Dose-response relationship of pregabalin in patients with generalized anxiety disorder. A pooled analysis of four placebo-controlled trials.
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.


METHODS
Both the full HAM-A (14) and the six-item subscale covering the core items of GAD (HAM-A (6)) 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-A (6) and HAM-A (14) 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-A (14) as well as the item of sleep, effect size was generally higher, but followed the same pattern as the HAM-A (6).


CONCLUSIONS
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.
Bech
P
P
Psychiatric Research Unit, Frederiksborg General Hospital, Hillerød, Denmark. pebe@noh.regionh.dk
D000293:Adolescent; D000328:Adult; D000368:Aged; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069583:Pregabalin; D016032:Randomized Controlled Trials as Topic; D011795:Surveys and Questionnaires; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D014151:Anti-Anxiety Agents; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid