Invited Review
Gabapentin and Dementia: Are the Benefits Worth the Risk for Spine-Related Pain?
John D. Hesling, MD
University of Colorado School of Medicine Aurora, CO
Austin Boos, DO
University of Colorado School of Medicine Aurora, CO
Key Takeaways
- Gabapentin prescriptions are increasing and emerging evidence suggests a weak link between gabapentin and dementia that prompts renewed evaluation of risk versus reward.
- Consistent with prior NASS guidelines, available efficacy data do not support the routine use of gabapentin for many common spine-related indications, including low back pain with or without radicular pain and neuropathic pain caused by neurogenic claudication.
- Prescribing decisions should be individualized with shared decision making while using risk-mitigating prescribing practices such as time-limited trials, using the lowest effective dose and avoiding unnecessarily long treatment duration.
Introduction
Gabapentin is commonly prescribed off-label to treat neuropathic pain conditions of spinal etiology, including radiculitis, painful radiculopathy, and central canal stenosis with radicular pain and/or neurogenic claudication. Recent studies have highlighted a potential association between gabapentin use and dementia, a concern that has gained broader visibility through lay media coverage and is increasingly being raised by patients. This article reviews the available literature exploring the potential association between gabapentin use and dementia, examines other established risks of gabapentin therapy and contrasts these potential harms with the evidence supporting its clinical efficacy.
Background
While gabapentin is approved by the United States Food and Drug Administration (FDA) for the treatment of partial seizures and postherpetic neuralgia, it is commonly prescribed off label by spine providers for a range of neuropathic and chronic pain conditions.1,2 Gabapentin is a structural analogue of γ-aminobutyric acid (GABA), but its analgesic activity is not attributable to direct agonism at GABA receptors or other primary GABAergic mechanisms.3–5 Instead, gabapentin binds with high affinity to the α2δ subunit of presynaptic voltage-gated calcium channels in neuronal tissue, including within central nociceptive pathways.3–5 This binding is thought to reduce functional calcium channel activity and/or membrane trafficking, thereby decreasing activity-dependent calcium influx at presynaptic terminals and reducing release of excitatory neurotransmitters such as glutamate that facilitate nociceptive transmission. In neuropathic pain models, α2δ expression is upregulated after nerve injury and is implicated in enhanced synaptic transmission and central sensitization; therefore, modulation of this subunit by gabapentin provides a biologically plausible mechanism for attenuating hyperexcitability, allodynia, and hyperalgesia in select chronic pain states.6