Gabapentin Side Effects
Gabapentin carries significant neuropsychiatric risks, particularly in patients with mood disorders or suicidal ideation, including an approximately doubled risk of suicidal thoughts or behavior (relative risk 1.8) compared to placebo, with the FDA requiring a black box warning for this effect. 1
Critical Neuropsychiatric Warnings
Suicidal Ideation and Behavior
All antiepileptic drugs (AEDs), including gabapentin, approximately double the risk of suicidal thoughts or behavior (adjusted relative risk 1.8,95% CI: 1.2-2.7) compared to placebo. 1
The absolute risk increases from 0.24% in placebo-treated patients to 0.43% in AED-treated patients, representing approximately one additional case of suicidal thinking or behavior for every 530 patients treated. 1
This increased risk can emerge as early as one week after starting gabapentin and persists throughout treatment. 1
For psychiatric indications specifically, the risk is 8.5 events per 1000 patients versus 5.7 per 1000 with placebo (relative risk 1.5). 1
Patients, caregivers, and families must be informed to monitor for emergence or worsening of depression, unusual mood or behavior changes, suicidal thoughts, or thoughts about self-harm, with immediate reporting to healthcare providers. 1
Mood and Behavioral Changes in Adults
Case reports document gabapentin-induced personality changes, including increased depression, frustration, and aggressive behavior leading to suicide attempts, with complete resolution upon discontinuation. 2
Psychotic and depressive symptoms can occur shortly after gabapentin initiation, despite its intended use as a mood stabilizer in some contexts. 3
Patients with underlying psychiatric disorders require careful screening, identification, and management prior to initiating gabapentin. 2
Pediatric-Specific Neuropsychiatric Effects (Ages 3-12)
Gabapentin use in children 3-12 years causes significant CNS-related adverse reactions including emotional lability (6% vs 1.3% placebo), hostility/aggressive behaviors (5.2% vs 1.3%), hyperkinesia/restlessness (4.7% vs 2.9%), and thought disorders/concentration problems (1.7% vs 0%). 1
These reactions are primarily mild to moderate in intensity but led to discontinuation in 1.3% for emotional lability and hyperkinesia, and 0.9% for hostility and thought disorder. 1
Common Central Nervous System Effects
Somnolence, Dizziness, and Ataxia
In controlled epilepsy trials, somnolence occurred in 19% of gabapentin-treated patients versus 9% placebo, dizziness in 17% versus 7%, and ataxia in 13% versus 6%. 1
For postherpetic neuralgia at doses up to 3600 mg/day, somnolence occurred in 21% versus 5% placebo, and dizziness in 28% versus 8% placebo. 1
Dizziness and somnolence are transient and paradoxically occur more frequently at lower doses (<1800 mg/day): dizziness 20.2% versus 7.4% placebo, somnolence 14.9% versus 5.8% placebo. 4
At doses ≥1800 mg/day, dizziness (9.7%) and somnolence (6.9%) rates become comparable to placebo, suggesting tolerance develops with dose titration. 4
These effects typically resolve within 10 hours in overdose situations and cause minimal toxicity even at doses up to 35 grams. 5
Impairment and Safety Concerns
Gabapentin can cause psychophysical indicators of CNS depression including horizontal gaze nystagmus and poor performance on field sobriety tests, even when used alone. 6
Blood concentrations in impaired driving cases ranged from <2.0 to 24.7 mg/L (mean 8.4 mg/L), though 93% involved polydrug use. 6
Patients must be carefully observed for CNS depression when gabapentin is combined with other sedating drugs due to potential synergy, and concomitant morphine treatment may increase gabapentin concentrations requiring dose adjustment. 1
Dose-Related Side Effects
Peripheral Edema
- Peripheral edema is the primary dose-dependent adverse effect, occurring in 7.5% of patients receiving ≥1800 mg/day versus 1.4% at <1800 mg/day and 1.6% with placebo (P<0.002). 4
Other Common Effects
Additional common adverse effects include fatigue, nausea/vomiting (leading to discontinuation in some cases), constipation, headache, and insomnia. 7, 1
In overdose cases, reported effects include drowsiness (most common), dizziness, nausea/vomiting, ataxia, tachycardia, and hypotension, though most resolve quickly without requiring hospital admission. 5
Serious but Rare Adverse Events
Allergic Reactions
Gabapentin can cause serious or life-threatening allergic reactions affecting skin, liver, or blood cells, potentially requiring hospitalization. 1
Warning signs include skin rash, hives, difficulty breathing, fever, swollen glands, facial/lip/throat swelling, yellowing of skin or eyes, unusual bruising/bleeding, severe fatigue, unexpected muscle pain, or frequent infections. 1
Seizure-Related Risks
Abrupt discontinuation can precipitate status epilepticus, with an incidence of 0.6% in gabapentin-treated patients versus 0.5% placebo in controlled trials. 1
Across all epilepsy studies, 1.5% (31 of 2074 patients) experienced status epilepticus, though causality versus underlying disease is unclear. 1
Special Population Considerations
Patients on hemodialysis, those with kidney problems, diabetes, or pre-existing depression/mood disorders require particular caution. 1
Pregnancy safety is unknown; gabapentin passes into breast milk with two case reports of seizures in breastfed infants. 1
Discontinuation rates are comparable between gabapentin and placebo overall, suggesting tolerability is generally acceptable despite the side effect profile. 4
Clinical Monitoring Recommendations
Immediate evaluation is required if suicidal thoughts, behavioral changes, allergic reaction symptoms, or severe CNS depression emerge. 1
The prescriber must balance the risk of suicidal thoughts/behavior against the risk of untreated illness, as epilepsy and chronic pain conditions themselves carry increased suicide risk. 1
Never abruptly discontinue gabapentin without medical supervision due to seizure risk. 1