New York Times health editor Jane Brody reported yesterday that the epilepsy drug Neurontin (gabapentin), prescribed off-label for her pain after knee replacement surgery, helped her menopausal hot flashes. Brody went back to her doctor and asked for more after her knee pain ceased.

Gabapentin was developed, Brody says, “to help avoid the addictive quality of drugs called GABA analogues (Valium, Ativan and Xanax) used for anxiety and seizure disorders. The modified drug proved nonaddictive.”

Since this drug is non-hormonal and works on the brain, I wonder if it relieves hot flashes in men taking androgen blockade for prostate cancer?

Last September, Brody says, she found a report in The Lancet, the medical journal:

by researchers from four medical centers who conducted a clinic trial using gabapentin to treat hot flashes in women with breast cancer. In the study, 420 women having two or more hot flashes a day were randomly assigned to take 300 or 900 milligrams of gabapentin or a look-alike placebo each day in three divided doses for eight weeks.

About one patient in five on the placebo reported a decline in hot flashes, while a third of those taking 300 milligrams of gabapentin did and nearly half of those on 900 milligrams reported a benefit. The researchers, led by Dr. Kishan J. Pandya of the James P. Wilmot Cancer Center at the University of Rochester Medical Center, found that “only the higher dose of gabapentin was associated with significant decreases in hot flash frequency and severity.” They recommended that the drug “be considered for treatment of hot flashes in women with breast cancer.”

Those who took 300 milligrams of gabapentin three times a day reported a 54 percent reduction in overall hot flash activity (frequency and severity) compared with a 31 percent drop in the placebo group.

In an interview, Dr. Guttuso, now at the Jacobs Neurological Institute at the University at Buffalo, discussed a soon-to-be-published study by Dr. Sireesha Y. Reddy and colleagues that pitted 2,400 milligrams of gabapentin daily against 0.625 milligram of estrogen, the gold standard for controlling hot flashes.

Participants suffered from moderate to severe hot flashes, defined as seven or more per day, accompanied by sweating. Gabapentin relieved hot flashes as effectively as estrogen, Dr. Guttuso said. Although about 40 percent of the women taking 2,400 milligrams of gabapentin daily reported side effects (sleepiness, dizziness and swelling of the feet), they felt that the benefit of the drug outweighed them, Dr. Guttuso said.

Gabapentin has other benefits. “It does not interact with any other medications, which is very unique,” Dr. Guttoso said, “so doctors don’t have to worry about other drugs a patient might be taking. Also, gabapentin is not metabolized, so it has no effect on the liver. It’s fully excreted in the urine.” He said that it works through a receptor on the membranes of brain and peripheral nerve cells.

Estrogen normally acts as a brake on cells in the brain’s temperature-regulating center through pathways called calcium channels. Gabapentin binds to a channel.

Properly designed clinical trials are needed to show just how helpful gabapentin is against various conditions and whether prolonged use may have unexpected adverse effects. At high doses, side effects like drowsiness, dizziness and weight gain from retained water can limit its usefulness.

Now that the drug is without patent protection, future F.D.A. approvals will depend on studies by two companies. One, PharmaNova, has patented a sustained-release formulation of gabapentin and is studying its role in treating hot flashes. Meanwhile, Pfizer has introduced a chemical cousin of gabapentin, sold as Lyrica and approved for treating nerve pain caused by shingles and diabetes. It should control hot flashes, too.

Lyrica is being studied in patients with hot flashes under a licensing agreement with the University of Rochester, which has patented new uses of gabapentin and other drugs that use the same mechanism.

Interesting to see how Brody traces the off-label history of gabapentin:

Aided by the Internet and, the government has said, an illegal marketing campaign by its parent company, Neurontin sales eventually exceeded $2 billion a year before its patent expired and the generic gabapentin entered the market in 2004.

The parent company, Warner-Lambert (since bought by Pfizer), was investigated after a whistle-blower said it had paid doctors to promote Neurontin to their colleagues for a host of additional symptoms not approved by the F.D.A. The whistle-blower also said the company had paid to have research articles prepared claiming benefits of a dubious nature.

As a result, Neurontin has been used for problems like migraines, social phobia.
Its most frequent off-label use is as an adjunct to drugs used to treat pain, especially pain thought to have nerve involvement. . . .

What the pharma industry wants now, of course, is to get this multi-use generic drug back onto patents so they can charge a bundle for it. Brody writes:

Now that the drug is without patent protection, future F.D.A. approvals will depend on studies by two companies. One, PharmaNova, has patented a sustained-release formulation of gabapentin and is studying its role in treating hot flashes. Meanwhile, Pfizer has introduced a chemical cousin of gabapentin, sold as Lyrica and approved for treating nerve pain caused by shingles and diabetes. It should control hot flashes, too. Lyrica is being studied in patients with hot flashes under a licensing agreement with the University of Rochester, which has patented new uses of gabapentin and other drugs that use the same mechanism.

Wonderful. Mabe eventually we’ll have TV ads 20 times a day for Lyrica (love those names) at a cost of how much per ad?

Read Jane Brody at:
A Chance Find, and Voilà! Goodbye, Hot Flashes. Hello, Sleep.