Janssen · JAMA psychiatry 2016 · double-blind randomized sham-controlled trial · n=34

Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial.

Cited 153 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 27172277 · doi:10.1001/jamapsychiatry.2016.1031 · record verified 2026-08-30

What was done

In a 6-week, double-blind, randomized trial, 34 medically healthy, unmedicated adults (aged 18–65 years) with major depressive disorder and a baseline 17-item Hamilton Depression Rating Scale (HDRS) score of 16 or greater were randomized to a single session of active whole-body hyperthermia (WBH) or a matched sham condition. Outcome assessments were conducted by blinded staff over 6 weeks, with 29 participants included in a modified intent-to-treat analysis measuring between-group differences in HDRS scores.

What was found

Active WBH produced statistically significant reductions in HDRS scores compared with sham across the 6-week study: week 1 difference of -6.53 (95% CI, -9.90 to -3.16; P < .001), week 2 difference of -6.35 (95% CI, -9.95 to -2.74; P = .001), week 4 difference of -4.50 (95% CI, -8.17 to -0.84; P = .02), and week 6 difference of -4.27 (95% CI, -7.94 to -0.61; P = .02). Immediately following treatment, 93.8% of the WBH group and 71.4% of the sham group believed they had received active WBH. Adverse events in both arms were generally mild.

Why it matters

This study provides sham-controlled evidence that a single acute session of whole-body hyperthermia can induce rapid and sustained antidepressant effects lasting up to 6 weeks.

Limits

The sample size was very small (29 analyzed out of 34 randomized from 338 screened). The population was limited to medically healthy, unmedicated patients. Blinding may have been imperfect given that 93.8% of the active group correctly identified their assignment compared to 71.4% in the sham group.

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