Neurontin is approved by the FDA for use, in combination with older seizure medications, for a relatively rare type of seizure disorder known as partial seizure, and pain after an episode of shingles known as postherpetic neuralgia. The potential number of patients needing Neurontin for these two uses is limited, yet over 15.6 million prescriptions were dispensed for this drug in 2003. Neurontin was originally marketed by Parke-Davis, a subsidiary of Warner-Lambert, which in turn was acquired by Pfizer, in 2000.
On March 14, 2002, the New York Times revealed that the manufacturer of Neurontin illegally promoted the drug to prescribing physicians for at least 11 "off-label" (unapproved) medical conditions, using their own employees, often physicians, euphemistically called "medical liaisons," as the messengers. Apparently, much of the "evidence" for the safety and effectiveness of Neurontin for these 11 unapproved uses was fabricated by the drug's manufacturer. The fabrications involved paying physicians for the use of their names as authors of medical journal articles on unapproved uses for Neurontin articles that had actually been written by others working under the direction of the company's marketing department.
The company's promotional strategy for Neurontin became public as the result of a lawsuit and the release of court papers. The questionable uses for Neurontin are :
1. Bipolar Disorder : Psychiatrists were told that early results from trials evaluating Neurontin in the treatment of bipolar disorder indicated a 90% response rate when the drug was started at 900 milligrams per day and increased to 4,800 milligrams per day. No such results existed. In fact, the only type of clinical trial being conducted at the time was a pilot study. According to court documents, Parke-Davis was in possession of clinical data indicating that increasing the dose did not increase Neurontin's effect. The FDA-approved dosage for Neurontin in adults is 900 to 1,800 milligrams per day.
Any data regarding Neurontin in bipolar disorder were anecdotal and of unclear scientific value. Most of the published reports on the use of Neurontin in bipolar disorder had been written and sponsored by Parke-Davis, a fact that was hidden. Medical liaisons of the company were trained to tell psychiatrists that there were no reports of adverse reactions with Neurontin when used in psychiatric illness. In fact, such reports had been given to Parke-Davis by health care professionals, but the company attempted to hide this information from physicians.
2. Pain Syndromes, Peripheral Neuropathy, and Diabetic Neuropathy : Parke-Davis medical liaisons were instructed to report that "leaks" from clinical trials demonstrated that Neurontin was highly effective in the treatment of a number of pain syndromes and that a 90% response rate in the management of pain was being reported. No such evidence existed. Medical liaisons were trained to claim support for these findings as a result of inside information despite the fact that no such information existed. The only basis for these claims was anecdotal evidence of minimal, if any, scientific value. Many of the published case reports, according to the court papers, had been created and sponsored by Parke-Davis in articles that frequently hid the company's involvement in the creation of the article. The company's payment for the creation of these case reports was also concealed.
3. Treatment of Epilepsy Alone (as Monotherapy) : Medical liaisons were strongly encouraged to push neurologists to prescribe Neurontin as the only drug to treat epilepsy, in spite of the fact that studies found it safe and effective only when used in combination with other seizure drugs. Neurologists were told that substantial evidence supported the company's claim that Neurontin was effective when used alone for seizure. In fact, at the time the court papers were filed, Parke-Davis knew that clinical trials using Neurontin alone in seizure were inconclusive. One of Parke-Davis's clinical trials showed that Neurontin alone was not effective. The vast majority of patients in the study taking Neurontin were unable to continue with Neurontin alone. In the same study, there was no significant difference between doses of 600, 1,200, and 2,400 milligrams. Nevertheless, Parke-Davis continued to urge doctors to use higher doses than approved by the FDA.
In 1997, the FDA rejected the company's application for approval of Neurontin as monotherapy in the treatment of seizures.
4. Reflex Sympathetic Dystrophy (RSD) : Physicians were informed that extensive evidence demonstrated the efficacy of Neurontin in the treatment of RSD, a condition of pain and tenderness following traumatic injury to a limb. Again, the only evidence was in anecdotal reports of little or no scientific value. The Parke-Davis medical liaisons were trained to imply that case reports, most of which had been created or sponsored by the company, were actually scientifically valid studies.
5. Attention Deficit Disorder (ADD) : Pediatricians were told that Neurontin was effective for the treatment of ADD. No hard data to support this claim existed only occasional anecdotal evidence. Parke-Davis medical liaisons were trained to report that large numbers of physicians had success in treating ADD with Neurontin when no such case reports existed.
6. Restless Leg Syndrome (RLS) : This is another condition in which company medical liaisons were trained to refer to a growing body of evidence relating to RLS when no such scientific data existed. The only reports were anecdotal, the majority of which had been sponsored or created by Parke-Davis.
