Therapeutic sleep deprivation for major depressive disorder: A randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is treated primarily using antidepressant drugs, but clinical effects may be delayed for weeks to months. This study investigated the efficacy of brief therapeutic sleep deprivation (TSD) for inducing rapid improvements in MDD symptoms. METHODS: From November 2020 to February 2023, 54 inpatients with MDD were randomly allocated to TSD and Control groups. The TSD group (23 cases) remained awake for 36 h, while the Control group (31 cases) maintained regular sleep patterns. All participants continued regular drug therapy. Mood was assessed using the 24-item Hamilton Depression Scale (HAMD-24) at baseline and post-intervention in both groups. In the TSD group, the Visual Analogue Scale (VAS) was utilized to evaluate subjective mood during and after the intervention. Cognitive function was assessed at baseline and post-intervention using the Montreal Cognitive Assessment (MoCA). Objective sleep parameters were recorded in the TSD group by polysomnography. The follow-up period spanned one week. RESULTS: HAMD-24 scores did not differ between groups at baseline or post-intervention. However, the clinical response rate was 34.8 % higher in the TSD group on day 3 post-intervention compared to the Control group (3.2 %), but not sustained by day 7. Moreover, responders demonstrated a faster improvement in the VAS score during TSD than non-responders (p = 0.047). There were no significant differences in MoCA scores or objective sleep parameters between the groups. LIMITATIONS: Small sample size and notable attrition rate. CONCLUSIONS: Therapeutic sleep deprivation can rapidly improve MDD symptoms without influencing sleep parameters or cognitive functions. Assessment of longer-term effects and identification of factors predictive of TSD response are warranted.

Synaptic plasticity model of therapeutic sleep deprivation in major depression.

Therapeutic sleep deprivation (SD) is a rapid acting treatment for major depressive disorder (MDD). Within hours, SD leads to a dramatic decrease in depressive symptoms in 50-60% of patients with MDD. Scientifically, therapeutic SD presents a unique paradigm to study the neurobiology of MDD. Yet, up to now, the neurobiological basis of the antidepressant effect, which is most likely different from today's first-line treatments, is not sufficiently understood. This article puts the idea forward that sleep/wake-dependent shifts in synaptic plasticity, i.e., the neural basis of adaptive network function and behavior, represent a critical mechanism of therapeutic SD in MDD. Particularly, this article centers on two major hypotheses of MDD and sleep, the synaptic plasticity hypothesis of MDD and the synaptic homeostasis hypothesis of sleep-wake regulation, and on how they can be integrated into a novel synaptic plasticity model of therapeutic SD in MDD. As a major component, the model proposes that therapeutic SD, by homeostatically enhancing cortical synaptic strength, shifts the initially deficient inducibility of associative synaptic long-term potentiation (LTP) in patients with MDD in a more favorable window of associative plasticity. Research on the molecular effects of SD in animals and humans, including observations in the neurotrophic, adenosinergic, monoaminergic, and glutamatergic system, provides some support for the hypothesis of associative synaptic plasticity facilitation after therapeutic SD in MDD. The model proposes a novel framework for a mechanism of action of therapeutic SD that can be further tested in humans based on non-invasive indices and in animals based on direct studies of synaptic plasticity. Further determining the mechanisms of action of SD might contribute to the development of novel fast acting treatments for MDD, one of the major health problems worldwide.

Tratamientos biológicos (no farmacológicos) en psiquiatría / Biological (non-pharmacological) treatments in psychiatry

Los psicofármacos y la psicoterapia son efectivos para muchos pacientes aquejados de trastornos mentales o problemáticas psicosociales. No obstante, algunos pacientes no responden a estas intervenciones, por lo que se necesitan de otras propuestas basadas en tratamientos biológicos (no farmacológicos). Estas técnicas se han ido desarrollando gracias a una mejor comprensión de los modelos neurofisiológicos y neuroanatómicos del humor, pensamiento y regulación del comportamiento, así como de estrategias más avanzadas para la modificación de la actividad neural. Con base en lo anterior, el objetivo de este artículo es presentar una actualización sobre los conceptos e indicaciones de la terapia electroconvulsiva, de las técnicas de estimulación cerebral, de la fototerapia y de la privación terapéutica del sueño.

Psychotropic drugs and psychotherapy are effective for many patients suffering from mental disorders or psychosocial problems. However, some patients do not respond to these interventions, so other proposals based on biological (non-pharmacological) treatments are needed. These techniques have been developed thanks to a better understanding of the neurophysiological and neuroanatomic models of mood, thought process and behavioral regulation, as well as more advanced strategies for the modification of neural activity. Based on the above, the objective of this article is to present an update on the concepts and indications of electroconvulsive therapy, brain stimulation techniques, phototherapy and therapeutic sleep deprivation.