Bupropion

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search

Bupropion
Skeletal formula of bupropion
Ball-and-stick model of the (S) isomer of the bupropion molecule
1 : 1 mixture (racemate)
Clinical data
Pronunciation/bjˈprpiɒn/
bew-PROH-pee-on
Trade namesWellbutrin, Zyban, others
Other namesAmfebutamone; 3-Chloro-N-tert-butyl-β-keto-α-methylphenethylamine;
3-Chloro-N-tert-butyl-β-ketoamphetamine;
Bupropion hydrochloride[1]
AHFS/Drugs.comMonograph
MedlinePlusa695033
License data
Pregnancy
category
Routes of
administration
By mouth
Drug classAntidepressants
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: ℞-only
  • UK: POM (Prescription only)
  • US: ℞-only
  • EU: Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding84% (bupropion), 77% (hydroxybupropion metabolite), 42% (threo-hydrobupropion metabolite)[3]
MetabolismLiver, intestines[5]
Elimination half-life11–21 hours[4][5]
ExcretionUrine (87%; 0.5% unchanged), faecal (10%)[5]
Identifiers
  • (RS)-2-(tert-Butylamino)-1-(3-chlorophenyl)propan-1-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC13H18ClNO
Molar mass239.74 g·mol−1
3D model (JSmol)
  • O=C(C(C)NC(C)(C)C)C1=CC=CC(Cl)=C1
  • InChI=1S/C13H18ClNO/c1-9(15-13(2,3)4)12(16)10-6-5-7-11(14)8-10/h5-9,15H,1-4H3 checkY
  • Key:SNPPWIUOZRMYNY-UHFFFAOYSA-N checkY
  (verify)

Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation.[6][7] Bupropion is an effective antidepressant on its own, but it is also popular as an add-on medication in the cases of incomplete response to the first-line selective serotonin reuptake inhibitor (SSRI) antidepressant.[7][8] Bupropion has several features that distinguish it from other antidepressants: it does not usually cause sexual dysfunction;[7] it is not associated with weight gain[7] and sleepiness,[9] and it is more effective than SSRIs at improving symptoms of hypersomnia and fatigue.[10]

Common adverse effects of bupropion with the greatest difference from placebo are dry mouth, nausea, constipation, insomnia, anxiety, tremor, and excessive sweating.[11] Raised blood pressure is notable.[12] Rare but serious side effects include seizure,[11] liver toxicity,[13] psychosis,[14] and risk of overdose.[15] Bupropion use during pregnancy may be associated with increased odds of congenital heart defects.[16]

Bupropion acts as a norepinephrine–dopamine reuptake inhibitor and a nicotinic receptor antagonist.[5] Chemically, it is an aminoketone that belongs to the class of substituted cathinones and more generally that of substituted amphetamines and substituted phenethylamines.[1][17]

Bupropion was invented by Nariman Mehta, who worked at Burroughs Wellcome, in 1969.[18] It was first approved for medical use in the United States in 1985.[19] Bupropion was originally called by the generic name amfebutamone, before being renamed in 2000.[20] In 2019, it was the 22nd most commonly prescribed medication in the United States, with more than 25 million prescriptions.[21][22] It is on the World Health Organization's List of Essential Medicines.[23]

Medical uses[edit]

Wellbutrin XL

Depression[edit]

A majority of controlled clinical trials support efficacy of bupropion for the treatment of depression.[24][7][25] However, the overall quality of the evidence is low,[25][7] with one meta-analysis, for example, finding a small[25] effect size of bupropion in depression and another finding a large[7] effect size. Comparative head-to-head clinical trials indicate that bupropion is similar in response rate against depression to fluoxetine, sertraline, paroxetine, and venlafaxine; meanwhile remission rate tends to favor buproprion.[7]

Given over the fall and winter months, bupropion prevents development of depression in those who suffer from recurring seasonal affective disorder: 15% of participants on bupropion experienced a major depressive episode vs. 27% of those on placebo.[26] Bupropion also improves depression in bipolar disorder, with the efficacy and risk of affective switch being similar to other antidepressants.[27]

Bupropion has several features that distinguish it from other antidepressants: for instance, unlike the majority of antidepressants, it does not usually cause sexual dysfunction, and the occurrence of sexual side effects is not different from placebo.[7][28] Bupropion treatment is not associated with weight gain; on the contrary, the majority of studies observed significant weight loss in bupropion-treated participants.[7] Bupropion treatment also is not associated with the sleepiness that may be produced by other antidepressants.[9] Bupropion is more effective than selective serotonin reuptake inhibitors (SSRIs) at improving symptoms of hypersomnia and fatigue in depressed patients.[29][10] There appears to be a modest advantage for the SSRIs compared to bupropion in the treatment of depression with high anxiety; they are equivalent for the depression with moderate or low anxiety.[30]

The addition of bupropion to a prescribed SSRI is a common strategy when people do not respond to the SSRI,[8] and it is supported by clinical trials;[7] however, it appears to be inferior to the addition of atypical antipsychotic aripiprazole.[31]

Smoking cessation[edit]

Prescribed as an aid for smoking cessation bupropion reduces the severity of craving for tobacco and withdrawal symptoms[32][33][34] such as depressed mood, irritability, difficulty concentrating, and increased appetite.[35] Initially, bupropion slows the weight gain that often occurs in the first weeks after quitting smoking. With time, however, this effect becomes negligible.[35]

The bupropion treatment course lasts for seven to twelve weeks, with the patient halting the use of tobacco about ten days into the course.[35][36] After the course, the effectiveness of bupropion for maintaining abstinence from smoking declines over time, from 37% of tobacco abstinence at 3 months to 20% at one year.[37] It is unclear whether extending bupropion treatment helps to prevent relapse of smoking.[38]

Overall, six months after the therapy, bupropion increases the likelihood of quitting smoking by approximately 1.6 fold as compared to placebo. In this respect, bupropion is as effective as nicotine replacement therapy but inferior to varenicline. Combining bupropion and nicotine replacement therapy does not improve the quitting rate.[39]

In children and adolescents, the use of bupropion for smoking cessation does not appear to offer any significant benefits.[40] The evidence for its use to aid smoking cessation in pregnant women is insufficient.[41]

Attention deficit hyperactivity disorder[edit]

The treatment of attention deficit hyperactivity disorder (ADHD) is not an approved indication of bupropion, and it is not mentioned in the current (2019) guideline on the ADHD treatment from the American Academy of Pediatrics.[42] Systematic reviews of bupropion for the treatment of ADHD in both adults and children note that bupropion may be effective for ADHD but warn that this conclusion has to be interpreted with caution, because clinical trials were of low quality due to small sizes and risk of bias.[43][44][45][46] Similarly to atomoxetine, bupropion has a delayed onset of action for ADHD, and several weeks of treatment are required for therapeutic effects.[43][47] This is in contrast to stimulants, such as amphetamine and methylphenidate, which have an immediate onset of effect in the condition.[47]

Sexual dysfunction[edit]

Bupropion is less likely than other antidepressants to cause sexual dysfunction.[48] A range of studies indicate that bupropion not only produces fewer sexual side effects than other antidepressants but can actually help to alleviate sexual dysfunction[49] including sexual dysfunction induced by SSRI antidepressants.[50] There have also been small studies suggesting that bupropion or a bupropion/trazodone combination may improve some measures of sexual function in women who have hypoactive sexual desire disorder (HSDD) and are not depressed.[51] According to an expert consensus recommendation from the International Society for the Study of Women's Sexual Health, bupropion can be considered as an off-label treatment for HSDD despite limited safety and efficacy data.[52]

Obesity[edit]

