Talk:Bupropion

Article needs work

Many of the refs are old. Some of the conclusions appear a little too positive. Needs updating and removal of primary sources. Doc James (talk · contribs · email) (if I write on your page reply on mine) 00:04, 23 January 2014 (UTC)

At least one named reference, "Dwoskin2014", is forwardly-defined, i.e. used as a refname before the reference has been defined. While Wikipedia permits this, the potential result is that adding a new use of the refname disrupts the reference numbering, spawning unnecessary changes. D A Patriarche, BSc 08:36, 24 March 2017 (UTC) — Preceding unsigned comment added by D A Patriarche (talk • contribs)

Contraindications - Alcohol and Benzodiazepines

The section on contraindications needs to be corrected on the subject of alcohol and benzodiazepines. It is correct that conditions and drugs that lower the seizure threshold would be contraindications to taking buprioprion because buproprion also lowers the seizure threshold.

I would suggest an edit to the beginning of the contraindication section along the lines of:

"GlaxoSmithKline 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, active brain tumors, or withdrawal from alcohol or benzodiazepines."

Use of alcohol or benzodiazepines while taking buproprion does not lower the seizure threshold. Abrupt withdrawal from these drugs lowers the seizure threshold.

Low to moderate alcohol intake while taking buprioprion, such that stopping for a while would not precipitate withdrawal, is not contraindicated while taking buproprion. It's still not adivsable when taking buproprion for depression, of course, because alcohol is a CNS depressant. It would tend to undermine the effects of buproprion. Buproprion can also decrease one's alcohol tolerance (so one would be impaired with less alcohol).

Heavier drinkers (and those already in withdrawal) shouldn't take buproprion because 1) heavy drinking with buproprion can increase side effects, and 2) if they decrease their intake substantially (or start to abstain), alcohol withdrawal puts them at higher risk for seizure (lowers their seizure threshold).

Benzodiazepines lower the seizure threshold. So much so, that they are first-line medications for interrupting seizures. IV lorazepam (Ativan) is typically the first med given for seizures. It is also what is given as needed for patients going through alcohol withdrawal - partly because it decreases their withdrawal symptoms (because many of the pharmacologic effects are similar to alcohol), and because it decreases their risk of seizure. Abrupt withdrawal from regular benzodiazepine usage, however, does lower the seizure threshold - similar to alchol.

1) Wellbutrin tablet package insert: http://us.gsk.com/products/assets/us_wellbutrin_tablets.pdf 2) https://en.wikipedia.org/wiki/Alcohol_withdrawal#Treatment 3) https://en.wikipedia.org/wiki/Benzodiazepine#Seizures

(Wikipedia entries aren't the most authoritative, but they're more accessible than pharmacology texts for the average reader - and are sourced in the reference section). — Preceding unsigned comment added by Gnirps05 (talk • contribs) 13:58, 7 March 2014 (UTC)

Bupropion toxicity study in British Columbia

This article in the British Columbia Medical Journal "Bupropion toxicity with unintentional exposure or abuse: More common than you think" may be worth mentioning in this article. This is a television news article about the study. Eastmain (talk • contribs) 04:33, 20 November 2014 (UTC)

Typically we try to use secondary sources and major textbooks rather than primary sources for content. Doc James (talk · contribs · email) 23:24, 22 November 2014 (UTC)

Adverse effects

There are several opportunities for improvement in this section. I outline these below followed by a proposed change in the text.

• The list of "Adverse effects" is inaccurate and misleading, as these are not "adverse effects" but "adverse events". The former phrase implies causality. But for example, the "Very common (>10%) adverse effect" of headache was seen in 26% of people treated with drug and 25% of people treated with placebo in clinical trials. Several other "adverse effects" are listed in the package insert at incidences dramatically different from those in the table. These include (but are not limited to) alopecia ("rare"), concentration disturbance (post marketing reports only, not 1-10%), depression (post marketing reports only, not 1-10%), visual disturbances (postmarketing reports only, not 1-10%). Virtually all of the adverse events in the 0.01% to 0.1% category appear to be from spontaneous postmarketing reports, and thus of unknown causation. These are not Adverse Effects, but Adverse Events of unknown causality.

• The section on the MRHA report from 2002 reporting 60 deaths "most of which are explained by the individual's underlying health conditions" is a little long in the tooth, and of questionable relevance if no better source suggesting increased mortality can be found after an additional 13 years of clinical use.

• The paragraph on "bupropion induced psychosis" is based on a case report and documents stating that causation is not completely clear. The causative role of bupropion is presented as an established fact here.

