Andrew Winokur

Sleep complaints are common in patients with major depressive disorder (MDD). Both MDD and antidepressant drugs characteristically alter objective sleep measures. This study compares the effects of mirtazapine and fluoxetine on sleep continuity measures in DSM-IV MDD patients with insomnia. Patients (N = 19) received initial baseline polysomnography evaluations over 2 consecutive nights. Subjects were randomly assigned to either fluoxetine (20-40 mg/day) or mirtazapine (15-45 mg/day) treatment for an 8-week, double-blind, double-dummy treatment trial. Single-night polysomnograms were conducted at weeks 1, 2, and 8, with depression ratings assessed at baseline and weeks 1, 2, 3, 4, 6, and 8. Statistical analysis was performed by repeated-measures analysis of variance followed by Dunnet's post hoc analyses. Patients receiving mirtazapine (N = 8) had significant improvement in objective sleep physiology measures at 8 weeks. Improvements in sleep latency, sleep efficiency, and wake after sleep onset were significant after only 2 weeks of mirtazapine treatment. No significant changes in sleep continuity measures were observed in the fluoxetine group (N = 11). Both groups improved clinically in mood and subjective sleep measures from baseline, with no differences between groups. These data demonstrate the differential effects of mirtazapine and fluoxetine, with significant improvement in favor of mirtazapine, on objective sleep parameters in MDD patients with insomnia.

This review summarizes current findings regarding effects of antidepressant compounds on sleep architecture and interprets their clinical relevance. Effects of the major classes of antidepressant drugs on sleep properties are presented, with the antidepressant compounds organized into categories based primarily on their putative mechanism of action. The majority of antidepressant compounds, across several different categories, exhibit robust suppression of REM sleep. Others, such as bupropion and nefazodone, lack REM suppressant effects. Such findings support the idea that critical neurochemical mechanisms involved in the regulation of discrete sleep stages can be elucidated by means of polysomnographic investigations utilizing pharmacologically targeted agents. Clinicians have appreciated the importance of antidepressant drug effects on sleep when considering therapeutic options for patients. While such decisions in the past were based on empirical observations, an increasing amount of information regarding specific effects of different antidepressant drugs on sleep continuity and sleep architecture is available. Thus, clinicians may choose to consider profiles of sleep effects for different antidepressant drugs in the initial selection of an antidepressant compound. Depression and Anxiety 14:19–28, 2001.

Circadian and sleep components modulate anterior pituitary release of thyrotropin (TSH), the chemical substance regulating the thyroid hormones, thyroxine (T4), and triiodothyronine (T3). The present study examined TSH, T4, and T3 concentrations across the wake-sleep boundary time (2300-0130 hours) before, during, and after a 64-h sleep deprivation paradigm. Additionally, adrenocorticotropic hormone (ACTH) and cortisol were measured as an index of hypothalamic-pituitary-adrenal axis activation. Activity levels and ratings of effort required to perform cognitive tasks were also incorporated to evaluate physical and cognitive load, respectively, across the study period. Assessing the combined effects of activity and sleep deprivation on thyroid hormone economy is relevant to the relationship of high physical and/or cognitive performance demands during sleep deprivation inherent in extended military operations and space exploration. There were 12 healthy subjects who were monitored during a 2-d baseline period, 3 d of total sleep deprivation, and 2 nights of recovery sleep. Serum samples were collected at 2300 hours and 0130 hours across the entire study period, and measured for TSH, T4, T3, and glucocorticoids. Change scores evaluated at the wake-sleep boundary time demonstrated significant inhibitory effects of sleep on thyroid hormone measures. As expected, sleep deprivation was associated with elevated TSH. However, sleep deprivation also significantly increased circulating levels of T3 at 2300 hours and T4 concentration change scores (2300-0130 hours). Glucocorticoid levels did not track thyroid hormone changes. Physical activity remained constant while subjective ratings of effort to perform cognitive tasks increased significantly during sleep deprivation. Compared to sleep deprivation studies under constant conditions reporting no change in peripheral T4 and T3 levels, the present study suggests activity level, including cognitive effort to perform, during total sleep deprivation may produce substantive changes in the thyroid axis.