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SummaryAs with other drugs it is necessary to look for changes induced by anxiolytics on vital signs, laboratory parameters and adverse events. In return, in a more specific way for anxiolytics, we will look at side effects at the central nervous system level with psychological and physiological battery tests. We will also assess the safety of use of anxiolytics in certain specific conditions, such as overdose or withdrawal and in certain populations such as the elderly, neonates and children. The assessment of safety and side effects, whatever the drug type studied, must come early in the developing process of a drug (phases I, II and III).

Objective:There appears to be no dose-response effect for pregabalin at doses of 300-600 mg, and a modest dose-response effect in the range of 150-300 mg. The goal of the current investigation was to determine the effect of the starting dose on the speed of onset of anxiolytic efficacy.Methods:Data were analyzed from 7 trials of outpatients with DSM-IV GAD and a HAM-A total score ≥18. Starting doses of pregabalin ranged from 100 mg (N=301) or 150 mg (N=104), to 200 mg (N=167) and 300 mg (N=388). Assessment of early improvement included the HAM-A total score and CGI-Severity and Improvement scores.Results:The mean Week 1 HAM-A change score was similar for a starting dose of 200 mg/d with no titration (-8.24) when compared to patients who started on 200 mg/d and then titrated up to 400 mg/d on Day 4 (-8.64). The mean Week 1 HAM-A change score was somewhat higher for patients started on 300 mg/d, and then titrated to 450 mg/d on Day 4/5 (-8.84) when compared to patients started on a lower (100/150 mg/d) dose and titrated on Day 5 to 400/450 mg/d (-7.32). Starting on a dose of 300 mg/d with no titration resulted in an intermediate Week 1 change score (-7.87). The interaction of starting dose and titration schedule with baseline anxiety severity will be summarized in detail.Conclusion:The initial dose of pregabalin appears to have only a weak effect on the speed of onset of anxiolytic improvement.