• I suggest replacing this entire section with the following text:

Common adverse events seen in clinical trials

Common adverse events seen in clinical trials with an incidence at least 5% greater in people treated with bupropion compared to people treated with a sugar pill include agitation, anxiety, insomnia, weight loss, dry mouth, and nausea.

Lowering of the seizure threshold

Epileptic seizures are the most important adverse effect of bupropion. A high incidence of seizures was responsible for the temporary withdrawal of the drug from the market between 1986 and 1989. The risk of seizure is strongly dose-dependent, but also dependent on the preparation. The sustained-release preparation is associated with a seizure incidence of 0.1% at daily dosages of less than 300 mg of bupropion and 0.4% at 300–400 mg. The immediate release preparation is associated with a seizure incidence of 0.4% for dosages below 450 mg; the incidence climbs to 5% for dosages between 450–600 mg per day. 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 0.6% at recommended dosage levels. Given that clinical depression itself has been reported to increase the occurrence of seizures, it has been suggested that low to moderate doses of antidepressants may not actually increase seizure risk at all. However, this same study found that bupropion and clomipramine were unique among antidepressants in that they were associated with increased incidence of seizures.

Psychiatric

Suicidal thought and behavior are rare in clinical trials, and 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. 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.

Suicidal behavior is less of a concern when bupropion is prescribed for smoking cessation. According to a 2007 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."

Psychiatric events, including agitation, hostility, and depressed mood have been observed in people using bupropion as an aid to smoking cessation. Though the relative contributions of bupropion and nicotine withdrawal to the emergence of these symptoms is unclear, the U.S. package insert includes a boxed warning that people should stop taking the drug if these symptoms appear. The package insert further states that people should weigh these risks against the benefits of bupropion in helping people quit smoking, noting that "The health benefits of quitting smoking are immediate and substantial".

— Preceding unsigned comment added by Formerly 98 (talk • contribs) 16:23, 21 December 2014 (UTC)

FWIW, I don't think this article is FA-quality at all anymore. The OD and synthesis sections are hardly comprehensive and there's noticeable prose issues like the numerous of 1–2 sentence paragraphs scattered throughout the article. Seppi333 (Insert 2¢)

References

Source of naming info

Hi, I've noticed that the lead has picked up some erroneous naming info. Bupropion is the INN and BAN (according to Martindale) while bupropion hydrochloride is the USAN for this salt specifically (no USAN for freebase bupropion is mentioned, in this source). Amfepramone was the former INN. I felt I should raise this issue here, instead of just editing the article accordingly off the bat because I felt anyone that made these changes must have had a decent reason which should be heard. Brenton (contribs · email · talk · uploads) 06:50, 30 April 2015 (UTC)

I am a Chemist

Bupropion is technically of the amphetamine "class" or "family"... Moralistic hysteria does not require us to self-censor... — Preceding unsigned comment added by 2602:304:B34B:A940:F051:AB0F:3A76:DE48 (talk) 18:17, 18 June 2015 (UTC)

Yes, and it says so at the bottom of the lead. Sizeofint (talk) 18:29, 18 June 2015 (UTC)

Confirmed.  Done D Anthony Patriarche (talk)

New(er) Research on Bupropion and False-Positives for Amphetamines

I would suggest adding the following sentence at the end of Pharmacokinetics paragraph: "However, a 2011 study found that therapeutic use of bupropion could and did appear to cause false positives for amphetamines."

Here's the reference: Casey, E.R.; Scott, M.G.; Tang, S.; Mullins, M.E. (2011) "Frequency of false positive amphetamine screens due to bupropion using the Syva EMIT II immunoassay." J Med Toxicol 7:105–108 DOI 10.1007/s13181-010-0131-5 — Preceding unsigned comment added by Domineditor (talk • contribs) 01:36, 11 December 2015 (UTC)

Edited the statement and added the ref. Seppi333 (Insert 2¢) 06:19, 16 December 2015 (UTC)

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Clinical trial suggesting abuse liability of bupropion in 6% of smokers

A randomized placebo-controlled double-blind crossover study of the subjective effects produced by bupropion (given at a clinical dose, i.e., in its slow-relase form, 150 mg twice daily) vs caffeine in male smokers found subjective effects, i.e., pronounced self-rating of "high" in 6% of the tested subjects (total sample size = 50) suggesting that bupropion, like caffeine, might be of some abuse liability in about 6% of the smokers (PMID: 15001822). I think that this is important information with respect to estimating the abuse liability of bupropion. That bupropion may be of some abuse liability for some patients/users is supported by an ever-increasing number of case reports reporting abuse (some of which are cited on the Bupropion page in wiki). Anecdotally, some intravenous drug users also do abuse bupropion, although I have no data on that. Therefore, I would like to add that information and the reference to the bupropion page. I did and Doc James removed my text (I already have contacted Doc James and asked him why, he seems to be on vacation). I am a new user, so please advise what I have to do to get that information stably inserted into the bupropion page. Thank you very much! Stoopormundi, April 5, 2016 Stoopormundi (talk) 15:49, 5 April 2016 (UTC)

