Advertisement

Pharmaceutisch Weekblad

, Volume 9, Issue 5, pp 249–260 | Cite as

Spasticity and drug therapy

  • E. W. Wuis
Review Articles

Abstract

An overview is presented of pathophysiology, classification and measurement of spasticity and of its treatment, especially with dantrolene and baclofen. In spasticity, the balance between excitatory and inhibitory neurotransmitters in the central nervous system is impaired by mechanisms that are for the greater part unknown. Spasticity includes various disorders of motor control, and classification is needed for a meaningful evaluation of antispastic therapy. Cerebral palsy is a specific disorder, sometimes also called spasticity. Measurement of spasticity is complicated and should include signs characteristic of spasticity and parameters for clinical improvement. Dantrolene and baclofen have established their place in the treatment of spastic disorders, but a preference for either drug is hard to give. For tizanidine it is still too early to determine its place in therapy. Dantrolene is a direct acting muscle relaxant which should be avoided in patients with pre-existing liver damage. Its mechanism of metabolism and excretion is for the greater part unknown. The GABA b agonist baclofen is a centrally acting muscle relaxant. In patients with impaired renal function the dose should be reduced. Abrupt withdrawal carries the risk of unwanted reactions. TheR(−)-enantiomer has proved to be the active isomer. This means that human trials need reappraisal, especially those relating to the pharmacokinetics of the racemate.

