Before You Prescribe Gabapentin, Consider These Risks

Prescriptions for the anticonvulsant gabapentin have been steadily rising for more than a decade, primarily due to off-label use of the medication for a variety of conditions including pain, substance use disorder, and more. In 2021, gabapentin was ranked among the top 10 most prescribed medications in the United States.

Though gabapentin was initially marketed as a medication with low potential for abuse and is commonly thought to be safe and effective, a growing body of evidence highlights the potential risks of overprescribing the medication. Here are several factors to keep in mind when considering gabapentin for your patients or working with patients who have been prescribed gabapentin by another doctor.

Why So Popular?

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.

What Are the Risks?

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.

What Can Psychiatrists Do?

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

• Educate patients: Engaging in open and honest discussions with patients about the risks and benefits of gabapentin is essential. Patients should be made aware of the potential for abuse, dependence, and overdose. They should also be educated about proper medication storage and disposal.

• Screen patients for substance use disorders and other medications: Before prescribing gabapentin, psychiatrists should routinely screen patients for substance use disorders and reconcile any medications the patient may be taking which may lead to deleterious interactions.

• Prescribe first-line medications: Before prescribing gabapentin, psychiatrists should prioritize the use of evidence-based first-line medications for specific symptoms and conditions. Superior agents exist for managing common issues such as anxiety, sleep disturbances, pain, and mood disorders, and should be considered as primary treatment options.

• Consider alternative pain management strategies: Psychiatrists should consider adopting multimodal pain management strategies, especially for chronic pain conditions. Combining non-opioid medications, physical therapies, and psychological interventions can often lead to better outcomes while minimizing reliance on a single medication.

• Regularly evaluate the effectiveness of gabapentin: Psychiatrists should periodically assess the effectiveness of gabapentin treatment. If the desired outcomes are not achieved within six months, alternative treatment options or adjustments to the treatment plan should be explored.

• Report adverse events: Psychiatrists should report adverse events related to gabapentin. Such information will contribute to a better understanding of the safety profile of the medication and help regulatory agencies take appropriate measures if needed.

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. ■

Dr. Egan would like to thank Dr. Smita Das and Dr. Michael Ostracher for their assistance with this article.

Donald Egan, M.D., M.P.H., is a third-year psychiatry resident at the University of Texas Southwestern Medical Center. He is the vice chair for the APA Diversity Leadership Fellowship and serves on the Council on Addiction Psychiatry for the APA.