Whole-Body Hyperthermia Can Improve MDD Outcomes

A new 6-week, double-blind study has shown that whole-body hyperthermia (WBH) has specific antidepressant effects when compared with a sham condition for treatment of major depressive disorder (MDD).

According to lead author Charles L Raison, MD (pictured), professor, Department of Psychiatry, University of Wisconsin, Madison, the study compared temperature ranges from preliminary studies involving thermoafferent pathways, which resulted in antidepressant actions with lower temperature ranges not expected to activate these pathways as a control condition. The goal was to evaluate whether previous conclusions were related to the temperature range in question, or if they could be achieved with other levels.

"We found that when compared to people that received the sham treatment, people that received the real hyperthermia had a huge antidepressant response," Raison told MD Magazine. "The sham treatment didn’t make people feel much better, which is no real surprise because it didn’t do anything biologically, but the average decrease in reduction of depressive scores in the active hyperthermia group was about 45%. Now for 1 treatment that’s probably a little less than you would see for 6 weeks of antidepressant, but it’s still pretty striking."

Participants ranged from 18—65 years old, with a mean age of 36.7 years in the WBH and 41.47 years in the sham group. Eligible participants were medically healthy, had MDD for at least 4 weeks prior to signing consent and scored a 16 or greater on the 17-item Hamilton Depression Rating Scale (HDRS). Of the 34 randomized participants, 11 were enrolled with a screening score of 18 or greater and 23 were enrolled with a screening score of 16 or greater.

The study’s primary outcome measure was reduction in depression severity across the 6-week study period as assessed by the 17-item HDRS at 1, 2, 4 and 6 weeks following exposure to either treatment.

Secondary outcome measures included Inventory of Depression Symptomatology — Self-report (IDS-SR) scores at posttreatment days 1, 2 and 3, and weeks 1, 2, 4 and 6; Sheehan Disability Scale and Quality of Life Enjoyment Satisfaction Scale — short-form scores at posttreatment weeks 1, 2, 4 and 6; core body temperature monitoring; skin conductance level; heart rate variability; Electronically Activated Recorder (EAR); sleep assessment; and plasma concentrations of biological predictors of response and mechanism of action for WBH.

Participants were randomized in blocks of 6 to a single treatment of WBH or sham based. Immediately following the intervention 10 participants, 71.4%, randomized to the sham treatment, believed they received WBH versus 15 participants, 93.8%, randomized to WBH.

A single session of active WBH versus a sham condition matched for length of WBH and mimicked all aspects of WBH expect intense heat. Subjects experiencing WBH were induced to levels of heat that increases core body temperature to 37.5—38.5°C using the Whole Body Hyperthermia system, while subjects randomized to the sham treatment experienced low intensity whole-body infrared heating that causes only a minor increase in body temperature.

The active WBH group showed significantly reduced Hamilton Depression Rating Scale scores across the post intervention study period versus the sham. The outcomes remained significant after evaluating potential moderating effects of between-group differences in baseline expectancy scores.

"There does seem to be evidence that a single treatment did have a prolonged effect, and that’s interesting because it suggests in future studies if it turns out to be true, and many people come in depressed and they receive a treatment and feel better for 3, 4 or 5 weeks, this could become a real treatment," Raison noted.

Adverse effects in both groups were generally mild.

WBH holds promise as a safe, rapid-acting antidepressant modality with a prolonged therapeutic benefit. Future studies will be conducted to identify both the optimal temperature, number and timing of treatments likely to produce the largest and longest-lasting clinical response amongst patients.

MDD is predicted to be the second leading cause of disability worldwide by year 2020, and the economic burden of depression continues to rise from $83.1 billion in 2000. Much is burdened from the high rate of sub-optimal treatment outcomes, as about 50% of MDD patients recover in less than 12 weeks with adequate treatment.

"[Major depression] It’s not that easy to treat, only about 30% of depressed people in the US will have an adequate response," Raison said.

Current treatments include significant central nervous (CNS) side effects, highlighting the need for more effective treatments with fewer side effects.

The study, “Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder,” can be found in The JAMA Network.