BMJ 1995;311:1047-1052 (21 October)

Papers

Anticonvulsant drugs for management of pain: a systematic review

Henry McQuay, clinical reader in pain relief,a Dawn Carroll, senior research nurse,a Alejandro R Jadad, research fellow,a Philip Wiffen, principal pharmacist,b Andrew Moore, consultant biochemist a

a Oxford Pain Relief Unit, Churchill Hospital, Oxford OX3 7LJ, b Pharmacy Department, Churchill Hospital

Correspondence to: Dr McQuay.

Abstract

Objective: To determine effectiveness and adverse effects of anticonvulsant drugs in management of pain.
Design: Systematic review of randomised controlled trials of anticonvulsants for acute, chronic, or cancer pain identified by using Medline, by hand searching, by searching reference lists, and by contacting investigators.
Subjects: Between 1966 and February 1994, 37 reports were found; 20 reports, of four anticonvulsants, were eligible.
Main outcome measures: Numbers needed to treat were calculated for effectiveness, adverse effects, and drug related withdrawal from study.
Results: The only placebo controlled study in acute pain found no analgesic effect of sodium valproate. For treating trigeminal neuralgia, carbamazepine had a combined number needed to treat of 2.6 for effectiveness, 3.4 for adverse effects, and 24 for severe effects (withdrawal from study). For treating diabetic neuropathy, anticonvulsants had a combined number needed to treat of 2.5 for effectiveness, 3.1 for adverse effects, and 20 for severe effects. For migraine prophylaxis, anticonvulsants had a combined number needed to treat of 1.6 for effectiveness, 2.4 for adverse effects, and 39 for severe effects. Phenytoin had no effect on the irritable bowel syndrome, and carbamazepine had little effect on pain after stroke. Clonazepam was effective in one study for temporomandibular joint dysfunction. No study compared one anticonvulsant with another.
Conclusions: Anticonvulsants were effective for trigeminal neuralgia and diabetic neuropathy and for migraine prophylaxis. Minor adverse effects occurred as often as benefit.

Key messages

  • Key messages

  • To evaluate the effectiveness of these drugs, we conducted a systematic review of all randomised controlled trials reported between 1966 and February 1994

  • Only 20 trials were eligible for inclusion, and three pain syndromes were subject to more than one trial: trigeminal neuralgia, diabetic neuropathy, and migraine prophylaxis.

  • Overall number needed to treat to produce benefit (improved pain scores) was about 2.5, for minor adverse effects it was about 3, and for severe adverse effects it was 20-30

  • Anticonvulsants do have an analgesic effect, although at similar risk of minor adverse effects


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to StumbleUpon StumbleUpon   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

This article has been cited by other articles:

