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A Benefit-Risk Assessment of Baclofen in Severe Spinal Spasticity

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Abstract

Baclofen is used for treatment of the spasticity of spinal origin that is a common sequela of spinal cord injury and multiple sclerosis; spasticity occurs in about 50% of patients affected by these disorders.

In open-label studies of oral baclofen, the drug improved spasticity in 70–87% of patients; additionally, improvement in spasms was reported in 75–96% of patients. In double-blind, crossover, placebo-controlled trials, baclofen was reported to be effective, producing statistically significant improvements in spasticity. Tizanidine is the antispasticity drug that has been most widely compared with oral baclofen; studies have generally found the two drugs to have equivalent efficacy. However, tizanidine has better tolerability, in particular weakness was reported to be occur less frequently with tizanidine than with baclofen.

The main adverse effects of oral baclofen include: sedation or somnolence, excessive weakness, vertigo and psychological disturbances. The incidence of adverse effects is reported to range from 10% to 75%. The majority of adverse effects are not severe; most are dose related, transient and/or reversible. The main risks of oral baclofen administration are related to withdrawal: seizures, psychic symptoms and hyperthermia can occur. These symptoms improve after the reintroduction of baclofen, usually without sequelae. When not related to withdrawal; these symptoms mainly present in patients with brain damage and in the elderly. The limited data on baclofen toxicity in patients with renal disease suggest that administration of the drug in these persons may carry an unnecessarily high risk.

Intrathecal baclofen is indicated for use in patients with spasticity of spinal origin unresponsive to treatment with maximum doses of oral baclofen, tizanidine and/or dantrolene. The benefits of continuous intrathecal baclofen infusion have been demonstrated: >80% and >65% of patients have improvement in tone and spasms, respectively. The main risks of intrathecal baclofen infusion are symptoms related to overdose or withdrawal; the latter is more important because of the associated severe effects on clinical status and the possibility of death, but it is responsive to rapid treatment. Overdose primarily arises from drug test doses or human error during refill and programming of the pump, and withdrawal most commonly occurs as a result of a problem with the delivery system.

Since the adverse consequences do not exceed the benefits of oral and intrathecal baclofen for patients with spinal spasticity, the benefit/risk assessment is favourable.

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References

  1. Walter JS, Sacks J, Othman R, et al. A database of self-reported secondary medical problems among VA spinal cord injury patients: its role in clinical care and management. J Rehabil Res Dev 2002 Jan-Feb; 39(1): 53–61

    PubMed  Google Scholar 

  2. Noreau L, Proulx P, Gagnon L, et al. Secondary impairments after spinal cord injury: a population-based study. Am J Phys Med Rehabil 2000 Nov-Dec; 79(6): 526–35

    Article  PubMed  CAS  Google Scholar 

  3. Daverat P, Petit H, Kemoun G, et al. The long term outcome in 149 patients with spinal cord injury. Paraplegia 1995 Nov; 33(11): 665–8

    Article  PubMed  CAS  Google Scholar 

  4. Knutsdottir S. Spinal cord injuries in Iceland 1973-1989: A follow up study. Paraplegia 1993 Jan; 31(1): 68–72

    Article  PubMed  CAS  Google Scholar 

  5. Gerhart KA, Johnson RL, Whiteneck GG. Health and psychosocial issues of individuals with incomplete and resolving spinal cord injuries. Paraplegia 1992 Apr; 30(4): 282–7

    Article  PubMed  CAS  Google Scholar 

  6. Maynard FM, Karunas RS, Waring III WP. Epidemiology of spasticity following traumatic spinal cord injury. Arch Phys Med Rehabil 1990 Jul; 71(8): 566–9

    PubMed  CAS  Google Scholar 

  7. Barolat G, Maiman DJ. Spasms in spinal cord injury: a study of 72 subjects. J Am Paraplegia Soc 1987 Jul-Oct; 10(2): 35–9

    PubMed  CAS  Google Scholar 

  8. Johnson RL, Gerhart KA, McCray J, et al. Secondary conditions following spinal cord injury in a population-based sample. Spinal Cord 1998 Jan; 36(1): 45–50

    Article  PubMed  CAS  Google Scholar 

  9. Anson CA, Shepherd C. Incidence of secondary complications in spinal cord injury. Int J Rehabil Res 1996 Mar; 19(1): 55–66

    Article  PubMed  CAS  Google Scholar 

  10. Levic ZM, Dujmovic I, Pekmezovic T, et al. Prognostic factors for survival in multiple sclerosis. Mult Scler 1999 Jun; 5(3): 171–8

    PubMed  CAS  Google Scholar 

  11. Goodin DS. Survey of multiple sclerosis in northern California. Northern California MS Study Group. Mult Scler 1999 Apr; 5(2): 78–88

    PubMed  CAS  Google Scholar 

  12. Pirotte B, Heilporn A, Joffroy A, et al. Chronic intrathecal baclofen in severely disabling spasticity: selection, clinical assessment and long-term benefit. Acta Neurol Belg 1995 Dec; 95(4): 216–25

    PubMed  CAS  Google Scholar 

  13. Abbruzzese G. The medical management of spasticity. Eur J Neurol 2002 May; 9Suppl. 1: 30–4

    Article  PubMed  Google Scholar 

  14. Burchiel KJ, Hsu FP. Pain and spasticity after spinal cord injury: mechanisms and treatment. Spine 2001 Dec 15; 26(24 Suppl.): S146–60

    Article  PubMed  CAS  Google Scholar 

  15. Schapiro RT. Management of spasticity, pain, and paroxysmal phenomena in multiple sclerosis. Curr Neurol Neurosci Rep 2001 May; 1(3): 299–302

    Article  PubMed  CAS  Google Scholar 

  16. Elovic E. Principles of pharmaceutical management of spastic hypertonia. Phys Med Rehabil Clin N Am 2001 Nov; 12(4): 793–816, vii

