Publications about Phenytoin for pain

An overview of publications about Phenytoin for neuropathic pain. Fabry’s Disease, Dysesthesia (Painful Touching), Tabes, Post-Herpetic Neuralgia, Refractory Chronic Pain, Pain in Multiple Sclerose, Reflex Sympathetic Dystrophy, Abdominal Pain, Analgesia.

Neuropathy

  • 3249. Wiffen, P., McQuay, H., Carroll, D., Jadad, A., and Moore, A., Anticonvulsant drugs for the management of acute and chronic pain, Cochrane Database of Systematic Reviews, 4, 1998.
  • 3250. Sindrup, S.H. and Jensen, T.S., Pharmacologic treatment of pain in polyneuropathy, Neurology, 55(7):915-920, 2000.
  • 3251. Ross, E.L., The evolving role of anti-epileptic drugs in treating neuropathic pain, Neurology, 55(S1):S41-S46, 2000.
  • 3252. Tanelian, D.L. and Victory, R.A., Sodium channel-blocking agents, Pain Forum, 4(2):75-80, 1995.
  • 3253. Jensen, T.S., Anticonvulsants in neuropathic pain: Rationale and clinical evidence, Eur. J. Pain, 6:61-68, 2002.
  • 3254. Carter, G.T. and Galer, B.S., Advances in the management of neuropathic pain, Arch. Phys.Med. Rehabil., 12(2):447-459, 2001.
  • 3255. Tremont-Lukats, I.W., Megeff, C. and Backonja, M.M., Anticonvulsants for neuropathic pain syndromes, Drugs, 60(5):1029-52, 2000.
  • 3256. Chojnowska, E., Which intravenous sodium channel blocker for neuropathic pain? (Letter), Anesth. Analg., 90(4):1007-1008, 2000.
  • 3257. Belgrade, M.J. and Lev, B.I., Diabetic neuropathy – helping patients cope with their pain, Postgrad. Med., 90(5): 263-70, 1991.
  • 3258. Thomas, P.K. and Scadding, J.W., Treatment of pain in diabetic neuropathy, Diabetic Neuropathy, 216-22, Dyck, P.J., et al, Eds., W. B. Saunders, Philadelphia, PA, 1987.

Fabry’s Disease

Lockman, Hunninghake, Krivit and Desnick, Neurology (1973),1299 based on a double-blind study, report the effectiveness of PHT in the relief of the pain of Fabry’s  disease, a rare lipid storage disorder. The authors state that the single most debilitating and morbid aspect of Fabry’s disease is the pain.

Excruciating crises of abdominal, chest and muscle pain, as well as arthralgias and fever, may occur episodically and last several days. A double-blind cross over study with eight patients was conducted comparing PHT with aspirin and placebo. In the comparison, relief with PHT was statistically sicnificant (p < 0.0001). The authors note that the pain in Fabry’s disease is only partially relieved by narcotics at soporific doses.

1299. Lockman, L. A., Hunninghake, D. B., Krivit, W., and Desnick, R. J., Relief of pain of Fabry’s disease by diphenylhydantoin, Neurology, 23: 871-875, 1973.

Duperrat, Puissant, Saurat, Delanoe, Doyard and Grunfels, Annales de Dermatologie et de Syphiligraphie (1975),1813 described a twenty-three-year-old male patiënt who from birth had suffered from angiokeratomas and Fabry’s disease. Pain progressed in intensity over the years PHT (200 mg/day) resulted in complete disappearance of pain in less than a week. (See also Ref. 2352.)

1813. Duperrat, B., Puissant, A., Saurat, J. H., Delanoe, J., Doyard, P. A. and Grunfels, J. P., Fabry’s disease neonatal angiokeratomas. Effect of diphenylhydantoin on acute pain episodes, Ann. Derm. Syph. (Paris), 102(4): 392-3, 1975. 2352. Brady, R. O., King, F. M., Fabry’s disease, Peripheral Neuropathy, Vol. 2, Dyck, P. J., et al., Eds., W. B. Saunders Co., Philadelphia, 914-27, 1975.

