Clemens W Janssen1, Christopher A Lowry2, Matthias R Mehl3, John J B Allen3, Kimberly L Kelly4, Danielle E Gartner5, Angelica Medrano6, Tommy K Begay7, Kelly Rentscher3, Joshua J White8, Andrew Fridman9, Levi J Roberts9, Megan L Robbins10, Kay-U Hanusch11, Steven P Cole12, Charles L Raison7. 1. 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. 2. Department of Integrative Physiology, Center for Neuroscience, University of Colorado-Boulder. 3. Department of Psychology, College of Science, University of Arizona, Tucson. 4. Department of Psychiatry, College of Medicine, University of Arizona, Tucson6School of Anthropology, University of Arizona, Tucson. 5. Department of Psychiatry, College of Medicine, University of Arizona, Tucson7Office of the Senior Vice President for Health Sciences, University of Arizona, Tucson. 6. Norton School of Family and Consumer Sciences, College of Agriculture, University of Arizona, Tucson5Department of Psychiatry, College of Medicine, University of Arizona, Tucson. 7. 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. 8. Department of Psychiatry, College of Medicine, University of Arizona, Tucson8Midwestern University, Glendale, Arizona. 9. Department of Psychiatry, College of Medicine, University of Arizona, Tucson. 10. Department of Psychology, University of California, Riverside. 11. University of Applied Science Fresenius Idstein Medical School, Idstein, Germany. 12. Research Design Associates Inc, Yorktown Heights, New York.
Abstract
IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01625546.
RCT Entities:
IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01625546.
Authors: H Petra Kok; Erik N K Cressman; Wim Ceelen; Christopher L Brace; Robert Ivkov; Holger Grüll; Gail Ter Haar; Peter Wust; Johannes Crezee Journal: Int J Hyperthermia Date: 2020 Impact factor: 3.914
Authors: Jari Tiihonen; Pirjo Halonen; Laura Tiihonen; Hannu Kautiainen; Markus Storvik; James Callaway Journal: Sci Rep Date: 2017-07-28 Impact factor: 4.379