title: Smoking cessation with varenicline: a suicidal fatality.
abstract: The most effective smoking cessation programs involve a combination of pharmacotherapy and behavioral and/or cognitive counseling to improve abstinence rates. Varenicline (Champix in France and the U.K.), the most recently approved agent for tobacco cessation, is the first drug in a new class (alpha4beta2 partial agonist) that binds to the nicotinic receptors to release dopamine and alleviate withdrawal symptoms. As the literature reports psychiatric disorders being linked to varenicline as an issue, we describe the case of a man who committed suicide while receiving therapy with this drug. The deceased (a 39-year-old man) was found dead at his home address with slash wounds to his wrist. The deceased had been prescribed varenicline for several months at a dose of 1 tablet (1 mg) twice daily. The lab received a blood specimen to perform a screening for unknown drugs, including varenicline. Because of its selectivity and sensitivity, liquid chromatography coupled to tandem mass spectrometry was chosen as the best approach to develop a procedure for varenicline. One milliliter of blood was extracted with 5 mL of a mixture of dichloromethane/isopropanol/n-heptane (25:10:65) at pH 9.5 (phosphate buffer) in the presence of diazepam-d(5), which was used as an internal standard (IS). The resultant blood extract was separated on an XTerra MS C18 column using a gradient of acetonitrile and formic acid in water. Drugs were identified by three or two transitions (m/z 212 > 169, 212 > 183, and 212 > 195 and 290 > 154 and 290 > 198 for varenicline and IS, respectively). The limit of quantitation of varenicline was 1 ng/mL. The concentration of varenicline in the blood was determined to be 10 ng/mL. This concentration could not be compared with therapeutic levels, as there are no therapeutic concentrations reported in the literature. Because of its potential effects on behavior, the influence of the drug on the mental functioning of the user should be considered in cases of suicide.
authors.affiliation: Laboratoire ChemTox, 3 rue Gruninger, 67400 Illkirch, France. pascal.kintz@wanadoo.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Kintz
authors.forename: Julie
authors.initials: J
authors.lastname: Evans
authors.forename: Marion
authors.initials: M
authors.lastname: Villain
authors.forename: Vincent
authors.initials: V
authors.lastname: Cirimele
mesh_terms: D000328:Adult; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D011810:Quinoxalines / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D011978:Receptors, Nicotinic / Q000378:metabolism*; D016540:Smoking Cessation / Q000379:methods; D013405:Suicide / Q000523:psychology; D053719:Tandem Mass Spectrometry; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D000068580:Varenicline