The effects of the GABA agonist, baclofen, on sleep and breathing

Abstract

We therefore conducted a double-blind, placebo-controlled, cross-over study of baclofen 25 mg, administered before sleep in 10 snorers with mild sleep-disordered breathing (respiratory disturbance index <30 events per sleep hour). Each subject underwent two standard polysomnographic assessments, one week apart.Total sleep time was significantly prolonged by baclofen (placebo 356±9.9 SEM min; baclofen 386±9.9 min). Both nonrapid eye movement(REM) and REM sleep duration were increased (nonREM: placebo 295±6.8 min; baclofen 311±8.9 min; REM: placebo 61±7.5 min; baclofen 76±9.0 min). Time spent awake after sleep onset was reduced after baclofen (placebo 71±10.3 min; baclofen 51±9.7 min). There was a slight reduction in mean overnight oxygen saturation (placebo 95.2±0.5%; baclofen 94.4±0.7%). The frequency of apnoeas plus hypopnoeas (respiratory disturbance index (RDI)) did not change significantly (placebo 9±1.8 events·h· -1 ; baclofen 13±3.4 events·h· -1 ).We conclude that a single, therapeutic dose of baclofen alters sleep architecture and produces a small reduction in mean sleep oxygen saturation, but does not significantly increase sleep-disordered breathing. Eur Respir J., 1995, 8, 230-234 Baclofen is a centrally-acting gamma aminobutyric acid (GABA)-B agonist with muscle relaxant and antispasmodic properties. It is widely used in the treatment of painful spasms in patients with spinal cord lesions, multiple sclerosis and other neurological disorders [1]. It has also been used experimentally to treat periodic limb movements during sleep [2]. GABA is a neurotransmitter with mainly inhibitory effects in the central nervous system and appears to decrease central ventilatory drive. It has been shown to decrease ventilation and ventilatory responsiveness to hypercapnia in experimental animals [3][4][5], and is a putative mediator of hypoxic ventilatory depression [6].In a preliminary study, we found a high prevalence of significant nocturnal hypoxia in quadriplegic patients [7]. Subsequent polysomnographic studies of 40 quadriplegics from the same population (unpublished data) have shown a high prevalence of obstructive sleep apnoea (OSA); which concurs with the results of preliminary studies reported by other groups [8][9][10]. We conducted a survey of quadriplegic patients in South Australia, and found that 75% were treated with baclofen at an average evening dose of 30 mg (range 10-50 mg); whereas, other anti-spasmodic agents were used less frequently (diazepam, 5-10 mg nocte in 58%, and dantrolene in 28%). It seemed important, therefore, to objectively assess the effects of baclofen on breathing during sleep.We hypothesized that the adverse effects of baclofen on respiratory control would be most evident during sleep, especially in patients with a pre-existing tendency to sleep-disordered breathing. Because of its muscle relaxant properties, baclofen could increase the tendency to upper airway collapse during sleep and increase obstructive apnoeas (e.g. in snorers); whilst its depressant effect on respiratory dr...

Obstructive sleep apneas in relation to severity of cervical spinal cord injury

“…It has been shown that a single dose of 25 mg baclofen alters the sleep architecture and produces a small reduction in mean sleep oxygen saturation although it does not signi®cantly increase sleep-disordered breathing. 33 Thus, baclofen might be a risk factor for OSA but our data indicates that moderate doses are not a major risk factor.…”

“…However, the majority 22,33 of the tetraplegic subjects in the present study had difficulties in changing sleeping position during the night and thus spent all night in the supine position. Previous studies of non-injured subjects indicate that the supine position increases the risk for OSA 31 while the lateral position reduces the risk.…”

Selective loss of GABA B receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture

“…GABA A receptor activation is well known to induce sleep-promoting responses (26). Administration of the GABA B agonist baclofen (25 mg) before sleep in a clinical study also significantly prolonged total sleep time and reduced the time spent awake after sleep onset (27). On the other hand, the GABA B antagonist CGP35348 increased the duration of both non-REM and REM sleep in aged rats compared to those in saline-injected controls when injected during the night (28) and decreased non-REM sleep while increasing the duration of waking and REM sleep when injected during the day (29).…”

Sleep disturbances in the spinal cord injured: an epidemiological questionnaire investigation, including a normal population

“…Spasmolytic medication in itself may compromise the sleep. 55 Another major issue disturbing sleep among SCI individuals was di culty with voiding. For those with suprasacral lesions using re¯ex-voiding by tapping, bladder distension with autonomic dysre¯exia may be one reason for waking during the night.…”