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NEW YORK (Reuters Health) - In 2004, Pfizer, the world's largest drug company, agreed to plead guilty and pay more than $430 million to settle charges it had illegally marketed the epilepsy drug Neurontin for unapproved uses.
Now, a study in the Journal of Clinical Psychiatry questions whether the lawsuit ended up fueling spending on other epilepsy drugs instead of curbing so-called off-label prescribing.
Doctors are allowed to prescribe drugs for uses that haven't been approved by U.S. health regulators, but companies are prohibited from marketing their products for such purposes.
"In recent years there have been several large lawsuits setting out to punish pharmaceutical companies for illegal off-label promotion," said Meredith Chace, a pharmaceutical policy fellow at Harvard Medical School in Boston. "We suspected that it might be possible that there could be unintended consequences of that."
She and her colleagues analyzed data from the federal health insurance programs Medicare and Medicaid spanning the years 2001 to 2005.
They focused on bipolar disorder, one of several disorders treated off-label with Neurontin (known generically as gabapentin).
Since the first media report about the off-label lawsuit surfaced in March 2002, Neurontin's market share dropped from 21 percent of the total epilepsy drugs prescribed for bipolar disorder to 15 percent.
Meanwhile, off-label use of four other epilepsy drugs - one of which was later approved - took off or continued to rise in patients with bipolar disorder. Even spending on Neurontin rose, despite the lower use.
"Unfortunately, the study suggests that doctors continued to turn to unproven medications to treat bipolar disorder," said Dr. Daniel Carlat, a psychiatrist and director of the Pew Prescription Project, which promotes policies to limit doctor-industry relationships that could affect patient care.
NOT AS DAMAGING AS INTENDED?
According to the new report, in 2000 - two years before news of the lawsuit broke - Neurontin sales approached $1 billion, mostly due to off-label use. Chace said she felt certain the negative media coverage of Neurontin accounted for part of the market share drop and that it's possible the manufacturer raised prices in anticipation of this.
Overall, the researchers estimate that government spending on epilepsy drugs for bipolar disorder increased by more than $200 million following the Neurontin lawsuit.
And that's not counting potential prescription changes in other diseases where the drug was used off-label, such as migraine, restless legs syndrome and various pain conditions.
"The unintended consequences are substitution of similarly unsubstantiated products and an increase in spending overall," Chace told Reuters Health.
She added that clinical trials have shown Neurontin is not effective in bipolar disorder, although it may still help some patients.
One of the study's limitations is that it doesn't include information on how much drugmakers spent on marketing their products. It's possible that Pfizer's competitors pounced on the chance to ramp up promotion of their own medications, explaining some of the increase in spending, Chace said.
That caveat was echoed by Carlat, whose position is partly funded by a grant that came out of the Neurontin settlement.
"It's not clear that the lawsuit was responsible for the increase in anticonvulsant prescribing and therefore increased spending," Carlat told Reuters Health by email. "The study did not control for the effects of other influences on prescribing decisions, such as marketing by other anticonvulsant manufacturers and scientific information about the efficacy of the other drugs."
Dr. Randall S. Stafford, who has studied drug marketing but was not involved in the new work, said it's likely the lawsuit was "not as damaging to Pfizer as intended."
"Neurontin was coming off patent anyway and the lawsuits simply accelerated the desired shift from off-label Neurontin use to off-label Lyrica use," Stafford told Reuters Health by email.
Lyrica, an epilepsy drug whose generic name is pregabalin, is still on patent. It was involved in another marketing lawsuit against Pfizer, which resulted in a $2.3 billion settlement in 2009.
Pfizer declined to comment on the new findings, saying that they relate "to a nearly decade-old settlement."
Chace said authorities should work closely with medical organizations to inform doctors about crackdowns on off-label marketing so they can respond appropriately.
"They should know what is going on and what the treatment guidelines recommend," she said.
Carlat argued that the issue is not how doctors get their news.
"What's most important is that the medical community - academic medicine, medical association, etc. - do a better job of teaching doctors about evidence-based treatment guidelines," he said.
SOURCE: bit.ly/Rmgspg Journal of Clinical Psychiatry, online October 16, 2012.