What medications can induce seizures?

Medications That Can Induce Seizures

Several medications can lower the seizure threshold and induce seizures, particularly in susceptible individuals, with antipsychotics, antidepressants, and certain antimicrobials being the most common culprits.

Common Medication Classes Associated with Seizures

Antidepressants

• Bupropion carries a significant dose-dependent seizure risk, with incidence of approximately 0.4% at therapeutic doses but increasing almost tenfold between 450-600 mg/day 1, 2
• Tricyclic antidepressants (TCAs) such as amitriptyline, desipramine, and nortriptyline have a seizure rate between 0.3% and 0.6% at therapeutic doses 3
• Trazodone has been reported to cause prolonged seizures, particularly when used concurrently with electroconvulsive therapy 4

Antipsychotics

• Most antipsychotic medications lower the seizure threshold in a dose-dependent manner, with seizure incidence usually <1% at therapeutic doses 4
• Clozapine has a significantly higher seizure risk (approximately 5%) at high dosages compared to other antipsychotics 4, 5
• Phenothiazines, butyrophenones, and other typical antipsychotics have been associated with seizures 4

Antimicrobials and Antivirals

• Certain fluoroquinolones (particularly levofloxacin and geprafloxacin) can induce QT prolongation and seizures 4
• Pentamidine used for Pneumocystis pneumonia treatment has been associated with polymorphic ventricular arrhythmias and seizures 4
• Imidazole antifungal agents like ketoconazole can block potassium channels and potentially lower seizure threshold 4

Stimulants and Other CNS-Active Drugs

• Theophylline, at both therapeutic and toxic levels, is known to prolong seizure duration 4
• Amantadine has been associated with increased seizure activity in patients with seizure disorders 4
• Naltrexone/bupropion combination therapy carries a seizure risk due to the bupropion component 4

Risk Factors for Medication-Induced Seizures

• History of epilepsy or previous seizures 6, 3
• Central nervous system disorders or structural abnormalities 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1
• Polypharmacy, especially with multiple drugs that lower seizure threshold 6
• Extremes of age (very young or elderly) 6
• Impaired liver or kidney function affecting drug metabolism 6
• Electrolyte abnormalities, particularly hyponatremia 1
• Fever and acute medical illness 6

Medication Combinations with Heightened Seizure Risk

• Bupropion and clozapine combination has been reported to cause seizures even in patients without seizure history 5
• Lithium with electroconvulsive therapy has been associated with an acute brain syndrome 4
• Concurrent use of multiple antipsychotics or antidepressants 6
• Combination of drugs that inhibit cytochrome P450 enzymes (like macrolide antibiotics or imidazoline fungicides) with tricyclic antidepressants can increase plasma levels and seizure risk 4

Prevention and Management

• Carefully select optimal doses of seizure-threshold-lowering medications, especially in high-risk patients 6
• Monitor serum drug levels, electrolytes, and liver function when using medications with known seizure risk 6
• Avoid simultaneous administration of multiple drugs that stimulate the central nervous system 6
• For medication-induced status epilepticus, benzodiazepines are first-line treatment, followed by barbiturates and propofol 6
• When using bupropion, maintain doses below 450 mg daily to minimize seizure risk 1, 2
• Consider prophylactic anticonvulsant therapy in high-risk patients requiring medications known to lower seizure threshold 5

Special Considerations

• Rimantadine should be used with caution in patients with seizure disorders as seizure-like activity has been observed 4
• Naltrexone/bupropion should be avoided in patients with history of seizures or conditions predisposing to seizures 4
• Antipsychotic-induced seizures are rare (<1%) at therapeutic doses except for clozapine (5% at high doses) 4
• Patients with febrile seizures should not receive antipyretics solely to prevent seizures, as this is not effective 4