View source for Bupropion

{{drugbox | verifiedrevid = 376805011
|
| IUPAC_name = (±)-2-(''tert''-butylamino)-1-(3-chlorophenyl)propan-1-one
| image = Bupropion skeletal.svg
| imagename = 1 : 1 mixture (racemate)<br />
| image2 = Bupropion-3d-CPK.png
| width = 240px
| InChI = 1/C13H18ClNO/c1-9(15-13(2,3)4)12(16)10-6-5-7-11(14)8-10/h5-9,15H,1-4H3
| InChIKey = SNPPWIUOZRMYNY-UHFFFAOYAJ
| CASNo_Ref = {{cascite}}
| CAS_number = 34841-39-9
|  ChemSpiderID = 431
| ATC_prefix = N06
| ATC_suffix = AX12
| PubChem = 444
| smiles = O=C(c1cc(Cl)ccc1)C(NC(C)(C)C)C
| DrugBank = APRD00621
| C = 13 | H = 18 | Cl = 1 | N = 1 | O = 1
| molecular_weight = 239.74 g/mol
| bioavailability = 5 to 20% in animals; no studies in humans
| protein_bound = 84%
| metabolism = [[Liver|Hepatic]]—important [[CYP2B6]] and [[CYP2D6|2D6]] involvement
| elimination_half-life = 20 hours
| excretion = [[Kidney|Renal]] (87%), fecal (10%)
| pregnancy_AU = B2
| pregnancy_US = C
| legal_US = Rx-only
| legal_UK = POM
| routes_of_administration = Oral, insufflation, IV
}}

'''Bupropion''' (also known as '''Wellbutrin''',  '''Zyban''', '''Voxra''', '''Budeprion''', or '''Aplenzin'''; formerly known as '''amfebutamone'''<ref>The INN originally assigned in 1974 by the [[World Health Organization]] was "amfebutamone". In 2000, the INN was reassigned as ''bupropion''. See {{cite journal | author = [[World Health Organization]] | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 83 | journal = WHO Drug Information | volume = 14 | issue = 2 | year = 2000 | url = http://82.77.46.154/gsdldata/collect/whodruginfo/index/assoc/h1463e/h1463e.pdf|format=PDF|accessdate=2009-06-22}}</ref>) is an atypical [[antidepressant]] and [[smoking cessation]] aid. It is different than most antidepressants commonly prescribed in that it acts as a [[norepinephrine reuptake inhibitor]] and [[nicotinic acetylcholine receptor]] [[receptor antagonist|antagonist]].<ref>{{cite journal | author = Slemmer J E, Martin R M, Damaj M I | title = Bupropion is a Nicotinic Antagonist | journal = J Pharmacol Exp Ther | volume = 295| issue = 1 |pages = 321–327 | year = 2000 | pmid = 10991997}}</ref><ref>{{cite journal | author = Fryer J D, Lukas R J | title = Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine | journal = J Pharmacol Exp Ther | volume = 288|issue=6|pages = 88–92 | year = 1999 |pmid=9862757}}</ref> Bupropion belongs to the [[chemical class]] of [[aminoketone]]s and is similar in [[chemical structure|structure]] to stimulants [[cathinone]] and [[diethylpropion]], and to [[substituted phenethylamine|phenethylamine]]s in general.

Initially researched and marketed as an antidepressant, bupropion was subsequently found to be effective as a smoking cessation aid.  With over 20 million retail prescriptions in 2007, it was the fourth-most prescribed antidepressant in the United States retail market after [[sertraline]], [[escitalopram]], and [[fluoxetine]].<ref>The bupropion prescriptions were calculated as a total of prescriptions for Wellbutrin XL, Budeprion XL, Budeprion SR, Bupropion SR and Bupropion ER using data from the charts for generic and brand-name drugs, see: {{cite web | url = http://www.drugtopics.com/drugtopics/article/articleDetail.jsp?id=491181 | title = Top 200 Generic Drugs by Units in 2007| accessdate = 2008-03-30 |date = 2008-02-18| format = PDF| publisher = Drug Topics}} and {{cite web | url = http://www.drugtopics.com/drugtopics/article/articleDetail.jsp?id=491207 | title = Top 200 Brand Drugs by Units in 2007| accessdate = 2008-03-30 | author = Verispan|date = 2008-02-18| format = PDF | publisher = Drug Topics}}</ref>

Bupropion lowers [[seizure threshold]], and its potential to cause seizures has been widely publicized. However, at the recommended dose the risk of seizures is comparable to that observed for other antidepressants. 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 [[selective serotonin reuptake inhibitor]] (SSRI) antidepressant. In contrast to many other antidepressants, bupropion does not cause [[weight gain]] or [[sexual dysfunction]].

==History==
Bupropion was invented by [[Nariman Mehta]] of Burroughs Wellcome (now [[GlaxoSmithKline]]) in 1969, and the US patent for it was granted in 1974.<ref name="United States Patent: 3819706">{{cite web |url=http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=3819706.PN.&OS=PN/3819706&RS=PN/3819706 |title=United States Patent 3,819,706: Meta-chloro substituted α-butylamino-propiophenones |author=Mehta NB |date=1974-06-25 |work= |publisher=USPTO |accessdate=2008-06-02}}</ref> It was approved by the United States [[Food and Drug Administration]] (FDA) as an antidepressant on December 30, 1985 and marketed under the name Wellbutrin.<ref>WELLBUTRIN Label and Approval History. U.S. [[Food and Drug Administration]] [[Center for Drug Evaluation and Research]]. Retrieved on 2007-08-18. Data available for download on [http://www.fda.gov/cder/drugsatfda/datafiles/default.htm FDA website].</ref> However, a significant incidence of [[seizures]] at the originally recommended dosage (400–600&nbsp;mg) caused the withdrawal of the drug in 1986. Subsequently, the risk of seizures was found to be highly dose-dependent, and bupropion was re-introduced to the market in 1989 with a maximum recommended dose of 450&nbsp;mg/day.

[[Image:Wellbutrin.jpg|thumb|Wellbutrin XL]]
In 1996, the FDA approved a [[sustained release|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).<ref name="NIDA_notes">"[http://www.drugabuse.gov/NIDA_notes/NNvol20N5/Bupropion.html Bupropion Helps People With Schizophrenia Quit Smoking]." ''[[National Institute on Drug Abuse]].'' ''Research Findings'', Vol. 20, No. 5 (April 2006). Retrieved on August 19, 2007.</ref> In 2003 the FDA approved another sustained-release formulation called Wellbutrin XL, intended for once-daily dosing. Wellbutrin SR and XL are available in [[generic drug|generic]] form in the United States, while in Canada, only the SR formulation is available in generic form. In 1997, bupropion was approved by the FDA for use as a smoking cessation aid under the name Zyban.<ref name="NIDA_notes"/> In 2006, Wellbutrin XL was similarly approved as a treatment for [[seasonal affective disorder]].<ref name="wellbutrin_seasonal">Staff Writer. "[http://www.cnn.com/HEALTH/library/DI/00069.html Seasonal affective disorder drug Wellbutrin XL wins approval]." ''[[CNN]].'' June 14, 2006. Retrieved on August 19, 2007.</ref>

==Therapeutic uses==
===Depression===
[[Placebo]]-controlled [[double-blind]] [[clinical studies]] have confirmed the efficacy of bupropion for [[Major depressive disorder|clinical depression]].<ref>{{cite journal | author = Fava M, Rush AJ, Thase ME, Clayton A, Stahl SM, Pradko JF, Johnston JA. | title = 15 years of clinical experience with bupropion HCl: from bupropion to bupropion SR to bupropion XL | journal = Prim Care Companion J Clin Psychiatry| volume = 7|issue = 3|pages = 106–113| year = 2005 |pmid=16027765 |url=http://www.psychiatrist.com/pcc/pccpdf/v07n03/v07n0305.pdf|format=PDF|accessdate=2008-12-30 | pmc = 1163271 | doi = 10.4088/PCC.v07n0305}}</ref> Comparative clinical studies demonstrated the equivalency of bupropion and [[sertraline]] (Zoloft), [[fluoxetine]] (Prozac), [[paroxetine]] (Paxil)<ref>{{cite journal | author = Thase ME, Haight BR, Richard N, Rockett CB, Mitton M, Modell JG, VanMeter S, Harriett AE, Wang Y| title = Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized controlled trials | journal =  J Clin Psychiatry| volume = 66| issue=6 |pages = 974–981 | year = 2005|pmid = 16086611 | doi = 10.4088/JCP.v66n0803}}</ref> and [[escitalopram]] (Lexapro)<ref>{{cite journal | author = Clayton AH, Croft HA, Horrigan JP, Wightman DS, Krishen A, Richard NE, Modell JG| title = Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies | journal =  J Clin Psychiatry| volume = 67| issue=5 |pages = 736–746 | year = 2006|pmid =  1684162 | doi = 10.4088/JCP.v67n0507}}</ref> as antidepressants. A significantly higher [[remission (medicine)|remission]] rate with bupropion treatment than for [[venlafaxine]] (Effexor) was observed in a recent study.<ref>{{cite journal | author = Thase ME, Clayton AH, Haight BR, Thompson AH, Modell JG, Johnston JA| title = A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability | journal =  J Clin Psychopharmacol| volume = 26| issue=5 |pages = 482–488 | year = 2006|pmid = 16974189 | doi = 10.1097/01.jcp.0000239790.83707.ab}}</ref>  Unlike all other antidepressants, except [[mirtazapine]] (Remeron), [[maprotiline]] (Ludiomil) and [[tianeptine]] (Stablon), bupropion does not cause sexual dysfunction and the occurrence of sexual side effects is not different from placebo.<ref> For the review, see: {{cite journal | author = Clayton AH| title = Antidepressant-Associated Sexual Dysfunction: A Potentially Avoidable Therapeutic Challenge | journal =  Primary Psychiatry| volume = 10| issue=1 |pages = 55–61 | year = 2003}}</ref><ref> For another review, see: {{cite journal | author = Kanaly KA, Berman JR| title = Sexual side effects of SSRI medications: potential treatment strategies for SSRI-induced female sexual dysfunction | journal =  Curr Women's Health Rep| volume = 2| issue=6 |pages = 409–16 | year = 2002|pmid=12429073}}</ref> Bupropion treatment is not associated with weight gain; on the contrary, at the end of every study comparing bupropion with placebo or other antidepressants the bupropion group had a lower average weight.<ref> For a short review, see: {{cite journal | author = Zimmerman M, Posternak MA, Attiullah N, Friedman M, Boland RJ, Baymiller S, Berlowitz SL, Rahman S, Uy KK, Singer S, Chelminski I, Thongy, T| title = Dr. Zimmerman and colleagues reply to MJ Menaster | journal =  J Clin Psychiatry| volume = 66| issue=10 |pages = 1336–9 | year = 2005}}</ref> Bupropion is more effective than [[SSRI]]s at improving symptoms of [[hypersomnia]] and fatigue in depressed patients.<ref>{{cite journal | author = Baldwin DS, Papakostas GI| title = Symptoms of Fatigue and Sleepiness in Major Depressive Disorder | journal =  J Clin Psychiatry| volume = 67 (suppl 6)| pages = 9–15 | year = 2006 |pmid=16848671}}</ref> In a comparative meta-analysis, there appeared to be a modest advantage for the SSRIs compared to bupropion in the treatment of depression with high anxiety, while these medications were equivalent for the depression with moderate or low anxiety.<ref name="pmid18605812">{{cite journal |author=Papakostas GI, Stahl SM, Krishen A, ''et al.'' |title=Efficacy of Bupropion and the Selective Serotonin Reuptake Inhibitors in the Treatment of Major Depressive Disorder With High Levels of Anxiety (Anxious Depression): A Pooled Analysis of 10 Studies |journal=J Clin Psychiatry |volume= 69|issue= 8|pages=e1–e6 |year=2008 |month=July |pmid=18605812 |doi= |url=http://article.psychiatrist.com/?ContentType=START&ID=10003663}}</ref>

