Int Immunopharmacol. 2006 Jun;6(6):903-7. Epub 2006 Jan 25. Links
A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice.Brustolim D, Ribeiro-dos-Santos R, Kast RE, Altschuler EL, Soares MB.
Centro de Pesquisas Gonçalo Moniz, FIOCRUZ. Rua Waldemar Falcão, 121- Candeal, Salvador, BA, Brazil, 40296-750.

In a wide range of human diseases of inflammatory nature like Crohn's disease, pathology is mediated in part by pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF) or interferon-gamma. We show here that a commonly used generic antidepressant bupropion, in wide use worldwide to treat depression in humans for a decade now, profoundly lowers levels of TNF, interferon-gamma, and interleukin-1 beta in vivo, in a mouse lipopolysaccharide (LPS) induced inflammation model. Mice challenged with an otherwise lethal dose of LPS were protected by bupropion and levels of the anti-inflammatory cytokine interleukin-10 were increased. Previous data in rodents and humans indicate antidepressant effects of bupropion are mediated by its weak reuptake inhibition of norepinephrine and dopamine. Concordant with this, TNF suppression by bupropion in our mouse LPS model was largely abrogated by beta-adrenergic or dopamine D1 receptor antagonists but not by a D2 antagonist. TNF synthesis is controlled by an inverse relationship with intracellular cyclic adenosine monophosphate (cAMP) and stimulation of either beta-adrenoreceptors or D1 dopaminergic receptors result in increased cAMP but stimulation of D2 receptors lowers cAMP. We conclude that bupropion may suppress TNF synthesis by mediating increased signaling at beta-adrenoreceptors and D1 receptors, resulting in increased cAMP that inhibits TNF synthesis. Bupropion is well tolerated also in non-psychiatric populations and has less risk with long term use than current anti-inflammatory, immunosuppressive or TNF suppressive treatments such as prednisone, azathioprine, infliximab, or methotrexate. New anti-inflammatory treatments are needed. We believe a new chapter in antiinflammatory, TNF lowering treatment of disease has been opened. Bupropion's use for this in humans should be explored.


Leuk Res. 2005 Dec;29(12):1459-63. Epub 2005 Jun 17. Links
Evidence of a mechanism by which etanercept increased TNF-alpha in multiple myeloma: new insights into the biology of TNF-alpha giving new treatment opportunities--the role of bupropion.Kast RE.
University of Vermont, School of Medicine, Department of Psychiatry, Burlington, VT 05401, USA. kast887@hotmail.com

Etanercept is a commercially available pharmaceutical protein approved for treatment of rheumatoid arthritis, RA. Given subcutaneously, etanercept binds and inactivates soluble tumor necrosis factor-alpha, TNF. Etanercept has a good safety record and is of benefit in lowering pain, inflammation, and joint destruction in RA. RA is mediated by many factors, TNF among them. Malignant myeloma, MM, is a malignant clonal expansion of a post-germinal center B lymphocyte. Since TNF is a necessary growth factor for expansion and maintenance of MM cells, and etanercept binds soluble TNF and is of clinical benefit in RA, etanercept was tried experimentally in MM. Contrary to expectations, etanercept resulted in increased levels of TNF and possibly shortened survival. This paper presents an hypothesis of how this happened. There are two cognate receptors for TNF, termed R1 and R2 and two forms of TNF, soluble and transmembrane. Soluble TNF has greater affinity for TNF-R1 than for TNF-R2. Transmembrane TNF has equal affinity for the two receptors. Since TNF-R2 signaling tends to be more anti-apoptotic and activating of nuclear factor kappa B, NFkB, than is TNF-R1, and TNF-R1 tends to be more pro-apoptotic than is TNF-R2, by inactivating soluble TNF while leaving transmembrane TNF signaling relatively unchanged, etanercept changed the balance in TNF signaling from TNF-R1 towards TNF-R2 weighting. Anti-apoptosis and TNF synthesis would have been up-regulated by that shift. Early data indicates that the common generic antidepressant bupropion may ameliorate Crohn's disease course by down regulating TNF synthesis, maybe it will slow the course of MM as well

There are a couple more, mostly by the same author. However, besides its other applications in psychiatric disease, buproprion should have wide ranging effects on all sorts of inflammatory conditions if the above is true. RA and chron's, and ulcerative colitis come to mind as there is high levels of cirulating Tnf-a. CFS has tnf-a implicated in its pathogenesis. However, the first abstract indicates lower tnf-alpha, higher il-10 and increased cAMP which should make it perfect for atopic disease on top of all that, combined with higher levels of norepinephrine due to re-uptake pump blockade you have a potent anti allergy med, anti inflammatory, fatigue reducing med. A general immunostimulating effect should be produced by the above actions as well, as higher cAMP and anti-inflammatory mediators are signs of immunoefficiency

So just looking at it you have most auto-immune conditions (well the major ones), allergy, asthma, mood disorders and general fatigue and malaise attenuated.

any one have any thoughts or comments?