    PubMed  CAS  Google Scholar 

  17. Metz L. Multiple sclerosis: symptomatic therapies. Semin Neurol 1998; 18(3): 389–95

    Article  PubMed  CAS  Google Scholar 

  18. Paisley S, Beard S, Hunn A, et al. Clinical effectiveness of oral treatments for spasticity in multiple sclerosis: a systematic review. Mult Scler 2002 Aug; 8(4): 319–29

    Article  PubMed  CAS  Google Scholar 

  19. Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2001: CD001332

    Google Scholar 

  20. Taricco M, Adone R, Pagliacci C, et al. Pharmacological interventions for spasticity following spinal cord injury. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, Cochrane Database Syst Rev 2000: CD001131

    Google Scholar 

  21. Kita M, Goodkin DE. Drugs used to treat spasticity. Drugs 2000 Mar; 59(3): 487–95

    Article  PubMed  CAS  Google Scholar 

  22. Rushton DN, Lloyd AC, Anderson PM. Cost-effectiveness comparison of tizanidine and baclofen in the management of spasticity. Pharmacoeconomics 2002; 20(12): 827–37

    Article  PubMed  CAS  Google Scholar 

  23. Groves L, Shellenberger MK, Davis CS. Tizanidine treatment of spasticity: a meta-analysis of controlled, double-blind, comparative studies with baclofen and diazepam. Adv Ther 1998 Jul-Aug; 15(4): 241–51

    PubMed  CAS  Google Scholar 

  24. Wallace JD. Summary of combined clinical analysis of controlled clinical trials with tizanidine. Neurology 1994 Nov; 44(11 Suppl. 9): S60–8

    PubMed  CAS  Google Scholar 

  25. Pellkofer M, Paulig M. Comparative double-blind study of the effectiveness and tolerance of baclofen, tetrazepam and tizanidine in spastic movement disorders of the lower extremities [in German]. Med Klin 1989 Jan 15; 84(1): 5–8

    CAS  Google Scholar 

  26. Hoogstraten MC, van der Ploeg RJ, vd Burg W, et al. Tizanidine versus baclofen in the treatment of spasticity in multiple sclerosis patients. Acta Neurol Scand 1988 Mar; 77(3): 224–30

    Article  PubMed  CAS  Google Scholar 

  27. Bass B, Weinshenker B, Rice GP, et al. Tizanidine versus baclofen in the treatment of spasticity in patients with multiple sclerosis. Can J Neurol Sci 1988 Feb; 15(1): 15–9

    PubMed  CAS  Google Scholar 

  28. Stien R, Nordal HJ, Oftedal SI, et al. The treatment of spasticity in multiple sclerosis: a double-blind clinical trial of a new antispastic drug tizanidine compared with baclofen. Acta Neurol Scand 1987 Mar; 75(3): 190–4

    Article  PubMed  CAS  Google Scholar 

  29. Smolenski C, Muff S, Smolenski-Kautz S. A double-blind comparative trial of new muscle relaxant, tizanidine (DS 103-282), and baclofen in the treatment of chronic spasticity in multiple sclerosis. Curr Med Res Opin 1981; 7(6): 374–83374-83

    PubMed  CAS  Google Scholar 

  30. Lataste X, Emre M, Davis C, et al. Comparative profile of tizanidine in the management of spasticity. Neurology 1994 Nov; 44(11 Suppl. 9): S53–9

    PubMed  CAS  Google Scholar 

  31. Eyssette M, Rohmer F, Serratrice G, et al. Multi-centre, double-blind trial of a novel antispastic agent, tizanidine, in spasticity associated with multiple sclerosis. Curr Med Res Opin 1988; 10(10): 699–708

    Article  PubMed  CAS  Google Scholar 

  32. From A, Heltberg A. A double-blind trial with baclofen (Lioresal) and diazepam in spasticity due to multiple sclerosis. Acta Neurol Scand 1975 Feb; 51(2): 158–66

    Article  PubMed  CAS  Google Scholar 

  33. Roussan M, Terrence C, Fromm G. Baclofen versus diazepam for the treatment of spasticity and long-term follow-up of baclofen therapy. Pharmatherapeutica 1985; 4(5): 278–84

    PubMed  CAS  Google Scholar 

  34. Lazorthes Y, Sol JC, Sallerin B, et al. The surgical management of spasticity. Eur J Neurol 2002 May; 9Suppl. 1: 35–41

    Article  PubMed  Google Scholar 

  35. Zieglgansberger W, Howe JR, Sutor B. The neuropharmacology of baclofen. In: Muller H, ed. Local-spinal therapy of spasticity. Heidelberg: Springer, 1988: 37–49

    Chapter  Google Scholar 

  36. Davidoff RA. Antispasticity drugs: mechanisms of action. Ann Neurol 1985 Feb; 17(2): 107–16

    Article  PubMed  CAS  Google Scholar 

  37. Pedersen E, Arlien-Soborg P, Grynderup V, et al. Gaba derivative in spasticity. (β- (4-chlorophenyl)-γ-aminobutyric acid, Ciba 34.647-Ba). Acta Neurol Scand 1970; 46(3): 257–66

    Article  PubMed  CAS  Google Scholar 

  38. Polacek L, Schuppen W. Results of four years experience with CIBA 34.647-Ba (Lioresal) in the treatment of multiple sclerosis. In: Birkmeier W, editor. Spasticity: a topical survey. Wien: Huber, 1972: 123–7

    Google Scholar 

  39. Pinto Ode S, Polikar M, Debono G. Results of international clinical trials with Lioresal. Postgrad Med J 1972 Oct; 48:Suppl. 5: 18–25

    PubMed  Google Scholar 

  40. Jones RF, Lance JW. Baclofen (Lioresal) in the long-term management of spasticity. Med J Aust 1976 May 1; 1(18): 654–7

    PubMed  CAS  Google Scholar 

  41. Feldman RG, Kelly-Hayes M, Conomy JP, et al. Baclofen for spasticity in multiple sclerosis: double-blind crossover and three-year study. Neurology 1978 Nov; 28(11): 1094–8

    Article  PubMed  CAS  Google Scholar 

  42. Duncan GW, Shahani BT, Young RR. An evaluation of baclofen treatment for certain symptoms in patients with spinal cord lesions: a double-blind, cross-over study. Neurology 1976 May; 26(5): 441–6

