On April 16 of this year, the journal PLOS Medicine<\/b> published a study by scientists from the University College London (UCL) School of Pharmacy<\/b>, stating that the use of gabapentinoids (gabapentin and pregabalin) is associated with an increased risk of drug-induced intoxication. A particularly high risk was identified during the initial phase of treatment and in cases where these drugs were used in combination with benzodiazepines or opioids.<\/p>\n
Gabapentinoids are widely used to treat epilepsy, neuropathic pain, and anxiety disorders, and are increasingly prescribed for chronic pain as an alternative to opioids.<\/p>\n
Data for the study were obtained from the UK Clinical Practice Research Datalink (CPRD Aurum)<\/b>, linked to Hospital Episode Statistics (HES)<\/b> and Office for National Statistics (ONS)<\/b> records. The study included 16,827 individuals<\/b> (mean age 46.9 years; 53.5% female) who were prescribed gabapentinoids between January 1, 2010, and December 31, 2020, and who experienced an episode of drug-induced intoxication of any etiology. Using a self-controlled case series (SCCS)<\/b> design, the researchers assessed the risk of intoxication during predefined risk periods: 90 days before treatment, the first 28 days of treatment, days 29\u201356, days 57\u201384, and the remainder of the treatment period. The impact of concomitant use of opioids and benzodiazepines was also evaluated. The mean observation period was 8.18 years.<\/p>\n
Patients with epilepsy or cancer diagnosed before the start of the observation period were excluded from the study. In cases where such a diagnosis was made during the observation period, follow-up was censored from the date of diagnosis, as these patients have different treatment regimens and risk profiles for drug intoxication. The study also excluded individuals who had received gabapentinoids in the year prior to the observation start, those who experienced intoxication on the very first day of treatment, and individuals with insufficient demographic information in the databases.<\/p>\n
During the observation period:<\/p>\n
45.4%<\/b> of patients took gabapentin only.<\/p>\n<\/li>\n 34.7%<\/b> took pregabalin only.<\/p>\n<\/li>\n 19.9%<\/b> used both drugs.<\/p>\n<\/li>\n<\/ul>\n Patients presented with the following comorbid conditions: 83.7%<\/b> had neuropathic or chronic pain, 76.2%<\/b> had mental health issues, and 47.6%<\/b> had a history of illicit substance use. A significant portion of patients were subject to polypharmacy: 89%<\/b> were prescribed opioids, and 54.7%<\/b> were prescribed benzodiazepines.<\/p>\n Using the SCCS design, researchers compared the risk of drug intoxication between periods of gabapentinoid exposure and non-exposure within the same individuals, adjusting for age, season, and concomitant medication use.<\/p>\n The risk of drug-induced intoxication doubled during the 90 days prior to starting treatment and remained elevated during the first 28 days of treatment. Although the risk decreased over time, it remained high throughout the entire treatment period. Concomitant use of other medications further increased the risk: during the first month of treatment, the probability of intoxication nearly quadrupled<\/b> when combined with benzodiazepines and doubled<\/b> when combined with opioids. Throughout the total treatment period, concomitant opioid prescription increased the risk by approximately 30%<\/b>, while benzodiazepines approximately doubled<\/b> it.<\/p>\n “While gabapentinoids are effective for pain management and generally have a better safety profile compared to opioids, significant risks remain that must be considered by both clinicians and patients. Our findings do not imply that gabapentinoids are dangerous or should not be prescribed; however, clinicians should exercise caution when prescribing them, especially if the patient is taking other medications, and ensure continuous monitoring. Our data do not allow us to determine the specific clinical reasons for the increased risk of intoxication observed in the 90-day interval before treatment begins. Further in-depth research is needed in this direction,” said the study’s lead author, Kenneth Man (PhD, UCL School of Pharmacy)<\/b>.<\/p>\n Due to the observational nature of the study, a direct causal relationship cannot be established, especially since the prescription of medications often coincides with periods of worsening clinical status. Furthermore, the data relied on prescription records, which may not reflect actual adherence or capture mild cases of intoxication.<\/p>\n