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Author: admin | 25.01.2015 | Category: Relieve Tinnitus

Initially researched and marketed as an antidepressant, bupropion was subsequently found to be effective as a smoking cessation aid. Bupropion lowers seizure threshold and its potential to cause seizures was widely publicized. In 1996, the FDA approved a sustained-release formulation of bupropion called Wellbutrin SR, intended to be taken twice a day (as compared to three times a day for immediate-release Wellbutrin).[7] In 2003 the FDA approved another sustained-release formulation called Wellbutrin XL, intended for once-daily dosing. Placebo-controlled double-blind clinical studies have confirmed the efficacy of bupropion for clinical depression.[9] Comparative clinical studies demonstrated the equivalency of bupropion and sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil)[10] and escitalopram (Lexapro)[11] as antidepressants. According to several surveys, the augmentation of a prescribed SSRI with bupropion is the preferred strategy among clinicians when the patient does not respond to the SSRI.[18] For example, the combination of bupropion and citalopram (Celexa) was observed to be more effective than switching to another antidepressant.
According to a survey, bupropion is the drug of choice among psychiatrists for the treatment of SSRI-induced sexual dysfunction, although it is not an FDA-approved indication. Several studies have indicated that bupropion also relieves sexual dysfunction in people who do not have depression.
A recent meta-analysis of anti-obesity medications pooled the results of three double-blind, placebo-controlled trials of bupropion.
A study of prophylactic bupropion for the prevention of smoking among teenagers with ADHD yielded unexpected results. No properly controlled double-blind studies of bupropion for Parkinson's disease have been conducted.
GlaxoSmithKline advises that bupropion should not be prescribed to individuals with epilepsy or other conditions that lower the seizure threshold, such as alcohol or benzodiazepine discontinuation, anorexia nervosa, bulimia, or active brain tumors.
According to a retrospective case series published in 1993, bupropion treatment may exacerbate tics in children with co-occurring ADHD and Tourette syndrome.[55] No further research of this side effect has been conducted. The FDA requires all antidepressants, including bupropion, to carry a black box warning stating that antidepressants may increase the risk of suicide in persons younger than 25.
The common adverse effects associated with 12-hour sustained-release bupropion (with the greatest difference from placebo) are dry mouth, nausea, insomnia, tremor, excessive sweating and tinnitus. Seizure is the most controversial side effect of bupropion, and was responsible for its initial withdrawal from the market. There is evidence of several neuropsychiatric symptoms associated with bupropion in patients with depression, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion.
The prescribing information notes that hypertension, sometimes severe, was observed in some patients, both with and without pre-existing hypertension. In the UK, more than 7,600 reports of suspected adverse reactions were collected in the first two years after bupropion's approval by the MHRA as part of the Yellow Card Scheme, which monitored side effects. Bupropion is a dopamine and norepinephrine reuptake inhibitor.[89] It is about twice as potent an inhibitor of dopamine reuptake than of norepinephrine reuptake.
The biological activity of bupropion can be attributed to a significant degree to its active metabolites, in particular to S,S-hydroxybupropion. Bupropion is metabolized to hydroxybupropion by CYP2B6, an isoenzyme of the cytochrome P450 system. There have been two reported cases of false-positive urine amphetamine tests in persons taking bupropion. Since bupropion is metabolized to hydroxybupropion by the CYP2B6 enzyme, drug interactions with CYP2B6 inhibitors are possible: this includes medications like paroxetine, sertraline, norfluoxetine (the active metabolite of fluoxetine), diazepam, clopidogrel, and orphenadrine. Hydroxybupropion (but not bupropion) is itself an inhibitor of CYP2D6, as well as a substrate of that enzyme. Brand-name and generic bupropion tablets are available in three forms, each as the hydrochloride salt: immediate release (Wellbutrin), sustained release (Wellbutrin SR), and extended release (Wellbutrin XL or XR).
According to the US government classification of psychiatric medications, bupropion is "non-abusable"[121] or has low abuse potential.[122] In animal studies, however, squirrel monkeys[123] and rats[124] maintained the intravenous self-administration of bupropion, which may indicate abuse potential. However, at the recommended dose the risk of seizures is comparable to that observed for other antidepressants. Wellbutrin SR and XL are available in generic form in the United States, while in Canada, only the SR formulation is available in generic form. After a seven-week treatment, 27% of subjects who received bupropion reported that an urge to smoke was a problem, versus 56% of those who received placebo. In a mixed-gender double-blind study, 63% of subjects on a 12-week course of bupropion rated their condition as improved or much improved, versus 3% of subjects on placebo.[33] Two studies, one of which was placebo-controlled, demonstrated the efficacy of bupropion for women with hypoactive sexual desire,[34][35] resulting in significant improvement of arousal, orgasm and overall satisfaction.


