Metylfenidat och atomoxetin vid histaminintolerans

Fråga: Stämmer det att metylfenidat och atomoxetin bör undvikas vid histaminintolerans? Har ni någon tillförlitlig lista över histaminfrisättande/DAO-hämmande läkemedel att dela med er av?

Svar: No studies were found that assessed the effect of the stimulant drug methylphenidate or the non-stimulant noradrenaline reuptake inhibitor atomoxetine in histamine intolerance patients (1).

No studies/reports were found that suggested that methylphenidate and atomoxetine should be avoided in histamine intolerance in humans (1).

No list/s of histamine-releasing/diamine oxidase (DAO)-inhibiting drugs to be avoided was/were found with search in Micromedex and Uptodate (2, 3). With search in Pubmed an article (4) was found that listed drugs releasing histamine or inhibiting DAO. However, neither central stimulants, methylphenidate nor atomoxetine are in the list (see attached file). Recently, Tan and colleagues (5) stated that there are as many as 94 known inhibitors of DAO, such as dihydrazine, nafamostat, isoniazid, d-tubocurarine, pancuronium, clavulanic acid, promethazine, verapamil, metoclopramide, numerous antibiotics. However, we were not able to locate the full list of these inhibitors.

Data on methylphenidate and atomoxetine on histamine release, effect on DAO activity, the main enzyme for the catabolism of ingested histamine in the gastrointestinal tract and its deficiency has been linked to allergy-like symptoms, were from animal studies (1).

Methylphenidate treatment does not reduce DAO activity. This is a result of a very recent in vitro study (6) published July 2023, that evaluated the effects of psychostimulant drugs (methylphenidate and lisdexamfetamine) on DAO activity. The authors suggest that these findings could be useful for physicians prescribing these psychostimulant drugs to ADHD patients affected by DAO deficiency.

On the other hand, methylphenidate, and atomoxetine, have been shown to stimulate cortical histamine release and produced robust increases in the extracellular levels of histamine without any affinity for the H3 receptor in animal models (Horner et al., 2007, Liu LL, 2008). The authors suggested that enhanced histamine release may contribute to methylphenidate, and atomoxetine efficacy as ADHD treatment (7, 8).

1. Pubmed
2. MICROMEDEX Healthcare Series, Thomson MICROMEDEX, Greenwood Village, Colorado. http://www.micromedexsolutions.com
3. https://www.uptodate.com
4. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007 May;85(5):1185-96. doi: 10.1093/ajcn/85.5.1185. PMID: 17490952.
5. Tan, Z.; Ou, Y.; Cai, W.; Zheng, Y.; Li, H.; Mao, Y.; Zhou, S.; Tu, J. Advances in the Clinical Application of Histamine and Diamine Oxidase (DAO) Activity: A Review. Catalysts 2023, 13, 48. https://doi.org/10.3390/ catal1301004
6. Tobajas Y, Alemany-Fornés M, Samarra I, Romero-Giménez J, Tintoré M, Del Pino A, Canela N, Del Bas JM, Ortega-Olivé N, de Lecea C, Escoté X. Interaction of Diamine Oxidase with Psychostimulant Drugs for ADHD Management. J Clin Med. 2023 Jul 13;12(14):4666. doi: 10.3390/jcm12144666. PMID: 37510782; PMCID: PMC10380856.
7. Horner WE, Johnson DE, Schmidt AW, Rollema H. Methylphenidate and atomoxetine increase histamine release in rat prefrontal cortex. Eur J Pharmacol. 2007 Mar 8;558(1-3):96-7. doi: 10.1016/j.ejphar.2006.11.048. Epub 2006 Dec 1. PMID: 17198700.
8. Liu LL, Yang J, Lei GF, Wang GJ, Wang YW, Sun RP. Atomoxetine increases histamine release and improves learning deficits in an animal model of attention-deficit hyperactivity disorder: the spontaneously hypertensive rat. Basic Clin Pharmacol Toxicol. 2008 Jun;102(6):527-32. doi: 10.1111/j.1742-7843.2008.00230.x. Epub 2008 Mar 16. PMID: 18346050.