  • Kissin, I. (2010). The Development of New Analgesics Over the Past 50 Years: A Lack of Real Breakthrough Drugs. Anesth. Analg. 110: 780-789 [Abstract] [Full text]  
  • Rutkove, S. B. (2009). A 52-Year-Old Woman With Disabling Peripheral Neuropathy: Review of Diabetic Polyneuropathy. JAMA 302: 1451-1458 [Abstract] [Full text]  
  • Rogers, M., Rasheed, A., Moradimehr, A., Baumrucker, S. J. (2009). Memantine (Namenda) for Neuropathic Pain. AM J HOSP PALLIAT CARE 26: 57-59 [Abstract]  
  • Eskandar, E., Barker, F. G. II, Rabinov, J. D. (2006). Case records of the Massachusetts General Hospital. Case 21-2006. A 61-year-old man with left-sided facial pain.. NEJM 355: 183-188 [Full text]  
  • Bansal, V, Kalita, J, Misra, U K (2006). Diabetic neuropathy. Postgrad. Med. J. 82: 95-100 [Abstract] [Full text]  
  • Rathur, H. M., Boulton, A. J. M. (2005). Recent advances in the diagnosis and management of diabetic neuropathy. J Bone Joint Surg Br 87-B: 1605-1610 [Full text]  
  • Irving, G. A. (2005). Contemporary assessment and management of neuropathic pain. Neurology 64: S21-S27 [Abstract] [Full text]  
  • Rainone, F. (2004). Treating Adult Cancer Pain in Primary Care. J Am Board Fam Med 17: S48-S56 [Abstract] [Full text]  
  • Raskin, P., Donofrio, P. D., Rosenthal, N. R., Hewitt, D. J., Jordan, D. M., Xiang, J., Vinik, A. I. (2004). Topiramate vs placebo in painful diabetic neuropathy: Analgesic and metabolic effects. Neurology 63: 865-873 [Abstract] [Full text]  
  • Decosterd, I., Allchorne, A., Woolf, C. J. (2004). Differential Analgesic Sensitivity of Two Distinct Neuropathic Pain Models. Anesth. Analg. 99: 457-463 [Abstract] [Full text]  
  • Boulton, A. J.M., Malik, R. A., Arezzo, J. C., Sosenko, J. M. (2004). Diabetic Somatic Neuropathies. Diabetes Care 27: 1458-1486 [Full text]  
  • Chow, T. K. F., To, E., Goodchild, C. S., McNeil, J. J. (2004). A Simple, Fast, Easy Method to Identify the Evidence Base in Pain-Relief Research: Validation of a Computer Search Strategy Used Alone to Identify Quality Randomized Controlled Trials. Anesth. Analg. 98: 1557-1565 [Abstract] [Full text]  
  • Attal, N., Rouaud, J., Brasseur, L., Chauvin, M., Bouhassira, D. (2004). Systemic lidocaine in pain due to peripheral nerve injury and predictors of response. Neurology 62: 218-225 [Abstract] [Full text]  
  • Bennett, M. I, Simpson, K. H (2004). Gabapentin in the treatment of neuropathic pain. Palliat Med 18: 5-11 [Abstract]  
  • Kochar, D.K., Rawat, N., Agrawal, R.P., Vyas, A., Beniwal, R., Kochar, S.K., Garg, P. (2004). Sodium valproate for painful diabetic neuropathy: a randomized double-blind placebo-controlled study. QJM 97: 33-38 [Abstract] [Full text]  
  • Dworkin, R. H., Backonja, M., Rowbotham, M. C., Allen, R. R., Argoff, C. R., Bennett, G. J., Bushnell, M. C., Farrar, J. T., Galer, B. S., Haythornthwaite, J. A., Hewitt, D. J., Loeser, J. D., Max, M. B., Saltarelli, M., Schmader, K. E., Stein, C., Thompson, D., Turk, D. C., Wallace, M. S., Watkins, L. R., Weinstein, S. M. (2003). Advances in Neuropathic Pain: Diagnosis, Mechanisms, and Treatment Recommendations. Arch Neurol 60: 1524-1534 [Abstract] [Full text]  
  • Milligan, E. D., Twining, C., Chacur, M., Biedenkapp, J., O'Connor, K., Poole, S., Tracey, K., Martin, D., Maier, S. F., Watkins, L. R. (2003). Spinal Glia and Proinflammatory Cytokines Mediate Mirror-Image Neuropathic Pain in Rats. J. Neurosci. 23: 1026-1040 [Abstract] [Full text]  
  • Pandey, C. K., Bose, N., Garg, G., Singh, N., Baronia, A., Agarwal, A., Singh, P. K., Singh, U. (2002). Gabapentin for the Treatment of Pain in Guillain-Barre Syndrome: A Double-Blinded, Placebo-Controlled, Crossover Study. Anesth. Analg. 95: 1719-1723 [Abstract] [Full text]  
  • Watkins, L. R., Maier, S. F. (2002). Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States. Physiol. Rev. 82: 981-1011 [Abstract] [Full text]  
  • Laughlin, T. M., Tram, K. V., Wilcox, G. L., Birnbaum, A. K. (2002). Comparison of Antiepileptic Drugs Tiagabine, Lamotrigine, and Gabapentin in Mouse Models of Acute, Prolonged, and Chronic Nociception. J. Pharmacol. Exp. Ther. 302: 1168-1175 [Abstract] [Full text]  
