Sequenced Treatment Alternatives to Relieve Adolescent Depression (STAR-AD)

Summary

This project aims to investigate the effectiveness of existing common antidepressants and to provide new evidence for depressed children and adolescents who are not responding to their first treatment.

Timeline

Start

2023-02-20

Primary completion

2026-12-31

Completion

2027-07-01

Publications

• Background Gunlicks-Stoessel M, Mufson L, Bernstein G, Westervelt A, Reigstad K, Klimes-Dougan B, Cullen K, Murray A, Vock D. Critical Decision Points for Augmenting Interpersonal Psychotherapy for Depressed Adolescents: A Pilot Sequential Multiple Assignment Randomized Trial. J Am Acad Child Adolesc Psychiatry. 2019 Jan;58(1):80-91. doi: 10.1016/j.jaac.2018.06.032. Epub 2018 Oct 27.
• Background Hawton K, van Heeringen K. Suicide. Lancet. 2009 Apr 18;373(9672):1372-81. doi: 10.1016/S0140-6736(09)60372-X.
• Background van Ettekoven KM, Rasing SPA, Vermulst AA, Engels RCME, Kindt KCM, Creemers DHM. Cross-Lagged Associations between Depressive Symptoms and Response Style in Adolescents. Int J Environ Res Public Health. 2020 Feb 21;17(4):1380. doi: 10.3390/ijerph17041380.
• Background Twenge JM, Cooper AB, Joiner TE, Duffy ME, Binau SG. Age, period, and cohort trends in mood disorder indicators and suicide-related outcomes in a nationally representative dataset, 2005-2017. J Abnorm Psychol. 2019 Apr;128(3):185-199. doi: 10.1037/abn0000410. Epub 2019 Mar 14.
• Background McCarty CA, Weisz JR. Effects of psychotherapy for depression in children and adolescents: what we can (and can't) learn from meta-analysis and component profiling. J Am Acad Child Adolesc Psychiatry. 2007 Jul;46(7):879-86. doi: 10.1097/chi.0b013e31805467b3.
• Background Birmaher B, Brent D; AACAP Work Group on Quality Issues; Bernet W, Bukstein O, Walter H, Benson RS, Chrisman A, Farchione T, Greenhill L, Hamilton J, Keable H, Kinlan J, Schoettle U, Stock S, Ptakowski KK, Medicus J. Practice parameter for the assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child Adolesc Psychiatry. 2007 Nov;46(11):1503-26. doi: 10.1097/chi.0b013e318145ae1c.
• Background Luxton R, Kyriakopoulos M. Depression in children and young people: identification and management NICE guidelines. Arch Dis Child Educ Pract Ed. 2022 Feb;107(1):36-38. doi: 10.1136/archdischild-2020-320020. Epub 2021 May 10. No abstract available.
• Background MacQueen GM, Frey BN, Ismail Z, Jaworska N, Steiner M, Lieshout RJ, Kennedy SH, Lam RW, Milev RV, Parikh SV, Ravindran AV; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 6. Special Populations: Youth, Women, and the Elderly. Can J Psychiatry. 2016 Sep;61(9):588-603. doi: 10.1177/0706743716659276. Epub 2016 Aug 2.
• Background Cheung AH, Zuckerbrot RA, Jensen PS, Laraque D, Stein REK; GLAD-PC STEERING GROUP. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part II. Treatment and Ongoing Management. Pediatrics. 2018 Mar;141(3):e20174082. doi: 10.1542/peds.2017-4082.
• Background Feng Y, Xiao L, Wang WW, Ungvari GS, Ng CH, Wang G, Xiang YT. Guidelines for the diagnosis and treatment of depressive disorders in China: The second edition. J Affect Disord. 2019 Jun 15;253:352-356. doi: 10.1016/j.jad.2019.04.104. Epub 2019 May 1.
• Background March J, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, Burns B, Domino M, McNulty S, Vitiello B, Severe J; Treatment for Adolescents With Depression Study (TADS) Team. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial. JAMA. 2004 Aug 18;292(7):807-20. doi: 10.1001/jama.292.7.807.
• Background Mufson L, Dorta KP, Wickramaratne P, Nomura Y, Olfson M, Weissman MM. A randomized effectiveness trial of interpersonal psychotherapy for depressed adolescents. Arch Gen Psychiatry. 2004 Jun;61(6):577-84. doi: 10.1001/archpsyc.61.6.577.