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.<ref> For the most recent review, see: {{cite journal |author=Zisook S, Rush AJ, Haight BR, Clines DC, Rockett CB |title=Use of bupropion in combination with serotonin reuptake inhibitors |journal=Biol Psychiatry |volume=59 |issue=3 |pages=203–10 |year=2006 |pmid=16165100 |doi=10.1016/j.biopsych.2005.06.027}}</ref> For example, the combination of bupropion and [[citalopram]] (Celexa) was observed to be more effective than switching to another antidepressant. The addition of bupropion to an SSRI (primarily fluoxetine or sertraline) resulted in a significant improvement in 70–80% of patients who had an incomplete response to the first-line antidepressant.<ref name="pmid9614595">{{cite journal |author=Spier SA |title=Use of bupropion with SRIs and venlafaxine |journal=Depression and anxiety |volume=7 |issue=2 |pages=73–5 |year=1998 |pmid=9614595|doi=10.1002/(SICI)1520-6394(1998)7:2<73::AID-DA4>3.0.CO;2-6}}</ref><ref name="pmid9164423">{{cite journal |author=Bodkin JA, Lasser RA, Wines JD, Gardner DM, Baldessarini RJ |title=Combining serotonin reuptake inhibitors and bupropion in partial responders to antidepressant monotherapy |journal=The Journal of clinical psychiatry |volume=58 |issue=4 |pages=137–45 |year=1997 |pmid=9164423 |doi=}}</ref> Bupropion improved ratings of "energy", which had decreased under the influence of the SSRI; also noted were improvements of mood and motivation, and some improvement of cognitive and sexual functions. Sleep quality and anxiety ratings in most cases were unchanged.<ref name="pmid9164423"/> In the STAR*D study, the patients who did not respond to [[citalopram]] (Celexa) were randomly assigned to augmentation by bupropion or [[buspirone]] (Buspar). Approximately 30% of subjects in both groups achieved a remission. However, bupropion augmentation gave better results based on the patients' self-ratings and was much better tolerated. The authors observed that "these findings reveal a consistently more favorable outcome with sustained-release bupropion than with buspirone augmentation of citalopram."<ref name="pmid16554526">{{cite journal |author=Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D, Ritz L, Nierenberg AA, Lebowitz BD, Biggs MM, Luther JF, Shores-Wilson K, Rush AJ |title=Medication augmentation after the failure of SSRIs for depression |journal=N. Engl. J. Med. |volume=354 |issue=12 |pages=1243–52 |year=2006 |pmid=16554526 |doi=10.1056/NEJMoa052964}}</ref> The same study indicated a possibility of higher remission rate when the non-responders to citalopram received bupropion augmentation instead of being switched to bupropion (30% vs. 20%).<ref name="pmid16554525">{{cite journal |author=Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF, Shores-Wilson K, Niederehe G, Fava M |title=Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression |journal=N. Engl. J. Med. |volume=354 |issue=12 |pages=1231–42 |year=2006 |pmid=16554525 |doi=10.1056/NEJMoa052963}}</ref>

===Anxiety===
Bupropion has shown some success in treating [[social phobia]]<ref name="bpsrsocial">{{cite journal |author=Emmanuel NP, Brawman-Mintzer O, Morton WA, Book SW, Johnson MR, Lorberbaum JP, Ballenger JC, Lydiard RB. |title=Bupropion-SR in treatment of social phobia |journal=Depression and Anxiety |volume=12 |issue=2 |pages=111–3 |year=2000 |pmid=11091936 |doi=10.1002/1520-6394(2000)12:2<111::AID-DA9>3.0.CO;2-3}}</ref> and [[anxiety]] comorbid with depression,<ref name="bpanxidepress">{{cite journal |author=Trivedi MH, Rush AJ, Carmody TJ, Donahue RM, Bolden-Watson C, Houser TL, Metz A.|title=Do bupropion SR and sertraline differ in their effects on anxiety in depressed patients? |journal=Journal of Clinical Psychiatry |volume=62 |issue=10 |pages=776–81 |year=2001 |pmid=11816866 |doi=10.4088/JCP.v62n1005 |doi_brokendate=2010-08-28}}</ref> but not [[panic disorder]] with [[agoraphobia]].<ref name="bppanic">{{cite journal |author=Sheehan DV, Davidson J, Manschreck T, Van Wyck Fleet J. |title=Lack of efficacy of a new antidepressant (bupropion) in the treatment of panic disorder with phobias |journal=Journal of Clinical Psychopharmacology |volume=3 |issue=1 |pages=28–31 |year=1983 |pmid=6403599 |doi=}}</ref> Its [[anxiolytic]] potential has been compared to that of [[sertraline]]<ref name="bpanxidepress"></ref> and [[doxepin]].<ref name="bpdoxepin">{{cite journal |author=Feighner J, Hendrickson G, Miller L, Stern W.|title=Double-Blind Comparison of Doxepin Versus Bupropion in Outpatients with a Major Depressive Disorder |journal=Journal of Clinical Psychopharmacology |volume=6 |issue=1 |pages=27–32 |year=1986 |pmid=3081600 |doi=}}</ref> However, it can cause agitation in some patients, especially at higher doses, and often increases anxiety, much like [[methylphenidate]].<ref name="bpsideeffect">{{cite journal |author=Settle EC. |title=Bupropion sustained release: side effect profile |journal=Journal of Clinical Psychopharmacology |volume=59 |issue=Supplement 4 |pages=32–6 |year=1998 |pmid=9554319 |doi=}}</ref> As a psychostimulant, it is inherently an [[anxiogenic]] compound and contrary benefits are poorly understood and seemingly paradoxical.

===Smoking cessation===
Bupropion reduces the severity of [[nicotine]] cravings and [[withdrawal]] symptoms.
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.<ref name = "Tonnesen2003">{{cite journal | author = Tonnesen P, Tonstad S, Hjalmarson A, Lebargy F, Van Spiegel P I, Hider A, Sweet R, Townsend J| title = A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation | journal = J Intern Med| volume = 254|issue = 2|pages = 184–192| year = 2003 |pmid=12859700 | doi = 10.1046/j.1365-2796.2003.01185.x}}</ref> The 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 the treatment, the odds of sustaining smoking cessation are still 1.5 times higher in the bupropion group than in the placebo group.<ref>{{cite journal | author = Wu P, Wilson K, Dimoulas P, Mills E J | title = Effectiveness of smoking cessation therapies: a systematic review and meta-analysis | journal = BMC Public Health| volume = 6|pages = 300–315 | year = 2006 | pmid = 17156479 | pmc = 1764891 | doi = 10.1186/1471-2458-6-300}}</ref> The combination of bupropion and nicotine appears not to further increase the cessation rate. In a direct comparison, [[varenicline]] (Chantix) showed superior efficacy: after one year, the rate of continuous abstinence was 10% for placebo, 15% for bupropion, and 23% for varenicline.<ref>{{cite journal | author = Jorenby D E, Hays J T, Rigotti N A, Azoulay S, Watsky E J, Williams K E, Billing C B, Gong J, Reeves K R| title = Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial | journal = JAMA| volume = 296|issue = 1|pages = 56–63| year = 2006 |pmid=16820547 | doi = 10.1001/jama.296.1.56}}</ref> Bupropion slows the weight gain that often occurs in the first weeks after quitting smoking (after seven weeks, the placebo group had an average 2.7&nbsp;kg increase in weight, versus 1.5&nbsp;kg for the bupropion group). With time, however, this effect becomes negligible (after 26 weeks, both groups recorded an average 4.8&nbsp;kg weight gain).<ref name = "Tonnesen2003"/>

===Sexual dysfunction===
Bupropion is one of few antidepressants that does not cause sexual dysfunction.<ref>{{cite journal |author=Serretti A, Chiesa A |title=Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis |journal=J Clin Psychopharmacol |volume=29 |issue=3 |pages=259–66 |year=2009 |month=June |pmid=19440080 |doi=10.1097/JCP.0b013e3181a5233f}}</ref> 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 FDA-approved indication. Thirty-six percent of psychiatrists preferred switching patients with SSRI-induced sexual dysfunction to bupropion, and 43% favored the augmentation of the current medication with bupropion.<ref>{{cite journal | author =Dording CM, Mischoulon D, Petersen TJ, Kornbluh R, Gordon J, Nierenberg AA, Rosenbaum JE, Fava M.| title = The pharmacologic management of SSRI-induced side effects: a survey of psychiatrists| journal = Ann Clin Psychiatry| volume = 14|issue=3| pages = 143–7 | year = 2002|pmid=12585563 | doi =10.3109/10401230209147450}}</ref> There are studies demonstrating the efficacy of both approaches; improvement of the desire and orgasm components of sexual function were the most often noted. For the augmentation approach, the addition of at least 200&nbsp;mg/day of bupropion to the SSRI regimen may be necessary to achieve an improvement since the addition of 150&nbsp;mg/day of bupropion did not produce a statistically significant difference from placebo.<ref>{{cite journal | author = Walker PW, Cole JO, Gardner EA, Hughes AR, Johnston JA, Batey SR, Lineberry CG| title = Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion| journal = J Clin Psychiatry| volume = 54 |issue=12| pages = 459–65 | year = 1993|pmid=8276736}}</ref><ref>{{cite journal | author = Dobkin RD, Menza M, Marin H, Allen LA, Rousso R, Leiblum SR| title = Bupropion improves sexual functioning in depressed minority women: an open-label switch study| journal = J Clin Psychiatry| volume = 26|issue=1| pages = 21–6 | year = 2006|pmid=16415700}}</ref><ref>{{cite journal | author = Masand PS, Ashton AK, Gupta S, Frank B| title = Sustained-release bupropion for selective serotonin reuptake inhibitor-induced sexual dysfunction: a randomized, double-blind, placebo-controlled, parallel-group study| journal = Am J Psychiatry | volume = 158|issue=5| pages = 805–807 | year = 2001|pmid=11329407 | doi = 10.1176/appi.ajp.158.5.805}}</ref><ref>{{cite journal | author =DeBattista C, Solvason B, Poirier J, Kendrick E, Loraas E|title = A placebo-controlled, randomized, double-blind study of adjunctive bupropion sustained release in the treatment of SSRI-induced sexual dysfunction| journal = J Clin Psychiatry | volume = 66|issue=7| pages = 844–8 | year = 2005 | pmid =16013899 | doi =10.4088/JCP.v66n0706}}</ref><ref>{{cite journal | author = Ashton AK, Rosen RC| title = Bupropion as an antidote for serotonin reuptake inhibitor-induced sexual dysfunction| journal = J Clin Psychiatry| volume = 59|issue=3| pages = 112–5 | year = 1998|pmid=9541153}}</ref><ref>{{cite journal | author =Clayton AH, Warnock JK, Kornstein SG, Pinkerton R, Sheldon-Keller A, McGarvey EL| title = A placebo-controlled trial of bupropion SR as an antidote for selective serotonin reuptake inhibitor-induced sexual dysfunction| journal = J Clin Psychiatry | volume = 65|issue=1| pages = 62–7 | year = 2004|pmid=14744170 | doi =10.4088/JCP.v65n0110}}</ref>

