P Wiffen1, H McQuay, D Carroll, A Jadad, A Moore. 1. Cochrane Pain, Palliative and Supportive Care CRG, Pain Research Unit, Churchill Hospital, Old Road, Headington, OXFORD, UK, OX3 7LJ. phil.wiffen@pru.ox.ac.uk
Abstract
BACKGROUND: Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for neuropathic pain, especially when the pain is lancinating or burning. OBJECTIVES: To evaluate the analgesic effectiveness of anticonvulsant drugs compared to either placebo or other drugs in order to provide evidence-based recommendations for pain management in clinical practice and to identify a clinical research agenda. Adverse effects are also considered. SEARCH STRATEGY: Randomised trials of anticonvulsants in acute, chronic or cancer pain were identified by Medline (Silver Platter 3.0, 3.1 and 3.11) from 1966 to February 1994. In addition, 40 medical journals were hand searched (published between 1950 and 1990). Additional reports were identified from the reference list of the retrieved papers, and contacting investigators. Date of the most recent searches: 1994. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of anticonvulsant drugs in patients, with pain assessment as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Numbers-needed-to-treat (NNTs) were calculated from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal, for individual studies and for pooled data. MAIN RESULTS: Twenty trials of four anticonvulsants were considered eligible (746 patients). The only placebo-controlled study in acute pain found no analgesic effect of sodium valproate. Three placebo-controlled studies of carbamazepine in trigeminal neuralgia had a combined NNT for effectiveness of 2.6, for adverse effects 3.4, and for severe effects (withdrawal from study) 24. Three placebo-controlled studies of diabetic neuropathy had a combined NNT for effectiveness of 3, for adverse effects 2.5, and for severe effects 20. Three placebo-controlled studies of migraine prophylaxis had a combined NNT for effectiveness of 2.4, for adverse effects 2.4 and for severe effects 39. Phenytoin had no effect in irritable bowel syndrome, and carbamazepine little effect in post-stroke pain. Clonazepam was effective in one study of temporomandibular joint dysfunction. No study compared one anticonvulsant with another. Anticonvulsants fared poorly against other treatments. REVIEWER'S CONCLUSIONS: Although anticonvulsants are used widely in chronic pain surprisingly few trials show analgesic effectiveness. No trial compared different anticonvulsants. There is no evidence that anticonvulsants are effective for acute pain. In chronic pain syndromes other than trigeminal neuralgia anticonvulsants should be withheld until other interventions have been tried.
BACKGROUND: Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for neuropathic pain, especially when the pain is lancinating or burning. OBJECTIVES: To evaluate the analgesic effectiveness of anticonvulsant drugs compared to either placebo or other drugs in order to provide evidence-based recommendations for pain management in clinical practice and to identify a clinical research agenda. Adverse effects are also considered. SEARCH STRATEGY: Randomised trials of anticonvulsants in acute, chronic or cancer pain were identified by Medline (Silver Platter 3.0, 3.1 and 3.11) from 1966 to February 1994. In addition, 40 medical journals were hand searched (published between 1950 and 1990). Additional reports were identified from the reference list of the retrieved papers, and contacting investigators. Date of the most recent searches: 1994. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of anticonvulsant drugs in patients, with pain assessment as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Numbers-needed-to-treat (NNTs) were calculated from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal, for individual studies and for pooled data. MAIN RESULTS: Twenty trials of four anticonvulsants were considered eligible (746 patients). The only placebo-controlled study in acute pain found no analgesic effect of sodium valproate. Three placebo-controlled studies of carbamazepine in trigeminal neuralgia had a combined NNT for effectiveness of 2.6, for adverse effects 3.4, and for severe effects (withdrawal from study) 24. Three placebo-controlled studies of diabetic neuropathy had a combined NNT for effectiveness of 3, for adverse effects 2.5, and for severe effects 20. Three placebo-controlled studies of migraine prophylaxis had a combined NNT for effectiveness of 2.4, for adverse effects 2.4 and for severe effects 39. Phenytoin had no effect in irritable bowel syndrome, and carbamazepine little effect in post-stroke pain. Clonazepam was effective in one study of temporomandibular joint dysfunction. No study compared one anticonvulsant with another. Anticonvulsants fared poorly against other treatments. REVIEWER'S CONCLUSIONS: Although anticonvulsants are used widely in chronic pain surprisingly few trials show analgesic effectiveness. No trial compared different anticonvulsants. There is no evidence that anticonvulsants are effective for acute pain. In chronic pain syndromes other than trigeminal neuralgia anticonvulsants should be withheld until other interventions have been tried.
Authors: Hiltrud Liedgens; Nadine Hertel; Anja Gabriel; Mark Nuijten; Helen Dakin; Stephen Mitchell; Barbara Poulsen Nautrup Journal: Clin Drug Investig Date: 2008 Impact factor: 2.859