    Article  PubMed  CAS  Google Scholar 

  43. Sachais BA, Logue JN, Carey MS. Baclofen, a new antispastic drug: a controlled, multicenter trial in patients with multiple sclerosis. Arch Neurol 1977 Jul; 34(7): 422–8

    Article  PubMed  CAS  Google Scholar 

  44. Sawa GM, Paty DW. The use of baclofen in treatment of spasticity in multiple sclerosis. Can J Neurol Sci 1979 Aug; 6(3): 351–4

    PubMed  CAS  Google Scholar 

  45. Hinderer SR, Lehmann JF, Price R, et al. Spasticity in spinal cord injured persons: quantitative effects of baclofen and placebo treatments. Am J Phys Med Rehabil 1990 Dec; 69(6): 311–7

    Article  PubMed  CAS  Google Scholar 

  46. Hinderer SR. The supraspinal anxiolytic effect of baclofen for spasticity reduction. Am J Phys Med Rehabil 1990 Oct; 69(5): 254–8

    Article  PubMed  CAS  Google Scholar 

  47. Orsnes GB, Sorensen PS, Larsen TK, et al. Effect of baclofen on gait in spastic MS patients. Acta Neurol Scand 2000 Apr; 101(4): 244–8

    Article  PubMed  CAS  Google Scholar 

  48. Levine IM, Jossmann PB, DeAngelis V. Lioresal, a new muscle relaxant in the treatment of spasticity: a double-blind quantitative evaluation. Dis Nerv Syst 1977 Dec; 38(12): 1011–5

    PubMed  CAS  Google Scholar 

  49. Basmajian JV, Yucel V. Effects of a GABA: derivative (BA-34647) on spasticity: preliminary report of a double-blind cross-over study. Am J Phys Med 1974 Oct; 53(5): 223–8

    PubMed  CAS  Google Scholar 

  50. Brar SP, Smith MB, Nelson LM, et al. Evaluation of treatment protocols on minimal to moderate spasticity in multiple sclerosis. Arch Phys Med Rehabil 1991 Mar; 72(3): 186–9

    PubMed  CAS  Google Scholar 

  51. Smith CR, LaRocca NG, Giesser BS, et al. High-dose oral baclofen: experience in patients with multiple sclerosis. Neurology 1991 Nov; 41(11): 1829–31

    Article  PubMed  CAS  Google Scholar 

  52. Nance PW, Bugaresti J, Shellenberger K, et al. Efficacy and safety of tizanidine in the treatment of spasticity in patients with spinal cord injury: North American Tizanidine Study Group. Neurology 1994 Nov; 44(11 Suppl. 9): S44–51

    PubMed  CAS  Google Scholar 

  53. Cartlidge NE, Hudgson P, Weightman D. A comparison of baclofen and diazepam in the treatment of spasticity. J Neurol Sci 1974 Sep; 23(1): 17–24

    Article  PubMed  CAS  Google Scholar 

  54. Krach LE. Pharmacotherapy of spasticity: oral medications and intrathecal baclofen. J Child Neurol 2001 Jan; 16(1): 31–6

    Article  PubMed  CAS  Google Scholar 

  55. Gomar C, Carrero EJ. Delayed arousal after general anesthesia associated with baclofen. Anesthesiology. 1994 Nov; 81(5): 1306–7

    Article  PubMed  CAS  Google Scholar 

  56. Schutter N, Verhaar HJ, Ottervanger JP. Intestinal pseudo-obstruction during use of baclofen [in Dutch]. Ned Tijdschr Geneeskd 1995 Sep 16; 139(37): 1891–3

    PubMed  CAS  Google Scholar 

  57. Terrence CF, Fromm GH, Roussan MS. Baclofen: its effect on seizure frequency. Arch Neurol 1983 Jan; 40(1): 28–9

    Article  PubMed  CAS  Google Scholar 

  58. Terrence CF, Fromm GH. Complications of baclofen withdrawal. Arch Neurol 1981 Sep; 38(9): 588–9

    Article  PubMed  CAS  Google Scholar 

  59. Barker I, Grant IS. Convulsions after abrupt withdrawal of baclofen. Lancet 1982 Sep 4; II(8297): 556–7

    Article  Google Scholar 

  60. Kofler M, Arturo Leis A. Prolonged seizure activity after baclofen withdrawal. Neurology 1992 Mar; 42(3 Pt 1): 697–8

    PubMed  CAS  Google Scholar 

  61. Rivas DA, Chancellor MB, Hill K, et al. Neurological manifestations of baclofen withdrawal. J Urol 1993 Dec; 150(6): 1903–5

    PubMed  CAS  Google Scholar 

  62. Ratnayaka BD, Dhaliwal H, Watkin S. Drug points: neonatal convulsions after withdrawal of baclofen. BMJ 2001 Jul 14; 323(7304): 85

    Article  PubMed  CAS  Google Scholar 

  63. Swartzwelder HS, Sutch CP, Wilson WA. Attenuation of epileptiform bursting by baclofen: reduced potency in elevated potassium. Exp Neurol 1986 Dec; 94(3): 726–34

    Article  PubMed  CAS  Google Scholar 

  64. Saito K, Konishi S, Otsuka M. Antagonism between Lioresal and substance P in rat spinal cord. Brain Res 1975 Oct 24; 97(1): 177–80

    Article  PubMed  CAS  Google Scholar 

  65. Yassa RY, Iskandar HL. Baclofen-induced psychosis: two cases and a review. J Clin Psychiatry 1988 Aug; 49(8): 318–20

    PubMed  CAS  Google Scholar 

  66. White WB. Aggravated CNS depression with urinary retention secondary to baclofen administration. Arch Intern Med 1985 Sep; 145(9): 1717–8

    Article  PubMed  CAS  Google Scholar 

  67. Kirubakaran V, Mayfield D, Rengachary S. Dyskinesia and psychosis in a patient following baclofen withdrawal. Am J Psychiatry 1984 May; 141(5): 692–3

