Bupropion (/bjuːˈproʊpi.ɒn/ bew-proh-pee-on; ) is a drug that is primarily used as an atypical antidepressant and smoking cessation aid. Marketed as Wellbutrin, Budeprion, Prexaton, Elontril, Aplenzin, or other trade names, it is one of the most frequently prescribed antidepressants in the United States. Marketed in lower-dose formulations as Zyban, Voxra, or other names, it is also widely used to reduce nicotine cravings by people who are trying to quit smoking. It is taken in the form of pills, and in the United States is available only by prescription.
Bupropion lowers seizure threshold, and its potential to cause seizures has been widely publicized. Bupropion is an effective antidepressant on its own, but it is also popular as an add-on medication in cases of incomplete response to first-line SSRI antidepressants. In contrast to many other antidepressants, bupropion does not cause weight gain or sexual dysfunction.
Bupropion was patented in 1969 by Burroughs Wellcome, which later became part of what is now GlaxoSmithKline. It was originally called amfebutamone, before being renamed in 2000. Its chemical name is 3-chloro–N–tert-butyl-β-ketoamphetamine. It is asubstituted cathinone (β-ketoamphetamine), as well as a substituted amphetamine.
The drug is a mild psychostimulant. Its primary pharmacological action is as a dopamine reuptake inhibitor, and also to a lesser extent a norepinephrine reuptake inhibitor. Bupropion affects a number of neurotransmitter systems, and its mechanisms of action are only partly understood. It binds selectively to the dopamine transporter and makes dopamine reuptake inhibition twice as potent as norepinephrine reuptake inhibition.
It also acts as a nicotinic acetylcholine receptor antagonist. Bupropion belongs to the chemical class of aminoketones and is similar in structure to stimulants such as cathinone and amfepramone, and to phenethylamines in general. Medically, bupropion serves as a non-tricyclic antidepressant fundamentally different from most commonly prescribed antidepressants such asselective serotonin reuptake inhibitors (SSRIs).
The most common use for bupropion is in the treatment of depression, where it is marketed by GlaxoSmithKline under the trade name Wellbutrin, or as a generic version under a variety of other names.
Bupropion is one of the most widely prescribed antidepressants, and the available evidence indicates that it is effective in clinical depression — as effective as several other widely prescribed drugs, including sertraline (Zoloft), fluoxetine (Prozac), paroxetine(Paxil) and escitalopram (Lexapro). It has several features that distinguish it from other antidepressants. Unlike the majority of antidepressants, bupropion does not usually cause sexual dysfunction. Bupropion treatment also is not associated with the somnolence or weight gain that may be produced by other antidepressants.
The majority of depressed people suffer from insomnia, but there are some who instead experience constant sleepiness and fatigue. In this subgroup, bupropion has been found to be more effective than selective serotonin reuptake inhibitors (SSRIs) at alleviating the symptoms. There appears to be a modest advantage for the SSRIs compared to bupropion in the treatment of anxious depression.
According to surveys, the augmentation of a prescribed SSRI with bupropion is a common strategy among clinicians when the patient does not respond to the SSRI, even though this is not an officially approved indication for prescription. The addition of bupropion to an SSRI (most commonly fluoxetine or sertraline) results in a significant improvement in the majority of patients who have an incomplete response to the first-line antidepressant.
The next most common use is as an aid for smoking cessation, where it is marketed by GlaxoSmithKline under the trade name Zyban, or by other makers as a generic equivalent.
Numerous studies have provided evidence that bupropion substantially reduces the severity of nicotine cravings and withdrawal symptoms. For example, in one large-scale study, 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 the same study, 21% of the bupropion group reported mood swings, versus 32% of the placebo group. A typical bupropion treatment course lasts for seven to twelve weeks, with the patient halting the use of tobacco about ten days into the course. Bupropion approximately doubles the chance of quitting smoking successfully after three months. One year after treatment, the odds of sustaining smoking cessation are still 1.5 times higher in the bupropion group than in the placebo group.
