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Study results have suggested that patients who take gabapentinoids are at greater risk of drug toxicity if they are also taking another medication.
Publishing their findings in PLoS Medicine on 16 April 2026, researchers from University College London found that patients taking gabapentinoids with benzodiazepines were at double the risk of hospitalisation for drug poisoning, while taking the drugs with opioids was associated with a 30% increase in risk.
Researchers analysed up to ten years of data on 16,827 individuals who had been prescribed a gabapentinoid and hospitalised at least once for drug poisoning. To conduct their analysis, the researchers used the UK Clinical Practice Research Datalink database linked to the Hospital Episode Statistics and Office for National Statistics.
They assessed the risk of drug poisoning 90 days before treatment initiation, the first 28 days of treatment, days 29–56, days 57–84 and the remaining treatment time.
The risk of drug poisoning in the first 28 days of gabapentinoid treatment increased (adjusted incidence rate ratio [aIRR] = 1.81, 95% confidence interval [CI] 1.66 to 1.99; P < 0.001), before eventually dropping to 1.11 (95% CI 1.05 to 1.17; P < 0.001) in the remainder of the treatment period, the researchers found.
The authors noted the risk doubled during the 90-day preceding treatment initiation (aIRR = 2.09, 95% CI 1.98 to 2.21; P < 0.001).
“Co-administration with opioids elevated the risk by 30%, while benzodiazepines increased it two-fold,” the authors wrote.
They also noted that there was an increased adjusted odds ratio of 1.36 (95% CI 1.12 to 1.65; P = 0.002) of receiving gabapentinoid treatment within 30 days prior to a drug poisoning event.
The findings suggested gabapentinoids are often started during periods of heightened vulnerability to drug poisoning, the authors noted.
The authors also said that the study could not completely exclude the effect of confounders, such as changes in socioeconomic status, major life events or illicit drug use.
They also concluded that gabapentinoids are associated with increased risk of drug poisoning and that close monitoring during treatment is necessary
“Concomitant use with opioid or benzodiazepines should be avoided,” the authors added.
Gabapentinoids, such as gabapentin and pregabalin, are indicated for neuropathic pain, epilepsy and generalised anxiety disorder. The medications are also used off label for fibromyalgia, sleep disorders and other chronic pain conditions.
The use of gabapentinoids has grown substantially over the past decade. According to the results of a study, published in Nature in 2023, UCL researchers found that gabapentinoid consumption had increased four-fold across 65 countries between 2008 and 2018.
Emma Davies, principal pharmacist for pain, analgesic stewardship and harm reduction Cwm Taf Morgannwg University Health Board, commented: “The study adds to a growing body of evidence that gabapentinoids are not benign. Combinations with other central nervous system depressants, such as benzodiazepines and opioids are, once again, of particular concern.
“This study is especially valuable in quantifying that risk by showing a marked increase in drug poisoning when these medicines are co-prescribed.
“From a clinical perspective, the key message is the need to redouble efforts around safe prescribing and monitoring. These combinations are common in practice. This evidence reinforces that they should not be considered routine or low risk.”
She added: “Long-term co-prescribing should not be viewed as inherently safer. Clinicians need to be particularly vigilant when initiating or modifying treatment.
“Pharmacists, as medicines experts, have a particularly important role in addressing these risks. Identifying potentially harmful combinations, such as gabapentinoids with opioids or benzodiazepines, and taking action should be routine practice. Proactive reviews of prescribing, intervening where combinations pose a risk and supporting deprescribing or safer alternatives where appropriate should be built in.
“The study also prompts a broader reflection on prescribing culture. The evidence base for gabapentinoids, particularly in chronic pain and anxiety, is of low quality. Given the increasing recognition of harms, it would be sensible to encourage alternative approaches and move away from prescribing as the default response to these conditions.
“There are already frameworks to support this, such as NICE [National Institute for Health and Care Excellence] guidance for pain management and prescribing e.g., NG193 and NG215.”
Davies added that pharmacists “should support patients and prescribers to better understand these risks and help to challenge the perception that gabapentinoids are low-risk options.”
In January 2026, the Medicines and Healthcare products Regulatory Agency announced warnings on the risk of dependency and addiction for gabapentinoids, benzodiazepines and z-drugs are to be strengthened, following a safety review by the regulator.
