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Latest MS research update - Can the use of sleeping tablets increase levels of fatigue in people with MS? - 9 December 2014

The MS Trust runs a weekly search for interesting and relevant research articles relating to multiple sclerosis using Medline, a specialised search engine for medical journals. The original abstracts to each of the articles can be accessed via the links provided.

For further information on any topic please contact the information team at info@mstrust.org.uk.


This week's highlighted research...

Can the use of sleeping tablets increase levels of fatigue in people with MS?

Research by topic areas...

Assessment tools
Co-existing conditions
Disease modifying treatments
Economics
Epidemiology
Falls
Other treatments
Physical activity
Psychological aspects
Rehabilitation
Relapses
Stem cells
Symptoms and symptom management


Can the use of sleeping tablets increase levels of fatigue in people with MS?

Summary

Sleep problems and fatigue are both common in people with MS. Previous research has shown that a lack of sleep can make fatigue, as well as other MS symptoms, worse. Therefore in order to get a good night's sleep some people use sleeping tablets, however little is known about the use of sleeping tablets in MS and the effects that they can have on fatigue levels.

A group of 190 people with MS in the USA took part in the study and completed several questionnaires that explored their sleep habits, use of sleeping tablets, levels of fatigue and daytime sleepiness.

Nearly half of the participants (89 people) said they used sleeping tablets. 50 participants used prescription medication and 59 used over the counter products, some participants used both. The study found that more people who were suffering with fatigue were also using sleeping tablets. Participants taking sleeping tablets also had higher levels of fatigue. When the researchers investigated further, they found that the higher levels of fatigue were associated with using the over the counter products containing diphenhydramine, but not prescription medications.

The study found that there may be a risk of making MS fatigue worse by using over the counter sleeping tablets containing diphenhydramine. The researchers do stress that their study cannot prove that these medications are the cause of the higher levels of fatigue seen in these participants but their study highlights an area that warrants further investigation. They recommend that while the effect of these particular medications on MS fatigue are investigated, alternative approaches and treatments should perhaps be considered to help people with MS get a good night's sleep.


Background

Sleep problems are common in people with MS, with about 50% reported to experience some form of sleep disturbance. Fatigue is also extremely common in people with MS and previous research has shown that a lack of sleep can make fatigue, as well as other MS symptoms, worse. In order to get a good night's sleep some people may use sleeping tablets, either prescribed by their doctor or purchased over the counter at the chemist. However little is known about the use of sleeping tablets in MS and the effect that they can have. This study aimed to look at how many people used sleeping tablets, how often they used them and if their use had any effect on fatigue levels.


How this study was carried out

190 people with MS were recruited to take part in the study via a clinic held at a university medical centre in the USA. The participants completed several questionnaires to gather information on sleep, their use of sleeping tablets and several other factors can be related to sleep or MS. These were:

  • A MS-specific sleep survey – to collect information on sleep quality, sleep quantity, daytime and night time symptoms.
  • Sleeping tablet use – to collect information on how often these were used (never, occasionally, frequently, or always) and which medications from a list of those commonly available they used.
  • Fatigue Severity Scale (FSS) – to determine their fatigue level
  • Epworth Sleepiness Scale (ESS) – to determine levels of daytime sleepiness
  • Insomnia Severity Index (ISI) – to collect more information on the severity and impact of insomnia

Information was also collected about the participants MS, including symptoms that interfered with sleep such as pain, tingling, spasticity and bladder problems.


What was found

Nearly half of the participants (89 people) said they used sleeping tablets. 50 participants said they used prescription medication and 59 used over the counter products, some participants used both. Of those that used over the counter products, 47 were using a product that contained a medicine called diphenhydramine.

The study found that more people who were suffering with fatigue were also using sleeping tablets at least on an occasional basis.

Participants taking sleeping tablets also had higher levels of fatigue. When the researchers investigated further, they found that the higher levels of fatigue were associated with using the over the counter products containing diphenhydramine, but not prescription medications.


What does it mean?

The study found that there may be a risk of making MS fatigue worse by using over the counter sleeping tablets containing diphenhydramine. The researchers do stress that their study cannot prove that these medications are the cause of the higher levels of fatigue seen in these participants but their study highlights an area that warrants further investigation. They suggest that these medications may still be having an effect the day after the person has used them, as their common side effects after use are decreased mental alertness and drowsiness, which may be contributing to fatigue levels in people with MS and make it appear worse.

They recommend that while the effect of these particular medications on MS fatigue are investigated, alternative approaches and treatments should perhaps be considered to help people with MS get a good night's sleep.


Comment

The study looked at two categories of sleeping tablets, those only available on prescription and those available over the counter. Prescription medications such as benzodiazepines are tranquillisers that can reduce anxiety and promote calmness, relaxation and sleep. In the UK temazepam is the benzodiazepine that's often prescribed as its effects are short lived. Z medicines are a newer type medicine that work in a similar way to benzodiazepines, these include zaleplon, zolpidem and zopiclone.

