The P-I-E-N-O Parkinsn's List Drug Database
bupropion / WellbutrinTM
ANTIDEPRESSANT:
Tricyclic: HIGH RISK
Description: Bupropion is an oral antidepressant drug of the aminoketone class. It is not a tricyclic antidepressant and is unrelated to other known antidepressants. Bupropion has been well tolerated in patients experiencing orthostatic hypotension with tricyclic antidepressant drugs, however, it shows a greater potential for causing seizures than other antidepressants. Bupropion is used to treat major depression. It was originally approved by the FDA in December 1985 but subsequently removed from marketing due to concern over drug-induced seizures. It was reintroduced in July 1989. Bupropion is currently undergoing investigation for use in combination with nicotine patches for treating the symptoms of smoking cessation.
Mechanism of Action: The action of bupropion is not fully understood. Bupropion selectively inhibits the neuronal reuptake of dopamine and is significantly more potent than either imipramine or amitriptyline in this regard. Actions on dopaminergic systems, however, require doses higher than those needed for a clinical antidepressant effect. The blockade of norepinephrine and serotonin reuptake at the neuronal membrane is weaker for bupropion than for tricyclic antidepressants. Bupropion does not inhibit monoamine oxidase. CNS-stimulant effects are dose-related.
Pharmacokinetics: Bupropion is absorbed orally and appears to be about 80% absorbed from the GI tract. Peak plasma levels are achieved in about 2 hours. The drug readily crosses the blood- brain barrier and the placenta. Plasma protein binding is about 80%.
Metabolism takes place in the liver, producing several active metabolites as a result of presystemic or first-pass metabolism. Full bioavailability studies have not been performed, but it appears that only about 5-20% of the drug reaches systemic circulation intact following oral administration. The metabolites have a longer half-life than the parent drug. Prolonged use increases the risk of developing toxicity from accumulation of metabolites, especially in patients with factors influencing metabolic capacity. Bupropion appears to induce its own metabolism. The elimination half-life ranges from 2-7 hours, and drug is excreted into the urine for 8-24 hours.
CONTRAINDICATIONS/PRECAUTIONS: Bupropion should not be used by patients with a preexisting seizure disorder. There is a higher than proportional increase in the possibility of seizure as the dose is increased. Patients who have a history of seizure are most at risk, but patients with eating disorders (anorexia or bulimia nervosa) have been shown to have an increased incidence of seizures. Other predisposing factors, such as head trauma or an intracranial mass, also can aggravate seizure risk.
Bupropion can cause weight loss and should not be used in patients with depressive states in which loss of weight is a factor such as anorexia nervosa.
Bupropion should be avoided in patients with a history of a previous hypersensitivity or severe adverse reaction to bupropion.
Bupropion should be used during pregnancy only when clearly needed. There is insufficient evidence to indicate whether use of the drug is detrimental to the fetus. Bupropion is classified as FDA category B.
Bupropion should not be used by nursing mothers because the drug is excreted into breast milk, potentially causing adverse effects in the infant. Breast-feeding should be avoided during therapy with bupropion.
Bupropion should be used with caution in patients with hepatic disease or renal impairment because active metabolites could accumulate. Bupropion undergoes hepatic conjugation and excretion in the urine.
Bupropion should be used with caution in patients with a history of bipolar disorder, or psychosis (especially in schizoaffective disorders). Latent psychosis or mania may be precipitated in susceptible patients, for example, bipolar patients in the depressed phase.
Bupropion can cause a fast or irregular heart beat. It should be used with caution in patients with a recent history of a myocardial infarction or cardiac disease.
Bupropion should be used with caution in patients with a history of substance abuse (e.g., amphetamine or stimulant abuse). These patients are more susceptible to increased motor activity and agitation/excitement. However, at normal dosage levels bupropion appears unlikely to reinforce substance abuse. The risk of seizures at higher doses has restricted studies to determine the potential for abuse.
The clearance and/or elimination of many drugs are reduced in the elderly. Delayed elimination can either intensify or prolong the actions, or adverse reactions, of the drug. In elderly patients, both initial and maintenance doses should be reduced.
DRUG INTERACTIONS: Bupropion-induced adverse reactions and toxicity appear to be enhanced by phenelzine in animals. Until more data are available, this drug combination should be avoided, if possible.
Bupropion can induce hepatic enzymes. Because of this, bupropion should be used cautiously with drugs known to be metabolized by inducible hepatic enzymes. Conversely, drug-drug interactions can occur between bupropion and other drugs that affect hepatic enzyme function such as carbamazepine, cimetidine, phenobarbital, phenytoin, or rifampin.
Limited data suggest that adverse effects increase if bupropion is administered concomitantly with levodopa. Until more data are available, this drug combination should be avoided, if possible.