Key words

Baclofen Cerebral palsy Dantrolene Drug therapy Muscle relaxants Pathology Spasticity Tizanidine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lataste X. Spasticity. Sandorama, 1984/1.Google Scholar
  2. 2.
    Feldman RG, Young RR, Koella WP, eds. Spasticity: disordered motor control. Chicago: Year Book Medical Publishers, 1980.Google Scholar
  3. 3.
    Paneth N. Birth and the origins of cerebral palsy. N Engl J Med 1986;315:124–6.PubMedGoogle Scholar
  4. 4.
    Anonymous. Zorg voor de spastische patiënt vandaag en morgen. Onderzoek naar het aantal spastici in Nederland [Care of the spastic patient today and tomorrow. Investigation into the number of spastics in the Netherlands]. Bussum: Dr. W.M. Phelps-Stichting voor Spastici, 1982.Google Scholar
  5. 5.
    Young RR, Delwaide PJ. Spasticity. N Engl J Med 1981;304:28–33,96–9.PubMedGoogle Scholar
  6. 6.
    Delwaide PJ, Young RR, eds. Clinical neurophysiology in spasticity. Amsterdam: Elsevier, 1985.Google Scholar
  7. 7.
    Pedersen E. Spasticity. Mechanism, measurement, management. Springfield: Charles C. Thomas Publisher, 1969.Google Scholar
  8. 8.
    Knutsson E. Antispastic medication. Scand J Rehabil Med 1980;7:80–4.Google Scholar
  9. 9.
    De Vries JS. Spastische kinderen (infantiele encefalopathie) [Spastic children (cerebral palsy)]. 2nd ed. Leiden: Stafleu's Wetenschappelijke Uitgeversmaatschappij, 1977.Google Scholar
  10. 10.
    Ashworth B. Preliminary trial of carisoprodol in multiple sclerosis. Practitioner 1964;192:540–2.PubMedGoogle Scholar
  11. 11.
    Meyler WJ. Pharmacological studies of dantrolene sodium, a muscle relaxant for the treatment of spasticity. Groningen: State University of Groningen, 1978. Dissertation.Google Scholar
  12. 12.
    Grynderup V. A comparison of some rating systems in multiple sclerosis. Acta Neurol Scand 1969;45:611–22.PubMedGoogle Scholar
  13. 13.
    Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md State Med J 1965;14:61–5.Google Scholar
  14. 14.
    Gresham GE, Phillips TF, Labi MLC. ADL status in stroke: relative merits of three standard indexes. Arch Phys Med Rehabil 1980;61:355–8.PubMedGoogle Scholar
  15. 15.
    Postema K. Spastische parese bij infantiele encephalopathie [Spastic paresis in cerebral palsy]. Amsterdam: Free University, 1983. Dissertation.Google Scholar
  16. 16.
    Delwaide PJ. Electrophysiological analysis of the mode of action of muscle relaxants in spasticity. Ann Neurol 1985;17:90–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Jukes AM, ed. Baclofen: spasticity and cerebral pathology. Northampton: Cambridge Medical Publications Ltd., 1978.Google Scholar
  18. 18.
    Banham KM. Measuring functional motor rehabilitation of cerebral palsied infants and young children. Rehabil Lit 1978;39:111–5.PubMedGoogle Scholar
  19. 19.
    Bobath K. The motor deficit in patients with cerebral palsy. London: W. Heinemann Medical Books Ltd., 1966.Google Scholar
  20. 20.
    Domino EF. Centrally acting skeletal-muscle relaxants. Arch Phys Med Rehabil 1974;55:369–73.PubMedGoogle Scholar
  21. 21.
    Berger FM, Bradley W. The pharmacological properties of α:β-dihydroxy-γ-(2-methylphenoxy)-propane (Myanesin). Br J Pharmacol 1946;1:265–72.Google Scholar
  22. 22.
    Berger FM. Pharmacological properties of 2-methyl-2-n-propyl-1,3-propanediol dicarbamate (Miltown), a new interneuronal blocking agent. J Pharmacol Exp Ther 1954;112:413–23.PubMedGoogle Scholar
  23. 23.
    Randell LO. Pharmacology of chlordiazepoxide (Librium). Dis Nerv System 1961;22(suppl):7–15.Google Scholar
  24. 24.
    Birkmayer W, Danielczyk W, Weiler G. Zur Objektivierbarkeit des myotonolytischen Effektes eines Aminobuttersäurederivates (CIBA 34647-Ba). Wien Med Wochenschr 1967;117:7–9.PubMedGoogle Scholar
  25. 25.
