27 In one longitudinal study, there was about a 50% chance that an abnormal sleep profile

(on the basis of reduced REM latency, increased REM density, and decreased slowwave sleep) would normalize following 16 weeks of cognitive behavior therapy.28 As research by our group suggested that such sleep abnormalities predicted Inhibitors,research,lifescience,medical a poorer response to both cognitive behavior therapy29 and interpersonal psychotherapy30- but not pharmacotherapy30- they may help to define a neurobiological profile that is more responsive to somatic antidepressant interventions. Antidepressants and sleep neurophysiology Although longitudinal studies of patients withdrawn from antidepressant medications suggest that pharmacotherapy, like psychotherapy, can selleck inhibitor result in

a partial normalization of sleep disturbances,1 antidepressant medications also have pronounced, direct effects on sleep neurophysiology that are also evident in studies of healthy individuals.31 Most antidepressants directly suppress REM sleep, as evident by a marked (ie, Inhibitors,research,lifescience,medical >50%) Inhibitors,research,lifescience,medical reduction in REM time and prolongation (ie, >150%) of REM latency. 1,31 Suppression of REM sleep is evident within hours of beginning therapy with both selective serotonin reuptake inhibitors (SSRIs) and relatively selective norepinephrine reuptake inhibitors such as desipramine or maprotiline.31 Pronounced REM suppression Inhibitors,research,lifescience,medical also is evident during treatment with nonselective monoamine oxidase inhibitors such as phenelzine32 and tranylcypromine.33 Mirtazapine, which enhances noradrenergic activity via blockade of inhibitory α2 receptors, likewise suppresses REM sleep.34 Thus,

as antidepressants with diverse mechanisms of action suppress REM sleep, it is likely that potent modulation of either noradrenergic or serotoninergic Inhibitors,research,lifescience,medical neurotransmission underpins this effect. Among currently available antidepressants, there are only a handful that do not suppress REM sleep- trazodone, bupropion, and nefazodone.1,31 A fourth compound, trimipramine, which is a weaker REM suppressor than the Non-specific serine/threonine protein kinase rest of the tricyclics, does not exert much suppressant effect at lower doses.35 The common link among these medications is that none of the three has potent, direct effects on norepinephrine or serotonin neurotransmission. In one small study, bupropion therapy actually resulted in an intensification of REM sleep in a subset of patients.36 It is not clear if this potentially unique pharmacologic effect is attributable to the proposed mechanism of action of bupropion (ie, potentiation of dopamine neurotransmission) or if it is simply an epiphenomenon of an enhancement of positive affectivity.37 Beyond improvements in sleep efficiency directly resulting from resolution of the depressive syndrome, some antidepressants also exert more rapid beneficial effects on initiation and/or maintenance of sleep.