The impact of whole-body hyperthermia interventions on mood and depression – are we ready for recommendations for clinical application?

Figures & data

Figure 1. PRISMA study flowchart.

Table 1. Overview of all studies included.

	Year	Journal/book	Design	N all/exp	Control	Include/out
Studies summary information
Lampert [11]	1967	Bruno-Wilkens Verlag Hannover	Qualitative	–	No	Out
Bühring [12]	1984	Hippokrates Verlag Stuttgart	Qualitative	–	No	Out
Koltyn [13]	1992	Int J Hyperthermia	Case report	7/7	No	Out
Schaper [14]	1996	Universitätsbibliothek Freiburg	Cohort pro-post design	20/20	No	Include
Gödl [15]	2000	Universitätsbibliothek Graz	Cohort pre-post design	10/10	No	Include
Hüppe [19]	2009	Act Nerv Super Rediviva	RCT	36/12	Yes	Include
Janssen [20]	2011	NHK	Qualitative	–	No	Out
Hanusch [16]	2013	NHK	Cohort pre-post design (same sample AJP)	12/12	No	Out
Hanusch [17]	2013	NHK	Cohort pre-post design (same sample AJP)	15/12	No	Out
Hanusch [18]	2013	AJP	Cohort pre-post design	17/17	No	Include
Romeyke [21]	2014	Journal of Musculoskeletal Pain	CCT	103/55	Yes	Include
Janssen [22]	2016	JAMA	RCT	35/17	Yes	Include
Naumann [23]	2017	BMC	RCT	36/17	Yes	Include

NHK: Die Naturheilkunde; AJP: American Journal of Psychiatry; BMC: Complementary and Alternative Medicine; RCT: randomized controlled study; CCT: controlled clinical study.

Table 2. Risk of bias analysis for controlled studies.

	Sum Risk of bias (%)	Selection bias Were the study randomized? Was the randomized adequate?	Selection bias Was allocation concealment adequate?	Performance bias Were groups similar at baseline?	Performance bias Were outcome assessors blinded	Performance bias Were care providers blinded?	Performance bias Were patients blinded?	Performance bias Was treatment in all groups the same	Attrition bias Was overall attrition >20%	Attrition bias Was differential attrition >15%	Attrition bias Did the study use ITT analysis correct?	Reporting bias Is selective reporting suspected	Reporting bias Were outcome measures equal, valid and reliable
Counts of the bias components
Schaper [14]	100%	- -	- -	- -	- -	- -	- -	- -	- -	- -	- -	- -	- -
Hüppe [19]	56%	+	+	+ +	–	- -	- -	- -	+ +	+ +	- -	+	- -
Gödl [15]	100%	- -	- -	- -	- -	- -	- -	- -	- -	- -	- -	- -	- -
Romeyke [21]	64%	- -	- -	+ +	- -	- -	- -	–	+ +	+ +	- -	+ +	- -
Hanusch [18]	100%	- -	- -	- -	- -	- -	- -	- -	- -	- -	- -	- -	- -
Janssen [22]	14%	+	+	+ +	+ +	+ +	+ +	+ +	+ +	+ +	+ +	/	+ +
Naumann [23]	25%	+ +	+ +	+ +	- -	- -	- -	+ +	+ +	+ +	+ +	+ +	+

Table 3. Risk of bias analysis for non-controlled studies.

	Sum risk of bias (%)	Selection bias Was a prospective study planning applied?	Selection bias Were inclusion criteria defined beforehand?	Performance bias Was a standardized intervention defined beforehand?	Detection bias Were study end-points defined beforehand?	Reporting bias Was all required information from all patients included or information suppressed?	Reporting bias Patient information was transparently reported and not selectively?	Reporting bias Was a complete report of the intervention provided?	Reporting bias Was a complete report of all results provided?
Counts of the bias components
Schaper [14]	25%	+ +	+ +	+ +	- -	/	+ +	+ +	+ +
Hüppe [19]	13%	+ +	+ +	- -	+ +	+ +	+ +	+ +	+ +
Gödl [15]	50%	+ +	+ +	+ +	+ +	/	- -	- -	- -
Romeyke [21]	17%	+ +	+ +	+	- -	+ +	+ +	+ +	+ +
Hanusch [18]	29%	- -	- -	+ +	+	+ +	+ +	+ +	+ +
Janssen [22]	0%	+ +	+ +	+ +	+ +	+ +	+ +	+ +	+ +
Naumann [23]	0%	+ +	+ +	+ +	+ +	+ +	+ +	+ +	+ +

Table 4. Pre-post treatment effect sizes (Cohen’s d) with 95% confidence intervals, effect sizes >0.80 were considered large, 0.50–0.80 moderate and 0.20–0.50 small.

	Week-1	Week-2	Week-3	Week-4	Week-5	Week-6
Standardized mean change for the intervention group
Schaper [14]	0.61 [−0.03–1.24]	1.26 [0.58–1.94]	1.30 [0.62–1.98]	1.62 [0.84–2.34]	1.69 [0.83–2.34]	1.71 [0.90–2.43]
Gödl [15]		0.38 [−0.80–1.54]	1.20 [−0.09–1.73]	1.70 [0.25–2.16]	1.41 [0.10–1.97]	1.85 [0.33–2.26]
Hüppe [19]	0.47 [−034–1.28]				0.41 [−041–1.22]
Hanusch [18]	1.00 [0.29–1.72]					1.85 [0.80–2.67]
Romeyke [21]		1.28 [0.87–1.69]
Janssen [22]	1.15 [0.41–1.89]	1.38 [0.60–2.15]		1.59 [0.79–2.39]		1.61 [0.82–2.41]
Naumann [23]		0.84 [0.12–1.52]				0.86 [0.13–1.53]

Figure 2. Relationship between risk of bias (%) and effect sizes from all studies; the bubble size = sample size (n) of studies experimental groups.

Figure 3. (A) Relationship between core body temperature during the intervention (y-axis) and effect sizes (x-axis) in °Celsius as grouped by measuring method (orange = rectal temperature, green = sublingual temperature, red = ear temperature). (B) Relationship between the ratio of highest core body temperature and time to reach the temperature (y-axis) and effect size (x-axis), grouped by intervention type (orange = infrared heating with IRATHERM device or Heckel device, green = intervention in a bath tub, red = hot tub). (C) Relationship between study end-point (y-axis) and effect size (x-axis) grouped by intervention frequency (green = single session, red = multiple sessions). (D) Relationship between the different methods of measuring core body temperature (x-axis) and core body temperature (y-axis).

Figure 4. Effect sizes at study end-points (weeks); the bubble size = sample size (n) of studies experimental groups.

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