Steep Jump in Gabapentinoid Use Among US Patients With Cancer

Veronica Hackethal, MD

November 07, 2019

A steep increase in the use of gabapentin and pregabalin (known collectively as gabapentinoids) among adults in the United States with cancer is reported in a study published online October 25 in Supportive Care in Cancer.

This increase among cancer patients echoes a broader nationwide trend, with speculation that these drugs are being prescribed off-label in place of opioids. 

For the study, researchers analyzed data from the Medical Expenditure Panel Survey (MEPS), a nationally representative sample of American adults, and calculated the annual percentages of gabapentinoid use in American adults with cancer between 2005 and 2015.

Results adjusted for age, sex, and region of residence showed that annual percentage use of gabapentinoids in this population increased from 2.3% in 2005 to 5.6% in 2015 (rate ratio 2.39; P < .001).

"For 2005–2015, we observed greater than a twofold increase in the number of adults with cancer in the US who used gabapentinoid medications," study author Alex Fauer, RN, a PhD candidate at the University of Michigan School of Nursing in Ann Arbor, told Medscape Medical News.

"Prescriptions increased to about 3.5 million in 2015, which was also a twofold increase since 2005," he added.

The MEPS data did not have information on indications for use, so the study cannot draw conclusions on the appropriateness of gabapentinoid prescribing in this population. But, given the current opioid crisis, it's possible prescribers have turned to gabapentinoids to replace opioids, suggest the authors.

"These findings are largely reflective of what I have observed in my practice in recent years," said Kirk Evoy, PharmD, an ambulatory care clinical pharmacist and clinical assistant professor at the the University of Texas at Austin who was not involved in the study.

"As prescribers seek to reduce opioid prescribing in light of the opioid overdose crisis, they frequently turn to nonopioid pain adjuvants such as gabapentinoids," he told Medscape Medical News.

Indeed, recent research suggests use of these medications more than tripled nationwide between 2002 and 2015.

Gabapentin and pregabalin are both approved by the Food and Drug Administration (FDA) for use in the treatment of seizures and neurologic pain caused by shingles. In addition to these two indications, pregabalin is also FDA-approved to treat diabetic neuropathy.

However, the vast majority of prescriptions for these two drugs — about 95% according to one study of Medicaid beneficiaries — are for a wide range of off-label uses such as migraines, hot flashes, mental health conditions, and restless legs syndrome. There is little evidence to support efficacy outside of the FDA-approved indications, the authors of this study noted.

May Be Appropriate for Patients With Cancer

Gabapentinoids may benefit some individuals with cancer, such as those with comorbid disorders like partial seizures or restless legs syndrome, said Jordan Covvey, PharmD, PhD, assistant professor at Duquesne University School of Pharmacy, Pittsburgh, Pennsylvania, in an email. He has conducted research on trends in gabapentinoid use in the US, but was not involved in this current study.

"The choice of medication is highly dependent on individual patient characteristics and risk factors. For some patients with cancer, gabapentinoids may be completely appropriate, while for others, other treatment options may be preferred," she said.

The effects of cancer treatment don't stop after completing therapy. Many cancer survivors have received neurotoxic chemotherapies, and they can experience chronic neuropathic pain up to five years after completing cancer treatment.

"Given that cancer pain can be very difficult to manage and that often this pain may be neuropathic in nature, I think prescribing gabapentinoids for patients with cancer pain may be appropriate in many situations," Evoy said, agreeing with Covvey.

However, Evoy urged providers to weigh the lack of evidence about the effectiveness of gabapentinoids for most non-neuropathic pain against the potential risks and side effects of these drugs.

"These drugs have traditionally been thought to have very little risk associated with their use, but there is now sufficient evidence indicating this is not the case when they are taken alongside opioids," Evoy said.

Research suggests that using gabapentinoids at the same time as opioids may increase the risk for respiratory depression and death.  Also, gabapentinoids are increasingly being recognized as potential drugs of abuse. One study found that use of gabapentin to "get high" increased almost 3000% between 2008 and 2012 among rural Appalachian injection drug users.

Some states have already acknowledged the potential for abuse of gabapentinoids and have taken action. In Michigan, Virginia, and Alabama gabapentin and pregabalin are now schedule 5 controlled substances. Ohio, Kentucky, and West Virginia consider them controlled substances at the state level, though these drugs remain noncontrolled substances at the federal level.

Other adverse effects of gabapentinoids include fatigue and weight gain. Chronic users may have symptoms of clumsiness, depression, physical dependence, and withdrawal. And although evidence is mixed, use of gabapentinoids among people with mental health problems has been linked to increased risk for suicide.

The study was supported by the National Cancer Institute. The authors have disclosed no relevant financial relationships.

Supportive Care in Cancer. Published online October 25, 2019. Abstract

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