Bupropion, when used for treating obesity over a period of 6 to 12 months, results in an average weight loss of 2.7 kg (5.9 lbs) over placebo.[53] This is not much different from the weight loss produced by several other weight-loss medications such as sibutramine or orlistat.[53] The combination drug naltrexone/bupropion has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of obesity.[54][55]

Other uses[edit]

Bupropion is not effective in the treatment of cocaine dependence,[56] but it is showing promise in reducing drug use in light methamphetamine users.[57] Based on studies indicating that bupropion lowers the level of the inflammatory mediator TNF-alpha, there have been suggestions that it might be useful in treating inflammatory bowel disease, psoriasis, and other autoimmune conditions, but very little clinical evidence is available.[58][59][60] Bupropion is not effective in treating chronic low back pain.[61]

Available forms[edit]

Bupropion is available as an oral tablet in a number of different formulations.[62] It is formulated mostly as the hydrochloride salt but also to a lesser extent as the hydrobromide salt.[62] The available forms of bupropion hydrochloride include IR (instant-release) tablets (50, 75, 100 mg), SR (sustained-release) tablets (50, 100, 150, 200 mg), and XL (extended-release) tablets (150, 300, 450 mg).[62] The only marketed form of bupropion hydrobromide is Aplenzin, an extended-release oral tablet (174, 348, 522 mg).[62] In addition to single-drug formulations, bupropion is formulated in combinations including naltrexone/bupropion (Contrave; 8 mg/90 mg extended-release tablets)[62] and the pending-approval bupropion/dextromethorphan (AXS-05; 105 mg/45 mg tablets).[63][64]

Contraindications[edit]

The drug label advises that bupropion should not be prescribed to individuals with epilepsy or other conditions that lower the seizure threshold, such as anorexia nervosa, bulimia nervosa, benzodiazepine or alcohol withdrawal. It should be avoided in individuals who are taking monoamine oxidase inhibitors (MAOIs). When switching from MAOIs to bupropion, it is important to include a washout period of about two weeks between the medications.[65] The label recommends that caution should be exercised when treating people with liver damage, severe kidney disease, and severe hypertension, and in children, adolescents and young adults due to the increased risk of suicidal ideation.[65]

Side effects[edit]

The common adverse effects of bupropion with the greatest difference from placebo are dry mouth, nausea, constipation, insomnia, anxiety, tremor, and excessive sweating.[11] Bupropion has the highest incidence of insomnia of all second-generation antidepressants, apart from desvenlafaxine.[66] It is also associated with about 20% increased risk of headache.[67]

Bupropion raises systolic blood pressure by 6 mm Hg and the heart rate by 7 beats per minute.[12] The prescribing information notes that hypertension, sometimes severe, is observed in some people taking bupropion, both with and without pre-existing hypertension.[11] Safety of bupropion in people with cardiovascular conditions and its general cardiovascular safety profile remain unclear due to the lack of data.[68][69]

Seizure is a rare but serious adverse effect of bupropion. It is strongly dose-dependent: for the immediate release preparation, the seizure incidence is 0.4% at the dose 300–450 mg per day; the incidence climbs almost ten-fold for the higher than recommended dose of 600 mg.[11] For comparison, the incidence of unprovoked seizure in the general population is 0.07 to 0.09%, and the risk of seizure for a variety of other antidepressants is generally between 0 and 0.5% at the recommended doses.[70]

Cases of liver toxicity leading to death or liver transplantation have been reported for bupropion. It is considered to be one of several antidepressants with greater risk of hepatotoxicity.[13]

The prescribing information warns about bupropion triggering an angle-closure glaucoma attack.[65] On the other hand, bupropion may decrease the risk of development of open angle glaucoma.[71]

Bupropion use by mothers in the first trimester of pregnancy is associated with 23% increase of the odds in congenital heart defects in their children.[16]

Bupropion has rarely been associated with instances of Stevens–Johnson syndrome.[72][73]

Psychiatric[edit]

The FDA requires all antidepressants, including bupropion, to carry a boxed 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 in suicidal thought and behavior in children and adolescents, and 1.5-fold increase in the 18–24 age group.[74] For this analysis the FDA combined the results of 295 trials of 11 antidepressants in order to obtain statistically significant results. Considered in isolation, bupropion was not statistically different from placebo.[74]

Bupropion prescribed for smoking cessation results in 25% increase of the risk of psychiatric side effects, in particular, anxiety (about 40% increase) and insomnia (about 80% increase). The evidence is insufficient to determine whether bupropion is associated with suicides or suicidal behavior.[75]

In rare cases, bupropion-induced psychosis may develop. It is associated with higher doses of bupropion; many cases described are at higher than recommended doses. Concurrent antipsychotic medication appears to be protective.[14] In most cases the psychotic symptoms are eliminated by reducing the dose, ceasing treatment or adding antipsychotic medication.[65][14]

Although studies are lacking, a handful of case reports suggest that abrupt discontinuation of bupropion may cause antidepressant discontinuation syndrome.[76]

Overdose[edit]

Bupropion is considered moderately dangerous in overdose.[77][78] According to an analysis of US National Poison Data System, adjusted for the number of prescriptions, bupropion and venlafaxine are the two new generation antidepressants (that is excluding tricyclic antidepressants) that result in the highest mortality and morbidity.[15] For significant overdoses, seizures have been reported in about a third of all cases; other serious effects include hallucinations, loss of consciousness, and abnormal heart rhythms. When bupropion was one of several kinds of pills taken in an overdose, fever, muscle rigidity, muscle damage, hypertension or hypotension, stupor, coma, and respiratory failure have been reported. While most people recover, some people have died, having suffered multiple uncontrolled seizures and heart attacks.[65]

Interactions[edit]

Since bupropion is metabolized to hydroxybupropion by the enzyme CYP2B6, drug interactions with CYP2B6 inhibitors are possible: this includes such medications as paroxetine, sertraline, norfluoxetine (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 inducers such as carbamazepine, clotrimazole, rifampicin, ritonavir, St John's wort, and phenobarbital.[79] Indeed, carbamazepine decreases exposure to bupropion by 90% and increases exposure to hydroxybupropion by 94%.[80] Ritonavir, lopinavir/ritonavir, and efavirenz have been shown to decrease levels of bupropion and/or its metabolites.[81] Ticlopidine and clopidogrel, both potent CYP2B6 inhibitors, have been found to considerably increase bupropion levels as well as decrease levels of its metabolite hydroxybupropion.[81]

Bupropion and its metabolites are inhibitors of CYP2D6, with hydroxybupropion responsible for most of the inhibition. Additionally, bupropion and its metabolites may decrease expression of CYP2D6 in the liver. The end effect is a significant slowing of the clearance of other drugs metabolized by this enzyme.[5] For instance, bupropion has been found to increase area-under-the-curve of desipramine, a CYP2D6 substrate, by 5-fold.[81] Bupropion has also been found to increase levels of atomoxetine by 5.1-fold, while decreasing the exposure to its main metabolite by 1.5-fold.[82] As another example, the ratio of dextromethorphan (a drug that is mainly metabolized by CYP2D6) to its major metabolite dextrorphan increased approximately 35-fold when it was administered to people being treated with 300 mg/day bupropion.[79] When people on bupropion are given MDMA, about 30% increase of exposure to both drugs is observed, with enhanced mood but decreased heart rate effects of MDMA.[83][84] Interactions with other CYP2D6 substrates, such as metoprolol, imipramine, nortriptyline,[84] venlafaxine,[79] and nebivolol[5] have also been reported. However, in a notable exception, bupropion does not affect the concentrations of CYP2D6 substrates fluoxetine and paroxetine.[79]

Bupropion lowers the seizure threshold, and therefore can potentially interact with other medications that also lower it, such as antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids.[65] The prescribing information recommends minimizing the use of alcohol, since in rare cases bupropion reduces alcohol tolerance.[65]