    PubMed  CAS  Google Scholar 

  68. Swigar ME, Bowers MB. Baclofen withdrawal and neuropsychiatric symptoms: a case report and review of other case literature. Compr Psychiatry 1986 Jul-Aug; 27(4): 396–400

    Article  PubMed  CAS  Google Scholar 

  69. Harrison SA, Wood Jr CA. Hallucinations after preoperative baclofen discontinuation in spinal cord injury patients. Drug Intell Clin Pharm 1985 Oct; 19(10): 747–9

    PubMed  CAS  Google Scholar 

  70. Skausig OB, Korsgaard S. Hallucinations and baclofen [letter]. Lancet 1977 Jun 11; I(8024): 1258

    Article  Google Scholar 

  71. Liu HC, Tsai SC, Liu TY, et al. Baclofen-induced frontal lobe syndrome: case report. Paraplegia 1991 Oct; 29(8): 554–6

    Article  PubMed  CAS  Google Scholar 

  72. Roy CW, Wakefield IR. Baclofen pseudopsychosis: case report. Paraplegia 1986 Oct; 24(5): 318–21

    Article  PubMed  CAS  Google Scholar 

  73. Hachen HJ, Krucker V. Clinical and laboratory assessment of the efficacy of baclofen (Lioresal) on urethral sphincter spasticity in patients with traumatic paraplegia. Eur Urol 1977; 3(4): 237–40

    PubMed  CAS  Google Scholar 

  74. Wolf ME, Almy G, Toll M, et al. Mania associated with the use of baclofen. Biol Psychiatry 1982 Jun; 17(6): 757–9

    PubMed  CAS  Google Scholar 

  75. Stewart JT. A case of mania associated with high-dose baclofen therapy. J Clin Psychopharmacol 1992 Jun; 12(3): 215–7

    PubMed  CAS  Google Scholar 

  76. Ryan DM, Blumenthal FS. Baclofen-induced dyskinesia. Arch Phys Med Rehabil 1993 Jul; 74(7): 766–7

    Article  PubMed  CAS  Google Scholar 

  77. Sandyk R. Orofacial dyskinesia induced by baclofen in a patient with hypothyroidism [letter]. Clin Pharm 1986 Feb; 5(2): 109

    PubMed  CAS  Google Scholar 

  78. Rubin DI, So EL. Reversible akinetic mutism possibly induced by baclofen. Pharmacotherapy 1999 Apr; 19(4): 468–70

    Article  PubMed  CAS  Google Scholar 

  79. Struck TH. Jamais vu episodes in relationship to baclofen treatment: a case report. Arch Phys Med Rehabil 2002 Jun; 83(6): 846–9

    Article  PubMed  Google Scholar 

  80. Lazzarino LG, Nicolai A, Valassi F. Acute transient cerebral intoxication induced by low doses of baclofen. Ital J Neurol Sci 1991 Jun; 12(3): 323–5

    Article  PubMed  CAS  Google Scholar 

  81. Hormes JT, Benarroch EE, Rodriguez M, et al. Periodic sharp waves in baclofen-induced encephalopathy. Arch Neurol 1988 Jul; 45(7): 814–5

    Article  PubMed  CAS  Google Scholar 

  82. Parmar MS. Akinetic mutism after baclofen. Ann Intern Med 1991 Sep 15; 115(6): 499–500

    PubMed  CAS  Google Scholar 

  83. Pauker SL, Brown R. Baclofen-induced catatonia. J Clin Psychopharmacol 1986 Dec; 6(6): 387–8

    Article  PubMed  CAS  Google Scholar 

  84. Zak R, Solomon G, Petito F, et al. Baclofen-induced generalized nonconvulsive status epilepticus. Ann Neurol 1994 Jul; 36(1): 113–4

    Article  PubMed  CAS  Google Scholar 

  85. Mandac BR, Hurvitz EA, Nelson VS. Hyperthermia associated with baclofen withdrawal and increased spasticity. Arch Phys Med Rehabil 1993 Jan; 74(1): 96–7

    PubMed  CAS  Google Scholar 

  86. Turner MR, Gainsborough N. Neuroleptic malignant-like syndrome after abrupt withdrawal of baclofen. J Psychopharmacol 2001 Mar; 15(1): 61–3

    Article  PubMed  CAS  Google Scholar 

  87. Aisen ML, Dietz M, McDowell F, et al. Baclofen toxicity in a patient with subclinical renal insufficiency. Arch Phys Med Rehabil 1994 Jan; 75(1): 109–11

    PubMed  CAS  Google Scholar 

  88. Chen KS, Bullard MJ, Chien YY, et al. Baclofen toxicity in patients with severely impaired renal function. Ann Pharmacother 1997 Nov; 31(11): 1315–20

    PubMed  CAS  Google Scholar 

  89. Mery JP, Kenouch S. Oral baclofen may be effective in patients with spasticity due to spinal cord injury or disease [letter]. Am J Kidney Dis 1987 Oct; 10(4): 326

    PubMed  CAS  Google Scholar 

  90. Himmelsbach FA, Kohler E, Zanker B, et al. Baclofen intoxication in chronic hemodialysis and kidney transplantation. [in German] Dtsch Med Wochenschr 1992 May 8; 117(19): 733–7

    Article  PubMed  CAS  Google Scholar 

  91. Seyfert S, Straschill M. Electroencephalographic changes induced by baclofen. [in German] EEG EMG Z Elektroenzephalogr Elektromyogr Verwandte Geb 1982 Dec; 13(4): 161–6

    PubMed  CAS  Google Scholar 

  92. Lee TH, Chen SS, Su SL, et al. Baclofen intoxication: report of four cases and review of the literature. Clin Neuropharmacol 1992 Feb; 15(1): 56–62

    Article  PubMed  CAS  Google Scholar 

  93. Bassilios N, Launay-Vacher V, Mercadal L, et al. Baclofen neurotoxicity [correction of unerotoxicity] in a chronic haemodialysis patient. Nephrol Dial Transplant 2000 May; 15(5): 715–6

