What are the symptoms of a gabapentin (Neurontin) overdose?

Gabapentin Overdose Symptoms

Gabapentin overdose typically presents with double vision, slurred speech, drowsiness, lethargy, diarrhea, dizziness, ataxia, and in severe cases can progress to coma, particularly in patients with renal impairment. 1

Central Nervous System Effects

The predominant manifestations of gabapentin toxicity involve CNS depression:

• Drowsiness and sedation are the most commonly reported symptoms, occurring in the majority of overdose cases 1, 2
• Ataxia and lack of coordination develop early in the course of toxicity 1, 2
• Slurred speech is a characteristic finding in acute overdoses 1
• Altered mental status, including confusion and lethargy, occurs with increasing severity 3, 4
• Coma can develop in severe cases, particularly in patients with chronic renal failure where gabapentin accumulates 1

Visual and Neurological Symptoms

• Double vision (diplopia) is a hallmark sign of gabapentin overdose 1
• Dizziness is frequently reported, even at therapeutic doses in susceptible patients 2, 4
• Ptosis (drooping eyelids) has been observed in animal toxicity studies and may occur in severe human overdoses 1

Gastrointestinal Effects

• Diarrhea is commonly reported in acute overdose situations 1
• Nausea and vomiting occur in a subset of patients 2

Cardiovascular and Respiratory Effects

• Tachycardia has been documented in some overdose cases 2
• Hypotension can occur, though less commonly than CNS effects 2
• Labored breathing was noted in animal toxicity studies at very high doses 1

Dose-Response Relationship

The severity of symptoms correlates with dose and renal function:

• Acute overdoses up to 49 grams have been reported with patients recovering with supportive care alone 1
• Postmortem blood concentrations of 88 μg/mL have been documented in a fatal case, though death solely from gabapentin is extremely rare 5
• Sustained overuse (particularly ≥2,400 mg/day) significantly increases risk of falls, fractures, and altered mental status 4

High-Risk Populations

Patients with renal impairment are at dramatically increased risk for severe toxicity:

• The elimination half-life extends from 5-9 hours in normal renal function to 132 hours in dialysis patients 6
• Coma resolving with dialysis has been specifically reported in patients with chronic renal failure 1
• Plasma gabapentin concentrations increase linearly with declining creatinine clearance 6

Potentiation with Other Substances

Concomitant overuse of gabapentin with opioids quadruples the odds of all-cause hospitalization, drug-related hospitalization, and events involving altered mental status or respiratory depression 3. This combination represents a particularly dangerous scenario requiring immediate recognition.

Clinical Course and Resolution

• Symptoms develop early after ingestion, typically within hours 2
• Resolution occurs within 10 hours in most patients with normal renal function 2
• Hemodialysis effectively removes gabapentin and may be indicated in severe overdoses, particularly in patients with significant renal impairment 1

Critical Pitfall

The most important clinical pitfall is failing to recognize gabapentin toxicity in dialysis patients or those with renal impairment, where standard dosing can lead to severe accumulation and prolonged symptoms requiring extensive diagnostic workup that could be avoided with drug level monitoring 6. Always consider gabapentin toxicity in the differential diagnosis of altered mental status in patients with kidney disease taking this medication.