Phase Advance Is an Actimetric Correlate of Antidepressant Response to Sleep Deprivation and Light Therapy in Bipolar Depression

Abstract

The combination of total sleep deprivation (TSD) and light therapy (LT) in bipolar depression causes rapid antidepressant effects, and its mechanism of action has been hypothesized to involve the enhancement of all of the monoaminergic systems targeted by antidepressant drugs (serotonin, dopamine, norepinephrine). It is still unknown if the clinical effects are paralleled by changes in biological rhythms. In a before/after design of a study of biological correlates of response, 39 inpatients affected by Type I Bipolar Disorder whose current depressive episode was without psychotic features were treated for one week with repeated TSD combined with morning LT. Wrist actigraphy was recorded throughout the study. Two-thirds of the patients responded to treatment (50% reduction in Hamilton Depression score). Responders showed an increase in daytime activity, phase-advance of the activity-rest rhythm of 57 min compared to the pre-treatment baseline, and reduced nighttime sleep. Non-responders did not show significant changes in the parameters of their activity-rest rhythm. Phase advance of the activity-rest rhythm is an actimetric correlate of the antidepressant response to TSD and LT in bipolar depression. Results are consistent with the known effects of sleep-wake manipulations and neurotransmitter function on the suprachiasmatic nucleus.

Circadian rest–activity rhythm in individuals at risk for psychosis and bipolar disorder

“…More severe depression was associated with later circadian oscillators about the onset of sleep. It is interesting that a phase advance in actimetric parameters correlates with an antidepressant response in bipolar patients to chronotherapeutic interventions (Benedetti et al, 2007). Similarly, in the present study, the ARMS group began their M10 (the most active 10 h of the day) later, showing a gap between sleep onset.…”

Sleep Deprivation in Mood Disorders

“…In reported trials, recovery sleep is free and undisturbed, with the patient choosing the most appropriate bedtime and waking up when the night sleep ends spontaneously. Actigraphic evidence showed that after total SD patients significantly anticipate bedtime and sleep onset, and sleep more and better than before treatment (when sleep was usually disturbed by depressive insomnia) [52] .…”

“…Our group developed a treatment schedule based on repeated total SD, three times a week, resulting in a lengthening of the sleep-wake period from the usual 24 to 48 h [1, [45][46][47][48][49][50][51][52] . Each SD cycle is composed of a period of 36 h awake, and on the 1st, 3rd and 5th day, patients are totally sleep deprived from 07: 00 h until 19.00 h of the following day.…”

Selective serotonin reuptake inhibitors and raft inhibitors shorten the period of Period1-driven circadian bioluminescence rhythms in rat-1 fibroblasts

“…A recent study has shown that when total sleep deprivation and light therapy advance phase of activity-rest rhythms in bipolar depression patients, the degree of depression is significantly reduced/improved (Benedetti et al, 2007). Phase advancing effects of these two therapies support the significant relations between circadian rhythm generations and regulation of mood.…”