Neurontin is available as a tablet, capsule and oral solution. Neurontin accounted for $2.3 billion of Pfizer's sales in 2002 and is one of company's top-selling drugs.

Neurontin is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy. Neurontin is also indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients age 3-12 years.

On May 24, 2002, the FDA approved the use of Neurontin to treat post-herpetic neuralgia in adults. This is the residual pain some shingles patients suffer long after the original lesions have healed.

These are the only two FDA-approved uses for Neurontin. However, Neurontin is widely prescribed for other, off-label uses. While physicians are allowed to prescribe a drug for conditions other than those for which the drug is approved, drug companies are not allowed to promote off-label use.

Parke-Davis has been accused of heavily promoting Neurontin for more than a dozen off-label uses. According to the New York Times, much of the evidence supporting these off-label uses may have been fabricated. This story began to emerge after a former Parke-Davis employee, Dr. David P. Franklin, filed a "whistleblower" lawsuit against Parke-Davis in 1996. The U.S. government has intervened and is seeking millions of dollars in damages.

It is unclear whether this conduct continued after Pfizer acquired Warner-Lambert in 2000. Pfizer says that it did not. However, as recently as 2000, according to court papers from Dr. Franklin's suit, 88% of the revenue from Neurontin was for off-label uses.

A Series of Off-Label Uses

According to court documents from Dr. Franklin's lawsuit, and analysis by the respected consumer advocacy group Public Citizen, Parke-Davis pushed the following off-label uses for Neurontin:

1. Bipolar Disorder. Psychiatrists were told that early results from trials evaluating Neurontin in the treatment of bipolar disorder indicated a 90 percent 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 the 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 was 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 trained 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 percent 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 anti-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' 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 or 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 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 the 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 less expensive painkillers.

8. Essential Tremor and Periodic Limb Movement. No scientific data supported Parke-Davis' claim that Neurontin was effective for this disorder--just anecdotal reports of dubious scientific value.

9. 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 was purely anecdotal and most case reports were either created or sponsored by Parke-Davis.

10. 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.

Neurontin's Side Effects

The following side effects were observed in clinical trials of Neurontin for epilepsy:

Body As A Whole: Frequent: asthenia, malaise, face edema. Infrequent: allergy, generalized edema, weight decrease, chill. Rare: strange feelings, lassitude, alcohol intolerance, hangover effect.

Cardiovascular System: Frequent: hypertension. Infrequent: hypotension, angina pectoris, peripheral vascular disorder, palpitation, tachycardia, migraine, murmur. Rare: atrial fibrillation, heart failure, thrombophlebitis, deep thrombophlebitis, myocardial infarction, cerebrovascular accident, pulmonary thrombosis, ventricular extrasystoles, bradycardia, premature atrial contraction, pericardial rub, heart block, pulmonary embolus, hyperlipidemia, hypercholesterolemia, pericardial effusion, pericarditis.

Digestive System: Frequent: anorexia, flatulence, gingivitis. Infrequent: glossitis, gum hemorrhage, thirst, stomatitis, increased salivation, gastroenteritis, hemorrhoids, bloody stools, fecal incontinence, hepatomegaly. Rare: dysphagia, eructation, pancreatitis, peptic ulcer, colitis, blisters in mouth, tooth discolor, perlèche, salivary gland enlarged, lip hemorrhage, esophagitis, hiatal hernia, hematemesis, proctitis, irritable bowel syndrome, rectal hemorrhage, esophageal spasm.

Endocrine System: Rare: hyperthyroid, hypothyroid, goiter, hypoestrogen, ovarian failure, epididymitis, swollen testicle, cushingoid appearance.

Hematologic and Lymphatic System: Frequent: purpura most often described as bruises resulting from physical trauma. Infrequent: anemia, thrombocytopenia, lymphadenopathy. Rare: WBC count increased, lymphocytosis, non-Hodgkin's lymphoma, bleeding time increased.

Musculoskeletal System: Frequent: arthralgia. Infrequent: tendinitis, arthritis, joint stiffness, joint swelling, positive Romberg test. Rare: costochondritis, osteoporosis, bursitis, contracture.

Nervous System: Frequent: vertigo, hyperkinesia, paresthesia, decreased or absent reflexes, increased reflexes, anxiety, hostility. Infrequent: CNS tumors, syncope, dreaming abnormal, aphasia, hypesthesia, intracranial hemorrhage, hypotonia, dysesthesia, paresis, dystonia, hemiplegia, facial paralysis, stupor, cerebellar dysfunction, positive Babinski sign, decreased position sense, subdural hematoma, apathy, hallucination, decrease or loss of libido, agitation, paranoia, depersonalization, euphoria, feeling high, doped-up sensation, suicidal, psychosis. Rare: choreoathetosis, orofacial dyskinesia, encephalopathy, nerve palsy, personality disorder, increased libido, subdued temperament, apraxia, fine motor control disorder, meningismus, local myoclonus, hyperesthesia, hypokinesia, mania, neurosis, hysteria, antisocial reaction, suicide gesture.

Respiratory System: Frequent: pneumonia. Infrequent: epistaxis, dyspnea, apnea. Rare: mucositis, aspiration pneumonia, hyperventilation, hiccup, laryngitis, nasal obstruction, snoring, bronchospasm, hypoventilation, lung edema.

Dermatological: Infrequent: alopecia, eczema, dry skin, increased sweating, urticaria, hirsutism, seborrhea, cyst, herpes simplex. Rare: herpes zoster, skin discolor, skin papules, photosensitive reaction, leg ulcer, scalp seborrhea, psoriasis, desquamation, maceration, skin nodules, subcutaneous nodule, melanosis, skin necrosis, local swelling.

Urogenital System: Infrequent: hematuria, dysuria, urination frequency, cystitis, urinary retention, urinary incontinence, vaginal hemorrha ge, amenorrhea, dysmenorrhea, menorrhagia, breast cancer, unable to climax, ejaculation abnormal. Rare: kidney pain, leukorrhea, pruritus genital, renal stone, acute renal failure, anuria, glycosuria, nephrosis, nocturia, pyuria, urination urgency, vaginal pain, breast pain, testicle pain.

Special Senses: Frequent: abnormal vision. Infrequent: cataract, conjunctivitis, eyes dry, eye pain, visual field defect, photophobia, bilateral or unilateral ptosis, eye hemorrhage, hordeolum, hearing loss, earache, tinnitus, inner ear infection, otitis, taste loss, unusual taste, eye twitching, ear fullness. Rare: eye itching, abnormal accommodation, perforated ear drum, sensitivity to noise, eye focusing problem, watery eyes, retinopathy, glaucoma, iritis, corneal disorders, lacrimal dysfunction, degenerative eye changes, blindness, retinal degeneration, miosis, chorioretinitis, strabismus, eustachian tube dysfunction, labyrinthitis, otitis externa, odd smell.