ASMs Have Varied Effects on Polysomnography Sleep Parameters

March 11, 2021
Victoria Johnson
Victoria Johnson

Victoria Johnson, Assistant Editor for NeurologyLive, joined the MJH Life Sciences team in October 2020. Follow her on Twitter @VictoriaJNeuro or email her at vjohnson@neurologylive.com

Researchers from Kaohsiung Medical University performed a meta-analysis of 18 RCTs to investigate associations between ASMs and sleep parameters.

Data from a recent study published in Sleep Medicine by Elsevier suggest that antiseizure medications (ASMs) can have a statistically significant effect on sleep parameters as measured by polysomnography (PSG).

Researchers found that, compared to placebo, calcium channel blockers significantly increased slow-wave sleep (SWS; k = 9; Hedges’ g = 0.350 [95% CI, 0.156-0.544]; P <.001) and significantly increased sleep efficiency (k = 7; Hedges’ g = 0.630 [95% CI, 0.361-0.899]; P <.001). GABA enhancers significantly increased SWS (k = 4; Hedges’ g = 0.576 [95% CI, 0.131-1.021]; P = .011) and decreased rapid eye movement (REM) sleep percentage (k = 4; Hedges’ g = −0.539 [95% CI, −0.958 to −0.120]; P = .012).

Senior author Chung-Yao Hsu, MD, PhD, department of neurology, Kaohsiung Medical University, and colleagues wrote that “current guidelines for the prescription of ASMs in patients with epilepsy mainly focus on seizure control but lack consideration of the adverse impact they might have on sleep, which could worsen seizure control. Any worsening in seizure control could, in turn, further disrupt sleep. This study aims to resolve conflicts and uncertainties between studies.”

Hsu and colleagues performed a meta-analysis of 18 randomized clinical trials. They studied associations between sodium channel blockers, calcium channel blockers, GABA enhancers, synaptic vesicle glycoprotein 2A (SV2A) ligand, and broad-spectrum ASMs and SWS, REM sleep, and SE.

Based on your experiences, which kinds of antiseizure medications do you think have the biggest effects on sleep measures?

While both calcium channel blockers and GABA enhancers significantly increased SWS, no statistically significant effects on these parameters were seen with broad-spectrum ASMs, sodium channel blockers, or SV2A ligand. Additionally, significant heterogeneity was determined among GABA enhancers (Q = 9.884; df = 3; I2 = 69.523%; P = .020) and SV2A ligand (Q = 11.291; df = 1; I2 = 91.143%; P <.001) but not in calcium channel blockers, broad-spectrum ASMs, and sodium channel blockers.

The researchers performed a subgroup analysis that revealed gabapentin (k = 5; Hedges’ g = 0.254 [95% CI, 0.089-0.420]; P = .003), tiagabine (k = 4; Hedges’ g = 0.576 [95% CI, 0.131-1.021]; P = .011), and pregabalin (k = 4; Hedges’ g = 0.530 [95% CI, 0.079-0.980]; P = .021) significantly increased the percentage of SWS compared to placebo but not levetiracetam (P = 0.821).

GABA enhancers were the only ASMs that significantly decreased REM sleep percentage and no statistically significant effects on these parameters were evident for broad-spectrum ASMs, calcium channel blockers, sodium channel blockers or SV2A ligand.

Again, significant heterogeneity was seen among calcium channel blockers (Q = 20.610; df = 7; I2 = 66.035%; P = .004), GABA enhancers (Q = 8.829; df = 3; I2 = 66.020%; P = .032), and SV2A ligand (Q = 4.042; df = 1; I2 = 75.262%; P = .044) but not in broad-spectrum ASMs, sodium channel blockers or SV2A ligand.

READ MORE: Sleep Disorders Have Significant Impact on Patients With Epilepsy

Subgroup analysis revealed tiagabine significantly decreased the percentage of REM sleep compared to placebo (k = 4; Hedges’ g = −0.539 [95% CI, −0.958 to −0.120]; P = .012), while gabapentin, pregabalin, and levetiracetam did not.

Only calcium channel blockers significantly increased SE, while broad-spectrum ASMs, GABA enhancers, sodium 2 channel blockers, and SV2A ligand did not. Significant heterogeneity was noted among SV2A ligands (Q = 10.205; df = 1; I2 = 90.201%; P <.001), but not in broad-spectrum ASMs, calcium blockers, GABA enhancers, or sodium channel blockers. Subgroup analysis revealed that only pregabalin significantly increased SE compared to placebo (k = 4; Hedges’ g = 0.589 [95% CI, 0.372-0.805]; P <.001) and gabapentin, levetiracetam, and tiagabine did not.

Hsu and colleagues also analyzed the effects of ASMs according to treatment duration. They found that less than 1 week of gabapentin (k = 2; Hedges’ g = 0.305 [95% CI, 0.096-0.514]; P = .004) and tiagabine (k = 4; Hedges’ g = 0.576 [95% CI, 0.131-1.021]; P = .011) significantly increased percentage of SWS compared to placebo. Over 1 week of gabapentin did not significantly affect SWS.

Less than 1 week of tiagabine significantly decreased REM sleep percentage compared to placebo (k = 4; Hedges’ g = 0.214 [95% CI, -0.958 to -0.120]; P = .012), while both less than and over 1 week of gabapentin and over 1 week of pregabalin or levetiracetam did not. 

Over 1 week of pregabalin significantly increased SE compared to placebo (k = 3; Hedges’ g = 0.525 [95% CI, 0.292-0.757]; P < .001), while over 1 week of gabapentin or levetiracetam and less than 1 week of tiagabine did not. 

“The clarification of the potential effects of ASMs on sleep architecture could help physicians to adjust ASM prescription in order to prevent worsening of sleep disturbance and to enhance epilepsy control,” Hsu and colleagues concluded.

REFERENCE
Yeh WC, Lu SR, Wu MN, et al. The impact of antiseizure medications on polysomnographic parameters: a systematic review and meta-analysis. Sleep Med. Published online March 4, 2021. doi: 10.1016/j.sleep.2021.02.056