Drug Class Review on Antiepileptic Drugs in Bipolar Mood Disorder, Neuropathic Pain, and Fibromyalgia
Published in: Drug Effectiveness Review Project / Mark Helfand, Oregon Evidence-Based Practice Center (Portland Oregon: Oregon Health and Science University, 2006), p. 1-139
Posted on RAND.org on December 31, 2005
The primary goal was to compare the effectiveness and adverse event profiles of AEDs in the treatment of bipolar mood disorder, neuropathic pain, and fibromyalgia. The Oregon Evidence based Practice Center wrote preliminary key questions, identifying the populations, interventions, and outcomes of interest, and based on these, the eligibility criteria for studies. These were reviewed and revised by representatives of organizations participating in the Drug Effectiveness Review Project (DERP). The participating organizations of DERP are responsible for ensuring that the scope of the review reflects the populations, drugs, and outcome measures of interest to both clinicians and patients. There is a paucity of good-quality data on the effectiveness, safety, and tolerability of AEDs in the management of bipolar disorder and neuropathic pain. The authors found no clear evidence of superior effectiveness of one AED over another, although there was fair-quality evidence from randomized controlled trials that gabapentin is ineffective in the treatment of bipolar disorder. Indirect evidence suggests that gabapentin is ineffective, whereas carbamazepine, lamotrigine, and valproate / divalproex are effective in bipolar disorder. For neuropathic pain, there was indirect evidence from overall results that gabapentin and pregabalin are similar in analgesic effects, whereas lamotrigine, topiramate, and valproate/divalproex showed inconsistent results. There was no conclusive (i.e., head-to-head) evidence of differences between AEDs. The authors conclusion that gabapentin and pregabalin are effective for neuropathic pain (specifically, painful diabetic neuropathy and postherpetic neuralgia) is stronger than their conclusion for other AEDs. Limited comparative data on the safety and tolerability of the AEDs suggest that the agents differ in their adverse event profiles. Except for fair-quality evidence that topiramate is associated with clinically significant weight loss (? 5% from baseline) in one fourth to one third of patients, they did not detect clearly discernible differences between any of the AEDs in the rates of adverse events or withdrawals due to adverse events. The best quality evidence (from a systematic review) suggested that carbamazepine, gabapentin, and phenytoin are similar in safety and tolerability in the treatment of neuropathic pain. No conclusive evidence could be obtained from analyses of subgroup response predictors.