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Review
. 2006 Mar;31(2):93-100.

The "delayed onset" of antipsychotic action--an idea whose time has come and gone

Ofer Agid  1 , Phillip Seeman, Shitij Kapur
Affiliations
Review

The "delayed onset" of antipsychotic action--an idea whose time has come and gone

Ofer Agid et al. J Psychiatry Neurosci. 2006 Mar.

Abstract
in English, French

For years, it has been known that the "onset" of the antipsychotic response is "delayed," and this notion is expressed in many major textbooks, informs clinical decisions and has even led to the search for biological markers responsible for this delayed onset. But is the onset of antipsychotic action really delayed? In this review, we bring together data from several recent studies of antipsychotic drugs that show that the onset of the antipsychotic effect is within the first day; the effect is distinguishable from behavioural sedation; is specific to antipsychotic drugs; is seen with oral and parenteral preparations; and is seen with typical and atypical antipsychotics. More anti- "psychotic" improvement is seen within the first 2 weeks than in any other 2-week period thereafter, and more improvement is seen in the first month than in the rest of the year of follow-up. This body of data convincingly refutes the notion of "delay" in the onset of antipsychotic action and suggests an "early" onset instead. The implications of this finding for clinical decision-making, mechanisms of antipsychotic action and drug discovery are discussed.

On sait depuis des années que « l'apparition » de la réponse aux antipsychotiques est « tardive » et ce concept exprimé dans nombre de manuels réputés éclaire des décisions cliniques et est même à l'origine de la recherche de marqueurs biologiques responsables de cette apparition tardive. L'apparition de l'effet des antipsychotiques est-elle toutefois véritablement tardive? Dans cette critique, nous réunissons des données provenant de plusieurs études récentes sur des antipsychotiques qui montrent que leur effet se fait sentir au cours de la première journée, qu'il est possible de distinguer l'effet de la sédation comportementale, que l'effet est spécifique aux antipsychotiques, qu'on le constate avec des préparations orales et parentérales et qu'il se fait sentir avec des antipsychotiques typiques et atypiques. On constate davantage d'améliorations anti « psychotiques » au cours des deux premières semaines qu'au cours de toute autre période de deux semaines par la suite et une amélioration plus marquée au cours du premier mois que pendant le reste de l'année de suivi. Cette masse de données réfute de façon convaincante le concept d'apparition « tardive » de l'effet antipsychotique et indique plutôt une apparition « précoce ». Les répercussions de cette constatation sur la prise de décisions cliniques, les mécanismes de l'effet antipsychotique et la découverte des médicaments font l'objet de discussions.

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Figures

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Fig. 1: Delayed-onset hypothesis versus early onset hypothesis.
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Fig. 2: Response to antipsychotic treatment over time. (A) Mean (and standard error [SE]) overall clinical improvement over time (total score) (p < 0.001). (B) Mean (and SE) change in core psychotic symptoms over time (p < 0.01). The p values are for the main effect of time. The error bars represent standard error. Figure reproduced with permission from the American Medical Association (Arch Gen Psychiatry 2003;60:1228-3538).
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Fig. 3: Response to antipsychotic treatment over time after removal of the placebo effect. (A) Mean (and standard error [SE]) weekly overall clinical improvement (p < 0.001). (B) Mean (and SE) weekly change in core psychotic symptoms (p = 0.08). The p values are for the main effect of time. The error bars represent standard error. Figure reproduced with permission from the American Medical Association (Arch Gen Psychiatry 2003;60:1228-3538).
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Fig. 4: Response to antipsychotic treatment over time (n = 748). (A) Mean overall clinical improvement over time (total Brief Psychiatric Rating Scale score). (B) Mean change in core psychotic symptoms over time. Figure reproduced with permission from the Society of Biological Psychiatry (Biol Psychiatry 2005;57:1543-941).
See this image and copyright information in PMC

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