Prospective, open trial of adjunctive triple chronotherapy for the acute treatment of depression in adolescent inpatients
Abstract
OBJECTIVE: The aim of this pilot study was to explore the feasibility and proof of concept of triple chronotherapy (TCT) as a nonpharmacological adjunctive treatment in the acute management of depression in the adolescent population. METHODS: Thirty-one adolescents with nonpsychotic moderate-to-severe depression were included in the study. The 4-day TCT intervention comprised one night of sleep deprivation followed by 3 days of sleep phase advancement and daily bright light therapy. Primary outcomes were feasibility and depression, as measured by the Hamilton Depression Scale-17 (HAMD-17). Secondary outcomes included severity of illness, anxiety, self-harm, insomnia, and suicidality. RESULTS: Twenty-nine (94%) adolescents completed the 4-day TCT intervention. Twenty-six (84%) of the 31 enrolled patients experienced a reduction in depressive symptoms of at least 50% from baseline; 24 (77%) achieved remission, defined as a HAMD-17 score less than 8. The mean depression score was severe before the start of the intervention ( \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$\overline X$$ \end{document} = 21.8 ± 3.8) and dropped below the remission threshold by day 4 ( \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$\overline X$$ \end{document} = 4.4 ± 5.1; p < 0.001); the mean depression score was mild at 1 week (n = 17; \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$\overline X$$ \end{document} = 9.3 ± 5.2; p < 0.001) and 1 month (n = 10, \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$\overline X$$ \end{document} = 7.8 ± 5.2; p < 0.001). Severity of illness scores according to the Clinical Global Impressions severity subscale improved from a mean of 5.3 at baseline to 3.1 following the TCT intervention (p < 0.0001); the effect was sustained through the 1-week postdischarge and the 1-month follow-up. Secondary outcomes showed significant improvement following the 4-day TCT intervention; improvement was sustained through the 1-week and 1-month follow-up periods. CONCLUSIONS: This pilot study determined TCT to be a feasible, safe, rapid, and potentially effective adjunctive treatment for depression in the adolescent population.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Two open-label studies showed promising results of combined chronotherapy in depressed suicidal inpatients.
“However, two open-label studies showed promising results of combined chronotherapy in depressed suicidal inpatients (22, 23).”
From Total Sleep Deprivation Followed by Bright Light Therapy as Rapid Relief for Depression: A Pragmatic Randomized Controlled Trial (2021) · cites this paper as [22]
Recent studies on combined chronotherapy have reported lower response rates than the presumed average of 50% with the exception of two cohort studies.
“Moreover, recent studies on combined chronotherapy have reported lower response rates (20, 39, 44, 58) than the presumed average of 50% (45) with the exception of two cohort studies (22, 62).”
From Total Sleep Deprivation Followed by Bright Light Therapy as Rapid Relief for Depression: A Pragmatic Randomized Controlled Trial (2021) · cites this paper as [22]
Cites
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369 · see citing works
Posner, K., Brown, G. K., Stanley, B., Brent, D. A., Yershova, K. V., Oquendo, M. A., Currier, G. W., Melvin, G. A., Greenhill, L., Shen, S., et al. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10111704 · Cited by 5,157 · cited 1× · see citing works
“It has been validated in the assessment of suicidality in adolescents; internal consistency ranges from 0.73 to 0.95 (Posner et al. 2011).”
InfluentialGulliver, A., Griffiths, K. M., & Christensen, H. (2010) · BMC Psychiatry · doi:10.1186/1471-244x-10-113 · Cited by 3,292 · see citing works
BIRMAHER, B., BRENT, D. A., CHIAPPETTA, L., BRIDGE, J., MONGA, S., & BAUGHER, M. (1999) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199910000-00011 · Cited by 2,252 · see citing works
The Hamilton Depression Rating Scale: Has the Gold Standard Become a Lead Weight?
Bagby, R. M., Ryder, A. G., Schuller, D. R., & Marshall, M. B. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.12.2163 · Cited by 1,148 · see citing works
Chung, K.-F., Kan, K. K.-K., & Yeung, W.-F. (2011) · Sleep Medicine · doi:10.1016/j.sleep.2010.09.019 · Cited by 454 · see citing works
Wu, J. C., Kelsoe, J. R., Schachat, C., Bunney, B. G., DeModena, A., Golshan, S., Gillin, J. C., Potkin, S. G., & Bunney, W. E. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.02.018 · Cited by 263 · see citing works
Light therapy for non-seasonal depression
Tuunainen, A., Kripke, D. F., & Endo, T. (2004) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004050.pub2 · Cited by 261 · see citing works
KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS
Abdallah, C. G., Adams, T. G., Kelmendi, B., Esterlis, I., Sanacora, G., & Krystal, J. H. (2016) · Depression and Anxiety · doi:10.1002/da.22501 · Cited by 206 · see citing works
Bright light therapy for nonseasonal depression: meta-analysis of clinical trials
Al-Karawi, D., & Jubair, L. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.03.016 · Cited by 189 · see citing works
Pflug, B., & Tölle, R. (2017) · International Pharmacopsychiatry · doi:10.1159/000468269 · Cited by 167 · see citing works
The clinical global impression scale and the influence of patient or staff perspective on outcome
Forkmann, T., Scherer, A., Boecker, M., Pawelzik, M. R., Jostes, R., & Gauggel, S. (2011) · BMC Psychiatry · doi:10.1186/1471-244x-11-83 · Cited by 160 · see citing works
Light therapy for preventing seasonal affective disorder.
