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. 2013 Jun 5;2013(6):CD005226.
doi: 10.1002/14651858.CD005226.pub3.

Drug therapy for pain in amyotrophic lateral sclerosis or motor neuron disease

Johannes Brettschneider  1 , Jerome Kurent, Albert Ludolph
Affiliations

Drug therapy for pain in amyotrophic lateral sclerosis or motor neuron disease

Johannes Brettschneider et al. Cochrane Database Syst Rev. .

Abstract

Background: Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is the most common neurodegenerative disorder of the motor system in adults. Pain in ALS is a frequent symptom especially in the later stages of disease and can have a pronounced influence on quality of life and suffering. Treatment of pain therefore should be recognised as an important aspect of palliative care in ALS. This is an update of a review first published in 2008.

Objectives: To systematically review the evidence for the efficacy of drug therapy in relieving pain in ALS. We also aimed to evaluate possible adverse effects associated with the different drugs and their influence on survival and quality of life.

Search methods: On 2 July 2012, we searched the following databases: the Cochrane Neuromuscular Disease Group Specialized Register (2 July 2012), CENTRAL (2012, Issue 6 in The Cochrane Library), MEDLINE (January 1966 to June 2012), EMBASE (January 1980 to June 2012), CINAHL (January 1982 to June 2012), AMED (January 1985 to June 2012) and LILACS (January 1982 to June 2012). We checked the bibliographies of trials identified and contacted other disease experts to identify further published and unpublished trials.

Selection criteria: We searched for randomised or quasi-randomised controlled trials on drug therapy for pain in amyotrophic lateral sclerosis.

Data collection and analysis: We collected data using a specially designed form and analysed them using the Cochrane Review Manager software.

Main results: We found no randomised or quasi-randomised controlled trials on drug therapy for pain in ALS or MND.

Authors' conclusions: There is no evidence from randomised controlled trials about the management of pain in ALS. Further research on this important aspect of palliative care in ALS is needed. Randomised controlled trials should be initiated to determine the effectiveness of different analgesics for treatment of pain in ALS.

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Conflict of interest statement

JB, JK: none known

AL and his institution has received research and other support from various sources, as follows, but none related to this review. AL has received lecture or consulting fees, travel support or honoraria from Biogen Idec, Merz Pharma, Nutricia, Novartis, Thierry Latran Foundation, Stifterverband; board membership fees from Biogen Idec; and fees for expert testimony from Teva. His institution has grants or grants pending from Biogen Idec, GSK, Teva, Merz Pharma. Royalties have been paid to AL or his institution from Thieme Verlag, Cambridge University Press.

