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Bupropion (also amfebutamone, brand names Wellbutrin and Zyban) is an antidepressant of the aminoketone class, chemically unrelated to tricyclics or selective serotonin reuptake inhibitors (SSRIs). It is similar in structure to the stimulant cathinone, and to phenethylamines in general. It is a chemical derivative of diethylpropion, an amphetamine-like substance used as an anorectic. Bupropion is both a dopamine reuptake inhibitor and a norepinephrine reuptake inhibitor. It is used as a smoking cessation aid under the brand name Zyban, and as an antidepressant under the brand name Wellbutrin and Wellbutrin XL.
Mode of action
Bupropion is a selective catecholamine (dopamine and norepinephrine) reuptake inhibitor. It has a small effect, if any, on the serotonin reuptake mechanism. It has however been shown to indirectly enhance firing of serotonergic neurons (via activation of downstream norepinephrine flow). Bupropion does not inhibit MAO. The antidepressant effect of bupropion is considered to be mediated primarily by its dopaminergic and noradrenergic action. Bupropion has also been shown to act as a competitive nicotinic antagonist; the antagonism has been shown to interrupt certain addictions in studies of other drugs such as ibogaine. This antagonism correlates quite well with the observed effect of interrupting addiction.
Contraindications
* Epilepsy and other conditions that lower the seizure threshold (alcohol withdrawal, active brain tumors etc.)
* Concomitant treatment with MAO inhibitors. When switching medications it is important that there be a short period of about two weeks between the medications in order to reduce risk of complications that might lead to things such as a decrease in seizure threshold.
* Caution with the concomitant use of sympathomimetic drugs (e.g. ephedrine)
* Active liver damage (e.g. cirrhosis)
* Anorexia nervosa and bulimia which might lead the patient to have a decreased seizure threshold
* Severe kidney disease
* Severe hypertension
* Anxiety disorders (caution), agitated patients
* Pediatric patients
* Use considerable caution in treating patients where suicide may be a risk (risk is no higher than any other antidepressant)
* Psychosis, as bupropion therapy has a record of worsening and sometimes causing hallucinations, paranoia, and feelings of persecution.
Abuse liability
In animal studies and small studies with persons having experience with the use of amphetamines or cocaine, bupropion caused drug-seeking behaviour (animal experiments) and was recognized as an amphetamine-like drug by humans. In a scale ranging from placebo on the lower side to amphetamine, it was given an intermediate score indicating moderate likelihood of abuse. The stimulant effect reliably produced in mice however, has not been reliably seen in humans. There are isolated reports of patients crushing and insufflating bupropion and increasing dosages to attain a cocaine-like stimulant effect; however this often results in seizures and other severe side effects. In clinical practice, bupropion has been shown that the dose required for significant abuse would cause seizures in most patients. Abuse has not become a significant problem in clinical usage, but the drug should be given with caution to patients with a history of drug or alcohol abuse or dependence.
Side effects
Common side effects include dry mouth, tremors, anxiety, loss of appetite, agitation, dizziness, headache, excessive sweating such as night sweats, increased risk of seizure (its most controversial side effect, found in 4/1000 during trials), aggressiveness, tinnitus, and both initial and terminal insomnia. Activation of mania and psychosis have both been encountered. The side effect profile is consistent with that observed in mixed dopamine and norepinephrine reuptake inhibition. Some patients may also require less than the normal dosing which usually starts at around 75 mg for the first few weeks and is then switched to the normal 150–300 mg dosage; these patients may be kept on the 150 mg regimen however, some patients are experimentally placed on doses as high and sometimes exceeding, 600 mg/day. Dosage is strictly on a patient to patient basis and can vary greatly.

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