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Young patients might be at increased risk of suicidal behavior, unintentional overdose, injuries, and traffic incidents during treatment periods with gabapentinoids, compared with periods without treatment with those medications, a cohort study of almost 200,000 people shows. Pregabalin is associated with higher hazards of those outcomes than is gabapentin, and the associations are strongest in patients aged 15-24 years, the researchers reported.
“If our findings are triangulated with other forms of evidence, ,” wrote Yasmina Molero, PhD, and associates. “Further restrictions for off-label prescription may need consideration.” The study was published in BMJ.
The use of gabapentinoids has risen in the United States (JAMA Intern Med. 2018;178[2]:292-4), and overdose deaths tied to gabapentin have led some states to explore reclassification of the drug as a controlled substance (Risk Manag Healthc Policy. 2018;11:109-16). In the United Kingdom, gabapentinoids are being reclassified as a class C controlled drug because of concerns about the risk of addiction, overdose, and safety, wrote Dr. Molero of the department of psychiatry at Warneford Hospital at the University of Oxford, England, and associates.
To study associations between gabapentinoids and adverse outcomes related to coordination, mental health, and criminality, Dr. Molero and her associates analyzed data from 191,973 people from the Swedish Prescribed Drug Register who collected prescriptions for pregabalin or gabapentin between 2006 and 2013. The researchers included patients aged 15 years and older in their analyses.
They examined suicidal behavior, unintentional overdoses, head or body injuries, road traffic incidents and offenses, and arrests for violent crime using the Swedish Patient Register and the National Crime Register. In addition, they defined suicidal behavior as emergency hospital visits attributable to self-injurious behavior or suicide attempt, or death by suicide. Unintentional overdoses were defined as emergency hospital visits or death attributable to poisoning by illicit drugs, medications, or biologic substances; accidental poisoning by noxious substances; or acute intoxications and overdoses by alcohol and illicit drugs, excluding intentional self-poisoning, wrote Dr. Molero, who is affiliated with the Karolinska Institute in Stockholm, and her associates.
Of the nearly 192,000 participants who collected prescriptions of gabapentinoids on at least two consecutive occasions, 120,664 received pregabalin, and 85,360 received gabapentin; 14,051 of the participants received both drugs. Fifty-nine percent were women, and most patients were aged 45 or older.
During the study period, 10,026 participants (5.2%) were treated for suicidal behavior or died from suicide, 17,144 participants (8.9%) experienced an unintentional overdose, and 12,070 participants (6.3%) had a road traffic incident or offense. In addition, 70,522 participants (36.7%) had head or body injuries, and 7,984 participants (4.1%) were arrested for a violent crime.
The study used a within-individual design that compared when a person was taking a gabapentinoid with when he or she was not. During treatment periods, participants were at increased risk of suicidal behavior or death from suicide (age-adjusted hazard ratio, 1.26), unintentional overdose (1.24), head or body injuries (1.22), and road traffic incidents or offenses (1.13). Associations with arrests for violent crime were not significant.
Gabapentinoid treatment was associated with increased hazards of suicidal behavior in people young than 55 years, but hazards were reduced or not significant in participants aged 55 years and older. Participants aged 15-24 years had the highest hazards of suicidal behavior (1.67).
In a sensitivity analysis, the researchers examined participants who had a diagnosis of comorbid epilepsy, psychiatric disorders, or musculoskeletal disorders before the start of gabapentinoid treatment. Among patients with comorbid epilepsy, gabapentinoids were not significantly associated with suicidal behavior and were associated with reduced hazards for all other outcomes.
“In comorbid psychiatric disorders, gabapentinoids were associated with lower risk for all outcomes,” the researchers said. Among patients with comorbid musculoskeletal disorders, gabapentinoids were associated with reductions in head or body injuries, traffic incidents, and arrests for violent crime.
Dr. Molero and her associates noted that they lacked information about alcohol and drug use, as well as treatment adherence and the conditions for which gabapentinoids had been prescribed. Furthermore, differences in prescription practices and outcome rates might affect the generalizability of the results to other countries.
The different results for pregabalin and gabapentin “could be due to their different pharmacodynamic and pharmacokinetic profiles; pregabalin has a higher potency, greater bioavailability, and quicker absorption than gabapentin. Pregabalin also has been associated with withdrawal symptoms following rapid discontinuation, which could be related to suicidal behavior,” Dr. Molero and colleagues said. “The reduced hazards in older people could reflect pharmacodynamic differences related to age, less concurrent use of alcohol or drugs, different indications for treatment, or reduced symptom severity of underlying conditions.”