Caution should be observed when combining bupropion with a monoamine oxidase inhibitor (MAOI), as it may result in hypertensive crisis.[85]

Pharmacology[edit]

Pharmacology of bupropion and its metabolites.
  Bupropion R,R-
Hydroxy
bupropion
S,S-
Hydroxy
bupropion
Threo-
hydro
bupropion
Erythro-
hydro
bupropion
Exposure and half-life
AUC relative
to bupropion[86][87]
1 23.8 0.6 11.2 2.5
Half-life[4] 11 h 19 h 15 h 31 h 22 h
Inhibition IC50 (μM) in human cells, unless noted otherwise
DAT, uptake[88] 0.66 inactive 0.63 47 (rat)[89] no data
NET, uptake[88] 1.85 9.9 0.24 16 (rat)[89] no data
SERT, uptake[88] inactive inactive inactive 67 (rat)[89] no data
α3β4 nicotinic[88] 1.8 6.5 11 14 (rat)[90] no data
α4β2 nicotinic[91] 12 31 3.3 no data no data
α1β1γδ nicotinic[91] 7.9 7.6 28 no data no data

Pharmacodynamics and mechanism of action[edit]

The mechanism of action of bupropion is unclear but believed to be related to the fact that bupropion is a norepinephrine–dopamine reuptake inhibitor (NDRI) and antagonist of several nicotinic acetylcholine receptors.[5] It is uncertain if it is a norepinephrine–dopamine releasing agent.[5] Pharmacological actions of bupropion, to a significant degree, are due to its active metabolites hydroxybupropion, threo-hydrobupropion, and erythro-hydrobupropion that are present in the blood plasma at comparable or higher levels.[5] Overall action of these metabolites, and particularly one enantiomer S,S-hydroxybupropion, is also characterized by inhibition of norepinephrine and dopamine reuptake and nicotinic antagonism (see the Chart on the right).[5] Bupropion has no meaningful direct activity at a variety of receptors, including α- and β-adrenergic, dopamine, serotonin, histamine, and acetylcholine receptors (besides nicotinic receptors).[9]

The occupancy of dopamine transporter (DAT) by bupropion (300 mg/day) and its metabolites in the human brain as measured by several positron emission tomography (PET) studies is approximately 20%, with a mean occupancy range of about 14 to 26%.[92][93][43] For comparison, the NDRI methylphenidate at therapeutic doses is thought to occupy greater than 50% of DAT sites.[43] In accordance with its low DAT occupancy, no measurable dopamine release in the human brain was detected with bupropion (150 mg/day) in a PET study.[92][93] These findings raise questions about the role of dopamine reuptake inhibition in the pharmacology of bupropion, and suggest that other actions may be responsible for its therapeutic effects.[92][43][93] More research is needed in this area.[94] No data are available on occupancy of the norepinephrine transporter (NET) by bupropion and its metabolites.[92]

Pharmacokinetics[edit]

Principal pathways of bupropion metabolism.

After oral administration, bupropion is rapidly and completely absorbed reaching the peak blood plasma concentration after 1.5 hours (tmax). Sustained release (SR) and extended release (XL) formulations have been designed to slow down absorption resulting in tmax of 3 hours and 5 hours, respectively.[79] Absolute bioavailability of bupropion is unknown but is presumed to be low, at 5–20%, due to the first-pass metabolism. As for the relative biovailability of the formulations, XL formulation has lower bioavailability (68%) compared to SR formulation and immediate release bupropion.[5]

Bupropion is metabolized in the body by a variety of pathways. The oxidative pathways are by cytochrome P450 isoenzymes CYP2B6 leading to R,R- and S,S-hydroxybupropion and, to a lesser degree, CYP2C19 leading to 4'-hydroxybupropion. The reductive pathways are by 11β-hydroxysteroid dehydrogenase type 1 in the liver and AKR7A2/AKR7A3 in the intestine leading to threo-hydrobupropion and by yet unknown enzyme leading to erythro-hydrobupropion.[5] (see Scheme on the right)

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 (with a half-life of 12–30 hours), while the effective doses of hydroxybupropion may differ by as much as 7.5 times (with a half-life of 15–25 hours).[65][95][96] Based on this, some researchers have advocated monitoring of the blood level of bupropion and hydroxybupropion.[97]

Chemistry[edit]

Bupropion is an aminoketone that belongs to the class of substituted cathinones and the more general class of substituted phenethylamines.[1][17] The clinically used bupropion is racemic, that is a mixture of two enantiomers: S-bupropion and R-bupropion. Although the optical isomers on bupropion can be separated, they rapidly racemize under physiological conditions.[5][98]

There have been reported cases of false-positive urine amphetamine tests in persons taking bupropion.[99][100][101]

Synthesis[edit]

It is synthesized in two chemical steps starting from 3'-chloro-propiophenone. The alpha position adjacent to the ketone is first brominated followed by nucleophilic displacement of the resulting alpha-bromoketone with t-butylamine and treated with hydrochloric acid to give bupropion as the hydrochloride salt in 75–85% overall yield.[18][102]

Bupropion synthesis diagram
3'-chloro-propiophenone
3'-chloro-2-bromopropiophenone
bupropion hydrochloride
This diagram shows the synthesis of bupropion via 3'-chloro-propiophenone.

History[edit]

Comparison of steady-state plasma bupropion levels with bupropion IR 100 mg t.i.d. (3x/day), bupropion SR 150 mg b.i.d. (2x/day), and bupropion XL 300 mg q.d. (1x/day).[103][79]

Bupropion was invented by Nariman Mehta of Burroughs Wellcome (now GlaxoSmithKline) in 1969, and the US patent for it was granted in 1974.[18] It was approved by the U.S. Food and Drug Administration (FDA) as an antidepressant on 30 December 1985, and marketed under the name Wellbutrin.[19][104] However, a significant incidence of seizures at the originally recommended dosage (400–600 mg/day) 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 lower maximum recommended daily dose of 450 mg/day.[105]

In 1996, the FDA approved a sustained-release formulation of alcohol-resistant bupropion called Wellbutrin SR, intended to be taken twice a day (as compared with three times a day for immediate-release Wellbutrin).[106] In 2003, the FDA approved another sustained-release formulation called Wellbutrin XL, intended for once-daily dosing.[107] Wellbutrin SR and XL are available in generic form in the United States and Canada. In 1997, bupropion was approved by the FDA for use as a smoking cessation aid under the name Zyban.[108][106] In 2006, Wellbutrin XL was similarly approved as a treatment for seasonal affective disorder.[109][110]

In France, marketing authorization was granted for Zyban on 3 August 2001, with a maximum daily dose of 300 mg; only sustained-release bupropion is available, and only as a smoking cessation aid.[111]

On 11 October 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.[112] 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."[113] The FDA investigated these complaints and concluded that Budeprion XL is equivalent to Wellbutrin XL in regard to bioavailability of bupropion and its main active metabolite hydroxybupropion. The FDA also said 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.[114] On 3 October 2012, however, the FDA reversed this opinion, announcing that "Budeprion XL 300 mg fails to demonstrate therapeutic equivalence to Wellbutrin XL 300 mg."[115] The FDA did not test the bioequivalence of any of the other generic versions of Wellbutrin XL 300 mg, but requested that the four manufacturers submit data on this question to the FDA by March 2013.[115] As of October 2013 the FDA has made determinations on the formulations from some manufacturers not being bioequivalent.[115]

In April 2008, the FDA approved a formulation of bupropion as a hydrobromide salt instead of a hydrochloride salt, to be sold under the name Aplenzin by Sanofi-Aventis.[116][117][118]