Hi Stoopormundi. Welcome to the editing side of Wikipedia! I hope we haven't damped your enthusiasm. Most articles on Wikipedia require reliable sources for their content, as you are probably aware (WP:RS). For medical and health related content the standard for a reliable source is higher (WP:MEDRS has the details). Essentially, we prefer meta-analyses and review articles to individual studies. The reason being that individuals studies often have conflicting conclusions. Hope this helps! Sizeofint (talk) 18:02, 5 April 2016 (UTC)

Dear Sizeofint, thank you very much for your help! I understand the meta-analysis / review approach. However, in the bupropion page, I have counted two CASE REPORTS among the references. The trial I was referring to was a randomized placebo-controlled crossover in 50 (FIFTY) smokers. So I think it only fair to include it as well (50 subjects tested under controlled experimental conditions with the best possible design as opposed to CASE reports). What about the following text, a very brief and concise one: "In a randomized controlled trial, 6% of the bupropion users reported a profound "high", suggesting that bupropion may have abuse liability in some."

References

StoopormundiStoopormundi (talk) 04:56, 9 April 2016 (UTC)

We can wait for this to be discussed in a review. If it is important in the field, it will be; there are lots of reviews on smoking cessation and if this is really a significant side effect and it will be addressed. There is WP:NODEADLINE here and high quality sourcing is important to maintain. 06:06, 9 April 2016 (UTC)

Editors aren't always aware of MEDRS so lower quality sources can sneak in. WP:Other stuff exists talks about this a bit. We should judge content on its own merits and not based on the existence of similar content. Actually, if you could point out the references we can try to replace them with better sources if necessary. Sizeofint (talk) 07:16, 9 April 2016 (UTC)

I looked through this and got rid of most of the primary sources. The only one that i found and couldn't get rid of was the 2002 case report of withdrawal-symptoms. I was tempted to delete that per UNDUE (2 case reports in zillions of uses is really nothing - and i found no reviews talking about this. it is also hard to find reviews b/c the search is messed up by the nicotine dependence use...). Jytdog (talk) 12:07, 9 April 2016 (UTC)

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The references support the dopaminergic action in humans.

I have a problem with the summary where it says: "However, bupropion does not appear to have significant dopaminergic actions in humans under normal clinical circumstances." I had a look in reference [13] it says no such thing. Actually the opposite, so this sentence should be removed. --ADDextron (talk) 13:25, 5 January 2018 (UTC)

 Fixed: I revised the lead and rewrote the entire "Dopaminergic activity" section in this edit. Seppi333 (Insert 2¢) 04:39, 6 January 2018 (UTC)

NPOV

User:Sbelknap this was way, way over the top. Please see Oseltamivir#Medical_use for how we handle it when meta-analyses and clinical guidelines are in tension. Jytdog (talk) 01:03, 15 July 2018 (UTC)

What clinical guideline? Sbelknap (talk) 01:49, 15 July 2018 (UTC)

FWIW, this article really does need an update of its sources for clinically relevant statements. A number of them appear to be 10–15 years old. As with linezolid, I'm guessing that's due to its FA promotion date being ~10 years ago and no one actively maintaining the article. Seppi333 (Insert 2¢) 02:36, 15 July 2018 (UTC)

I've looked at the articles cited as supporting efficacy of bupropion as an antidepressant. I didn't find a quality citation that supported efficacy. I remember the history of bupropion from its time of FDA approval to now, as I was on hospital formulary committees, IRBs, and NBME committees during much of this time. I'm unaware of any quality primary-care literature that ever supported the assertion that bupropion is an effective antidepressant. There were at least 2 unpublished clinical trials the results of which were not published, but which (apparently) showed null effect of bupropion, so there is likely also publication bias. The problem is not that this article hasn't aged well; the problem is that it states many things that were never true. Sbelknap (talk) 02:57, 15 July 2018 (UTC)

