S27-01 - Sleep Timing and Sleep Manipulation as Antidepressants

Psychiatry Research, 2009

Profound disturbances in sleep architecture occur in major depressive disorders (MDD) and in bipolar affective disorders. Reduction in slow wave sleep, decreased latency of rapid eye movement (REM) sleep and abnormalities in the timing of REM/non-REM sleep cycles have all been documented in patients with MDD. It is thus evident that an understanding of the basic mechanisms of sleep regulation is essential for an analysis of the pathophysiology of depressive disorders. The suprachiasmatic nucleus (SCN), which functions as the body's master circadian clock, plays a major role in the regulation of the sleep/wakefulness rhythm and interacts actively with the homeostatic processes that regulate sleep. The control of melatonin secretion by the SCN, the occurrence of high concentrations of melatonin receptors in the SCN, and the suppression of electrical activity in the SCN by melatonin all underscore the major influence which this neurohormone has in regulating the sleep/wake cycle. The transition from wakefulness to high sleep propensity is associated with the nocturnal rise of endogenous melatonin secretion. Various lines of evidence show that depressed patients exhibit disturbances in both the amplitude and shape of the melatonin secretion rhythm and that melatonin can improve the quality of sleep in these patients. The choice of a suitable antidepressant that improves sleep quality is thus important while treating a depressive disorder. The novel antidepressant agomelatine, which combines the properties of a 5-HT 2C antagonist and a melatonergic MT 1 /MT 2 receptor agonist, has been found very effective for resetting the disturbed sleep/wake cycle and in improving the clinical status of MDD. Agomelatine has also been found useful in treating sleep problems and improving the clinical status of patients suffering from seasonal affective disorder.

Journal of Affective Disorders, 2019

Background: There are a dozen studies on double or triple chronotherapy in depression (sleep deprivation [wake therapy] + light therapy + sleep advance/stabilization). We investigated efficacy and feasibility of a modified triple chronotherapy protocol. Methods: Thirty-five hospitalized patients with moderately severe non-seasonal depressive disorder, mostly free from antidepressants, underwent a 6-day protocol consisting of partial sleep deprivation late in the second half of the night (from 4:00 to 8:00) in a light therapy room (blue-enhanced white light increased hourly from 600→ 1300→2200→2800 lx) alternating with recovery nights with morning light treatment from 7:00 to 8:00. Patients were randomized to wear glasses with no filter (clear, N = 19) or filtering blue wavelength (orangeappearance, light intensity diminution by ∼70%, N = 16) during the treatments. Sleep was targeted to be shifted at least 1 h earlier. Depression was scored using HDRS-17 (Hamilton Depression Rating Scale) and BDI-II (Beck Depression Inventory-II)-before and after the 6-days treatment, HDRS-6-SR-daily, and visual analogue scales (VAS) for mood and energy-several times every day. Results: Depression levels significantly declined following the first night and after 6-days treatment, with no difference between white and orange lights. Nevertheless, some superiority of white light emerged with respect to response rate (mood VAS), immediate effect during the 4-h treatment sessions (energy VAS), and expected treatment outcomes. All patients successfully advanced bedtime/wake-up (by 30-40 minutes) and resisted naps during daytime. Limitations: Relatively small sample size. Conclusions: The modified triple chronotherapy was well tolerated and improved depression. Light spectrum/ intensity plays some role in the response.

Acta Psychiatrica Scandinavica, 2017

ER. Wake and light therapy for moderate-to-severe depressiona randomized controlled trial Objective: To examine the efficacy of using wake and light therapy as a supplement to standard treatment of hospitalized patients with depression. Method: In this randomized, controlled study, 64 patients with moderate-to-severe depression were allocated to standard treatment or to the intervention, which additionally consisted of three wake therapy sessions in one week, 30-min daily light treatment and sleep time stabilization over the entire nine-week study period. Results: Patients in the wake therapy group had a significant decrease in depressive symptoms in week one as measured by HAM-D 17 , 17.39 (CI 15.6-19.2) vs. 20.19 (CI 18.3-22.09) (P = 0.04), whereas no statistically significant differences were found between the groups in weeks two to nine. At week nine, the wake therapy group had a significantly larger increase in general self-efficacy (P = 0.001), and waking up during nights was a significantly less frequent problem (1.9 times vs. 3.2) (P = 0.0008). In most weeks, significantly fewer patients in the wake therapy group slept during the daytime, and if they slept, their naps were shorter (week three: 66 min vs. 117 min P = 0.02). Conclusion: The antidepressant effect initially achieved could not be maintained during the nine-week study period. However, sleep and general self-efficacy improved.

