title: Effects of short-term varenicline administration on cortisol in healthy, non-smoking adults: a randomized, double-blind, study.
abstract: BACKGROUND
  Varenicline is the most effective drug for smoking cessation, but its use decreased because of reports of depressogenic side effects. However, because smoking and smoking cessation on their own are associated with depression, it remains unclear whether reported depressogenic effects are attributable to varenicline, or to smoking, and/or smoking cessation themselves.
  
  
  OBJECTIVE
  Previously, we observed no depressogenic effects of varenicline on a psychological level. In the present study, we aimed at investigating potential depressogenic effects of the partial nicotinergic acetylcholine receptor agonist varenicline on a biological level. A possible pathway would be an effect of varenicline on the hypothalamic-pituitary-adrenal (HPA) axis, considering the relation between the HPA axis and (1) the cholinergic system and (2) depression.
  
  
  METHODS
  In a randomized, double-blind design, we administered varenicline or placebo for 7 days (0.5 mg/day first 3 days, then 1 mg/day) to healthy never-smoking subjects, thereby eliminating bias by (previous) smoking status. We used repeated measures (before and after treatment) of the salivary free cortisol awakening response to measure HPA axis activity and flexibility.
  
  
  RESULTS
  Salivary cortisol data of 34 subjects were included in the analysis. Results showed no effect of varenicline on height (F₁,₃₂ = 0.405; P = 0.529) or shape (F₂,₃₁ = 0.110; P = 0.164) of the cortisol awakening response.
  
  
  CONCLUSIONS
  Results do not suggest depressogenic effects of varenicline on the HPA axis. Although this does not preclude other biological depressogenic effects of varenicline, it seems that concerns about effects of varenicline on the HPA axis should not limit its potential to treat nicotine and related addictions.
authors.affiliation: Department of Psychiatry, Warneford Hospital, Oxford, UK, R.J.Mocking@amc.uva.nl.
authors.forename: Roel J T
authors.initials: RJ
authors.lastname: Mocking
authors.forename: Stephany A
authors.initials: SA
authors.lastname: Wever
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Pflanz
authors.forename: Abbie
authors.initials: A
authors.lastname: Pringle
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Parsons
authors.forename: Sarah F
authors.initials: SF
authors.lastname: McTavish
authors.forename: Phil J
authors.initials: PJ
authors.lastname: Cowen
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Harmer
authors.forename: Aart H
authors.initials: AH
authors.lastname: Schene
mesh_terms: D000293:Adolescent; D000328:Adult; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011810:Quinoxalines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012463:Saliva / Q000378:metabolism; D016540:Smoking Cessation; D000068580:Varenicline; D055815:Young Adult
chemical_list: D001552:Benzazepines; D011810:Quinoxalines; D000068580:Varenicline; D006854:Hydrocortisone
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