Contribution of sleep research to the development of new antidepressants

Olivier Le Bon, Olivier Le Bon
unpublished
ince the discovery by Kupfer and Foster 1 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-analysis 2 could be summarized as follows. The sleep of depressive patients is usually accompanied by several anomalies when compared with controls: (i) increased
more » ... ep onset latency; (ii) increased percentage of REMS; (iii) increased REMS density; (iv) decreased sleep maintenance ; (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-analysis 2 also indicated that no sleep anomaly unambiguously distinguishes depression from other psychiatric symptoms, such as panic disorder, 3 generalized anxiety disorder, 4 obsessive-compulsive disorder , 5 schizophrenia, 6 severe dementia, 7 or borderline personality 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 biological markers, 10,11 but the results do not support qualitative distinctions and mutually exclusive subtypes. Instead, only quantitative differences emerged, favoring the concept of a "depressive spectrum." 305 B a s i c r e s e a r c h S Several sleep anomalies are known to accompany depression 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 majority 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 particular is carefully examined during development, for insomnia is currently considered to be a major health concern in industrialized countries. © 2005, LLS SAS Dialogues Clin Neurosci. 2005;7:305-313.
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