Before You Prescribe Gabapentin, Consider These Risks

Gabapentin (Neurontin) and pregabalin (Lyrica) are both gabapentinoids—psychotropic medications that cross the blood-brain barrier and mimic the inhibitory neurotransmitter Gamma-aminobutyric acid (GABA). Gabapentin was first approved by the Food and Drug Administration (FDA) in 1993 as an adjunctive treatment for partial seizures. In 2002, the medication was approved for the treatment of postherpetic neuralgia, a painful complication of shingles.

Since these FDA approvals, the off-label use of gabapentin for other conditions has risen steadily. A report in JAMA Internal Medicine found that as U.S. prescriptions for gabapentin prescriptions climbed from 2006 to 2018; prescriptions for opioids leveled off before eventually beginning to fall over this timeframe. Another study found that nearly 1 in 5 adults with chronic pain were prescribed gabapentinoids in 2018.

In addition to being used to treat pain, gabapentin is used off label to treat anxiety, alcohol use disorder (AUD), alcohol withdrawal, depression, substance use disorders (SUDs), sleep problems, and more. However, the data to support these off-label uses of gabapentin are mixed, especially for long-term use.

The rise in gabapentin prescribing is multifactorial but thought to be due in part to efforts by the pharmaceutical industry to promote the use of the medication for off-label uses. (In 2004, the manufacturer of Neurontin, Pfizer, pleaded guilty to multiple counts of illegally promoting the off-label use of gabapentin, resulting in nearly $430 million in fines.) Additionally, gabapentinoids are still considered relatively benign medications and safer alternatives to controlled substances such as opioids for pain or benzodiazepines for sleep or anxiety.

The rising use of gabapentin in combination with the ongoing opioid crisis has contributed to a surge of negative health outcomes including hospitalizations and death.

In 2019 the FDA issued a warning about the potential risks of respiratory depression in patients taking gabapentin or pregabalin in combination with central nervous system (CNS) depressants such as opioids, antidepressants, and benzodiazepines. The FDA also warned the medication could increase breathing difficulties in patients with underlying lung disorders, such as asthma or COPD, as well as the elderly.

Despite this warning, gabapentin prescribing has continued to increase in the United States. According to IQVIA National Prescription Audit, total prescriptions dispensed for gabapentin were approximately 68.3 million in 2019, 69.0 million in 2020, and 70.9 million in 2021. At least 40% to 65% of individuals with prescriptions for gabapentin and roughly 20% for individuals who misuse opioids report gabapentin misuse.

Gabapentin misuse may in part be driven by dependence and withdrawal symptoms. Studies have demonstrated that patients who have taken as little as 400 mg daily for three weeks may experience withdrawal symptoms—including anxiety, pain, nausea, fatigue, and restlessness—that can begin within 12 hours of stopping the medication and can last up to 10 days.

Such misuse can quickly turn deadly: The Centers for Disease Control and Prevention (CDC) in 2022 issued a report that found the number of overdose deaths involving gabapentin approximately doubled from 2019 to 2020.

There are actions psychiatrists can take to reduce the use of gabapentin:

Amidst the emerging evidence of the adverse consequences of over prescribing of gabapentin, there is a pressing need for medical professionals to discuss the prescribing practices involving these medications. These conversations should focus on evidence-based interventions over unsupported off-label applications that do not have data to support their efficacy and may lead to long-term impacts on health. This is not to say that there is not a role for gabapentin in modern medical practice, but rather a need to reevaluate prescribing practices in order to maximize patient care as well as prevent the potential development of a medication-related crisis. ■

“Gabapentin Misuse, Abuse and Diversion: A Systematic Review”

“Trends in Gabapentin Prescribing in a Commercially Insured U.S. Adult Population, 2009-2016”

“Trends in the Concurrent Prescription of Opioids and Gabapentin in the US, 2006 to 2018”

“Gabapentin and Pregabalin for Pain — Is Increased Prescribing a Cause for Concern?”

“Trends in Gabapentin Detection and Involvement in Drug Overdose Deaths — 23 States and the District of Columbia, 2019–2020”