Nussbaumer, B., Kaminski-Hartenthaler, A., Forneris, C., Morgan, L., Sonis, J., Gaynes, B., Greenblatt, A., Wipplinger, J., Lux, L., Winkler, D., et al. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011269.pub2 · Cited by 124 · see citing works
Benedetti, F., Riccaboni, R., Locatelli, C., Poletti, S., Dallaspezia, S., & Colombo, C. (2014) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13m08455 · Cited by 116 · see citing works
Cao, B., Luo, Q., Fu, Y., Du, L., Qiu, T., Yang, X., Chen, X.-L., Chen, Q., Soares, J. C., Cho, R. Y., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-23685-9 · Cited by 115 · see citing works
Meinck, F., Cosma, A. P., Mikton, C. R., & Băban, A. (2017) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2017.08.016 · Cited by 105 · see citing works
Duncan, W. C., Slonena, E., Hejazi, N. S., Brutsche, N., Yu, K. C., Park, L., Ballard, E. D., & Zarate, C. A. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.03.011 · Cited by 93 · see citing works
Martiny, K., Refsgaard, E., Lund, V., Lunde, M., Sørensen, L., Thougaard, B., Lindberg, L., & Bech, P. (2012) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.11m07625 · Cited by 87 · cited 1× · see citing works
“TCT is an approach that combines sleep deprivation, bright light therapy, and sleep phase advancement in the acute treatment of depression (Martiny et al. 2012; Benedetti et al. 2014; Martiny et al. 2015).”
Echizenya, M., Suda, H., Takeshima, M., Inomata, Y., & Shimizu, T. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.06.022 · Cited by 71 · see citing works
Sahlem, G. L., Kalivas, B., Fox, J. B., Lamb, K., Roper, A., Williams, E. N., Williams, N. R., Korte, J. E., Zuschlag, Z. D., El Sabbagh, S., et al. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.08.015 · Cited by 71 · see citing works
Child and Adolescent Depression Intervention Overview: What Works, for Whom and How Well?
Maalouf, F. T., & Brent, D. A. (2012) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2012.01.001 · Cited by 54 · see citing works
Martiny, K., Refsgaard, E., Lund, V., Lunde, M., Thougaard, B., Lindberg, L., & Bech, P. (2015) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12402 · Cited by 37 · see citing works
Sun, X., Wang, M., Wang, Y., Lian, B., Sun, H., Wang, G., Li, Q., & Sun, L. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.01.015 · Cited by 35 · see citing works
Chronotherapeutic treatments for depression in youth
Gest, S., Holtmann, M., Bogen, S., Schulz, C., Pniewski, B., & Legenbauer, T. (2016) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-015-0720-6 · Cited by 32 · see citing works
Noguchi, T., Lo, K., Diemer, T., & Welsh, D. K. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.02.030 · Cited by 28 · see citing works
Lithium lengthens circadian period of cultured brain slices in area specific manner
Yoshikawa, T., & Honma, S. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.07.045 · Cited by 28 · see citing works
Severe mood dysregulation: In the “light” of circadian functioning
Heiler, S., Legenbauer, T., Bogen, T., Jensch, T., & Holtmann, M. H. (2011) · Medical Hypotheses · doi:10.1016/j.mehy.2011.07.019 · Cited by 17 · see citing works
Depression in adolescence: from qualitative research to measurement
Lachal, J., Speranza, M., Schmitt, A., Spodenkiewicz, M., Falissard, B., Moro, M.-R., & Revah-Levy, A. (2012) · Adolescent Psychiatrye · doi:10.2174/2210676611202040296 · Cited by 17 · see citing works
Feifel, D. (2016) · Drug Development Research · doi:10.1002/ddr.21347 · Cited by 14 · see citing works
Clinical Predictors of Response to Magnetic Seizure Therapy in Depression
Kayser, S., Bewernick, B. H., Wagner, S., & Schlaepfer, T. E. (2018) · Journal of Ect · doi:10.1097/yct.0000000000000495 · Cited by 14 · see citing works
Chronotherapeutics: An alternative treatment of juvenile depression
Gest, S., Legenbauer, T., Bogen, S., Schulz, C., Pniewski, B., & Holtmann, M. H. (2014) · Medical Hypotheses · doi:10.1016/j.mehy.2014.01.002 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Perspectives in affective disorders: Clocks and sleep
Wirz‐Justice, A., & Benedetti, F. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14362 · Cited by 108 · see citing works
