1,721,168 research outputs found
Regulatory policies on medicines for psychiatric disorders: is Europe on target?
No full textThe European Medicines Agency (EMEA) is the regulatory body that provides the institutions of the European Community with the best possible scientific advice on the quality, safety and efficacy of medicinal products. Drugs approved by the EMEA are automatically marketable in all the European member states. Since the beginning of the EMEA’s activities a number of drugs acting on the central nervous system obtained marketing authorisation. This editorial highlights some aspects of the EMEA rules that may negatively affect the evaluation of medicines for psychiatric disorder
Mild depression in general practice: is the automatism of antidepressant prescribing an evidence-based approach?
No full textClinical trials of new antipsychotics: a critical appraisal.
No full textIn recent years the efficacy of new antipsychotics has been investigated through a number of randomized controlled trials. This paper considers some methodological flaws that affect these studies and proposes possible solutions. The final goal is the implementation of a new generation of trials with the aim of demonstrating superiority of effect of the new antipsychotic over the reference one
Does placebo help establish equivalence in trials of new antidepressants?
No full textClinical trials of new antidepressants usually compare a new drug to a reference antidepressant and to a placebo. The placebo is intended to validate the trial in the case of a no-difference outcome, i.e., it helps in assessing equivalence. The aim of the present paper is to test whether placebo has indeed helped establish equivalence of effect in comparative trials of new antidepressants. We carried out an example of sample size determination first in a trial to show a difference between the new and control drug, and second in a trial to assess equivalence between two competing drugs. Finally, we retrospectively calculated the maximum difference accepted as equivalence of effect in published trials of new antidepressants. Assuming a response rate to antidepressants of 70%, 294 subjects for each treatment group are needed to show a 10% difference between two antidepressant drugs and more than 1,300 to assess equivalence at a 5% level of δ, the maximum difference acceptable as equivalence of effect. The level of δ in published trials of new antidepressants ranges between 12 and 43%, suggesting they cannot claim to demonstrate equivalence of effect. Therefore, the presence of a placebo arm for comparison didn't help establish whether both drugs really worked the same way. Comparative trials of new antidepressants should adopt a two-arm design, a suitable number of patients and a high standard in the experimental design in order to minimise possible control-event rate variation. (C) 2000 Editions scientifiques et medicales Elsevier SAS
Antidepressant agents: from tricyclics to serotonin uptake inhibitors.
No full textThe number of antidepressant drugs available in the market has grown rapidly in the last few years. The present paper underlines some of the pre-clinical and clinical problems that call close attention from the regulatory authorities when approving new drugs.We present here a review of the literature.A wide heterogeneity in the action of the various antidepressants precludes any single theory about the pathogenesis and therapy of depression. Antidepressant activity, in fact, may be achieved by acting on a number of different monoaminergic mechanisms. The variety in the neurochemical effects of antidepressants is not reflected in clinical trials, which tend to stereotypy. In many cases clinical trials aim at demonstrating equivalence rather than differences in efficacy. Regulatory authorities should, therefore, pay attention in accepting the equivalence of effects of a new drug in relation to a reference one: most clinical trials of new antidepressant drugs do not have the power to detect clinically relevant differences.Unconventional new pre-clinical tests are needed to generate antidepressants with a different mechanism of action. Clinical studies are needed to promote objective comparative evaluation of the cost, benefits and toxic effects of new antidepressants
Fluoxetine dose and outcome in antidepressant drug trials
No full textObjective: One potential for bias in the evaluation of a new drug is the dose used, both for the new compound and for the reference drug. The present study compared fluoxetine dose and outcome in trials in which fluoxetine was the experimental drug with trials in which it was the comparator.
Methods: Systematic review of randomised controlled trials comparing fluoxetine with any other antidepressant in depressive patients. Studies were allocated to one of the following two groups: group 1 = fluoxetine was the experimental drug; group 2 = fluoxetine was the control drug. Trials were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Controlled Trials Register.
Results: The systematic search yielded 103 randomised trials. Studies in which fluoxetine was the experimental drug adopted a higher dose regimen than group-2 studies. In the efficacy analysis, the weighted rate of fluoxetine responders was 70.1% (confidence interval 67.4%, 72.8%) in group-1 studies and 57.9% (57.2%, 58.7%) in group-2 studies. In the effectiveness analysis, the weighted rate of fluoxetine responders was 56.4% (55.3%, 57.6%) in group-1 studies and 51.9% (51.2%, 52.7%) in group-2 studies. The weighted rate of fluoxetine dropouts was higher in group-1 studies.
Conclusion: Fluoxetine dose and outcome changed according to whether this drug was used as a new compound or as a reference
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