What are the side effects of gabapentin (Neurontin)?

Gabapentin Side Effects

The most common side effects of gabapentin include dizziness, somnolence (drowsiness), and peripheral edema, with approximately 10% of patients discontinuing treatment due to these adverse effects. 1

Common Side Effects

Gabapentin's side effect profile is well-documented in both FDA labeling and clinical guidelines. The most frequently reported adverse effects include:

• Central Nervous System Effects:

  • Dizziness (28% of patients)
  • Somnolence/drowsiness (21% of patients)
  • Ataxia (coordination problems) (3%)
  • Fatigue
  • Abnormal thinking
  • Abnormal gait
  • Incoordination 1

• Gastrointestinal Effects:

  • Dry mouth (5%)
  • Nausea (4%)
  • Constipation (4%)
  • Diarrhea (6%)
  • Vomiting (3%) 1

• Other Common Effects:

  • Peripheral edema (swelling, usually of legs and feet) (8%)
  • Weight gain (2%)
  • Visual disturbances (diplopia, blurred vision) 1

Serious Side Effects

While gabapentin is generally considered to have a favorable safety profile compared to some other anticonvulsants, several serious adverse effects require monitoring:

1. Suicidal Thoughts and Behavior:

   • Like other antiepileptic drugs, gabapentin may increase the risk of suicidal thoughts or actions (approximately 1 in 500 patients)
   • Patients should be monitored for emergence or worsening of depression, suicidal thoughts/behavior, or unusual changes in mood or behavior 1

2. Allergic Reactions:

   • Serious or life-threatening allergic reactions affecting skin, liver, or blood cells
   • May present as skin rash, hives, difficulty breathing, fever, swollen glands, yellowing of skin/eyes, unusual bruising/bleeding 1

3. Neuropsychiatric Effects:

   • In children 3-12 years: emotional changes, aggressive behavior, concentration problems, hyperactivity
   • In adults: confusion, disorientation 1

4. Falls and Fractures:

   • Increased risk of falls or fractures (RR 1.35,95% CI 1.28 to 1.44)
   • Risk increases with dose, with highest risk at doses ≥2,400 mg/day (RR 1.90) 2

Risk Factors for Adverse Effects

Certain patient populations may be at higher risk for gabapentin-related adverse effects:

• Elderly patients: More susceptible to CNS effects and falls
• Patients with renal impairment: Require dose adjustment as gabapentin is eliminated via the kidneys
• Patients with history of substance use disorders: May be at increased risk for misuse 3, 4
• Patients taking other CNS depressants: Increased risk of sedation and respiratory depression 1

Dose-Related Side Effects

There appears to be a dose-response relationship for certain side effects:

• Side effects are typically dose-related, with higher doses (>1800 mg/day) associated with greater incidence of adverse effects 3
• In clinical trials for neuropathic pain, withdrawal due to side effects was approximately 10% 5
• Risk of falls and fractures shows a clear dose-response relationship, with highest risk at doses ≥2,400 mg/day 2

Withdrawal and Discontinuation

Abrupt discontinuation of gabapentin can lead to withdrawal symptoms and increased seizure risk in epilepsy patients:

• Discontinuation symptoms with gabapentin may occur but are uncommon 5
• Gabapentin should be tapered gradually over at least one week rather than stopped abruptly 1

Misuse Potential

While gabapentin has traditionally been considered to have low abuse potential, recent evidence suggests some risk:

• Misuse has been reported, particularly among patients with history of substance use disorders
• Main reasons for misuse include getting high, alleviating opioid withdrawal symptoms, and potentiating methadone effects 6
• Pregabalin appears to have somewhat higher misuse potential than gabapentin 4

Clinical Recommendations

1. Start Low, Go Slow:

   • Begin with lower doses and titrate gradually to minimize side effects
   • Doses for neuropathic pain typically range from 900-3600 mg/day in divided doses 3

2. Monitor for CNS Effects:

   • Warn patients about potential for dizziness, drowsiness, and coordination problems
   • Advise against driving or operating machinery until effects are known 1

3. Renal Function Considerations:

   • Adjust dosing based on creatinine clearance:
     • CrCl ≥60 mL/min: 900-3600 mg/day (300-1200 mg TID)
     • CrCl 30-59 mL/min: 400-1400 mg/day (200-700 mg BID)
     • CrCl 15-29 mL/min: 200-700 mg/day (QD)
     • CrCl ≤15 mL/min: 100-300 mg/day (QD) 3

4. Avoid Abrupt Discontinuation:

   • Taper gradually over at least one week to minimize withdrawal symptoms 1

5. Monitor for Psychiatric Changes:

   • Assess for mood changes, depression, or suicidal ideation
   • Particularly important when initiating therapy or changing doses 1

By understanding gabapentin's side effect profile and implementing appropriate monitoring, clinicians can optimize therapeutic benefits while minimizing adverse effects in patients requiring this medication for neuropathic pain, seizures, or other approved indications.