ABSTRACT
Joseph C Wu, Blynn G Bunney, Steven G Potkin
The identification of mechanisms associated with the rapid (within 24 hours) and often robust antidepressant actions of sleep deprivation could poten - tially revolutionize the understanding, prevention, and treatment of depression. Sleep deprivation studies have been conducted for more than 45 years,1 and despite the wide range of protocols (e.g., differing environmental settings, inpatient versus outpatient studies, diagnoses, gender, age, and medications), it is effective in an estimated 40-50% of depressed patients.2 Further, the improvement in depressive symptoms (significant reductions on the Hamilton Depression Rating Scale, HDRS) that can occur within several hours of sleep deprivation are comparable to long-term (2-6 weeks) treatment with conventional anti - depressant medications.3 The evidence that sleep deprivation is effective even in chronic treatmentresistant patients (albeit at lower rates than non-refractory patients)4,5 may imply that it temporarily reverses some fundamental abnormality in depression. On the downside, recovery sleep (even short naps) precipitates relapse in approximately 80% of responders,2,6-9 suggesting that it also affects these same networks. Analyses of recovery sleep architecture (e.g., cumulative sleep time, slow-wave sleep (SWS), and rapid eye movement (REM) sleep density) fail to account for the relapse.2 Circadian factors are likely involved, as evidence suggests that recovery sleep in the morning
hours is more detrimental than sleep at other times of the day in some7,9,10 but not all11 responders. A longitudinal electroencephalographic (EEG) study conducted over a period of 60 hours showed that some patients have repeated periods of microsleep (20 seconds). It was found that an accumulation of these episodes, particularly in the morning hours, is associated with a greater number of postsleep deprivation relapses.9 An ongoing challenge and a focus of current research is the identification of mechanisms to extend the rapid antidepressant responses of sleep deprivation by counteracting the apparent depressiogenic mechanisms associated with recovery sleep.
