Sleep Medicine 16 (2015) 131–137
Contents lists available at ScienceDirect
Sleep Medicine j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s l e e p
Original Article
Hypnotic use and fatigue in multiple sclerosis Tiffany J. Braley a,b,*, Benjamin M. Segal a, Ronald D. Chervin b a b
Department of Neurology and Multiple Sclerosis Center, University of Michigan, Ann Arbor, MI, USA Department of Neurology and Sleep Disorders Center, University of Michigan, Ann Arbor, MI, USA
A R T I C L E
I N F O
Article history: Received 10 July 2014 Received in revised form 14 September 2014 Accepted 23 September 2014 Available online 28 September 2014 Keywords: Multiple sclerosis MS Fatigue Fatigue severity scale Hypnotic Diphenhydramine Insomnia Sleepiness
A B S T R A C T
Objectives: Sleep disturbances and fatigue are common in patients with multiple sclerosis (MS), but little is known about hypnotic use patterns in MS, or the relationship between these medications and fatigue. The objectives of this study were to investigate the prevalence of prescription and over-the-counter (OTC) hypnotic use among MS patients, and to assess the relationships between fatigue severity and hypnotic use among persons with MS. Methods: Data on hypnotic use frequency, hypnotic agents of choice, and clinical characteristics were extracted from medical records and a survey dataset from 190 MS patients who completed questionnaires regarding sleep quality, sleep quantity, nocturnal symptoms, sleepiness (Epworth Sleepiness Scale), obstructive sleep apnea risk (STOP-Bang questionnaire), insomnia (Insomnia Severity Index), and fatigue level (Fatigue Severity Scale – FSS). Results: Eighty-nine subjects (47%) endorsed hypnotic use occasionally, frequently, or always. OTC diphenhydramine-containing products accounted for the majority of utilization, reported by 47 (25%). The occurrence of occasional or more frequent hypnotic use correlated with daytime fatigue (Spearman rho = 0.28, P = 0.0002), but not sleepiness. Regression of FSS scores on hypnotic use confirmed the association [beta (SE) = 0.55 (0.21), P = 0.0092] after adjustment for clinical and sleep-related confounds. In separate, similarly adjusted models, the use of OTC hypnotics but not prescription hypnotics was independently associated with higher FSS scores [0.54 (0.22), P = 0.0159]. An analogous association was observed more specifically for the use of diphenhydramine-containing products (0.49 (0.24), P = 0.044). Conclusions: Hypnotic use is highly prevalent among MS patients. Carryover effects from hypnotic agents, and in particular OTC diphenhydramine-containing products, could contribute to daytime fatigue. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system (CNS) that results in myelin destruction and axonal degeneration in the brain and spinal cord. This condition affects nearly half a million people in the United States, and is the leading cause of nontraumatic neurological disability among young adults. In addition to neurological disability, persons with MS disproportionately suffer from a variety of comorbidities and chronic symptoms that affect quality of life, including fatigue. Fatigue affects up to 90% of patients with MS at some point during their disease course. Despite recent evidence that sleep disturbances – experienced by at least 50% of MS patients [1,2] – are linked to fatigue in persons with MS [3–5], the use of hypnotic agents in this population has received scant attention, and the potential relationship between hypnotic use and fatigue in MS remains
* Corresponding author. Department of Neurology, University of Michigan, C728 Med Inn Bldg, 1500 E. Medical Center Dr, Ann Arbor, MI 48109, USA. Tel.: +1 734 232 1147; fax: +1 734 232 9986. E-mail address: [email protected] (T.J. Braley). http://dx.doi.org/10.1016/j.sleep.2014.09.006 1389-9457/© 2014 Elsevier B.V. All rights reserved.
unstudied. This is a critical gap in knowledge, as the treatment or elimination of factors that can exacerbate fatigue is an essential component of managing this symptom. The purpose of this study was to evaluate the frequency of prescription and over-the-counter (OTC) hypnotic use among outpatients at a tertiary MS center, and to assess the relationships between hypnotic use, fatigue severity, and other clinical characteristics.
