Side effects versus outcomes
My experience as a patient prescribed the drug Pregabalin (Lyrica) – Medical Matters, October 25th, 2016 – sparked a considerable reader reaction. You responded to my experience of feeling an unpleasant “muzziness” in my head while taking the drug. And my description of reducing the dose also struck a chord:
“Some strange symptoms emerged. I developed aches and pains all over, as you would with a dose of the flu. The muzziness became a strange kind of floating feeling accompanied by intermittent dizzy spells. And I felt incredibly tense, as if pressure was building up inside my head.”
The column also triggered a response from medical colleagues. A Dublin GP said, “I have had multiple problems with its [pregabalin] price, its gastrointestinal side effects, its weight problems and its titration downwards.”
Dr Eamon Shanahan, a GP in Farranfore, Co Kerry, kindly searched his practice database and reckons about 2-5 per cent of patients taking pregabalin experience a side effect. “Looking down the list of patients who are taking pregabalin, the vast majority of those were given it for neuropathic pain,” he said.
Lingering pain post shingles infection was the most common reason readers said they were taking Lyrica. One man in his 70s experienced good pain relief in the first week, but then noticed quite specific problems with his memory. He was especially upset at not being able to remember prayers and poems he has recited since he was a child.
A woman who was told to come off Lyrica “cold turkey” said she nearly “went mad” with withdrawal symptoms, including aches all over, shivers, crying and lightheadedness. Another reader said she was in a haze while taking the drug. “I described it at the time as feeling drunk at all times – my thinking was compromised.”
Meanwhile, another correspondent praised Lyrica for enabling her to sleep despite pain “but within a month I noticed that I felt ‘not quite with it’, as if I was walking round in a fog. This got worse, to the point where it was affecting my work.” However, she had no problem coming off the drug.
For a younger man, even though Lyrica didn’t eradicate his back pain, “I actually did not care because I felt really good. It was like being in a fog completely stoned.” He was emphatic he wouldn’t take the medication again.
A grandmother with low back pain said she stopped Lyrica without any weaning: “I definitely noticed an immediate reaction – not in pain levels [slightly up] but in mood. I was most definitely depressed, thankfully not for long, a few weeks]. . . I felt very low, a cloud of sadness hung over me and I was close to tears a lot.”
Another reader, taking a small dose at night, said she felt “dopey” and spaced out in the morning. “As you described, I thought my head would explode and only I have low blood pressure I would have thought I was about to have a stroke. The slightest stress raised anxiety levels.”
An 88-year-old man said Lyrica did not eliminate pain but allowed him sit comfortably. However, he felt he was faced with Hobson’s Choice given the side effects he experienced which included severe constipation, dizziness, tremor, weight gain and sleep disturbance.
My description of muzziness resonated with a number of correspondents. “I couldn’t continue with the muzziness and general peculiar feeling in my head which you described so well,” said one.
A retiree who went back to study got a shock when he sat an exam while prescribed Lyrica: “I was surprised by how I felt during the written exam – my writing was awful, my thinking was slow even though the paper suited me. Your word ‘muzziness’ is the best I can use to describe it. I was physically exhausted afterwards.”
While some of the stories you shared resonated with mine, others wrote to say how they had no problems when prescribed Lyrica – as was the case for this woman with post shingles pain:
“I found them extremely effective, and stopped them once I no longer needed them. I noticed no side effects, and had no withdrawal problems. I was very conscious of this, as a friend of mine had been prescribed them after back surgery and found the side effects so bad she stopped immediately.”
A 69-year-old male started taking Lyrica in 2009 and stopped abruptly last year. He went from a dose of 150mg three times a day to zero “and since then have had no reaction that I am aware of”. And a 91-year-old said of his two years taking pregabalin – “Works and no side effects.”
Meanwhile, a 66-year-old correspondent said Lyrica prescribed for her residual pain after shingles “worked very well. Was only mildly woozy for a day or two at first. So was pleased with outcome.”