Over the counter medications that contain diphenhydramine include Nytol and many chemist and supermarket own brand of sleeping tablets, it can also occasionally be found in cold and flu remedies designed to be taken at bedtime. Diphenhydramine is an antihistamine that has sedative effects, so can also be found in anti-allergy products such as Benadryl.

Braley TJ, Segal BM, Chervin RD.
Hypnotic use and fatigue in multiple sclerosis..
Sleep Med. 2014 Sep 28. pii: S1389-9457(14)00391-8.[Epub ahead of print]
abstract
Read the full text of this paper

More about sleep

Poor sleep is common in people with multiple sclerosis. Poor sleep quality and quantity can impact on daily life, causing daytime sleepiness, decreased concentration and memory, worsening depression, and the inability to work effectively. A lack of sleep can also lead to low energy levels or make fatigue and other symptoms of MS worse.

There can be many reasons why getting good quality sleep can be difficult. Some are well known: a new baby can mean you are up and down throughout the night or worries playing on your mind can make it difficult to 'switch off' resulting in trouble dropping off or a restless night.

Some MS related symptoms can also make sleeping difficult or interrupted. These include: spasms, pain (neuropathic or musculoskeletal), high levels of daytime fatigue and nocturia (the urge to urinate frequently at night). In such cases sleep quality can often be improved by treating the symptoms. Many treatments are available, including medications some of which have the dual advantage of treating the symptom as well as having a sedative effect, such as gabapentin used to treat neuropathic pain and spasms in MS.

Sleep quality can also be improved by following a routine, as your body and mind will become used to these regular habits.

  • Try to stay as physically active as possible during the day, but avoid getting overtired by doing too much, as being too tired can make it difficult to get to sleep.
  • Avoid unnecessary stress or stimulants (eg caffeine, chocolate, alcohol) in the late afternoon and evening.
  • Establish a bedtime routine such as having a warm milky drink before you go to settle down or a period of quiet time and try to follow the same routine every day of the week
  • Wind down before it is time to sleep. Avoid rushing around or vigorous exercise just before bedtime and write a to do list for the following day to clear your mind of distractions.

You can read more suggestions for improving sleep in Living with fatigue which can be read online, downloaded as a pdf file or ordered as a printed version.

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Assessment tools

Raimo S, Trojano L, Spitaleri D, et al.
Apathy in multiple sclerosis: a validation study of the apathy evaluation scale.
J Neurol Sci. 2014 Oct 23;347(1-2):295-300. [Epub ahead of print]
abstract

Schwartz CE, Ayandeh A, Motl RW.
Investigating the minimal important difference in ambulation in multiple sclerosis: a disconnect between performance-based and patient-reported outcomes?
J Neurol Sci. 2014 Oct 18;347(1-2):268-274. [Epub ahead of print]
abstract

Sandroff BM, Motl RW, Sosnoff JJ, et al.
Further validation of the Six-Spot Step Test as a measure of ambulation in multiple sclerosis.
Gait Posture. 2014 Oct 23. [Epub ahead of print]
abstract

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Co-existing conditions

Tettey P, Simpson S Jr, Taylor BV, et al.
The co-occurrence of multiple sclerosis and type 1 diabetes: shared aetiologic features and clinical implication for MS aetiology.
J Neurol Sci. 2014 Nov 20. [Epub ahead of print]
abstract

Sieminski M, Losy J, Partinen M.
Restless legs syndrome in multiple sclerosis.
Sleep Med Rev. 2014 Oct 12. [Epub ahead of print]
abstract

Tseng CH, Huang WS, Lin CL, et al.
Increased risk of ischaemic stroke among patients with multiple sclerosis.
Eur J Neurol. 2014 Nov 29. [Epub ahead of print]
abstract

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Disease modifying treatments

Kalincik T, Jokubaitis V, Izquierdo G, et al.
Comparative effectiveness of glatiramer acetate and interferon beta formulations in relapsing-remitting multiple sclerosis.
Mult Scler. 2014 Dec 5. [Epub ahead of print]
abstract

Grey Née Cotte S, Salmen Née Stroet A, von Ahsen N, et al.
Lack of efficacy of mitoxantrone in primary progressive multiple sclerosis irrespective of pharmacogenetic factors: a multi-center, retrospective analysis.
J Neuroimmunol. 2014 Nov 20. [Epub ahead of print]
abstract

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Economics

Raftery J.
Health economic evaluation in England.
Z Evid Fortbild Qual Gesundhwes. 2014;108(7):367-74.
abstract

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Epidemiology

Benjaminsen E, Olavsen J, Karlberg M, et al.
Multiple sclerosis in the far north - incidence and prevalence in Nordland County, Norway, 1970 - 2010.
BMC Neurol. 2014 Dec 4;14(1):226. [Epub ahead of print]
abstract

Read the full text of this paper (PDF)

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Falls

Matsuda PN, Verrall AM, Finlayson ML, et al.
Falls among adults aging with disability.
Arch Phys Med Rehabil. 2014 Oct 19. [Epub ahead of print]
abstract