In 2009, the FDA issued a health advisory warning that the prescription of bupropion for smoking cessation has been associated with reports about unusual behavior changes, agitation and hostility. Some people, according to the advisory, have become depressed or have had their depression worsen, have had thoughts about suicide or dying, or have attempted suicide.[119] This advisory was based on a review of anti-smoking products that identified 75 reports of "suicidal adverse events" for bupropion over ten years.[120] Based on the results of follow-up trials this warning was removed in 2016.[121]

In 2012, the U.S. Justice Department announced that GlaxoSmithKline had agreed to plead guilty and pay a $3-billion fine, in part for promoting the unapproved use of Wellbutrin for weight loss and sexual dysfunction.[122]

In 2017, the European Medicines Agency recommended suspending a number of nationally approved medicines due to misrepresentation of bioequivalence study data by Micro Therapeutic Research Labs in India.[123] The products recommended for suspension included several 300 mg modified-release bupropion tablets.[124]

Society and culture[edit]

Recreational use[edit]

While bupropion demonstrates some potential for misuse, this potential is less than of other commonly used stimulants, being limited by features of its pharmacology.[125] Bupropion misuse is uncommon.[125] There have been a number of anecdotal and case-study reports of bupropion abuse, but the bulk of evidence indicates that the subjective effects of bupropion when taken orally are markedly different from those of addictive stimulants such as cocaine or amphetamine.[126] However, bupropion, by non-conventional routes of administration like injection or insufflation has been reported to be misused in the United States and Canada, notably in prisons.[127][128][129][130]

Legal status[edit]

In Russia bupropion is banned as a narcotic drug, yet not per se but rather as a derivative of methcathinone.[131] In Australia and the UK, smoking cessation is the only licensed use of bupropion.[132][133]

References[edit]

