When a drug is approved for release, it is approved for a specific use and normally in specific doses to a particular age group.  This could be an antidepressant that was approved for the treatment of depression in adults.  If it were prescribed by a doctor to a child, it would be an off-label use.  While this use is not recommended by the FDA, a licensed medical doctor can legally prescribe the drug for a totally different use.  

One of the disturbing trends in society today is the increase of off-label prescribing to children.  In an article entitled “Off-label Prescribing to Children in the United States Outpatient Setting”, in the March-April 2009 Academy of Pediatrics, a study of pediatric prescriptions to children 0-17 concluded that 62% of these visits resulted in off-label prescribing. 

David C. Radley, MPH, Stan N. Finkelstein, MD and Randall S. Stafford, MD, PhD did a study for the American Medical Association on off-label prescribing.  They concluded that in 2001 an estimated 150 million prescriptions, approximately one-fifth of all prescriptions filled that year, were off-label.  They concluded, “Off-label medication use is common in outpatient care, and most occurs without scientific support. Efforts should be made to scrutinize underevaluated off-label prescribing that compromises patient safety or represents wasteful medication use.”

Dr. Randal Stafford co-wrote “Off-label Prescribing Among Office-Based Physicians”.  This article was published in the May 8, 2006 Archives of Internal Medicine.  The article concluded,

“Off-label medication use is common in outpatient care, and most occurs without scientific support. Efforts should be made to scrutinize under-evaluated off-label prescribing that compromises patient safety or represents wasteful medication use. Many drugs are being prescribed to treat things for which they were not approved by the FDA.  For example, many antidepressants are being prescribed for the treatment of pre-menstrual syndrome (PMS) or elbow pain or are being used to promote weight loss.”  

One off-label use that has led to many cases of dependence and even addiction relates to Actiq, contained in a lollipop.  Actiq contains fentanyl citrate, an opioid that acts in the body in the same manner as heroin.
Prime Therapeutics LLC, a pharmacy benefit management company, did a study that    concluded that there were  significant patterns of “off-label” prescribing for Actiq among patients taking the powerful painkilling “lollipop.”  According to Pat Gleason, PharmD, Director of Medical and Pharmacy Integration Services for Prime, “The FDA has only approved Actiq for use by cancer patients who are already taking a long-acting, chronic painkiller but suffer from severe spikes in pain.  The Prime study, however, found that only slightly more than 10 percent of the patients receiving the drug over a three-month period in 2005 met those guidelines. Nearly 90 percent of Actiq prescriptions in our study were off-label, or not prescribed according to the guidelines set forth by the FDA.”
Why is the off-label use of this synthetic heroin drug disturbing?  The Actiq label contains the following warning:


ACTIQ contains fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. ACTIQ can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing ACTIQ in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion.

Actiq is a dangerous drug and is often prescribed by physicians not trained in pain management and who are treating only the symptoms and not the cause of the pain.  The use of this drug leads to physical dependence and even addiction.  (Dependence is when you experience uncomfortable withdrawal symptoms when you stop taking the substance.  Addiction is when you continue to use a drug because of the way that you feel after taking the drug—often described as a type of euphoria feeling or a “mellow” feeling or sometimes, in the case of many drugs, to not feel something such as pain or sorrow.)

Wellbutrin is approved for treating depression, for weight loss or even to treat the side effects of other anti-depressant drugs.  Zoloft is approved for the treating of depression but it is often prescribed to treat premature ejaculation.

While it is legal for the doctor to prescribe drugs for off-label uses, it has been not legal for the drug manufacturers to promote off-label use.  (Food, Drug, and Cosmetic Act (FDAC) at U.S.C. 21 §§301-97).   There was an exception included in the Food and Drug Administration Modernization Act of 1997  if a doctor, without prompting from the drug company or its representatives, asks the drug company for information on off-label use of their drug. 

The FDA takes the position that a drug manufacturer may not promote its drug for an unapproved use, and that any such promotion is false and misleading simply because it is not FDA-approved.  This position has led to a number of very large settlements against drug companies.

The drug companies have consistently been caught violating this prohibition on marketing the unsolicited use of their drugs.  The settlements have resulted in fines totaling billions of dollars, but most agree that until the drug company executives are imprisoned for their crimes, which often caused deaths or serious health problems, there will be no real incentive for the drug companies to stop marketing off-label uses.  The reason is that  the settlements, even though large by any standard, are only a fraction of what the drug companies make from their activities and are regarded as marketing expenses.

As they have repeatedly stated in presentations to the stock brokerage community, the primary purpose of the drug companies is to increase their profits by increasing the sale of their drugs.  This is not unreasonable for a company owned by stockholders, but it is important to understand when looking at some of the methods used by these companies to withhold vital information that might cause doctors to prescribe another drug.  

Many pharmaceutical sales representatives have written articles and books on how they were trained to convince doctors that their company’s drug would work for things that were off-label and, all too often, for uses for which there was no unbiased medical evidence of any kind.  Drug company promotion of off-label uses for their drugs is against the law, but it is apparently happening all the time.  

How do the drug companies ensure that more and more of their drugs are sold—often for off-label use?  One way is by spending 2.5 times as much on marketing and administration as they do on research and development of new drugs. 

In his excellent book Fight For Your Health, Byron Richards points out the marketing efforts of the drug companies and what they do to sell their products.  He quotes from an article by Dr. Jerome Kassirer, professor at Tufts University School of Medicine, that appeared in the Boston Globe titled, “How Drug Lobbyists Influence Doctors.”  

Dr. Kassirer said,

“While lobbying groups spend about $2 billion to convince politicians to do their bidding, pharmaceutical companies spend nearly 10 times that much to influence the nation’s 700,000 physicians to prescribe the newest and most expensive drugs.  I imagine that many people who regularly watch television assume that the companies are spending most of their advertising budget to influence consumers, but no.  Nearly 85-90 percent is spent on doctors, for free drug samples, speakers’ fees, consultation fees, and ‘educational’ grants… It is difficult enough to get reliable data on drug benefits and risks from industry-supported studies, but when physicians and physicians’ organizations, who should know better, knowingly exaggerate the efficacy of new drugs and underplay their complications, the consequences for the health of the public and individuals like you and me are too close for comfort.”

However, the future of off-label marketing prosecutions is in doubt. In UNITED STATES Of America, Appellee, v. Alfred CARONIA, Defendant–Appellant, Docket No. 09–5006–cr, in a two to one decision, the court held,

“We conclude simply that the government cannot prosecute pharmaceutical manufacturers and their representatives under the FDCA (Federal Food, Drug, and Cosmetic Act) for speech promoting the lawful, off-label use of an FDA-approved drug.”  

It is important to point out that this case does not prevent the prosecution of  false and misleading off-label marketing, and it is only binding on courts in Connecticut, New York, the District of Columbia and Vermont.  The FDA has apparently decided not to appeal this ruling and it is likely that any future FDA prosecutions for promoting off-label use will be more difficult.