Kumudchandra and Bernhard, Arthritis and Rheumatism (1979), 3259 describe a twenty-five year-old patiënt with confirmed Fabry disease. This patiënt had experienced joint pains and stiffness of shoulders, wrists, fingers and knees for six years. Salicylates and mild analgesics did not help, but codeine afforded some relief. Oral phenytoin treatment controlled the joint
pains in both the patiënt and his mother, who also required treatment.

3259. Kumudchandra, J.S. and Bernhard, G.C., The arthropathy of Fabry disease, Arthritis Rheum., 22(7): 781-3, 1979.

Dysesthesia (Painful Touching)

Gerz, Physician’s Drug Manual (1972),1066 reports and unusual case of  “painful touching” (dysesthesia) in which a forty-year-old male patiënt showed dramatic response to PHT. The patiënt reported that a painful, intolerable, cold stream would run all over his body when touched by human hands.

Because of t extreme pain on being touched, he frequently became dangerous and violent, and wanted a certificate form the clinic stating that he suffered from a “mental problem.” He was tried on a variety of medications without success. Finally he was given PHT, 100mg t.i.d. within two weeks he was completely free of disturbing symptoms.

1066. Getz, H. O., Dilantin against “painful touching” (dysthesia), Physician’s Drug Manual, 3: 144, 1972

Tabes

Dattner, in the course of a discussion of a paper by Caveness, Adams, Pope and Wegner,Transactions of the American Neurological Association (1949),48 said that some patients with lightning pains in tabes showed a favorable response to PHT or Tridione.

48. Caveness, W., Adams, R. D., Pope, A., and Wegner, W. R., The role of the dorsal root ganglia in the production of the lancinating pains of central nervous system syphilis, Trans. Amer. Neurol. Assn., 60-64, 1949.

Braham and Saia, Lancet (1960),31 reported PHT effective in treating lightning pains in  two cases of tabes.

31. Braham, J. and Saia, A., Phenytoin in the treatment of trigeminal and other neuralgias, Lancet, 2: 892-893, 1960.

Green, Neurology (1961),129 reported that PHT was administered to two patients with severe lightning pains due to tabes dorsalis. Remarkable relief was obtained in both cases.

129. Green, J. B., Dilantin in the treatment of lightning pains, Neurology, 11: 257-258, 1961.

Post-Herpetic Neuralgia

Reeve, Lancet (1961),611 reported that PHT was effective in four cases of post-herpetic neuralgia, and recommended that a trial of PHT precede more radical treatment.

611. Reeve, H. S., Phenytoin in the treatment of trigeminal neuralgia, Lancet, 1: 404, 1961.

Hallaq and Harris, Journal of American Osteopathic Association (1969),1116 give a detailed report on the successful use of PHT in a case of post-herpetic neuralgia, with motor paralysis of an extremity, a rare complication. The patiënt, a seventy-six-year-old woman, had persistent pain in the right upper extremity, causing the entire limb to assume a semiflexed and adducted position.

Diagnosis after examination was post-herpetic right brachial neuralgia and monoparesis. After seven days in the hospital the patiënt was placed on PHT, 100 mg t.i.d. Within three days she was free of pain and remained so when narcotic analgesics were with drawn and an extra 100mg of PHT was added. The patiënt continued free of pain as long as she to PHT.

1116. Hallaq, I. Y. and Harris, J. D., The syndrome of postherpetic neuralgia: complication and an approach to therapy, Amer. Osteopath. Assoc., 68: 1265-1267, 1969.

Thomas and Muthuswami, Indian Journal of Dermatology and Venereology (1988), 3260 conducted a study to determine the usefulness of phenytoin for post-herpetic neuralgia. Thirty patients, all over 50 years old, with herpes zoster were treated with oral phenytoin 100 mg twice daily for ten days.

The incidence of post-herpetic neuralgia was compared with that of post-herpetic neuralgia in another group of thirty patients treated with conventional analgesics, antacids, antihistamines and anti-biotics. In the PHT-treated group, only six (20%) of the patients developed persistent neuralgia, as compared to twenty-four (80%) in the control group.

3260. Thomas, J. and Muthuswami, T.C., Diphenylhydantoin in post-herpetic neuralgia, Indian J. Dermatol. Venereol. Leprol., 54: 303-304, 1988.

