Gabapentin for Off-Label Use: Evidence-Based or Cause for Concern?

Abstract

Gabapentin is widely used in the United States for a number of off-label indications, often as an alternative to opioid therapy. Increasing evidence has emerged suggesting that gabapentin may not be as benign as once thought and may be associated with substance abuse in concert with opioids. With concerns for safety mounting, it is prudent to examine the efficacy of gabapentin across its many uses to understand the risk-benefit balance. Reviews on off-label indications such as migraine, fibromyalgia, mental illness, and substance dependence have found modest to no effect on relevant clinical outcomes. This high-quality evidence has often been overshadowed by uncontrolled studies and limited case reports. Furthermore, the involvement of gabapentin in questionable marketing schemes further calls its use into question. Overall, clinicians should exercise rigorous appraisal of the available evidence for a given indication, and researchers should conduct larger, higher-quality studies to better assess the efficacy of gabapentin for many of its off-label uses.

A case of gabapentin overdose induced rhabdomyolysis requiring renal replacement therapy

“…Gabapentin functions as a γ‐aminobutyric acid (GABA)‐mimetic agent, binding to the alpha‐2‐delta subunit of the voltage‐gated calcium channels . Gabapentin was originally approved by the US Food and Drug Administration (FDA) in 1993 for epilepsy and later, postherpetic neuralgia . Recently, gabapentin has been increasingly used in some off‐label indications as a desired alternative of opioids for pain management, probably due to its relative low rate of adverse effect and low cost.…”

“…Gabapentin was originally approved by the US Food and Drug Administration (FDA) in 1993 for epilepsy and later, postherpetic neuralgia . Recently, gabapentin has been increasingly used in some off‐label indications as a desired alternative of opioids for pain management, probably due to its relative low rate of adverse effect and low cost. However, in recent years, reports of recreational gabapentin abuse or intentional misuse have increased at an alarming rate with reported adverse effects .…”

“…For differential diagnosis, trauma, exertion, genetic defects, muscle hypoxia, infection, body-temperature changes, drugs and toxins, metabolic, and electrolyte disorders are common causes of rhabdomyolysis. 1 Lipid-lowering drugs (fibrates, statins), alcohol, heroin, and cocaine were common drugs that can cause rhabdomyolysis. For our patient, he denied any recent trauma, seizure, any intense physical activities, opioid and cocaine intake, and family history of muscular disease.…”

“…Gabapentin is an anticonvulsant drug, also used in neuropathic pain caused by herpes zoster or diabetes, and restless legs syndrome. It has more and more widely used for off‐label indications such as migraine, fibromyalgia, mental illness, and substance dependence . Its common side effects include dizziness, drowsiness, ataxia, fatigue, tremor, nausea, and vomiting.…”

“…It has more and more widely used for off-label indications such as migraine, fibromyalgia, mental illness, and substance dependence. 1 Its common side effects include dizziness, drowsiness, ataxia, fatigue, tremor, nausea, and vomiting. Here, we report a rare toxicity by gabapentin overdose: rhabdomyolysis and acute renal failure.…”