title: Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Limitations of current antidepressants highlight the need to identify novel treatments for major depressive disorder. A prior open trial found that a single session of whole-body hyperthermia (WBH) reduced depressive symptoms; however, the lack of a placebo control raises the possibility that the observed antidepressant effects resulted not from hyperthermia per se, but from nonspecific aspects of the intervention.
  
  
  OBJECTIVE
  To test whether WBH has specific antidepressant effects when compared with a sham condition and to evaluate the persistence of the antidepressant effects of a single treatment.
  
  
  METHODS
  A 6-week, randomized, double-blind study conducted between February 2013 and May 2015 at a university-based medical center comparing WBH with a sham condition. All research staff conducting screening and outcome procedures were blinded to randomization status. Of 338 individuals screened, 34 were randomized, 30 received a study intervention, and 29 provided at least 1 postintervention assessment and were included in a modified intent-to-treat efficacy analysis. Participants were medically healthy, aged 18 to 65 years, met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score of 16 or greater.
  
  
  METHODS
  A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat.
  
  
  METHODS
  Between-group differences in postintervention Hamilton Depression Rating Scale scores.
  
  
  RESULTS
  The mean (SD) age was 36.7 (15.2) years in the WBH group and 41.47 (12.54) years in the sham group. Immediately following the intervention, 10 participants (71.4%) randomized to sham treatment believed they had received WBH compared with 15 (93.8%) randomized to WBH. When compared with the sham group, the active WBH group showed significantly reduced Hamilton Depression Rating Scale scores across the 6-week postintervention study period (WBH vs sham; week 1: -6.53, 95% CI, -9.90 to -3.16, P < .001; week 2: -6.35, 95% CI, -9.95 to -2.74, P = .001; week 4: -4.50, 95% CI, -8.17 to -0.84, P = .02; and week 6: -4.27, 95% CI, -7.94 to -0.61, P = .02). These outcomes remained significant after evaluating potential moderating effects of between-group differences in baseline expectancy scores. Adverse events in both groups were generally mild.
  
  
  CONCLUSIONS
  Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01625546.
authors.affiliation: Department of Human Development and Family Studies, School of Human Ecology, University of Wisconsin-Madison2Norton School of Family and Consumer Sciences, College of Agriculture, University of Arizona, Tucson.
authors.forename: Clemens W
authors.initials: CW
authors.lastname: Janssen
authors.affiliation: Department of Integrative Physiology, Center for Neuroscience, University of Colorado-Boulder.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
authors.affiliation: Department of Psychology, College of Science, University of Arizona, Tucson.
authors.forename: Matthias R
authors.initials: MR
authors.lastname: Mehl
authors.affiliation: Department of Psychology, College of Science, University of Arizona, Tucson.
authors.forename: John J B
authors.initials: JJ
authors.lastname: Allen
authors.affiliation: Department of Psychiatry, College of Medicine, University of Arizona, Tucson6School of Anthropology, University of Arizona, Tucson.
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Kelly
authors.affiliation: Department of Psychiatry, College of Medicine, University of Arizona, Tucson7Office of the Senior Vice President for Health Sciences, University of Arizona, Tucson.
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Gartner
authors.affiliation: Norton School of Family and Consumer Sciences, College of Agriculture, University of Arizona, Tucson5Department of Psychiatry, College of Medicine, University of Arizona, Tucson.
authors.forename: Angelica
authors.initials: A
authors.lastname: Medrano
authors.affiliation: Department of Human Development and Family Studies, School of Human Ecology, University of Wisconsin-Madison2Norton School of Family and Consumer Sciences, College of Agriculture, University of Arizona, Tucson5Department of Psychiatry, College of Medicine.
authors.forename: Tommy K
authors.initials: TK
authors.lastname: Begay
authors.affiliation: Department of Psychology, College of Science, University of Arizona, Tucson.
authors.forename: Kelly
authors.initials: K
authors.lastname: Rentscher
authors.affiliation: Department of Psychiatry, College of Medicine, University of Arizona, Tucson8Midwestern University, Glendale, Arizona.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: White
authors.affiliation: Department of Psychiatry, College of Medicine, University of Arizona, Tucson.
authors.forename: Andrew
authors.initials: A
authors.lastname: Fridman
authors.affiliation: Department of Psychiatry, College of Medicine, University of Arizona, Tucson.
authors.forename: Levi J
authors.initials: LJ
authors.lastname: Roberts
authors.affiliation: Department of Psychology, University of California, Riverside.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Robbins
authors.affiliation: University of Applied Science Fresenius Idstein Medical School, Idstein, Germany.
authors.forename: Kay-U
authors.initials: KU
authors.lastname: Hanusch
authors.affiliation: Research Design Associates Inc, Yorktown Heights, New York.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Cole
authors.affiliation: Department of Human Development and Family Studies, School of Human Ecology, University of Wisconsin-Madison2Norton School of Family and Consumer Sciences, College of Agriculture, University of Arizona, Tucson5Department of Psychiatry, College of Medicine.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Raison
mesh_terms: D000328:Adult; D000818:Animals; D001130:Arizona; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000523:psychology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D011817:Rabbits; D016896:Treatment Outcome; D055815:Young Adult