“There is very little data to justify how these drugs are being used and why they should be in the top 10 in sales,” a researcher said.
One of the most widely prescribed prescription drugs, gabapentin, is being taken by millions of patients despite little or no evidence that it can relieve their pain.
In 2006, I wrote about gabapentin after discovering accidentally that it could counter hot flashes. [that article is posted below]
The drug was initially approved 25 years ago to treat seizure disorders, but it is now commonly prescribed off-label to treat all kinds of pain, acute and chronic, in addition to hot flashes, chronic cough and a host of other medical problems.
The F.D.A. approves a drug for specific uses and doses if the company demonstrates it is safe and effective for its intended uses, and its benefits outweigh any potential risks.
Off-label means that a medical provider can legally prescribe any drug that has been approved by the Food and Drug Administration for any condition, not just the ones for which it was approved.
This can leave patients at the mercy of what their doctors think is helpful.
With our doctors writing into the electronic medical records that follow us for the rest of our lives, we are already at the mercy of incompetent or hostile doctors writing what they “believe” or making assumptions and errors in their entries, like that we are addicted to our pain medicine or that our pain is “psychosomatic”.
Such comments can leave a permanent stain on our records that becomes almost impossible to “clean up”.
Thus, it can become a patient’s job to try to determine whether a medication prescribed off-label is both safe and effective for their particular condition.
Two doctors recently reviewed published evidence for the benefits and risks of off-label use of gabapentin (originally sold under the trade name Neurontin) and its brand-name cousin Lyrica (pregabalin) for treating all kinds of pain.
Dr. Goodman said in an interview, “There is very little data to justify how these drugs are being used and why they should be in the top 10 in sales. Patients and physicians should understand that the drugs have limited evidence to support their use for many conditions, and there can be some harmful side effects, like somnolence, dizziness and difficulty walking.”
Yes, but since there is supposedly an “opioid crisis”, any non-opioid medication that provides even the slightest pain control in just a few patients is instantly popular.
The gabapentinoids are symbolic of three currently challenging problems in the practice of medicine:
- a deadly national epidemic of opioid addiction prompting doctors to seek alternative drugs for pain;
- the limited training in pain management received by most doctors; and
- the influence of aggressive and sometimes illegal promotion of prescription drugs, including through direct-to-consumer advertising.
Gabapentin and Lyrica, both sold by Pfizer, have been approved by the Food and Drug Administration to treat only four debilitating pain problems: postherpetic neuralgia, diabetic neuropathy, fibromyalgia and spinal cord injury.
Even for these approved uses, the evidence for relief offered by the drugs is hardly dramatic.
In many well-controlled studies they found there was less than a one-point difference on the 10-point pain scale between patients taking the drug versus a placebo, a difference often clinically meaningless.
But when patients complain of pain related to conditions ranging from sciatica and osteoarthritis to foot pain and migraine, clinicians often reach for the prescription pad and order either gabapentin or the more costly Lyrica.
As Dr. Michael E. Johansen, a family doctor in Columbus, Ohio, put it, “I use gabapentin clinically and try to stay close to the approved indications, but occasionally we run out of options when faced with patients who hurt. It’s rare that these drugs eliminate pain, and I don’t tell patients their pain will go away. If there’s any benefit, it’s probably marginal.”
But when someone is suffering from relentless pain, any improvement at all can be very valuable.
the number of people taking gabapentinoids more than tripled from 2002 to 2015, with more than four in five taking the inexpensive generic, gabapentin.
“While working in inpatient and outpatient settings,” they wrote, “we have observed that clinicians are increasingly prescribing gabapentin and pregabalin for almost any type of pain.”
Dr. Johansen cited several serious concerns about overuse of gabapentinoids, including
- “a dearth of long-term safety data, small effect sizes,
- concern for increased risk of overdose in combination with opioid use, and
- high rates of off-label prescribing, which are associated with high rates of adverse effects.”
Dr. Johansen pointed out that “there is no recipe book” for treating pain with gabapentinoids. “Doctors need to work with one patient at a time and figure out what works and what doesn’t work,” he said.
The correct practice of medicine seems to be so rare these days that doctors have to be specifically told to “work with one patient at a time and figure out what works and what doesn’t work”
But Dr. Goodman cautioned against going off the drug cold turkey because there can be unpleasant withdrawal symptoms.
And here’s the article about gabapentin soothing hot flashes:
A widely used drug that has been mired in controversy for most of its decade-long life may now bring relief to postmenopausal women whose lives have been disrupted by unrelenting hot flashes.
The drug, best known by its trade name, Neurontin, but now prescribed generically as gabapentin, was approved by the Food and Drug Administration in 1994 to treat epileptic seizures.
In 2002, it was approved to treat postherpetic neuralgia, horrific pain that sometimes follows shingles.
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
- social phobia,
- attention-deficit disorder in children,
- gastric ulcers,
- restless leg syndrome,
- essential tremor,
- bipolar disorder,
- panic attacks and
- withdrawal from cocaine and alcohol
— all known as off-label uses.
I’m surprised that a reasonably intelligent person, like a doctor, would not immediately see a problem with this: no single drug can be effective for so many different problematic symptoms of so many different body systems.
This long list puts gabapentin the same class as meditation, which is also touted as a remedy for all of the above.
Thus, gabapentin was part of the medication prescribed for my unrelenting pain after a double knee-replacement operation last year
It was prescribed again last fall when I developed debilitating back and leg pain caused by a pinched nerve in my back.
Between the two prescriptions, I made a discovery that changed my life for the better:
While taking Neurontin three times a day for the knee pain, I had none of the hot flashes that had plagued me day and night after breast cancer in 1999 made me stop postmenopausal hormones.
But when I weaned myself from gabapentin last May, the hot flashes returned, resulting in three sleepless nights in a row. I wondered whether it could be a factor and decided, with my doctor’s approval, to try just one 300-milligram capsule before bedtime. Voilà! No hot flashes. No waking up damp and clammy and unable to go back to sleep.
I 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.”
Reducing the Heat
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.
Yet the difference between 54% and 31% is only 22%, so only 1/5th reduction can be credited to the drug.
Gabapentin relieved hot flashes as effectively as estrogen,
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.
This shows that “hot flashes”, commonly thought of as merely annoying can, in some people, we life-limiting. Even with such serious side-effects, patients still prefer using the drug.
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.”
Gabapentin was developed 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.
…and non-effective for the problem it was supposed to solve, anxiety.
At high doses, side effects like drowsiness, dizziness and weight gain from retained water can limit its usefulness.