Beta-Blockers as a Cause of Violent Rapid Eye Movement Sleep Behavior Disorder: A Poorly Recognized but Common Cause of Violent Parasomnias

Abstract

A 44-year-old man presented with a 3-year history of violent behavior, occurring 2 to 3 times per month within 2 hours of sleep onset. He would shout and swear, punch his wife, and attempt to strangle her, during which he would have repetitive, stereotyped dreams in which he was arguing or fighting. He had no forensic history and was considered a nonviolent person by friends and family. He snored occasionally during sleep and had intermittent choking and gasping arousals but no apnea. He denied daytime sleepiness. His Epworth sleepiness score was 4/24. Three years before the onset of these symptoms, he had a period of insomnia in the context of life stress with a total sleep time of 2 hours per night. He was treated for depression with fluoxetine, and his insomnia improved over an 18-month period. The fluoxetine was then stopped. He had no sleep history of note. His other medical history included chronic back pain and hypercholesterolemia. He had been taking gabapentin, ibuprofen, and atorvastatin for years. Around the time of his presenting symptom onset, he was diagnosed as hypertensive and treated with propranolol LA, 160 mg daily. On examination, he had a body mass index of 36 kg/m2 and was normotensive. His throat was narrow with moderately enlarged tonsils. There were no Parkinsonian features. Full blood count and renal function testing were normal. Overnight polysomnography showed an apnea/hypopnea index of 25 events per hour, consistent with moderate sleep apnea. No behavioral events were captured on overnight video recording. A diagnosis of rapid eye movement sleep behavior disorder caused by propranolol was made. Propranolol was reduced by 20 mg every 3 days until stopped, and replaced by lisinopril 2.5 mg. Clonazepam 0.25 mg at night also was prescribed during the tapering period to stop 1 week after discontinuing the beta-blocker. On review at 6 weeks and 6 months, his violent behavior had stopped completely and he was no longer taking clonazepam. He remained normotensive on lisinopril and declined treatment for his sleep-disordered breathing. This case report describes a violent, rapid eye movement behavior disorder resulting from the prescription of a beta-blocker for hypertension. Lipophilic beta-blockers have been associated with a number of sleep disturbances, including insomnia, hypnogogic hallucinations, sleep-walking, and nightmares.1Boriani G. Biffi M. Strocchi E. Branzi A. Nightmares and sleep disturbances with simvastatin and metoprolol.Ann Pharmacother. 2001; 35: 1292Crossref PubMed Scopus (3) Google Scholar, 2Pradalier A. Giroud M. Dry J. Somnambulism, migraine and propranolol.Headache. 1987; 27: 143-145Crossref PubMed Scopus (37) Google Scholar The mechanism for this interaction is unknown, although serotonin has been implicated.3Juszczak G.R. Swiergiel A.H. Serotonergic hypothesis of sleepwalking.Med Hypotheses. 2005; 64: 28-32Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar Further, selective serotonin reuptake inhibitors have been shown to suppress rapid eye movement sleep and dream content, supporting a link between serotonin and rapid eye movement sleep.4Pace-Schott E.F. Gersh T. Silvestri R. et al.SSRI treatment suppresses dream recall frequency but increases subjective dream intensity in normal subjects.J Sleep Res. 2001; 10: 129-142Crossref PubMed Scopus (76) Google Scholar A relationship between 5-hydroxytyptamine receptor occupancy and beta-blocker–induced sleep disorder has also been described.5Yamada Y. Shibuya F. Hamada J. et al.Prediction of sleep disorders induced by beta-adrenergic receptor blocking agents based on receptor occupancy.J Pharmacokinet Biopharm. 1995; 23: 131-145Crossref PubMed Scopus (46) Google Scholar It is therefore possible that beta-blockers bind to 5-hydroxytyptamine receptors and precipitate abnormal rapid eye movement and non-rapid eye movement sleep behavior. Beta-blockers have also been shown to bind to central beta-adrenoreceptors6Fisher A.A. Davis M. Jeffery I. Acute delirium induced by metoprolol.Cardiovasc Drugs Ther. 2002; 16: 161-165Crossref PubMed Scopus (32) Google Scholar and influence melatonin release;7Stoschitzky K. Sakotnik A. Lercher P. et al.Influence of beta-blockers on melatonin release.Eur J Clin Pharmacol. 1999; 55: 111-115Crossref PubMed Scopus (178) Google Scholar therefore, it is equally possible that these actions could result in increased arousal during sleep and abnormal behaviors as a consequence. This case illustrates an important, easily treated, and common cause of potentially harmful sleep behavior.