Normobaric oxygen treatment for mild-to-moderate depression: a randomized, double-blind, proof-of-concept trial

Yehudit Bloch, R H Belmaker, Pesach Shvartzman, Pnina Romem, Arkady Bolotin, Yuly Bersudsky, Abed N Azab, Yehudit Bloch, R H Belmaker, Pesach Shvartzman, Pnina Romem, Arkady Bolotin, Yuly Bersudsky, Abed N Azab

Abstract

Oxygen enriched air may increase oxygen pressure in brain tissue and have biochemical effects even in subjects without lung disease. Consistently, several studies demonstrated that normobaric oxygen treatment has clinical benefits in some neurological conditions. This study examined the efficacy of normobaric oxygen treatment in subjects with depression. In a randomized, double-blind trial, 55 participants aged 18-65 years with mild to moderate depression (had a Hamilton Rating Scale for Depression [HRSD] score of ≥ 8) were recruited to the study from the Southern district in Israel. Participants underwent a psychiatric inclusion assessment at baseline and then were randomly assigned to either normobaric oxygen treatment of 35% fraction of inspired oxygen or 21% fraction of inspired oxygen (room air) through a nasal tube, for 4 weeks, during the night. Evaluations were performed at baseline, 2 and 4 weeks after commencement of study interventions, using the following tools: HRSD; Clinical Global Impression (CGI) questionnaire; World Health Organization-5 questionnaire for the estimation of Quality of Life (WHO-5-QOL); Sense of Coherence (SOC) 13-item questionnaire; and, Sheehan Disability Scale (SDS). A multivariate regression analysis showed that the mean ± standard deviation [SD] changes in the HRSD scores from baseline to week four were - 4.2 ± 0.3 points in the oxygen-treated group and - 0.7 ± 0.6 in the control group, for a between-group difference of 3.5 points (95% confidence interval [CI] - 5.95 to - 1.0; P = 0.007). Similarly, at week four there was a between-group difference of 0.71 points in the CGI score (95% CI - 1.00 to - 0.29; P = 0.001). On the other hand, the analysis revealed that there were no significant differences in WHO-5-QOL, SOC-13 or SDS scores between the groups. This study showed a significant beneficial effect of oxygen treatment on some symptoms of depression.Trial registration: NCT02149563 (29/05/2014).

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s).

Figures

Figure 1
Figure 1
Screening and enrollment to the study. BMI denotes body mass index.
Figure 2
Figure 2
Effect of 35% oxygen treatment on total HRSD score. Results are presented as mean ± SEM. *Multivariate regression analysis: The mean ± SD changes in the scores from baseline to week four were − 4.2 ± 0.3 points in the oxygen-treated group and − 0.7 ± 0.6 in the control group, for a between-group difference of 3.5 points (95% confidence interval [CI] − 5.95 to − 1.0; P = 0.007).
Figure 3
Figure 3
Effect of 35% oxygen treatment on CGI improvement score at 4 weeks. The data are presented as the change from baseline to week four. There were significantly more improved patients in the 35% oxygen treatment group as opposed to the control group, as measured by CGI improvement (Chi-square 11.5, df = 3, P 

Figure 4

Effect of 35% oxygen treatment…

Figure 4

Effect of 35% oxygen treatment on WHO-5QOL score. Results are presented as mean…

Figure 4
Effect of 35% oxygen treatment on WHO-5QOL score. Results are presented as mean ± SEM. Multivariate regression analysis: The mean ± SD changes in the scores from baseline to week four were 4.5 ± 0.5 points in the oxygen-treated group and 2.6 ± 1.44 in the control group, for a between-group difference of 1.9 points (95% CI − 1.08 to 1.86; P = 0.597).

Figure 5

Effect of 35% oxygen treatment…

Figure 5

Effect of 35% oxygen treatment on SOC-13 score. Results are presented as mean…

Figure 5
Effect of 35% oxygen treatment on SOC-13 score. Results are presented as mean ± SEM. Multivariate regression analysis: The mean ± SD changes in the scores from baseline to week four were 7.2 ± 3.7 points in the oxygen-treated group and 6.2 ± 2.9 in the control group, for a between-group difference of 0.97 points (95% CI − 3.18 to 9.99; P = 0.303).

Figure 6

Effect of 35% oxygen treatment…

Figure 6

Effect of 35% oxygen treatment on SDS score. Results are presented as mean…

Figure 6
Effect of 35% oxygen treatment on SDS score. Results are presented as mean ± SEM. Multivariate regression analysis: The mean ± SD changes in the scores from baseline to week four were − 5.7 ± 0.6 points in the oxygen-treated group and 1.6 ± 2.2 in the control group, for a between-group difference of 4.1 points (95% CI − 9.84 to 0.22; P = 0.06).
Figure 4
Figure 4
Effect of 35% oxygen treatment on WHO-5QOL score. Results are presented as mean ± SEM. Multivariate regression analysis: The mean ± SD changes in the scores from baseline to week four were 4.5 ± 0.5 points in the oxygen-treated group and 2.6 ± 1.44 in the control group, for a between-group difference of 1.9 points (95% CI − 1.08 to 1.86; P = 0.597).
Figure 5
Figure 5
Effect of 35% oxygen treatment on SOC-13 score. Results are presented as mean ± SEM. Multivariate regression analysis: The mean ± SD changes in the scores from baseline to week four were 7.2 ± 3.7 points in the oxygen-treated group and 6.2 ± 2.9 in the control group, for a between-group difference of 0.97 points (95% CI − 3.18 to 9.99; P = 0.303).
Figure 6
Figure 6
Effect of 35% oxygen treatment on SDS score. Results are presented as mean ± SEM. Multivariate regression analysis: The mean ± SD changes in the scores from baseline to week four were − 5.7 ± 0.6 points in the oxygen-treated group and 1.6 ± 2.2 in the control group, for a between-group difference of 4.1 points (95% CI − 9.84 to 0.22; P = 0.06).

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