Triple Chronotherapy in Adolescents
Condition: Depressive Disorder, Major; Bipolar Depression; Suicidal Ideation
MeSH terms: Depression; Depressive Disorder; Bipolar Disorder; Suicidal Ideation; Depressive Disorder, Major
Study type: Interventional

Summary: 
      Study Purpose This study is a randomized controlled trial examining the effectiveness of TCT
      in the acute treatment of depression and suicidality in adolescents compared to usual
      treatment care, which includes individual and group therapy, and medication adjustments. All
      potential participants will be identified at admission to the Psychiatric Youth Inpatient
      Unit of Billings Clinic and invited to participate. The length of participation is 2 months.

      Study Design The primary research question of this RCT is whether adjunctive TCT in depressed
      adolescents is more effective in the management of depression symptoms and in reducing
      suicidal ideation at two months follow-up, than those adolescents who are receiving usual
      care. A total of three aims are proposed.

      Hypothesis: Adjunctive TCT is more effective in the management of depression symptoms and in
      reducing suicidal ideation at two month follow-up than those adolescents who are receiving
      usual care.

      The first aim is to track the trajectories of depression symptoms, suicidal ideation, and
      insomnia severity in participants receiving TCT and in those receiving treatment as usual
      over 4 days of initial treatment, thereby answering the question of whether adjunctive TCT
      can effectively reduce the severity of depression, insomnia and suicidal ideation.

      The second aim is to examine whether TCT is more effective than usual care in sustaining
      treatment effects to the end of study period (2 months follow-up), therefore answering the
      question whether the effectiveness of the 4-day intervention of adjunctive TCT arm is
      sustainable up to the end of a two-month follow-up.

      Hypothesis: TCT is more effective than usual care in sustaining treatment effects to the end
      of the study period than usual care.

      The third aim is to assess the link to the clinical outcomes (change in depression symptoms,
      suicidal ideation, insomnia severity, and disease-associated quality of life) and patient
      satisfaction with the treatment.

      Hypothesis: Clinical outcomes (depression symptoms, suicidal ideation, insomnia, and
      disease-related quality of life) and patient satisfaction are more effective than usual care
      alone.
    

Detailed description: 
      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.
    

Intervention name(s): Triple Chronotherapy; Treatment as Usual
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Day 0: One night of total sleep deprivation. The first 24 hours are spent with 1:1 nursing care for provision of comfort measures to stimulate wakefulness and to encourage completion of the intervention.
Day 1-4: Sleep phase advancement Day 1: Sleep from 6 PM to 1 AM Day 2: Sleep from 8 PM to 3 AM Day 3: Sleep from 10 PM and 5 AM Day 4: Awaken at 5 AM; discharge following light therapy
On days 1-4 patients will receive bright light therapy at 7am to 7:30am using a 10,000 Verilux light box. At discharge patients will be given a light box, strongly advised to continue the maintenance sleep schedule and bright light therapy at 7am daily for 30 minutes. Patients will be scheduled for follow-up appointments at 1-week, 1-month and 2-month following discharge.; Normal inpatient care, including pharmacotherapy, psychotherapy, milieu therapy and social work interventions
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized Control Trial
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Bright Light Therapy; Sleep Deprivation; Adolescent; Depression; Suicidal Ideation