The teenagers taking bupropion were two times more likely (close to statistical significance) to begin smoking than the teenagers in the placebo group. For the above analysis, the FDA combined the results of 295 trials of 11 antidepressants for psychiatric indications in order to obtain statistically significant results.
According to a Cochrane Database review, there have been four suicides per one million prescriptions and one case of suicidal ideation per ten thousand prescriptions of bupropion for smoking cessation in the UK. In some cases, these symptoms are reduced or eliminated by decreasing the dose or ceasing treatment.
Approximately 540,000 people were treated with bupropion for smoking cessation during that period.
Three cases of liver toxicity have been described in the literature,[73] a very low incidence given the widespread use of the drug. As bupropion is rapidly converted in the body into several metabolites with differing activity, its action cannot be understood without reference to its metabolism. It has several active metabolites: R,R-hydroxybupropion, S,S-hydroxybupropion, threo-hydrobupropion and erythro-hydrobupropion, which are further metabolized to inactive metabolites and eliminated through excretion into the urine.
Alcohol causes an increase of CYP2B6 in the liver, and persons with a history of alcohol use metabolize bupropion faster.
Bupropion metabolites erythro-hydrobupropion and threo-hydrobupropion, which have a phenethylamine structure resembling amphetamine are likely to have been responsible for this reaction. The expected result is the increase of bupropion and decrease of hydroxybupropion blood concentration. A significant increase in the concentration of some drugs metabolized by CYP2D6 (venlafaxine, desipramine and dextromethorphan, but not fluoxetine or paroxetine) has been observed when they are taken with bupropion.[109][110] It is also important to note that prodrugs such as Codeine may not be effective when combined with Bupropion due to Hydroxybupropion's inhibition of CYP2D6.
The tests showed that "one of a few generic versions of Wellbutrin XL 300 mg, sold as Budeprion XL 300 mg, didn't perform the same as the brand-name pill in the lab."[117] The FDA investigated these complaints and concluded that the Budeprion XL is equivalent to Wellbutrin XL in regard to bioavailability of bupropion and its main active metabolite hydroxybupropion. They also reported feeling alert, vigorous, elated and energetic, reflecting the general stimulating properties of bupropion. Bupropion is an effective antidepressant on its own but it is particularly popular as an add-on medication in the cases of incomplete response to the first-line SSRI antidepressant. Sleep quality and anxiety ratings in most cases were unchanged.[20] In the STAR*D study, the patients who did not respond to citalopram (Celexa) were randomly assigned to augmentation by bupropion or buspirone (Buspar).
In the same study, 21% of the bupropion group reported mood swings, versus 32% of the placebo group.[23] The bupropion treatment course lasts for seven to twelve weeks, with the patient halting the use of tobacco about ten days into the course. Considered separately, bupropion and nine other antidepressants were not statistically different from placebo. The development of mild to moderate skin rashes is associated with sensitivity to dye components within the pill coating. The MHRA received 60 reports of "suspected [emphasis MHRA's] adverse reactions to Zyban which had a fatal outcome".
The occupancy of dopamine transporter (DAT) by bupropion and its metabolites in the human brain as measured by positron emission tomography was 6a€“22% in an independent study[90] and 12a€“35% according to GlaxoSmithKline researchers.[91] Based on analogy with serotonin reuptake inhibitors, higher than 50% inhibition of DAT would be needed for the dopamine reuptake mechanism to be a major mechanism of the drug's action. The mechanism of formation of erythro-hydrobupropion and threo-hydrobupropion has not been studied but is probably mediated by one of the carbonyl reductase enzymes.
In contrast to many psychiatric drugs, including nearly all antidepressants, bupropion does not cause weight gain or sexual dysfunction. However, bupropion augmentation gave better results based on the patients' self-ratings and was much better tolerated.
Bupropion approximately doubles the chance of quitting smoking successfully after three months.
However, it has been shown to indirectly enhance the firing of serotonergic neurons, via activation of downstream norepinephrine flow. The authors observed that "these findings reveal a consistently more favorable outcome with sustained-release bupropion than with buspirone augmentation of citalopram."[21] The same study indicated a possibility of higher remission rate when the non-responders to citalopram received bupropion augmentation rather than were switched to bupropion (30% vs. Bupropion has also been shown to act as a noncompetitive I±3I?4 nicotinic antagonist.[92] The degree of inhibition of I±3I?4 receptors correlates well with the decrease in self-administration of morphine and methamphetamine in rats,[93] and may be relevant to the effect of bupropion on nicotine addiction.



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