Several studies have indicated that bupropion also relieves sexual dysfunction in people who do not have depression. 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.<ref>{{cite journal | author =Crenshaw TL, Goldberg JP, Stern WC| title = Pharmacologic modification of psychosexual dysfunction| journal =  J Sex Marital Ther| volume = 13|issue=4| pages = 239–52 | year = 1987|pmid=3121861}}</ref> Two studies, one of which was placebo-controlled, demonstrated the efficacy of bupropion for women with hypoactive sexual desire,<ref>{{cite journal | author = Segraves RT, Croft H, Kavoussi R, Ascher JA, Batey SR, Foster VJ, Bolden-Watson C, Metz A| title = Bupropion sustained release (SR) for the treatment of hypoactive sexual desire disorder (HSDD) in nondepressed women| journal =  J Sex Marital Ther| volume = 27|issue=3| pages = 303–16 | year = 2001|pmid=11354935| doi = 10.1080/009262301750257155}}</ref><ref>{{cite journal | author = Segraves RT, Clayton A, Croft H, Wolf A, Warnock J.| title =Bupropion sustained release for the treatment of hypoactive sexual desire disorder in premenopausal women| journal =  J Clin Psychopharmacol| volume = 24|issue=3| pages = 339–42 | year = 2004|pmid=15118489 | doi = 10.1097/01.jcp.0000125686.20338.c1}}</ref> resulting in significant improvement of arousal, orgasm and overall satisfaction. Bupropion also showed promise as a treatment for sexual dysfunction caused by [[chemotherapy]] for breast cancer<ref>{{cite journal | author =Mathias C, Cardeal Mendes CM, Ponde de Sena E, Dias de Moraes E, Bastos C, Braghiroli MI, Nunez G, Athanazio R, Alban L, Moore HC, del Giglio A| title = An open-label, fixed-dose study of bupropion effect on sexual function scores in women treated for breast cancer| journal =  Ann Oncol| volume = 17|issue=12| pages = 1792–6 | year = 20060|pmid=16980597| doi = 10.1093/annonc/mdl304}}</ref> and for orgasmic dysfunction.<ref>{{cite journal | author =Modell JG, May RS, Katholi CR| title =Effect of bupropion-SR on orgasmic dysfunction in nondepressed subjects: a pilot study| journal =  J Sex Marital Ther| volume = 26|issue=3| pages = 231–40 | year = 2000|pmid=10929571| doi =10.1080/00926230050084623}}</ref> As with the treatment of SSRI-induced sexual disorder, a higher dose of bupropion (300&nbsp;mg) may be necessary: a randomized study employing a lower dose (150&nbsp;mg) failed to find a significant difference between bupropion, sexual therapy or combined treatment.<ref>{{cite journal | author = Cabello F| title = Effectiveness of the Treatment of Female Hypoactive Sexual Desire Disorder | journal = J Sex Research| month = February| year = 2006| accessdate = 2007-04-05 | url = http://www.findarticles.com/p/articles/mi_m2372/is_1_43/ai_n16102437}}</ref> Bupropion does not adversely affect any measures of sexual functioning in healthy men.<ref>{{cite journal | author =Labbate LA, Brodrick PS, Nelson RP, Lydiard RB, Arana GW| title =Effects of bupropion sustained-release on sexual functioning and nocturnal erections in healthy men| journal =  J Clin Psychopharmacol| volume = 22|issue=1| pages = 99–103 | year = 2001|pmid=11199957| doi =10.1097/00004714-200102000-00018}}</ref>

===Obesity===
A recent [[meta-analysis]] of [[anti-obesity drug|anti-obesity medication]]s pooled the results of three double-blind, placebo-controlled trials of bupropion. It confirmed the efficacy of bupropion given at 400&nbsp;mg per day for treating [[obesity]]. Over a period of 6 to 12 months, weight loss in the bupropion group (4.4&nbsp;kg) was significantly greater than in the placebo group (1.7&nbsp;kg). The same review found the differences in weight loss between bupropion and other established weight-loss medications, such as [[sibutramine]], [[orlistat]] and [[diethylpropion]], to be statistically insignificant.<ref>{{cite journal | author =Li Z, Maglione M, Tu W, Mojica W, Arterburn D, Shugarman LR, Hilton L, Suttorp M, Solomon V, Shekelle PG, Morton SC.| title = Meta-analysis: pharmacologic treatment of obesity| journal =  Ann Intern Med| volume = 142|issue=7| pages = 532–46 | year = 2005|pmid=15809465 }}</ref> Combinations of bupropion and [[zonisamide]] ([[Empatic]]) and of bupropion and [[naltrexone]] ([[Contrave]]) are currently being studied for obesity.<ref name="pmid19885278">{{cite journal |author=Klonoff DC, Greenway F |title=Drugs in the pipeline for the obesity market |journal=J Diabetes Sci Technol |volume=2 |issue=5 |pages=913–8 |year=2008 |month=September |pmid=19885278 |pmc=2769782 |doi= |url=}}</ref>

===Attention-deficit hyperactivity disorder===
Although [[attention-deficit hyperactivity disorder]] (ADHD) is not an approved indication, bupropion was found to be effective for adult ADHD.<ref name="pmid15820237">{{cite journal |author=Wilens TE, Haight BR, Horrigan JP, Hudziak JJ, Rosenthal NE, Connor DF, Hampton KD, Richard NE, Modell JG |title=Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study |journal=Biol. Psychiatry |volume=57 |issue=7 |pages=793–801 |year=2005 |pmid=15820237 |doi=10.1016/j.biopsych.2005.01.027}}</ref> There have been many positive case studies and other uncontrolled clinical studies of bupropion for ADHD in minors.<ref name="pmid9554326">For the review, see: {{cite journal |author=Cantwell DP |title=ADHD through the life span: the role of bupropion in treatment |journal=The Journal of clinical psychiatry |volume=59 Suppl 4 |issue= |pages=92–4 |year=1998 |pmid=9554326 |doi=}}</ref> However, in the largest to date double-blind study, 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.<ref name="pmid9554326"/> 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."<ref>{{cite web |url=http://www.aacap.org/galleries/PracticeParameters/New_ADHD_Parameter.pdf |title= PRACTICE PARAMETER FOR THE ASSESSMENT AND TREATMENT OF CHILDREN AND ADOLESCENTS WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER |accessdate=2007-09-02 |author= Steven Pliszka et al. |authorlink= |year= 2007 |format=PDF |work= |publisher=American Academy of Child and Adolescent Psychiatry |page=16 |language= |archiveurl= |archivedate= |quote=}} {{Dead link|date=September 2010|bot=H3llBot}}</ref> Similarly, the 2006 guideline from the Texas Department of State Health Services recommends considering bupropion or a [[tricyclic antidepressant]] as a fourth-line treatment after trying two different stimulants and [[atomoxetine]] (Strattera).<ref>{{cite web |url=http://www.dshs.state.tx.us/mhprograms/adhdpage.shtm |title= The Texas Children's Medication Algorithm Project: attention-deficit/hyperactivity disorder.|accessdate=2007-09-02 |author= Pliszka SR et al.|authorlink= |year=2006 |work= |publisher=Texas Department of State Health Services |pages= |language= |archiveurl= |archivedate= |quote=}}</ref><ref>{{cite web |url=http://www.dshs.state.tx.us/mhprograms/ADHD_Algo_Schematics_With_NO_Sig_Co_Dis.pdf |title= Algorithm Stages Flowsheets. ADHD with no significant comorbidity algorithm |accessdate=2007-09-02 |author= |authorlink= |month=May | year=2006 |format=PDF|work= |publisher=Texas Department of State Health Services |pages= |language= |archiveurl=http://web.archive.org/web/20060822172713/http://www.dshs.state.tx.us/mhprograms/ADHD_Algo_Schematics_With_NO_Sig_Co_Dis.pdf|archivedate=August 22, 2006|quote=}}</ref>

A study of prophylactic bupropion for the prevention of smoking among teenagers with ADHD yielded unexpected results. The teenagers taking bupropion were two times more likely (close to statistical significance) to begin smoking than the teenagers in the placebo group. However, because significance was not reached, this difference can be attributed entirely to chance.  Therefore, this study showed no indication that teenagers taking bupropion were any more likely to begin smoking.  At the same time, the sub-group of patients taking stimulants in addition to bupropion or placebo had a five times lower risk of smoking initiation.<ref name="pmid17685748">{{cite journal |author=Monuteaux MC, Spencer TJ, Faraone SV, Wilson AM, Biederman J |title=A randomized, placebo-controlled clinical trial of bupropion for the prevention of smoking in children and adolescents with attention-deficit/hyperactivity disorder |journal=The Journal of clinical psychiatry |volume=68 |issue=7 |pages=1094–101 |year=2007 |pmid=17685748 |doi=10.4088/JCP.v68n0718}}</ref>

===Other uses===
Bupropion has been approved by the FDA<ref name="pmid17328102">{{cite journal |author= |title=First drug for seasonal depression |journal=FDA Consumer |volume=40 |issue=5 |page=7 |year=2006 |pmid=17328102 |doi=}}</ref> for the prevention of [[seasonal affective disorder]].<ref name="pmid16271314">{{cite journal |author=Modell JG, Rosenthal NE, Harriett AE, Krishen A, Asgharian A, Foster VJ, Metz A, Rockett CB, Wightman DS |title=Seasonal affective disorder and its prevention by anticipatory treatment with bupropion XL |journal=Biol Psychiatry |volume=58 |issue=8 |pages=658–67 |year=2005 |pmid=16271314 |doi=10.1016/j.biopsych.2005.07.021}}</ref> According to several case studies and a pilot study, bupropion lowers the level of an inflammatory mediator [[Tumor necrosis factor-alpha|TNF-alpha]]<ref name="pmid14552325"/> and may be useful in autoinflammatory conditions such as [[Crohn's disease]]<ref name="pmid14552325">{{cite journal |author=Kane S, Altschuler EL, Kast RE |title=Crohn's disease remission on bupropion |journal=Gastroenterology |volume=125 |issue=4 |page=1290 |year=2003 |month=October |pmid=14552325 |doi= 10.1016/j.gastro.2003.02.004|url=}}</ref><ref name="pmid11706830">{{cite journal |author=Kast RE, Altschuler EL |title=Remission of Crohn's disease on bupropion |journal=Gastroenterology |volume=121 |issue=5 |pages=1260–1 |year=2001 |month=November |pmid=11706830 |doi= 10.1053/gast.2001.29467|url=}}</ref> and [[psoriasis]].<ref name="pmid12883127">{{cite journal |author=Altschuler EL, Kast RE |title=Bupropion in psoriasis and atopic dermatitis: decreased tumor necrosis factor-alpha? |journal=Psychosom Med |volume=65 |issue=4 |page=719 |year=2003 |pmid=12883127 |doi= 10.1097/01.PSY.0000073874.55003.EE|url=}}</ref><ref name="pmid12271115">{{cite journal |author=Modell JG, Boyce S, Taylor E, Katholi C |title=Treatment of atopic dermatitis and psoriasis vulgaris with bupropion-SR: a pilot study |journal=Psychosom Med |volume=64 |issue=5 |pages=835–40 |year=2002 |pmid=12271115 |doi= 10.1097/01.PSY.0000021954.59258.9B|url=}}</ref>

No properly controlled double-blind studies of bupropion for [[Parkinson's disease]] have been conducted. A small 1984 study funded by bupropion's manufacturer found that addition of bupropion to [[carbidopa]] or [[levodopa]] improved Parkinson's symptoms in ten out of twenty patients; however, the side effects, particularly nausea and vomiting, were frequent.<ref name="pmid6431314">{{cite journal |author=Goetz CG, Tanner CM, Klawans HL |title=Bupropion in Parkinson's disease |journal=Neurology |volume=34 |issue=8 |pages=1092–4 |year=1984 |pmid=6431314 |doi=}}</ref> The [[American Psychiatric Association]] notes that, "there is no evidence favoring any particular antidepressant medication from the standpoint of therapeutic efficacy in patients with Parkinson’s disease complicated by major depressive disorder".<ref>{{cite web |url=http://www.psych.org/psych_pract/treatg/pg/MDD2e_05-15-06.pdf |title=Practice guideline for the treatment of patients with major depressive disorder. Second edition. |accessdate=2007-08-24 |author=American Psychiatric Association |authorlink= |year= 2000|format= PDF|work= |publisher= |page= 37|language= |archiveurl= |archivedate= |quote=}}</ref>

There is considerable disagreement regarding whether it is useful to add an antidepressant, including bupropion, to a [[mood stabilizer]] in patients with [[bipolar depression]].<ref name="pmid17392295">For the review indicating that antidepressants are not better than placebo, see: {{cite journal |author=Sachs GS, Nierenberg AA, Calabrese JR, Marangell LB, Wisniewski SR, Gyulai L, Friedman ES, Bowden CL, Fossey MD, Ostacher MJ, Ketter TA, Patel J, Hauser P, Rapport D, Martinez JM, Allen MH, Miklowitz DJ, Otto MW, Dennehy EB, Thase ME |title=Effectiveness of adjunctive antidepressant treatment for bipolar depression |journal=N. Engl. J. Med. |volume=356 |issue=17 |pages=1711–22 |year=2007 |pmid=17392295 |doi=10.1056/NEJMoa064135}}</ref><ref name="pmid15337640">For the review in favor of the antidepressant use, see: {{cite journal |author=Gijsman HJ, Geddes JR, Rendell JM, Nolen WA, Goodwin GM |title=Antidepressants for bipolar depression: a systematic review of randomized, controlled trials |journal=The American journal of psychiatry |volume=161 |issue=9 |pages=1537–47 |year=2004 |pmid=15337640 |doi=10.1176/appi.ajp.161.9.1537}}</ref><ref name="pmid17156158">For the guidelines recommending the use of bupropion with a mood stabilizer, see: {{cite journal |author=Yatham LN, Kennedy SH, O'Donovan C, Parikh SV, MacQueen G, McIntyre RS, Sharma V, Beaulieu S |title=Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: update 2007 |journal=Bipolar Disord |volume=8 |issue=6 |pages=721–39 |year=2006 |pmid=17156158 |doi=10.1111/j.1399-5618.2006.00432.x}}</ref> 

