Treatment with gabapentinoids, a class of epilepsy and anxiety drug, is not directly associated with an increased risk of self-harm, finds a study led by UCL researchers.
However, rates of self-harm were higher before and shortly after treatment, highlighting the need for close monitoring of patients throughout their treatment journey, say the authors of the new BMJ study.
Gabapentinoids - drugs such as gabapentin and pregabalin - are widely prescribed for conditions such as epilepsy, nerve pain, and anxiety disorders.
Lead author Dr Kenneth Man (UCL School of Pharmacy) said: "In recent years, there have been growing concerns around whether gabapentinoids may raise the risk of self-harm, but the prior research has been inconclusive.
"Here, we found that the risk of self-harm was already elevated in people prescribed the medication before they began taking the drug, the risk then decreased during the treatment period, and then spiked again shortly after discontinuation. Our findings challenge the assumption of a direct causal link between gabapentinoids and self-harm and underscore the need for close monitoring of patients throughout the treatment journey."
Previous studies have raised concerns about potential side effects, including an increased risk of self-harm, but did not examine the risks immediately before starting or after stopping gabapentinoids, despite the fact that these drugs are often prescribed for conditions associated with self-harm. As such, the nature of this relationship is still not fully understood.
To obtain a clearer picture, researchers analysed electronic health records for 10,002 individuals in the UK aged 18 and over who were prescribed gabapentinoids between 2000 and 2020 and had at least one hospital record of self-harm.
They examined rates of self-harm in four distinct time periods for each individual - 90 days before starting treatment, the treatment period, the 14 days after stopping treatment, and any other period, which acted as the reference category.
By comparing each individual with themselves across time, the researchers were able to account for all potentially influential factors, including genetic risks, childhood environment and early-onset conditions. They also accounted for age, seasonality, and other prescribed opioid and psychotropic medications.
Of the 10,002 individuals, 4,767 (48%) took gabapentin only, 3,164 (32%) took pregabalin only and 2,071 (21%) took both over an average follow-up period of 13 years.
The researchers found that the rate of self-harm was higher in the 90 days leading up to the start of treatment, suggesting that individuals prescribed these drugs may already be at an increased risk.
Compared with the reference period, the rate of self-harm increased by 69% (to 16.8 incidentsper 100 person years) in the 90 days leading up to the start of treatment, suggesting that individuals prescribed these drugs may already be at an increased risk.
This risk declined during the treatment period (to 6.75 per 100 person years), but markedly increased to 29.6 per 100 person years in the two-week period after treatment had ended, before returning to reference levels, suggesting that gabapentanoids are unlikely to be linked to self-harm risk.
The researchers acknowledge that these are observational findings and results may be limited by the small sample sizes within some groups. What's more, they were only able to capture prescriptions issued by a general practitioner and cases severe enough to be admitted to hospital.
Nevertheless, their use of a large population-based database provided sufficient statistical power to evaluate the association between gabapentinoid use and self-harm, and results were similar after further analyses, suggesting they are robust.
This study provides valuable insights into the association between gabapentinoid treatment and self-harm risks, the authors write. And while further studies are needed in different populations, they say these findings underscore the necessity for close patient monitoring of self-harm before beginning drug treatment, during, and after.
This investigation shows the importance of testing associations in primary and secondary care, and the authors' novel approach of considering periods before and after treatment is an important contribution, note a separate pair of researchers in a linked editorial. They point to some important study limitations, but acknowledge in the editorial that, "clinically, their results suggest that routine and periodic follow-up of people prescribed gabapentinoids should be considered, particularly in the weeks after medication has been discontinued." The editorial authors add: "Whether young adults and people with no psychiatric diagnoses need more supervision while taking gabapentinoids requires further research to clarify."
The study was supported by the National Institute for Health Research UCLH Biomedical Research Centre.
