Since 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: (1) increased sleep 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-analysis2
also indicated that no sleep anomaly unambiguously distinguishes depression from other psychiatric symptoms, such as panic disorder,3
generalized anxiety disorder,4
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,10,41
but the results do not support qualitative distinctions and mutually exclusive subtypes. Instead, only quantitative differences emerged, favoring the concept of a “depressive spectrum.”
As a consequence, sleep anomalies and manipulations are currently generally considered to be more useful for uncovering neurophyslological mechanisms underlying psychiatric disorders and symptoms and for understanding sleep itself than as a diagnostic tool for clinicians. Theories have been developed to explain what is observed in the sleep of untreated patients with major depressive disorder (MDD), the effects of drugs on their sleep, and the effects of sleep manipulations, such as total sleep deprivation or specific REMS deprivation.
Many interesting questions are still only partially resolved. Do effective antidepressants counteract what is observed in the sleep of untreated MDD patients? Does this mean that whatever is counteracted reflected depression in the first place? Is it through sleep modification that drugs act on depression, or are the observations merely epiphenomena? Are there clues that a given treatment will be effective in a fortnight? Are sleep anomalies signs of a biological trait? Do they represent the depressive state or do they go away after the clinical episode is gone? Do they represent scars of previous episodes? The situation for neuromediators is just as complex. Serotonin (5-hydroxytryptamine [5-HT]), for instance, is a target of choice in the fields of both depression and sleep disorders. Selective serotonergic agents are available, which could help us clarify the relationships between these two entities. However, the existence of several receptor sites (5-HT1A_D, 5-HT2A_C, 5-HT3, and 5-HT4), which have agonist or antagonist interactions with each other, not to mention their potential interactions with γ-aminobutyric acid (GABA), noradrenaline (NA), or dopamine (DA) receptors, means that the map to be built is likely to be a complicated one.
Sleep research is also now an important part of the development of new psychotropic drugs, and almost every new agent has its effects on sleep carefully analyzed. As these data are the property of the patent owners and few are published in peer-re viewed journals, it is not always possible to precisely evaluate how sleep studies actually influence the future of these drugs, but it is likely to be substantial.
Insomnia is probably the main reason why action on sleep is studied so rigorously Poor sleep has received an increasing amount of attention in the last decade.12,13
More than 90% of depressive patients experience insomnia, whereas only 5% to 8% experience hypersomnia.14
Persistent insomnia multiplies the risk of developing MDD within a year by three.15
It increases the risk of recurrence of depression.16
Mood disorders are frequent, but often go undiagnosed in chronic poor sleepers.17
Optimal treatment of insomnia is thus currently a major health concern in industrialized countries. Since drugs can alleviate or worsen sleep initiation and maintenance, the development and selection of antidepressants in patients should take insomnia into account. Also, antidepressants may exacerbate restless legs or periodic limb movement syndromes, which results in a worsening of insomnia.
In this review, we will (i) describe the effects of the main antidepressants on sleep; (ii) examine which signs are predictive of good prognosis; and (iii) analyze the theoretical aspects of sleep anomalies in depression and actions on sleep by antidepressants.