• Background Brent D, Emslie G, Clarke G, Wagner KD, Asarnow JR, Keller M, Vitiello B, Ritz L, Iyengar S, Abebe K, Birmaher B, Ryan N, Kennard B, Hughes C, DeBar L, McCracken J, Strober M, Suddath R, Spirito A, Leonard H, Melhem N, Porta G, Onorato M, Zelazny J. Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial. JAMA. 2008 Feb 27;299(8):901-913. doi: 10.1001/jama.299.8.901.
• Background Emslie GJ, Mayes T, Porta G, Vitiello B, Clarke G, Wagner KD, Asarnow JR, Spirito A, Birmaher B, Ryan N, Kennard B, DeBar L, McCracken J, Strober M, Onorato M, Zelazny J, Keller M, Iyengar S, Brent D. Treatment of Resistant Depression in Adolescents (TORDIA): week 24 outcomes. Am J Psychiatry. 2010 Jul;167(7):782-91. doi: 10.1176/appi.ajp.2010.09040552. Epub 2010 May 17.
• Background El-Hage W. [Roadmap for therapeutic strategies of treatment resistant depression]. Presse Med. 2016 Mar;45(3):320-2. doi: 10.1016/j.lpm.2016.02.001. Epub 2016 Mar 9. No abstract available. French.
• Background Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.
• Background Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME, Ritz L, Biggs MM, Warden D, Luther JF, Shores-Wilson K, Niederehe G, Fava M; STAR*D Study Team. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006 Mar 23;354(12):1231-42. doi: 10.1056/NEJMoa052963.
• Background Sinyor M, Schaffer A, Levitt A. The sequenced treatment alternatives to relieve depression (STAR*D) trial: a review. Can J Psychiatry. 2010 Mar;55(3):126-35. doi: 10.1177/070674371005500303.
• Background Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D, Ritz L, Nierenberg AA, Lebowitz BD, Biggs MM, Luther JF, Shores-Wilson K, Rush AJ; STAR*D Study Team. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006 Mar 23;354(12):1243-52. doi: 10.1056/NEJMoa052964.
• Background Malhi GS, Bassett D, Boyce P, Bryant R, Fitzgerald PB, Fritz K, Hopwood M, Lyndon B, Mulder R, Murray G, Porter R, Singh AB. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry. 2015 Dec;49(12):1087-206. doi: 10.1177/0004867415617657.
• Background Cleare A, Pariante CM, Young AH, Anderson IM, Christmas D, Cowen PJ, Dickens C, Ferrier IN, Geddes J, Gilbody S, Haddad PM, Katona C, Lewis G, Malizia A, McAllister-Williams RH, Ramchandani P, Scott J, Taylor D, Uher R; Members of the Consensus Meeting. Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015 May;29(5):459-525. doi: 10.1177/0269881115581093. Epub 2015 May 12.
• Background Bauer M, Pfennig A, Severus E, Whybrow PC, Angst J, Moller HJ; World Federation of Societies of Biological Psychiatry. Task Force on Unipolar Depressive Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry. 2013 Jul;14(5):334-85. doi: 10.3109/15622975.2013.804195. Epub 2013 Jul 3.
• Background DeBattista C, Doghramji K, Menza MA, Rosenthal MH, Fieve RR; Modafinil in Depression Study Group. Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry. 2003 Sep;64(9):1057-64. doi: 10.4088/jcp.v64n0911.
• Background Murphy SA. An experimental design for the development of adaptive treatment strategies. Stat Med. 2005 May 30;24(10):1455-81. doi: 10.1002/sim.2022.
• Background Ogbagaber SB, Karp J, Wahed AS. Design of sequentially randomized trials for testing adaptive treatment strategies. Stat Med. 2016 Mar 15;35(6):840-58. doi: 10.1002/sim.6747. Epub 2015 Sep 27.
• Background Liu Y, Zeng D, Wang Y. Use of personalized Dynamic Treatment Regimes (DTRs) and Sequential Multiple Assignment Randomized Trials (SMARTs) in mental health studies. Shanghai Arch Psychiatry. 2014 Dec;26(6):376-83. doi: 10.11919/j.issn.1002-0829.214172.
