HJ McQuay

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.

Introduction METHODS Finding all the relevant trials Judging the quality of trials Pain measurement: study design and validity Estimating relative effectiveness Combining data and interpreting the results Existing systematic reviews ACUTE PAIN Introduction Oral Ibuprofen and diclofenac in postoperative pain Comparing analgesic efficacy of non-steroidal anti-inflammatory drugs given by different routes in acute and chronic pain Topically applied non-steroidal anti-inflammatory drugs Injected morphine in postoperative pain Dihydrocodeine in postoperative pain Dextropropoxyphene in postoperative pain Single patient data meta-analysis of 3,453 postoperative patients: oral tramadol versus placebo, codeine, and combination analgesics Pain relief from intra-articular morphine after knee surgery Analgesic efficacy of peripheral opioids Pre-emptive analgesia: a systematic review of clinical studies to 1994 Trancutaneous Electrical Nerve Stimulation in Acute Postoperative Pain TENS in labour pains Acute pain - conclusion CHRONIC PAIN Introduction Radiotherapy for painful bone metastases Transcutaneous Electrical Pain stimulation in chronic pain Intravenous regional sympathetic blockade for reflex sympathetic dystrophy Epidural corticosteroids for sciatica Spinal cord stimulators for back pain Steroid injections for shoulder disorders Anticonvulsant drugs Antidepressants in neuropathic pain Systemic local anaesthetic type drugs in chronic pain Topical capsaicin Chronic pain conclusion

1 A 10 h study of plasma drug concentrations of the opiate buprenorphine after use was designed because a previous 3 h study had shown that peak plasma drug concentrations in some patients had not occurred by 3 h after the sublingual dose. 2 Fifteen postoperative patients were studied: at 3 h after a 0.3 mg intravenous dose five patients received a sublingual preparation of 0.4 mg of buprenorphine, five 0.8 mg of buprenorphine and five placebo. Plasma drug concentrations of buprenorphine were measured by specific radioimmuno-assay. 3 Plasma drug concentrations after sublingual buprenorphine were significantly higher than those in the placebo group by 1 h. They remained significantly higher over the succeeding nine hours. The mean time to peak plasma drug concentration was about 200 min in both the 0.4 mg and 0.8 mg groups (range 90-360 min). The plasma drug concentrations in the 0.8 mg group were approximately twice those in the 0.4 mg group; the ratio of the relative systemic availabilities was similarly 1.8:1. The absolute systemic availability was estimated at about 55% for both groups. Uptake of buprenorphine from the sublingual site was essentially complete by 5 h after the dose was given. 4 The implications for the timing of sublingual doses in clinical use are discussed.