Bupropion, similarly to other antidepressants, is not efficacious in chronic low back pain.<ref>{{cite journal |author=Katz J, Pennella-Vaughan J, Hetzel RD, Kanazi GE, Dworkin RH |title=A randomized, placebo-controlled trial of bupropion sustained release in chronic low back pain |journal=J Pain |volume=6 |issue=10 |pages=656–61 |year=2005 |month=October |pmid=16202958 |doi=10.1016/j.jpain.2005.05.002}}</ref><ref>{{cite journal |author=Urquhart DM, Hoving JL, Assendelft WW, Roland M, van Tulder MW |title=Antidepressants for non-specific low back pain |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD001703 |year=2008 |pmid=18253994 |doi=10.1002/14651858.CD001703.pub3}}</ref> However, it has been found to have surprisingly high efficacy in the treatment of neuropathic pain.<ref name="pmid10741812">{{cite journal | author = Semenchuk MR, Davis B | title = Efficacy of sustained-release bupropion in neuropathic pain: an open-label study | journal = The Clinical Journal of Pain | volume = 16 | issue = 1 | pages = 6–11 | year = 2000 | month = March | pmid = 10741812 | doi = 10.1097/00002508-200003000-00002| url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0749-8047&volume=16&issue=1&spage=6}}</ref><ref name="pmid11706096">{{cite journal | author = Semenchuk MR, Sherman S, Davis B | title = Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain | journal = Neurology | volume = 57 | issue = 9 | pages = 1583–8 | year = 2001 | month = November | pmid = 11706096 | doi = | url = http://www.neurology.org/cgi/pmidlookup?view=long&pmid=11706096}}</ref><ref name="pmid20185402">{{cite journal | author = Shah TH, Moradimehr A | title = Bupropion for the Treatment of Neuropathic Pain | journal = The American Journal of Hospice & Palliative Care | volume = 27| issue = 5| pages = 333–6| year = 2010 | month = February | pmid = 20185402 | doi = 10.1177/1049909110361229 | url = http://ajh.sagepub.com/cgi/pmidlookup?view=long&pmid=20185402}}</ref>

==Contraindications==
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. It should be avoided in individuals who are also taking [[MAO inhibitor]]s (MAOIs). When switching from MAOIs to bupropion, it is important to include a washout period of about two weeks between the medications.<ref name="WellbutrinPI"/> The prescribing information approved by the FDA recommends that caution should be exercised when treating patients with liver damage, severe [[kidney disease]], and severe [[hypertension]], as well as in pediatric patients, adolescents and young adults due to the increased risk of [[suicidal ideation]].<ref name="WellbutrinPI"/>

According to a [[retrospective]] [[case series]] published in 1993, bupropion treatment may exacerbate [[tic]]s in children with co-occurring [[Attention-deficit hyperactivity disorder|ADHD]] and [[Tourette syndrome]].<ref>{{cite journal |author=Spencer T, Biederman J, Steingard R, Wilens T |title=Bupropion exacerbates tics in children with attention-deficit hyperactivity disorder and Tourette's syndrome |journal=J Am Acad Child Adolesc Psychiatry |volume=32 |issue=1 |pages=211–4 |year=1993 |pmid=8428875 |doi=10.1097/00004583-199301000-00030}}</ref> No further research of this side effect has been conducted.

==Adverse effects==
[[Seizure]] is the most controversial side effect of bupropion, and was responsible for its initial withdrawal from the market. The risk of seizure is highly dose-dependent: 0.1% at 100–300&nbsp;mg of bupropion, 0.4% at 300–450&nbsp;mg, and 2% at 600&nbsp;mg. For comparison, the incidence of the first unprovoked seizure in the general population is 0.07–0.09%. The risk of seizure for other antidepressants is as follows: 0.1–0.6% for [[imipramine]], depending on dosage; 0–0.06% for [[amitriptyline]], depending on dosage; 0.5% for [[clomipramine]]; 0.4% for [[maprotiline]]; and 0.2% for [[fluoxetine]] and [[fluvoxamine]].<ref>{{cite journal |author=Pisani F, Oteri G, Costa C, Di Raimondo G, Di Perri R |title=Effects of Psychotropic Drugs on Seizure Threshold |journal=Drug Safety|volume=25 |issue=2 |pages=91–110 |year=2002 |doi=10.2165/00002018-200225020-00004 |pmid=11888352}}</ref>  Experiments on mice indicate that increased susceptibility to seizure is a general side effect of chronically using antidepressants that inhibit norepinephrine transporters, such as [[imipramine]], [[desipramine]] and [[reboxetine]].<ref>{{cite journal |author=Ahern TH, Javors MA, Eagles DA, Martillotti J, Mitchell HA, Liles LC, Weinshenker D |title=The effects of chronic norepinephrine transporter inactivation on seizure susceptibility in mice |journal=Neuropsychopharmacology |volume=31 |issue=4 |pages=730–8 |year=2006 |pmid=16052243 |doi=10.1038/sj.npp.1300847}}</ref> Clinical depression itself was reported to increase the occurrence of seizures two-to-sevenfold compared with the general population; in this light, the above statistics could indicate that low to moderate doses of antidepressants, including bupropion, may actually have an anti-convulsive action.<ref>{{cite journal |author=Alper K, Schwartz KA, Kolts RL, Khan A |title=Seizure Incidence in Psychopharmacological Clinical Trials: An Analysis of Food and Drug Administration (FDA) Summary Basis of Approval Reports |journal=Biol Psychiatry |volume=62 |issue=4 |pages=345–54 |year=2007 |pmid=17223086 |doi=10.1016/j.biopsych.2006.09.023}}</ref>

The prescribing information notes that [[hypertension]], sometimes severe, was observed in some patients, both with and without pre-existing hypertension. The frequency of this adverse effect was under 1% and not significantly higher than that found with placebo.<ref name="WellbutrinPI"/> In a group of cardiac patients with depression, high doses of bupropion (400–500&nbsp;mg/day) caused a rise in [[supine position|supine]] blood pressure but had no effect on pulse rate.<ref name="pmid1900980">{{cite journal |author=Roose SP, Dalack GW, Glassman AH, Woodring S, Walsh BT, Giardina EG |title=Cardiovascular effects of bupropion in depressed patients with heart disease |journal=Am J Psychiatry |volume=148 |issue=4 |pages=512–6 |year=1991 |pmid=1900980 |doi=}}</ref> No statistically significant changes in blood pressure or heart rate occurred in patients with or without heart conditions at a lower dose of 300&nbsp;mg/day.<ref name="pmid12109935">{{cite journal |author=Aubin HJ |title=Tolerability and safety of sustained-release bupropion in the management of smoking cessation |journal=Drugs |volume=62 Suppl 2 |issue= |pages=45–52 |year=2002 |pmid=12109935 |doi=10.2165/00003495-200262002-00005}}</ref> In a study of bupropion for [[ADHD]], a rise of [[systole (medicine)|systolic]] blood pressure by 6&nbsp;mm&nbsp;Hg and of heart rate by 7 beats per minute (both statistically significant) were observed.<ref name="pmid15705013">{{cite journal |author=Wilens TE, Hammerness PG, Biederman J, Kwon A, Spencer TJ, Clark S, Scott M, Podolski A, Ditterline JW, Morris MC, Moore H |title=Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder |journal=J Clin Psychiatry |volume=66 |issue=2 |pages=253–9 |year=2005 |pmid=15705013 |doi=10.4088/JCP.v66n0215}}</ref> A study of smokers hospitalized for heart disease found a 1.5-fold increase (close to being statistically significant) in subsequent cardiovascular events in the bupropion group, compared with the placebo group, but found no difference in blood pressure.<ref name="pmid17145253">{{cite journal |author=Rigotti NA, Thorndike AN, Regan S, McKool K, Pasternak RC, Chang Y, Swartz S, Torres-Finnerty N, Emmons KM, Singer DE |title=Bupropion for smokers hospitalized with acute cardiovascular disease |journal=Am J Med |volume=119 |issue=12 |pages=1080–7 |year=2006 |pmid=17145253 |doi=10.1016/j.amjmed.2006.04.024}}</ref> Although the cardiovascular side effects of bupropion appear to be mild, it cannot be recommended for patients with heart disease, since the safety comparison with SSRIs (such as [[sertraline]] and [[fluoxetine]], which may have a preventative effect after a [[myocardial infarction]]<ref name="pmid17112303">{{cite journal |author=van Melle JP, de Jonge P, van den Berg MP, Pot HJ, van Veldhuisen DJ |title=Treatment of depression in acute coronary syndromes with selective serotonin reuptake inhibitors |journal=Drugs |volume=66 |issue=16 |pages=2095–107 |year=2006 |pmid=17112303 |doi=10.2165/00003495-200666160-00005}}</ref>) is not in its favor.

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 [[Medicines and Healthcare products Regulatory Agency|MHRA]] as part of the [[Yellow Card Scheme]], which monitored side effects. Approximately 540,000 people were treated with bupropion for smoking cessation during that period. The MHRA received 60 reports of "''suspected'' [emphasis MHRA's] adverse reactions to Zyban which had a fatal outcome". The agency concluded that "in the majority of cases the individual’s underlying condition may provide an alternative explanation."<ref name=MHRA>{{cite web | title = Zyban (bupropion hydrochloride) &ndash; safety update | publisher = [[Medicines and Healthcare products Regulatory Agency]] | date = 2002-07-24 | accessdate = 2006-10-07 | url = http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dID=2556&noSaveAs=0&Rendition=WEB| archiveurl = http://web.archive.org/web/20070928004349/http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dID=2556&noSaveAs=0&Rendition=WEB| archivedate = September 28, 2007}}</ref> This is consistent with a large, 9,300-patient safety study that showed that the mortality of smokers taking bupropion is not higher than the natural mortality of smokers of the same age.<ref name=Hubbard>{{cite journal | author = Hubbard R, Lewis S, West J, Smith C, Godfrey C, Smeeth L, Farrington P, Britton J | title = Bupropion and the risk of sudden death: a self-controlled case-series analysis using The Health Improvement Network | journal = Thorax | volume = 60 | issue = 10 | pages = 848–50 | year = 2005 | pmid = 16055620 | doi = 10.1136/thx.2005.041798 | pmc = 1747199}} [http://thorax.bmj.com/cgi/content/full/60/10/848 Free full text]</ref>

Other isolated adverse affects have been reported. Three cases of liver toxicity have been described,<ref name="pmid11785718">For the most recent report, see: {{cite journal |author=Alvaro D, Onetti-Muda A, Moscatelli R, Atili AF |title=Acute cholestatic hepatitis induced by bupropion prescribed as pharmacological support to stop smoking. A case report |journal=Digestive and liver disease|volume=33 |issue=8 |pages=703–6 |year=2001 |pmid=11785718 |doi=10.1016/S1590-8658(01)80049-9}}</ref> a very low incidence given the widespread use of the drug. A single case of clitoral priapism ([[clitorism]]) has been reported in the literature.<ref>{{cite journal | author = Levenson JL | title = Priapism associated with bupropion treatment | journal = Am J Psychiatry | volume = 152 | issue = 5 | page = 813 | year = 1995 | pmid = 7726332}}</ref>

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]]. Those that most often resulted in interruption of the treatment in the same trial were rash (2.4%) and nausea (0.8%).<ref name="WellbutrinPI"/>

===Suicidality and other psychiatric side effects===
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. This warning is based on a statistical analysis conducted by the FDA which found a 2-fold increase of the [[suicidal ideation]] and behavior in children and adolescents, and 1.5-fold increase of suicidality in the 18–24 age group.<ref name=FDA>{{cite web | author = Levenson M, Holland C| title =Antidepressants and Suicidality in Adults: Statistical Evaluation. (Presentation at Psychopharmacologic Drugs Advisory Committee; December 13, 2006)|accessdate = 2007-05-13 | url =  http://www.fda.gov/ohrms/dockets/ac/06/slides/2006-4272s1-04-FDA.ppt}}</ref>