The Wellcome Trust, Swedish Research Council, and Karolinska Institute supported the study. The authors had no disclosures relevant to the study. One author reported grants from Shire and Evolan and has served as a speaker for Shire.
SOURCE: Molero Y et al. BMJ. 2019 Jun 12. doi: 10.1136/bmj.l2147.
The findings by Molero et al. advance clinical knowledge about the drug class of gabapentinoids, wrote Derek K. Tracy, MB BCh. Though the study does not establish causality, it does rely on a solid, large dataset. The study shows the importance of uncoupling pregabalin and gabapentin. Both drugs are indeed gabapentinoids, but their use can lead to different outcomes, depending on the age of patients. For example, pregabalin – not gabapentin – appears tied to higher risks of harm. The demographic group that is most vulnerable is patients aged 15-24, the researchers found. Factors driving those age-related differences in risks tied to the drugs need to be understood.
Dr. Tracy is a consultant psychiatrist at Queen Mary’s Hospital in London. He is a trustee of the charity Mentor and has received honoraria from Janssen for delivering educational talks on novel psychoactive substances. His comments were adapted from an editorial (BMJ. 2019 Jun 12. doi: 10.1136/bmj.14021 ).
The findings by Molero et al. advance clinical knowledge about the drug class of gabapentinoids, wrote Derek K. Tracy, MB BCh. Though the study does not establish causality, it does rely on a solid, large dataset. The study shows the importance of uncoupling pregabalin and gabapentin. Both drugs are indeed gabapentinoids, but their use can lead to different outcomes, depending on the age of patients. For example, pregabalin – not gabapentin – appears tied to higher risks of harm. The demographic group that is most vulnerable is patients aged 15-24, the researchers found. Factors driving those age-related differences in risks tied to the drugs need to be understood.
Dr. Tracy is a consultant psychiatrist at Queen Mary’s Hospital in London. He is a trustee of the charity Mentor and has received honoraria from Janssen for delivering educational talks on novel psychoactive substances. His comments were adapted from an editorial (BMJ. 2019 Jun 12. doi: 10.1136/bmj.14021 ).
The findings by Molero et al. advance clinical knowledge about the drug class of gabapentinoids, wrote Derek K. Tracy, MB BCh. Though the study does not establish causality, it does rely on a solid, large dataset. The study shows the importance of uncoupling pregabalin and gabapentin. Both drugs are indeed gabapentinoids, but their use can lead to different outcomes, depending on the age of patients. For example, pregabalin – not gabapentin – appears tied to higher risks of harm. The demographic group that is most vulnerable is patients aged 15-24, the researchers found. Factors driving those age-related differences in risks tied to the drugs need to be understood.
Dr. Tracy is a consultant psychiatrist at Queen Mary’s Hospital in London. He is a trustee of the charity Mentor and has received honoraria from Janssen for delivering educational talks on novel psychoactive substances. His comments were adapted from an editorial (BMJ. 2019 Jun 12. doi: 10.1136/bmj.14021 ).
Young patients might be at increased risk of suicidal behavior, unintentional overdose, injuries, and traffic incidents during treatment periods with gabapentinoids, compared with periods without treatment with those medications, a cohort study of almost 200,000 people shows. Pregabalin is associated with higher hazards of those outcomes than is gabapentin, and the associations are strongest in patients aged 15-24 years, the researchers reported.
“If our findings are triangulated with other forms of evidence, ,” wrote Yasmina Molero, PhD, and associates. “Further restrictions for off-label prescription may need consideration.” The study was published in BMJ.
The use of gabapentinoids has risen in the United States (JAMA Intern Med. 2018;178[2]:292-4), and overdose deaths tied to gabapentin have led some states to explore reclassification of the drug as a controlled substance (Risk Manag Healthc Policy. 2018;11:109-16). In the United Kingdom, gabapentinoids are being reclassified as a class C controlled drug because of concerns about the risk of addiction, overdose, and safety, wrote Dr. Molero of the department of psychiatry at Warneford Hospital at the University of Oxford, England, and associates.
To study associations between gabapentinoids and adverse outcomes related to coordination, mental health, and criminality, Dr. Molero and her associates analyzed data from 191,973 people from the Swedish Prescribed Drug Register who collected prescriptions for pregabalin or gabapentin between 2006 and 2013. The researchers included patients aged 15 years and older in their analyses.
