In the early 1960s, a benzodiazepine called Valium became the first drug to enter the mass market to treat anxiety. It took decades of overprescribing “mother’s little helper” before doctors finally acknowledged that the drug was highly addictive. Twenty years later, a group of pain-killing drugs called gabapentinoids looks set to follow the same pattern, but this time it’s older people who are at most risk of getting hooked.
In 1993, the first gabapentinoid, called “gabapentin”, was given a licence in the US to treat epilepsy. In 2004, it was also granted a licence in the US to treat pain, specifically following shingles.
Europe was slower to approve the drug. In 2006, the European Medicines Agency, approved gabapentin for treating epilepsy and pain associated with certain types of nerve damage. It was also prescribed off-label to treat restless legs syndrome, migraine, changes in blood flow to the upper body in menopause, as well as alcohol withdrawal.
Gabapentin’s successor, pregabalin, also received a licence for treating epilepsy and pain and became the first drug to receive a licence in the US to treat fibromyalgia, a medical disorder characterised by extreme fatigue, muscle pain and sleep problems. In Europe and the US it was approved by the regulators to treat generalised anxiety disorder, but the drug was classified as a schedule five drug in the US. Schedule five indicates that there is a potential for dependence and people who come off the drug may experience withdrawal symptoms.
The structure of gabapentinoids resembles the neurotransmitter GABA, which has its own brain receptors. GABA is central to the anxiety relieving action of some drugs of addiction such as benzodiazepines and alcohol and explains their potential for misuse. However, gabapentinoids do not act directly on brain GABA receptors. Yet gabapentinoids are effective at treating alcohol withdrawal, indicating an indirect interaction with GABA receptors and hence a propensity for addiction. It is known that pregabalin has considerable potential for addiction at higher than recommended doses, producing sensations of detachment and euphoria.
There is now growing evidence that gabapentinoids are being used primarily for their pleasurable effects, with certain patterns of use now emerging. Recreational use of gapapentinoids is more common in females and involves the drug being taken in pill form, although some addicts also inject it or administer it rectally.
As tolerance to gapapentinoids develops very rapidly, there is usually a rapid escalation in the dose needed to produce the same effect so people become addicted quickly. Their use as part of addiction to other substances means that recreational users of pregabalin and gabapentin are often also addicted to opioid painkillers and illegal drugs.
In 2014, there were 9m prescriptions for gabapentinoids, most of which will have been prescribed for their licensed use: to alleviate anxiety or to reduce pain. This has been accompanied by a rise in gabapentinoid misuse, with a fivefold increase in the number of reports of “abuse”, “misuse” and “dependence” for both drugs as part of adverse drug reaction reporting since 2010. One in every hundred people in the UK has used a gabapentinoid at some time in their life, which is higher than that of novel psychoactive substance misuse.
Baby boomers most at risk
The increasing use of gabapentinoids for the treatment of pain in end-of-life cancer care has arisen from the need to avoid prescribing opiate drugs. In the US, two thirds of people with cancer are now surviving five years or more after receiving a diagnosis. This will have implications for gabapentinoid addiction in cancer services. Older people of the baby boomer generation have already shown increasing rates of substance misuse and so may be at particular risk of gabapentinoid addiction.
Gabapentinoid treatment for common medical and mental disorders such as pain and anxiety risks their therapeutic use being replaced by predominant misuse. This is especially so for specific groups of people such as those with mental health disorders or chronic pain.
It’s time that doctors become more aware of the growing use of gabapentinoids and their true potential for addiction. Unlike benzodiazepines, this time we can’t say that we did not see it coming.