ADVERSE REACTIONS: Bupropion shows a greater potential for causing seizures than other antidepressants. Patients with eating disorders or patients receiving higher doses may be more susceptible. The incidence is 0.5% in patients receiving less than 450 mg/day, but rises to 2.2% at doses above 450 mg/day. Patients with preexisting seizure disorders can experience an increase in seizure frequency. It is not known if increasing the dose of a concomitantly administered anticonvulsant will be effective in reducing the seizure disorder. Strict adherence to the dosage schedule should be maintained. Ethanol should be avoided because this might also lower the seizure threshold.
A substantial number of patients taking bupropion experience increased agitation, anxiety, restlessness and insomnia. In some cases these can necessitate treatment with sedative/hypnotic therapy. Treatment with antidepressants can activate psychosis in susceptible patients, with the possibility of manic episodes in patients with bipolar illness. Bupropion has been associated with a number of other neuropsychiatric signs and symptoms, such as delusions, hallucinations, psychotic episodes, confusion, and paranoia. Causal effect may be uncertain as trials were not always conducted with adequate controls. However, some effects are found to resolve upon dose reduction or discontinuation of therapy. Excessive diaphoresis occurred in 22.3% of patients taking bupropion, compared to 14.6% taking placebo. Other neurological adverse events include headache, and tremor. The incidence of tremor is high; 21.1% of patients reported tremor during trials, compared to 7.6% taking placebo.
Bupropion appears to initiate weight loss. A weight loss of more than 5 pounds occurred in 28% of patients taking bupropion, approximately double that seen for patients on tricyclics or placebo. The incidence of anorexia reported during trials was 18.3% for patients taking bupropion, compared to 18.4% for patients on placebo and may represent a symptom of the depressive illness rather than an adverse event. Weight loss contrasts with a high incidence of weight gain for tricyclic antidepressant use. Weight gain was seen in 9.4% of patients on bupropion therapy, compared to 34.5% of patients on tricyclic antidepressants.
Cardiac toxicity appears to be less for bupropion than for tricyclic antidepressants, although palpitations, ventricular tachycardia, premature ventricular contractions (PVCs), or other cardiac arrhythmias are possible. Hypertension occurred in 4.3% of patients taking bupropion, compared to 1.6% taking placebo. However, 22.3% of patients experienced dizziness, compared to 16.2% taking placebo, with 1.2% of patients on bupropion experiencing episodes of syncope.
Bupropion has some anticholinergic effects. In a placebo- controlled trial, 27.6% of patients experienced xerostomia, compared to 18.4% taking placebo. Constipation is another frequent adverse reation. Blurred vision affected 14.6% of patients, compared to 10.3% taking placebo.
Nausea/vomiting occur frequently during therapy with bupropion but require medical attention only if they persist or are troublesome. Some patients reported dysgeusia.
Twice as many patients taking bupropion reported libido decrease compared to patients taking placebo. Menstrual irregularity was reported as unspecified menstrual complaints by 4.7% of patients.
Other adverse reactions that occur infrequently with bupropion use include pruritus, and maculopapular rash.
PATIENT INFORMATION:
What do bupropion tablets do?
Bupropion (WellbutrinTM ) is an antidepressant, a medicine that helps to lift mental depression. Bupropion acts differently from other antidepressants and is useful for treating patients who have had unusual or limiting effects from other antidepressants. Generic bupropion tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take bupropion?
They need to know if you have any of these conditions:
How should I take this medicine?
Take bupropion tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. It is important to take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking the tablets except on your doctor's advice.
Special precautions for use in children:
This medication is not for children under 18 years old.
Elderly patients over 65 years old may have a stronger reaction to this medicine and need smaller doses.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is less than four hours to your next dose, take only that dose and skip the missed dose. Do not take double or extra doses.
What other medicines can interact with bupropion?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking bupropion?
Serious side effects with bupropion include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with bupropion include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take bupropion?
Visit your doctor for regular checks on your progress. You may have to take bupropion for several days before you see the effects. If you have been taking bupropion for some time, do not suddenly stop taking it. Your doctor may want you to gradually reduce the dose; ask for advice.
You may get dizzy or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how bupropion affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol may increase dizziness or drowsiness; avoid alcoholic drinks.
Bupropion can make your mouth dry. Chewing sugarless gum, sucking hard candy and drinking plenty of water will help. Do not treat yourself for coughs, colds, or allergies without asking your doctor or pharmacist for advice. Some ingredients may increase possible side effects.
If you are going to have surgery, tell your doctor or dentist well before your scheduled surgery that you are taking bupropion.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 25C (59 and 77F). Throw away any unused medicine after the expiration date.
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