A couple of readers described classic allergic reactions to the drug, complete with swelling of the tongue and an extensive skin rash, which settled once they stopped taking pregabalin.
For some correspondents, the drug simply didn’t work. A woman who was prescribed Lyrica after a bout of shingles said: “It isn’t really doing anything to alleviate the pain so I’m thinking of coming off it, following my next consultation with my doctor. I don’t at all like the ‘zombie’-like feeling it gives me.”
Drugs not working and causing allergic reactions are, of course, not unique to pregabalin. Research suggests that, in general, medication for chronic pain tends not to work in the longer term.
According to the European Medicines Agency (EMA), in 10 studies involving more than 3,000 patients with peripheral neuropathic pain, 35 per cent of patients treated with Lyrica had a decrease in pain scores of 50 per cent or more, compared with 18 per cent of the patients treated with placebo.
In a smaller study involving 137 patients with central neuropathic pain due to a spinal cord injury, 22 per cent of patients treated with Pfizer’s version of the drug had a decrease in pain scores of 50 per cent or more, compared with 8 per cent of the patients treated with placebo.
In the Republic, the Health Products Regulatory Agency (HPRA) has received 303 reports of suspected adverse events and events associated with the use of Lyrica – from the time the drug was first authorised in 2004 up to the end of November 2016. Just over a half occurred in females.
According to the agency’s director of human medicines, Dr Joan Gilvarry, the majority of reports received by the HPRA have been consistent with the expected pattern of adverse effects for the drug.
“Gastrointestinal and nervous system disorders, such as vomiting, nausea, diarrhoea, dizziness and headache, have been among the most commonly reported effects.
Other commonly reported symptoms include malaise, headache, dizziness, somnolence and tremor,” she told The Irish Times.
“There have also been some reports describing psychiatric-type reactions such as anxiety, confusion, hallucination and drug abuse or dependence. Issues with drug withdrawal have also been reported.”
In general, patients were prescribed Lyrica for either neuropathic pain or generalised anxiety disorder, she added.
There is concern among GPs and doctors working in addiction medicine about pregabalin’s growing popularity as a drug of abuse. Usually part of multiple drug addiction, pregabalin is also a primary addictive substance and weaning addicts off it is difficult. There has been a five-fold increase in the number of reports of “abuse”, “misuse” and “dependence” for gabapentinoids as part of adverse drug reaction reporting in the UK since 2010. Researchers from the National Drug Treatment Centre, writing in the Irish Medical Journal last January, flagged their concerns about pregabalin.
“Our study [which showed a misuse rate of 7 per cent] confirms that pregabalin abuse is taking place among the addiction services population. We believe that misuse of this prescription drug is a serious emerging issue which should be monitored carefully.”
It’s a point echoed by Dr Shanahan: “Given that pregabalin has a street value and there are case reports of dependence, further work needs to be done to minimise these outcomes.”
Asked if the company had been approached by either the HPRA or European regulators with concerns about either the side effects or addiction potential of Lyrica, a spokeswomen for Pfizer said: “Pfizer reviews all safety data on Lyrica with the European regulators in accordance with legislative and regulatory requirements. The Summary of Product Characteristics presents the relevant information for doctors to prescribe Lyrica appropriately.”
She also confirmed that the prescribing of Lyrica was not restricted to specialist doctors anywhere in the European Union.
Pfizer and the manufacturers of generic pregabalin are obliged to conduct post-marketing surveillance of the drug.
Given the drug’s addiction potential, in particular, it would be helpful if the pharmaceutical firms could deepen this data collection and share the results directly with consumers (as well as with regulators).
Such a move would add a further layer of patient safety for those legitimately prescribed pregabalin and other gabapentinoids.
* I would like to thank the many readers who took the time to share their experiences with me.
There have been reports describing psychiatric-type reactions such as anxiety, confusion, hallucination and drug abuse or dependence, as well as issues with drug withdrawal
The Health Products Regulatory Agency has received 303 reports of suspected adverse events and events associated with the use of Lyrica. Just over a half occurred in females.