P-110 - (Poster #110) What are the mechanisms and clinical implications of gabapentin-induced myoclonus?

Background: Gabapentin is widely prescribed for neuropathic pain and sensory pathway disorders due to its efficacy and favorable safety profile. However, myoclonus a sudden, involuntary muscle jerk has emerged as a rare yet clinically significant adverse effect, raising concern about patient safety, especially in individuals with underlying sensory or renal dysfunction. The true incidence and risk factors remain poorly characterized, with mechanisms thought to involve calcium channel modulation, serotonergic pathways, and renal drug accumulation. As gabapentin use continues to expand in populations vulnerable to neurological side effects, such as those with diabetic neuropathy or chronic kidney disease, understanding gabapentin-induced myoclonus is vital for optimal care and informed prescribing.

Purpose/Objectives:

This systematic review aims to comprehensively characterize the mechanisms, clinical presentation, and risk factors associated with gabapentin-induced myoclonus in patients with neuropathic pain or sensory pathway disorders. The primary objective is to synthesize all available clinical and mechanistic evidence to inform clinicians about the scope, underlying causes, and best management practices for this adverse event. Secondary objectives include identifying gaps in current knowledge and providing recommendations for future research and clinical guidelines in the context of pain management and pharmacovigilance.

Methods:

A systematic search of PubMed, Embase, and other medical databases was conducted in accordance with PRISMA guidelines to identify clinical trials, case reports, observational studies, and reviews reporting gabapentin-induced myoclonus. Studies involving human subjects with neuropathic pain or sensory pathway disorders were included, with exclusion criteria set for non-human, pediatric-only (if adult focus), and studies lacking gabapentin exposure or myoclonus outcomes. Data were extracted on patient demographics, gabapentin dosing, renal function, co-medications, myoclonus characteristics, and outcomes. Methodological quality was assessed using established tools, and a narrative synthesis, supplemented by quantitative summary where feasible, was performed to elucidate patterns and mechanistic insights.

Results:

The review identified over 50 eligible studies, including case reports, series, and observational analyses, highlighting that gabapentin-induced myoclonus, though rare, is a clinically relevant adverse event predominantly reported in patients with impaired renal function or advanced age. Myoclonus typically developed within days to weeks of gabapentin initiation or dose escalation, presenting as focal, multifocal, or generalized jerks that impaired daily activities. Mechanistic data implicate impaired renal clearance, leading to drug accumulation, as a major risk factor, with additional proposed roles for altered calcium channel activity and serotonergic pathways. Notably, some cases occurred even in patients with normal renal function, particularly the elderly, suggesting possible age-related pharmacodynamic susceptibility or undiagnosed subclinical renal impairment.

Renal adjustment of gabapentin dosing significantly reduced the risk, and withdrawal of the drug led to resolution of myoclonus in the vast majority of cases. A minority of patients required additional interventions, such as hemodialysis or anti-myoclonic agents, with no deaths attributable to this complication. Several studies emphasized the importance of close monitoring, dose titration, and awareness among prescribers, especially for high-risk patient subgroups. Limitations in reporting and data heterogeneity precluded meta-analysis, but the evidence strongly supports the need for tailored prescribing and vigilance for new-onset movement disorders in this context.

Conclusions/Implications for future research and/or clinical care: Gabapentin-induced myoclonus is an underrecognized adverse event with important implications for the management of neuropathic pain, particularly in adults with renal impairment or advanced age. Clinicians should maintain a high index of suspicion for new movement symptoms shortly after initiating or increasing gabapentin, and routinely assess renal function to guide dosing. Routine pharmacovigilance and clear protocols for symptom driven drug discontinuation are recommended. Further research is warranted to clarify the precise mechanistic pathways, to develop predictive risk models, and to assess the impact of alternative neuropathic pain therapies in high risk populations. Improved case reporting and prospective studies may inform evidence-based guidelines, ultimately enhancing patient safety and therapeutic outcomes.