Dronabinol Treatment of Obstructive Sleep Apnea: Effects on Sleep EEG
Author List
Ahana Gupta1, Magdy Younes2, Bethany Gerardy3, Phyllis Zee4, David Carley5, Bharati Prasad6
1. GPPA Medical Scholars Program, University of Illinois at Chicago, 2. Sleep Disorders Centre, University of Manitoba, Winnipeg, Manitoba, Canada, 3. YRT Ltd, Winnipeg, Manitoba, Canada. 4. Department of Neurology, Northwestern University Feinberg School of Medicine, 5. Department of Biobehavioral Nursing Science, University of Illinois at Chicago, 6. Department of Medicine, University of Illinois at Chicago.
Introduction
Recent studies have examined the therapeutic role for Dronabinol (DRO), a
cannabimimetic drug, in obstructive sleep apnea (OSA). However, there are limited data on the effect of DRO on sleep electroencephalography (EEG) in OSA. We examined the effects of six weeks of DRO treatment (2.5 or 10 mg daily) on novel EEG based sleep parameters derived from spectral analysis of polysomnography EEG. Further, we explored the association of DRO related change in EEG to change in the apnea hypopnea index (AHI), and the effects of DRO vs. placebo (PLA) on EEG.
Methods
Fifty-six participants (DRO, N=39 and PLA, N=17), completing a DRO clinical trial were included (NCT01755091). A subset of the sample with complete data were analyzed (DRO, N=33 and PLA, N=16). The EEG spectral analysis parameters included power in EEG bands, average EEG power, spindle characteristics (frequency, power, and density), time in each sleep stage, percent time awake, number of arousals plus awakenings, and odds ratio product (ORP) related parameters. The primary analysis was paired t-tests (before and after DRO). Exploratory analyses included Pearson or Spearman correlations and two-group t-tests (change in EEG in DRO vs. PLA) using STATA 15.
Results
The participants were middle-aged (mean ± standard deviation, 55.2±7.3 years) and mostly men (53/56), with obesity (body mass index=33.8±5.3 kg/m2). OSA was moderate to severe (AHI=25.9±11.6 and time<90% oxygen saturation=18±33.2 minutes). The only difference between DRO and PLA groups was age (DRO=53.7±7.3 vs. PLA=58.7±6.1, p=0.01). The table shows the significant within-group changes in EEG (DRO) and correlations of these parameters with change in AHI (left 4 columns). The between-group comparisons (change in PLA – change in DRO) of the EEG parameters are shown in the right 2 columns.
Conclusion
Short-term DRO treatment of OSA shifts EEG to deeper sleep (defined by ORP), increases sleep drive (ORP9) and stage 2 sleep, and reduces spindles and sleep fragmentation. The reduction in sleep fragmentation is positively associated with a reduction in AHI. DRO increases stage 2 sleep and reduces sleep fragmentation compared to PLA. Future studies should examine the temporal correlation of sleep fragmentation with respiratory events to further define the relative effects of DRO on sleep related breathing and sleep EEG. This will shed light on the mechanisms by which DRO improves sleep and breathing in OSA.
Ahana Gupta1, Magdy Younes2, Bethany Gerardy3, Phyllis Zee4, David Carley5, Bharati Prasad6
1. GPPA Medical Scholars Program, University of Illinois at Chicago, 2. Sleep Disorders Centre, University of Manitoba, Winnipeg, Manitoba, Canada, 3. YRT Ltd, Winnipeg, Manitoba, Canada. 4. Department of Neurology, Northwestern University Feinberg School of Medicine, 5. Department of Biobehavioral Nursing Science, University of Illinois at Chicago, 6. Department of Medicine, University of Illinois at Chicago.
Introduction
Recent studies have examined the therapeutic role for Dronabinol (DRO), a
cannabimimetic drug, in obstructive sleep apnea (OSA). However, there are limited data on the effect of DRO on sleep electroencephalography (EEG) in OSA. We examined the effects of six weeks of DRO treatment (2.5 or 10 mg daily) on novel EEG based sleep parameters derived from spectral analysis of polysomnography EEG. Further, we explored the association of DRO related change in EEG to change in the apnea hypopnea index (AHI), and the effects of DRO vs. placebo (PLA) on EEG.
Methods
Fifty-six participants (DRO, N=39 and PLA, N=17), completing a DRO clinical trial were included (NCT01755091). A subset of the sample with complete data were analyzed (DRO, N=33 and PLA, N=16). The EEG spectral analysis parameters included power in EEG bands, average EEG power, spindle characteristics (frequency, power, and density), time in each sleep stage, percent time awake, number of arousals plus awakenings, and odds ratio product (ORP) related parameters. The primary analysis was paired t-tests (before and after DRO). Exploratory analyses included Pearson or Spearman correlations and two-group t-tests (change in EEG in DRO vs. PLA) using STATA 15.
Results
The participants were middle-aged (mean ± standard deviation, 55.2±7.3 years) and mostly men (53/56), with obesity (body mass index=33.8±5.3 kg/m2). OSA was moderate to severe (AHI=25.9±11.6 and time<90% oxygen saturation=18±33.2 minutes). The only difference between DRO and PLA groups was age (DRO=53.7±7.3 vs. PLA=58.7±6.1, p=0.01). The table shows the significant within-group changes in EEG (DRO) and correlations of these parameters with change in AHI (left 4 columns). The between-group comparisons (change in PLA – change in DRO) of the EEG parameters are shown in the right 2 columns.
Conclusion
Short-term DRO treatment of OSA shifts EEG to deeper sleep (defined by ORP), increases sleep drive (ORP9) and stage 2 sleep, and reduces spindles and sleep fragmentation. The reduction in sleep fragmentation is positively associated with a reduction in AHI. DRO increases stage 2 sleep and reduces sleep fragmentation compared to PLA. Future studies should examine the temporal correlation of sleep fragmentation with respiratory events to further define the relative effects of DRO on sleep related breathing and sleep EEG. This will shed light on the mechanisms by which DRO improves sleep and breathing in OSA.
