Seizure bupropion-related

Seizures Bupropion is associated with a dose-related risk of seizures. Discontinue bupropion and do not restart in patients who experience a seizure while on treatment. Use extreme caution when bupropion is administered to patients with a history of seizure, cranial trauma, or other predisposition(s) toward seizure, or prescribed with other agents (eg, antipsychotics, other antidepressants, theophylline, systemic steroids) that lower seizure threshold. 

Rosenblatt J, Rosenblatt N. More about spontaneous postmarketing reports of bupropion related seizures. Curr Affect Illness 1992 11 18-20. 

A. Most agents cause CNS depression. Bupropion is a stimulant that can also cause seizures, presumably related to inhibition of reuptake of dopamine and norepinephrine. 

The occurrence of seizures with bupropion is dose related and may be increased by predisposing factors (e.g., history of head trauma or CNS tumor). At the ceiling dose (450 mg/day), the incidence of seizures is 0.4%. Other side effects include nausea, vomiting, tremor, insomnia, dry mouth, and skin reactions. It is contraindicated in patients with bulimia or anorexia nervosa. 

In 1986, just prior to its release, seizures were reported in a small number of nondepressed, bulimic patients taking bupropion. Bupropion was removed from the market by the manufacturer until it was determined that seizures in this vulnerable population appeared to be related to high doses (>450 mg) of bupropion used in the context of metabolic instability. The drug was finally released in the United States in 1989. 

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. 

Pesola GR, Avasarala J. Bupropion seizure proportion among new-onset generalized seizures and drug related seizures presenting to an emergency department. J Emerg Med 2002 22(3) 235-9. 

AMPHETAMINES BUPROPION 1. t plasma concentrations of these substrates, with risk of toxic effects 2. t risk of seizures. This risk is marked in elderly people, patients with a history of seizures, those with an addiction to opiates/ cocaine/stimulants, and those with diabetes treated with oral hypoglycaemics or insulin 1. Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 2. Bupropion is associated with a dose-related risk of seizures. These drugs that lower seizure threshold are individually epileptogenic. They have additive effects when combined 1. Initiate therapy with these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. amphetamines) 2. Extreme caution. The dose of bupropion should not exceed 450 mg/day (or 150 mg/day in those with severe hepatic cirrhosis)... 

Bupropion (100 mg p.o. b.i.d.) is indicated in the treatment of depression. It is reserved for patients who cannot tolerate or have not responded to other medications. Bupropion does not alter the uptake of serotonin, has an equivocal effect on the uptake of norepinephrine, but blocks the uptake of dopamine. Bupropion has no affinity for alpha-1 and alpha-2-adrenergic receptors, H,-histamine receptors, muscarinic cholinergic receptors, or D2-dopaminergic receptors. It does not cause sedation or orthostatic hypotension. However, because it is structurally related to amphetamine, it may cause insomnia, agitation, and anxiety shortly after initiation of therapy. Bupropion lowers the seizure threshold and hence is contraindicated in patients with a history of seizure disorder (see also Tables 5 through 7). 

Bupropion appears to reduce nicotine withdrawal symptoms and may simulate the actions of nicotine on the brain reward system. The most common side-effects related to bupropion are insomnia (30-45% at a dose of 300 mg/day) and dry mouth. Other commonly reported adverse events include hypertension, headache, and nausea. Seizures are a known risk associated with the use of somewhat higher doses compared with other antidepressants (0.1-0.4%), especially for the immediate-release form of the drug and when given at dosages of 450 mg/day or higher. Bupropion, unlike the TCAs, is virtually free of adverse cardiovascular effects, which makes it quite attractive for specific populations. 

Visual hallucinations have been seen in one patient given zolpi-dem with bupropion. Bupropion is contraindicated during the abrupt withdrawal from any drug known to be associated with seizures on withdrawal, particularly benzodiazepines and related drugs. 

Although clinieal evidence is limited it is supported by in vitro data, and so an interaction would seem to be established. It would seem prudent to be alert for increased trieyelie adverse effects if any of these drugs listed here is given with bupropion, and reduce the tricyclic dose as necessary. Note that bupropion is predicted to increase the risk of seizures with tricyclics, and this effect is dose-related. See Bupropion + Miscellaneous ,... 

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