[[Suicidal ideation]] and behavior in clinical trials are rare. 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. Considered separately, bupropion and nine other antidepressants were not statistically different from placebo. Only [[fluoxetine]] caused a significant decrease in suicidal ideation.<ref name=FDA/>

Suicidal behavior is less likely when bupropion is prescribed for smoking cessation. According to a 2007 [[Cochrane Library|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. The review concludes, "Although some suicides and deaths while taking bupropion have been reported, thus far there is insufficient evidence to suggest they were caused by bupropion."<ref> {{cite journal |author = Hughes JR, Stead LF, Lancaster T|title = Antidepressants for smoking cessation |journal = Cochrane Database Syst Rev. |volume=24 |issue=1|pages=CD000031 |year=2007 |pmid=17253443|doi = 10.1002/14651858.CD000031.pub3}}</ref>

Two years later, the FDA issued a health advisory, which warned that the prescription of bupropion and [[varenicline]] for smoking cessation has been associated with reports about unusual behavior changes, agitation and hostility.  Some patients have become depressed or have had their depression worsen, have had thoughts about suicide or dying, or have attempted suicide.<ref name=warning>{{cite web | author = | title = Public Health Advisory: FDA Requires New Boxed Warnings for the Smoking Cessation Drugs Chantix and Zyban|accessdate = 2009-07-03 | url =  http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm169988.htm}} {{Dead link|date=September 2010|bot=H3llBot}}</ref><ref name=warning2>{{cite web | author = | title = Information for Healthcare Professionals: Varenicline (marketed as Chantix) and Bupropion (marketed as Zyban, Wellbutrin, and generics)|accessdate = 2009-07-03 | url =  http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm169986.htm}}</ref> This advisory was based on the postmarket review of anti-smoking products, which identified 153 reports of the suicidal adverse events for varenicline over the first year it was marketed and 75 reports for bupropion over ten years. No clear association with suicidality was identified for [[nicotine patch]] products.<ref> {{cite journal |author = |title = THE SMOKING CESSATION AIDS VARENICLINE (MARKETED AS CHANTIX) AND BUPROPION (MARKETED AS ZYBAN AND GENERICS) Suicidal Ideation and Behavior |journal = Drug Safety Newsletter |volume=2 |issue=1|pages=1–4 |year=2009 | publisher=FDA| url = http://www.fda.gov/downloads/Drugs/DrugSafety/DrugSafetyNewsletter/UCM107318.pdf|format=PDF}}</ref>

[[Mania]] is one of the rare side effects of bupropion. The prescribing information notes that "it is generally believed (though not established in controlled trials)" that, should an episode of depression actually be the first presentation of [[bipolar disorder]], treating it with antidepressants, including bupropion, may precipitate a manic episode.<ref name="WellbutrinPI"/> More recent data indicate that the addition of newer antidepressants, including bupropion, to a [[mood stabilizer]] does not cause the switch to mania more often than the addition of placebo.<ref name="pmid15337640"/>  Moreover, when added to a mood stabilizer, bupropion and sertraline had a twice lower switch risk than venlafaxine.<ref name="pmid16880481">{{cite journal |author=Post RM, Altshuler LL, Leverich GS, Frye MA, Nolen WA, Kupka RW, Suppes T, McElroy S, Keck PE, Denicoff KD, Grunze H, Walden J, Kitchen CM, Mintz J |title=Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline |journal=Br J Psychiatry |volume=189 |issue= |pages=124–31 |year=2006 |pmid=16880481 |doi=10.1192/bjp.bp.105.013045}}</ref>

Like many of the antidepressants, bupropion is associated with the potential risk for causing anxiety as a side effect. How common or severe this anxiety is remains to be fully discovered. Some studies show that it has similar anxiety side effects to the SSRI antidepressants, while others show an elevated risk for [[akathisia]], or extreme anxiety, as high as 13.9%, or three times that from sertraline.<ref>{{Cite web |url=http://healthlifeandstuff.com/2010/02/wellbutrin-and-anxiety-concerns/ |title=Wellbutrin – Anxiety Treatment Concerns |publisher=Health and Life }}</ref>

[[Psychotic]] symptoms associated with bupropion are rare. They may include delusions, hallucinations, [[paranoia]], and confusion. Often, these symptoms can be reduced or eliminated by decreasing the dose or ceasing treatment.<ref name="WellbutrinPI"/><ref name="pmid3934991">{{cite journal | author = Golden RN, James SP, Sherer MA, Rudorfer MV, Sack DA, Potter WZ | title = Psychoses associated with bupropion treatment | journal = The American Journal of Psychiatry | volume = 142 | issue = 12 | pages = 1459–62 | year = 1985 | month = December | pmid = 3934991 | doi = | url = http://ajp.psychiatryonline.org/cgi/pmidlookup?view=long&pmid=3934991}}</ref><ref name="pmid3092682">{{cite journal | author = Johnston JA, Lineberry CG, Frieden CS | title = Prevalence of psychosis, delusions, and hallucinations in clinical trials with bupropion | journal = The American Journal of Psychiatry | volume = 143 | issue = 9 | pages = 1192–3 | year = 1986 | month = September | pmid = 3092682 | doi = | url = }}</ref><ref name="pmid3151278">{{cite journal | author = Golden RN | title = Diethylpropion, bupropion, and psychoses | journal = The British Journal of Psychiatry : the Journal of Mental Science | volume = 153 | issue = | pages = 265–6 | year = 1988 | month = August | pmid = 3151278 | doi = 10.1192/bjp.153.2.265| url = }}</ref><ref name="pmid1541606">{{cite journal | author = Ames D, Wirshing WC, Szuba MP | title = Organic mental disorders associated with bupropion in three patients | journal = The Journal of Clinical Psychiatry | volume = 53 | issue = 2 | pages = 53–5 | year = 1992 | month = February | pmid = 1541606 | doi = | url = }}</ref><ref name="pmid10588428">{{cite journal | author = Howard WT, Warnock JK | title = Bupropion-induced psychosis | journal = The American Journal of Psychiatry | volume = 156 | issue = 12 | pages = 2017–8 | year = 1999 | month = December | pmid = 10588428 | doi = | url = }}</ref><ref name="pmid12518275">{{cite journal | author = Neumann M, Livak V, Paul HW, Laux G | title = Acute psychosis after administration of bupropion hydrochloride (Zyban) | journal = Pharmacopsychiatry | volume = 35 | issue = 6 | pages = 247–8 | year = 2002 | month = November | pmid = 12518275 | doi = 10.1055/s-2002-36393 | url = http://www.thieme-connect.com/DOI/DOI?10.1055/s-2002-36393}}</ref><ref name="pmid18467537">{{cite journal | author = Bailey J, Waters S | title = Acute psychosis after bupropion treatment in a healthy 28-year-old woman | journal = Journal of the American Board of Family Medicine : JABFM | volume = 21 | issue = 3 | pages = 244–5 | year = 2008 | pmid = 18467537 | doi = 10.3122/jabfm.2008.03.070236 | url = http://www.jabfm.org/cgi/pmidlookup?view=long&pmid=18467537}}</ref><ref name="pmid19039677">{{cite journal | author = Javelot H, Baratta A, Weiner L, ''et al.'' | title = Two acute psychotic episodes after administration of bupropion: a case of involuntary rechallenge | journal = Pharmacy World & Science : PWS | volume = 31 | issue = 2 | pages = 238–40 | year = 2009 | month = April | pmid = 19039677 | doi = 10.1007/s11096-008-9272-x}}</ref><ref name="pmid19742195">{{cite journal | author = Grover S, Das PP | title = Can bupropion unmask psychosis | journal = Indian Journal of Psychiatry | volume = 51 | issue = 1 | pages = 53–4 | year = 2009 | month = January | pmid = 19742195 | pmc = 2738405 | doi = 10.4103/0019-5545.44907 | url = http://www.indianjpsychiatry.org/article.asp?issn=0019-5545;year=2009;volume=51;issue=1;spage=53;epage=54;aulast=Grover}}</ref> In many of these case reports, psychotic symptoms are associated with such risk factors as old age, the history of bipolar disorder or psychosis, and concomitant medications, for example, lithium or benzodiazepines.<ref name="isbn1-58562-243-5">{{cite book |author=Nemeroff, Charles B.; Schatzberg, Alan F. |title=Essentials of Clinical Psychopharmacology |publisher=American Psychiatric Publishing |location=Washington, D.C |year=2006 |page=146 |isbn=1-58562-243-5}}</ref> Most researchers have attributed the psychosis to bupropion's dopaminergic action.<ref name="pmid18467537"/><ref name="pmid17890983">{{cite journal | author = Hahn M, Hajek T, Alda M, Gorman JM | title = Psychosis induced by low-dose bupropion: sensitization of dopaminergic system by past cocaine abuse? | journal = Journal of Psychiatric Practice | volume = 13 | issue = 5 | pages = 336–8 | year = 2007 | month = September | pmid = 17890983 | doi = 10.1097/01.pra.0000290673.32978.e8 | url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1527-4160&volume=13&issue=5&spage=336}}</ref>

According to several case reports, stopping bupropion abruptly may result in [[withdrawal syndrome|discontinuation syndrome]] expressed as [[dystonia]], irritability, anxiety, [[mania]], headache, aches and pains.<ref>{{cite journal
| pmid=17218049
| year=2007
| month=April
| author=Wang, Hy; Chou, Wj; Huang, Ty; Hung, Cf
| title=Acute dystonia resulting from abrupt bupropion discontinuation
| volume=31
| issue=3
| pages=766–8
| doi=10.1016/j.pnpbp.2006.12.003
| journal=Progress in neuro-psychopharmacology & biological psychiatry
}}</ref><ref> {{cite journal
| unused_data=DUPLICATE DATA: page=78
| pmid=15014751
| url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15014751
| author=Berigan, Tr
| title=Bupropion-Associated Withdrawal Symptoms Revisited: A Case Report
| volume=4
| issue=2
| page=78
| issn=1523-5998
| pmc=181231
| journal=Primary care companion to the Journal of clinical psychiatry
| date= April 14, 2002 }}</ref><ref> {{cite journal
| pmid=15014696
| url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15014696
| author=Berigan, Tr; Harazin, Js
| title=Bupropion-Associated Withdrawal Symptoms: A Case Report
| volume=1
| issue=2
| pages=50–51
| issn=1523-5998
| pmc=181057
| journal=Primary care companion to the Journal of clinical psychiatry
| date= April 1, 1999 }}</ref><ref> {{cite journal
| pmid=15003088
| year=2004
| month=February
| author=Michael, N; Erfurth, A; Bergant, V
| title=A case report of mania related to discontinuation of bupropion therapy for smoking cessation
| volume=65
| issue=2
| page=277
| issn=0160-6689
| journal=The Journal of clinical psychiatry
}}</ref> The prescribing information recommends dose tapering after bupropion has been used for [[seasonal affective disorder]];<ref name="WellbutrinPI"/> however it states that dose tapering is not required when discontinuing treatment for smoking cessation.<ref>{{cite web |accessdate = 2010-01-06
| title=PRESCRIBING INFORMATION - ZYBAN® (bupropion hydrochloride) Sustained-Release Tablets
| url=http://us.gsk.com/products/assets/us_zyban.pdf}}</ref>

