Monthly Archives: June 2014

06/4/14

Twentieth Century Snake Oil

My wake up call to the deceptive practices of some pharmaceutical companies came when I read The Truth About Drug Companies by Marcia Angell in 2004. Angell speaks credibly to the issue since she is a former editor-in-chief of the prestigious The New England Journal of Medicine. One example that stayed with me over the years because of its sheer, incredible audacity was how Neurontin was made into a multi-billion dollar selling drug.

In 1994 Neurontin was approved by the FDA as a secondary treatment for epilepsy—to be used when patients failed to respond to other anti-seizure drugs. The patent was due to expire in 1998 (it eventually received a two year extension). So the company began to target doctors to prescribe it for unapproved, off-label uses, “mainly common but vague conditions like pain and anxiety, and also as the sole treatment for epilepsy.”

Although doctors are legally permitted to prescribe an FDA approved drug for any use whatsoever, it is illegal for a drug company to market a drug for off-label uses. According to Angell, what Parke-Davis did was to pay academic experts to put their names on flimsy research papers that showed the drug worked for certain off-label conditions. This “research” typically fell below the standard required by the FDA for an approval of the drug for a particular condition.

Angell said the studies were small and poorly designed. “Some of the articles contained no new data at all, just favorable comments about Neurontin.” Parke-Davis hired medical education and communication companies to prepare the articles and paid academic researchers to put their names on the articles as authors. Once the articles were published in academic journals, “medical liaisons” would visit doctor’s offices to answer questions about the research.

Parke-Davis also sponsored educational meetings and conferences. The “authors” of the papers would describe the positive results of the drug’s off-label uses. Not only were the speakers paid, “but often the doctors in the audience were paid” as consultants. This was to get around the anti-kickback laws. “Consultant meetings were sometimes little more than vacations for potential high prescribers of Neurontin.”

The result was Neurontin becoming a blockbuster drug, with over 2 billion in sales for 2003. “About 80 percent of prescriptions that year were for unapproved uses—conditions like bipolar disorder, post-traumatic stress, disorder, insomnia, restless legs syndrome, hot flashes, migraines, and tension headaches.” In fact, Neurontin became an all-purpose restorative for chronic discomfort. An internal company e-mail described Neurontin as “the ‘snake oil’ of the twentieth century.”

A generic version of Neurontin (gabapentin) went on sale in August of 2004. The website Drugs.com reported that Neurontin sales in 2004 were approximately $2 billion dollars. In 2005, sales dropped to $259.4 million. It dropped from the 10th best selling drug in 2004 to the 123rd best selling drug in 2005. By 2006, Neurontin had dropped out of the top 200 best selling drugs.

In May of 2004 the pharmaceutical manufacturer Warner-Lambert, of which Parke-Davis was then a division, agreed to pay $430 million to resolve criminal charges and civil liabilities in connection with its “illegal and fraudulent promotion of unapproved uses” for Neurontin. See the Department of Justice announcement here. Part of the global agreement was that Pfizer, Inc., the owner of Warner-Lambert since June of 2000, agreed to training and supervision of its marketing and sales staff to ensure that “any future off-label marketing conduct is detected and corrected on a timely basis.”

In December of 2013, the U.S. Supreme Court upheld a $142 million award to the Kaiser Foundation Health Plan by Pfizer for marketing Neurontin for unapproved uses. The court also allowed two other lawsuits against Pfizer to proceed. A key factor in the court’s decision apparently was an analysis by Meredith Rosenthal of the Harvard School of Public Health. “Her analysis found that marketing Neurontin for such unapproved uses as bipolar disorder, neuropathic pain and migraines caused physicians to write 43 million off-label prescriptions.” She further calculated that 99.4 percent of the prescriptions for bipolar disorder were caused by illegal marketing.