More

http://www.psychosomaticmedicine.org/cgi/c...t/full/65/4/719


"We read with great interest the important and fascinating paper of Modell et al. (1) in which they found bupropion to be clinically significantly effective for a majority of patients with psoriasis and atopic dermatitis. The patients were selected a priori, as well as demonstrated a posteori, not to be depressed. Modell et al. (1) conclude that a psychiatric effect is not the reason for the effectiveness of bupropion, and the mechanism by which bupropion might work in psoriasis and atopic dermatitis is not known."

The ref study

http://www.psychosomaticmedicine.org/cgi/c...pe2=tf_ipsecsha

"Six of the 10 subjects with atopic dermatitis showed a reduction in affected body surface area by the end of 6 weeks of bupropion treatment, with affected area increasing toward the prestudy baseline in all responders following bupropion discontinuation—a highly significant treatment effect "

That is very convenient.

Might as well throw it out there as it supports the topic indirectly

Int J Psychiatry Med. 2007;37(1):23-8.Links
Bupropion in the treatment of outpatients with asthma and major depressive disorder.Brown ES, Vornik LA, Khan DA, Rush AJ.
Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, 75390-8849, USA. Sherwood.Brown@UTSouthwestern.edu

OBJECTIVE: Depressive disorders are common in asthma. Despite the high prevalence, antidepressant therapy in asthma patients with depression remains under-investigated. The objective of this pilot study was to investigate the use of bupropion for depression and anxiety in depressed asthma patients. METHOD: We conducted a 12-week open-label study of bupropion in 18 depressed asthma patients. Participants were assessed with the Hamilton Rating Scale for Depression (HAM-D-17), Hamilton Rating Scale for Anxiety (HAM-A), Inventory of Depressive Symptomatology--Self-Report (IDS-SR), Asthma Control Questionnaire (ACQ) and spirometry at baseline and weeks 1, 2, 4, 8, and 12. RESULTS: Significant baseline to exit improvements were observed on the HAM-D-17 (mean change = 4.72, SD = 7.78, p = 0.02) and the HAM-A (mean change = 2.12, SD = 3.97, p = 0.04). Based on the HAM-D-17 scores, 27.8% of the patients were responders and 16.7% were remitters. Significant correlations were found between changes in ACQ score and HAM-D-17 r = 0.73, p = 0.001), ACQ score and IDS-SR r = 0.58, = 0.012), and FEV1% Predicted and HAM-D-17 r = -0.66, p = 0.006). CONCLUSIONS: Bupropion treatment was associated with significant improvements in depression and anxiety symptoms in asthma patients. Improvements in asthma correlated significantly with improvements in depression

Sweetness. I've been on bupropion for going on 3 months now and love the stuff. I did have to add some blood pressure lowering supplements to my arsenal, though, as it took my bp out of the normal range. I'm back close to normal now, though.

This is a bit off from the topic, but for those of you who have been inspired to use it:

If during your use you suddenly find sleeping difficult i.e. hard time falling asleep, waking up after several hours wide awake ready to go/decreased need for sleep accompanied with feeling pretty damn good and very creative. Stop taking it. This drug can be a good way to see if you're bi-polar. If you do notice this and think this is awesome, stop taking it, mania may occur and isn't so awesome.

That being said I think some find jumping in on it too much (can't recall what problem) but it is often first given at a lower dose for a few days or a week I've seem labels stating 1 a day for a week then 2 a day there after. Hope that helps.

doubtful that because someone has difficulty falling asleep, has increased creativity, and slight mania from it automatically means that they are bi polar

Great post Necrosis. You´re right up there with ATB et al.

Does IBS qualify as an inflammatory illness ?

It was a caveat, but you're right if such did occur you'd have to look at past history to determine if you are or not. I'm unaware of Wellbutrin affecting non bipolar people with hypomaniania or full blown mania. So based on a balance of probabilities...

The worst case scenario I see is someone who is type two (and probably unaware of it) taking this and having the hypomania amplified into full blown mania.

As far as slight mania, it could very, and depends on your definition of slight. In the beginning it might be low like being strung out on coffee all day. At first it maybe controllable but after awhile they'd lose control due to the sleep deprivation and enter full blown mania - panadoras box is now open. In short that's why I placed my warning.

Thanks.

Traditionally IBS is a non inflammatory bowel issue, the lack of inflammation and obvious markers seperates it from IBD, along with other obvious diagnostic criteria. However, some research shows that low grade inflammation may be present.


2002 by Gut

--------------------------------------------------------------------------------

VISCERAL PERCEPTION

A role for inflammation in irritable bowel syndrome?
G Barbara, R De Giorgio, V Stanghellini, C Cremon, R Corinaldesi
Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process. Human and animal studies support the concept that inflammation may perturb gastrointestinal reflexes and activate the visceral sensory system even when the inflammatory response is minimal and confined to the mucosa. Thus abnormal neuroimmune interactions may contribute to the altered gastrointestinal physiology and hypersensitivity that underlies IBS. A brief review of the human and animal studies that have focused on the putative role of intestinal inflammation and infections in the pathogenesis of IBS is given.

http://ibs.about.com/gi/dynamic/offsite.ht...6blobtype%3Dpdf

It is more likely that the gastric motility pathology characterized by IBS is due to enteric nervous system malfunction, hence the reason stress is a huge trigger and often brings on the symptoms, with sympathetic overstimulation leading to visceral hypersensivity in the smalll intestine, namely the Ileum. That is also interesting if it has any immune components since the ileum is most abundent with GALT, peyers patches etc if the syndrome also had immune dysfunction.