    Article  PubMed  CAS  Google Scholar 

  94. Dahlin PA, George J. Baclofen toxicity associated with declining renal clearance after ibuprofen. Drug Intell Clin Pharm 1984 Oct; 18(10): 805–8

    PubMed  CAS  Google Scholar 

  95. Aisen ML, Dietz MA, Rossi P, et al. Clinical and pharmacokinetic aspects of high dose oral baclofen therapy. J Am Paraplegia Soc 1992 Oct; 15(4): 211–6

    PubMed  CAS  Google Scholar 

  96. Dicpinigaitis PV, Nierman DM, Miller A. Baclofen-induced bronchoconstriction. Ann Pharmacother 1993 Jul-Aug; 27(7-8): 883–4

    PubMed  CAS  Google Scholar 

  97. Ayas NT, Epstein LJ, Lieberman SL, et al. Predictors of loud snoring in persons with spinal cord injury. J Spinal Cord Med 2001 Spring; 24(1): 30–4

    PubMed  CAS  Google Scholar 

  98. Silverglat MJ. Baclofen and tricyclic antidepressants: possible interaction [letter]. JAMA 1981 Oct 9; 246(15): 1659

    Article  PubMed  CAS  Google Scholar 

  99. Stolp-Smith KA, Harmon RL. Drug interactions and spasticity. Arch Phys Med Rehabil 1999 Mar; 80(3): 339–42

    Article  PubMed  CAS  Google Scholar 

  100. Ghose K, Holmes KM, Matthewson K. Complications of baclofen overdosage. Postgrad Med J 1980 Dec; 56(662): 865–7

    Article  PubMed  CAS  Google Scholar 

  101. Lipscomb DJ, Meredith TJ. Baclofen overdose. Postgrad Med J 1980 Feb; 56(652): 108–9

    Article  PubMed  CAS  Google Scholar 

  102. May CR. Baclofen overdose. Ann Emerg Med 1983 Mar; 12(3): 171–3

    Article  PubMed  CAS  Google Scholar 

  103. Perry HE, Wright RO, Shannon MW, et al. Baclofen overdose: drug experimentation in a group of adolescents. Pediatrics 1998 Jun; 101(6): 1045–8

    Article  PubMed  CAS  Google Scholar 

  104. Roberge RJ, Martin TG, Hodgman M, et al. Supraventricular tachyarrhythmia associated with baclofen overdose. J Toxicol Clin Toxicol 1994; 32(3): 291–7

    Article  PubMed  CAS  Google Scholar 

  105. Nugent S, Katz MD, Little TE. Baclofen overdose with cardiac conduction abnormalities: case report and review of the literature. J Toxicol Clin Toxicol 1986; 24(4): 321–8

    Article  PubMed  CAS  Google Scholar 

  106. Weissenborn K, Wilkens H, Hausmann E, et al. Burst suppression EEG with baclofen overdose. Clin Neurol Neurosurg 1991; 93(1): 77–80

    Article  PubMed  CAS  Google Scholar 

  107. Peng CT, Ger J, Yang CC, et al. Prolonged severe withdrawal symptoms after acute-on-chronic baclofen overdose. J Toxicol Clin Toxicol 1998; 36(4): 359–63

    Article  PubMed  CAS  Google Scholar 

  108. Wagstaff AJ, Bryson HM. Tizanidine: a review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs 1997 Mar; 53(3): 435–52

    Article  PubMed  CAS  Google Scholar 

  109. Broseta J, Garcia-March G, Sanchez-Ledesma MJ, et al. Chronic intrathecal baclofen administration in severe spasticity. Stereotact Funct Neurosurg 1990; 54–55: 147-53

    Google Scholar 

  110. Pinder RM, Brogden RN, Speight TM, et al. Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity. Drugs 1977 Jan; 13(1): 3–23

    Article  PubMed  CAS  Google Scholar 

  111. Penn RD, Kroin JS. Intrathecal baclofen alleviates spinal cord spasticity [letter]. Lancet 1984 May 12; I(8385): 1078

    Article  Google Scholar 

  112. Porter B. A review of intrathecal baclofen in the management of spasticity. Br J Nurs 1997 Mar 13-26; 6(5): 253–60

    PubMed  CAS  Google Scholar 

  113. Stempien L, Tsai T. Intrathecal baclofen pump use for spasticity: a clinical survey. Am J Phys Med Rehabil 2000 Nov-Dec; 79(6): 536–41

    Article  PubMed  CAS  Google Scholar 

  114. Coffey JR, Cahill D, Steers W, et al. Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study. J Neurosurg 1993 Feb; 78(2): 226–32

    Article  PubMed  CAS  Google Scholar 

  115. Herman RM, D’Luzansky SC, Ippolito R. Intrathecal baclofen suppresses central pain in patients with spinal lesions: a pilot study. Clin J Pain 1992 Dec; 8(4): 338–45

    Article  PubMed  CAS  Google Scholar 

  116. Hugenholtz H, Nelson RF, Dehoux E, et al. Intrathecal baclofen for intractable spinal spasticity: a double-blind cross-over comparison with placebo in 6 patients. Can J Neurol Sci 1992 May; 19(2): 188–95

    PubMed  CAS  Google Scholar 

  117. Loubser PG, Narayan RK, Sandin KJ, et al. Continuous infusion of intrathecal baclofen: long-term effects on spasticity in spinal cord injury. Paraplegia 1991 Jan; 29(1): 48–64

    Article  PubMed  CAS  Google Scholar 

  118. Steers WD, Meythaler JM, Haworth C, et al. Effects of acute bolus and chronic continuous intrathecal baclofen on genitourinary dysfunction due to spinal cord pathology. J Urol 1992 Dec; 148(6): 1849–55

    PubMed  CAS  Google Scholar 

  119. Penn RD. Intrathecal baclofen for spasticity of spinal origin: seven years of experience. J Neurosurg 1992 Aug; 77(2): 236–40

    Article  PubMed  CAS  Google Scholar 

  120. Meythaler JM, Steers WD, Tuel SM, et al. Continuous intrathecal baclofen in spinal cord spasticity: a prospective study. Am J Phys Med Rehabil 1992 Dec; 71(6): 321–7

