Epilepsy drugs linked to increased risk of suicidal behaviour

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A group of drugs often prescribed for epilepsy and neuropathic pain are linked to an increased risk of suicidal behaviour, according to a study by international researchers from Sweden, the UK and the US.

They found gabapentinoids, used for epilepsy, nerve pain and anxiety disorders, were linked with a higher risk of suicidal behaviour and unintentional overdose, as well as injuries, and road traffic incidents. And the group most at risk were 15- to 24-year-olds, prompting the researchers to suggest that treatment guidelines for young people should be reviewed.

The authors of the study, published in the British Medical Journal, noted that prescriptions had risen steeply in recent years and gabapentinoids were among the top 15 drugs globally in terms of revenue.

They said that, while previous studies had linked gabapentinoids to suicidal behaviour and overdose related deaths, the findings were inconsistent and data on longer term harms was lacking. They highlighted that concerns that these drugs were also being used as an opioid substitute and for recreational use had led to prescribing restrictions in several countries. As a result, the researchers examined links between gabapentinoids and a range of harms including suicidal behaviour.

Using national prescription, patient, death, and crime registers, they identified 191,973 people aged 15 years and over who were prescribed pregabalin or gabapentin in Sweden between 2006 and 2013. Overall, 59% of participants were women, and most were 45 years or older. The researchers then compared the risk of harms during treatment periods with baseline risk during periods without treatment.

They found that during treatment periods, participants were at a 26% increased risk of suicidal behaviour or death from suicide.

They also found participants were at a 24% increased risk of unintentional overdose, a 22% increased risk of head or body injuries, and a 13% increased risk of road traffic incidents or offences. However, there were no statistically significant associations between gabapentinoid treatment and violent crime.

When the results were analysed by age, the risks were found to be greatest among 15- to 24-year-olds, warned the researchers. They suggested this finding on age could be due to impulsivity and risk taking behaviour, or use of alcohol and illicit drugs alongside gabapentinoids. “The increased risks found in adolescents and young adults prescribed gabapentinoids, particularly for suicidal behaviour and unintentional overdoses, warrant further research,” the authors said.

“If our findings are triangulated with other forms of evidence, clinical guidelines may need review regarding prescriptions for young people, and those with substance use disorders,” they said.

When drugs were examined separately, only pregabalin, not gabapentin, was associated with increased risks of harm.

In a linked editorial in the BMJ, Dr. Derek Tracy, a consultant psychiatrist at Queen Mary’s Hospital in London, said the new findings provided “solid data to inform patients on the risks associated with treatment”.

“This very large trial provides important information that pregabalin, but not gabapentin, increased the risk of a range of adverse outcomes, including suicidal thinking and completed suicide, head injuries, and road traffic accidents. The risk was ‘dose-related’ which is to say the more one takes, the more likely such outcomes were, and young people aged 15 to 24 seem particularly susceptible,” he said.

He noted that gabapentinoids “remain a valued therapeutic option for many people” but suggested it might be time to “uncouple” pregabalin and gabapentin in guidelines.

“We also need to understand what is driving the age-related differences in risks. Medicines can harm as well as heal, and the best treatment decisions are made in full partnership with patients, after consideration of all available evidence on both,” he said.