title: Embryotoxicity of mirtazapine: a study using Chick Embryotoxicity Screening Test.
abstract: OBJECTIVE
  Mirtazapine is a new antidepressant used in last years, however experience with it during pregnancy is unsatisfactory on the present. Its wide therapeutic range and only little proved side effects may be an advantage for treatment during pregnancy. Aim of our study was to contribute to the knowledge on possible risks.
  
  
  METHODS
  For embryotoxicity testing we used an alternative method - CHEST, that used chicken embryos as experimental model. Fertilized eggs of outbred Grey Leghorn stock (AVČR farm Koleč) were treated on embryonic day (ED) 4 by Mirtazapine, incubated till 9ED, when they were weighed and examined. Summing the proportions of dead and malformed embryos, the beginning of the embryotoxicity dose range was estimated.
  
  
  RESULTS
  Mirtazapine solved in 15% DMSO in water revealed low embryotoxicity corresponding data from preclinical studies. If 100% DMSO was used as a solvent, the dose 0.05 μg/3 μL resulted in 57% mortality (LD50). Typical malformations were microphtalmia and malformation (shortening) of limbs on left side, which is a place of contact the embryonic body with maximal Mirtazapine concentration. Approximation of doses in chick embryos to mammals is complicated by low solubility of mirtazapine.
  
  
  CONCLUSIONS
  If the embryotoxic dose was close to LD50, risk at therapeutical doses will be probably low. Mirtazapine according to results of testing and cases published in literature is relatively safe for pregnant women, only higher rate of abortions was demonstrated, however more information is needed to exclude all potential risks.
authors.affiliation: 3rd Faculty of Medicine, Department of Histology and Embryology, Charles University, Prague, Czech Republic. eva.manak@post.cz
authors.forename: Eva
authors.initials: E
authors.lastname: Manakova
authors.forename: Lucie
authors.initials: L
authors.lastname: Hubickova
authors.forename: Jana
authors.initials: J
authors.lastname: Kostalova
authors.forename: Zdena
authors.initials: Z
authors.lastname: Zemanova
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000494:pharmacology*; D002642:Chick Embryo / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D006801:Humans; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078785:Mirtazapine; D023421:Models, Animal; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000523:psychology; D012307:Risk Factors; D013723:Teratogens / Q000494:pharmacology*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D013723:Teratogens; D008803:Mianserin; D000078785:Mirtazapine