2009

2011

Circadian rhythm abnormalities, as shown by sleep/wake cycle disturbances, constitute one the most prevalent signs of depressive illness, advances or delays in the circadian phase, or changes in rhythms' amplitude, being documented in patients with major depressive disorder (MDD), seasonal affective disorder or bipolar disorder. The disturbances in the amplitude and rhythm of melatonin secretion that occur in patients with depression resemble those seen in subjects with chronobiological disorders, thus suggesting that a link between chronobiological disturbances and depressed mood exists. Studies testing variants of genes that control the circadian system have reported circadian gene polymorphisms in depressive illness. Although many antidepressants such as the tricyclics, monoamine oxidase inhibitors, serotonin-norepinephrine reuptake inhibitors, several serotonin receptor antagonists and selective serotonin reuptake inhibitors (SSRIs) have all been found successful in treating depression, their use is often associated with a disruptive effect on the sleep/wake cycle. SSRIs, currently the most widely prescribed of the antidepressants, are well known for their exacerbation of insomnia. The recently introduced melatonin agonist and selective serotonin antagonist antidepressant, agomelatine, which has melatonin MT t and MT 2 receptor agonist and 5-HT 2c antagonist properties, has been useful in treating patients with MDD. Its rapid onset of action and effectiveness in improving the mood of depressed patients has been attributed to its ability to improve sleep/wake cycle quality. Thus, current conceptualization of depressive illness needs to be expanded to include the role of circadian dysregulation in the development of the disease.

Behavioral Sleep Medicine, 2016

Background-There are complex, bidirectional associations between major depressive disorder and insomnia. In the present study, we evaluated insomnia as a moderator of response to antidepressant therapy in the context of a sleep manipulation (time in bed restriction) for major depressive disorder. Methods-Fifty-eight adults with major depressive disorder received 8 weeks of fluoxetine 20-40 mgs and were randomized to 8 hours' time in bed (8h TIB) or 6 hours' time in bed (6h TIB) for the first 2 weeks (participants in the 6h TIB condition were further randomized to a delayed bedtime (Late Bedtime) or advanced risetime (Early Risetime) group). Insomnia was assessed at baseline using the Insomnia Severity Index. Depression symptom severity was determined by the clinician-rated 17-item Hamilton Rating Scale for Depression (HAMD-17), completed weekly. Results-A group by time interaction was observed whereby HAMD-17 scores were higher for participants assigned to the 6h TIB group (without insomnia, weeks 3 through 7; with insomnia from week 3 through 6, ps < .05) relative to participants without insomnia assigned to the 8h TIB group. There were no differences in HAMD-17 scores for participants with insomnia in the 6h TIB group relative to the 8h TIB group. Conclusion-These preliminary findings suggest that response to fluoxetine may be hindered by TIB restriction in individuals without insomnia. Individuals with insomnia respond similarly to fluoxetine regardless of whether their TIB is restricted. Limitations include exclusive use of selfreport measures to categorize insomnia, and small sample sizes in several of the subgroups. Sleep disturbances are exceedingly common in depression. Nearly 85% of adults with major depressive disorder (MDD) subjectively report at least one symptom of insomnia (Sunderajan et al., 2010). The number of nights with insomnia symptoms and frequency of nighttime awakenings are associated with depression severity (Taylor, Lichstein, Durrence, Reidel, & Bush, 2005). Depression is also associated with objective sleep disturbances, including shorter REM onset latency, less slow wave sleep, and less efficient sleep

BMJ Open

IntroductionSleep-wake and circadian disturbance is a key feature of mood disorders with a potential causal role and particular relevance to young people. Brexpiprazole is a second-generation antipsychotic medication with demonstrated efficacy as an adjunct to antidepressant treatment for major depressive disorder (MDD) in adults, with preliminary evidence suggesting greater effectiveness in subgroups of depressed patients with sleep disturbances. This clinical trial aims to evaluate the relationships between changes in sleep-wake and circadian parameters and changes in depressive symptoms following adjunctive brexpiprazole treatment in young adults with MDD and sleep-wake disturbance.Methods and analysisThis study is designed as a 16 week (8 weeks active treatment, 8 weeks follow-up) mechanistic, open-label, single-arm, phase IV clinical trial and aims to recruit 50 young people aged 18–30 with MDD and sleep-wake cycle disturbance through an early intervention youth mental health c...

The Journal of clinical psychiatry, 1998

Sleep disturbances are an integral feature of depressive disorders. Like the disorders themselves, the sleep disturbances associated with depression are heterogeneous, ranging from hypersomnia to marked difficulties maintaining sleep. These difficulties are to some extent age dependent and reflect abnormalities of central nervous system arousal. Moreover, the sleep disturbances associated with depression have both reversible, or state-dependent, and more persistent trait-like characteristics. Polysomnographic recordings can be used to document sleep maintenance difficulties, and they often also reveal reduced slow wave sleep, an early onset of the first episode of rapid eye movement (REM) sleep, and increased phasic REM sleep. A deficit of serotonergic neurotransmission, a relative increase in pontine cholinergic activity, and, perhaps, an excess of noradrenergic and corticotropin-releasing hormone activity have been implicated in the pathogenesis of the sleep disturbances of more s...

Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2000

This paper reviews sleep disturbances in patients with major depressive disorders and the effects of different classes of antidepressants on sleep. It is clear from the studies reviewed that not all antidepressants improve sleep, and, indeed, some worsen sleep disturbances in patients with depression. Whether sleep is improved or further disrupted is of high clinical significance, because persistent sleep problems elevate the risk of relapse, recurrence, or suicide, as well as the need for augmenting medications.

Handbook of clinical neurology, 2012