Can Antidepressant Overdose Alone Cause Complex Partial Seizures?
Yes, antidepressant overdose can absolutely cause complex partial (focal) seizures as the sole etiology, and this is well-documented in both clinical case series and toxicology literature. 1
Evidence for Antidepressant-Induced Complex Partial Seizures
The most compelling evidence comes from a 2013 case series that used video-EEG monitoring to capture the actual ictal characteristics of antidepressant-induced seizures. 1 This study documented that very high-dose antidepressants caused complex partial seizures with secondary generalization and produced characteristic EEG discharges—this was the first reported series to capture the ictal EEG features specifically associated with antidepressants. 1
Which Antidepressants Are Most Likely to Cause Seizures?
The seizure potential varies significantly by antidepressant class and specific agent:
Highest seizure risk antidepressants in overdose:
- Bupropion has the highest seizure potential at 31.6% (6 of 19 overdose cases resulted in seizures) 2
- Venlafaxine causes seizures in 13.7% of overdoses 2
- Citalopram causes seizures in 13.1% of overdoses 2
- Tricyclic antidepressants (TCAs) like amitriptyline and trimipramine are well-established seizure triggers, with 19% of brain-injured patients developing seizures during therapeutic TCA use 3
Clinical Presentation Pattern
Complex partial seizures from antidepressants may present subtly and be easily missed. 4 These seizures can manifest as:
- Brief episodes of behavioral arrest 4
- Loss of consciousness with or without automatisms 4
- Confusion or apparent memory loss 4
Critical pitfall: These subtle presentations are often misinterpreted as confusion or memory problems rather than recognized as seizure activity, leading to significant underdiagnosis. 4
Mechanism and Risk Factors
Antidepressants lower the seizure threshold through multiple mechanisms, and the risk increases with: 5, 6
- Dose-dependent relationship: Higher ingested doses directly correlate with increased seizure probability for agents like citalopram, venlafaxine, and trimipramine 2
- Lipophilic agents (like propranolol among beta-blockers) penetrate the blood-brain barrier more readily and cause CNS effects including seizures 4
- Patient age: Adolescents (15-19 years) show 22.0% seizure risk with citalopram overdose versus 10.9% in adults 2
Important Clinical Distinctions
Do not confuse antidepressant-induced seizures with other overdose complications:
The 2023 American Heart Association guidelines specifically warn that flumazenil (used for benzodiazepine reversal) can precipitate dysrhythmias "particularly in the presence of dysrhythmogenic drugs (such as cyclic antidepressants)." 4 This indicates that cyclic antidepressants themselves are recognized as dysrhythmogenic and seizure-provoking agents in overdose settings. 4
Tricyclic antidepressant overdose can cause TdP and other arrhythmias due to sodium channel blocker toxicity, though seizures remain a distinct and common complication. 4
Management Implications
For suspected antidepressant overdose with seizures: 5, 6
- Benzodiazepines are first-line treatment for drug-induced status epilepticus 6
- Barbiturates and propofol are second-line agents 6
- Monitor for at least 6-8 hours for immediate-release formulations, longer for sustained-release 4
- Obtain video-EEG monitoring if seizure semiology is unclear, as this can definitively capture antidepressant-induced ictal patterns 1
The bottom line: Complex partial seizures occurring solely from antidepressant overdose are not only possible but relatively common with certain agents, particularly bupropion, venlafaxine, citalopram, and tricyclic antidepressants. 1, 5, 2