Rewriting the depression section with the current sourcing to account for the variation in conclusions actually seems like a bad idea IMO. What this article really needs is an update of its sourcing to reflect conclusions about treatment efficacy from the most recent and highest quality sources available. That basically means the efficacy statements in each section need to be updated to incorporate the findings of (1) the most recent systematic reviews which include a meta-analysis and/or (2) the most recent ordinary meta-analyses, depending upon what's available. Failing that, systematic reviews w/o meta-analysis or just plain review articles of its treatment efficacy would be the only alternative. Once we have a representative sample of newer secondary sources that assess its efficacy, we can update the article's coverage of treatment efficacy

Until we have newer sources on hand to update each sub-section, I think just dating the statements that are cited to recent reviews/meta-analyses and including the update banner in the medical uses section is the best approach. Seppi333 (Insert 2¢) 03:15, 15 July 2018 (UTC)

OK, just did that for the depression section and smoking cessation section.Sbelknap (talk) 03:41, 15 July 2018 (UTC)

and clinical guidelines. NICE for example has this drug as first line for smoking cessation. See here. We need to check others, and clinical guidelines for MDD as well. Jytdog (talk) 03:57, 15 July 2018 (UTC)

Good point. Yes, those too are high-quality references. Seppi333 (Insert 2¢) 04:05, 15 July 2018 (UTC)

@Sbelknap: You may want to use this tool to generate a citation template for sources with a PMID number. All you need to do is click the "Add ref tag" check box, copy/paste an article's PMID number into the text field, and hit submit; it will provide you with a formatted citation template.

This wikitext – <ref name=pmid24402784/> – only works in an article if there's already a pre-existing citation template in the article. A citation template is a block of code that looks like this: <ref name="pmid24402784">{{cite journal | vauthors = Hughes JR, Stead LF, Hartmann-Boyce J, Cahill K, Lancaster T | title = Antidepressants for smoking cessation | journal = The Cochrane Database of Systematic Reviews | volume = | issue = 1 | pages = CD000031 | date = January 2014 | pmid = 24402784 | doi = 10.1002/14651858.CD000031.pub4 | url = }}</ref>. The tool I've linked generates that citation template. Seppi333 (Insert 2¢) 04:02, 15 July 2018 (UTC)

Pubmed-indexed meta-analyses

So, running this search "bupropion"[Title/abstract] AND ("depression"[Title/abstract] OR "depressive disorder"[Title/abstract] OR "major depressive disorder"[Title/abstract] OR "antidepressant"[Title/abstract]) AND (Meta-Analysis[ptyp] OR "meta-analysis"[Title/abstract]) AND ("2012/07/18"[PDat] : "2018/07/15"[PDat]), I found 23 potentially relevant meta-analyses, including the recent Bayesian one (i.e., the 2nd entry in this list). I'll go through it now and see what we have. If anyone has a better idea for a search string, feel free to tell me! Seppi333 (Insert 2¢) 06:12, 15 July 2018 (UTC)

• PMID 27141292, 26558418, 25919841, 29677603 these 4 assess the efficacy of bupropion for MDD/"depression", seasonal affective disorder, and treatment-resistant depression. Haven't gone through them yet. I'm going to see if there's any relevant ones from 6-8 years ago first. Seppi333 (Insert 2¢) 06:37, 15 July 2018 (UTC)
• PMID 22244025, 21527126 the same search with a modified date range found these 2 from 2011 that assess the efficacy for dysthymia and "late-life depression". Seppi333 (Insert 2¢) 06:41, 15 July 2018 (UTC)

Meh. I'll go through the other 5 tomorrow. This is a lot of reading. Seppi333 (Insert 2¢) 06:47, 15 July 2018 (UTC)

Haven’t forgotten about this. Will include the relevant findings by tmrw morning soon.  Partly done (can't access PMID 25919841) Seppi333 (Insert 2¢) 01:06, 18 July 2018 (UTC)

I can't access PMID 25919841.

This meta-analysis indicates that it's superior to placebo for depression. There's a massive discussion and comparative analysis with other drugs, but it's not really summarized well in the paper. The abstract just states Methodologically more robust trials support the superiority of bupropion over placebo, and most head-to-head antidepressant trials showed an equivalent effectiveness, though some of these are hindered by a lack of a placebo arm. So, this basically says that the evidence suggests it has comparable effectiveness to other drugs, but some of that evidence is low-quality.

The Cochrane review on bupropion for SAD has a somewhat depressing conclusion.

