Generalized Seizure in Three Adolescents with Bupropion Overdose

Introduction

B upropion hydrochloride is an aminoketone that has been shown to be efficacious and well tolerated in the treatment of depression (Zung et al. 1983; Feighner et al. 1991). Across studies, bupropion has also been shown to be relatively free of anticholenergic, cardiovascular, sedative, and sexual side effects (Zung et al. 1983; Feighner et al. 1986; Feighner et al. 1991).

Bupropion has been associated with the occurrence of seizures in a small percentage of patients. Data from two independent study samples in which depressed patients received bupropion immediate release (IR) demonstrate a seizure rate of 0.4% at dosages of up to 450 mg/day (Davidson 1989; Johnston et al. 1991). At a dose of 450 mg/day and above, the rate of seizure with bupropion IR was strongly dose-related, and an increase in seizure rate was noted in patients with bulimia (Horne et al. 1988). The risk of seizure with bupropion sustained release (SR) with a daily dose of 150 mg twice daily (bid) is 0.1% (Dunner et al. 1998). Data regarding the risk of seizure with bupropion extended release (XL) is sparse.

In addition to its use as an antidepressant, bupropion has also been shown to be effective in treating children with attention-deficit/hyperactivity disorder (ADHD) (Barrickman et al. 1995), and recently it has been used as an aid in cigarette smoking cessation (Kane et al. 1999). The latter indication has resulted in significant publicity concerning its use and a relative availability in households. As a result, intentional and unintentional ingestion of bupropion may become frequent. To date, report of overdose in pediatric patients is limited. Here we are reporting seizures induced by overdose on bupropion XL in three adolescents. These patients have no history of any neurological abnormality eating disorder and none of the risk factors for seizure including central nervous system infections, febrile convulsion, trauma, or family history.

Case 1

A. is a 17-year-old white male with history of bipolar disorder. He has been on Lamictal 100 mg/day and Wellbutrin 150 mg/day. A. reported that for the last three days he has been feeling depressed and hopeless. On the day of admission, he overdosed on 20 tablets of Wellbutrin XL 150 mg. After that he contacted a friend. When the friend reached A.'s home, he found him seizing. Paramedics were called. A. had a second seizure in the presence of paramedics, lasting about 60–90 seconds, characterized by tonic-clonic seizure, loss of consciousness, and tongue biting. He was admitted to the intensive care unit. He was given Ativan 2 mg and later intubated and stabilized with propofol.

Complete blood count and serum chemistries were normal except for a potassium reading of 3.5 mEq/L. and electrocardiogram (ECG) showed sinus tachycardia (heart rate (HR) was 138 beats per minute (BPM)) with incomplete right bundle branch block and prolonged QT interval (QTc 563 msec). After 24 hrs, repeated ECG was normal with no prolongation of QT interval and resolution of incomplete right bundle branch block. Once A. was medically stable, he was transferred to the psychiatric unit and stabilized on Depakote extended release 750 mg at bedtime (HS).

Case 2

B. is a 14-year-old white female with a history of major depressive disorder. She has been taking Wellbutrin XL 150 mg bid and risperidone 1 mg bid. She has a history of multiple suicidal behaviors in the past. On the day of admission she had an argument with her sister and then overdosed on 18 tablets of Wellbutrin and 15 tablets of risperidone. After that, she was feeling nauseous and later told her sister about the overdose. B. was taken to the hospital. On examination she was drowsy and disoriented with slurred speech. Vital signs showed a heart rate of 126 bpm. Complete blood count and serum chemistries were normal. ECG was normal with a QTc of 443 msec. While in the emergency room, she had one generalized seizure. Ativan 2 mg was given and A. was transferred to the ICU. She did not have any more seizures. Later she was transferred to the adolescent psychiatric unit for further stabilization.

Case 3

C. is a 17-year-old white male with history of major depressive disorder and ADHD. C. was taking Wellbutrin XL 150 mg. He has a history of one prior psychiatric hospitalization for suicidal ideation. As per mother, he recently was feeling more depressed. On the day prior to admission, C. overdosed on approximately 14 tablets of Wellbutrin XL 150 mg. The next morning, C. woke up with gastrointestinal upset and visual hallucinations, seeing spiders and tactile hallucinations, feeling something crawling underneath his skin. His mother called the ambulance. While in the ambulance, C. had a generalized tonic-clonic seizure lasting about 1 minute. On examination, C. was confused. Vital signs showed a heart rate of 166 bpm and QTc within normal limit. Complete blood count was normal, and serum chemistries were normal. Urine toxicology and CT scan were normal. Once C. was medically stable, he was transferred to the adolescent psychiatric unit.

Discussion

Treatment of an overdose of bupropion is supportive, as there is no antidote available (White et al. 2002). Gastric lavage (American Academy of Clinical Toxicology 1997) and oral activated charcoal (American Academy of Clinical Toxicology 1997) may be considered within an hour of overdose, but the value of further doses of charcoal or whole bowel irrigation in bupropion overdose has not been established. Seizures are often short lived; benzodiazepines may be required for seizure control and hallucinations but antipsychotics should be avoided as these lower the seizure threshold. Electrocardiographic abnormalities usually resolve without treatment, although adenosine has been successfully used to treat broad complex tachycardia resulting from massive overdose (Cassidy et al. 2002).

Reports of toxicity in children related to bupropion are limited. Tilton reported the occurrence of seizures in a 10-year-old girl treated with bupropion 100 mg TID for ADHD (Tilton 1998). She was also receiving guanfacine. Storrow reported the occurrence of a single, 45-second tonic-clonic seizure in an 18-year-old girl following the intentional ingestion of 9 g of bupropion (Storrow 1994). In the three cases reported here, patients developed generalized tonic-clonic seizures after an overdose on Wellbutrin XL. Cardiovascular effects included primarily tachycardia and one of the patients had prolongation of QTc interval and incomplete right bundle branch block that reversed in 24 hours. Van Wyck Fleet et al. (1991) reported tachycardia as one of the adverse reactions with bupropion. Clinical studies comparing the cardiovascular effects of bupropion with classic tricyclic antidepressants such as amitriptyline have demonstrated no effect of bupropion on cardiac conduction (Wenger et al. 1983). Paris and Saucier (1998) reported an adult male who ingested 9 g of bupropion and developed intraventricular conduction delay.

Bupropion has novel properties and minimal anticholinergic toxicity, sedation, and sexual side effects compared with most other available antidepressants. As it has widespread use as an antidepressant and as an effective treatment for ADHD and smoking cessation, clinicians need to be aware that there is a non-negligible risk that patients with bupropion overdose may develop a seizure and even cardiac toxicity–even in the absence of any premorbid history of predisposing factors. Clinicians should be cautious when using bupropion in high-risk patients who have a significant history of suicidality.