Dose-response Relationship of Pregabalin in Patients with Generalized Anxiety Disorder. A Pooled Analysis of Four Placebo-controlled Trials

Abstract

Background: Pregabalin has been evaluated in randomised clinical trials in patients with generalised anxiety disorder (GAD) in a fixed-dose design and with the Hamilton Anxiety Scale (HAM-A) as outcome measure. Four of the available six placebo-controlled trials were found acceptable for a pooled analysis of dose-response relationship.

Method: Both the full HAM-A₁₄ and the six-item subscale covering the core items of GAD (HAM-A₆) were analysed. The unbiased effect size statistic was used to evaluate the advantage of pregabalin over placebo. An effect size of 0.40 or higher was used to indicate a clinically significant effect.

Results: Four placebo-controlled trials running over four weeks and covering the dose range from 150 mg to 600 mg pregabalin were sufficiently homogeneous to be pooled for the analysis. Both HAM-A₆ and HAM-A₁₄ showed that for the dose of 150 mg pregabalin daily the effect size was clearly below 0.40. For the dose range of 200-450 mg daily, the effect sizes exceeded 0.40, with a plateau-like curve. The maximum dose of 600 mg daily did not increase effect size. On the HAM-A₁₄ as well as the item of sleep, effect size was generally higher, but followed the same pattern as the HAM-A₆.

Discussion: The dose of 150 mg pregabalin over the four weeks of the trials was found insufficient for the treatment of GAD. In the dose range of 200-450 mg daily, a clinically significant effect was obtained, although with a plateau-like curve which was not increased for the maximum dose of 600 mg daily.

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1 EF=(1-3/[4^*(N1+N2-2)-1)]^*{(M1-M2)/SQRT[(N1-1)^*S1^**2+(N2-1)^*S2^**2/(N1+N2-2)]} where M1, M2=means in the two groups; S1, S2=SDs in the two groups, and N1, N2=number of patients in the two groups.

Correspondence