How addictive are gabapentin and pregabalin? A systematic review

In the last ten years, gabapentin and pregabalin have been becoming dispensed broadly and sold on black markets, thereby, exposing millions to potential side-effects. Meanwhile, several pharmacovigilance-databases have warned for potential abuse liabilities and overdose fatalities in association with both gabapentinoids. To evaluate their addiction risk in more detail, we conducted a systematic review on PubMed/Scopus and included 106 studies. We did not find convincing evidence of a vigorous addictive power of gabapentinoids which is primarily suggested from their limited rewarding properties, marginal notes on relapses, and the very few cases with gabapentinoid-related behavioral dependence symptoms (ICD-10) in patients without a prior abuse history (N=4). In support, there was no publication about people who sought treatment for the use of gabapentinoids. Pregabalin appeared to be somewhat more addictive than gabapentin regarding the magnitude of behavioral dependence symptoms, transitions from prescription to self-administration, and the durability of the self-administrations. The principal population at risk for addiction of gabapentinoids consists of patients with other current or past substance use disorders (SUD), mostly opioid and multi-drug users, who preferred pregabalin. Pure overdoses of gabapentinoids appeared to be relative safe but can become lethal (pregabalin > gabapentin) in mixture with other psychoactive drugs, especially opioids again and sedatives. Based upon these results, we compared the addiction risks of gabapentin and pregabalin with those of traditional psychoactive substances and recommend that in patients with a history of SUD, gabapentinoids should be avoided or if indispensable, administered with caution by using a strict therapeutic and prescription monitoring.