triple chronotherapy

The experts who provide CET with clinical updates have the most experience with light therapy, particularly for SAD. However, light alone may not be sufficient for many patients with non-seasonal depression. Over the years, various other non-pharmacological treatments have also been developed, the most unexpected and fast acting being a single night of sleep deprivation, which is now called, in a more positive perspective, wake therapy. Francesco Benedetti, a member of CET’s Advisory Board, has been a pioneer in the research of wake and light therapy, as well as the effect of advancing and stabilizing sleep timing in non-seasonal, predominantly bipolar-depressed, patients.

David Veale, also a member of CET’s Advisory Board, has taken the challenge of trying — for the first time — a combination of all three modalities in a pilot randomized, controlled study of outpatients with major depression. Veale’s group succeeded in recruiting a good number of participants (n=82) and demonstrated that the seemingly complicated protocol called triple chronotherapy — total sleep deprivation for 36 hours, early sleep on the next 4 days, combined with daily morning bright light therapy for 6 months — was feasible for outpatients. A control group received psychoeducation, information on sleep hygiene, and morning exposure to a dim amber light. Within only one week, 52% of the triple chronotherapy group responded, in contrast with 18% of the controls. This is fast! By week 26, 70% achieved response compared with 22% of the controls.

What were the drawbacks or limitations? Only a quarter of those screened completed the trial, and the triple chronotherapy group showed more dropouts than the control group, both before treatment commenced, as well as after. Perhaps the protocol sounded too daunting despite its potential benefits. An infrastructure needs to be created if triple chronotherapy is to become a regular outpatient service, with supporting information to guide the patient throughout.

Veale’s was a feasibility study suggesting that triple chronotherapy, combined with maintenance on light therapy, is a high-benefit, low-risk intervention.  So, it’s time to get moving and seriously investigate this paradigm with more patients in different environments. What other treatment offers patients with major depression such improvement within one week, followed by stable, incremental benefit over months?

Reference: Veale D, Serfaty M, Humpston C,  Papageorgiou A, Markham S,  Hodsoll J, Young AH. Out-patient triple chronotherapy for the rapid treatment and maintenance of response in depression: feasibility and pilot randomised controlled trial. BJPsych Open 2021;7,e2

by Anna Wirz-Justice Centre for Chronobiology, Transfaculty Research Platform, Molecular and Cognitive Neurosciences, Psychiatric Hospital of the University of Basel, Switzerland