• Background Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori PW, Rush AJ, Weissman MM. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991 Sep;48(9):851-5. doi: 10.1001/archpsyc.1991.01810330075011.
• Background Cheung A, Kusumakar V, Kutcher S, Dubo E, Garland J, Weiss M, Kiss A, Levitt A. Maintenance study for adolescent depression. J Child Adolesc Psychopharmacol. 2008 Aug;18(4):389-94. doi: 10.1089/cap.2008.0001.
• Background Emslie GJ, Mayes TL. Mood disorders in children and adolescents: psychopharmacological treatment. Biol Psychiatry. 2001 Jun 15;49(12):1082-90. doi: 10.1016/s0006-3223(01)01149-0.
• Background Emslie GJ, Heiligenstein JH, Wagner KD, Hoog SL, Ernest DE, Brown E, Nilsson M, Jacobson JG. Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial. J Am Acad Child Adolesc Psychiatry. 2002 Oct;41(10):1205-15. doi: 10.1097/00004583-200210000-00010.
• Background Thome-Souza MS, Kuczynski E, Valente KD. Sertraline and fluoxetine: safe treatments for children and adolescents with epilepsy and depression. Epilepsy Behav. 2007 May;10(3):417-25. doi: 10.1016/j.yebeh.2007.01.004. Epub 2007 Feb 15.
• Background Zhou X, Teng T, Zhang Y, Del Giovane C, Furukawa TA, Weisz JR, Li X, Cuijpers P, Coghill D, Xiang Y, Hetrick SE, Leucht S, Qin M, Barth J, Ravindran AV, Yang L, Curry J, Fan L, Silva SG, Cipriani A, Xie P. Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis. Lancet Psychiatry. 2020 Jul;7(7):581-601. doi: 10.1016/S2215-0366(20)30137-1.
• Background Wagner KD, Ambrosini P, Rynn M, Wohlberg C, Yang R, Greenbaum MS, Childress A, Donnelly C, Deas D; Sertraline Pediatric Depression Study Group. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA. 2003 Aug 27;290(8):1033-41. doi: 10.1001/jama.290.8.1033.
• Background Cipriani A, Zhou X, Del Giovane C, Hetrick SE, Qin B, Whittington C, Coghill D, Zhang Y, Hazell P, Leucht S, Cuijpers P, Pu J, Cohen D, Ravindran AV, Liu Y, Michael KD, Yang L, Liu L, Xie P. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet. 2016 Aug 27;388(10047):881-90. doi: 10.1016/S0140-6736(16)30385-3. Epub 2016 Jun 8.
• Background Hetrick SE, McKenzie JE, Bailey AP, Sharma V, Moller CI, Badcock PB, Cox GR, Merry SN, Meader N. New generation antidepressants for depression in children and adolescents: a network meta-analysis. Cochrane Database Syst Rev. 2021 May 24;5(5):CD013674. doi: 10.1002/14651858.CD013674.pub2.
• Background Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12.
• Background Findling RL, DelBello MP, Zuddas A, Emslie GJ, Ettrup A, Petersen ML, Schmidt SN, Rosen M. Vortioxetine for Major Depressive Disorder in Adolescents: 12-Week Randomized, Placebo-Controlled, Fluoxetine-Referenced, Fixed-Dose Study. J Am Acad Child Adolesc Psychiatry. 2022 Sep;61(9):1106-1118.e2. doi: 10.1016/j.jaac.2022.01.004. Epub 2022 Jan 13.
• Background Makrogiannis S, Zheng K, Harris C. Discriminative Localized Sparse Approximations for Mass Characterization in Mammograms. Front Oncol. 2021 Dec 30;11:725320. doi: 10.3389/fonc.2021.725320. eCollection 2021.
• Background Thase ME, Mahableshwarkar AR, Dragheim M, Loft H, Vieta E. A meta-analysis of randomized, placebo-controlled trials of vortioxetine for the treatment of major depressive disorder in adults. Eur Neuropsychopharmacol. 2016 Jun;26(6):979-93. doi: 10.1016/j.euroneuro.2016.03.007. Epub 2016 Mar 25.
• Background Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JPT, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JPA, Geddes JR. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357-1366. doi: 10.1016/S0140-6736(17)32802-7. Epub 2018 Feb 21.