Update of

References

References to studies excluded from this review

Abe 2008 {published data only}
    1. Abe Y, Miyashita M, Ito N, Shirai Y, Momose Y, Ichikawa Y, et al. Attitude of outpatients with neuromuscular diseases in Japan to pain and use of analgesics. Journal of the Neurological Sciences 2008;267(1‐2):22‐7. [PUBMED: 17916366] - PubMed
Adelman 2004 {published data only}
    1. Adelman EE, Albert SM, Rabkin JG, Bene ML, Tider T, O'Sullivan I. Disparities in perceptions of distress and burden in ALS patients and family caregivers. Neurology 2004;62(10):1766‐70. [PUBMED: 15159475] - PubMed
Amtmann 2004 {published data only}
    1. Amtmann D, Weydt P, Johnson KL, Jensen MP, Carter GT. Survey of cannabis use in patients with amyotrophic lateral sclerosis. American Journal of Hospice and Palliative Care 2004;21(2):95‐104. [PUBMED: 15055508] - PubMed
Bedlack 2009 {published data only}
    1. Bedlack RS, Pastula DM, Hawes J, Heydt D. Open‐label pilot trial of levetiracetam for cramps and spasticity in patients with motor neuron disease. Amyotrophic Lateral Sclerosis 2009;10(4):210‐5. [PUBMED: 18821142] - PubMed
Borasio 2001a {published data only}
    1. Borasio GD, Shaw PJ, Hardiman O, Ludolph AC, Sales Luis ML, Silani V, European ALS Study Group. Standards of palliative care for patients with amyotrophic lateral sclerosis: results of a European survey. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2001;2(3):159‐64. [PUBMED: 11771773] - PubMed
Bradley 2001 {published data only}
    1. Bradley WG, Anderson F, Bromberg M, Gutmann L, Harati Y, Ross M, et al. ALS CARE Study Group. Current management of ALS: comparison of the ALS CARE Database and the AAN Practice Parameter. The American Academy of Neurology. Neurology 2001;57(3):500‐4. [PUBMED: 11502920] - PubMed
Carter 2010 {published data only}
    1. Carter GT, Abood ME, Aggarwal SK, Weiss MD. Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials. The American Journal of Hospice and Palliative Care 2010;27(5):347‐56. [PUBMED: 20439484] - PubMed
Chio 2001 {published data only}
    1. Chiò A, Silani V, Italian ALS Study Group. Amyotrophic lateral sclerosis care in Italy: a nationwide study in neurological centers. Journal of the Neurological Sciences 2001;191(1‐2):145‐50. [PUBMED: 11677006] - PubMed
de Carvalho 2001 {published data only}
    1. Carvalho M. Gabapentin for the treatment of spasticity in patients with amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2001;2(1):47‐8. [PUBMED: 11465933] - PubMed
de Castro‐Costa 1999 {published data only}
    1. Castro‐Costa CM, Oria RB, Machado‐Filho JA, Franco MT, Diniz DL, Giffoni SD, et al. Amyotrophic lateral sclerosis. Clinical analysis of 78 cases from Fortaleza (northeastern Brazil). Arquivos de Neuro‐Psiquiatria 1999;57(3B):761‐74. [PUBMED: 10751910] - PubMed
Drake 1983 {published data only}
    1. Drake ME Jr. Chronic pain syndrome in amyotrophic lateral sclerosis. Archives of Neurology 1983;40(7):453‐4. [PUBMED: 6860189] - PubMed
Forshew 2003 {published data only}
    1. Forshew DA, Bromberg MB. A survey of clinicians' practice in the symptomatic treatment of ALS. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2003;4(4):258‐63. [PUBMED: 14753660] - PubMed
Ganzini 1998 {published data only}
    1. Ganzini L, Johnston WS, McFarland BH, Tolle SW, Lee MA. Attitudes of patients with amyotrophic lateral sclerosis and their care givers toward assisted suicide. New England Journal of Medicine 1998;339(14):967‐73. [PUBMED: 9753713] - PubMed
Ganzini 1999 {published data only}
    1. Ganzini L, Johnston WS, Hoffman WF. Correlates of suffering in amyotrophic lateral sclerosis. Neurology 1999;52(7):1434‐40. [PUBMED: 10227631] - PubMed
Ganzini 2002a {published data only}
    1. Ganzini L, Silveira MJ, Johnston WS. Predictors and correlates of interest in assisted suicide in the final month of life among ALS patients in Oregon and Washington. Journal of Pain and Symptom Management 2002;24(3):312‐7. [PUBMED: 12458112] - PubMed
Ganzini 2002b {published data only}
    1. Ganzini L, Johnston WS, Silveira MJ. The final month of life in patients with ALS. Neurology 2002;59(3):428‐31. [PUBMED: 12177378] - PubMed
Hecht 2002 {published data only}
    1. Hecht M, Hillemacher T, Gräsel E, Tigges S, Winterholler M, Heuss D, et al. Subjective experience and coping in ALS. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2002;3(4):225‐31. [PUBMED: 12710513] - PubMed
