Triple Chronotherapy in Adolescents

According to the Centers for Disease Control, almost 11% of youth will have met criteria for a depressive disorder by the time they are 18 years of age. Depression can significantly impact quality of life and is associated with increased risk of suicide, the second leading cause of death among individuals between ages 10 -24 years. While evidence-based treatments for the management of depression in adolescents exist, social stigma, perception that depression can be self-managed without treatment and side effects of antidepressants all pose treatment barriers. Moreover, the two most widely used evidence-based treatments, antidepressants and cognitive behavioral therapy, have medium to small effect sizes, and a significant need exists to develop more effective strategies to manage depression in adolescents. Adjunctive treatments for depression such as electroconvulsive therapy, transcranial magnetic stimulation, and ketamine have been shown to be effective in producing an antidepressant response in the adult population; however, none are yet recommended for safe use in adolescents. Moreover, ketamine and electroconvulsive therapy are associated with significant side effects, making each a less desirable treatment for depression among adolescent patients and their families. Chronotherapy, defined as the therapeutic manipulation of sleep-wake cycles, is a promising approach for the treatment of adolescent depression. The study of chronotherapeutic interventions as an adjunctive treatment for depression began in the 1970s, when investigators noted a rapid, albeit transient, antidepressant response to sleep deprivation. Another chronotherapeutic technique, bright light therapy, has consistently shown benefit in the treatment of seasonal affective disorders. Its use in the treatment of non-seasonal unipolar and bipolar depression has also shown promising results. Combination chronotherapeutics, such as triple chronotherapy (TCT), have also been trialed with some demonstrated efficacy. TCT is an approach that combines sleep deprivation, bright light therapy, and sleep phase advancement in the acute treatment of depression. One of the first open label TCT studies enrolled 143 consecutive patients; of the 141 adults who completed the study, a significant acute antidepressant response was found in up to 70% of patients with bipolar depression, and a sustained response in up to 55% of patients at 1-month. A more recent randomized control trial of 75 adults employed an abbreviated protocol that included one night of sleep deprivation, three nights of sleep phase advancement, and bright light therapy in each of the four mornings of the intervention. This study demonstrated similar, accelerated antidepressant responses along with a decrease in suicidality and improved sleep quality. Although evidence is growing for the use of TCT to manage acute depression and suicidality in adults, studies in the adolescent population are lacking. It was hypothesized by Gest et al. (2014) that the use of chronotherapy in adolescents could be an effective treatment modality, and researchers were urged to explore this area. In 2016, Gest et al. compared combined sleep deprivation and bright light therapy to bright light therapy alone in adolescents and found a significant antidepressant response to bright light therapy alone, but no significant benefit was gained with the addition of one night of total sleep deprivation. Sleep phase advancement was absent in this study. No studies were found that examined the use of comprehensive TCT in adolescents compared to usual practice in the inpatient setting.