The evidence is clear that bupropion is effective at reducing nicotine cravings. Whether it is more effective than other treatments is not as clear, due to a limited number of studies. The evidence that is available suggests that bupropion is comparable to nicotine replacement therapy, but somewhat less effective than varenicline (Chantix).
Seasonal Affective Disorder
Attention deficit hyperactivity disorder
There have been numerous reports of positive results for bupropion as a treatment for attention deficit hyperactivity disorder (ADHD), both in minors and adults. However, in the largest to date double-blind study of children, which was conducted by GlaxoSmithKline, the results were inconclusive. Aggression and hyperactivity as rated by the children’s teachers were significantly improved in comparison to placebo; in contrast, parents and clinicians could not distinguish between the effects of bupropion and placebo. The 2007 guideline on the ADHD treatment from American Academy of Child and Adolescent Psychiatry notes that the evidence for bupropion is “far weaker” than for the FDA-approved treatments. Its effect may also be “considerably less than of the approved agents… Thus it may be prudent for the clinician to recommend a trial of behavior therapy at this point, before moving to these second-line agents.” Similarly, the Texas Department of State Health Services guideline recommends considering bupropion or a tricyclic antidepressant as a fourth-line treatment after trying two different stimulants and atomoxetine.
Bupropion is one of few antidepressants that do not cause sexual dysfunction. A range of studies demonstrate that bupropion not only produces fewer sexual side effects than other antidepressants, but can actually help to alleviate sexual dysfunction. According to a survey of psychiatrists, it is the drug of choice for the treatment of SSRI-induced sexual dysfunction, although this is not an indication approved by the U.S. Food and Drug Administration. 36% of psychiatrists preferred switching patients with SSRI-induced sexual dysfunction to bupropion, and 43% favored the augmentation of the current medication with bupropion. There have also been a few studies suggesting that bupropion can improve sexual function in women who are not depressed, if they have hypoactive sexual desire disorder.
A recent meta-analysis of anti-obesity medications pooled the results of three double-blind, placebo-controlled trials of bupropion. It confirmed the efficacy of bupropion given at 400 mg per day for treating obesity. Over a period of 6 to 12 months, weight loss in the bupropion group (4.4 kg) was significantly greater than in the placebo group (1.7 kg). It was not, however, significantly different from the weight loss produced by several other established medications, such as sibutramine, orlistat and amfepramone.
There has been controversy about whether it is useful to add an antidepressant such as bupropion to a mood stabilizer in patients with bipolar depression, but recent reviews have concluded that bupropion in this situation does no significant harm and may sometimes give significant benefit.
Bupropion has shown no effectiveness in the treatment of cocaine dependence, but there is weak evidence that it may be useful in treating methamphetamine dependence.
Based on studies indicating that bupropion lowers the level of the inflammatory mediator TNF-alpha, there have been suggestions that it might be useful in treatinginflammatory bowel disease or other autoimmune conditions, but very little clinical evidence is available.
Bupropion—like other antidepressants, with the exception of duloxetine (Cymbalta)—is not effective in treating chronic low back pain. It does, however, show some promise in the treatment of neuropathic pain.
Bupropion is a substituted cathinone. It is synthesized in two chemical steps starting from 3′-chloro-propiophenone. The alpha position adjacent to the ketone is firstbrominated followed by nucleophilic displacement of the resulting alpha-bromoketone with t-butylamine and treated with hydrochloric acid to give bupropion as the hydrochloride salt in 75–85% overall yield.a, b a Mehta NB (June 25, 1974). “United States Patent 3,819,706: Meta-chloro substituted α-butylamino-propiophenones”. USPTO. Retrieved June 2, 2008. b, ^ Perrine DM, Ross JT, Nervi SJ, Zimmerman RH (2000). “A Short, One-Pot Synthesis of Bupropion (Zyban, Wellbutrin)”. Journal of Chemical Education 77 (11): 1479.Bibcode:2000JChEd..77.1479P. doi:10.1021/ed077p1479.
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