David Neubauer, associate director at the Johns Hopkins Sleep Disorder Center.
In most cases, off-label uses lack big placebo-controlled trials; therefore pharmaceutical companies play a large role in influencing doctors' prescribing patterns, experts said.
For instance, the makers of trazodone rivals Ambien and Lunesta funded several studies highlighting rare side effects of trazodone such as irregular heartbeat, which one researcher said are biased.
"In a move that may astonish even the most jaded critics, makers of sleeping pills are now paying doctors to publish bad things about competing drugs," Tufts University psychiatry professor Daniel Carlat wrote in a May 9 New York Times opinion piece.
Drugmakers more often seek to broaden the potential patient pool for their drugs and step over the line in marketing drugs beyond approved uses, according to Stanford's Stafford and other doctors.
"In consumer advertising, I've been struck by the fact that there are some ads that don't focus on what the drug is used for," he said, leaving a drug name and a vague idea in patients' minds before they enter the doctor's office.
Stafford emphasized that some off-label uses do have hard evidence, despite lack of official FDA approval. But the FDA should become more involved in helping doctors and patients figure out which ones work, he said.
The study concluded: "Should the decision to sanction additional therapeutic uses without regulatory scrutiny consider the evidence or be left to market forces?" |