They examined suicidal behavior, unintentional overdoses, head or body injuries, road traffic incidents and offenses, and arrests for violent crime using the Swedish Patient Register and the National Crime Register. In addition, they defined suicidal behavior as emergency hospital visits attributable to self-injurious behavior or suicide attempt, or death by suicide. Unintentional overdoses were defined as emergency hospital visits or death attributable to poisoning by illicit drugs, medications, or biologic substances; accidental poisoning by noxious substances; or acute intoxications and overdoses by alcohol and illicit drugs, excluding intentional self-poisoning, wrote Dr. Molero, who is affiliated with the Karolinska Institute in Stockholm, and her associates.
Of the nearly 192,000 participants who collected prescriptions of gabapentinoids on at least two consecutive occasions, 120,664 received pregabalin, and 85,360 received gabapentin; 14,051 of the participants received both drugs. Fifty-nine percent were women, and most patients were aged 45 or older.
During the study period, 10,026 participants (5.2%) were treated for suicidal behavior or died from suicide, 17,144 participants (8.9%) experienced an unintentional overdose, and 12,070 participants (6.3%) had a road traffic incident or offense. In addition, 70,522 participants (36.7%) had head or body injuries, and 7,984 participants (4.1%) were arrested for a violent crime.
The study used a within-individual design that compared when a person was taking a gabapentinoid with when he or she was not. During treatment periods, participants were at increased risk of suicidal behavior or death from suicide (age-adjusted hazard ratio, 1.26), unintentional overdose (1.24), head or body injuries (1.22), and road traffic incidents or offenses (1.13). Associations with arrests for violent crime were not significant.
Gabapentinoid treatment was associated with increased hazards of suicidal behavior in people young than 55 years, but hazards were reduced or not significant in participants aged 55 years and older. Participants aged 15-24 years had the highest hazards of suicidal behavior (1.67).
In a sensitivity analysis, the researchers examined participants who had a diagnosis of comorbid epilepsy, psychiatric disorders, or musculoskeletal disorders before the start of gabapentinoid treatment. Among patients with comorbid epilepsy, gabapentinoids were not significantly associated with suicidal behavior and were associated with reduced hazards for all other outcomes.
“In comorbid psychiatric disorders, gabapentinoids were associated with lower risk for all outcomes,” the researchers said. Among patients with comorbid musculoskeletal disorders, gabapentinoids were associated with reductions in head or body injuries, traffic incidents, and arrests for violent crime.
Dr. Molero and her associates noted that they lacked information about alcohol and drug use, as well as treatment adherence and the conditions for which gabapentinoids had been prescribed. Furthermore, differences in prescription practices and outcome rates might affect the generalizability of the results to other countries.
The different results for pregabalin and gabapentin “could be due to their different pharmacodynamic and pharmacokinetic profiles; pregabalin has a higher potency, greater bioavailability, and quicker absorption than gabapentin. Pregabalin also has been associated with withdrawal symptoms following rapid discontinuation, which could be related to suicidal behavior,” Dr. Molero and colleagues said. “The reduced hazards in older people could reflect pharmacodynamic differences related to age, less concurrent use of alcohol or drugs, different indications for treatment, or reduced symptom severity of underlying conditions.”
The Wellcome Trust, Swedish Research Council, and Karolinska Institute supported the study. The authors had no disclosures relevant to the study. One author reported grants from Shire and Evolan and has served as a speaker for Shire.
SOURCE: Molero Y et al. BMJ. 2019 Jun 12. doi: 10.1136/bmj.l2147.
Young patients might be at increased risk of suicidal behavior, unintentional overdose, injuries, and traffic incidents during treatment periods with gabapentinoids, compared with periods without treatment with those medications, a cohort study of almost 200,000 people shows. Pregabalin is associated with higher hazards of those outcomes than is gabapentin, and the associations are strongest in patients aged 15-24 years, the researchers reported.
“If our findings are triangulated with other forms of evidence, ,” wrote Yasmina Molero, PhD, and associates. “Further restrictions for off-label prescription may need consideration.” The study was published in BMJ.
The use of gabapentinoids has risen in the United States (JAMA Intern Med. 2018;178[2]:292-4), and overdose deaths tied to gabapentin have led some states to explore reclassification of the drug as a controlled substance (Risk Manag Healthc Policy. 2018;11:109-16). In the United Kingdom, gabapentinoids are being reclassified as a class C controlled drug because of concerns about the risk of addiction, overdose, and safety, wrote Dr. Molero of the department of psychiatry at Warneford Hospital at the University of Oxford, England, and associates.
To study associations between gabapentinoids and adverse outcomes related to coordination, mental health, and criminality, Dr. Molero and her associates analyzed data from 191,973 people from the Swedish Prescribed Drug Register who collected prescriptions for pregabalin or gabapentin between 2006 and 2013. The researchers included patients aged 15 years and older in their analyses.
