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By Herb Newborg

Medical Doctors Often Wrong About Drugs' FDA Approval Status
Physicians prescribe medications for off-label uses, mistakenly believing there's FDA approval.

Physicians frequently prescribe medications for off-label uses, mistakenly believing there's FDA approval for those indications, according to a survey of doctors.

More than 40% of respondents believed one or more drugs had FDA approval for indications that have uncertain or no supporting evidence, said G. Caleb Alexander, MD, of the University of Chicago, and colleagues.

Overall, the survey participants knew the FDA approval-status for only about half of 14 drug-indication pairs, such as gabapentin (Neurontin) for diabetic neuropathy (off label, some supporting evidence), they reported online in Pharmacoepidemiology and Drug Safety.

"These results indicate an urgent need for effective methods of disseminating information to physicians about the level of evidence supporting off-label drug uses, with specific attention to common off-label uses known to be ineffective or to carry unacceptable risk of harm," the authors concluded.

Off-label prescribing is common in clinical practice. In some settings, off-label prescribing may represent the standard of care, the authors noted. However, studies have shown that off-label prescribing frequently occurs when there is uncertain or no evidence supporting the efficacy of a drug for an indication. FDA approval of a drug for a specific indication reflects a threshold of supporting evidence, the authors continued. On the other hand, lack of approval for specific indications may occur for reasons that do not relate to supporting evidence, such as the safety of a drug for an unapproved use.

To examine physicians' knowledge of evidence supporting common drug-indication pairs, the authors conducted a random-sample national survey of primary care physicians and psychiatrists identified from the AMA Masterfile.

Physicians selected for the study received a three-page, 63-item questionnaire based on 14 common drug-indication pairs. The pairs varied with respect to FDA-approval status and level of supporting evidence. Respondents indicated whether each pair had FDA approval.

Psychiatrists and primary care physicians were given lists of drug-indication pairs that differed except for six pairs: Depakote for bipolar disorder, mania; Lexapro for panic disorder; Neurontin for diabetic neuropathy; Trazodone for insomnia; Effexor for adjustment disorder; and Seroquel for dementia with agitation.

The authors received 457 usable surveys, 54% from psychiatrists and 46% from primary care physicians. On average, primary care physicians had prescribed 10 of the drugs at least once in the previous year for any indication, and psychiatrists had prescribed 11.

Respondents knew the correct FDA-approval status of only 55% of the drug-indication pairs.

When the pairs were limited to drugs the respondents had prescribed in the past year, the mean accuracy increased slightly to 60%.

Overall, psychiatrists demonstrated better knowledge of FDA approval status (66% ) than did primary care physicians (38%).

The authors found a significant association between a physician's belief that an indication had FDA approval and greater evidence supporting efficacy for the indication. However, 41% of physicians believed that at least one drug-indication pair with uncertain or no supporting evidence had FDA approval, such as Seroquel for dementia with agitation.

All of the drugs erroneously prescribed for conditions without documented efficacy or formal safety testing for non approved uses carry serious side effects. Among them: constipation, agitation, dizziness, drowsiness, weight gain, dry mouth, fatigue, increased sweating, diarrhea, stomach upset, blurred vision, decrease in sexual desire or ability, headache, convulsions (seizures), itching or skin rash, lightheadedness or fainting, lockjaw, menstrual changes, problems in urinating or in holding urine, swelling, talking, feeling, and acting with excitement and activity you cannot control, trouble in breathing , anxiety, agitation, panic attacks, hostility or aggressiveness, engaging in unusual or dangerous activities, restlessness or inability to sit still, extreme elation or feeling of happiness that may switch back and forth with a depressed or sad mood, hallucinations, fast heart rate, chest palpitations, difficulty sleeping, nausea, ejaculation problems, extreme tiredness and insomnia.

At least five of the drugs wrongly prescribed carry the FDA’s most severe warning: an increased risk of suicide and suicidal thoughts.