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Biomedical subjects

Roger M Pinder

Publications and source records attributed to Roger M Pinder.

5 recordsLinked to original sources
PubMed2002

Enhancing the technology of clinical trials and the trials model to evaluate newly developed, targeted antidepressants.

Concern about disappointing results from recent multi-center trials of new antidepressants prompted several ACNP workshops on "improving the technology of clinical trials." The workshops focused on technical problems, such as patient screening, reliability of clinical ratings, and the role of the placebo control. They aimed to determine how to more effectively apply the current clinical trials model for evaluating antidepressant drugs. The problems confronting the field of clinical trials, however, extend beyond technology. They also included conceptual issues concerning changes in the understanding of depressive disorders and of the multiple actions of antidepressant drugs. Such problems have been further complicated by the rapidly changing field of drug development itself, which is continually refining the targeting of new antidepressant agents. Drugs are increasingly being developed to try to change specific behavioral facets more rapidly and may be less likely, therefore, to act initially on "whole" disorders. To address such issues, a symposium was held in Rhodes in 2000 that focused on such conceptual changes with the goal of developing recommendations to revise the clinical evaluation model. Its purpose was to integrate new knowledge on depression and the mechanisms of action of antidepressant drugs toward developing more efficient methods of drug development. Since the evaluation process will eventually require changes in governmental policy, senior staff from the National Institute of Mental Health (NIMH) , Unites States and Food and Drug Administration (FDA), Unites States participated as well as members of academia, industry and clinical practice. Recommendations for altering clinical trial methodology were made in four areas: patient selection, methodology of evaluation, measuring onset of action, and FDA and NIMH perspectives on current practice. This article discusses these four areas and presents the consensus of the panel participants.

Antidepressive Agents↗
PubMed2002

Selecting methodologies for the evaluation of differences in time to response between antidepressants.

BACKGROUND: The delay in the therapeutic effect of antidepressants is a considerable impediment to their successful clinical use, and attention has recently been focused on antidepressant drugs that may have a faster onset of action. DATA SYNTHESIS: Several methodologies exist for evaluating differences in time to response between antidepressants including the identification of the timepoint at which statistically or clinically significant differences between treatment groups emerge, pattern analysis, and survival analytical approaches. All have conceptual as well as practical advantages and disadvantages. CONCLUSION: The survival analytical approach is generally considered to be the most rigorous and sensitive in detecting differences in the speed of response of antidepressants, but the other methodologies provide useful information.

Antidepressive Agents↗
PubMed2001

On the feasibility of designing new antidepressants.

Modern antidepressants lack many of the side-effects and much of the toxicity of the first generation tricyclics and monoamine oxidase inhibitors. Knowledge of the receptor interactions that are responsible for poor tolerability and potential lethality in overdosage has enabled the design of agents that have low or no affinity for such receptors. Nevertheless, even the second generation selective serotonin reuptake inhibitors (SSRIs), the serotonin noradrenaline reuptake inhibitors (SNRIs) and the noradrenaline and serotonin specific antidepressants (NaSSAs) have not substantially improved upon the efficacy of the older agents. They still take some time to be effective, although venlafaxine and mirtazapine may be faster in onset than SSRIs, and they leave a substantial minority of patients unaffected.Innovative new antidepressants may be based upon a variety of mechanisms, including receptors, G-proteins, second messengers, gene transcription factors and the hypothalamic - pituitary - adrenal axis, but their availability may be hindered by recent advances in pharmaceutical research technology. Thus, the creation of large chemical libraries containing millions of new entities has increased structural diversity, but pharmacological evaluation has narrowed down to simple assays in high-throughput screening systems. Such assays depend to a major extent on how well they reflect the biological aetiology of the disease under study. While new antidepressant moieties will undoubtedly emerge, optimal use of the new research tools will necessitate a more sophisticated level of knowledge about the true causes of depression. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