Jensen 2005 {published data only}
    1. Jensen MP, Abresch RT, Carter GT, McDonald CM. Chronic pain in persons with neuromuscular disease. Archives of Physical Medicine and Rehabilitation 2005;86(6):1155‐63. [PUBMED: 15954054] - PubMed
Maessen 2010 {published data only}
    1. Maessen M, Veldink JH, Berg LH, Schouten HJ, Wal G, Onwuteaka‐Philipsen BD. Requests for euthanasia: origin of suffering in ALS, heart failure, and cancer patients. Journal of Neurology 2010;257(7):1192‐8. [PUBMED: 20148336] - PubMed
Mandler 2001 {published data only}
    1. Mandler RN, Anderson FA Jr, Miller RG, Clawson L, Cudkowicz M, Bene M, ALS C.A.R.E. Study Group. The ALS Patient Care Database: insights into end‐of‐life care in ALS. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2001;2(4):203‐8. [PUBMED: 11958732] - PubMed
McClelland 2008 {published data only}
    1. McClelland S 3rd, Bethoux FA, Boulis NM, Sutliff MH, Stough DK, Schwetz KM, et al. Intrathecal baclofen for spasticity‐related pain in amyotrophic lateral sclerosis: efficacy and factors associated with pain relief. Muscle and Nerve 2008;37(3):396‐8. [PUBMED: 17894358] - PubMed
Neudert 2001 {published data only}
    1. Neudert C, Oliver D, Wasner M, Borasio GD. The course of the terminal phase in patients with amyotrophic lateral sclerosis. Journal of Neurology 2001;248(7):612‐6. [PUBMED: 11518004] - PubMed
Newrick 1984 {published data only}
    1. Newrick PG, Langton‐Hewer R. Motor neurone disease: can we do better? A study of 42 patients. British Medical Journal 1984;289(6444):539‐42. [PUBMED: 6235890] - PMC - PubMed
Newrick 1985 {published data only}
    1. Newrick PG, Langton‐Hewer R. Pain in motor neuron disease. Journal of Neurology, Neurosurgery, and Psychiatry 1985;48(8):838‐40. [PUBMED: 4031936] - PMC - PubMed
O'Brien 1992 {published data only}
    1. O'Brien T, Kelly M, Saunders C. Motor neuron disease: a hospice perspective. BMJ 1992;304(6825):471‐3. [PUBMED: 1547416] - PMC - PubMed
Oliver 1996 {published data only}
    1. Oliver D. The quality of care and symptom control ‐ the effects on the terminal phase of ALS/MND. Journal of the Neurological Sciences 1996;139 Suppl:134‐6. [PUBMED: 8899674] - PubMed
Oliver 1998 {published data only}
    1. Oliver D. Opioid medication in the palliative care of motor neurone disease. Palliative Medicine 1998;12(2):113‐5. [PUBMED: 9616447] - PubMed
Saunders 1981 {published data only}
    1. Saunders C, Walsh TD, Smith M. Hospice care in motor neuron disease. In: Saunders C, Summers DH, Teller N editor(s). Hospice: The Living Idea. London: Edward Arnold, 1981. [0713143983]
Shibata 2003 {published data only}
    1. Shibata M, Abe K, Jimbo A, Shimizu T, Mihara M, Sadahiro S, et al. Complex regional pain syndrome type I associated with amyotrophic lateral sclerosis. Clinical Journal of Pain 2003;19(1):69‐70. [PUBMED: 12514459] - PubMed
Tedman 1997 {published data only}
    1. Tedman BM, Young CA, Williams IR. Assessment of depression in patients with motor neuron disease and other neurologically disabling illness. Journal of the Neurological Sciences 1997;152(Suppl 1):S75‐9. [PUBMED: 9419059] - PubMed
Trail 2003 {published data only}
    1. Trail M, Nelson ND, Van JN, Appel SH, Lai EC. A study comparing patients with amyotrophic lateral sclerosis and their caregivers on measures of quality of life, depression, and their attitudes toward treatment options. Journal of the Neurological Sciences 2003;209(1‐2):79‐85. [PUBMED: 12686407] - PubMed
Weber 2010 {published data only}
    1. Weber M, Goldman B, Truniger S. Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: a randomised, double‐blind crossover trial. Journal of Neurology, Neurosurgery and Psychiatry 2010;81(10):1135‐40. [PUBMED: 20498181] - PubMed
Winter 2010 {published data only}
    1. Winter Y, Schepelmann K, Spottke AE, Claus D, Grothe C, Schröder R, et al. Health‐related quality of life in ALS, myasthenia gravis and facioscapulohumeral muscular dystrophy. Journal of Neurology 2010 Apr 10 [Epub ahead of print];257(9):1473‐81. [PUBMED: 20383521] - PubMed
Wu 1998 {published data only}
    1. Wu PY. The management of patients with advanced motor neuron disease. Zhonghua Yi Xue Za Zhi 1998;61(3):141‐5. [PUBMED: 9556945] - PubMed

