Bupropion overdose

Bupropion overdose (n = 58) and combined overdoses of bupropion and benzodiazepines (n = 9) have been associated with symptoms of neurological toxicity, including lethargy, tremors, and seizures, and an absence of cardiovascular toxicity (Spiller et ah, 1994). 

Spiller, H.A., Ramoska, E.A., Krenzelok, E.P., Sheen, S.R., Borys, D.J., Villalobos, D., Muir, S., and Jones-Easom, L. (1994) Bupropion overdose a 3-year multi-center retrospective analysis. Am J Emerg Med 12 43 5. 

The danger of bupropion overdose is limited to the risk of seizures for the most part. However, seizures are seldom life threatening unless they result in motor vehicle accidents, falls, or other trauma-related events. Bupropion s lack of significant cardiovascular or respiratory toxicity means that it is rarely lethal in overdose. 

Isbister GK, Balit CR. Bupropion overdose QTc prolongation and its clinical significance. Ann Pharmacother 2003 37 999-1002. 

Bhattacharjee C, Smith M, Todd F, Gillespie M. Bupropion overdose a potential problem with the new miracle antismoking drug. Int J Clin Pract 2001 55(3) 221-2. 

Ayers S, Tobias JD. Bupropion overdose in an adolescent. Pediatr Emerg Care 2001 17(2) 104-6. 

Biswas AK, Zabrocki LA, Mayes KL, Morris-Kukoski CL. Cardiotoxicity associated with intentional ziprasidone and bupropion overdose. J Toxicol Clin Toxicol 2003 41 79-82. 

A grand mal seizure in a child, which was attributed to an interaction between bupropion and guanfacine, was later identified as being more probably due to a bupropion overdose. 

Nortriptyline (Pamelor). A recent study suggested that the tricyclic antidepressant nortriptyline, like bupropion, is effective in the treatment of smoking cessation. Nortriptyline does not have any significant effect on dopamine reuptake activity, but it does increase norepinephrine availability. Like bupropion, nortriptyline may therefore reduce the physical symptoms of nicotine withdrawal. Because nortriptyline carries the danger of lethality in overdose and has the unfavorable side effect profile of the tricyclics, we do not recommend its use for smoking cessation. However, it does raise the question as to whether other newer antidepressants that increase norepinephrine activity (e.g., venlafaxine, mirtazapine, duloxetine) may also prove to be effective treatments for nicotine withdrawal. 

Much more is known about overdose with the immediate-release formulation of bupropion than with the newer, SR and XL formulations. Reported reactions to overdose with the immediate-release form include seizures, hallucinations, loss of consciousness, and sinus tachycardia. Treatment of overdose should include induction of vomiting, administration of activated charcoal, and electrocardiographic and electroencephalographic monitoring. For seizures, an intravenous benzodiazepine preparation is recommended. 

Those who fail to respond to an SSRI may respond to a TCA, and vice versa. Thus, these two broad-spectrum classes can be used in a sequential strategy to adequately treat the majority of cases. However, many physicians try another newer antidepressant (e.g, venlafaxine, bupropion, nefazodone) in such patients because of the safety and tolerability problems associated with TCAs. Of note, the tolerability profile of secondary amine TCAs such as desipramine is as favorable as any of the newer antidepressants and probably better than nefazodone. Nevertheless, the secondary amine TCAs have a therapeutic index as narrow as tertiary amine TCAs (e.g., amitriptyline, imipramine) in terms of lethality in overdoses resulting from cardiotoxicity. 

Bupropion falls between TCAs and SSRIs in terms of safety in overdose. Death is a rare possibility with an overdose of bupropion alone because there are no adverse effects on the cardiovascular or the respiratory systems (461). Seizures may occur but are readily treatable in a hospital setting. 

