The Advance Project - Advancing Sleep Timing to Improve Depression, a Randomised Clinical Trial.

Objective Patients treated at outpatient psychiatric services for major depression improves slowly from their depression despite use of psychopharmacological, psychological, and supportive methods. This is in many cases due to severe sleep disturbances as part of their current depressive episode. Typically, these patients have difficulties keeping their habitual sleep-wake cycle, that drifts to later in the evening and morning. Thus, patients who, before being depressed, sleeps around 11 PM and wake up around 7 AM, often drift to a later sleep schedule at around 1 AM and a wake-up time at 9 AM or even later during their depressive period. The reason for the drift of the sleep schedule is mainly caused by reduced signals to the circadian system from daylight, social input, dieting and exercise. This reduced input is partly a result of the changed behavior of patients due to their depressive symptoms making them less structured, less socially active, less physically active, eating erratically, and staying more indoors thereby receiving less daylight. Another reason for the sleep drift is the presence of diurnal variation of depressive symptoms with morning worsening and evening improvement tempting patients to stay up later because of the better evening mood. The sleep drift makes patients out of synchrony with societal and workplace rhythms, and the investigators have clinical and research evidence for mood worsening associated with sleep drift and of improvement of depression when patients correct their sleep drift.

The physiological background behind why late sleep worsens and maintain depression is thought to be caused by a sleep induced inhibition of the raphe nuclei in the brain stem downregulating the serotonergic activity in the forebrain in the late phase of the sleep period.

The association between depression and sleep/sleep timing is well established from the bulk of literature on sleep deprivation, and sleep phase advance. Regulation of sleep disturbances thus has a great potential as a specific new treatment target.

Our recent study showed that a newly developed psychoeducation method, Circadian Reinforcement Therapy (CRT) could prevent sleep drift and improve mood in patients discharged from inpatient wards. The standard psychoeducation manuals used at psychiatric services do not focus adequately on the relation between signals to the circadian system, sleep timing, and mood. The principle in the CRT is based on scientific findings that sleep timing and thus mood is for a large part a result of how the actual day is spend - what signals is reaching the circadian system. The influence of light during the day is termed Prior Light History and has been documented to influence sleep, circadian rhythms, and melatonin secretion/suppression. The main time signals to the circadian system (zeitgebers) are light (electrical or daylight), social activity, exercise, and diet. The CRT method aimed to strengthen all these time signals and normalize the sleep timing leading to improvement of depression.

The objective of this project is to investigate whether the use of an adjusted CRT method named CRT-Advance focusing even more on advancement of the sleep-wake cycle can induce an antidepressant effect in selected patients that have drifted in their sleep during their depressive episode (enriched sample).