==Overdose==
Overdose of bupropion results in significant clinical effects in over one-third of cases.<ref name="Balit"/> The most common symptoms include [[sinus tachycardia]], [[hypertension]], drowsiness, lethargy, agitation, nausea and vomiting, and in particular [[delirium]] and seizures.<ref name="Balit">{{cite journal |author=Balit CR, Lynch CN, Isbister GK |title=Bupropion poisoning: a case series |journal=Med. J. Aust. |volume=178 |issue=2 |pages=61–3 |year=2003 |pmid=12526723 |doi=}}</ref><ref name="Buckley">{{cite journal |author=Buckley NA, Faunce TA |title='Atypical' antidepressants in overdose: clinical considerations with respect to safety |journal=Drug safety: an international journal of medical toxicology and drug experience |volume=26 |issue=8 |pages=539–51 |year=2003 |pmid=12825968 |doi=}}</ref><ref name=" Spiller">{{cite journal |author=Spiller HA, Ramoska EA, Krenzelok EP, Sheen SR, Borys DJ, Villalobos D, Muir S, Jones-Easom L |title=Bupropion overdose: a 3-year multi-center retrospective analysis |journal=The American journal of emergency medicine |volume=12 |issue=1 |pages=43–5 |year=1994 |pmid=8285970|doi=10.1016/0735-6757(94)90195-3}}</ref> Less commonly additional symptoms include auditory and visual [[hallucination]]s,<ref>{{cite journal |author=Mainie I, McGurk C, McClintock G, Robinson J |title=Seizures after buproprion overdose |journal=Lancet |volume=357 |issue=9268 |page=1624 |year=2001 |pmid=11386326 |doi=10.1016/S0140-6736(00)04770-X}}</ref> [[coma]],<ref name=" Spiller"/> and [[Electrocardiogram|ECG]] changes such as conduction disturbance or [[cardiac arrhythmia|arrhythmia]].<ref name="Shepherd">{{cite journal |author=Shepherd G, Velez LI, Keyes DC |title=Intentional bupropion overdoses |journal=The Journal of emergency medicine |volume=27 |issue=2 |pages=147–51 |year=2004 |pmid=15261357 |doi=10.1016/j.jemermed.2004.02.017}}</ref><ref>{{cite journal |author=Curry SC, Kashani JS, LoVecchio F, Holubek W |title=Intraventricular conduction delay after bupropion overdose |journal=The Journal of emergency medicine |volume=29 |issue=3 |pages=299–305 |year=2005 |pmid=16183450 |doi=10.1016/j.jemermed.2005.01.027}}</ref><ref>{{cite journal |author=Tracey JA, Cassidy N, Casey PB, Ali I |title=Bupropion (Zyban) toxicity |journal=Irish medical journal |volume=95 |issue=1 |pages=23–4 |year=2002 |pmid=11928786 |doi=}}</ref>

In the majority of childhood exploratory ingestions involving one or two tablets, children will remain asymptomatic.<ref name="Shepherd2">{{cite journal |author=Shepherd G, Velez LI, James DK, Keyes DC |title=Pediatric bupropion exposures reported in Texas: 1998–1999 [abstract] |journal=J Toxicol Clin Toxicol|volume=39 |issue= |page=263 |year=2001 |pmid= |doi=}}</ref><ref name="Colbridge">{{cite journal |author=Colbridge MG, Dargan PI, Jones AL |title=Bupropion - the experience of the National Poisons Information Service (London) [abstract] |journal=J Toxicol Clin Toxicol|volume=40 |issue= |pages=398–9 |year=2002 |pmid= |doi=}}</ref> In teenagers and adults seizures are more commonly observed with the seizure rate increasing tenfold with doses of 600&nbsp;mg daily.<ref name=" Johnston ">{{cite journal |author=Johnston JA, Lineberry CG, Ascher JA, Davidson J, Khayrallah MA, Feighner JP, Stark P |title=A 102-center prospective study of seizure in association with bupropion |journal=The Journal of clinical psychiatry |volume=52 |issue=11 |pages=450–6 |year=1991 |pmid=1744061 |doi=}}</ref> One overdose study suggested a dose-dependent relationship with seizures; patients ingesting more than 4.5&nbsp;g were likely to have a seizure and nearly all patients ingesting more than 9&nbsp;g had a seizure.<ref name="Balit"/>

There is no specific antidote for bupropion; treatment is supportive, and focuses on maintaining airway patency and controlling seizures with high dose intravenous [[benzodiazepine]]s or [[barbiturate]]s if seizures are refractory to benzodiazepines.<ref name="Buckley"/> Gastric decontamination may be of little benefit given the risk of seizures and aspiration<ref name="Buckley"/> but [[activated charcoal]] is recommended.<ref name="Balit"/>  Additionally, [[whole bowel irrigation]] should be undertaken in those ingesting sustained release formulations.<ref name="Buckley"/> Toxic effects may be delayed in onset, with seizures developing as late as 32&nbsp;hours.<ref name="Buckley"/> Subsequently patients should undergo [[electroencephalography|electroencephalographic]] monitoring for 48&nbsp;hours.<ref name="WellbutrinPI">{{cite web | title = Wellbutrin XL Prescribing Information | month = December | year = 2008 | publisher = [[GlaxoSmithKline]] | url = http://us.gsk.com/products/assets/us_wellbutrinXL.pdf |format=PDF|accessdate=2010-01-16}}</ref>

Bupropion overdose rarely results in death, although cases have been reported.<ref name="Shepherd"/><ref>{{cite journal |author=Harris CR, Gualtieri J, Stark G |title=Fatal bupropion overdose |journal=J Toxicol Clin Toxicol |volume=35 |issue=3 |pages=321–4 |year=1997 |pmid=9140330 |doi=10.3109/15563659709001220}}</ref><ref>{{cite journal |author=Friel PN, Logan BK, Fligner CL |title=Three fatal drug overdoses involving bupropion |journal=Journal of analytical toxicology |volume=17 |issue=7 |pages=436–8 |year=1993 |pmid=8309220 |doi=}}</ref> Fatalities are typically associated with large overdosage and related to [[metabolic acidosis]] and [[hypoxia (medical)|hypoxia]] as complications of [[status epilepticus]] with associated [[cardiorespiratory arrest]].<ref>{{cite journal |author=Paoloni R, Szekely I |title=Sustained-release bupropion overdose: a new entity for Australian emergency departments |journal=Emergency medicine (Fremantle, W.A.) |volume=14 |issue=1 |pages=109–12 |year=2002 |pmid=11993828 |doi=10.1046/j.1442-2026.2002.00295.x}}</ref> There is one published case report of successful treatment of refractory cardiac arrest in overdose of bupropion and [[lamotrigine]] using [[lipid rescue]].<ref>{{cite journal |author=Sirianni AJ, Osterhoudt KC, Calello DP, ''et al.'' |title=Use of Lipid Emulsion in the Resuscitation of a Patient With Prolonged Cardiovascular Collapse After Overdose of Bupropion and Lamotrigine |journal=Ann Emerg Med |volume= 51|issue=  4|page=412|year=2007 |pmid=17766009 |doi=10.1016/j.annemergmed.2007.06.004}}</ref>

===Detection in biological fluids===
Bupropion may be quantitated in blood, plasma or serum to monitor therapeutic use, confirm a diagnosis of poisoning or assist in a medicolegal death investigation. The drug is unstable in biological fluids at room temperature and therefore specimens should be maintained at the coldest possible temperature prior to analysis.<ref> R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 193-195.</ref>

==Mechanism of action==
Bupropion is a [[dopamine reuptake inhibitor|dopamine]] and [[norepinephrine reuptake inhibitor]].<ref>{{cite journal | author = Stahl S, Pradko J, Haight B, Modell J, Rockett C, Learned-Coughlin S | title = A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor | journal = Prim Care Companion J Clin Psychiatry | volume = 6 | issue = 4 | pages = 159–166 | year = 2004 | pmid = 15361919 | url = http://www.psychiatrist.com/pcc/pccpdf/v06n04/v06n0403.pdf|format=PDF|accessdate=2008-12-30 | doi = 10.4088/PCC.v06n0403 | pmc = 514842}} {{PMC|514842}}</ref> It is about twice as potent an inhibitor of dopamine reuptake than of norepinephrine reuptake.<ref>[http://www.atypon-link.com/GPI/doi/abs/10.1521/capn.2008.13.5.6?cookieSet=1&journalCode=capn ''Prescriptions Into Practice: Bupropion'']</ref> As bupropion is rapidly converted in the body into several metabolites with differing activity, its action cannot be understood without reference to its metabolism. The occupancy of [[dopamine transporter]] (DAT) by bupropion and its metabolites in the human brain as measured by [[positron emission tomography]] was 6–22% in an independent study<ref>{{cite journal | author = Meyer J, Goulding V S, Wilson A A, Hussey D, Christensen B K, Houle S | title = Bupropion occupancy of the dopamine transporter is low during clinical treatment | journal = Psychopharmacology | volume = 163 | pages = 102–105 | year = 2002 |pmid=12185406 |doi=10.1007/s00213-002-1166-3 | issue = 1}}</ref> and 12–35% according to GlaxoSmithKline researchers.<ref>{{cite journal | author = Learned-Coughkin S M, Bergstrom M, Savitcheva I, Ascher J, Schmith V D, Langstrom B | title = ''In vivo'' activity of bupropion at the human dopamine transporter as measured by positron emission tomography | journal = Biol Psychiatry | volume = 54| pages = 800–805 | year = 2003 |pmid=14550679 | doi = 10.1016/S0006-3223(02)01834-6 | issue = 8}}</ref> Based on analogy with [[serotonin reuptake inhibitor]]s, higher than 50% inhibition of DAT would be needed for the dopamine reuptake mechanism to be a major mechanism of the drug's action.  By contrast, approximately 65% occupancy or greater of DAT is required to achieve euphoria and reach abuse potential.<ref>Howell, L.L. and Wilcox, K.M. The dopamine transporter and cocaine medication development: Drug self-administration in nonhuman primates. JPET, 298: 1-6, 2001. [http://research.yerkes.emory.edu/Howell/JPET298.pdf PDF]</ref> However recent research indicates that dopamine is inactivated by norepinephrine reuptake in the frontal cortex, which largely lacks dopamine transporters, therefore bupropion can increase dopamine neurotransmission in this part of the brain, and this may be one possible explanation for any additional dopaminergic effects.<ref>{{cite web|url=http://stahlonline.cambridge.org/prescribers_drug.jsf?page=0521683505c09_p53-58.html.therapeutics&name=Bupropion&title=Therapeutics |title=Bupropion |work=Stahlonline.cambridge.org | publisher=[[Cambridge University Press]] |date= |accessdate=2010-04-27}}</ref>
Bupropion does not inhibit [[monoamine oxidase]] or serotonin reuptake. However, it has been shown to indirectly enhance the firing of serotonergic neurons, via activation of downstream norepinephrine flow. Bupropion has also been shown to act as a noncompetitive [[Nicotinic acetylcholine receptor#Subunits|α<sub>3</sub>β<sub>4</sub>]] [[nicotinic antagonist]].<ref>{{cite journal | author = Fryer J D,
Lukas R J | title = Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine | journal = J Pharmacol Exp Ther | volume = 288|issue=6|pages = 88–92 | year = 1999 |pmid=9862757}}</ref> The degree of inhibition of α<sub>3</sub>β<sub>4</sub> receptors correlates well with the decrease in self-administration of morphine and methamphetamine in rats,<ref>{{cite web | author = Glick S D| title = Ibogaine Analogues: Drug Development for Addictive Disorders. (Presentation at Addiction Medicine State of the Art 2003 Conference October 8–11, 2003, Radisson-Miyako Hotel, San Francisco)  | publisher = www.csam-asam.org| accessdate = 2007-03-24 | url =  http://www.csam-asam.org/pdf/misc/Glick.ppt}}</ref> and may be relevant to the effect of bupropion on nicotine addiction. The drug is supplied as a [[racemic]] mixture, and  the activities of the individual enantiomers were not found to differ.<ref>Musso D.L. et al.(1993) Synthesis and evaluation of the antidepressant activity of enantiomers of bupropion.  Chirality 5:495-500}</ref>

Two [[Structure-activity relationship|SAR]] studies date from 2009<ref>{{cite journal | pmid = 19821577 | year = 2009 | last1 = Carroll | first1 = FI | last2 = Blough | first2 = BE | last3 = Abraham | first3 = P | last4 = Mills | first4 = AC | last5 = Holleman | first5 = JA | last6 = Wolckenhauer | first6 = SA | last7 = Decker | first7 = AM | last8 = Landavazo | first8 = A | last9 = McElroy | first9 = KT | title = Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for cocaine addiction. | volume = 52 | issue = 21 | pages = 6768–81 | doi = 10.1021/jm901189z | journal = Journal of medicinal chemistry}}</ref> and 2010.<ref>{{cite journal | pmid =20158204 | year =2010 | last1 =Carroll | first1 =FI | last2 =Blough | first2 =BE | last3 =Mascarella | first3 =SW | last4 =Navarro | first4 =HA | pmc =2841507 | last5 =Eaton | first5 =JB | last6 =Lukas | first6 =RJ | last7 =Damaj | first7 =MI | title =Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for smoking cessation. | volume =53 | issue =5 | pages =2204–14 | doi =10.1021/jm9017465 | journal =Journal of medicinal chemistry}}</ref>

