What are the potential adverse reactions of gabapentin (Neurontin)?

Gabapentin Adverse Reactions

Gabapentin commonly causes dizziness, somnolence, and peripheral edema, with approximately 63% of patients experiencing at least one adverse event compared to 49% with placebo. 1

Most Common Adverse Reactions

Neurological Effects (Most Frequent)

• Dizziness occurs in 19-28% of patients, representing the most common adverse reaction 1, 2
• Somnolence/sedation affects 14-21% of patients 1, 2
• Ataxia develops in 13% of patients taking gabapentin for epilepsy 1
• Nystagmus occurs in 8% of patients 1
• Tremor affects 7% of patients 1
• Diplopia (double vision) occurs in 6% of patients 1

Other Common Reactions

• Peripheral edema develops in 7-8% of patients 1, 2
• Fatigue/asthenia affects 6-11% of patients 1
• Gait disturbance occurs in 14% of patients 2
• Dry mouth affects 5% of patients 1
• Confusion has been reported in clinical trials 3
• Nausea occurs in 4% of patients 1

Dose-Response Relationship

Higher doses are associated with increased adverse event risk, particularly for falls and fractures. 4

• Doses ≥600 mg/day show increased risk of altered mental status 4
• Doses ≥2,400 mg/day carry the highest risk (RR 1.90) for falls or fractures 4
• Somnolence and ataxia demonstrate clear positive dose-response relationships 1

Serious Adverse Reactions

Falls and Fractures

• Incidence of 1.81 per 100 person-years in exposed patients versus 1.34 per 100 person-years in unexposed patients (RR 1.35) 4
• Risk increases substantially with doses ≥2,400 mg/day 4

Altered Mental Status

• Incidence of 1.08 per 100 person-years in exposed patients versus 0.97 per 100 person-years in unexposed patients (RR 1.12) 4
• Includes confusion, memory loss, and cognitive impairment 3, 1

Life-Threatening Reactions

• DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)/Multiorgan Hypersensitivity 1
• Anaphylaxis and angioedema 1
• Withdrawal-precipitated seizures and status epilepticus when discontinued abruptly 1
• Suicidal behavior and ideation 1
• Eight deaths reported in clinical trials, though serious adverse events were not significantly more common than placebo (3.2% vs 2.8%) 2

Less Common but Notable Reactions

• Hepatitis has been reported in pharmacovigilance data 5
• Blurred vision (amblyopia) occurs in 3-4% of patients 1
• Headache reported in some patients 3

Withdrawal Rates

Adverse events lead to treatment discontinuation in 11% of gabapentin-treated patients versus 8.2% with placebo (NNH 30). 2

• In postherpetic neuralgia trials, 16% discontinued gabapentin versus 9% on placebo 1
• Most common reasons for withdrawal: dizziness, somnolence, nausea, ataxia, and fatigue 1
• In epilepsy trials, approximately 7% of patients discontinued due to adverse reactions 1

Special Populations

Pediatric Patients (Ages 3-12)

• Neuropsychiatric reactions are particularly concerning, including emotional lability (4%), hostility (8%), and hyperkinesia (3%) 1
• Viral infection (11%) and fever (10%) occur more frequently than in adults 1

Elderly Patients

• Increased incidence of adverse reactions with advancing age 1
• Weight gain and peripheral edema are especially problematic in elderly patients 6
• Lower starting doses and slower titration are recommended 3, 7

Patients with Renal Impairment

• Dose adjustment is mandatory as gabapentin is eliminated unchanged in urine 6
• Even moderate renal failure (creatinine clearance <60 mL/min) requires dose reduction 6

Clinical Context Considerations

Perioperative Use

When used preoperatively for pain management, gabapentin provides analgesia but carries risk of sedation, dizziness, and blurred vision that may be particularly concerning in ambulatory patients. 3

• Side effects were surprisingly not reported in breast surgery studies despite high doses used 3
• Single lowest dose is recommended to minimize sedative effects 3

Chronic Cough Treatment

In unexplained chronic cough trials, adverse events occurred in 31% of gabapentin patients versus 10% of placebo patients, though this difference was not statistically significant 3

Neuropathic Pain

Over half of patients treated with gabapentin for neuropathic pain will not achieve worthwhile pain relief but may still experience adverse events. 2

• NNH for any adverse event is 7.5 (6.1 to 9.6) 2
• Benefits must be reassessed regularly, with guidelines suggesting evaluation at 6 months 3

Important Clinical Pitfalls

• Do not abruptly discontinue gabapentin in patients with epilepsy due to risk of withdrawal seizures 1
• Monitor closely for suicidal ideation, particularly when initiating therapy 1
• Adjust doses in renal impairment to prevent accumulation and increased toxicity 7, 6
• Use caution with concomitant CNS depressants due to synergistic sedative effects 3
• Screen for falls risk in elderly patients and those on higher doses (≥600 mg/day) 4