Vol 7 No.4 - Sleep Disorders, Neuropsychiatry, and Psychotropics
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ince the discovery by Kupfer and Foster1 of a link between depression and a shorter interval between sleep onset and the first episode of rapid eye movement sleep (REMS) than in controls, the relationship between psychiatric  disorders  and  sleep  has  been  the  focus  of intense research.Twenty years later, the results of a large meta-analysis2 could be summarized as follows.The sleep of depressive patients is usually accompanied by several anomalies when compared with controls: (i) increased sleep onset latency; (ii) increased percentage of REMS; (iii) increased REMS density; (iv) decreased sleep main- tenance; (v)  decreased  percentage  of  slow-wave  sleep (SWS); and (vi) shortened REMS latency (RL).Although the relative influences of age, gender, and severity of the depressive episode on the observed sleep anomalies still need to be fully clarified, it is relatively easy to distinguish patients from controls on the basis of their sleep. The above meta-analysis2 also indicated that no sleep anomaly unambiguously distinguishes depression from other psychiatric symptoms, such as panic disorder,3 gen- eralized anxiety disorder,4 obsessive-compulsive disor- der,5 schizophrenia,6 severe dementia,7 or borderline per- sonality disorder.8 Furthermore, no obvious distinction between depression subclasses (primary, endogenous, atypical, etc) has been demonstrated by elements of sleep polysomnography. Perhaps the best supported distinction is that between psychotic and nonpsychotic depression.9 A few studies have tried the opposite route, ie, to cluster psychiatric disorders or subtypes as a function of biolog- ical markers,10,11 but the results do not support qualitative distinctions and mutually exclusive subtypes. Instead, only quantitative differences emerged, favoring the con- cept of a “depressive spectrum.” 3 0 5 B a s i c   r e s e a r c h S Copyright © 2005 LLS SAS.  All rights reserved www.dialogues-cns.org Contribution of sleep research to the development of new antidepressants Olivier Le Bon, MD, PhD Keywords:  sleep research; drug development; antidepressant; treatment
efficacy; EEG Author  affiliations:  Olivier  Le  Bon,  MD,  PhD,  Université  Libre  de  Bruxelles, Brussels, Belgium Address  for  correspondence:  Prof  Olivier  Le  Bon,  CHU  Brugmann,  Place  Van Gehuchten 4, 1020 Brussels, Belgium (e-mail: lebono@skynet.be) Several sleep anomalies are known to accompany depres- sion and other psychiatric disorders, and to be partially modified by drugs efficient on clinical symptoms. Many puzzling theoretical questions remain, even after 30 years of research, because these drugs do not act in a uniform way: some reduce slow-wave sleep while others increase it; some prolong rapid-eye movement sleep latency, while others do not. The relationship between insomnia and depression is likely to be a close one, since a large major- ity of patients with depression suffer insomnia, and that insomnia can predate depression by a few years. However, questions remain here, too, since sleep deprivation is also an  effective  means  to  combat  depression,  and  some patients present with hypersomnia rather than insomnia. This review details the action of all current classes of anti- depressants on sleep. It examines the predictive value of baseline electronencephalographic sleep symptoms or early modifications due to treatment for eventual clinical efficiency. We will also discuss the two main theories on the relationship between sleep and depression. The action on sleep of all new drugs—and antidepressants in partic- ular—is  carefully  examined  during  development,  for insomnia is currently considered to be a major health con- cern in industrialized countries.     © 2005, LLS SAS Dialogues Clin Neurosci. 2005;7:305-313.