Suicide attempts reported to poison control among patients taking gabapentin, a widely prescribed anticonvulsant embraced as an alternative pain medication in the wake of curtailed opioid prescribing, increased over 80% between 2013 and 2017.
Minnesota and South Dakota were among the states with the fastest-growing number of poisoning calls for individuals on gabapentin and other drugs during the period of study. With a 762% increase, North Dakota led the nation in relative rate increase for gabapentin-only poisoning calls.
Those are among the findings of a new study on calls to poison centers involving gabapentin and the muscle relaxant baclofen, by researchers from the University of Pittsburgh and published online Monday, Dec. 2, in the journal Clinical Toxicology.
"Opioids have been getting a lot of attention in the media and prescribing rates have been declining over the past few years," says Kimberly Reynolds DNP, University of Pittsburgh, who authored the study with five other U-Pitt nursing and toxicology clinicians. "We hypothesized this has led to an increased rate of prescribing of nonopioid medications, including gabapentin and baclofen. We wanted to see what the outcome of those changes were."
The 10th-most widely prescribed drug in the U.S. as of 2017, gabapentin, commonly sold under the brand name Neurontin, is FDA-approved only for epileptic seizures and the treatment of nerve pain from shingles, though it is widely prescribed off-label for a litany of psychiatric, pain and other conditions.
The drug is believed to have attained an illicit demand for its mild euphoria at excess doses. Minnesota and North Dakota are among eight states nationally with mandated reporting of gabapentin prescribing in a Prescription Drug Monitoring Program database. Its ability to to prevent pain is considered questionable. A 2017 Chochrane review found that "over half of those treated with gabapentin will not have worthwhile pain relief but may experience adverse events."
Critics say the profligate prescribing practices surrounding gabapentin stem from years of illegal marketing practices by its manufacturer Pfizer, which has thus far paid nearly a billion dollars in penalties for overstating the drug's benefits. It has also been the subject of wrongful death litigation settlements due to reports of suicidal thinking and actions in a small percentage of users.
Pharmacologically, the drug interrupts pain signals through a process that causes a reduction in dopamine, serotonin and norepinephrine. This down-regulation of mood- and impulsivity-related neurotransmitters is believed to precipitate the characteristic agitation and distress precipitating drug-induced suicidal thinking and actions.
The FDA added suicidality warnings to all epilepsy drugs in 2008. Today, the label insert for Nuerontin states that "antiepileptic drugs (AEDs), including Neurontin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication."
Observational and challenge-dechallenge reports show a link with gabapentin and suicidality. Earlier this year, a large cohort study from Sweden published in the journal BMJ comparing treatment and non-treatment periods within the same individuals found gabapentinoids increased suicidal thinking and actions, especially in those under 24. In 2018, case reports in the journal Surgical Neurology International describe patients for whom gabapentin preceded personality change and suicidal urges, effects which subsided upon discontinuation.
Calling the increase in drug-related suicide attempts "pretty notable, and pretty surprising," Reynolds believes the findings suggest the need for greater screening prior to prescribing the medications.
"I think it could be anticipated that some of these patients prescribed gabapentin and baclofen would be more likely to be treated for mood disorders and pain, because they're frequently co-morbid conditions," she says. "Patients who are prescribed these medications should be screened for substance use disorders, mood disorders and suicidal ideation utilizing screening tools."
Reynolds believes the findings are potentially an undercounting of the problem, given that they are gleaned from only those cases resulting in calls to poison centers. She also noted the recent spike in gabapentin-related suicide calls come during a decline in poisoning calls nationwide.
"It's definitely safer than opioids," she says of the drugs, "but there's still risks. Which is why I think there's room for exploration of these issues in the whole arena of pain management."