    Ringwald E, Campean SJ, Gerstenbrand F, Lorincz A, Lorincz P, Ludin HP. Klinische Erfahrungen mit einem neuartigen Myotonolytikum (DS 103–282 Sandoz). Nervenarzt 1977;48:355–8.PubMedGoogle Scholar
  26. 26.
    Conrad B. Benecke R, Bauer HJ, eds. Die klinische Wertung der Spastizität. Stuttgart: Schattauer Verlag, 1984.Google Scholar
  27. 27.
    Newman PM, Nogues M, Newman PK, Weightman D, Hudgson P. Tizanidine in the treatment of spasticity. Eur J Clin Pharmacol 1982;23:31–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Snyder HR Jr, Davis CS, Bickerton RK, Halliday RP. 1-[(5-arylfurfurylidene)amino] hydantoins. A new class of muscle relaxants. J Med Chem 1967;10:807–10.CrossRefPubMedGoogle Scholar
  29. 29.
    Cohan SL, Raines A, Panagakos J, Armitage P. Phenytoin and chlorpromazine in the treatment of spasticity. Arch Neurol 1980;37:360–4.PubMedGoogle Scholar
  30. 30.
    Inotsume N, Nakano M. Hydrolytic behaviour of dantrolene in acidic media at body temperature. Int J Pharm 1983;17:357–60.CrossRefGoogle Scholar
  31. 31.
    Faling LJ, Petusevsky ML, Snider GL. Nitrofurantoin and dantrolene; liver and lung. Ann Intern Med 1980;93:151.Google Scholar
  32. 32.
    Ellis KO, Wessels FL. The pharmacology of clodanolene sodium, a new skeletal muscle contraction antagonist. Arzneimittelforsch 1978;28:1100–5.PubMedGoogle Scholar
  33. 33.
    Sullivan JS, Galloway GJ, Denborough MA. Clodanolene sodium and malignant hyperpyrexia. Br J Anaesth 1982;54:1237.Google Scholar
  34. 34.
    Ward A, Chaffman MO, Sorkin EM. Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update on its use in muscle spasticity. Drugs 1986;32:130–68.PubMedGoogle Scholar
  35. 35.
    Arnold TH Jr, Epps JM, Cook HR, Hamrick ME. Dantrolene sodium: urinary metabolites and hepatotoxicity. Res Comm Chem Pathol Pharmacol 1983;39:381–8.Google Scholar
  36. 36.
    White RL Jr, Wessels FL, Schwan TJ, Ellis KO. 1-[[[5-(Substituted phenyl)-2-oxazolyl]methylene] amino]-2,4-imidazolidinones, a new class of skeletal muscle relaxants. J Med Chem 1987;30:263–6.CrossRefPubMedGoogle Scholar
  37. 37.
    Leslie GC, Part NJ. The effect of dantrolene sodium on intrafusal muscle fibers in the rat soleus muscle. J Physiol 1981;318:73–83.PubMedGoogle Scholar
  38. 38.
    Ellis KO, Butterfield JL, Wessels FL, Carpenter JF. A comparison of skeletal, cardiac, and smooth muscle actions of dantrolene sodium — a skeletal muscle relaxant. Arch Int Pharmacodyn Ther 1976;224:118–32.PubMedGoogle Scholar
  39. 39.
    Davidenko J, Delmar M, Oates R, Jalife J. Electrophysiological actions of dantrolene sodium in isolated sinoatrial and atrioventricular nodes and in a model of ischemia. J Pharmacol Exp Ther 1986;238:206–16.PubMedGoogle Scholar
  40. 40.
    Lynch III C, Durbin CG Jr, Fischer NA, Veselis RA, Althaus JS. Effects of dantrolene and verapamil on atrioventricular conduction and cardiovascular performance in dogs. Anesth Analg 1986;65:252–8.PubMedGoogle Scholar
  41. 41.
    Farquhar R, Leslie GC, Part NJ. How is ventilation maintained in the presence of the muscle relaxant, dantrolene sodium? A study in the anaesthesized rat. Br J Pharmacol 1986;88:79–86.PubMedGoogle Scholar
  42. 42.
    Rivera VM, Breitbach WB, Swanke L. Dantrolene in amyotrophic lateral sclerosis. JAMA 1975;233:863–4.CrossRefPubMedGoogle Scholar
  43. 43.
    Watson CB, Reierson N, Norfleet EA. Clinically significant muscle weakness induced by oral dantrolene sodium prophylaxis for malignant hyperthermia. Anesthesiology 1986;65:312–4.PubMedGoogle Scholar
  44. 44.
    Hollifield RD, Conklin JD. A spectrophotofluorimetric procedure for the determination of dantrolene in blood and urine. Arch Int Pharmacodyn Ther 1968;174:333–41.PubMedGoogle Scholar
  45. 45.
    Hollifield RD, Conklin JD. Determination of dantrolene in biological specimens containing drug-related metabolites. J Pharm Sci 1973;62:271–4.PubMedGoogle Scholar
  46. 46.
