Sleep mechanisms and the pathophysiology of depression are closely interrelated. Monoaminergic and cholinergic neurotransmission are heavily involved in both. Therefore, it is not surprising that depression is almost invariably associated with sleep abnormalities. Several hypotheses have been advanced to explain their occurrence. One suggests that an increased pressure of REM sleep might be responsible. Another proposes that a deficiency in the mechanism responsible for non-REM sleep, as explained by the two-process model of sleep regulation, may be implicated. Finally, a third hypothesis suggests that an imbalance between the monoaminergic and cholinergic systems in the central nervous system (CNS) could be responsible for the pathophysiology of depression and the observed sleep aberrations.
In principle, most antidepressants increase synaptic levels of norepinephrine, serotonin, and dopamine; yet they may also act on muscarinic and histamine (H1) receptors. These effects purportedly underlie their principal therapeutic mode of action, as well as their potential mechanism of altering sleep architecture. In this line of thought it has been proposed that central to the therapeutic effect of the majority of antidepressants is the observed strong and sustained suppression of REM sleep, without overlooking other factors involved in the mechanisms underlying treatment response. Moreover, tryptophan depletion and studies of selective serotonin reutake inhibitors (SSRIs) in sleep have shown that increases in serotonin levels could mediate the effect on REM sleep, which is often observed during antidepressant treatment. However, changes in non-REM sleep and sleep maintenance may be mediated through the action of other neurotransmitter systems.
Although each antidepressant drug affects sleep architecture differently, there are some common features that characterize the various types of antidepressants. Thus, the majority of antidepressant drugs suppress REM sleep. Some, however, with little or no noradrenergic or serotoninergic reuptake inhibition, such as amineptine, tianeptine, nefazodone, trazodone, bupropion, and trimipramine, do not have clear-cut REM suppressant effects. Sleep continuity and total sleep time are improved with sedative medications, such as most tricyclic antidepressants (TCAs) and several antidepressants with 5-HT2c receptor antagonist properties, such as mianserin, mirtazapine, nefazodone, and trazodone. On the other hand, most (SSRIs) and clomipramine, show evidence early in treatment of stimulating effects, thereby reducing total sleep time and sleep efficiency, and promote wakefulness. However, these effects are fairly short-lived and there are few significant differences among drugs after a few weeks of treatment.
In conclusion, the majority of antidepressant drugs suppress REM sleep and increase REM latency, although this is not always the case. As far as sleep efficiency and total sleep time are concerned, antidepressants can be distinguished as either sedative or energizing agents. This individualized profiling of antidepressants provides a diversity of therapeutic options in terms of the management of concomitant sleep disturbances in depression.