At present, SSRIs are the most commonly prescribed first-line agents in the treatment of both MDD and anxiety disorders. Their popularity comes from their ease of use, tolerability, and safety in overdose. The starting dose of the SSRIs is usually the same as the therapeutic dose for most patients, and so titration may not be required. In addition, most SSRIs are now generically available and inexpensive. Other agents, including the SNRIs, bupropion, and mirtazapine, are also reasonable first-line agents for the treatment of MDD. Bupropion, mirtazapine, and nefazodone are the antidepressants with the least association with sexual side effects and are often prescribed for this reason. However, bupropion is not thought to be effective in the treatment of the anxiety disorders and may be poorly tolerated in anxious patients. The... 

None of the newer antidepressants have been shown to be more effective overall than the tricyclics with which they have been compared. Solid evidence to support a claim of more rapid onset of action has been difficult to obtain. Amoxapine and maprotiline seem to have as many sedative and autonomic actions as most tricyclics more recently introduced antidepressants such as bupropion and venlafaxine have fewer, although nefazodone and mirtazapine are very sedating. Amoxapine and maprotiline are at least as dangerous as the tricyclics when taken in overdoses the other newer agents seem to be safer. 

Mercerolle M, Denooz R, Lachatre G et al (2008) A fatal case of bupropion (Zyban) overdose. J Anal Toxicol 32 192-196... 

Because this group as a whole engages in frequent suicidal acting out, it is advisable to treat borderline patients with medications that have been found to have a low degree of toxicity when taken in overdose. These include antipsychotics and the following antidepressants fluoxetine, paroxetine, bupropion (note above caution), trazodone, and sertraline. Most other antidepressants are quite toxic when taken in overdose. 

Amoxapine, bupropion, and maprotiline are atypical antidepressants associated with a higher incidence of seizures on overdose amoxapine produces minimal cardiotoxicity," " but... 

Atomoxetine, bupropion, and TCAs are second-line alternatives to the stimulants for treatment of ADHD in children, teens, and adults. The potential benefits of these agents in comparison with stimulants include reduced risk of abuse and somewhat lower potential for sleep disturbance. TCAs are the most dangerous in overdose and pose the greatest risk for cardiovascular side effects. The monoamine oxidase inhibitor tranylcypromine is effective but used infrequently due to the potential for dangerous drug and dietary interactions. Selective serotonin reuptake inhibitors (SSRIs) are not effective for ADHD. ... 

Wellbutrin and Zyban (an aid in smoking cessation treatment) are trade name products for bupropion. Therefore, the potential exists for an overdose toxicity in a patient receiving multiple brand name and generic prescriptions containing bupropion for the treatment of depression, smoking cessation, and other off-label uses. 

Toxic dose. The noncyclio antidepressants generally have a wide therapeutic index, with doses in excess of 10 times the usual therapeutic dose tolerated without serious toxicity. Bupropion can cause seizures in some patients with moderate overdose or even in therapeutic doses. 

A. Central nervous system. The usual presentation after overdose includes ataxia, sedation, and coma. Respiratory depression may occur, especially with co-ingestion of alcohol or other drugs. These agents, particularly bupropion, can cause restlessness, anxiety, and agitation. Tremor and seizures are common with bupropion but occur occasionally after overdose with an SSRI. 

Belson MG, Kelley TR Bupropion exposures clinical manifestations and medical outcome. J Emerg Med2002 23(3) 223-230. [PMID 12426011] (Retrospective review of over 7000 calls to poison control centers seizures occurred In 15% of Intentional overdoses.)... 

Drug overdose The incidence and nature of seizures after overdoses of bupropion XL have been reported in a study of 117 patients who presented to five poison centers in the USA [70. Seizures occurred in 32%, and the median dose of those who had a seizure was 4350 mg, compared with 2400 mg in those who did not. One-third had delayed initial convulsions, defined as occurring more than 8 hours after the overdose. This suggests the need for a minimum observation period of 24 hours after overdosage with bupropion. 

Starr P, Klein-Schwartz W, Spiller H, Kern P, Ekleberry SE, Kunkel S. Incidence and onset of delayed seizures after overdoses of extended-release bupropion. Am J Emerg Med 2009 27(8) 911-5. 

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