Dear Sir: Some patients with Crohn’s disease (CD) are not controlled by current treatments. Also, multiple toxicity issues are associated with taking medicines such as azathioprine, methotrexate, and steroids over time. 1 Here we point out that the literature strongly supports the notion that monoaminergic and dopaminergic treatments can lower levels of tumor necrosis factor (TNF) alpha via increased intracellular adenosine 3, 5-cyclic monophosphate (cAMP), and describe 2 cases in which bupropion (Welbutrin, Zyban) has produced near complete and long-lasting (2 years) remissions of CD without significant side effects or toxicities. In CD, TNF is increased, and TNF is thought to play a central role in CD pathogenesis. 2 A monoclonal anti-TNF antibody has been found of some efficacy in CD, for example, in closing fistulas. 3 However, the antibody is expensive, it must be given intravenously, and although not common, there is potential for severe side effects. Also, long-term effects of repeated treatments with anti-TNF antibody are unknown. In CD studies even in patients who benefit from a given medicine, frequently, enough CD activity remains to significantly lower quality of life even though the Crohn’s Disease Activity Index (CDAI4) is under the somewhat arbitrary cutoff of 150 used to define remission. Clearly, easing of disease burden is of great value, but remission of all signs and symptoms of disease remains our goal. Agonist binding to the-adrenergic receptor increases intracellular cAMP. 5 cAMP is believed to be a key intracellular regulator of TNF, and increases of cAMP from any origin have been shown to decrease TNF in a variety of in vitro and in vivo situations in animals and humans. 6–8 Phosphodiesterases mediate a step in cAMP catabolism. Phosphodiesterase inhibitors increase cAMP levels and lower TNF levels. The phosphodiesterase inhibitor rolipram has been shown in different experimental models to not only lower TNF levels, but also be effective in mitigating disease severity in several animal models of human inflammatory/autoimmune disease (eg, Sommer et al. 8). Recently, the-adrenergic agonist isoproteronol has been found to lower TNF levels when infused into humans. 9 Similarly, we suggest that cases of CD remission seen after phenelzine treatment of depression10 may be driven by increased cAMP-associated TNF decreases. Consistent with this notion, in a fascinating recent abstract it has been found that the levels of norepinephine were lower in gut mucosa in CD patients than in healthy controls or ulcerative colitis (UC) patients, and dopamine levels were lower in gut mucosa in CD and UC patients than in controls. 11 Also we note that, amazingly, an MAO-I12 has been reported to induce remission in rheumatoid arthritis, and we have suggested that increased monoamine-mediated TNF decrease is the mechanism behind this observation as well. 13

Given the long-term experience with and safety of phenelzine, further study of phenelzine in CD might be considered. However, phenelzine carries some risks: hypertensive crisis associated with dietary restriction breaches can be serious, and fatal hypertensive crises are seen with multiple medicine incompatibilities (eg, meperidine). Other medicines that can increase monoaminergic tone with-