Whole-body hyperthermia for the treatment of major depressive disorder: A randomized clinical trial

Clemens W. Janssen, Christopher A. Lowry, Matthias R Mehl, John JB Allen, Kimberly L Kelly, Danielle E. Gartner, Angelica Medrano, Tommy K. Begay, Kelly Rentscher, Joshua J. White, Andrew Fridman, Levi J. Roberts, Megan L. Robbins, Kay U. Hanusch, Steven P. Cole, Charles L Raison

Research output: Contribution to journalArticle

42 Citations (Scopus)

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, -9.95to-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.

Original languageEnglish (US)
Pages (from-to)789-795
Number of pages7
JournalJAMA Psychiatry
Volume73
Issue number8
DOIs
StatePublished - Aug 1 2016

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Major Depressive Disorder
Fever
Randomized Controlled Trials
Antidepressive Agents
Therapeutics
Depression
Placebos
Random Allocation
Double-Blind Method
Hot Temperature

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Whole-body hyperthermia for the treatment of major depressive disorder : A randomized clinical trial. / Janssen, Clemens W.; Lowry, Christopher A.; Mehl, Matthias R; Allen, John JB; Kelly, Kimberly L; Gartner, Danielle E.; Medrano, Angelica; Begay, Tommy K.; Rentscher, Kelly; White, Joshua J.; Fridman, Andrew; Roberts, Levi J.; Robbins, Megan L.; Hanusch, Kay U.; Cole, Steven P.; Raison, Charles L.

In: JAMA Psychiatry, Vol. 73, No. 8, 01.08.2016, p. 789-795.

Research output: Contribution to journalArticle

Janssen, CW, Lowry, CA, Mehl, MR, Allen, JJB, Kelly, KL, Gartner, DE, Medrano, A, Begay, TK, Rentscher, K, White, JJ, Fridman, A, Roberts, LJ, Robbins, ML, Hanusch, KU, Cole, SP & Raison, CL 2016, 'Whole-body hyperthermia for the treatment of major depressive disorder: A randomized clinical trial', JAMA Psychiatry, vol. 73, no. 8, pp. 789-795. https://doi.org/10.1001/jamapsychiatry.2016.1031
Janssen, Clemens W. ; Lowry, Christopher A. ; Mehl, Matthias R ; Allen, John JB ; Kelly, Kimberly L ; Gartner, Danielle E. ; Medrano, Angelica ; Begay, Tommy K. ; Rentscher, Kelly ; White, Joshua J. ; Fridman, Andrew ; Roberts, Levi J. ; Robbins, Megan L. ; Hanusch, Kay U. ; Cole, Steven P. ; Raison, Charles L. / Whole-body hyperthermia for the treatment of major depressive disorder : A randomized clinical trial. In: JAMA Psychiatry. 2016 ; Vol. 73, No. 8. pp. 789-795.
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T1 - Whole-body hyperthermia for the treatment of major depressive disorder

T2 - A randomized clinical trial

AU - Janssen, Clemens W.

AU - Lowry, Christopher A.

AU - Mehl, Matthias R

AU - Allen, John JB

AU - Kelly, Kimberly L

AU - Gartner, Danielle E.

AU - Medrano, Angelica

AU - Begay, Tommy K.

AU - Rentscher, Kelly

AU - White, Joshua J.

AU - Fridman, Andrew

AU - Roberts, Levi J.

AU - Robbins, Megan L.

AU - Hanusch, Kay U.

AU - Cole, Steven P.

AU - Raison, Charles L

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N2 - 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, -9.95to-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.

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