2. Methods 2.1. Subjects/Data collection This study was approved by the University of Michigan (U-M) Institutional Review Board. Written informed consent was obtained. The data collection methods for this study have been described previously, in an analysis of associations between obstructive sleep apnea (OSA) symptoms and fatigue [3]. Briefly, patients who presented to the U-M MS Clinic completed an MS-specific sleep survey designed by the authors, consisting of questions regarding perceived sleep quality, sleep quantity, daytime symptoms, and
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T.J. Braley et al./Sleep Medicine 16 (2015) 131–137
nocturnal symptoms and behaviors. Subjects were also queried with separate survey items regarding the frequency of prescription and OTC hypnotic use for the purpose of aiding with sleep (categorized as never, occasionally, frequently, or always), followed by questions regarding specific hypnotic agents of choice with multiplechoice response sets, wherein subjects were allowed to select one or more choices from a list of common medications. Medical records were reviewed to obtain additional data on hypnotic use (when available), and to extract additional data on clinical variables including age, gender, MS subtype (relapsing or progressive), MS disease duration at time of the survey (years), use of disease-modifying therapy (DMT) at the time of the survey (yes/ no), documented diagnosis of clinical depression or active symptoms of depression as documented by the treating physician during the subject’s assessment on the day of the survey (yes/no), and a dichotomized estimate of MS-related disability (defined as an Expanded Disability Status Scale or EDSS) score of
Contents lists available at ScienceDirect
Sleep Medicine j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s l e e p
Original Article
Hypnotic use and fatigue in multiple sclerosis Tiffany J. Braley a,b,*, Benjamin M. Segal a, Ronald D. Chervin b a b
Department of Neurology and Multiple Sclerosis Center, University of Michigan, Ann Arbor, MI, USA Department of Neurology and Sleep Disorders Center, University of Michigan, Ann Arbor, MI, USA
A R T I C L E
I N F O
Article history: Received 10 July 2014 Received in revised form 14 September 2014 Accepted 23 September 2014 Available online 28 September 2014 Keywords: Multiple sclerosis MS Fatigue Fatigue severity scale Hypnotic Diphenhydramine Insomnia Sleepiness
A B S T R A C T
Objectives: Sleep disturbances and fatigue are common in patients with multiple sclerosis (MS), but little is known about hypnotic use patterns in MS, or the relationship between these medications and fatigue. The objectives of this study were to investigate the prevalence of prescription and over-the-counter (OTC) hypnotic use among MS patients, and to assess the relationships between fatigue severity and hypnotic use among persons with MS. Methods: Data on hypnotic use frequency, hypnotic agents of choice, and clinical characteristics were extracted from medical records and a survey dataset from 190 MS patients who completed questionnaires regarding sleep quality, sleep quantity, nocturnal symptoms, sleepiness (Epworth Sleepiness Scale), obstructive sleep apnea risk (STOP-Bang questionnaire), insomnia (Insomnia Severity Index), and fatigue level (Fatigue Severity Scale – FSS). Results: Eighty-nine subjects (47%) endorsed hypnotic use occasionally, frequently, or always. OTC diphenhydramine-containing products accounted for the majority of utilization, reported by 47 (25%). The occurrence of occasional or more frequent hypnotic use correlated with daytime fatigue (Spearman rho = 0.28, P = 0.0002), but not sleepiness. Regression of FSS scores on hypnotic use confirmed the association [beta (SE) = 0.55 (0.21), P = 0.0092] after adjustment for clinical and sleep-related confounds. In separate, similarly adjusted models, the use of OTC hypnotics but not prescription hypnotics was independently associated with higher FSS scores [0.54 (0.22), P = 0.0159]. An analogous association was observed more specifically for the use of diphenhydramine-containing products (0.49 (0.24), P = 0.044). Conclusions: Hypnotic use is highly prevalent among MS patients. Carryover effects from hypnotic agents, and in particular OTC diphenhydramine-containing products, could contribute to daytime fatigue. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system (CNS) that results in myelin destruction and axonal degeneration in the brain and spinal cord. This condition affects nearly half a million people in the United States, and is the leading cause of nontraumatic neurological disability among young adults. In addition to neurological disability, persons with MS disproportionately suffer from a variety of comorbidities and chronic symptoms that affect quality of life, including fatigue. Fatigue affects up to 90% of patients with MS at some point during their disease course. Despite recent evidence that sleep disturbances – experienced by at least 50% of MS patients [1,2] – are linked to fatigue in persons with MS [3–5], the use of hypnotic agents in this population has received scant attention, and the potential relationship between hypnotic use and fatigue in MS remains
* Corresponding author. Department of Neurology, University of Michigan, C728 Med Inn Bldg, 1500 E. Medical Center Dr, Ann Arbor, MI 48109, USA. Tel.: +1 734 232 1147; fax: +1 734 232 9986. E-mail address: [email protected] (T.J. Braley). http://dx.doi.org/10.1016/j.sleep.2014.09.006 1389-9457/© 2014 Elsevier B.V. All rights reserved.
unstudied. This is a critical gap in knowledge, as the treatment or elimination of factors that can exacerbate fatigue is an essential component of managing this symptom. The purpose of this study was to evaluate the frequency of prescription and over-the-counter (OTC) hypnotic use among outpatients at a tertiary MS center, and to assess the relationships between hypnotic use, fatigue severity, and other clinical characteristics.
2. Methods 2.1. Subjects/Data collection This study was approved by the University of Michigan (U-M) Institutional Review Board. Written informed consent was obtained. The data collection methods for this study have been described previously, in an analysis of associations between obstructive sleep apnea (OSA) symptoms and fatigue [3]. Briefly, patients who presented to the U-M MS Clinic completed an MS-specific sleep survey designed by the authors, consisting of questions regarding perceived sleep quality, sleep quantity, daytime symptoms, and
132
T.J. Braley et al./Sleep Medicine 16 (2015) 131–137
nocturnal symptoms and behaviors. Subjects were also queried with separate survey items regarding the frequency of prescription and OTC hypnotic use for the purpose of aiding with sleep (categorized as never, occasionally, frequently, or always), followed by questions regarding specific hypnotic agents of choice with multiplechoice response sets, wherein subjects were allowed to select one or more choices from a list of common medications. Medical records were reviewed to obtain additional data on hypnotic use (when available), and to extract additional data on clinical variables including age, gender, MS subtype (relapsing or progressive), MS disease duration at time of the survey (years), use of disease-modifying therapy (DMT) at the time of the survey (yes/ no), documented diagnosis of clinical depression or active symptoms of depression as documented by the treating physician during the subject’s assessment on the day of the survey (yes/no), and a dichotomized estimate of MS-related disability (defined as an Expanded Disability Status Scale or EDSS) score of