    Article  PubMed  CAS  Google Scholar 

  121. Parke B, Penn RD, Savoy SM, et al. Functional outcome after delivery of intrathecal baclofen. Arch Phys Med Rehabil 1989 Jan; 70(1): 30–2

    PubMed  CAS  Google Scholar 

  122. Kravitz HM, Corcos DM, Hansen G, et al. Intrathecal baclofen: effects on nocturnal leg muscle spasticity. Am J Phys Med Rehabil 1992 Feb; 71(1): 48–52

    Article  PubMed  CAS  Google Scholar 

  123. Ochs G, Struppler A, Meyerson BA, et al. Intrathecal baclofen for long-term treatment of spasticity: a multi-centre study. J Neurol Neurosurg Psychiatry 1989 Aug; 52(8): 933–9

    Article  PubMed  CAS  Google Scholar 

  124. Sahuquillo J, Muxi T, Noguer M, et al. Intraspinal baclofen in the treatment of severe spasticity and spasms. Acta Neurochir (Wien) 1991; 110(3-4): 166–73

    Article  CAS  Google Scholar 

  125. Stewart-Wynne EG, Silbert PL, Buffery S, et al. Intrathecal baclofen for severe spasticity: five years experience. Clin Exp Neurol 1991; 28: 244–55244-55

    PubMed  CAS  Google Scholar 

  126. Saltuari L, Kronenberg M, Marosi MJ, et al. Indication, efficiency and complications of intrathecal pump supported baclofen treatment in spinal spasticity. Acta Neurol (Napoli) 1992 Jun; 14(3): 187–94

    CAS  Google Scholar 

  127. Abel NA, Smith RA. Intrathecal baclofen for treatment of intractable spinal spasticity. Arch Phys Med Rehabil 1994 Jan; 75(1): 54–8

    PubMed  CAS  Google Scholar 

  128. Nance P, Schryvers O, Schmidt B, et al. Intrathecal baclofen therapy for adults with spinal spasticity: therapeutic efficacy and effect on hospital admissions. Can J Neurol Sci 1995 Feb; 22(1): 22–9

    PubMed  CAS  Google Scholar 

  129. Becker WJ, Harris CJ, Long ML, et al. Long-term intrathecal baclofen therapy in patients with intractable spasticity. Can J Neurol Sci 1995 Aug; 22(3): 208–17

    PubMed  CAS  Google Scholar 

  130. Azouvi P, Mane M, Thiebaut JB, et al. Intrathecal baclofen administration for control of severe spinal spasticity: functional improvement and long-term follow-up. Arch Phys Med Rehabil 1996 Jan; 77(1): 35–9

    Article  PubMed  CAS  Google Scholar 

  131. Middel B, Kuipers-Upmeijer H, Bouma J, et al. Effect of intrathecal baclofen delivered by an implanted programmable pump on health related quality of life in patients with severe spasticity. J Neurol Neurosurg Psychiatry 1997 Aug; 63(2): 204–9

    Article  PubMed  CAS  Google Scholar 

  132. Gianino JM, York MM, Paice JA, et al. Quality of life: effect of reduced spasticity from intrathecal baclofen. J Neurosci Nurs 1998 Feb; 30(1): 47–54

    Article  PubMed  CAS  Google Scholar 

  133. Lazorthes Y, Sallerin B, Verdie JC, et al. Treatment of spasticity with the intrathecal administration of baclofen [in French]. Neurochirurgie 1998 Sep; 44(3): 201–8

    PubMed  CAS  Google Scholar 

  134. Vidal J, Fenollosa P, Martin E, et al. Safety and efficacy of intrathecal baclofen infusion by implantable pump for the treatment of severe spinal spasticity: a spanish multicenter study. Neuromodulation 2000; 3(4): 175–82

    Article  PubMed  Google Scholar 

  135. Dario A, Scamoni C, Bono G, et al. Functional improvement in patients with severe spinal spasticity treated with chronic intrathecal baclofen infusion. Funct Neurol 2001 Oct-Dec; 16(4): 311–5

    PubMed  CAS  Google Scholar 

  136. Ordia JI, Fischer E, Adamski E, et al. Continuous intrathecal baclofen infusion by a programmable pump in 131 consecutive patients with severe spasticity of spinal origin. Neuromodulation 2002; 5(1): 16–24

    Article  PubMed  Google Scholar 

  137. Korenkov AI, Niendorf WR, Darwish N, et al. Continuous intrathecal infusion of baclofen in patients with spasticity caused by spinal cord injuries. Neurosurg Rev 2002 Aug; 25(4): 228–30

    Article  PubMed  Google Scholar 

  138. Staal C, Arends A, Ho S. A self-report of quality of life of patients receiving intrathecal baclofen therapy. Rehabil Nurs 2003 Sep-Oct; 28(5): 159–63

    Article  PubMed  Google Scholar 

  139. Beard S, Hunn A, Wight J. Treatments for spasticity and pain in multiple sclerosis: a systematic review. Health Technol Assess. 2003; 7(40): iii, ix–x, 1-111

    Google Scholar 

  140. Campbell SK, Almeida GL, Penn RD, et al. The effects of intrathecally administered baclofen on function in patients with spasticity. Phys Ther 1995 May; 75(5): 352–62

    PubMed  CAS  Google Scholar 

  141. Broggi G, Servello D, Broch S, et al. The treatment of spasticity by intrathecal administration of baclofen: a preliminary personal experience. J Neurosurg Sci 1993 Dec; 37(4): 203–8

    PubMed  CAS  Google Scholar 

  142. Patterson V, Watt M, Byrnes D, et al. Management of severe spasticity with intrathecal baclofen delivered by a manually operated pump. J Neurol Neurosurg Psychiatry 1994 May; 57(5): 582–5

    Article  PubMed  CAS  Google Scholar 

  143. Mertens P, Parise M, Garcia-Larrea L, et al. Long-term clinical, electrophysiological and urodynamic effects of chronic intrathecal baclofen infusion for treatment of spinal spasticity. Acta Neurochir Suppl (Wien) 1995; 64: 17–25