The fourth trial (i.e., the 2018 meta-analysis) is already in the article; I really just need PMID 25919841 to finish covering bupropion's treatment efficacy. Seppi333 (Insert 2¢) 11:29, 20 July 2018 (UTC)

Thanks to Jytdog, I have the last meta-analysis – "Comparative Efficacy, Acceptability, and Tolerability of Augmentation Agents in Treatment-Resistant Depression: Systematic Review and Network Meta-Analysis" (uploaded here for accessibility). It doesn't state this outright, but based upon the statistical tables, there's insufficient evidence on bupropion augmentation to support its efficacy vs placebo or other any of the other augmentation agents in the study. That's sort of consistent with what the other meta-analysis discussed re: bupropion as an add-on therapy. I might add something on the lack of evidence on effectiveness as an add-on therapy within the next week, citing both meta-analyses, but I need to finish adding content in 2 other articles before I get around to summarizing that. Seppi333 (Insert 2¢) 18:50, 29 July 2018 (UTC)

References

list of adverse effects in separate article

I'm curious why the list of adverse effects of bupropion is in a separate article. I suggest that this separate article be merged into the main bupropion article. I would simply make this change, but this is a featured article, so thought I'd ask here on the talk page first.Sbelknap (talk) 04:37, 14 March 2019 (UTC)

I don't know how to make changes, but bupropion is NOT an SSRI. According to this article's own source, it is an NDRI.

Correct, though I don't see where the article makes that mistake (quote it for us?). Also, welcome to Wikipedia! Here's a tutorial on how to edit (register to keep track of your edits) https://en.wikipedia.org/wiki/Wikipedia:Tutorial

Any reason why the Cl group in the skeletal/ball-and-stick model is in the 5 position instead of the 3 position?

This seems like a significant oversight. The Cl group on the phenyl ring is clearly stated as being in the 3 position (3-Chloro-N-tert-butyl-β-keto-α-methylphenethylamine) however in both images representing the chemical structure of bupropion, the Cl group is in the 5 position. Is this intentional? I feel as though this could lead to some confusion. Any input? — Preceding unsigned comment added by TropickTX (talk • contribs) 17:24, 30 August 2020 (UTC)

The two conformers you mention should be able to interconvert by rotation about the benzene-carbonyl C-C single bond, providing the barrier to rotation is not too high. I looked at a few crystal structures of bupropion salts and found both conformers (e.g. KUMCAX01 and KUMCAX03), as discussed here.

Ben (talk) 23:17, 5 March 2021 (UTC)

The use of Bupropion in Methamphetamine dependence and or recovery

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916165/ Kindly update the page if you are a moderator with the following research outcome. I oppose the use of the word 'weak' as it is not referenced in any of the articles you have referenced and creates a presumption which is not based on any correlational nor cause and effect methodology. Kindly stick to science, as well expand the matter due to the number of related deaths being claimed in the USA in specific jurisdictions being that this is a point of reference for many, additionally consider updating the https://en.wikipedia.org/wiki/Methamphetamine page concurrently noting it does not reference what is referenced here. Additionally this page should be frequently updated with regular updates on all science and medical journal publications related to the same (both the medications and the article in reference to the substance. — Preceding unsigned comment added by WM324AHI (talk • contribs) 07:41, 24 January 2021 (UTC)

Still an antidepressant?

Package insert doesn't say it's an antidepressant anymore, some insurance won't pay for it now

Weird I wonder what country you live it its still covered in the United States by my insurance — Preceding unsigned comment added by 64.222.180.90 (talk) 19:17, 7 February 2022 (UTC)

Certain generics are considered generic Zyban while others are considered generic wellbutrin. I’ve noticed 150mg SR being zyban and 200mg SR being wellbutrin. It’s likely just manufacturer/insurance oddities. 73.194.66.37 (talk) 00:37, 17 April 2023 (UTC)

Insurance still covers in the US. But they might not cover if you're already taking a similar drug ? Danski14^(talk) 12:12, 26 March 2023 (UTC)

Higher risk of seizures?

Is true that bupropion causes a higher risk of seizures compared to other antidepressants? A reference would be good if that is the case: I see some sources saying that is a myth. 95.127.161.43 (talk) 06:44, 21 December 2021 (UTC)

If suddenly stopped there is a risk of seizures 50.110.102.54 (talk) 02:37, 25 July 2023 (UTC)

TAAR-activity

Are bupropion and methylphenidate TAAR-active? Requesting binding profile. --0dorkmann (talk) 08:15, 11 February 2023 (UTC)

Confused about half life figure

If the half life is 10-19 hours, which several studies attest to, then why in the figure in the "History" section does it look like the half-life is only ~4-5 hours for the immediate/instant release formulation? Is it two-compartment kinetics? What is more clinically meaningful, the blood level, or the level in tissue? I'm confused... By the way, I have taken immediate release, and the chief effects seem to diminish after a few hours.. Danski14^(talk) 12:12, 26 March 2023 (UTC)