By Pat Anson, Editor
When the Food and Drug Administration last week endorsed the CDC’s controversial guidelines to limit opioid prescribing, the agency promised it would prioritize development of non-opioid alternatives for chronic pain relief.
“We are also working closely with industry and the National Institutes of Health to develop additional alternative medications that alleviate pain but do not have the addictive properties of opioids,” said Dr. Robert Califf, FDA Deputy Commissioner for Medical Products and Tobacco, who co-authored a “special report” on the FDA's new opioid policies the New England Journal of Medicine.
“The FDA has approved non-opioid medications for treatment of various chronic-pain syndromes, including gabapentin (Neurontin), pregabalin (Lyrica), milnacipran (Savella), duloxetine (Cymbalta), and others, and a number of promising development programs are in the pipeline. But we need more. The FDA will use all the tools at its disposal to move these alternatives along as expeditiously as possible, while remaining mindful that all medicines have risks.”
The four drugs mentioned by Califf all have mixed track records, and many chronic pain sufferers have told Pain News Network the medications either don’t relieve their pain or have intolerable side effects.
“Gaba (Neurontin) did nothing for me and Lyrica seemed to help a very little with nerve pain but it made me very shaky, as if I drank a gallon of coffee,” wrote Pam Cushion.
“The side effects of Cymbalta were more than I could bear. I got terrible pains in the skin on my upper back and shoulders, and it made me feel downright awful,” said Tracy W.
“As opiate medications are lowered, my Lyrica dosage has gone up. It does have side effects like weight gain and next day fogginess,” wrote Kenneth McKenna. “I look for physicians to use other medicines in a similar fashion, (due to of the opioid restrictions) which may turn out to be a worse problem than the opioids themselves.”
Both Lyrica and Neurontin are coming under scrutiny in the UK because of increasing reports they are being abused by addicts to get high. Since 2012, over 60 overdose deaths in the UK have been linked to pregabalin and gabapentin.
Researchers in British Columbia also recently warned about the limitations of gabapentin, pregabalin, duloxetine, and venlafaxine (Effexor) when used to treat neuropathic pain.
“The best available evidence now indicates that as few as one in ten people can expect much pain relief from these drugs,” said Dr. Aaron Tejani, a Clinical Assistant Professor in the Faculty of Pharmaceutical Sciences and a member of the University of British Columbia's (UBC) Therapeutics Initiative Working Group. “Many people who improve are getting a placebo effect, or would improve in time without any drug treatment. Others end up sedated, with impaired thinking, balance disturbance, dry mouth, or other side effects that cause more harm than good.”
The drugs may be ineffective for most patients, but Tejani says many doctors continue to prescribe them because of an exaggerated belief in their effectiveness. From 2005 to 2014, the number of British Columbians receiving pregabalin increased by 17 fold, according to UBC Therapeutics. Over three times as many prescriptions for duloxetine were written during that period, while gabapentin prescriptions nearly doubled. The use of venlafaxine, mostly for depression or anxiety, has been stable.
“Increasing evidence suggests that drugs have relatively little useful role for most patients with chronic pain. We should be much more cautious about prescribing them, and warn patients about their side effects,” said Dr. Tom Perry, a Clinical Assistant Professor in the Department of Anesthesiology, Pharmacology and Therapeutics and Chair of the UBC Therapeutics Initiative team.
Califf Nomination Still Stalled
The FDA’s sudden reversal on many of its opioid policies may have been intended to reduce opposition in the U.S. Senate to Robert Califf’s nomination as the agency’s new commissioner. Early indications are that strategy may not have worked.
“I will continue to strongly pressure the FDA to strengthen its oversight of opioid medications and will continue to push for the strongest possible framework for drug approval to ensure that the agency doesn’t simply continue to approve ever stronger and more deadly opioid medications under this new process,” said Sen. Joe Manchin (D) of West Virginia, one of five senators who are blocking Califf’s nomination.
Manchin has been particularly critical of the FDA’s failure on several occasions to accept the advice of its advisory committees, which have been reluctant to support the approval of new opioids. Last week Califf promised to appoint new advisory panels to review every new opioid that doesn’t have abuse deterrent properties.
“I believe the FDA should use the advisory committee’s expert advice for all opioid medications, including abuse-deterrent formulations, which are just as addictive and can be just as deadly as non-abuse deterrent opioids. The FDA also needs to commit to adhering to the recommendations that the advisory committee puts forward,” said Manchin.
Sen. Edward Markey (D) of Massachusetts also believes the FDA policy changes “fall short of what is needed.”
“While this is a good start, even more is required to ensure the FDA’s approval process protects Americans from the dangers of opioid painkillers,” Markey said in a statement. "Whether an opioid is abuse deterrent or not hasn’t prevented tens of thousands of people who have had their wisdom teeth removed or experienced lower back pain from getting addicted to these painkillers. That is why the FDA must change its decision not to seek expert advice about the risks of addiction before it approves abuse-deterrent opioids.”