Time-dependent psychotropic drug effects: Hints of pharmacochronomics, broader than circadian time structures

Haruo Nagayama, Germaine Cornélissen, S. R. Pandi-Perumal, Franz Halberg

Research output: Chapter in Book/Report/Conference proceedingChapter


The importance of timing medications is noted in the context of the effects of psychotropic drugs. The information here assembled as yet is examined mostly by inspection with the unaided eye and conventional (rather than time series-related) statistics. An effect of time, shown by an analysis of variance, however, awaits an inferential statistical estimation of the cycles' parameters and of their uncertainties. In summarizing drug effects, only peak times may be tabulated-time-macroscopically (tma)-as clock-hours and times in relation to the synchronizing 12-hourly alternation of light and darkness, a proxy for a marker rhythm. A large body of such carefully collected information here included, however, awaits further time-microscopic (tmi) computer-implemented time series analyses that rely on all available data. Among many other procedures, curve-fitting assesses the uncertainties involved in detecting a reproducible rhythm and/or provides interval as well as point estimates of parameters, such as amplitudes, A, and acrophases, φ, when a single component is fitted. The magnitude and orthophase are the predictable extent of change within a cycle and peak of the fitted model when two or more components are considered. The period involved should be estimated as soon as the length of the time series permits. The A and φ values here computed from mean values taken off a graph should be only an incentive to tmi analyze the original data, so that charts can be mapped that are based on all of the data, rather than depending on the vagaries of peak locations. Putative mechanisms underlying variations, if not rhythms, in drug efficacy are noted. Some tmi considerations are added as concepts and tools for further work that takes more than synchronization with the lighting regimen and/or an obvious living routine into account. Chronomes-time structures, consisting of deterministic and other chaos, trends and a broader-than-circadian spectral element-are pertinent to pharmacology. Chronomes in us resonate with chronomes in our environment, far beyond the photic day and calendar year. Whether the transyears, e.g., of ∼ 1.3 and/or 1.6 years, among other biological (evolutionary?) near-matches of non-photic environmental cycles are also pertinent to the time-structure-based pharmacochronomics of psychotropic drugs prompts the suggestion to collect data replicated along the scales of months and years as well as along that of a day. Estimations of the characteristics of circadian, circaseptan or circannual rhythms based on just one cycle in a day, a week or a year are comparable to taking the pulse for only a heartbeat, i.e., one second! Treatment timed by marker rhythm, rather than by clock-hour, can not only save the amount of needed drug and reduce side effects; it also aims at optimizing the conventional desired effect and to pursue the goal of detecting new effects by focusing on elevated disease risk and the timely development of countermeasures. In the field of drugs affecting sleep and broader brain function, the importance of assessing time structure remains a worthwhile challenge, based on evidence that constitutes a complementary system to the partial system of timing psychotropic drugs.

Original languageEnglish (US)
Title of host publicationSleep and Sleep Disorders
Subtitle of host publicationA Neuropsychopharmacological Approach
PublisherSpringer US
Number of pages40
ISBN (Electronic)9780387276823
ISBN (Print)0387276815, 9780387276816
StatePublished - 2006

Bibliographical note

Publisher Copyright:
© 2006 Springer-Verlag US.


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