Seizures bupropion

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. 

A 29-year-old woman was admitted during withdrawal from intravenous bupropion dependence. She denied experiencing physical withdrawal symptoms, however admitted to physical withdrawal symptoms, irritability, labUity and low mood when abstinent as weU as attending detoxification facilities on 12 occasions to quit bupropion abuse. She had a 2-year history of using bupropion intravenously and admitted to using 1200 mg daily (4 x 300 mg tablets), dissolved in water and injected every 2-3 h (the recommended maximum oral daily dose of 450mg). She denied any history nasal insufflation of bupropion, seizures or exposure in a correctional facility. 

Adverse reactions with administration of bupropion include citation, dry mouth, insomnia, headache, nausea, constipation, anorexia, weight loss, and seizures. Fluoxetine administration may result in headache, activation of mania or hypomania, insomnia, anxiety, nervousness, nausea, vomiting, and sexual dysfunction. Trazodone administration may cause the following adverse reactions drowsiness, skin disorders, anger, hostility, anemia, priapism, nausea, and vomiting. Additional... 

Side effects. The primary side effects reported with bupropion administration in cigarette smokers are headache, dry mouth, nausea and vomiting, insomnia, and activation. Although most of these adverse effects occur during the first week of treatment, insomnia can persist. Seizures are of exceedingly low occurrence (<0.5%) at doses of 300 mg daily or less, but a prior history of seizures or a seizure disorder contraindicate its use. 

Isolated seizures that are not epilepsy can be caused by stroke, central nervous system trauma, central nervous system infections, metabolic disturbances (e.g., hyponatremia and hypoglycemia), and hypoxia. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures I or epilepsy. Medications can also cause seizures. Some drugs that are commonly associated with seizures include tramadol, bupropion, theophylline, some antidepressants, some antipsy-chotics, amphetamines, cocaine, imipenem, lithium, excessive doses of penicillins or cephalosporins, and sympathomimetics or stimulants. 

Bupropion causes insomnia, nightmares, decreased appetite, anxiety, and tremors, but the most concerning adverse effect is seizures. Because of the risk for seizures, patients who should not receive the drug include those with a CNS lesion or those with a history of seizures, head trauma, or bulimia. The daily dose of bupropion should not exceed 450 mg/day, and any single dose of the immediate-release formulation should not exceed 150 mg/day Occurrences of insomnia and/or nightmares often respond to moving the last daily dose from bedtime to late afternoon.7,9,22,23... 

The tricyclic antidepressants (TCAs), such as imipramine, can alleviate symptoms of ADHD. Like bupropion, TCAs likely will improve symptoms associated with comorbid anxiety and depression. The mechanism of action of TCAs is in blocking norepinephrine transporters, thus increasing norepinephrine concentrations in the synapse the increase in norepinephrine is believed to alleviate the symptoms of ADHD. TCAs have been demonstrated to be an effective non-stimulant option for ADHD but less effective than stimulants. However, their use in ADHD has declined owing to case reports of sudden death and anticholinergic side effects6,13 (Table 39-3). Further, TCAs may lower seizure threshold and increase the risk of car-diotoxicity, (e.g., arrythmias). Patients starting on TCAs should have a baseline and routine electrocardiograms. 

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. 

Bupropion sustained release (SR) is an effective smoking-cessation treatment. It is contraindicated in patients with a seizure disorder, a current or prior diagnosis of bulimia or anorexia nervosa, and use of a monoamine oxidase inhibitor within the previous 14 days. It can be used in combination with NRT. 

The most common side effects of bupropion are decreased appetite and abdominal discomfort. But more serious is the risk of seizure when high doses are taken. For this reason, patients with epilepsy should not take bupropion. 

Bupropion has also been used to treat the eating disorders anorexia nervosa and bulimia nervosa. Unfortunately, their electrolyte abnormalities leave patients with eating disorders especially vulnerable to seizures therefore, bupropion is no longer used to treat them. 

Carbamazepine and possibly the antidepressant mirtazapine should not be coadministered with clozapine because these drugs may further increase the risk of agranulocytosis. In addition, the antidepressant bupropion should not be coprescribed with clozapine because it may increase clozapine s seizure risk. 

Care should be taken when prescribing other medications with clozapine. The mood stabilizer carbamazepine (Tegretol) and perhaps the antidepressant mirtazap-ine (Remeron) should not be taken with clozapine because they might further increase the risk of agranulocytosis. Likewise, the antidepressant bupropion (Wellbutrin, Zyban) should not be taken with clozapine because it may add to the seizure risk. 

Side effects of bupropion such as stomach upset are relatively mild. The immediate-release form of bupropion increases the risk of seizure in patients... 