They examined suicidal behavior, unintentional overdoses, head or body injuries, road traffic incidents and offenses, and arrests for violent crime using the Swedish Patient Register and the National Crime Register. In addition, they defined suicidal behavior as emergency hospital visits attributable to self-injurious behavior or suicide attempt, or death by suicide. Unintentional overdoses were defined as emergency hospital visits or death attributable to poisoning by illicit drugs, medications, or biologic substances; accidental poisoning by noxious substances; or acute intoxications and overdoses by alcohol and illicit drugs, excluding intentional self-poisoning, wrote Dr. Molero, who is affiliated with the Karolinska Institute in Stockholm, and her associates.
Of the nearly 192,000 participants who collected prescriptions of gabapentinoids on at least two consecutive occasions, 120,664 received pregabalin, and 85,360 received gabapentin; 14,051 of the participants received both drugs. Fifty-nine percent were women, and most patients were aged 45 or older.
During the study period, 10,026 participants (5.2%) were treated for suicidal behavior or died from suicide, 17,144 participants (8.9%) experienced an unintentional overdose, and 12,070 participants (6.3%) had a road traffic incident or offense. In addition, 70,522 participants (36.7%) had head or body injuries, and 7,984 participants (4.1%) were arrested for a violent crime.
The study used a within-individual design that compared when a person was taking a gabapentinoid with when he or she was not. During treatment periods, participants were at increased risk of suicidal behavior or death from suicide (age-adjusted hazard ratio, 1.26), unintentional overdose (1.24), head or body injuries (1.22), and road traffic incidents or offenses (1.13). Associations with arrests for violent crime were not significant.
Gabapentinoid treatment was associated with increased hazards of suicidal behavior in people young than 55 years, but hazards were reduced or not significant in participants aged 55 years and older. Participants aged 15-24 years had the highest hazards of suicidal behavior (1.67).
In a sensitivity analysis, the researchers examined participants who had a diagnosis of comorbid epilepsy, psychiatric disorders, or musculoskeletal disorders before the start of gabapentinoid treatment. Among patients with comorbid epilepsy, gabapentinoids were not significantly associated with suicidal behavior and were associated with reduced hazards for all other outcomes.
“In comorbid psychiatric disorders, gabapentinoids were associated with lower risk for all outcomes,” the researchers said. Among patients with comorbid musculoskeletal disorders, gabapentinoids were associated with reductions in head or body injuries, traffic incidents, and arrests for violent crime.
Dr. Molero and her associates noted that they lacked information about alcohol and drug use, as well as treatment adherence and the conditions for which gabapentinoids had been prescribed. Furthermore, differences in prescription practices and outcome rates might affect the generalizability of the results to other countries.
The different results for pregabalin and gabapentin “could be due to their different pharmacodynamic and pharmacokinetic profiles; pregabalin has a higher potency, greater bioavailability, and quicker absorption than gabapentin. Pregabalin also has been associated with withdrawal symptoms following rapid discontinuation, which could be related to suicidal behavior,” Dr. Molero and colleagues said. “The reduced hazards in older people could reflect pharmacodynamic differences related to age, less concurrent use of alcohol or drugs, different indications for treatment, or reduced symptom severity of underlying conditions.”
The Wellcome Trust, Swedish Research Council, and Karolinska Institute supported the study. The authors had no disclosures relevant to the study. One author reported grants from Shire and Evolan and has served as a speaker for Shire.
SOURCE: Molero Y et al. BMJ. 2019 Jun 12. doi: 10.1136/bmj.l2147.
FROM BMJ
Key clinical point: Patients might be at increased risk of suicidal behavior, unintentional overdose, head and body injuries, and traffic incidents during periods of treatment with gabapentinoids. Pregabalin is associated with higher hazards of these outcomes than is gabapentin, and the associations are strongest in patients aged 15-24 years.
Major finding: During treatment periods, patients were at increased risk of suicidal behavior or death from suicide (age-adjusted hazard ratio, 1.26), unintentional overdose (1.24), head or body injuries (1.22), and road traffic incidents or offenses (1.13).
Study details: An analysis of data from 191,973 people from the Swedish Prescribed Drug Register, which collected prescriptions for pregabalin or gabapentin between 2006 and 2013.
Disclosures: The Wellcome Trust, Swedish Research Council, and Karolinska Institute supported the study. The authors had no relevant disclosures. One author reported grants from Shire and Evolan, and has served as a speaker for Shire.
Source: Molero Y et al. BMJ. 2019 Jun 12. doi: 10.1136/bmj.l2147.