See also

3261. Thomas, J. and Muthuswami, T.C., Diphenylhydantoin in post-herpetic neuralgia – A controlled study, Presented at the XVIth National Conference of Indian Association of Dermatologists, Venereologists and Leprologists, Calcutta, India, 1988.

3262. Watson, P.N. and Evans, R.J., Postherpetic neuralgia – A review, Arch. Neurol., 43:836-40, 1986.

Refractory Chronic Pain

Gabka, Medizinische Monatsschrift (1963),113 reported PHT (100-300 mg/day), combined with 0.025 g of caffeine, as the most effective treatment for the relief of pain in 115 out of 142 patients. 

The painful conditions included recurring headaches, migraine, genuine and symptomatic trigeminal neuralgia, post-operative jaw and facial pain, and pain following extensive facial tumor surgery. The authors state that PHT was by far the best conservative therapy in the treatment of these types of recurring head and facial pain.

113. Gabka, J., On the therapy of idiopathic and sy
mptomatic head and facial pains, Med. Mschr., 17: 430-443, 1963.

Raskin, Levinson, Pickett, Hoffman and Fields, American Journal of Surgery (1974),1444 as part of a larger study, reported that two of the patients with post-sympathectomy neuralgia, unresponsive to meperidine, had immediate relief with intravenous PHT.

1444. Raskin, N. H., Levinson, S. A., Pickett, J. B., Hoffman, P. M., and Fields, H. L., Postsympathectomy neuralgia,Amer. Surg., 128: 75-78, 1974.

Taguchi, Watanabe and Ioku, Neurologia Medico Chirurgica (Tokyo) (1981),2998 reported a patiënt with bulbar syringomyelia who developed severe, intractable pain and paresthesias in her legs, abdomen and chest after cervical laminectomy. She also developed muscle spasms of her upper body. PHT, 250 mg/day, stopped both the pain and muscle spasms.

2998. Taguchi, K., Watanabe, M., Ioku, M., A case of syringomyelia: electrophysiological analysis and treatment for attacks of periodical spasms and intractable pain, Neurol. Med. Chir., 21: 135-42, 1981.

Swerdlow, Clinical Neuropharmalcology (1984),2997 reviewed a series of 200 patients with various types of refractory chronic lancinating or paroxysmal pain. The etiologies of the pain included post-laminectomy, post-traumatic, post-herpetic, post-operative, and post-amputation neuralgias, as well as pain secondary to nerve of plexus injury or operation, atypical facial pain, and central pain syndromes.

Of fifty-two patients who received PHT as their first drug, twenty-four found it effective. This success rate was higher than that achieved with carbamazepine, clonazepam, and valproate.

2997. Swerdlow, M., Anticonvulsant drugs and chronic pain, Clin. Neuropharmacol., 7 (1): 51-82, 1984.

McCleane, Anesthesia and Analgesia (1999), 3263 reports on a randomized, double-blind, placebo-controlled, crossover study of patients suffering from neuropathic pain. Twenty patients, nine males and eleven females, with a mean age of forty years participated in the study. Patients were randomly assigned to one of two groups.

Group A received an infusion of 1000 ml 0.9% saline (placebo) followed one week later by an infusion of 15 mg/kg PHT in 1000 ml 0.9% saline. Group B received the PHT infusion in week 1 and the placebo/saline infusion in week 2. Analyzed results indicated a statistically and clinically evident decrease in scores for burning pain, shooting pain, sensitivity, numbness, and overall pain with phenytoin.

The authors conclude that intravenous phenytoin is a useful treatment for acute flare-ups of chronic neuropathic pain, when oral treatment is not effective or appropriate.

3263. McCleane, G.J., Intravenous infusion of phenytoin relieves neuropathic pain: a randomized, double-blind, placebo-controlled, crossover study, Anesth. Analg., 89:985-988, 1999.