Atypical Antidepressants. None of the so-called atypical antidepressants have been tested in the treatment of AN. However, mianserin, an antidepressant available in Europe, has been found to increase body weight in patients with various depressive disorders. Although bupropion (Wellbutrin, Zyban) has not been tested in the treatment of AN, it is effective in the treatment of BN. However, immediate-release bupropion is associated with an especially high risk for seizures in these patients and is therefore contraindicated in those with eating disorders. The seizure risk associated with sustained-release bupropion remains unclear at this time, as the doses studied have not been as high as those for immediate-release bupropion. 

Finally, although immediate-release bupropion is also effective in the treatment of BN, it is associated with a particularly high incidence of seizures in individuals with bulimia presumably due to electrolyte abnormalities and is now contraindicated for treatment of the disorder. 

Antidepressants. Depression after TBl is routinely treated with antidepressant medicines. Although all antidepressants are potentially helpful, antidepressants prone to burdensome side effects, particularly sedative and anticholinergic side effects, should generally be avoided, as they are likely to be tolerated poorly by these patients. In addition, antidepressants that may increase the risk for seizure, such as many of the older tricyclic antidepressants (TCAs) and bupropion (Well-butrin), should be avoided because post-TBl patients as a rule are already more vulnerable to seizures. 

Bupropion should not be administered with sedating antihistamines because of the increased risk of seizures. Bupropion is used for smoking cessation therapy and may cause insomnia as a side-effect. Patients are advised to avoid taking bupropion dose at bedtime. 

General It is particularly important to administer bupropion in a manner most likely to minimize the risk of seizure (see Warnings). Gradual escalation of dosage also is... 

Hypersensitivity to the drug seizure disorder current or prior diagnosis of bulimia or anorexia nervosa concurrent administration of a monoamine oxidase inhibitor (MAOl) (at least 14 days should elapse between discontinuation of an MAOl and initiation of treatment with bupropion) in patients being treated with other bupropion products (eg, for smoking cessation) in patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines). 

Anorexia nervosa/buiimia Do not give with current or prior diagnosis of bulimia or anorexia nervosa because of a higher incidence of seizures noted in patients treated for bulimia with the IR formulation of bupropion. 

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. 

Seizures Because the use of bupropion is associated with a dose-dependent risk of seizures, do not prescribe doses greater than 300 mg/day for smoking cessation. The seizure rate associated with doses of sustained —release bupropion 300 mg/day or less is approximately 0.1%. 

Reducing the risk of seizures - Retrospective analysis suggests that the risk of seizures may be minimized if the total daily dose of bupropion does not exceed 300 mg (the maximum recommended dose) and no single dose exceeds 150 mg. 

E. Nefazodone,fluoxetine,mirtazapine, and venlafaxine have minimal effects on seizure threshold. Bupropion in its original formulation caused seizures in 4 in 1000 patients. Although this has been reduced with the slow release form of the medication (Wellbutrin SR), it remains a contraindication to prescribe this medication to patients with a history of seizures. 

The risk of seizures increases in pafienfs taking more than 150 mg/dose of bupropion, in pafienfs with a history of bulimia or seizure disorders, and in patienfs discontinuing drugs that may lower the seizure threshold. 

Geriatric Considerations - Summary Bupropion has several advantages as an antidepressant agent for use in older adults. It has neither the anticholinergic or cardiac toxicities of the tricyclic antidepressants, and has fewer sexual side effects than selective serotonin reuptake inhibitors. Because this drug may lower seizure threshold, it should be used with caution in older adults with increased risk of seizures (e.g., previous stroke, early-onset Alzheimer s disease). 

Bupropion Potential additive effect on lowering of seizure threshold Increased risk of seizure with coadministration Avoid in history of seizure disorder Rosenstein et ah, 1993... 

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. 

One of the more worrisome adverse effects of bupropion is seizures. At dosages of 450 mg/day or less, the rate of seizures is 0.4% for individuals without risk factors (Davidson, 1989). Because of this risk, a single dose of bupropion should not exceed 150 mg and a second dose should be separated in time by a minimum of 8 hours. Also, patients who are metabolically unstable (i.e., have bulimia) should be carefully assessed for the risk of seizures before initiating medication. Finally, bupropion is not associated with sexual side effects. 

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). 

Particular attention should be paid to the risk of seizure. Education of the patient and family regarding dosing too closely in time (< 8 hours) and not doubling up on doses after a missed dose are critical to the safe use of bupropion. 

Davidson, J. (1989) Seizures and bupropion a review. J Clin Psychiatry 50 256-261. 

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