    Article  CAS  Google Scholar 

  144. Burns AS, Meythaler JM. Intrathecal baclofen in tetraplegia of spinal origin: efficacy for upper extremity hypertonia. Spinal Cord 2001 Aug; 39(8): 413–9

    Article  PubMed  CAS  Google Scholar 

  145. Rode G, Mertens P, Beneton C, et al. Regression of vasomotor disorders under intrathecal baclofen in a case of spastic paraplegia. Spinal Cord 1999 May; 37(5): 370–2

    Article  PubMed  CAS  Google Scholar 

  146. Dressnandt J, Conrad B. Lasting reduction of severe spasticity after ending chronic treatment with intrathecal baclofen. J Neurol Neurosurg Psychiatry 1996 Feb; 60(2): 168–73

    Article  PubMed  CAS  Google Scholar 

  147. Postma TJ, Oenema D, Terpstra S, et al. Cost analysis of the treatment of severe spinal spasticity with a continuous intrathecal baclofen infusion system. Pharmacoeconomics 1999 Apr; 15(4): 395–404

    Article  PubMed  CAS  Google Scholar 

  148. Sampson FC, Hayward A, Evans G, et al. Functional benefits and cost/benefit analysis of continuous intrathecal baclofen infusion for the management of severe spasticity. J Neurosurg 2002 Jun; 96(6): 1052–7

    Article  PubMed  Google Scholar 

  149. Sabbe MB, Grafe MR, Pfeifer BL, et al. Toxicology of baclofen continuously infused into the spinal intrathecal space of the dog. Neurotoxicology 1993 Winter; 14(4): 397–410

    PubMed  CAS  Google Scholar 

  150. Denys P, Mane M, Azouvi P, et al. Side effects of chronic intrathecal baclofen on erection and ejaculation in patients with spinal cord lesions. Arch Phys Med Rehabil 1998 May; 79(5): 494–6

    Article  PubMed  CAS  Google Scholar 

  151. Kofler M, Matzak H, Saltuari L. The impact of intrathecal baclofen on gastrointestinal function. Brain Inj 2002 Sep; 16(9): 825–36

    Article  PubMed  Google Scholar 

  152. Murphy NA. Deep venous thrombosis as a result of hypotonia secondary to intrathecal baclofen therapy: a case report. Arch Phys Med Rehabil 2002 Sep; 83(9): 1311–2

    Article  PubMed  Google Scholar 

  153. Silbert PL, Stewart-Wynne EG. Increased dystonia after intrathecal baclofen. Neurology 1991 Jul; 41(7): 1141–2

    Article  Google Scholar 

  154. Wu SS, Dolan KA, Michael Ferrante F. Febrile reaction to subarachnoid baclofen administration. Anesthesiology 2002 May; 96(5): 1270–2

    Article  PubMed  Google Scholar 

  155. Lyew MA, Mondy C, Eagle S, et al. Hemodynamic instability and delayed emergence from general anesthesia associated with inadvertent intrathecal baclofen overdose. Anesthesiology.2003 Jan; 98(1): 265–8

    Article  PubMed  Google Scholar 

  156. Delhaas EM, Verhagen J. Pregnancy in a quadriplegic patient treated with continuous intrathecal baclofen infusion to manage her severe spasticity: case report. Paraplegia 1992 Jul; 30(7): 527–8

    Article  PubMed  CAS  Google Scholar 

  157. Munoz FC, Marco DG, Perez AV, et al. Pregnancy outcome in a woman exposed to continuous intrathecal baclofen infusion [letter]. Ann Pharmacother 2000 Jul-Aug; 34(7-8): 956

    Article  PubMed  CAS  Google Scholar 

  158. Roberts AG, Graves CR, Konrad PE, et al. Intrathecal baclofen pump implantation during pregnancy. Neurology. 2003 Oct 28; 61(8): 1156–7

    Article  PubMed  CAS  Google Scholar 

  159. Akman MN, Loubser PG, Donovan WH, et al. Intrathecal baclofen: does tolerance occur? Paraplegia 1993 Aug; 31(8): 516–20

    Article  PubMed  CAS  Google Scholar 

  160. Nielsen JF, Hansen HJ, Sunde N, et al. Evidence of tolerance to baclofen in treatment of severe spasticity with intrathecal baclofen. Clin Neurol Neurosurg 2002 May; 104(2): 142–5

    Article  PubMed  Google Scholar 

  161. Vidal J, Gregori P, Guevara D, et al. Efficacy of intrathecal morphine in the treatment of baclofen tolerance in a patient on intrathecal baclofen therapy (ITB). Spinal Cord. 2004 Jan; 42(1): 50–1

    Article  PubMed  CAS  Google Scholar 

  162. Soni BM, Mani RM, Oo T, et al. Treatment of spasticity in a spinal cord-injured patient with intrathecal morphine due to intrathecal baclofen tolerance— a case report and review of literature. Spinal Cord. 2003 Oct; 41(10): 586–9

    Article  PubMed  CAS  Google Scholar 

  163. Garabedian-Ruffalo SM, Ruffalo RL. Adverse effects secondary to baclofen withdrawal. Drug Intell Clin Pharm 1985 Apr; 19(4): 304–6

    PubMed  CAS  Google Scholar 

  164. Dressnandt J, Weinzierl FX, Tolle TR, et al. Acute overdose of intrathecal baclofen. J Neurol 1996 Jun; 243(6): 482–3

    Article  PubMed  CAS  Google Scholar 

  165. Romijn JA, van Lieshout JJ, Velis DN. Reversible coma due to intrathecal baclofen [letter]. Lancet 1986 Sep 20; II(8508): 696

    Article  Google Scholar 

  166. Delhaas EM, Brouwers JR. Intrathecal baclofen overdose: report of 7 events in 5 patients and review of the literature. Int J Clin Pharmacol Ther Toxicol 1991 Jul; 29(7): 274–80