  1. ^ a b c "Compound Summary". Bupropion. PubChem Compound. United States National Library of Medicine – National Center for Biotechnology Information. 28 July 2018. Retrieved 29 July 2018.
  2. ^ "Bupropion Use During Pregnancy". Drugs.com. Retrieved 24 December 2018.
  3. ^ "Zyban 150 mg prolonged release film-coated tablets – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. GlaxoSmithKline UK. 1 August 2013. Retrieved 22 October 2013.
  4. ^ a b Masters AR, Gufford BT, Lu JB, Metzger IF, Jones DR, Desta Z (August 2016). "Chiral Plasma Pharmacokinetics and Urinary Excretion of Bupropion and Metabolites in Healthy Volunteers". Journal of Pharmacology and Experimental Therapeutics. 358 (2): 230–8. doi:10.1124/jpet.116.232876. PMC 4959100. PMID 27255113.
  5. ^ a b c d e f g h i j k l m Costa R, Oliveira NG, Dinis-Oliveira RJ (August 2019). "Pharmacokinetic and pharmacodynamic of bupropion: integrative overview of relevant clinical and forensic aspects". Drug Metab Rev. 51 (3): 293–313. doi:10.1080/03602532.2019.1620763. PMID 31124380. S2CID 163167323.
  6. ^ Sweetman S (2011). Martindale: The Complete Drug Reference (37th ed.). p. 402. ISBN 9780853699828.
  7. ^ a b c d e f g h i j k Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK (April 2016). "Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant". Therapeutic Advances in Psychopharmacology. 6 (2): 99–144. doi:10.1177/2045125316629071. PMC 4837968. PMID 27141292.
  8. ^ a b Arandjelovic K, Eyre HA, Lavretsky H (October 2016). "Clinicians' Views on Treatment-Resistant Depression: 2016 Survey Reports". Am J Geriatr Psychiatry. 24 (10): 913–7. doi:10.1016/j.jagp.2016.05.010. PMC 5540329. PMID 27591914.
  9. ^ a b c Dhillon S, Yang LP, Curran MP (2008). "Bupropion: a review of its use in the management of major depressive disorder". Drugs. 68 (5): 653–89. doi:10.2165/00003495-200868050-00011. PMID 18370448.
  10. ^ a b Baldwin DS, Papakostas GI (2006). "Symptoms of fatigue and sleepiness in major depressive disorder". J Clin Psychiatry. 67 Suppl 6 (Suppl 6): 9–15. PMID 16848671.
  11. ^ a b c d e "Wellbutrin XL® Prescribing Information" (PDF). GlaxoSmithKline. June 2006. Archived from the original (PDF) on 17 July 2011.
  12. ^ a b Wilens TE, Hammerness PG, Biederman J, Kwon A, Spencer TJ, Clark S, Scott M, Podolski A, Ditterline JW, Morris MC, Moore H (2005). "Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder". J Clin Psychiatry. 66 (2): 253–9. doi:10.4088/jcp.v66n0215. PMID 15705013.CS1 maint: multiple names: authors list (link)
  13. ^ a b Voican CS, Corruble E, Naveau S, Perlemuter G (April 2014). "Antidepressant-induced liver injury: a review for clinicians". Am J Psychiatry. 171 (4): 404–15. doi:10.1176/appi.ajp.2013.13050709. PMID 24362450.
  14. ^ a b c Kumar S, Kodela S, Detweiler JG, Kim KY, Detweiler MB (November–December 2011). "Bupropion-induced psychosis: folklore or fact? A Systematic Review of the Literature". Gen Hosp Psychiatry. 33 (12): 612–7. doi:10.1016/j.genhosppsych.2011.07.001. PMID 21872337.
  15. ^ a b Nelson JC, Spyker DA (May 2017). "Morbidity and Mortality Associated With Medications Used in the Treatment of Depression: An Analysis of Cases Reported to U.S. Poison Control Centers, 2000-2014". Am J Psychiatry. 174 (5): 438–450. doi:10.1176/appi.ajp.2016.16050523. PMID 28135844.
  16. ^ a b De Vries C, Gadzhanova S, Sykes MJ, Ward M, Roughead E (March 2021). "A Systematic Review and Meta-Analysis Considering the Risk for Congenital Heart Defects of Antidepressant Classes and Individual Antidepressants". Drug Saf. 44 (3): 291–312. doi:10.1007/s40264-020-01027-x. PMID 33354752. S2CID 229357583.
  17. ^ a b Dye LR, Murphy C, Calello DP, Levine MD, Skolnik A (2017). Case Studies in Medical Toxicology: From the American College of Medical Toxicology. Springer. p. 85. ISBN 9783319564494.
  18. ^ a b c Mehta NB (25 June 1974). "United States Patent 3,819,706: Meta-chloro substituted α-butylamino-propiophenones". USPTO. Retrieved 2 June 2008.
  19. ^ a b "Wellbutrin approval package" (PDF). U.S. Food and Drug Administration (FDA). 30 December 1985. Retrieved 5 May 2020.
  20. ^ World Health Organization (2000). "International nonproprietary names for pharmaceutical substances (INN) : proposed international nonproprietary names : list 83". WHO Drug Information. 14 (2). hdl:10665/58135.
  21. ^ "The Top 300 of 2019". ClinCalc. Retrieved 16 October 2021.
  22. ^ "Bupropion - Drug Usage Statistics". ClinCalc. Retrieved 16 October 2021.
  23. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  24. ^ Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JP, Churchill R, Watanabe N, Nakagawa A, Omori IM, McGuire H, Tansella M, Barbui C (February 2009). "Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis". Lancet. 373 (9665): 746–58. doi:10.1016/S0140-6736(09)60046-5. PMID 19185342. S2CID 35858125.
  25. ^ a b c Monden R, Roest AM, van Ravenzwaaij D, Wagenmakers EJ, Morey R, Wardenaar KJ, de Jonge P (August 2018). "The comparative evidence basis for the efficacy of second-generation antidepressants in the treatment of depression in the US: A Bayesian meta-analysis of Food and Drug Administration reviews" (PDF). J Affect Disord. 235: 393–398. doi:10.1016/j.jad.2018.04.040. hdl:11370/842b1441-d0f3-4797-b95b-3a6a72262150. PMID 29677603.
  26. ^ Gartlehner G, Nussbaumer-Streit B, Gaynes BN, Forneris CA, Morgan LC, Greenblatt A, Wipplinger J, Lux LJ, Van Noord MG, Winkler D (March 2019). "Second-generation antidepressants for preventing seasonal affective disorder in adults". Cochrane Database Syst Rev. 3: CD011268. doi:10.1002/14651858.CD011268.pub3. PMC 6422318. PMID 30883669.
  27. ^ Li DJ, Tseng PT, Chen YW, Wu CK, Lin PY (March 2016). "Significant Treatment Effect of Bupropion in Patients With Bipolar Disorder but Similar Phase-Shifting Rate as Other Antidepressants: A Meta-Analysis Following the PRISMA Guidelines". Medicine (Baltimore). 95 (13): e3165. doi:10.1097/MD.0000000000003165. PMC 4998539. PMID 27043678.
  28. ^ Clayton AH (2003). "Antidepressant-Associated Sexual Dysfunction: A Potentially Avoidable Therapeutic Challenge". Primary Psychiatry. 10 (1): 55–61. Archived from the original on 4 June 2020. Retrieved 21 March 2013.
  29. ^ Baldwin DS, Papakostas GI (2006). "Symptoms of Fatigue and Sleepiness in Major Depressive Disorder". J Clin Psychiatry. 67 (suppl 6): 9–15. PMID 16848671.
  30. ^ Papakostas GI, Stahl SM, Krishen A, Seifert CA, Tucker VL, Goodale EP, Fava M (August 2008). "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". J Clin Psychiatry. 69 (8): 1287–92. doi:10.4088/JCP.v69n0812. PMID 18605812. S2CID 25267685.
  31. ^ Ruberto VL, Jha MK, Murrough JW (June 2020). "Pharmacological Treatments for Patients with Treatment-Resistant Depression". Pharmaceuticals (Basel). 13 (6): 116. doi:10.3390/ph13060116. PMC 7345023. PMID 32512768.
  32. ^ Wilkes S (2008). "The use of bupropion SR in cigarette smoking cessation". International Journal of Chronic Obstructive Pulmonary Disease. 3 (1): 45–53. doi:10.2147/copd.s1121. PMC 2528204. PMID 18488428.
  33. ^ Howes S, Hartmann-Boyce J, Livingstone-Banks J, Hong B, Lindson N (April 2020). "Antidepressants for smoking cessation". The Cochrane Database of Systematic Reviews. 4: CD000031. doi:10.1002/14651858.CD000031.pub5. PMC 7175455. PMID 32319681.
  34. ^ Wu P, Wilson K, Dimoulas P, Mills EJ (2006). "Effectiveness of smoking cessation therapies: a systematic review and meta-analysis". BMC Public Health. 6: 300. doi:10.1186/1471-2458-6-300. PMC 1764891. PMID 17156479.
  35. ^ a b c Mooney ME, Sofuoglu M (July 2006). "Bupropion for the treatment of nicotine withdrawal and craving". Expert Rev Neurother. 6 (7): 965–81. doi:10.1586/14737175.6.7.965. PMID 16831112. S2CID 19195413.
