Efficacy and safety of carisbamate in patients with diabetic neuropathy or postherpetic neuralgia: results from 3 randomized, double-blind placebo-controlled trials.

The results of 3 proof-of-concept studies to evaluate carisbamate's efficacy and safety in treating neuropathic pain are presented. In studies 1 (postherpetic neuralgia, n = 91) and 2 (diabetic neuropathy, n = 137), patients received carisbamate 400 mg/day or placebo for 4 weeks and then crossed over to the other treatment for 4 weeks. In study 3 (diabetic neuropathy, higher carisbamate doses), patients (n = 386) were randomized (1:1:1:1) to receive either carisbamate 800 mg/day, 1200 mg/day, pregabalin 300 mg/day or placebo for 15 weeks. Primary efficacy end point was the mean of the last 7 average daily pain scores obtained on days the study drug was taken, for all 3 studies. Least square mean (95% CI) differences between carisbamate and placebo groups on the primary end point were as follows: study 1: -0.512 (-1.32, 0.29) carisbamate 400 mg/day; study 2: -0.307 (-0.94, 0.33) carisbamate 400 mg/day; and study 3: -0.51 (-1.10, 0.08), carisbamate 800 mg/day; -0.55 (-1.13, 0.04), carisbamate 1200 mg/day; and -0.43 (-1.01, 0.15), pregabalin 300 mg/day. Neither carisbamate (all 3 studies) nor pregabalin (study 3) significantly differed from placebo, although multiple secondary end points showed significant improvement in efficacy with carisbamate in studies 1 and 2. Dizziness was the only treatment-emergent adverse event occurring at ≥10% difference in carisbamate groups versus placebo (study 1: 12% vs. 1%; study 3: 14% vs. 4%; study 2: 1% vs. 2%). Carisbamate, although well tolerated, did not demonstrate efficacy in neuropathic pain across these studies, nor did the active comparator pregabalin (study 3).

Child and adolescent psychopharmacology in the new millennium: a workshop for academia, industry, and government.

OBJECTIVE: To give academic researchers, government officials, and industry scientists an opportunity to assess the state of pediatric psychopharmacology and identify challenges facing professionals in the field. METHOD: Increased federal spending and the introduction of pediatric exclusivity led to large increases in pediatric psychopharmacology research in the 1990s. Despite the increase in research, concerns exist about methods and incentives for making new medications available for use in pediatric psychiatric disorders. In recognition of these concerns, the Duke Clinical Research Institute held a roundtable in September 2004. Participants from the National Institutes of Health, regulatory agencies, academia, and the pharmaceutical industry spoke about the effects of government regulations such as the U.S. Food and Drug Administration Modernization Act and the Pediatric Research Equity Act on pediatric research from academic, clinical, and industry perspectives, and bioethical considerations of such research. CONCLUSIONS: To ensure development of new drugs for treating psychiatric disorders in children and adolescents, we must address the challenges posed by the regulatory environment governing pediatric psychopharmacology research. Strategies were identified for improving the evidence base for psychopharmacologic interventions in youth before widespread use and for more effectively defining a research agenda for the future.

Effect of topiramate monotherapy on height in newly diagnosed children with epilepsy.

We conducted a post hoc assessment of the effect of ≥6 months of topiramate monotherapy on height in pediatric patients with newly diagnosed partial-onset seizure. Data on height measured nonsystematically up to 4 years from two randomized, double-blind studies and their open-label extensions were combined and converted to z scores and percentiles by patient's sex and age. Height velocity values (centimeters per year) and the associated z scores were computed for each postbaseline year using normative data. Median height velocity (centimeters per year) values and the associated z scores for patients ages 6-9 years were, year 1: 4.7 (-0.91); year 2: 4.2 (-1.62); year 3: 4.5 (-1.87); and for patients ages 10-15 years were, year 1: 4.0 (-0.76); year 2: 2.8 (-1.34); year 3: 3.1 (-0.74). There was a significant correlation between height velocity z score and change from baseline in height z score (r = 0.94 [n = 117]; P < 0.0001). Patient's bicarbonate status (low was defined as two postbaseline serum bicarbonate values <20 mmol/L) and sex had no effect on height velocity. In both age groups, continued growth was observed; however, the growth rate was slower than expected compared with a matched normal population from years 1 to 2 and showed minimal recovery from years 2 to 3.