7. Trigeminal Neuralgia : The company represented Neurontin as a treatment for trigeminal neuralgia, a syndrome of severe bursts of facial pain, when no scientific data supported this claim only occasional anecdotal reports. No evidence was available that Neurontin was as effective as currently available and less expensive painkillers.
8. Post-Herpetic Neuralgia (PHN) : This is a syndrome of severe pain following a herpes virus infection that causes shingles. Physicians were told that 75 to 80% of all PHN patients were successfully treated with Neurontin. Again, no clinical trial data supported such a claim at the time.
The FDA did approve Neurontin for PHN in June 2002. Two studies of Neurontin in PHN have been published, showing a modest effect for the drug compared to placebo. We will reserve our opinion on the therapeutic value of Neurontin in PHN until the FDA makes their reviews of the drug publicly available.
9. Essential Tremor Periodic Limb Movement : No scientific data supported Parke-Davis's claim that Neurontin was effective for this disorder, just anecdotal reports of dubious scientific value.
10. Migraine : Claims that Neurontin was effective in the treatment of migraine headache were made by company medical liaisons and were alleged to be based on early results from clinical trials. Pilot studies had been suggested and undertaken, but no early results existed to support these claims. The data were purely anecdotal and most case reports were either created or sponsored by Parke-Davis.
11. Drug and Alcohol Withdrawal Seizures : It was suggested by the company that Neurontin be used in the treatment of drug and alcohol withdrawal seizures despite the lack of any evidence supporting the use of the drug for these conditions.
Parke-Davis's made-up uses for Neurontin turned the drug into a "blockbuster" the Wall Street description for any drug that brings in $1 billion a year or more.
The court papers offer a remarkable insight into the ethics (or lack thereof) of a major multinational pharmaceutical company. A senior marketing executive at Parke-Davis was quoted during a meeting as saying to medical liaisons :
Pain management, now that's money. Monotherapy, that's money. We don't want to share these patients with everybody, we want them on Neurontin only. We want their whole drug budget, not a quarter, not half, the whole thing....That's where we need to be holding their hand and whispering in their ear: 'Neurontin for pain, Neurontin for bipolar, Neurontin for monotherapy, Neurontin for everything...' I don't want to hear that safety crap either, have you tried Neurontin, every one of you should take one just to see there is nothing [that the drug is safe], it's a great drug.
If you or a family member are taking Neurontin for one of the unapproved uses listed above, you and the prescribing doctor should evaluate your need for Neurontin.
On March 14, 2002, the New York Times revealed that the manufacturer of Neurontin illegally promoted the drug to prescribing physicians for at least 11 "off-label" (unapproved) medical conditions, using their own employees, often physicians, euphemistically called "medical liaisons," as the messengers. Apparently, much of the "evidence" for the safety and effectiveness of Neurontin for these 11 unapproved uses was fabricated by the drug's manufacturer. The fabrications involved paying physicians for the use of their names as authors of medical journal articles on unapproved uses for Neurontin articles that had actually been written by others working under the direction of the company's marketing department.
The company's promotional strategy for Neurontin became public as the result of a lawsuit and the release of court papers. The questionable uses for Neurontin are :
1. Bipolar Disorder : Psychiatrists were told that early results from trials evaluating Neurontin in the treatment of bipolar disorder indicated a 90% response rate when the drug was started at 900 milligrams per day and increased to 4,800 milligrams per day. No such results existed. In fact, the only type of clinical trial being conducted at the time was a pilot study. According to court documents, Parke-Davis was in possession of clinical data indicating that increasing the dose did not increase Neurontin's effect. The FDA-approved dosage for Neurontin in adults is 900 to 1,800 milligrams per day.
Any data regarding Neurontin in bipolar disorder were anecdotal and of unclear scientific value. Most of the published reports on the use of Neurontin in bipolar disorder had been written and sponsored by Parke-Davis, a fact that was hidden. Medical liaisons of the company were trained to tell psychiatrists that there were no reports of adverse reactions with Neurontin when used in psychiatric illness. In fact, such reports had been given to Parke-Davis by health care professionals, but the company attempted to hide this information from physicians.
2. Pain Syndromes, Peripheral Neuropathy, and Diabetic Neuropathy : Parke-Davis medical liaisons were instructed to report that "leaks" from clinical trials demonstrated that Neurontin was highly effective in the treatment of a number of pain syndromes and that a 90% response rate in the management of pain was being reported. No such evidence existed. Medical liaisons were trained to claim support for these findings as a result of inside information despite the fact that no such information existed. The only basis for these claims was anecdotal evidence of minimal, if any, scientific value. Many of the published case reports, according to the court papers, had been created and sponsored by Parke-Davis in articles that frequently hid the company's involvement in the creation of the article. The company's payment for the creation of these case reports was also concealed.
