Out-patient triple chronotherapy for the rapid treatment and maintenance of response in depression: feasibility and pilot randomised controlled trial

TY - JOUR

T1 - Out-patient triple chronotherapy for the rapid treatment and maintenance of response in depression

T2 - feasibility and pilot randomised controlled trial

AU - Veale, David

AU - Serfaty, Marc

AU - Humpston, Clara

AU - Papageorgiou, Andriani

AU - Markham, Sarah

AU - Hodsoll, John

AU - Young, Allan H.

N1 - Funding Information: This study represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. We thank all study participants for their time and Brett Hayes for his assistance in data collection. Funding Information: This study was supported by the MRC Confidence in Concept award to King's College London (Grant ref: MC PC 16048). Publisher Copyright: © The Author(s), 2021. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists.

PY - 2021/11/24

Y1 - 2021/11/24

N2 - Background Triple chronotherapy (sleep deprivation for 36 h, followed by 4 days of advancing the time of sleep and daily morning bright-light therapy for 6 months) has demonstrated benefits for the rapid treatment of depressive symptoms in four small controlled trials of in-patients. Aims To test the feasibility of recruitment and delivery of triple chronotherapy for out-patients with depression (ISRCTN17706836; NCT03405493). Method In a single-blind trial, 82 participants were randomised to triple chronotherapy or a control intervention. The primary outcome was the number of participants recruited per month and adherence to the protocol. Secondary outcomes included the 6-item Hamilton Rating Scale for Depression (HRSD-6) at 1 week. Timings of observer ratings were baseline and 1, 2, 4, 8 and 26 weeks after randomisation. Results The triple chronotherapy group stayed awake for the planned 36 h and 89.9% adhered to the plan of phase advance of their sleep over the following 4 days. We achieved our recruitment target (60 participants completed the trial within 13 months). There were no reported adverse side-effects. We found a significant difference between the groups by intention-to-treat analysis for the HRSD-6 at weeks 1, 8 and 26. There was a large effect size of Cohen's d = 0.8 on HRSD-6 score at week 1, increasing to d = 1.30 at week 26. A response (≥50% reduction in symptoms) was achieved by 33.3% in the triple chronotherapy group and 16.2% in the control group. This stayed relatively steady until week 26 (35.9 v. 13.9%). Conclusions Triple chronotherapy produced a significant and rapid benefit after 1 week in out-patients with depression that was sustained at 26 weeks. Cost-effectiveness trials with a larger clinical sample are required.

AB - Background Triple chronotherapy (sleep deprivation for 36 h, followed by 4 days of advancing the time of sleep and daily morning bright-light therapy for 6 months) has demonstrated benefits for the rapid treatment of depressive symptoms in four small controlled trials of in-patients. Aims To test the feasibility of recruitment and delivery of triple chronotherapy for out-patients with depression (ISRCTN17706836; NCT03405493). Method In a single-blind trial, 82 participants were randomised to triple chronotherapy or a control intervention. The primary outcome was the number of participants recruited per month and adherence to the protocol. Secondary outcomes included the 6-item Hamilton Rating Scale for Depression (HRSD-6) at 1 week. Timings of observer ratings were baseline and 1, 2, 4, 8 and 26 weeks after randomisation. Results The triple chronotherapy group stayed awake for the planned 36 h and 89.9% adhered to the plan of phase advance of their sleep over the following 4 days. We achieved our recruitment target (60 participants completed the trial within 13 months). There were no reported adverse side-effects. We found a significant difference between the groups by intention-to-treat analysis for the HRSD-6 at weeks 1, 8 and 26. There was a large effect size of Cohen's d = 0.8 on HRSD-6 score at week 1, increasing to d = 1.30 at week 26. A response (≥50% reduction in symptoms) was achieved by 33.3% in the triple chronotherapy group and 16.2% in the control group. This stayed relatively steady until week 26 (35.9 v. 13.9%). Conclusions Triple chronotherapy produced a significant and rapid benefit after 1 week in out-patients with depression that was sustained at 26 weeks. Cost-effectiveness trials with a larger clinical sample are required.

KW - Depressive disorders

KW - out-patient treatment

KW - outcome studies

KW - randomised controlled trial

KW - rehabilitation

UR - http://www.scopus.com/inward/record.url?scp=85120307118&partnerID=8YFLogxK

U2 - 10.1192/bjo.2021.1044

DO - 10.1192/bjo.2021.1044

M3 - Article

AN - SCOPUS:85120307118

SN - 2056-4724

VL - 7

JO - BJPsych Open

JF - BJPsych Open

IS - 6

M1 - e220

ER -