  36. ^ "DailyMed - BUPROPION HYDROCHLORIDE SR - bupropion hydrochloride tablet, film coated, extended release".
  37. ^ Rosen LJ, Galili T, Kott J, Goodman M, Freedman LS (2018). "Diminishing benefit of smoking cessation medications during the first year: a meta-analysis of randomized controlled trials". Addiction. 113 (5): 805–816. doi:10.1111/add.14134. PMC 5947828. PMID 29377409.
  38. ^ Livingstone-Banks, Jonathan; Norris, Emma; Hartmann-Boyce, Jamie; West, Robert; Jarvis, Martin; Chubb, Emma; Hajek, Peter (28 October 2019). "Relapse prevention interventions for smoking cessation". The Cochrane Database of Systematic Reviews. 2019 (10). doi:10.1002/14651858.CD003999.pub6. ISSN 1469-493X. PMC 6816175. PMID 31684681.
  39. ^ Patnode CD, Henderson JT, Coppola EL, Melnikow J, Durbin S, Thomas RG (January 2021). "Interventions for Tobacco Cessation in Adults, Including Pregnant Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force". JAMA. 325 (3): 280–298. doi:10.1001/jama.2020.23541. PMID 33464342.
  40. ^ Selph S, Patnode C, Bailey SR, Pappas M, Stoner R, Chou R (April 2020). "Primary Care-Relevant Interventions for Tobacco and Nicotine Use Prevention and Cessation in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force". JAMA. 323 (16): 1599–1608. doi:10.1001/jama.2020.3332. PMID 32343335.
  41. ^ Claire R, Chamberlain C, Davey MA, Cooper SE, Berlin I, Leonardi-Bee J, Coleman T (March 2020). "Pharmacological interventions for promoting smoking cessation during pregnancy". Cochrane Database Syst Rev. 2020 (3): CD010078. doi:10.1002/14651858.CD010078.pub3. PMC 7059898. PMID 32129504.
  42. ^ Wolraich ML, Hagan JF, Allan C, Chan E, Davison D, Earls M, Evans SW, Flinn SK, Froehlich T, Frost J, Holbrook JR, Lehmann CU, Lessin HR, Okechukwu K, Pierce KL, Winner JD, Zurhellen W (October 2019). "Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents". Pediatrics. 144 (4): e20192528. doi:10.1542/peds.2019-2528. PMC 7067282. PMID 31570648.
  43. ^ a b c d e Verbeeck W, Bekkering GE, Van den Noortgate W, Kramers C (October 2017). "Bupropion for attention deficit hyperactivity disorder (ADHD) in adults". Cochrane Database Syst Rev. 2017 (10): CD009504. doi:10.1002/14651858.CD009504.pub2. PMC 6485546. PMID 28965364.
  44. ^ Elliott J, Johnston A, Husereau D, Kelly SE, Eagles C, Charach A, Hsieh SC, Bai Z, Hossain A, Skidmore B, Tsakonas E, Chojecki D, Mamdani M, Wells GA (2020). "Pharmacologic treatment of attention deficit hyperactivity disorder in adults: A systematic review and network meta-analysis". PLOS ONE. 15 (10): e0240584. Bibcode:2020PLoSO..1540584E. doi:10.1371/journal.pone.0240584. PMC 7577505. PMID 33085721.
  45. ^ Cortese S, Adamo N, Del Giovane C, Mohr-Jensen C, Hayes AJ, Carucci S, Atkinson LZ, Tessari L, Banaschewski T, Coghill D, Hollis C, Simonoff E, Zuddas A, Barbui C, Purgato M, Steinhausen HC, Shokraneh F, Xia J, Cipriani A (September 2018). "Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis". Lancet Psychiatry. 5 (9): 727–738. doi:10.1016/S2215-0366(18)30269-4. PMC 6109107. PMID 30097390.
  46. ^ Ng QX (March 2017). "A Systematic Review of the Use of Bupropion for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents". J Child Adolesc Psychopharmacol. 27 (2): 112–116. doi:10.1089/cap.2016.0124. PMID 27813651.
  47. ^ a b Wilens TE, Morrison NR, Prince J (October 2011). "An update on the pharmacotherapy of attention-deficit/hyperactivity disorder in adults". Expert Rev Neurother. 11 (10): 1443–65. doi:10.1586/ern.11.137. PMC 3229037. PMID 21955201.
  48. ^ Serretti A, Chiesa A (June 2009). "Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis". J Clin Psychopharmacol. 29 (3): 259–66. doi:10.1097/JCP.0b013e3181a5233f. PMID 19440080. S2CID 1663570.
  49. ^ Stahl SM, Pradko JF, Haight BR, Modell JG, Rockett CB, Learned-Coughlin S (2004). "A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor". Prim Care Companion J Clin Psychiatry. 6 (4): 159–166. doi:10.4088/PCC.v06n0403. PMC 514842. PMID 15361919.
  50. ^ Basson R, Gilks T (2018). "Women's sexual dysfunction associated with psychiatric disorders and their treatment". Womens Health (Lond). 14: 1745506518762664. doi:10.1177/1745506518762664. PMC 5900810. PMID 29649948.
  51. ^ Clayton AH, Kingsberg SA, Goldstein I (June 2018). "Evaluation and Management of Hypoactive Sexual Desire Disorder". Sex Med. 6 (2): 59–74. doi:10.1016/j.esxm.2018.01.004. PMC 5960024. PMID 29523488.
  52. ^ Goldstein I, Kim NN, Clayton AH, DeRogatis LR, Giraldi A, Parish SJ, Pfaus J, Simon JA, Kingsberg SA, Meston C, Stahl SM, Wallen K, Worsley R (January 2017). "Hypoactive Sexual Desire Disorder: International Society for the Study of Women's Sexual Health (ISSWSH) Expert Consensus Panel Review". Mayo Clin Proc. 92 (1): 114–128. doi:10.1016/j.mayocp.2016.09.018. PMID 27916394.
  53. ^ a b Li Z, Maglione M, Tu W, Mojica W, Arterburn D, Shugarman LR, Hilton L, Suttorp M, Solomon V, Shekelle PG, Morton SC (April 2005). "Meta-analysis: pharmacologic treatment of obesity". Ann. Intern. Med. 142 (7): 532–46. doi:10.7326/0003-4819-142-7-200504050-00012. PMID 15809465.
  54. ^ "Drug Approval Package: Contrave (naltrexone hydrochloride/bupropion hydrochloride) Extended-Release Tablets NDA #200063". U.S. Food and Drug Administration (FDA). Retrieved 5 May 2020.
  55. ^ "Contrave Extended-Release - naltrexone hydrochloride and bupropion hydrochloride tablet, extended release". DailyMed. 26 April 2019. Retrieved 5 May 2020.
  56. ^ Kampman KM (June 2008). "The search for medications to treat stimulant dependence". Addict Sci Clin Pract. 4 (2): 28–35. doi:10.1151/ascp084228. PMC 2797110. PMID 18497715.
  57. ^ Cao DN, Shi JJ, Hao W, Wu N, Li J (June 2016). "Advances and challenges in pharmacotherapeutics for amphetamine-type stimulants addiction". Eur J Pharmacol. 780: 129–35. doi:10.1016/j.ejphar.2016.03.040. PMID 27018393.
  58. ^ Mikocka-Walus AA, Turnbull DA, Moulding NT, Wilson IG, Andrews JM, Holtmann GJ (2006). "Antidepressants and inflammatory bowel disease: a systematic review". Clin Pract Epidemiol Ment Health. 2: 24. doi:10.1186/1745-0179-2-24. PMC 1599716. PMID 16984660.
  59. ^ Thorkelson G, Bielefeldt K, Szigethy E (June 2016). "Empirically Supported Use of Psychiatric Medications in Adolescents and Adults with IBD". Inflamm Bowel Dis. 22 (6): 1509–22. doi:10.1097/MIB.0000000000000734. PMID 27167571.
  60. ^ Eskeland S, Halvorsen JA, Tanum L (August 2017). "Antidepressants have Anti-inflammatory Effects that may be Relevant to Dermatology: A Systematic Review". Acta Derm Venereol. 97 (8): 897–905. doi:10.2340/00015555-2702. PMID 28512664.
  61. ^ Urquhart DM, Hoving JL, Assendelft WW, Roland M, van Tulder MW (2008). Urquhart DM (ed.). "Antidepressants for non-specific low back pain". Cochrane Database Syst Rev (1): CD001703. doi:10.1002/14651858.CD001703.pub3. PMC 7025781. PMID 18253994.
  62. ^ a b c d e "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 20 September 2021.
  63. ^ "Bupropion/Dextromethorphan - Axsome Therapeutics - AdisInsight".
  64. ^ Majeed A, Xiong J, Teopiz KM, Ng J, Ho R, Rosenblat JD, Phan L, Cao B, McIntyre RS (March 2021). "Efficacy of dextromethorphan for the treatment of depression: a systematic review of preclinical and clinical trials". Expert Opin Emerg Drugs. 26 (1): 63–74. doi:10.1080/14728214.2021.1898588. PMID 33682569. S2CID 232141396.
  65. ^ a b c d e f g h "Wellbutrin SR - bupropion hydrochloride tablet, film coated". DailyMed. 5 November 2019. Retrieved 6 May 2020.