The two outstanding lawsuits noted above now seem be settled. In April of 2014 Pfizer agreed to pay $190 million to settle a lawsuit that was first filed in 2002.  The lawsuit claimed the pharmaceutical company took several steps to delay the entry of Neurontin into the generic drug market. According to a Reuters news article, along with other delay tactics, Pfizer allegedly filed “sham patent infringement lawsuits.” And just announced on May 30th, 2014 in this report by Bloomberg, Pfizer agreed to pay $325 million to settle a lawsuit brought by health-care providers claiming that Pfizer marketed Neurontin for unapproved uses. In both settlements, Pfizer did not admit to any wrongdoing.

So why does the history of unapproved marketing of Neurontin (gabapentin) rent so much space in my head and this blog? The Wall Street Journal recently ran an article titled “A Pill to Cure Addiction?” on “new medicines” that are being tested to help people quit drug and alcohol habits. The “new drug,” touted as a possible cure for addiction, is gabapentin.

06/2/14

Marijuana as a “Gateway” Drug

Marty O’Rourke, who discipled me when I was young in the Christian faith, would sometimes tell others that when he first met me, I was smoking a joint. Technically, I had just taken a toke and was passing the joint to another person. Yes, I did sometimes smoke marijuana in the 1970s and I did inhale. But I never went on to try harder drugs. There was no “gateway effect” with my marijuana use.

There has been a back-and-forth debate for years about whether or not marijuana is a “gateway” drug. Typically three truths support the idea:

  • Marijuana users are more likely than nonusers to progress to hard-drug use.
  • Almost all the individuals who have used both marijuana and hard drugs first used marijuana.
  • A higher frequency of marijuana use raises the likelihood of using hard drugs at a later time.

But like me, the overwhelming majority of marijuana users do not progress to other drugs.  The 2012 National Survey on Drug Use and Health found marijuana was the most commonly used illicit drug, with 18.9 million users in the month prior to the survey. This constituted 79 percent of all the reported illicit drug use. About two thirds (62.8%) of illicit drug users had used only marijuana in the past month.

Sociologists say marijuana is typically used within a specific social context. So the progression to more dangerous drugs happens as a result of the person associating with a subculture that condones drug experimentation. The social group, not marijuana, is the “gateway.”

Similarly, Andrew Morral suggested there was a common factor explanation for the gateway effect with marijuana. The individual’s opportunities and inclination determine the risk of future hard drug use, not prior marijuana use. He commented that his research did not disprove the gateway theory. But it showed another plausible explanation for the association of marijuana use and hard drug use.

The Marijuana Policy Project listed several articles (i.e., Is Marijuana a “Gateway Drug”?) that challenged the marijuana gateway theory. However, the articles tended to conclude there was a common factor explanation or a mediating factor, like stress or genetics, to the gateway effect with marijuana. They debunked the notion of marijuana use as a causative factor leading to harder drug use, but they do not effectively challenge the above three facts supporting the marijuana gateway theory.

Counseling people with drug and alcohol problems has shown me that they often experimented with marijuana before trying harder drugs. The three statements above have been true time and time again. Marijuana use may not be a causative gateway to future experimentation with more dangerous drugs, but it was often a stepping stone taken before an individual tried the cocaine, heroin, or prescription drug high. And a recent study by researchers at Yale concluded that previous alcohol, cigarette and marijuana use were each associated with the current abuse of prescription opioids. “Previous marijuana use was 2.5 times more likely than no previous marijuana to be associated with subsequent abuse of prescription opioids.”

The executive director of the Connecticut chapter of NORML, Erik Williams, said the Yale study failed to show a strong link between marijuana and the use of harder drugs. “This is just another propaganda study that tries to turn a casual link into a causal relationship.” The Yale’s study lead author agreed there wasn’t proof of a concrete connection between opioid abuse and prior marijuana use. But, she said, “It’s a red flag.” It suggests there is a potential association there.

Marijuana does not seem to be a “gateway” that leads to experimentation with more dangerous drugs. But it often is a stepping stone taken on the path to harder drugs in a person’s addictive career.