Assessing activity onset time and efficacy for clinically effective antidepressant and antimanic drugs in animal models based on dominant-submissive relationships.
There is confusion in the literature on the measurement of the drug activity onset time (AOT) for both clinical and non-clinical studies of antidepressant and antimanic drugs. The questions asked are: How often and at which time points should drug effects be measured? At what level of a drug effect should AOT be determined? Is the placebo (control) effect important for consideration of drug AOT? This paper reviews approaches taken to answer these questions and to assess drug therapeutic AOT. The first part of the paper is devoted to a review of methods used in clinical trials with depression as an indication. The second part is focused on approaches taken in animal models of depression and how they could help in assessing drug AOT. Finally, a summary of pharmacological values on which the AOT depends is presented and a new statistical approach to data analysis method proposed. The allied experimental design for pre-clinical and clinical studies may help to characterize and differentiate AOT for available and new generation of antidepressants and antimanic drugs.
Malatynska
Ewa
E
Drug Discovery, CNS Research Team, East Coast Research and Early Development, Johnson & Johnson Pharmaceutical Research & Development, P.O. Box 776, Welsh and McKean Rds., L.L.C., Spring House, PA 19477, USA. Emalatyn@PRDUS.jnj.com
Pinhasov
Albert
A
Creighton
Christopher J
CJ
Crooke
Jeffrey J
JJ
Reitz
Allen B
AB
Brenneman
Douglas E
DE
Lubomirski
Mariusz S
MS
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018692:Antimanic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001714:Bipolar Disorder / Q000188:drug therapy; D003866:Depressive Disorder / Q000188:drug therapy; D004195:Disease Models, Animal; D004291:Dominance-Subordination; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D011930:Reaction Time / Q000187:drug effects*; D013997:Time Factors
D000928:Antidepressive Agents; D018692:Antimanic Agents