3. Treatment of Epilepsy Alone (as Monotherapy) : Medical liaisons were strongly encouraged to push neurologists to prescribe Neurontin as the only drug to treat epilepsy, in spite of the fact that studies found it safe and effective only when used in combination with other seizure drugs. Neurologists were told that substantial evidence supported the company's claim that Neurontin was effective when used alone for seizure. In fact, at the time the court papers were filed, Parke-Davis knew that clinical trials using Neurontin alone in seizure were inconclusive. One of Parke-Davis's clinical trials showed that Neurontin alone was not effective. The vast majority of patients in the study taking Neurontin were unable to continue with Neurontin alone. In the same study, there was no significant difference between doses of 600, 1,200, and 2,400 milligrams. Nevertheless, Parke-Davis continued to urge doctors to use higher doses than approved by the FDA.
In 1997, the FDA rejected the company's application for approval of Neurontin as monotherapy in the treatment of seizures.
4. Reflex Sympathetic Dystrophy (RSD) : Physicians were informed that extensive evidence demonstrated the efficacy of Neurontin in the treatment of RSD, a condition of pain and tenderness following traumatic injury to a limb. Again, the only evidence was in anecdotal reports of little or no scientific value. The Parke-Davis medical liaisons were trained to imply that case reports, most of which had been created or sponsored by the company, were actually scientifically valid studies.
5. Attention Deficit Disorder (ADD) : Pediatricians were told that Neurontin was effective for the treatment of ADD. No hard data to support this claim existed only occasional anecdotal evidence. Parke-Davis medical liaisons were trained to report that large numbers of physicians had success in treating ADD with Neurontin when no such case reports existed.
6. Restless Leg Syndrome (RLS) : This is another condition in which company medical liaisons were trained to refer to a growing body of evidence relating to RLS when no such scientific data existed. The only reports were anecdotal, the majority of which had been sponsored or created by Parke-Davis.
7. Trigeminal Neuralgia : The company represented Neurontin as a treatment for trigeminal neuralgia, a syndrome of severe bursts of facial pain, when no scientific data supported this claim only occasional anecdotal reports. No evidence was available that Neurontin was as effective as currently available and less expensive painkillers.
8. Post-Herpetic Neuralgia (PHN) : This is a syndrome of severe pain following a herpes virus infection that causes shingles. Physicians were told that 75 to 80% of all PHN patients were successfully treated with Neurontin. Again, no clinical trial data supported such a claim at the time.
The FDA did approve Neurontin for PHN in June 2002. Two studies of Neurontin in PHN have been published, showing a modest effect for the drug compared to placebo. We will reserve our opinion on the therapeutic value of Neurontin in PHN until the FDA makes their reviews of the drug publicly available.
9. Essential Tremor Periodic Limb Movement : No scientific data supported Parke-Davis's claim that Neurontin was effective for this disorder, just anecdotal reports of dubious scientific value.
10. Migraine : Claims that Neurontin was effective in the treatment of migraine headache were made by company medical liaisons and were alleged to be based on early results from clinical trials. Pilot studies had been suggested and undertaken, but no early results existed to support these claims. The data were purely anecdotal and most case reports were either created or sponsored by Parke-Davis.
11. Drug and Alcohol Withdrawal Seizures : It was suggested by the company that Neurontin be used in the treatment of drug and alcohol withdrawal seizures despite the lack of any evidence supporting the use of the drug for these conditions.
Parke-Davis's made-up uses for Neurontin turned the drug into a "blockbuster" the Wall Street description for any drug that brings in $1 billion a year or more.
The court papers offer a remarkable insight into the ethics (or lack thereof) of a major multinational pharmaceutical company. A senior marketing executive at Parke-Davis was quoted during a meeting as saying to medical liaisons :
Pain management, now that's money. Monotherapy, that's money. We don't want to share these patients with everybody, we want them on Neurontin only. We want their whole drug budget, not a quarter, not half, the whole thing....That's where we need to be holding their hand and whispering in their ear: 'Neurontin for pain, Neurontin for bipolar, Neurontin for monotherapy, Neurontin for everything...' I don't want to hear that safety crap either, have you tried Neurontin, every one of you should take one just to see there is nothing [that the drug is safe], it's a great drug.
If you or a family member are taking Neurontin for one of the unapproved uses listed above, you and the prescribing doctor should evaluate your need for Neurontin.