  • Zeppetella, G., Ribeiro, M. D.C. (2002). Episodic pain in patients with advanced cancer. AM J HOSP PALLIAT CARE 19: 267-276 [Abstract]  
  • Hazelgrove, J. F., Rogers, P. D. (2002). Phantom Limb Pain--A Complication of Lower Extremity Wound Management. INT J LOW EXTREM WOUNDS 1: 112-124 [Abstract]  
  • Krupp, L. B., Rizvi, S. A. (2002). Symptomatic therapy for underrecognized manifestations of multiple sclerosis. Neurology 58: S32-39 [Abstract] [Full text]  
  • Harden, R. N. (2001). Complex regional pain syndrome. Br J Anaesth 87: 99-106 [Abstract] [Full text]  
  • Nurmikko, T. J., Eldridge, P. R. (2001). Trigeminal neuralgia--pathophysiology, diagnosis and current treatment. Br J Anaesth 87: 117-132 [Abstract] [Full text]  
  • (2000). Drug treatment of neuropathic pain. DTB 38: 89-93 [Abstract] [Full text]  
  • Sindrup, S. H., Jensen, T. S. (2000). Pharmacologic treatment of pain in polyneuropathy. Neurology 55: 915-920 [Abstract] [Full text]  
  • Gonzalez, M. I., Field, M. J., Hughes, J., Singh, L. (2000). Evaluation of Selective NK1 Receptor Antagonist CI-1021 in Animal Models of Inflammatory and Neuropathic Pain. J. Pharmacol. Exp. Ther. 294: 444-450 [Abstract] [Full text]  
  • Todorovic, S. M., Perez-Reyes, E., Lingle, C. J. (2000). Anticonvulsants But Not General Anesthetics Have Differential Blocking Effects on Different T-Type Current Variants. Mol. Pharmacol. 58: 98-108 [Abstract] [Full text]  
  • Luft, D. (1999). Neuropathic pain in diabetic nephropathy—update on analgesic strategies. Nephrol Dial Transplant 14: 2285-2288 [Full text]  
  • McCleane, G. J. (1999). Intravenous Infusion of Phenytoin Relieves Neuropathic Pain: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Study. Anesth. Analg. 89: 985-985 [Abstract] [Full text]  
  • Morello, C. M., Leckband, S. G., Stoner, C. P., Moorhouse, D. F., Sahagian, G. A. (1999). Randomized Double-blind Study Comparing the Efficacy of Gabapentin With Amitriptyline on Diabetic Peripheral Neuropathy Pain. Arch Intern Med 159: 1931-1937 [Abstract] [Full text]  
  • Bajwa, Z. H., Sami, N., Warfield, C. A., Wootton, J. (1999). Topiramate relieves refractory intercostal neuralgia. Neurology 52: 1917-1917 [Full text]  
  • Pan, H.-L., Eisenach, J. C., Chen, S.-R. (1999). Gabapentin Suppresses Ectopic Nerve Discharges and Reverses Allodynia in Neuropathic Rats. J. Pharmacol. Exp. Ther. 288: 1026-1030 [Abstract] [Full text]  
  • Backonja, M., Beydoun, A., Edwards, K. R., Schwartz, S. L., Fonseca, V., Hes, M., LaMoreaux, L., Garofalo, E., for the Gabapentin Diabetic Neuropathy Study Group, (1998). Gabapentin for the Symptomatic Treatment of Painful Neuropathy in Patients With Diabetes Mellitus: A Randomized Controlled Trial. JAMA 280: 1831-1836 [Abstract] [Full text]  
  • Rowbotham, M., Harden, N., Stacey, B., Bernstein, P., Magnus-Miller, L., for the Gabapentin Postherpetic Neuralgia Study Gr, (1998). Gabapentin for the Treatment of Postherpetic Neuralgia: A Randomized Controlled Trial. JAMA 280: 1837-1842 [Abstract] [Full text]  
  • Tfelt-Hansen, P (1998). Efficacy and Adverse Events of Subcutaneous, Oral, and Intranasal Sumatriptan Used for Migraine Treatment: A Systematic Review Based on Number Needed To Treat. Cephalalgia 18: 532-538 [Abstract]  
  • Todorovic, S. M., Lingle, C. J. (1998). Pharmacological Properties of T-Type Ca2+ Current in Adult Rat Sensory Neurons: Effects of Anticonvulsant and Anesthetic Agents. J. Neurophysiol. 79: 240-252 [Abstract] [Full text]  
  • Cooper, W. O., Federspiel, C. F., Griffin, M. R., Hickson, G. B. (1997). New Use of Anticonvulsant Medications Among Children Enrolled in the Tennessee Medicaid Program. Arch Pediatr Adolesc Med 151: 1242-1246 [Abstract]  
  • McQuay, H. J, Moore, R A. (1997). Antidepressants and chronic pain. BMJ 314: 763-763 [Full text]  
  • Mcquay, H., Moore, A. (1996). Placebo mania. BMJ 313: 1008a-1008 [Full text]  



Access jobs at BMJ Careers
Whats new online at Student 

BMJ