    Katogi Y, Tamaki N, Adachi M, Terao J, Mitomi M. Simultaneous determination of dantrolene and its metabolite, 5-hydroxydantrolene, in human plasma by high-performance liquid chromatography. J Chromatogr 1982;228:404–8.PubMedGoogle Scholar
  47. 47.
    Wuis EW, Grutters ACLM, Vree TB, Van der Kleijn E. Simultaneous determination of dantrolene and its metabolites, 5-hydroxydantrolene and nitro-reduced acetylated dantrolene (F 490), in plasma and urine of man and dog by high-performance liquid chromatography. J Chromatogr 1982;231:401–9.PubMedGoogle Scholar
  48. 48.
    Wuis EW, Driessen JJ, Evers J, Vree TB, Van der Kleijn E. Dantrolene plasma concentrations after oral pretreatment for malignant hyperthermia: report of a case. Eur J Anaesthesiol 1986;3:219–23.PubMedGoogle Scholar
  49. 49.
    Braude BM, Press P, Moyes DG, Isaacs H, Danilewitz MD, Kolb ME. Unexpected hyperthermia manifesting during outpatient anesthesia. Anesthesiology 1986;64:647–50.PubMedGoogle Scholar
  50. 50.
    Tomonaga F, Kobayashi T, Yago K, et al. Pharmaceutical studies of dantrolene sodium. Masui to Sosei 1979;15:101–8 (via Chemical Abstracts 1980;93:137923).Google Scholar
  51. 51.
    Kuroiwa M, Inotsume N, Iwaoku R, Nakano M. Reduction of dantrolene by enteric bacteria. Yakugaku Zasshi 1985;105:770–4.PubMedGoogle Scholar
  52. 52.
    Wuis EW, Hendriks HJ, Vree TB, Van der Kleijn. E. Pharmacokinetics of dantrolene in man after oral administration [Abstract]. II World Conference on Clinical Pharmacology and Therapeutics, Washington 1983:12.Google Scholar
  53. 53.
    Inotsume N, Higashi A, Matsukane I, Chikazawa S, Nakano M, Matsuda I. Relationship between serum concentration and daily dose of dantrolene in cerebral palsy patients. Pediatr Pharmacol 1986;5:253–9.Google Scholar
  54. 54.
    Nouhnejade P, Maleki S. Distribution and binding of dantrolene sodium in whole body section and fixed isolated organ — fluorescent observation. Arch Histochem Cytochem 1985;18:395–401.Google Scholar
  55. 55.
    Dehpour AR, Mahmoudian M.In vitro binding of dantrolene to bovine serum albumin and rabbit blood cell ghosts. Can J Physiol Pharmacol 1982;60:1307–11.PubMedGoogle Scholar
  56. 56.
    Dehpour AR, Mofakham S, Mahmoudian M.In vitro binding of dantrolene to sarcoplasmic reticulum of rabbit skeletal muscle. Biochem Pharmacol 1982; 31:965–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Roy S, Francis KT, Born CK, Hamrick ME. Interaction of dantrolene with the hepatic mixed function oxidase system. Res Commun Chem Pathol Pharmacol 1980;27:507–20.PubMedGoogle Scholar
  58. 58.
    Wilkie OL. Dantrolene deposited in connective tissue? JAMA 1976;235:1108.CrossRefGoogle Scholar
  59. 59.
    Morison DH. Placental transfer of dantrolene. Anesthesiology 1983;59:265.PubMedGoogle Scholar
  60. 60.
    Ellis KO, Wessels FL. Muscle relaxant properties of the identified metabolites of dantrolene. Naunyn Schmiedebergs Arch Pharmacol 1978;301:237–40.CrossRefPubMedGoogle Scholar
  61. 61.
    Roewer N, Rumberger E, Schulte am Esch J. Effect of 5-hydroxydantrolene on cardiac transmembrane potential and contractility. Anesthesiology 1985;63(suppl 3A): 275.Google Scholar
  62. 62.
    Asari H, Kitamura S, Higuchi S, Urano C. Intravenous dantrolene sodium in normal healthy man. Hiroshima J Anesth 1984;20:255–66.Google Scholar
  63. 63.
    Meyler WJ, Vermeer GA, Agoston S, Wesseling H. Excretion patterns of dantrolene sodium and metabolites in patients with and without cholecystectomy [Abstract]. I World Conference on Clinical Pharmacology and Therapeutics, London, 1980.Google Scholar
  64. 64.
    Chyatte SB, Birdsong JH, Roberson DL. Dantrolene sodium in athetoid cerebral palsy. Arch Phys Med Rehabil 1973;54:365–8.PubMedGoogle Scholar
  65. 65.
    Denhoff E, Feldman S, Smith MG, Litchman H, Holden W. Treatment of spastic cerebral-palsied children with sodium dantrolene. Dev Med Child Neurol 1975;17:736–42.PubMedGoogle Scholar