See also

  • 3264. Ashburn, M.A. and Staats, P.S., Management of chronic pain, Lancet, 353:1865-1869, 1999.
  • 3265. France, R.D. and Krishnan, K.R., Psychotropic drugs in chronic pain, 323-74, Chronic Pain, France, R.D. and Krishnan, K.R., Eds., American Psychiatric Press, Washington, DC, 1988.
  • 3266. Iacono, R.P., Linford, J., and Sandyk, R., Pain management after lower extremity amputation neurosurgery, Neurosurgery, 20: 496-500, 1987

Pain in Multiple Sclerose

Matthews, Brain (1958),1342 reported the effectiveness of PHT in the treatment of painful spasms in a patiënt with multiple Sclerose. When PHT, 100 mg t.i.d., was prescribed, the attacks stopped within two days.

1342. Matthews, W. B., Tonic seizures in disseminated Sclerose, Brain, 81: 193-206, 1958.

Kuroiwa and Shibasaki, Folia Psychiatrica et Neurologica Japonica (1968),1243 found that PHT and/or carbamazepine where useful in suppressing the painful tonic spasms in four patients with multiple Sclerose. In a further study, Shibaski and Kuroiwa, Archives of Neurology (1974),1541 reported the successful treatment of five of seven patients with PHT alone or in combination with carbanmazepine.

1243. Kuroiwa, Y. and Shibasakil H., Painful tonic seizures in multiple Sclerose-treatment with diphenylhydantoin and carbamazepine, Folia. Psychiat. Neurol. Jap., 22: 107-119, 1968.1541. Shibasaki, H. and Kuroiwa, Y., Painful tonic seizure in multiple Sclerose, Arch. Neurol., 30: 47-51, 1974.

Skillrud and Goldstein, Journal of the American Medical Association (1983),2963 reported in detail the case of a twenty-seven-year-old male physician with multiple Sclerose and paroxysmal limb hemiataxia and crossed facial paresthesias who became symptom free on 500 mg of PHT per day.

2963. Skillrud, D. M., Goldstein, N. P., Paroxysmal limb hemiataxia with crossed facial paresthesias in multiple Sclerose,JAMA, 250(20): 2843-4, 1983.

Clifford and Trotter, Archives of Neurology (1984),2396 reviewing the records of 317 multiple Sclerose patients with a wide variety of painful syndromes and therapies, reported PHT’s usefulness in the treatment of limb, facial, head and thoracic pain.

2396. Clifford, D. B., Trotter, J. L., Pain in multiple Sclerose, Arch. Neurol., 41: 1270-2, 1984.

Reflex Sympathetic Dystrophy

Chaturvedi, Pain (1989), 3267 describes the use of phenytoin to treat a thirty-year-old patiënt who had been complaining of pain in the left lower limb for two years. The symptoms had begun six months after a bicycle fall. The pain (a burning of moderate intensity) started gradually in the left lower limb and over time involved the entire leg to about 3 in. above the knee. Emotional reactions, touch, and heat all increased the pain.

He had been seen by several physicians, surgeons, orthopedists and physiotherapists in the past, but had not experienced any relief. Therapies tried unsuccessfully effects included: several analgesics; vitamin injections and tablets; minor tranquillizers; and tricyclic anti-depressants, alone or in combination; as well as vitamin B (B1, B6, B12) given for two months without any relief.

After receiving phenytoin (100 mg b.i.d) for two weeks, the patiënt reported a slight amelioration of his pain (20%). The dose of phenytoin was increased to 300 mg (100 mg t.i.d) and, after one month, the patiënt reported that he had more than 50% pain relief and was able to do his work effectively. When PHT was not taken for two weeks, the patient’s symptoms worsened.

On resuming PHT again, his symptoms promptly decreased. After one year of treatment, phenytoin was tapered and stopped. The patiënt continued to have good pain relief (75-80%).

3267. Chaturvedi, S.K., Phenytoin in reflex sympathetic dystrophy, Pain, 36: 379-380, 1989.

Koman, Barden, Smith, Pollock, Sinai and Poehling, Foot and Ankle (1993), 3268 present the case history of a patiënt with reflex sympathetic dystrophy of the foot. The patiënt, a 12-year-old girl, had injured her left foot on a lawn mower. Despite the use of analgesics, elevation, rest, crutches and protective splinting, she experienced increasing pain, cold intolerance, stiffness, and disability. Burning dysesthesia disrupted her sleep.

