Side Effects of Gabapentin
Gabapentin commonly causes dizziness, somnolence, and peripheral edema, with these side effects affecting up to 20-28% of patients, though most symptoms improve significantly after the first week of treatment and are largely resolved by week 4. 1, 2
Most Common Side Effects
The FDA-approved labeling and clinical guidelines identify a consistent pattern of adverse effects:
Central Nervous System Effects (Most Frequent)
- Dizziness occurs in 17-28% of patients 2, 3
- Somnolence (drowsiness) affects 14-21% of patients 2, 3
- Ataxia (unsteadiness/coordination problems) occurs in 13% of patients 2
- Fatigue affects approximately 11% of patients 2
Other Common Side Effects
- Peripheral edema (leg swelling) occurs in 7-8% of patients 2
- Nystagmus (abnormal eye movements) affects 8% of patients 2
- Weight gain occurs in 2-3% of patients 1, 2
- Gait disturbance affects 14% of patients 2
Serious but Rare Side Effects
Suicidal Ideation
Suicidal thoughts or behavior occur in approximately 1 in 500 patients (0.2%), similar to other antiepileptic drugs 4, 2. The FDA requires monitoring for new or worsening depression, anxiety, agitation, panic attacks, insomnia, irritability, hostility, or impulsivity 2.
Severe Allergic Reactions
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and anaphylaxis are rare but potentially life-threatening, presenting with skin rash, hives, difficulty breathing, swollen glands, fever, yellowing of skin/eyes, unusual bruising, or severe fatigue 2.
Altered Mental Status
Higher doses (>600 mg/day) are associated with increased risk of hospitalization for altered mental status, with an absolute risk difference of 0.21% compared to lower doses (number needed to harm: 477) 5. This risk is particularly relevant in older adults (mean age 76 years) 5.
Dose-Related Patterns
Side effects are typically dose-dependent, with higher incidence at doses above 1800 mg/day 4. The American Academy of Neurology recommends slow titration starting at 300 mg/day, increasing to 600 mg on day 2, and 900 mg on day 3 to minimize adverse effects 4, 6.
Most side effects are mild to moderate and transient, improving markedly after the first week and largely resolving by week 4 1, 6. Importantly, these side effects were not sufficient to cause discontinuation in most patients 1.
Discontinuation Rates
Overall, 11% of patients discontinue gabapentin due to adverse events compared to 8.2% on placebo (number needed to harm: 30) 3. The most common reasons for withdrawal are somnolence (1.2%), ataxia (0.8%), fatigue (0.6%), nausea/vomiting (0.6%), and dizziness (0.6%) 2.
Special Populations
Pediatric Patients (Ages 3-12)
Children may experience behavioral changes including emotional lability (1.6% discontinuation rate), hostility (1.3% discontinuation rate), hyperactivity, aggressive behavior, problems with concentration, restlessness, and changes in school performance 2.
Patients with Renal Impairment
Dose adjustment is required in patients with kidney disease or on hemodialysis due to reduced clearance of gabapentin 4, 2.
Important Clinical Considerations
Gabapentin has no known significant drug interactions, does not inhibit CYP2D6, and does not cause sexual dysfunction, making it advantageous over SSRIs/SNRIs in certain populations 1. Unlike some antidepressants, gabapentin does not have a withdrawal syndrome 1.
Serious adverse events occur at similar rates to placebo (3.2% vs 2.8%) 3. However, any adverse event occurs more frequently with gabapentin (63%) than placebo (49%), with a number needed to harm of 7.5 3.
Postmarketing Reports
Additional rare side effects identified after FDA approval include: jaundice, elevated liver enzymes, elevated creatine kinase, rhabdomyolysis, hyponatremia, movement disorders, breast enlargement, changes in libido, ejaculation disorders, and anorgasmia 2.