  66. 66.
    Ford F, Bleck EE, Aptekar RG, Collins FJ, Stevick D. Efficacy of dantrolene sodium in the treatment of spastic cerebral palsy. Dev Med Child Neurol 1976; 18:770–83.Google Scholar
  67. 67.
    Haslam RHA, Walcher JR, Lietman PS, Kallman CH, Mellits ED. Dantrolene sodium in children with spasticity. Arch Phys Med Rehabil 1974;55:384–8.PubMedGoogle Scholar
  68. 68.
    Joynt RL, Leonard JA Jr. Dantrolene sodium suspension in treatment of spastic cerebral palsy. Dev Med Child Neurol 1980;22:755–67.PubMedGoogle Scholar
  69. 69.
    Nogen AG. Medical treatment for spasticity in children with cerebral palsy. Childs Brain 1976;2:304–8.PubMedGoogle Scholar
  70. 70.
    Wolf ME, Keener S, Mathis P, Mosnaim AD. Phenylethylamine-like properties of baclofen. Neuropsychobiology 1983;9:219–22.PubMedGoogle Scholar
  71. 71.
    Hill DR, Bowery NG.3H-baclofen and3H-GABA bind to bicuculline-insensitive GABAb sites in rat brain. Nature 1981;290:149–52.CrossRefPubMedGoogle Scholar
  72. 72.
    Bowery NG. Baclofen: 10 years on. TIPS 1982;4:400–3Google Scholar
  73. 73.
    Riesz M, Erdo SL. GABAB receptors in the rabbit uterus may mediate contractile responses. Eur J Pharmacol 1985;119:199–204.CrossRefPubMedGoogle Scholar
  74. 74.
    Stevens DR, Gallagher JP, Shinnick-Gallagher P. Further studies on the action of baclofen on neurons of the dorsolateral septal nucleus of the rat,in vitro. Brain Res 1985;358:360–3.CrossRefPubMedGoogle Scholar
  75. 75.
    Peet MJ, McLennan H. Pre- and postsynaptic actions of baclofen: blockade of the late synaptically-evoked hyperpolarization of CA1 hippocampal neurons. Exp Brain Res 1986;61:567–74.CrossRefPubMedGoogle Scholar
  76. 76.
    Rägo L, Kiivet R-A, Harro J. Variation in behavioral response to baclofen: correlation with benzodiazepine binding sites in mouse forebrain. Naunyn Schmiedebergs Arch Pharmacol 1986;333:303–6.CrossRefPubMedGoogle Scholar
  77. 77.
    Terrence CF, Sax M, Fromm GH, Chang C-H, Yoo CS. Effect of baclofen enantiomorphs on the spinal trigeminal nucleus and steric similarities of carbamazepine. Pharmacology 1983;27:85–94.PubMedGoogle Scholar
  78. 78.
    Van Rijn CM, Van Berlo MJ, Schoofs MLF, Feenstra MGP, Hommes OR.R(−)-baclofen: focal epilepsy after intracortical administration in the rat. Epil Res (in press).Google Scholar
  79. 79.
    Ault B, Gruenthal M, Armstrong DR, Nadler JV, Wang CM. Baclofen suppresses bursting activity induced in hippocampal slices by differing convulsant treatments. Eur J Pharmacol 1986;126:289–92.CrossRefPubMedGoogle Scholar
  80. 80.
    Levy RA, Proudfit HK. The analgesic action of baclofen [β-(4-chlorophenyl)-γ-aminobutyric acid]. J Pharmacol Exp Ther 1977;202:437–45.PubMedGoogle Scholar
  81. 81.
    Sawynok J. Baclofen activates two distinct receptors in the rat spinal cord and guinea pig ileum. Neuropharmacology 1986;25:795–8.CrossRefPubMedGoogle Scholar
  82. 82.
    Fromm GH, Terrence CF, Chatta AS. Baclofen in the treatment of trigeminal neuralgia: double-blind study and long-term follow-up. Ann Neurol 1984;15:240–4.CrossRefPubMedGoogle Scholar
  83. 83.
    Terrence CF, Fromm GH, Tenicela R. Baclofen as an analgesic in chronic peripheral nerve disease. Eur Neurol 1985;24:380–5.PubMedGoogle Scholar
  84. 84.
    Kochak G, Honc F. Improved gas-liquid Chromatographic method for the determination of baclofen in plasma and urine. J Chromatogr 1984;310:319–26.PubMedGoogle Scholar
  85. 85.
    Wuis EW, Dirks RJM, Vree TB, Van der Kleijn E. High-performance liquid Chromatographic analysis of baclofen in plasma and urine of man after precolumn extraction and derivatization witho-phthaldialdehyde. J Chromatogr 1985;337:341–50.PubMedGoogle Scholar
  86. 86.