Bright Light Therapy for Nonseasonal Depressive Disorders
Menegaz de Almeida, A., Aquino de Moraes, F. C., Cavalcanti Souza, M. E., Cavalcanti Orestes Cardoso, J. H., Tamashiro, F., Miranda, C., Fernandes, L., Kreuz, M., & Alves Kelly, F. (2025) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2024.2871 · Cited by 47 · see citing works
D'Agostino, A., Ferrara, P., Terzoni, S., Ostinelli, E. G., Carrara, C., Prunas, C., Gambini, O., & Destrebecq, A. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.07.026 · Cited by 47 · see citing works
Chronotherapy for the rapid treatment of depression: a meta-analysis
Humpston, C., Benedetti, F., Serfaty, M., Markham, S., Hodsoll, J., Young, A. H., & Veale, D. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.09.078 · Cited by 45 · see citing works
Sleep difficulties and suicidality in youth: current research and future directions
Goldstein, T. R., & Franzen, P. L. (2019) · Current Opinion in Psychology · doi:10.1016/j.copsyc.2019.08.021 · Cited by 40 · see citing works
Hühne-Landgraf, A., Volkmann, P., Stephan, M., Rossner, M. J., & Landgraf, D. (2020) · Genes Brain & Behavior · doi:10.1111/gbb.12661 · Cited by 30 · see citing works
Goldstein, T., & Franzen, P. (2022) · Current Sleep Medicine Reports · doi:10.1007/s40675-022-00222-9 · Cited by 27 · see citing works
Ioannou, M., Szabó, Z., Widmark-Jensen, M., Vyrinis, G., Karlsson, C., & Steingrimsson, S. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.705090 · Cited by 13 · see citing works
Chen, R., Yan, Y., & Cheng, X. (2024) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1257093 · Cited by 11 · see citing works
Light Therapy for Adolescent Depression: A Scoping Review
Ballard, R., Parkhurst, J. T., Julian, K. M., Pasetes, L. N., Fawcett, A. J., Li, A., Goel, N., & Sit, D. K. Y. (2023) · Current Psychiatry Reports · doi:10.1007/s11920-023-01437-5 · Cited by 11 · see citing works
Teresi, G. I., Davis, M., Williamson, A. A., Young, J. F., Merranko, J. A., & Goldstein, T. R. (2024) · JAACAP Open · doi:10.1016/j.jaacop.2024.11.004 · Cited by 4 · see citing works
Herrera, M., Hurd, D., Riemann, L. A., Mullowney, Y., Pathak, M. K., Swift, K. D., Fairbanks, C., Winsky, J., & Brant, J. M. (2025) · Journal of Child and Adolescent Psychopharmacology · doi:10.1177/10445463251389899 · Cited by 2 · see citing works
Self-citationHarris, N. A., Banihashemi, L., & Hasler, B. P. (2024) · Current Addiction Reports · doi:10.1007/s40429-024-00609-4 · Cited by 2 · see citing works
Psychopharmacology for Pediatric Depressive Disorders
Rengasamy, M. L., Shalev, A., & Birmaher, B. B. (2024) · Springer eBooks · doi:10.1007/978-3-031-57472-6_16 · Cited by 2 · see citing works
Huang, F.-J., Zeng, J., Huang, S., Liu, T., & Wang, G. (2025) · Scientific Reports · doi:10.1038/s41598-025-05488-x · Cited by 4 · see citing works
Huber, R. S., Gaillard, M., Sievertsen, S. A., Ma, J., Shao, S., Rubin, D. Y. D., Jones, S. A., Hill, A. R., Bartholomeusz, R., McGlade, E. C., et al. (2025) · JAACAP Open · doi:10.1016/j.jaacop.2025.11.004
- Authors
- Hurd, D., Herrera, M., Brant, J. M., Coombs, N. C., & Arzubi, E.
- Affiliations
- Billings Clinic (US)
- Corresponding author
- Brant, Jeannine M.
- Venue
- Journal of Child and Adolescent Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2019-01-25
- Volume
- 29
- Issue
- 1
- Pages
- 20-27
- ISSN
- 1044-5463 (ISSN-L)
- 1557-8992
- OpenAlex
- W2899121804
- Cited by
- 16
- References
- 31
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 3
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Child and Adolescent Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- adolescent depression, sleep deprivation, bright light therapy, adolescent inpatients, depression remission, feasibility, suicidality, self-harm, insomnia, anxiety, treatment acceptability, treatment tolerability, treatment burden
- MeSH terms
- Adolescent, Anxiety, Depression, Female, Humans, Inpatients, Male, Phototherapy, Pilot Projects, Prospective Studies, Psychiatric Status Rating Scales, Sleep Deprivation, Sleep Wake Disorders, Chronotherapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