Her foot was anhidrotic, swollen, dysesthetic and allodynic. The patiënt was admitted to the hospital and started on a regimen of Amitriptyline (25 mg po, t.i.d), phenytoin (100 mg po t.i.d), and physical therapy with stress loading. Five days later, comparison of earlier results of the thermoregulatory and vasomotor capacity tests showed less vasomotor instability and more appropriate thermoregulatory responses.

In two weeks, the patiënt had returned to school. At this point, she was significantly improved and fully weight bearing, although she still experienced mild allodynia (pain resulting from non-noxious stimuli to normal skin). Phenytoin was discontinued and the Amitriptyline was tapered. When seen two months later, the patiënt had continued to improve, was taking no medications, and had normal vasomotor stability and thermoregulatory responses.

3268. Koman, L.A., Barden, A., Smith, B.P., Pollock, F.E., Sinai, S., and Poehling, G.G., Reflex sympathetic dystrophy in an adolescent, Foot and Ankle, 14(5): 273-77, 1993.

Abdominal Pain

Kellaway, Crawley and Kagawa, Epilepsia (1959-1960),551 in a review of experience with a group of 459 children who had consistent 14- and 6-per-second spike patterns on the EEG and whose primary complaints were headache and abdominal pain, found the most effective treatments were PHT and Diamoc, alone or in combination.

551. Kellaway, P.,Crawley,I.W.,and Kagawa, N., Paroxysmal pain and autonomic disturbances of cerebral origin: a specific electro-clinical syndrome, Epilepsia, 1: 466-483, 1959-1960.

Peppercorn, Herzog, Sichter and Mayman, JAMA (1978),2018 found PHT useful in the treatment of three patients with paroxysmal abdominal pain. When two of the patients stopped their medication the symptoms returned. With the resumption of the medication symptoms disappeared.

2018. Peppercorn, M. A., Herzog, A. G., Dichter, M. A. and Mayman, C. I., Abdominal epilepsy-a cause of abdominal pain in adults, JAMA, 240(22): 2450-51, 1978.

Schafler and Karbowski, Schweizerische Medizinische Wochenschrift (1981),2928 reported six cases of paroxysmal abdominal pain occurring in association with cerebral dysrhythmias, PHT controlled or reduced the severity of the attacks in the four cases in which it was used alone. In the one case, PHT, in combination with carbamazepine, was used successfully and, in another case, carbamaxepine was used alone.

2928. Schaffler, L., Karbowski, K., Relapsing paroxysmal abdominal pains of cerebral origin, Schweiz. Med. Wochenschr., 111(37): 2352-60, 1981.

Analgesia: General

Webb and Kamali, Pain, (1998), 3679 evaluated the analgesic effects of single doses of phenytoin (300 mg), lamotrigine (300 mg), and dihydrocodeine (90 mg) (each given on four occasions) in a double-blind, randomized, placebo-controlled crossover study in twelve non-smoking volunteers (age 20-26). A computerized cold-pressor test (CPT) was used to measure analgesia levels.

Psychomotor tests were carried out before each CPT to assess possible drug-induced sedation. Subjective assessments of concentration, vigilance, and relaxation were also measured using visual analog scales. Maximum pain relief was achieved at 1.25 hours post-dose for both lamotrigine and dihydrocodeine, whereas the maximum analgesic effect of PHT occurred at 4.25 hours.

There was a significant association between analgesia and plasma concentrations of both lamotrigine and phenytoin. Sedation was not seen with any of the drugs, compared to placebo. The authors suggest that both phenytoin and lamotrigine could have wider use as analgesics.

3679. Webb, J. and, Kamali, F., Analgesic effects of lamotrigine and phenytoin on cold-induced pain: a crossover placebo-controlled study in healthy volunteers, Pain, 76: 357-363, 1998.

Publications about Phenytoin and Cancer pain.