    Wuis EW, Van Beijsterveldt LEC, Dirks RJM, Vree TB, Van der Kleijn E. Rapid simultaneous determination of baclofen and its γ-hydroxy metabolite in urine by high-performance liquid chromatography with ultraviolet detection. J Chromatogr 1987;420:212–6.PubMedGoogle Scholar
  87. 87.
    Weatherby RP, Allan RD, Johnston GAR. Resolution of the stereoisomers of baclofen by high performance liquid chromatography. J Neurosci Meth 1984;10:23–8.CrossRefGoogle Scholar
  88. 88.
    Wuis EW, Beneken-Kolmer EWJ, Van Beijsterveldt LEC, Burgers RCM, Vree TB, Van der Kleijn E. Enantioselective high-performance liquid Chromatographic analysis of baclofen after derivatization with a chiral adduct ofo-phthaldialdehyde. J Chromatogr 1987;415:419–22.PubMedGoogle Scholar
  89. 89.
    Faigle JW, Keberle H. The chemistry and kinetics of Lioresal. Postgrad Med J 1972;Oct(suppl):9–13.Google Scholar
  90. 90.
    Peterson GM, McLean S, Millingen KS. Food does not affect the bioavailability of baclofen. Med J Aust 1985;142:689–90.PubMedGoogle Scholar
  91. 91.
    Kochak GM, Rakhit A, Wagner WE, Honc F, Waldes L, Kershaw RA. The pharmacokinetics of baclofen derived from intestinal infusion. Clin Pharmacol Ther 1985;38:251–7.PubMedGoogle Scholar
  92. 92.
    Knutsson E, Lindblom U, Mårtensson A. Plasma and cerebrospinal fluid levels of baclofen (Lioresal®) at optimal therapeutic responses in spastic paresis. J Neurol Sci 1974;23:473–84.CrossRefPubMedGoogle Scholar
  93. 93.
    Eriksson G, Swahn CG. Concentrations of baclofen in serum and breast milk from a lactating woman. Scand J Clin Lab Invest 1981:41:185–7.PubMedGoogle Scholar
  94. 94.
    Seyfert S, Kraft D, Wagner K. Baclofen-Dosis bei Haemodialyse und Nierinsuffizienz. Nervenarzt 1981:52:616–7.PubMedGoogle Scholar
  95. 95.
    Dahlin PA, George J. Baclofen toxicity associated with declining renal clearance after ibuprofen. Drug Intell Clin Pharm 1984:18:805–8.PubMedGoogle Scholar
  96. 96.
    Hulme A, Maclennan WJ, Ritchie RT, John VA, Shotton PA. Baclofen in the elderly stroke patients: its side effects and pharmacokinetics. Eur J Clin Pharmacol 1985:29:467–9.CrossRefPubMedGoogle Scholar
  97. 97.
    Lipscomb DJ, Meredith TJ. Baclofen overdose. Postgrad Med J 1980:56:108–9.PubMedGoogle Scholar
  98. 98.
    Ghose K, Holmes KM, Matthewson K. Complications of baclofen overdose. Postgrad Med J 1980;56:865–7.PubMedGoogle Scholar
  99. 99.
    Anderson P, Nohér H, Swahn CG. Pharmacokinetics in baclofen overdose. Clin Toxicol 1984:22:11–20.Google Scholar
  100. 100.
    McKinlay I, Hyde E, Gordon N. Baclofen: a team approach to drug evaluation of spasticity in childhood. Scot Med J 1980;suppl 1:26–8.Google Scholar
  101. 101.
    Schwartzman JS, Tilbery CP, Kogler E, Gusman S. Effects of Lioresal in cerebral palsy. Folha Med 1976:72:297–302.Google Scholar
  102. 102.
    Birkmayer W, ed. Spasticity — a topical survey. Bern: Hans Huber Publishers, 1972.Google Scholar
  103. 103.
    Müller H, Zierski J, Dralle D, Börner U, Hoffmann O. The effect of intrathecal baclofen on electrical muscle activity in spasticity. J Neurol 1987:234:348–52.CrossRefPubMedGoogle Scholar
  104. 104.
    Romijn JA, Van Lieshout JJ, Velis DN. Reversible coma due to intrathecal baclofen. Lancet 1986:2:696.CrossRefGoogle Scholar
  105. 105.
    Garabedian-Ruffalo SM, Ruffalo RL. Adverse effects secondary to baclofen withdrawal. Drug Intell Clin Pharm 1985:19:304–6.PubMedGoogle Scholar
  106. 106.
    Harrison SA, Wood Jr CA. Hallucinations after preoperative baclofen discontinuation in spinal cord injury patients. Drug Intell Clin Pharm 1985:19:747–9.PubMedGoogle Scholar
  107. 107.
    Terrence CF, Fromm GH. Complications of baclofen withdrawal. Arch Neurol 1981:38:588–9.PubMedGoogle Scholar

Copyright information

© Bohn, Scheltema & Holkema 1987

Authors and Affiliations

  • E. W. Wuis
    • 1
  1. 1.Department of Clinical PharmacySt. Radboud University HospitalGA NijmegenThe Netherlands

Personalised recommendations