Commentary on Smith et al. (2016): Gabapentin-looks like a drug that can be misused…, probably is a drug that can be misused.

Abstract

Gabapentin, a gabapentinoid commonly prescribed for pain or epilepsy, has a higher abuse liability than previously considered. Risks particularly exist for people with substance use disorders, especially those with concurrent opioid dependence. Clarification of the magnitude of abuse liability for gabapentin is warranted. In this issue of Addiction, Smith and colleagues 1 have highlighted the risks of misuse of gabapentin, a gabapentinoid now promoted as a first-line medication for epilepsy and neuropathic pain in some parts of Europe and North America. Similar concerns regarding misuse have also been raised regarding pregabalin, another gabapentinoid with similar indications 2. Smith and colleagues estimate misuse to occur at a general population prevalence of approximately 1%, but provide evidence this is likely to be much higher in subpopulations including those with substance use problems, particularly people who use or are prescribed opioids. They also note the lack of psychopharmacology studies describing in detail the abuse liability of gabapentin and cite studies that describe gabapentin tolerance, dependence and withdrawal as well as cases of gabapentin-related delirium. These issues should be a cause for concern, further examination and investigation, as even recently gabapentin has not been considered to have a significant abuse potential 3. It is important to learn from history. This pattern, of a medication initially being promoted as being highly effective, with a low abuse profile, that medication being enthusiastically prescribed by medical practitioners, then over time, significant side effects including dependence and withdrawal being detected, has been noted before, most infamously for the benzodiazepines 4. In the case of the gabapentinoids, clearer elucidation of the magnitude of risks and characterisation of these risks, should be a matter of priority. In the meantime, education of medical practitioners and patients should occur, especially for people with current substance use problems, so that risks including the development of dependence and withdrawal symptoms can be avoided. Strategies that have been used in close monitoring of patients with substance use disorders who are prescribed opioids or benzodiazepines could be employed: caution regarding dose escalation, limiting supply and regular clinical review to monitor patient adherence 5. Nonetheless, educating medical practitioners of these risks may be particularly challenging. Again, using the example of benzodiazepines, long periods of time occurred before benzodiazepine abuse and dependence were noted 6, and today many practitioners do not appear to be aware of risks of benzodiazepines. The recent case of alprazolam being successfully promoted and prescribed for panic disorder 7 despite a lack of level-one evidence for benzodiazepines for panic disorder 8 is a pertinent and interesting parallel. A recent review casts doubt on the use of gabapentin as a first line agent for pain 9. Clinical guidelines are promoted as a strategy to encourage appropriate prescribing. However, using the example of opioids, guidelines may not be an effective way to change medical practitioners prescribing behaviour, especially once patterns of prescribing have become part of standard medical care. Studies of primary care practitioners and registrars opioid prescribing patterns in North America and Australia show adherence to guidelines does not occur consistently 10-12. There is a need, therefore, not only to better understand abuse risks with the gabapentinoids, but also a need for effective strategies to communicate these risks to current prescribers and patient populations. It is interesting to note in the current review 1, that non-medical use of gabapentin does not appear to be occurring at elevated levels for people with alcohol use disorders. It also noteworthy that there may be a therapeutic role for gabapentin in alcohol dependence or withdrawal with some early positive findings in trials in this area 13. In summary, gabapentin is a medication that is being commonly prescribed for epilepsy, pain as well as many current ‘off-label’ uses. Despite previous work suggesting the contrary, gabapentin can be misused, especially in populations with substance use problems. Risks have been poorly recognised to date and significant challenges remain in educating practitioners and patients regarding these risks. Can we learn from experience with benzodiazepines and opioids? None.