IBS seems like such a shit diagnosis to me also, due to the wide variety of symptoms and total lack of etiology and testing other then elimination. Look at the potential causes for example, stress, flora imbalance, post-infectious inflammation, food allergy. The symptoms are also vague and extremely transient in my experience.


if yours is related to post infection inflmmation or allergy, i think you'd find great relief because of the mechanism of action. Sorry for the spelling etc if there are mistakes, im in a rush.

hope this helps.

SSRI'S can trigger the same reaction, perhaps more so.

I dunno... any stimulant could provoke this, and wellbutrin's half-life makes sleep disruption possible for almost anyone imo.

I really don't buy the "euphoric reaction to psychostimulant = bipolar". You give almost anyone enough of substance X and they'll have a euphoric reaction that shares some common ground with the hypomanic state.

Alright, I did I quick search for references.

"Mood stabilizers taken with newer (second generation) antidepressants induce mania less than older antidepressants - tricyclics and MAOI."
http://www.mhsanctuary.com/bipolar/network.htm

From the quick search it appears Wellbutrin is tollerated better than most anitdepressants for bipolar. Lower than normal doses are recomended, as is close monitoring for symptoms.

J Clin Psychiatry. 1992 Dec;53(12):443-6.
Related Articles, Links

Bupropion in the treatment of bipolar disorders: the same old story?

Fogelson DL, Bystritsky A, Pasnau R.

University of California Los Angeles Neuropsychiatric Institute and Hospital.

BACKGROUND: The treatment of bipolar disorders with mood stabilizing agents is complicated by breakthrough episodes of depression. Currently there are no consistently safe and effective medications for these episodes. The authors address the use of bupropion for this purpose. METHOD: Bupropion was added to the treatment regimens of 3 male and 8 female patients who had bipolar disorders as diagnosed by DSM-III-R criteria and were depressed and nonresponsive to current treatment. Ten of the 11 had previously cycled into manic episodes when treated with either a tricyclic antidepressant, fluoxetine, or phenelzine. RESULTS: Seven of the 11 patients had moderate-to-marked improvement after 6 weeks of treatment. A moderate-to-marked improvement continued in 4 of the 11 patients after a mean of 12 months of treatment (range, 0-20 months), justifying the continuation of bupropion. Baseline Global Assessment of Functioning scores, history of previous response to other antidepressants, treatment refractoriness, comorbid diagnoses, bipolar subtype, family history, cycle length, and demographics did not discriminate between bupropion responders and nonresponders. However, 6 of the 11 patients experienced manic or hypomanic episodes that necessitated discontinuation of bupropion. Five of the 6 patients who had manic episodes had been stabilized on lithium and carbamazepine or valproate prior to the addition of bupropion. CONCLUSION: These findings, based on consecutive cases, suggest that bupropion may pose the same risks as other antidepressants in precipitating manic episodes in depressed bipolar patients. The authors conclude that caution should be exercised when using bupropion in the treatment of bipolar disorders.

Necrosis
"When the patient with bipolar disorder becomes depressed, a selective serotonin reuptake inhibitor (SSRI) or bupropion (Wellbutrin) is recommended.26 The use of tricyclic antidepressants should be avoided because of the possibility of inducing rapid cycling of symptoms." http://www.aafp.org/afp/20000915/1343.html

26 - Hartmann PM. Strategies for managing depression complicated by bipolar disorder, suicidal ideation, or psychotic features. J Am Board Fam Pract 1996;9:261-9.


That being said there is plenty of info on this out there, and the info you'll find can be contradictory probably largely due to the nature of the bipolar disorder. For instance, if I recall correctly type 2's are more prone to rapid cycling and increased hypomania when administered antidepressants than type ones. I've spoken with a physiologist before on this matter and she strongly implied that if you enter into hypomania/mania while on an antidepressants there is a good chance your bipolar.

Graatch you're also right, any stimulant could provoke this. That being said the bipolars I've met can drink plenty of coffee no problem, but an antidepressant screws them right up. I've taken wellbutrin before bed and had no problems, I've heard pharmacists and psychiatrists recommend it for morning use for this reason, but I've also heard before bed is fine if your sleep isn't disturbed.

You don't have to buy it, but simply take my advice, if you experience euphoria please be careful if it is present with a sleep disturbance be even more concerned, if this sleep disturbance is even worst than normal disturbances and they don't appear to be getting better please consider stopping. Hypomania is pretty much euphoria, the problem is the length of the reaction and what it can lead to. FYI 50 - 100 mg is was one of the doses recommended for use with bipolar disorder.

I think ssris will have the lowest switch rate



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