==Pharmacokinetics==
[[Image:Metabolites of bupropion.png|thumb|right|176px|Important metabolites of bupropion.]]
Bupropion is metabolized in the liver. It has several active [[metabolite]]s: ''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. Pharmacological data on bupropion and its metabolites are presented in Table 1. Bupropion is known to weakly inhibit the  [[Alpha-1 adrenergic receptor|α<sub>1</sub> adrenergic receptor]], with a 14% potency of its dopamine uptake inhibition, and the [[histamine H1 receptor|H<sub>1</sub> receptor]], with a 9% potency.<ref name = "horst1998"/>

The biological activity of bupropion can be attributed to a significant degree to its active metabolites, in particular to ''S,S''-hydroxybupropion. GlaxoSmithKline developed this metabolite as a separate drug called [[radafaxine]],<ref>{{cite press release | url = http://www.biospace.com/news_story.aspx?StoryID=18222420&full=1 | title = GlaxoSmithKline (GSK) Reviews Novel Therapeutics For CNS Disorders And Confirms Strong Pipeline Momentum | date = November 23, 2004 | accessdate = 2007-08-18 | publisher = PRNewswire}}</ref> but discontinued development in 2006 due to "an unfavourable risk/benefit
assessment".<ref>
GlaxoSmithKline (July 26, 2006) {{PDFlink|[http://www.gsk.com/investors/reports/gsk_q22006/q22006.pdf ''Pipeline Update'']|136&nbsp;KB}}. [[Press release]]. Retrieved on 2007-08-18.</ref>

Bupropion is metabolized to hydroxybupropion by [[CYP2B6]], an [[isoenzyme]] of the [[cytochrome P450|cytochrome P450 system]]. Alcohol causes an increase of CYP2B6 in the liver, and persons with a history of alcohol use metabolize bupropion faster. 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. The metabolism of bupropion is highly variable: the effective doses of bupropion received by persons who ingest the same amount of the drug may differ by as much as 5.5 times (and the half-life from 3 to 16 hours), and of hydroxybupropion by as much as 7.5 times (and the half-life from 12 to 38 hours).<ref name="pmid14515060">{{cite journal |author=Kirchheiner J, Klein C, Meineke I, Sasse J, Zanger UM, Mürdter TE, Roots I, Brockmöller J |title=Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6 |journal=Pharmacogenetics |volume=13 |issue=10 |pages=619–26 |year=2003 |pmid=14515060 |doi=10.1097/00008571-200310000-00005}}</ref><ref name="pmid15083067">{{cite journal |author=Hesse LM, He P, Krishnaswamy S, Hao Q, Hogan K, von Moltke LL, Greenblatt DJ, Court MH |title=Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes |journal=Pharmacogenetics |volume=14 |issue=4 |pages=225–38 |year=2004 |pmid=15083067|doi=10.1097/00008571-200404000-00002}}</ref> Based on this, some researchers have advocated monitoring of the blood level of bupropion and hydroxybupropion.<ref name="pmid1813908">{{cite journal |author=Preskorn SH |title=Should bupropion dosage be adjusted based upon therapeutic drug monitoring? |journal=Psychopharmacology bulletin |volume=27 |issue=4 |pages=637–43 |year=1991 |pmid=1813908 |doi=}}</ref>

There are significant interspecies differences in the metabolism of bupropion, with [[guinea pig]]s' metabolism of the drug being closest to that of humans.<ref>{{cite journal |author =  Suckow R F, Smith T M, Perumal A S, Cooper T B |title = Pharmacokinetics of bupropion and metabolites in plasma and brain of rats, mice, and guinea pigs |journal = Drug Metab Dispos |volume=14 |issue=6|pages=692–697 |year=1986 |pmid=2877828}}</ref> Particular caution is needed when extrapolating the results of experiments on rats to humans since hydroxybupropion, the main metabolite of bupropion in humans, is absent in rats.<ref name="pharmacological287">{{cite journal |author =   Welch R M, Lai A A, Schroeder D H |title = Pharmacological significance of the species differences in bupropion metabolism |journal = Xenobiotica |volume=17 |issue=3|pages=287–289 |year=1987 |pmid=3107223 |doi =   10.3109/00498258709043939}}</ref>

There have been two reported cases of false-positive urine amphetamine tests in persons taking bupropion. Bupropion metabolites ''erythro''-hydrobupropion and ''threo''-hydrobupropion, which have a [[phenethylamine]] structure resembling amphetamine are likely to have been responsible for this reaction. More specific follow-up tests were negative.<ref name="pmid10999247">{{cite journal |author=Weintraub D, Linder MW |title=Amphetamine positive toxicology screen secondary to bupropion |journal=Depress Anxiety |volume=12 |issue=1 |pages=53–4 |year=2000 |pmid=10999247 |doi=10.1002/1520-6394(2000)12:1<53::AID-DA8>3.0.CO;2-4}}</ref><ref name="pmid7768026">{{cite journal |author=Nixon AL, Long WH, Puopolo PR, Flood JG |title=Bupropion metabolites produce false-positive urine amphetamine results |journal=Clin. Chem. |volume=41 |issue=6 Pt 1 |pages=955–6 |year=1995 |pmid=7768026 |doi=}}</ref>

{| class="wikitable" style="margin:auto; margin:1em auto 1em auto;"
|+'''Table 1. Pharmacology of bupropion and its metabolites.'''<ref name=horst1998>{{cite journal | author =Horst WD, Preskorn SH| title = Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupropion| journal =  J Affect Disord| volume = 51|issue=3| pages = 237–54 | year = 1998|pmid=10333980  | doi =10.1016/S0165-0327(98)00222-5}}</ref><ref>{{cite journal | author = Johnston AJ, Ascher J, Leadbetter R, Schmith VD, Patel DK, Durcan M, Bentley B | title = Pharmacokinetic optimisation of sustained-release bupropion for smoking cessation | journal = Drugs| volume = 62|issue=Suppl 2|pages = 11–24 | year = 2002 |pmid=12109932 | doi = 10.2165/00003495-200262002-00002}}</ref><ref>{{cite journal | author =Xu H, Loboz KK, Gross AS, McLachlan AJ| title = Stereoselective analysis of hydroxybupropion and application to drug interaction studies| journal =  Chirality| volume = 19|issue=3| pages = 163–70 | year = 2007|pmid=17167747  | doi =10.1002/chir.20356}}</ref><ref>{{cite journal | author = Bondarev ML, Bondareva TS, Young R, Glennon RA| title = Behavioral and biochemical investigations of bupropion metabolites| journal =  Eur J Pharmacol| volume = 474|issue=1| pages = 85–93 | year = 2003|pmid=12909199  | doi = 10.1016/S0014-2999(03)02010-7}}</ref><ref>{{cite journal | author = Damaj MI, Carroll FI, Eaton JB, Navarro HA, Blough BE, Mirza S, Lukas RJ, Martin BR| title = Enantioselective effects of hydroxy metabolites of bupropion on behavior and on function of monoamine transporters and nicotinic receptors| journal =  Mol Pharmacol| volume = 66|issue=3| pages = 675–82 | year = 2004|pmid=15322260 | doi = 10.1124/mol.104.001313}}</ref>'''
| colspan="6" | Exposure (concentration over time; bupropion exposure = 100%) and half-life
|- style="text-align:center;"

!

! Bupropion

! ''R,R''-<br/>Hydroxy<br/>bupropion

! ''S,S''-<br/>Hydroxy<br/>bupropion

! ''Threo''-<br/>hydro<br/>bupropion

! ''Erythro''-<br/>hydro<br/>bupropion
|- style="text-align:center;"
! Exposure
| 100%
| 800%
| 160%
| 310%
| 90%
|- style="text-align:center;"
! Half-life
| 10&nbsp;h (IR)<br/>17&nbsp;h (SR)
| 21&nbsp;h
| 25&nbsp;h
| 26&nbsp;h
| 26&nbsp;h
|- style="text-align:center;"
| colspan="6" | Inhibition potency (potency of DA uptake inhibition by bupropion = 100%)
|- style="text-align:center;"
! DA uptake
| 100%
| 0% (rat)
| 70% (rat)
| 4% (rat)
| No data
|- style="text-align:center;"
! NE uptake
| 27%
| 0% (rat)
| 106% (rat)
| 16% (rat)
| No data
|- style="text-align:center;"
! 5HT uptake
| 2%
| 0% (rat)
| 4%(rat)
| 3% (rat)
| No data
|- style="text-align:center;"
! α<sub>3</sub>β<sub>4</sub> nicotinic
| 53%
| 15%
| 10%
| 7% (rat)
| No data
|- style="text-align:center;"
! α<sub>4</sub>β<sub>2</sub> nicotinic
| 8%
| 3%
| 29%
| No data
| No data
|- style="text-align:center;"
! α<sub>1</sub>* nicotinic
| 12%
| 13%
| 13%
| No data
| No data
|- style="text-align:center;"
| colspan="6" | <small>DA = [[dopamine]]; NE = [[norepinephrine]]; 5HT = [[serotonin]].</small>
|}

==Interactions==
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]]. The expected result is the increase of bupropion and decrease of hydroxybupropion blood concentration. The reverse effect (decrease of bupropion and increase of hydroxybupropion) can be expected with CYP2B6 [[enzyme induction and inhibition|inducers]], such as [[carbamazepine]], [[clotrimazole]], [[rifampicin]], [[ritonavir]], [[St John's Wort]] and others.<ref name="pmid16368442">{{cite journal |author=Jefferson JW, Pradko JF, Muir KT |title=Bupropion for major depressive disorder: Pharmacokinetic and formulation considerations |journal=Clin Ther |volume=27 |issue=11 |pages=1685–95 |year=2005 |pmid=16368442 |doi=10.1016/j.clinthera.2005.11.011}}</ref>

Hydroxybupropion (but not bupropion) is itself an inhibitor of [[CYP2D6]], as well as a substrate of that enzyme. 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.<ref name="pmid16368442"/><ref name="pmid11926715">{{cite journal |author=Kennedy SH, McCann SM, Masellis M, McIntyre RS, Raskin J, McKay G, Baker GB |title=Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects |journal=J Clin Psychiatry |volume=63 |issue=3 |pages=181–6 |year=2002 |pmid=11926715 |doi=}}</ref>

Bupropion lowers the seizure threshold; accordingly, extreme care should be taken when prescribing bupropion with other medications that also lower it, such as antipsychotics, [[theophylline]], [[steroid]]s, and some [[tricyclic antidepressant]]s.<ref name="WellbutrinPI"/> Its combination with [[nicotine replacement therapy|nicotine replacement therapies]] can elevate blood pressure; since this combination is no more effective than either a nicotine patch or bupropion alone, it is not recommended.

