At least 21% of prescriptions written by American doctors are written for medical conditions that the drugs have not been proven to treat. The prescriptions are "off-label," which means that the drugs are being used in ways that have not been formally tested or approved by the Food and Drug Administration (FDA) as safe and effective.

A drug also is considered off-label if it's used…

  • For a type of person that the drug has not been tested on (such as children or the elderly).
  • At a dosage not approved by the FDA.
  • By itself, when labeling specifies it should be used with other drugs.
  • With other drugs, when labeling specifies it should be used alone.

Key finding: A study in Archives of Internal Medicine showed that 73% of off-label prescriptions do not have good scientific evidence justifying their use.

Off-Label, On Trial

It is illegal for pharmaceutical companies to promote their drugs for off-label use, but billions of dollars in possible profits are a strong incentive to circumvent the law. In a study published in PLoS Medicine, researchers from Harvard Medical School analyzed 18 cases where drug companies were prosecuted for off-label marketing that resulted in $79 billion in judgments against the companies.

The researchers found that the drug companies tried to expand the use of the drugs to unapproved unapproved disease subtypes (such as prescribing an antidepressant for mild depression when it has been approved only for severe depression and to unapproved drug doses.

They also found that the drug companies used marketing schemes to influence doctors, including direct financial incentives" (85% of the time)..."self-serving presentations of the scientific literature about the drug (76%)...sponsorships of teaching 64%) and research (20%)... and free drug samples (20%).

In other words, doctors were essentially being bribed and duped by drug companies to prescribe drugs off-label.

Randall S. Stafford, MD, PhD, from the Stanford Prevention Research Center, and his colleagues conducted research to identify the most problematic off-label drugs, publishing the results in Pharmacotherapy. Each of the riskiest drugs had one or more of the following problems…

1. It lacked scientific evidence for off-label use.

2. It raised safety concerns.

3. It was newer to the marketplace, meaning that rare or long-term adverse effects were less likely to be known.

4. It cost more than FDA-approved drugs for the same problem.

5. It was marketed heavily by drug companies.

Most of these drugs fall into three classes of medications...

Atypical Antipsychotics

This new generation of medicines is now the top-selling class of drugs in the US, replacing cholesterol-lowering agents as number one. They're called "atypical" to distinguish them from older antipsychotics. The drugs are approved to treat the psychosis of schizophrenia and bipolar disorder.

Main off-label uses: In 2008, there were 9 million off-label prescriptions written for antipsychotic drugs in the US, more than double the amount in 1995. They are used for a wide range of psychiatric conditions, including the behavioral problems of dementia, such as severe agitation (the most common use)...depression...long-term maintenance in bipolar disorder (the drugs are approved only for short-term use)...obsessive-compulsive disorder.. and post-traumatic stress disorder (PTSD).

Biggest risks: With long-term use, the drugs tend to cause weight gain and the subsequent development of type 2 diabetes. And in the elderly with dementia, they are linked to an increased incidence of heart problems and a higher death rate.

The drugs: Quetiapine (Seroquel), risperidone (Risperdal), olanzapine (Zyprexa), aripiprazole (Abilify) and ziprasidone (Geodon).

Shocking finding: Researchers in the department of psychiatry at the University of Pennsylvania studied 2,597 people with Parkinson's disease and psychosis (hallucinations and delusional thinking), a common symptom of the disease. Fifty percent of the patients were prescribed antipsychotic drugs. Of those, most received off-label atypical antipsychotics-in spite of the fact that there are no scientific studies showing that the prescribed drugs work for psychosis in Parkinson's...that two of the drugs (Zyprexa and Risperdal) have been shown to worsen Parkinson's symptoms.. and that there is a "black box" warning on these antipsychotics alerting doctors that they increase the risk for death in those patients who have been studied. Less than 2% of the patients received clozapine (Clozaril)-an older atypical antipsychotic that scientific studies show does improve psychosis in Parkinson's. The study was reported in the Archives of Neurology.


This is another top-selling class of drugs, approved for major depression and a few other conditions.

Main off-label uses: In a study of Medicaid patients, 75% of prescriptions for antidepressants were off-label. Off-label uses include treating mild depression (dysthymia)...bipolar disorder...insomnia... hot flashes...urinary incontinence and bladder infections...diabetic neuropathy...and chronic pain.

Biggest risks: Antidepressants don't pose the same level of health risk as antipsychotics. But while they may have a low risk of harming you, there is little scientific evidence showing that their off-label use helps the conditions for which they are being prescribed. Why spend money on a drug with potential side effects and no proven benefit?

The drugs: Escitalopram (Lexapro), bupropion (Wellbutrin), sertraline (Zoloft), venlafaxine (Effexor) and duloxetine (Cymbalta).

Antiseizure Drugs

These drugs are approved to treat epilepsy.

Main off-label uses: They're commonly prescribed for chronic pain-in fact, they're often used without making certain that other approaches have been tried.

Biggest risks: When an off-label drug replaces approved therapies for chronic pain and when there's evidence that the pharmaceutical industry is promoting that particular use, then there's a serious question as to whether that drug is the best treatment for chronic pain.

The drugs: Gabapentin (Neurontin) and pregabalin (Lyrica).

Questions To Ask Your Doctor

If you or a family member is prescribed an antipsychotic, antidepressant or anti-seizure drug. ask your doctor the following question...

  • Could you give me more background on the evidence that this drug will work. for the condition I have and be beneficial for me?

Best answer: The drug is FDA-approved for the condition and has been recommended by an expert group based on a review of the available scientific literature.

If that's not the answer, consider other treatment options.

Also, many doctors tend to prescribe new, expensive, brand-name drugs over tried-and-true drugs.

Example: The newer diabetes drug sitagliptin (Januvia) is often prescribed over the generic drug metformin-even though Januvia has not been proven to work better than metformin.

This practice is widespread for both off-label and FDA-approved drugs, so ask your doctor…

  • What's the rationale for putting me on this expensive new drug?

Best answer: The newer drug was proven in clinical studies to work better than the older drug. (This is rarely the case.) If that's not the answer, consider the older, safer, proven drug.

When Off-Label Drugs Are OK

There are several situations where off-label I drugs may be helpful…

Your doctor has tried FDA-approved drugs for your condition and they haven't worked... or there are no approved drugs for your condition. Using an off-label drug allows the doctor to explore other options that might work. The drug is moving through the process of FDA approval for your condition. An off-label prescription for that drug gives you early access to a valuable medication.

Antibiotics vs. Laser Surgery

Low-dose antibiotics for gum disease may contribute to antibiotic resistance. Dentists often use the antibiotic doxycycline hyclate (Periostat) to prevent infection during traditional oral surgery for gum disease—but this means that the patient may not respond when he/she later needs an antibiotic for an illness.

Self-defense: Laser surgery for gum disease. The laser kills bacteria, reducing risk for infection.

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