See also

  • 3276. Portenoy, R.K. and Lesage, P., Management of cancer pain, Lancet, 353:1695-1700, 1999.
  • Other clinical reviews and studies on the use of PHT in pain: facial pain including trigeminal neuralgia, glossopharyngeal neuralgia, and temporomandibular joint syndrome, Refs. 2470, 2472, 2492, 2523, 2593, 2619, 2801, 2847, 2943; headache including migraine, Refs. 2317, 2492; post-herpetic neuralgia, Ref. 2474, 2657; reflex sympathetic systrophy and post-sympathectomy pain, Refs. 2492, 3040; pain in multiple Sclerose Refs. 2601, 2929; central and other chronic pain syndromes, Refs. 2452, 2460, 2492, 2756, 2784, 2997.
  • 2470. Dworkin, S. F., Benign chronic orofacial pain. Clinical criteria and therapeutic approaches, Postgrad. Med., 74(3): 239-48, 1983.
  • 2472. Editor, Management of trigeminal neuralgia, Lancet, 662-3, Mar 24, 1984.
  • 2492. Fields, H. L., Raskin, N. H., Anticonvulsants and pain, Clinical Neuropharmacology, Klawans, H. L., Ed., Raven Press, New York, 173-83, 1976.
  • 2523. Gangarosa, L. P., Mahan, P. E., Pharmacologic management of TMJ-MPDS, Ear Nose Throat J., 61: 670-8, 1982.
  • 2593. Hier, D. B., Headache, Manual of Neurologic Therapeutics, 2nd Edition, Samuels, M. A., Ed., Little, Brown & Co., Boston, 15-29, 1982.
  • 2619. Jannetta, P. J., Medical treatment of trigeminal neuralgia, Neurological Surgery of the Ear and Skull Base, Brackmann, D. E., Ed., Raven Press, New York, 145-8, 1982.
  • 2801. Mohr, J. P., Facial pain, Manual of Clinical Problems in Neurology, Little, Brown and Co., Boston, 97-8, 1984.
  • 2847. Pagni, C. A., Trigeminal neuralgia, Panminerva Med., 24: 113-36, 1982.
  • 2943. Selby, G., Diseases of the fifth cranial nerve, Peripheral Neuropathy, Vol. 1, Dyck, P. J., et al., Eds., W. B. Saunders Co., Philadelphia, 533-69, 1975.
  • 2317. Behan, P., Migraine: a rational approach to therapy, Br. J. Clin. Pract., 36(10): 359-62, 1982.
  • 2474. Edwards, W. T., Approaches to managing chronic pain, Med. Times, 110: 3s-11s, 1982.
  • 2657. Kepes, E. R., Management of pain, Fundamentals of Geriatric medicine, Cape, R. D., et al., Eds., Raven Press, New York, 247-57, 1983.
  • 3040. Urbaniak, J. R., Roth, J. H., Office diagnosis and treatment of hand pain, Orthop. Clin. North Am., 13: 477-95, 1982.
  • 2601. Holland, N. J., Wiesel-Levison, P., McDonnel, M., Nursing care, Multiple Sclerose, A Guide for Patients and Their Families, Scheinberg, L. C., Ed., Raven Press, New York, 111-28, 1984.
  • 2929. Scheinberg, L., Giesser, B. S., Drug therapy, Multiple Sclerose a Guide for Patients and Their Families, Scheinberg, L., Ed., Raven Press, New York, 45-55, 1984.
  • 2452. Digregorio, G. J., Barbieri, E. J., Pharmacologic management of pain, Am. Fam. Physician, 27: 185-8, 1983.
  • 2460. Dougherty, R. J., Office management of chronic pain, Postgrad. Med., 76(2): 215-18, 1984.
  • 2756. Maciewicz, R., Bouckoms, A., Martin, J. B., Drug therapy of neuropathic pain, Clin. J. Pain, l(l): 1-10, 1985.
  • 2784. Mehta, M., Chronic pain, Recent Advances in Anaesthesia and Analgesia, Atkinson, R. S. and Hewer, L. C., Eds., Churchill Livingstone, New York, 157-77, 1982.
  • 2997. Swerdlow, M., Anticonvulsant drugs and chronic pain, Clin. Neuropharmacol., 7 (1): 51-82, 1984.

Prof. dr. J.M. Keppel Hesselink, Drs. D.J. Kopsky, arts
‘Publications about Phenytoin for pain’

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