The prescribing information recommends minimizing the use of alcohol, since in rare cases bupropion reduces alcohol tolerance, and because the excessive use of alcohol may lower the seizure threshold.<ref name="WellbutrinPI"/> A small study conducted by GlaxoSmithKline indicated that bupropion (100&nbsp;mg) may counteract the subjective effects of small doses of alcohol (16–32&nbsp;mL, slightly less than 1–2 standard US drinks). The volunteers reported feeling more sober and clear-headed and less sedated. Bupropion also reduced the detrimental effect of alcohol on auditory vigilance. The combination of bupropion (100&nbsp;mg) and two drinks of alcohol increased heart rate by six beats per minute, a statistically significant increase.<ref>{{cite web |url=http://ctr.gsk.co.uk/Summary/bupropion/I_031.pdf |title=P02-31UK I Examination of Bupropion and Ethanol, Alone and in Combination, on Human Performance Tests, Subjective Rating Scales, EEG and Autonomic Responses |accessdate=2007-06-04 |author= |authorlink= |date= |format=PDF |work=GlaxoSmithKline Clinical Trial Register. Bupropion Studies |publisher= |pages= |language= |archiveurl= |archivedate= |quote=}}</ref>

==Availability and dose forms==
[[Image:Budeprion-XL-300mg.jpg|thumb|Generic Brand-name Budeprion XL]]
Brand-name and generic bupropion tablets are available in three forms, each as the hydrochloride [[salt (chemistry)|salt]]: immediate release (Wellbutrin), [[sustained release]] (Wellbutrin SR), and extended release (Wellbutrin XL or XR).  "Sustained release" and "extended release" are generally interchangeable terms, but in this case Wellbutrin SR is intended for twice-daily dosing and Wellbutrin XL is intended for once-daily dosing. Not all generics have retained this naming scheme, and the [[United States Pharmacopeia]] requires all prolonged-release drug formulations (including generics for Wellbutrin SR) to be labeled "extended release", which has caused confusion and medication errors.<ref name="USPnews">{{cite web | title = Practitioner's Reporting News | publisher = [[United States Pharmacopeia]] | date = 2004-09-30 | url=http://www.usp.org/hqi/practitionerPrograms/newsletters/practitionerReportingNews/prn1202004-09-30.html#14 | accessdate = 2007-08-20}}</ref><ref>{{cite journal | unused_data = DUPLICATE DATA: page = 16 | last = Rosack | first = Jim | title = Company Tries to Clear Up Confusion About Bupropion | journal = Psychiatric News | volume=41 | issue=6 | page=16 | publisher = [[American Psychiatric Association]] | date = 2006-03-17 | url = http://pn.psychiatryonline.org/cgi/content/full/41/6/16 | accessdate = 2007-08-20 }}</ref>  According to GlaxoSmithKline, the SR tablets should not be split <ref>http://us.gsk.com/products/assets/us_wellbutrinSR.pdf</ref>. Merck indicates that splitting a 150&nbsp;mg Wellbutrin SR tablet decreases the time to peak levels, but that it will retain its sustained-release characteristics.<ref>{{cite web |url=http://www.merck.com/mmpe/print/lexicomp/bupropion.html |title=BuPROPion: Drug Information Provided by Lexi-Comp: Merck Manual Professional |accessdate=2007-06-16 |work=}}</ref> An extended-release form of bupropion [[hydrobromide]] was approved by the FDA in April 2008. It is being marketed under the trade name Aplenzin.<ref>{{cite web |url=http://www.medscape.com/viewarticle/574187 |title=FDA Approvals: Advair, Relistor, Aplenzin |accessdate=2008-05-09 |author=Waknine, Yael |date=2008-05-08 |publisher=[[Medscape]]}}</ref>

On October 11, 2007, two providers of consumer information on nutritional products and supplements, [[ConsumerLab.com]] and The People’s Pharmacy, released the results of comparative tests of different brands of bupropion.<ref name=peoples>{{cite web |url=http://www.peoplespharmacy.com/archives/generic_drug_problems/generic_drug_equality_questioned.php |title=Generic Drug Equality Questioned |accessdate=2007-10-13 |author= |authorlink= |date= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote=}}</ref> The People's Pharmacy received multiple reports of increased side effects and decreased efficacy of generic bupropion, which prompted it to ask ConsumerLab.com to test the products in question. 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."<ref name=msnbc>{{cite web |url=http://www.msnbc.msn.com/id/21142869/ |title=Report questions generic antidepressant - Health Care - MSNBC.com |accessdate=2007-10-13 |author=Jacqueline Stenson |authorlink= |date=2007-10-12 |work= |publisher=MSNBC |pages= |language= |archiveurl= |archivedate= |quote=}}</ref> 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. The FDA also noted that coincidental natural mood variation is the most likely explanation for the apparent worsening of depression after the switch from Wellbutrin XL to Budeprion XL.<ref name="urlReview of Therapeutic Equivalence: Generic Bupropion XL 300 mg and Wellbutrin XL 300 mg">{{cite web |url=http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm153270.htm |title=Review of Therapeutic Equivalence: Generic Bupropion XL 300 mg and Wellbutrin XL 300 mg |work= |accessdate=2008-04-19}}</ref>

In France, marketing authorization was granted on August 3, 2001, also solely as a smoking cessation aid, and with a maximum daily dose of 300&nbsp;mg;<ref>{{cite press release | url = http://afssaps.sante.fr/htm/10/filcoprs/020102c.htm | title = ZYBAN : sevrage tabagique et sécurité d’emploi | date = January 18, 2001 | accessdate = 2007-08-19 | publisher = Agence française de sécurité sanitaire des produits de santé | language = French}}</ref> only sustained-release bupropion is available. Bupropion was granted a licence for use in adults with major depression in the Netherlands in early 2007, with GlaxoSmithKline expecting subsequent approval in other European countries.<ref>{{cite press release | authorlink = GlaxoSmithKline | author = GlaxoSmithKline | title = GlaxoSmithKline receives first European approval for Wellbutrin XR | work = | publisher = GlaxoSmithKline | date = 2007-01-16 | url = http://www.gsk.com/ControllerServlet?appId=4&pageId=402&newsid=956 | accessdate = 2007-08-19}}</ref>

==Abuse potential==
According to the US government classification of psychiatric medications, bupropion is "non-abusable"<ref>{{cite web |url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat5.table.36258 |title=Exhibit 4-3 Abuse Potential of Common Psychiatric Medications |accessdate=2007-05-25 |work=Health Services/Technology Assessment Text (HSTAT)|publisher=U.S. [[National Library of Medicine]]}}</ref> or has low abuse potential.<ref>{{cite web |url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat5.table.67504 |title=Figure 3-4: Abuse Potential of Common Psychiatric Medications |accessdate=2007-05-25 |work=Health Services/Technology Assessment Text (HSTAT)|publisher=U.S. [[National Library of Medicine]]}}</ref> In animal studies, however, [[squirrel monkey]]s<ref name="pmid2529365">{{cite journal |author=Bergman J, Madras BK, Johnson SE, Spealman RD |title=Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by [[squirrel monkey]]s |journal=J. Pharmacol. Exp. Ther. |volume=251 |issue=1 |pages=150–5 |year=1989 |pmid=2529365 |doi=}}</ref> and rats<ref name="pmid9103538">{{cite journal |author=Tella SR, Ladenheim B, Cadet JL |title=Differential regulation of dopamine transporter after chronic self-administration of bupropion and nomifensine |journal=J Pharmacol Exp Ther |volume=281 |issue=1 |pages=508–13 |year=1997 |pmid=9103538 |doi=}}</ref> maintained the intravenous self-administration of bupropion, which may indicate abuse potential. However, significant interspecies differences of bupropion metabolism, particularly between rats and humans, make such extrapolations questionable.<ref name="pharmacological287"/>

Two studies on drug abusers indicated that the subjective effects of bupropion are markedly different from those of [[amphetamine]].<ref name="pmid6412263">{{cite journal |author=Miller L, Griffith J |title=A comparison of bupropion, dextroamphetamine, and placebo in mixed-substance abusers |journal=Psychopharmacology (Berl.) |volume=80 |issue=3 |pages=199–205 |year=1983 |pmid=6412263|doi=10.1007/BF00436152}}</ref><ref name="pmid6406459">{{cite journal |author=Griffith JD, Carranza J, Griffith C, Miller LL |title=Bupropion: clinical assay for amphetamine-like abuse potential |journal=J Clin Psychiatry |volume=44 |issue=5 Pt 2 |pages=206–8 |year=1983 |pmid=6406459 |doi=}}</ref> Healthy volunteers trained to discriminate amphetamine and placebo recognized bupropion (400&nbsp;mg) as amphetamine 20% of the time, compared to 10% for placebo and 75% for [[methylphenidate]] (20&nbsp;mg). They also reported feeling alert, vigorous, elated and energetic, reflecting the general stimulating properties of bupropion. In contrast to amphetamine and methylphenidate, there was no feeling of "liking the drug" and no desire to take it again.<ref name="pmid9526144">{{cite journal |author=Rush CR, Kollins SH, Pazzaglia PJ |title=Discriminative-stimulus and participant-rated effects of methylphenidate, bupropion, and triazolam in d-amphetamine-trained humans |journal=Experimental and clinical psychopharmacology |volume=6 |issue=1 |pages=32–44 |year=1998 |pmid=9526144|doi=10.1037/1064-1297.6.1.32}}</ref> A comparison of bupropion SR (150&nbsp;mg) and [[caffeine]] (178&nbsp;mg) indicated that caffeine may have higher abuse liability since it resulted in more reports of pleasant feelings and a "high" than bupropion.<ref name="pmid15001822">{{cite journal |author=Zernig G, De Wit H, Telser S, ''et al.'' |title=Subjective effects of slow-release bupropion versus caffeine as determined in a quasi-naturalistic setting |journal=Pharmacology |volume=70 |issue=4 |pages=206–15 |year=2004 |pmid=15001822 |doi=10.1159/000075550}}</ref>

There have been four reports of bupropion abuse in the literature. Three cases described teenagers crushing and [[insufflation (medicine)|insufflating]] (snorting) the drug, two of them resulting in seizures.<ref>{{cite journal |author=Khurshid KA, Decker DH |title=Bupropion insufflation in a teenager |journal=J Child Adolesc Psychopharmacol |volume=14 |issue=1 |pages=157–8 |year=2004 |pmid=15142406 |doi=10.1089/104454604773840634}}</ref><ref>{{cite journal |author=Lu JJ, Thompson TM, Narunatvanich D, Fischbein CB, Mycyk MB |title=Seizure after Nasal Insufflation of Bupropion [abstract] |journal= Clin Toxicol (Phila) |volume=45 |issue= |page=632 |year=2007 |pmid= |doi=}}</ref><ref>{{cite journal |author=Welsh CJ, Doyon S |title=Seizure induced by insufflation of bupropion |journal=N. Engl. J. Med. |volume=347 |issue=12 |page=951 |year=2002 |pmid=12239274 |doi=10.1056/NEJM200209193471222}}</ref> An additional case was reported where a teenager ingested bupropion believing the drug to be a stimulant.<ref>{{cite journal |author=McCormick J |title=Recreational bupropion abuse in a teenager |journal=Br J Clin Pharmacol |volume=53 |issue=2 |page=214 |year=2002 |pmid=11851650|doi=10.1046/j.0306-5251.2001.01538.x |pmc=1874291}}</ref> An article on medication abuse in prisons mentions bupropion as one of the psychotropic medications commonly abused by inmates.<ref>{{cite web |url=http://www.cnsnewsonline.com/index.asp?section_id=113&show=dept&article_id=4907 |title=Intervention Reduces Psychotropic Abuse in Correctional Facility; CNS News, JUNE 2005, VOLUME: 07:06 |accessdate=2007-05-27 |author=Volpe KD | archiveurl = http://web.archive.org/web/20070929071643/http://www.cnsnewsonline.com/index.asp?section_id=113&show=dept&article_id=4907| archivedate = September 29, 2007}}</ref>

==Synthesis==
Bupropion is synthesized by brominating 3'-chloropropiophenone, followed by [[nucleophilic substitution]] with [[t-butylamine|''t''-butylamine]].<ref name="United States Patent: 3819706"/><ref>{{Cite journal | journal = [[J. Chem. Ed.]] | title = A Short, One-Pot Synthesis of Bupropion | author = Daniel M. Perrine, Jason T. Ross, Stephen J. Nervi, and Richard H. Zimmerman | url = http://jchemed.chem.wisc.edu/Journal/Issues/2000/nov/PlusSub/V77N11/p1479.pdf |format=PDF| year = 2000 | volume = 77 | issue = 11 | page = 1479}}</ref>

:[[Image:Synthesis of bupropion.png|500px]]

== See also ==
* [[Butaxamine]]
* [[Substituted cathinone]]

==References==
{{Reflist|2}}

==External links==
{{Portal|Pharmacy and Pharmacology}}
* [http://www.wellbutrin-xl.com Official Wellbutrin website]
*[http://www.merck.com/mmpe/lexicomp/bupropion.html List of international brand names for bupropion]
* {{dmoz|Health/Pharmacy/Drugs_and_Medications/B/Bupropion/|Bupropion}}
* [http://www.rxlist.com/cgi/generic/buprop_cp.htm Wellbutrin Pharmacology, Pharmacokinetics, Studies, Metabolism - Bupropion - RxList Monographs]
* [http://www.nami.org/Template.cfm?Section=About_Medications&template=/ContentManagement/ContentDisplay.cfm&ContentID=7388 NAMI Wellbutrin]
* [http://www.mentalhealth.com/drug/p30-b04.html Bupropion article from mentalhealth.com]
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