Additional references

Ashworth 2006
    1. Ashworth NL, Satkunam LE, Deforge D. Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/14651858.CD004156.pub3] - DOI - PubMed
Baldinger 2012
    1. Baldinger R, Katzberg HD, Weber M. Treatment for cramps in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database of Systematic Reviews 2012, Issue 4. [DOI: 10.1002/14651858.CD004157.pub2] - DOI - PubMed
Borasio 1997
    1. Borasio GD, Voltz R. Palliative care in amyotrophic lateral sclerosis. Journal of Neurology 1997;244(Suppl 4):S11‐7. [PUBMED: 9402548] - PubMed
Borasio 2001b
    1. Borasio GD, Voltz R, Miller RG. Palliative care in amyotrophic lateral sclerosis. Neurologic Clinics 2001;19(4):829‐47. [PUBMED: 11854102] - PubMed
Brooks 2000
    1. Brooks BR, Miller RG, Swash M, Munsat TL, World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2000;1(5):293‐9. [PUBMED: 11464847] - PubMed
Brownell 1970
    1. Brownell B, Oppenheimer DR, Hughes JT. The central nervous system in motor neurone disease. Journal of Neurology, Neurosurgery, and Psychiatry 1970;33(3):338‐57. [PUBMED: 5431724] - PMC - PubMed
Clarke 2005
    1. Clarke DM, McLeod JE, Smith GC, Trauer T, Kissane DW. A comparison of psychosocial and physical functioning in patients with motor neurone disease and metastatic cancer. Journal of Palliative Care 2005;21(3):173‐9. [PUBMED: 16334972] - PubMed
Coderre 2007
    1. Coderre TJ, Kumar N, Lefebvre CD, Yu JS. A comparison of the glutamate release inhibition and anti‐allodynic effects of gabapentin, lamotrigine, and riluzole in a model of neuropathic pain. Journal of Neurochemistry 2007;100(5):1289‐99. [PUBMED: 17241130] - PubMed
Drory 2001
    1. Drory VE, Goltsman E, Reznik JG, Mosek A, Korczyn AD. The value of muscle exercise in patients with amyotrophic lateral sclerosis. Journal of the Neurological Sciences 2001;191(1‐2):133‐7. [PUBMED: 11677004] - PubMed
El Tawil 2010
    1. El‐Tawil S, Al Musa T, Valli H, Lunn MPT, El‐Tawil T, Weber M. Quinine for muscle cramps. Cochrane Database of Systematic Reviews 2010, Issue 12. [DOI: 10.1002/14651858.CD005044.pub2] - DOI - PubMed
FDA 2006
    1. US Food, Drug Administration. FDA orders unapproved quinine drugs from the market and cautions consumers about 'off‐label' use of quinine to treat leg cramps. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108799... 2006.
FDA 2010
    1. US Food, Drug Administration. FDA Drug Safety Communication: new risk management plan and patient Medication Guide for Qualaquin (quinine sulfate). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPa... 2010 (accessed 17 April 2013).
Gubbay 1985
    1. Gubbay SS, Kahana E, Zilber N, Cooper G, Pintov S, Leibowitz Y. Amyotrophic lateral sclerosis. A study of its presentation and prognosis. Journal of Neurology 1985;232(5):295‐300. [PUBMED: 4056836] - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. 2011. Available from www.cochrane‐handbook.org.
Lawyer 1953
    1. Lawyer TJr, Netsky MG. Amyotrophic lateral sclerosis. A. M. A. Archives of Neurology and Psychiatry 1953;69(2):171‐92. [PUBMED: 13007227] - PubMed
Lou 2003
    1. Lou JS, Reeves A, Benice T, Sexton G. Fatigue and depression are associated with poor quality of life in ALS. Neurology 2003;60(1):122‐3. [PUBMED: 12525733] - PubMed
Miller 1999
    1. Miller RG, Rosenberg JA, Gelinas DF, Mitsumoto H, Newman D, Sufit R, et al. Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence based review): report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS Practice Parameters Task Force. Neurology 1999;52(7):1311‐23. [PUBMED: 10227612] - PubMed
Miller 2001
    1. Miller RG, Moore DH 2nd, Gelinas DF, Dronsky V, Mendoza M, Barohn RJ, et al. Western ALS Study Group. Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis. Neurology 2001;56(7):843‐8. [PUBMED: 11294919] - PubMed
Pittenger 2008
    1. Pittenger C, Coric V, Banasr M, Bloch M, Krystal JH, Sanacora G. Riluzole in the treatment of mood and anxiety disorders. CNS Drugs 2008;22(9):761‐86. [PUBMED: 18698875] - PubMed
RevMan 2012 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan) [Computer Program]. Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Sung 2003
    1. Sung B, Lim G, Mao J. Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats. Journal of Neuroscience 2003;23(7):2899‐910. [PUBMED: 12684477] - PMC - PubMed
WHO 1990
    1. Cancer pain relief and palliative care. Report of a WHO Expert Committee. World Health Organization Technical Report Series 1990; Vol. 804:1‐75. [PUBMED: 1702248] - PubMed
Worms 2001
    1. Worms PM. The epidemiology of motor neuron diseases: a review of recent studies. Journal of the Neurological Sciences 2001;191(1‐2):3‐9. [PUBMED: 11676986] - PubMed

References to other published versions of this review

Brettschneider 2005
    1. Brettschneider J, Ludolph A, Mitchell JD. Drug therapy for pain in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD005226] - DOI - PubMed
Brettschneider 2008
    1. Brettschneider J, Kurent J, Ludolph A, Mitchell J. Drug therapy for pain in amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database of Systematic Reviews 2008, Issue 3. [DOI: 10.1002/14651858.CD005226.pub2] - DOI - PubMed

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