What are the signs of toxicity in a patient with a history of epilepsy or psychiatric conditions taking oxcarbazepine?

Signs of Oxcarbazepine Toxicity

The most common signs of oxcarbazepine toxicity include central nervous system depression (drowsiness, dizziness, ataxia, diplopia), gastrointestinal symptoms (nausea, vomiting), and potentially life-threatening hyponatremia, with severe cases presenting with altered mental status, seizures, or coma. 1

Central Nervous System Manifestations

The neurological signs dominate the clinical picture of oxcarbazepine toxicity:

• Drowsiness and somnolence are the most frequently reported symptoms, occurring in approximately 25% of exposures 1, 2
• Dizziness presents in 22-28% of patients and represents a cardinal sign of toxicity 1
• Ataxia and abnormal coordination indicate more significant toxicity, with ataxia occurring in 5-13% of cases 1
• Diplopia and abnormal vision occur in 12-17% of patients, representing ocular manifestations of CNS toxicity 1
• Nystagmus is a specific neurological finding that suggests significant drug effect 1
• Altered mental status ranging from confusion to coma occurs in approximately 0.8% of cases, with coma representing severe toxicity 1, 2
• Speech disorders and dysphonia may be present in toxic exposures 1

Gastrointestinal Symptoms

Digestive system manifestations are prominent early indicators:

• Nausea occurs in 16-19% of patients and often precedes more serious toxicity 1
• Vomiting presents in 7-33% of cases depending on age, with higher rates in pediatric patients 1

Cardiovascular and Autonomic Signs

While less common than CNS effects, cardiovascular manifestations require attention:

• Tachycardia occurs in approximately 3% of exposures 2
• Hypotension (including postural hypotension) presents in 0.9% of cases and can indicate significant toxicity 1, 2
• Bradycardia, syncope, and palpitations have been reported in post-marketing surveillance 1

Metabolic and Laboratory Abnormalities

Hyponatremia represents the most clinically significant metabolic complication:

• Serum sodium levels below 125 mmol/L have been documented in patients treated with oxcarbazepine 1
• Electrolyte disturbances occur in approximately 0.8% of exposures but can be severe 2
• Hyponatremia is reported in 22.2-50% of patients on chronic therapy, though symptomatic hyponatremia occurs in only 5.9% 3
• Symptoms of severe hyponatremia include nausea, malaise, diplopia, drowsiness, apathy, decreased diuresis, and paradoxical exacerbation of seizures 3

Severe Toxicity Indicators

Life-threatening manifestations that require immediate intervention:

• Seizures occur in approximately 0.6% of toxic exposures, though oxcarbazepine appears less proconvulsant than other anticonvulsants 1, 2
• Coma represents severe CNS depression and occurs in <1% of cases 1, 2
• Agitation and aggressive reactions may paradoxically occur in some patients 1, 2
• Extrapyramidal symptoms including dystonia and oculogyric crisis have been reported 1

Additional Clinical Findings

Other signs that may accompany toxicity:

• Tremor occurs in 4-6% of patients 1
• Headache is reported in 13-31% of cases 1
• Emotional lability and impaired concentration particularly in pediatric patients 1
• Rash occurs in approximately 4% of patients and may indicate hypersensitivity 1

Critical Clinical Context

Severe outcomes from oxcarbazepine toxicity are infrequent (<1%), with major effects occurring in less than 1% of exposures. 2 However, intentional exposures (suicide attempts) account for 68% of major effects and all reported fatalities, emphasizing the importance of assessing intent 2. Unlike other anticonvulsants, oxcarbazepine does not appear to be significantly proconvulsant in overdose 2.

Common Pitfalls

• Failing to check serum sodium levels in patients presenting with nonspecific symptoms like malaise, nausea, or worsening seizure control, as hyponatremia may be the underlying cause 3
• Overlooking the interaction between oxcarbazepine and diuretics, which significantly increases hyponatremia risk 3
• Dismissing mild CNS symptoms (drowsiness, dizziness) as benign when they may herald more serious toxicity requiring dose reduction 4, 5
• Not recognizing that pediatric patients may have different symptom profiles, with higher rates of vomiting and emotional lability 1