    PubMed  CAS  Google Scholar 

  167. Chabal C, Jacobson L, Terman G. Intrathecal fentanyl alleviates spasticity in the presence of tolerance to intrathecal baclofen. Anesthesiology 1992 Feb; 76(2): 312–4

    Article  PubMed  CAS  Google Scholar 

  168. Reeves RK, Stolp-Smith KA, Christopherson MW. Hyperthermia, rhabdomyolysis, and disseminated intravascular coagulation associated with baclofen pump catheter failure. Arch Phys Med Rehabil 1998 Mar; 79(3): 353–6

    Article  PubMed  CAS  Google Scholar 

  169. Saltuari L, Marosi MJ, Kofler M, et al. Status epilepticus complicating intrathecal baclofen overdose. Lancet 1992 Feb 8; 339(8789): 373–4

    Article  PubMed  CAS  Google Scholar 

  170. Kofler M, Kronenberg MF, Rifici C, et al. Epileptic seizures associated with intrathecal baclofen application. Neurology 1994 Jan; 44(1): 25–7

    Article  PubMed  CAS  Google Scholar 

  171. Fakhoury T, Abou-Khalil B, Blumenkopf B. EEG changes in intrathecal baclofen overdose: a case report and review of the literature. Electroencephalogr Clin Neurophysiol 1998 Nov; 107(5): 339–42

    Article  PubMed  CAS  Google Scholar 

  172. Kofler M, Saltuari L, Schmutzhard E, et al. Electrophysiological findings in a case of severe intrathecal baclofen overdose. Electroencephalogr Clin Neurophysiol 1992 Jul; 83(1): 83–6

    Article  PubMed  CAS  Google Scholar 

  173. Coffey RJ, Edgar TS, Francisco GE, et al. Abrupt withdrawal from intrathecal baclofen: recognition and management of a potentially life-threatening syndrome. Arch Phys Med Rehabil 2002 Jun; 83(6): 735–41

    Article  PubMed  Google Scholar 

  174. Siegfried RN, Jacobson L, Chabal C. Development of an acute withdrawal syndrome following the cessation of intrathecal baclofen in a patient with spasticity. Anesthesiology 1992 Nov; 77(5): 1048–50

    Article  PubMed  CAS  Google Scholar 

  175. Khorasani A, Peruzzi WT. Dantrolene treatment for abrupt intrathecal baclofen withdrawal. Anesth Analg 1995 May; 80(5): 1054–6

    PubMed  CAS  Google Scholar 

  176. Sampathkumar P, Scanlon PD, Plevak DJ. Baclofen withdrawal presenting as multiorgan system failure. Anesth Analg 1998 Sep; 87(3): 562–3

    PubMed  CAS  Google Scholar 

  177. Al-Khodairy AT, Vuagnat H, Uebelhart D. Symptoms of recurrent intrathecal baclofen withdrawal resulting from drug delivery failure: a case report. Am J Phys Med Rehabil 1999 May-Jun; 78(3): 272–7

    Article  PubMed  CAS  Google Scholar 

  178. Green LB, Nelson VS. Death after acute withdrawal of intrathecal baclofen: case report and literature review. Arch Phys Med Rehabil 1999 Dec; 80(12): 1600–4

    Article  PubMed  CAS  Google Scholar 

  179. Ng WK, Winkelmann MD, Yablon SA. Rhabdomiolysis and hyperthermia associated with intracranial baclofen in the absence of pump or catheter defect [abstract]. Am J Phys Med Rehabil 2000; 79: 214

    Article  Google Scholar 

  180. Grenier B, Mesli A, Cales J, et al. Severe hyperthermia caused by sudden withdrawal of continuous intrathecal administration of baclofen [in French]. Ann Fr Anesth Reanim 1996; 15(5): 659–62

    Article  PubMed  CAS  Google Scholar 

  181. Meinck HM, Tronnier V, Reike K, et al. Intrathecal baclofen treatment for stiff-man syndrome: pump failure may be fatal. Neurology. 1994 Nov; 44(11): 2209–10

    Article  PubMed  CAS  Google Scholar 

  182. Alden TD, Lytle RA, Park TS, et al. Intrathecal baclofen withdrawal: a case report and review of the literature. Childs Nerv Syst 2002 Oct; 18(9-10): 522–5

    Article  PubMed  Google Scholar 

  183. Samson-Fang L, Gooch J, Norlin C. Intrathecal baclofen withdrawal simulating neuroepileptic malignant syndrome in a child with cerebral palsy. Dev Med Child Neurol 2000 Aug; 42(8): 561–5

    Article  PubMed  CAS  Google Scholar 

  184. Colachis SC, Rea GL. Monitoring of creatinine kinase during weaning of intrathecal baclofen and with symptoms of early withdrawal. Am J Phys Med Rehabil. 2003 Jun; 82(6): 489–92

    PubMed  Google Scholar 

  185. Greenberg MI, Hendrickson RG. Baclofen withdrawal following removal of an intrathecal baclofen pump despite oral baclofen replacement. J Toxicol Clin Toxicol. 2003; 41(1): 83–5

    Article  PubMed  Google Scholar 

  186. Kao LW, Amin Y, Kirk MA, et al. Intrathecal baclofen withdrawal mimicking sepsis. J Emerg Med. 2003 May; 24(4): 423–7

    Article  PubMed  Google Scholar 

  187. Meythaler JM, Roper JF, Brunner RC. Cyproheptadine for intrathecal baclofen withdrawal. Arch Phys Med Rehabil. 2003 May; 84(5): 638–42

    Article  PubMed  Google Scholar 

  188. Medtronic Drug Delivery Inc. Important drug warning: Lioresal® intrathecal (baclofen injection). Available from URL: http://www.fda.gov/medwatchSafety/2002/Baclofen.pdf [Accessed 2002 Mar

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    Alessandro Dario & Giustino Tomei

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Dario, A., Tomei, G. A Benefit-Risk Assessment of Baclofen in Severe Spinal Spasticity. Drug-Safety 27, 799–818 (2004). https://doi.org/10.2165/00002018-200427110-00004

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