Effects of antidepressant drugs on sleep EEG in patients with major depression - Mechanisms and therapeutic implications

The ability of many antidepressant drugs to decrease rapid eye movement (RE M) sleep can be attributed to facilitation of noradrenergic and/or serotone rgic function or to muscarinic cholinergic blockade, A common characteristi c of antidepressant compounds devoid of a clear REM suppressant effect, suc h as amineptine, buspirone, iprindole, nefazodone, tianeptine, trazodone an d trimipramine, is their weak (or absent) ability to inhibit serotonergic u ptake, In this regard, some preliminary results suggest that serotonin (5-h ydroxytryptamine; 5-HT) may inhibit REM sleep via post-synaptic serotonin 5 -HT1A receptors, Sleep continuity and slow-wave sleep (SWS) are variously affected by antide pressants: sleep continuity is found to be improved by sedating antidepress ants such as the tricyclics, whereas selective serotonin reuptake inhibitor s, venlafaxine, amfebutamone (bupropion) and phenelzine exhibit alerting ef fects, i.e. tend to enhance vigilance and therefore to induce arousal durin g sleep. There is some evidence suggesting that the ability of antidepressa nt drugs to enhance SWS reflects their 5-HT2C antagonist properties. Redist ribution of slow wave activity in the first part of the night after antidep ressant administration has been consistently described. However. it can be concluded from data on citalopram, paroxetine, trazodone and venlafaxine th at antidepressants produce dissimilar electroencephalogram (EEG) spectral r esponse patterns. This may be attributable to differences in their pharmaco logical actions. Thus, although the studies reviewed in the present paper do not provide cle ar evidence of a common and unique pharmaco-sleep EEG profile of antidepres sant drugs, fundamental research on sleep microarchitecture will became inc reasingly important for interpreting the relevance of antidepressant drug e ffects on sleep physiology in major depression.