  66. ^ Alberti S, Chiesa A, Andrisano C, Serretti A (June 2015). "Insomnia and somnolence associated with second-generation antidepressants during the treatment of major depression: a meta-analysis". J Clin Psychopharmacol. 35 (3): 296–303. doi:10.1097/JCP.0000000000000329. PMID 25874915. S2CID 33102792.
  67. ^ Telang S, Walton C, Olten B, Bloch MH (August 2018). "Meta-analysis: Second generation antidepressants and headache". J Affect Disord. 236: 60–68. doi:10.1016/j.jad.2018.04.047. PMID 29715610.
  68. ^ Kittle J, Lopes RD, Huang M, Marquess ML, Wilson MD, Ascher J, Krishen A, Hasselblad V, Kolls BJ, Roe MT, McGuire DK, Russell SD, Mahaffey KW (October 2017). "Cardiovascular adverse events in the drug-development program of bupropion for smoking cessation: A systematic retrospective adjudication effort". Clin Cardiol. 40 (10): 899–906. doi:10.1002/clc.22744. PMC 6490529. PMID 28605035.
  69. ^ Grandi SM, Shimony A, Eisenberg MJ (December 2013). "Bupropion for smoking cessation in patients hospitalized with cardiovascular disease: a systematic review and meta-analysis of randomized controlled trials". Can J Cardiol. 29 (12): 1704–11. doi:10.1016/j.cjca.2013.09.014. PMID 24267809.
  70. ^ Pisani F, Oteri G, Costa C, Di Raimondo G, Di Perri R (2002). "Effects of psychotropic drugs on seizure threshold". Drug Saf. 25 (2): 91–110. doi:10.2165/00002018-200225020-00004. PMID 11888352. S2CID 25290793.
  71. ^ Wu A, Khawaja AP, Pasquale LR, Stein JD (January 2020). "A review of systemic medications that may modulate the risk of glaucoma". Eye (Lond). 34 (1): 12–28. doi:10.1038/s41433-019-0603-z. PMC 7002596. PMID 31595027.
  72. ^ "Naltrexone + bupropion (Mysimba). Too risky for only modest weight loss". Prescrire Int. 24 (164): 229–33. October 2015. PMID 26594724.
  73. ^ Herstowska M, Komorowska O, Cubała WJ, Jakuszkowiak-Wojten K, Gałuszko-Węgielnik M, Landowski J (May 2014). "Severe skin complications in patients treated with antidepressants: a literature review". Postepy Dermatol Alergol. 31 (2): 92–7. doi:10.5114/pdia.2014.40930. PMC 4112250. PMID 25097474.
  74. ^ a b Levenson M, Holland C. "Antidepressants and suicidality in adults: statistical evaluation. (Presentation at Psychopharmacologic Drugs Advisory Committee; December 13, 2006)". U.S. Food and Drug Administration (FDA). Archived from the original on 27 September 2007. Retrieved 13 May 2007.
  75. ^ Howes S, Hartmann-Boyce J, Livingstone-Banks J, Hong B, Lindson N (April 2020). "Antidepressants for smoking cessation". Cochrane Database Syst Rev. 4: CD000031. doi:10.1002/14651858.CD000031.pub5. PMC 7175455. PMID 32319681.
  76. ^ Henssler J, Heinz A, Brandt L, Bschor T (May 2019). "Antidepressant Withdrawal and Rebound Phenomena". Dtsch Arztebl Int. 116 (20): 355–361. doi:10.3238/arztebl.2019.0355. PMC 6637660. PMID 31288917.
  77. ^ Taylor D, Carol P, Shitij K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 978-0-470-97969-3.
  78. ^ White N, Litovitz T, Clancy C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type". Journal of Medical Toxicology. 4 (4): 238–250. doi:10.1007/BF03161207. PMC 3550116. PMID 19031375.
  79. ^ a b c d e f Jefferson JW, Pradko JF, Muir KT (November 2005). "Bupropion for major depressive disorder: Pharmacokinetic and formulation considerations". Clin Ther. 27 (11): 1685–95. doi:10.1016/j.clinthera.2005.11.011. PMID 16368442.
  80. ^ Ketter TA, Jenkins JB, Schroeder DH, Pazzaglia PJ, Marangell LB, George MS, Callahan AM, Hinton ML, Chao J, Post RM (October 1995). "Carbamazepine but not valproate induces bupropion metabolism". J Clin Psychopharmacol. 15 (5): 327–33. doi:10.1097/00004714-199510000-00004. PMID 8830063.
  81. ^ a b c https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/200063s015lbl.pdf
  82. ^ Todor, Ioana; Popa, Adina; Neag, Maria; Muntean, Dana; Bocsan, Corina; Buzoianu, Anca; Vlase, Laurian; Gheldiu, Ana-Maria; Briciu, Corina (2016). "Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers". Journal of Pharmacy & Pharmaceutical Sciences. 19 (2): 198–207. doi:10.18433/J3H03R. ISSN 1482-1826. PMID 27518170.
  83. ^ Schmid Y, Rickli A, Schaffner A, Duthaler U, Grouzmann E, Hysek CM, Liechti ME (April 2015). "Interactions between bupropion and 3,4-methylenedioxymethamphetamine in healthy subjects". Journal of Pharmacology and Experimental Therapeutics. 353 (1): 102–11. doi:10.1124/jpet.114.222356. PMID 25655950. S2CID 14761997.
  84. ^ a b Protti M, Mandrioli R, Marasca C, Cavalli A, Serretti A, Mercolini L (September 2020). "New-generation, non-SSRI antidepressants: Drug-drug interactions and therapeutic drug monitoring. Part 2: NaSSAs, NRIs, SNDRIs, MASSAs, NDRIs, and others". Med Res Rev. 40 (5): 1794–1832. doi:10.1002/med.21671. PMID 32285503. S2CID 215758102.
  85. ^ Feinberg SS (2004). "Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication". J Clin Psychiatry. 65 (11): 1520–4. doi:10.4088/jcp.v65n1113. PMID 15554766.
  86. ^ Kharasch ED, Neiner A, Kraus K, Blood J, Stevens A, Schweiger J, Miller JP, Lenze EJ (May 2019). "Bioequivalence and Therapeutic Equivalence of Generic and Brand Bupropion in Adults With Major Depression: A Randomized Clinical Trial". Clin Pharmacol Ther. 105 (5): 1164–1174. doi:10.1002/cpt.1309. PMC 6465131. PMID 30460996.
  87. ^ Kharasch ED, Neiner A, Kraus K, Blood J, Stevens A, Miller JP, Lenze EJ (November 2020). "Stereoselective Steady-State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults". Clin Pharmacol Ther. 108 (5): 1036–1048. doi:10.1002/cpt.1888. PMID 32386065. S2CID 218563059.
  88. ^ a b c d Lukas RJ, Muresan AZ, Damaj MI, Blough BE, Huang X, Navarro HA, Mascarella SW, Eaton JB, Marxer-Miller SK, Carroll FI (June 2010). "Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: aids to smoking cessation". J Med Chem. 53 (12): 4731–48. doi:10.1021/jm1003232. PMC 2895766. PMID 20509659.
  89. ^ a b c Sánchez C, Hyttel J (August 1999). "Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding". Cell Mol Neurobiol. 19 (4): 467–89. doi:10.1023/a:1006986824213. PMID 10379421. S2CID 19490821.
  90. ^ Bondarev ML, Bondareva TS, Young R, Glennon RA (August 2003). "Behavioral and biochemical investigations of bupropion metabolites". Eur. J. Pharmacol. 474 (1): 85–93. doi:10.1016/S0014-2999(03)02010-7. PMID 12909199.
  91. ^ a b Damaj MI, Carroll FI, Eaton JB, et al. (September 2004). "Enantioselective effects of hydroxy metabolites of bupropion on behavior and on function of monoamine transporters and nicotinic receptors". Mol. Pharmacol. 66 (3): 675–82. doi:10.1124/mol.104.001313. PMID 15322260. S2CID 1577336.
  92. ^ a b c d Eap CB, Gründer G, Baumann P, Ansermot N, Conca A, Corruble E, Crettol S, Dahl ML, de Leon J, Greiner C, Howes O, Kim E, Lanzenberger R, Meyer JH, Moessner R, Mulder H, Müller DJ, Reis M, Riederer P, Ruhe HG, Spigset O, Spina E, Stegman B, Steimer W, Stingl J, Suzen S, Uchida H, Unterecker S, Vandenberghe F, Hiemke C (May 2021). "Tools for optimising pharmacotherapy in psychiatry (therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests): focus on antidepressants". World J Biol Psychiatry. 22 (8): 561–628. doi:10.1080/15622975.2021.1878427. PMID 33977870. S2CID 234472488.
  93. ^ a b c Carroll FI, Blough BE, Mascarella SW, Navarro HA, Lukas RJ, Damaj MI (2014). Bupropion and bupropion analogs as treatments for CNS disorders. Adv Pharmacol. Advances in Pharmacology. 69. pp. 177–216. doi:10.1016/B978-0-12-420118-7.00005-6. ISBN 9780124201187. PMID 24484978.
  94. ^ Gründer G, Hiemke C, Paulzen M, Veselinovic T, Vernaleken I (September 2011). "Therapeutic plasma concentrations of antidepressants and antipsychotics: lessons from PET imaging". Pharmacopsychiatry. 44 (6): 236–48. doi:10.1055/s-0031-1286282. PMID 21959785.
  95. ^ Brunton L, Chabner B, Knollman B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.[page needed]
