Neurological Institute Outcomes

Rapid Eye Movement Sleep Behavior Disorder (RBD) is a sleep disorder in which individuals act out their dreams resulting in potential injurious behaviors to self or bed partner. RBD may affect as many as 1 in 20 older adults; unfortunately, it remains underdiagnosed. RBD is a precursor to alpha synecleopathy disorders including Parkinson's Disease and Dementia with Lewy Bodies and early detection may provide insight into the mechanism and progression of neurodegeneration. Dream enactment behaviors can vary widely with night-to-night variability, but the majority of movements are muscle twitches in the extremities. Most accredited sleep laboratories will monitor electromyography (EMG) of the anterior tibialis and mentalis muscle which can assess for RBD as well as other movement-related sleep disorders. However, in 2022, the Cleveland Clinic Sleep Disorders Center began routine monitoring of flexor digitorum superficialis EMG on all patients in order to assist with the underdiagnosis of this disorder. It is now easier to better identify RBD and capitalize on this unique window to better understand neurodegeneration.

A definitive diagnosis of RBD requires video polysomnography (PSG) demonstrating a loss of the normal skeletal muscle atonia during REM sleep, i.e. REM sleep without atonia (RSWA). Some antidepressants are associated with an increase in RSWA. The extent to which antidepressants affect RSWA has not been quantified by drug type using American Academy of Sleep Medicine scoring criteria incorporating upper extremity EMG. The objective was to assess the percentage of REM sleep epochs meeting criteria for RSWA in patients on selective serotonin reuptake inhibitors (SSRIs) serotonin and norepinephrine reuptake inhibitors (SNRIs), and/or tricyclic antidepressants (TCAs) compared to non-users incorporating flexor digitorum superficialis EMG.

A cross-sectional analysis of PSGs that included at least 5 minutes of REM sleep from the Cleveland Clinic STARLIT Registry (Sleep Signals, Testing, and Reports Linked to Patient Traits) from September 2018 to October 2023. REM epochs during a respiratory event or within 30 seconds after a respiratory event were excluded to prevent confounding by sleep-disordered breathing. Percent of REM epochs which meet criteria for RSWA and PSGs which meet criteria for RBD (>27% of REM sleep epochs which meet RSWA criteria) were compared between antidepressant users and non-users. Models were adjusted for age, sex, and body mass index.

The sample included 1075 patients, of those, 468 were using anti-depressants. The user group was more likely to be younger (age 51 ± 15.8 vs. 54.0 ± 17.2 years, p=0.003), more obese (BMI 33.4 ±8.4 vs. 32.0 ± 8.7 kg/m², p=0.007), and female (59.0% vs. 39.9%, p<0.001). The user group also had more REM epochs that met RSWA criteria (14.6 ± 18.9, vs. 9.5 ± 16.0 epochs), p<0.001) and more patients with PSGs meeting criteria for RBD (>27% REM epochs meeting RSWA criteria) (18.6% vs. 11.2%, p=0.001). In the user group, 60.7% were on SSRIs, 27% were on SNRIs, 6.6% were on TCAs, 1.7% were on SSRI and SNRI, 2.4% were on SSRI and TCA, and 1.5% were on SNRI and TCA. Patients on SSRIs had 4.1 percentage points more RSWA (coefficient=4.1, 95% CI=1.8-6.4), patients on SNRIs had 5.6 percentage points more RSWA (coefficient=13.6, 95% CI=2.4-8.8), patients on SSRI and SNRI had 13.6 percentage points more RSWA (coefficient=13.6, 95% CI=1.7-25.4), and patients on SNRI and TCA had 18.7 percentage points more RSWA (coefficient=18.7, 95% CI=6.1-31.4).

This study is the first to quantify RSWA including upper extremity EMG patients on different antidepressants. Combination antidepressant therapy, particularly including SNRIs, increases the percentage of epochs meeting RSWA criteria to the greatest extent. These findings have important implications for the laboratory diagnosis of RBD.

While highly reproducible in narcolepsy type 1, multiple sleep latency test (MSLT) results are more variable in other central disorders of hypersomnolence. The use of psychotropic medications is a known contributor to MSLT validity given the high comorbidity of psychiatric illness in patients with central disorders of hypersomnolence. The center leveraged a large MSLT database to study the impact of timing of washout of antidepressant medications with known rapid eye movement (REM)-suppressing effects on MSLT results.

This was a retrospective analysis of MSLTs performed between 2012 and 2023 at Cleveland Clinic. Medication groups studied included selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs). Date of last dose prior to MSLT was collected and categorized as ≤ 14 days or > 14 days prior to MSLT. Multivariable-adjusted regression analyses were conducted to predict the recording of ≥ 2 sleep onset REM periods (SOREMPs) and a mean sleep latency (MSL) <8 minutes as a function of short medication washout period defined as ≤ 14 days prior to MSLT. Models were adjusted for age, sex, and body mass index.

The sample included 180 patients who were 36.3 ± 16.4 years old, 68.9% female, with a body mass index of 27.8 ± 7.2 kg/m². Of these 80 patients, 20% were using SSRIs, 21.3% SNRIs, and/or 7.5% TCAs of whom 78.8% (N=63) had a short washout period. 8.8% (N=7) had ≥2 SOREMPs, and 33.8% (N=27) had an MSL<8 minutes. Those with a short washout period were 52% less likely to have ≥2 SOREMPs (coefficient = -0.57, CI=-0.88--0.25, p<0.001) compared to those without a short washout period. There was no effect on MSL (p=0.07).

Timing of REM suppressing antidepressant medication washout significantly impacts the recordings of SOREMPs but not MSL, with direct implications on the diagnosis of narcolepsy. The findings must be considered in the context of the high prevalence of patients in the sample unable to taper medications due to comorbidities. The findings underscore the importance of appropriately timed REM-suppressant washout prior to MSLT to optimize test validity.

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