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Other treatments

Levin AB, Hadgkiss EJ, Weiland TJ, et al.
Can meditation influence quality of life, depression, and disease outcome in multiple sclerosis? Findings from a large international web-based study.
Behav Neurol. 2014;2014:916519.
abstract

Read the full text of this paper

Crayton H, Sidovar M, Wulf S, et al.
Patient perspectives and experience with dalfampridine treatment in multiple sclerosis-related walking impairment: the step together program.
Patient. 2014 Dec 5. [Epub ahead of print]
abstract

Read the full text of this paper

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Physical activity

Huang M, Jay O, Davis SL.
Autonomic dysfunction in multiple sclerosis: implications for exercise.
Auton Neurosci. 2014 Oct 23. [Epub ahead of print]
abstract

Reynolds MA, McCully K, Burdett B, et al.
A pilot study: Evaluation of the effect of functional electrical stimulation cycling on muscle metabolism in non-ambulatory people with multiple sclerosis.
Arch Phys Med Rehabil. 2014 Nov 4. [Epub ahead of print]
abstract

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Psychological aspects

Cogo MG, Rota S, Fusco ML, et al.
Cognitive correlates of under-ambiguity and under-risk decision making in high-functioning patients with relapsing remitting multiple sclerosis.
J Clin Exp Neuropsychol. 2014 Dec 8:1-10. [Epub ahead of print]
abstract

Granberg T, Martola J, Bergendal G, et al.
Corpus callosum atrophy is strongly associated with cognitive impairment in multiple sclerosis: Results of a 17-year longitudinal study.
Mult Scler. 2014 Dec 5. [Epub ahead of print]
abstract

Gich J, Freixenet J, Garcia R, et al.
A new cognitive rehabilitation programme for patients with multiple sclerosis: the 'MS-line! Project'
Mult Scler. 2014 Dec 5. [Epub ahead of print]
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Cabib C, Llufriu S, Casanova-Mollà J, et al.
Defective sensorimotor integration in preparation for reaction time tasks in patients with multiple sclerosis.
J Neurophysiol. 2014 Dec 4:jn.00591.2014. [Epub ahead of print]
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Taylor KL, Hadgkiss EJ, Jelinek GA, et al.
Lifestyle factors, demographics and medications associated with depression risk in an international sample of people with multiple sclerosis.
BMC Psychiatry. 2014 Dec 3;14(1):327. [Epub ahead of print]
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Read the full text of this paper (PDF)

Mrabet S, Ben Ali N, Kchaou M, et al.
Depression in multiple sclerosis.
Rev Neurol (Paris). 2014 Nov;170(11):700-2.
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Pagnini F, Bosma CM, Phillips D, et al.
Symptom changes in multiple sclerosis following psychological interventions: a systematic review.
BMC Neurol. 2014 Nov 30;14(1):222. [Epub ahead of print]
abstract

Read the full text of this paper

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Rehabilitation

Uszynski M, Purtill H, Coote S.
Relationship between foot vibration threshold and walking and balance functions in people with Multiple Sclerosis (PwMS).
Gait Posture. 2014 Oct 18. [Epub ahead of print]
abstract

Wolfsegger T, Assar H, Topakian R.
3-week whole body vibration does not improve gait function in mildly affected multiple sclerosis patients-a randomized controlled trial.
J Neurol Sci. 2014 Sep 26;347(1-2):119-123. [Epub ahead of print]
abstract

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relapses

Li XL, Zhang ZC, Zhang B, et al.
Atorvastatin calcium in combination with methylprednisolone for the treatment of multiple sclerosis relapse.
Int Immunopharmacol. 2014 Dec;23(2):546-9.
abstract

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Stem cells

Connolly R, O'Brien T, Flaherty G.
Stem cell tourism - A web-based analysis of clinical services available to international travellers.
Travel Med Infect Dis. 2014 Oct 7;12(6PB):695-701. [Epub ahead of print]
abstract

Llufriu S, Sepúlveda M, Blanco Y, et al.
Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.
PLoS One. 2014;9(12):e113936.
abstract

Read the full text of this paper

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Symptoms and symptom management

Andretta E, Simeone C, Ostardo E, et al.
Usefulness of sacral nerve modulation in a series of multiple sclerosis patients with bladder dysfunction.
J Neurol Sci. 2014 Oct 12;347(1-2):257-261. [Epub ahead of print]
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Fogelberg DJ, Vitiello MV, Hoffman JM, et al.
Comparison of self-report sleep measures for individuals with multiple sclerosis and spinal cord injury.
Arch Phys Med Rehabil. 2014 Oct 23. [Epub ahead of print]
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Harrison AM, McCracken LM, Bogosian A, et al.
Towards a better understanding of MS pain: A systematic review of potentially modifiable psychosocial factors.
J Psychosom Res. 2014 Jul 15. [Epub ahead of print]
abstract