  96. ^ Hesse LM, He P, Krishnaswamy S, Hao Q, Hogan K, von Moltke LL, Greenblatt DJ, Court MH (April 2004). "Pharmacogenetic determinants of inter-individual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes". Pharmacogenetics. 14 (4): 225–38. doi:10.1097/00008571-200404000-00002. PMID 15083067.
  97. ^ Preskorn SH (1991). "Should bupropion dosage be adjusted based upon therapeutic drug monitoring?". Psychopharmacol Bull. 27 (4): 637–43. PMID 1813908.
  98. ^ Musso, David L.; Mehta, Nariman B.; Soroko, Francis E.; Ferris, Robert M.; Hollingsworth, Elizabeth B.; Kenney, Bernard T. (1993). "Synthesis and evaluation of the antidepressant activity of the enantiomers of bupropion". Chirality. 5 (7): 495–500. doi:10.1002/chir.530050704. PMID 8240925.
  99. ^ Weintraub D, Linder MW (2000). "Amphetamine positive toxicology screen secondary to bupropion". Depress Anxiety. 12 (1): 53–4. doi:10.1002/1520-6394(2000)12:1<53::AID-DA8>3.0.CO;2-4. PMID 10999247.
  100. ^ Nixon AL, Long WH, Puopolo PR, Flood JG (June 1995). "Bupropion metabolites produce false-positive urine amphetamine results". Clin. Chem. 41 (6 Pt 1): 955–6. doi:10.1093/clinchem/41.6.955. PMID 7768026.
  101. ^ Casey ER, Scott MG, Tang S, Mullins ME (June 2011). "Frequency of false positive amphetamine screens due to bupropion using the Syva EMIT II immunoassay". Journal of Medical Toxicology. 7 (2): 105–8. doi:10.1007/s13181-010-0131-5. PMC 3724447. PMID 21191682.
  102. ^ Perrine DM, Ross JT, Nervi SJ, Zimmerman RH (2000). "A Short, One-Pot Synthesis of Bupropion (Zyban, Wellbutrin)". Journal of Chemical Education. 77 (11): 1479. Bibcode:2000JChEd..77.1479P. doi:10.1021/ed077p1479.
  103. ^ Fava M, Rush AJ, Thase ME, Clayton A, Stahl SM, Pradko JF, Johnston JA (2005). "15 years of clinical experience with bupropion HCl: from bupropion to bupropion SR to bupropion XL". Prim Care Companion J Clin Psychiatry. 7 (3): 106–13. doi:10.4088/pcc.v07n0305. PMC 1163271. PMID 16027765.
  104. ^ "Wellbutrin entry in the Orange Book". U.S. Food and Drug Administration Center for Drug Evaluation and Research. Archived from the original on 25 February 2011. Retrieved 18 August 2007.
  105. ^ "Bupropion (Wellbutrin)". eMedExpert.com. 31 March 2008. Retrieved 20 August 2013.
  106. ^ a b Whitten L (April 2006). "Bupropion helps people with schizophrenia quit smoking". National Institute on Drug Abuse Research Findings. 20 (5). Archived from the original on 5 August 2007. Retrieved 27 May 2013.
  107. ^ "Drug Approval Package: Wellbutrin XL (Bupropion HCI) NDA #021515". U.S. Food and Drug Administration (FDA). 22 April 2005. Archived from the original on 5 December 2019. Retrieved 4 December 2019.
  108. ^ "Drug Approval Package: Zyban NDA# 020711". U.S. Food and Drug Administration (FDA). 8 August 2003. Archived from the original on 5 December 2019. Retrieved 4 December 2019.
  109. ^ "FDA approval letter" (PDF). U.S. Food and Drug Administration (FDA). 6 December 2006.
  110. ^ "Seasonal affective disorder drug Wellbutrin XL wins approval". CNN. 14 June 2006. Archived from the original on 30 June 2007. Retrieved 19 August 2007.
  111. ^ "Zyban : sevrage tabagique et sécurité d'emploi" [Zyban: smoking cessation and job security] (Press release) (in French). Agence française de sécurité sanitaire des produits de santé. 18 January 2002. Archived from the original on 23 July 2011. Retrieved 25 January 2011.
  112. ^ "Generic drug equality questioned". 12 October 2007. Archived from the original on 3 October 2012. Retrieved 13 October 2007.
  113. ^ Stenson J (12 October 2007). "Report questions generic antidepressant". NBC News. Retrieved 13 October 2007.
  114. ^ "Review of therapeutic equivalence: generic bupropion XL 300 mg and Wellbutrin XL 300 mg". Archived from the original on 6 June 2011. Retrieved 19 April 2008.
  115. ^ a b c "Budeprion XL 300 mg not therapeutically equivalent to Wellbutrin XL 300 mg". U.S. Food and Drug Administration (FDA). 3 October 2012. Retrieved 23 March 2013. Public Domain This article incorporates text from this source, which is in the public domain.
  116. ^ Waknine Y (8 May 2008). "FDA Approvals: Advair, Relistor, Aplenzin". Medscape. Retrieved 9 May 2008.
  117. ^ "Drug Approval Package: Aplenzin (Bupropion Hydrobromide) NDA 22108". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 5 May 2020.
  118. ^ "Aplenzin - bupropion hydrobromide tablet, extended release". DailyMed. 2 June 2020. Retrieved 21 October 2020.
  119. ^ "Public Health Advisory: FDA requires new boxed warnings for the smoking cessation drugs Chantix and Zyban". U.S. Food and Drug Administration (FDA). 1 July 2009. Archived from the original on 19 October 2010. Retrieved 3 July 2009.
  120. ^ "The smoking cessation aids varenicline (marketed as Chantix) and bupropion (marketed as Zyban and generics) suicidal ideation and behavior" (PDF). Drug Safety Newsletter. 2 (1): 1–4. 2009. Archived from the original (PDF) on 11 February 2017. Retrieved 16 December 2019.
  121. ^ "Safety Alerts for Human Medical Products - Chantix (varenicline) and Zyban (bupropion): Drug Safety Communication – Mental Health Side Effects Revised". U.S. Food and Drug Administration (FDA). Archived from the original on 20 December 2016. Retrieved 20 December 2016.
  122. ^ Thomas K, Schmidt MS (2 July 2012). "Glaxo agrees to pay $3 billion in fraud settlement". The New York Times.
  123. ^ "EMA recommends suspension of medicines due to unreliable studies from Micro Therapeutic Research Labs | European Medicines Agency".
  124. ^ "Products for which the marketing authorisations are recommended for suspension and marketing authorisation applications which do not satisfy the criteria for authorisation as adopted by the CHMP on 23 March 2017" (PDF).
  125. ^ a b Naglich AC, Brown ES, Adinoff B (2019). "Systematic review of preclinical, clinical, and post-marketing evidence of bupropion misuse potential". Am J Drug Alcohol Abuse. 45 (4): 341–354. doi:10.1080/00952990.2018.1545023. PMID 30601027. S2CID 58587857.
  126. ^ Lile JA, Nader MA (2003). "The abuse liability and therapeutic potential of drugs evaluated for cocaine addiction as predicted by animal models". Current Neuropharmacology. 1: 21–46. CiteSeerX 10.1.1.325.9635. doi:10.2174/1570159033360566.
  127. ^ Antidepressant Wellbutrin becomes 'poor man's cocaine' on Toronto streets Global News 18 September 2013.
  128. ^ Phillips D (February 2012). "Wellbutrin®: misuse and abuse by incarcerated individuals". Journal of Addictions Nursing. 23 (1): 65–9. doi:10.3109/10884602.2011.647838. PMID 22468662. S2CID 1310940.
  129. ^ Baribeau D, Araki KF (May–June 2013). "Intravenous bupropion: a previously undocumented method of abuse of a commonly prescribed antidepressant agent". Journal of Addiction Medicine. 7 (3): 216–7. doi:10.1097/ADM.0b013e3182824863. PMID 23519045.
  130. ^ Stassinos GL, Klein-Schwartz W (2016). "Bupropion "Abuse" Reported to US Poison Centers". J Addict Med. 10 (5): 357–62. doi:10.1097/ADM.0000000000000249. PMID 27504927. S2CID 24870292.
  131. ^ "Постановление Правительства РФ от 30 июня 1998 г. N 681 "Об утверждении перечня наркотических средств, психотропных веществ и их прекурсоров, подлежащих контролю в Российской Федерации" (с изменениями и дополнениями)" (in Russian). Гарант. Retrieved 28 April 2019. Эфедрон (меткатинон) и его производные, за исключением производных, включенных в качестве самостоятельных позиций в перечень
  132. ^ Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  133. ^ Joint Formulary Committee (2015). British National Formulary (BNF) (69 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-156-2.

External links[edit]