• Background Nunez NA, Joseph B, Pahwa M, Kumar R, Resendez MG, Prokop LJ, Veldic M, Seshadri A, Biernacka JM, Frye MA, Wang Z, Singh B. Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis. J Affect Disord. 2022 Apr 1;302:385-400. doi: 10.1016/j.jad.2021.12.134. Epub 2022 Jan 2.
• Background Seshadri A, Wermers ME, Habermann TJ, Singh B. Long-term Efficacy and Tolerability of Adjunctive Aripiprazole for Major Depressive Disorder: Systematic Review and Meta-analysis. Prim Care Companion CNS Disord. 2021 Jun 24;23(4):20r02799. doi: 10.4088/PCC.20r02799.
• Background Strawbridge R, Carter B, Marwood L, Bandelow B, Tsapekos D, Nikolova VL, Taylor R, Mantingh T, de Angel V, Patrick F, Cleare AJ, Young AH. Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis. Br J Psychiatry. 2019 Jan;214(1):42-51. doi: 10.1192/bjp.2018.233. Epub 2018 Nov 20.
• Background Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, Hasnain M, Jollant F, Levitt AJ, MacQueen GM, McInerney SJ, McIntosh D, Milev RV, Muller DJ, Parikh SV, Pearson NL, Ravindran AV, Uher R; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Can J Psychiatry. 2016 Sep;61(9):540-60. doi: 10.1177/0706743716659417. Epub 2016 Aug 2.
• Background Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC. Adjunctive Atypical Antipsychotic Treatment for Major Depressive Disorder: A Meta-Analysis of Depression, Quality of Life, and Safety Outcomes. Focus (Am Psychiatr Publ). 2016 Apr;14(2):244-265. doi: 10.1176/appi.focus.140202. Epub 2016 Apr 7.
• Background Vazquez GH, Bahji A, Undurraga J, Tondo L, Baldessarini RJ. Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium. J Psychopharmacol. 2021 Aug;35(8):890-900. doi: 10.1177/02698811211013579. Epub 2021 Jul 9.
• Background Birmaher B, Khetarpal S, Brent D, Cully M, Balach L, Kaufman J, Neer SM. The Screen for Child Anxiety Related Emotional Disorders (SCARED): scale construction and psychometric characteristics. J Am Acad Child Adolesc Psychiatry. 1997 Apr;36(4):545-53. doi: 10.1097/00004583-199704000-00018.
• Background Su L, Wang K, Fan F, Su Y, Gao X. Reliability and validity of the screen for child anxiety related emotional disorders (SCARED) in Chinese children. J Anxiety Disord. 2008 May;22(4):612-21. doi: 10.1016/j.janxdis.2007.05.011. Epub 2007 Jun 3.
• Background Phillips MR, Li X, Zhang Y. Suicide rates in China, 1995-99. Lancet. 2002 Mar 9;359(9309):835-40. doi: 10.1016/S0140-6736(02)07954-0.
• Background Viguera AC, Milano N, Laurel R, Thompson NR, Griffith SD, Baldessarini RJ, Katzan IL. Comparison of Electronic Screening for Suicidal Risk With the Patient Health Questionnaire Item 9 and the Columbia Suicide Severity Rating Scale in an Outpatient Psychiatric Clinic. Psychosomatics. 2015 Sep-Oct;56(5):460-9. doi: 10.1016/j.psym.2015.04.005. Epub 2015 May 8.
• Background Angst J, Adolfsson R, Benazzi F, Gamma A, Hantouche E, Meyer TD, Skeppar P, Vieta E, Scott J. The HCL-32: towards a self-assessment tool for hypomanic symptoms in outpatients. J Affect Disord. 2005 Oct;88(2):217-33. doi: 10.1016/j.jad.2005.05.011.
• Background Yang HC, Yuan CM, Liu TB, Li LJ, Peng HJ, Liao CP, Rong H, Fang YR, Angst J. Validity of the 32-item Hypomania Checklist (HCL-32) in a clinical sample with mood disorders in China. BMC Psychiatry. 2011 May 15;11:84. doi: 10.1186/1471-244X-11-84.
• Background Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.
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• Background Nolen-Hoeksema S, Morrow J. A prospective study of depression and posttraumatic stress symptoms after a natural disaster: the 1989 Loma Prieta Earthquake. J Pers Soc Psychol. 1991 Jul;61(1):115-21. doi: 10.1037//0022-3514.61.1.115.
• Background Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007 Jul;4(7):28-37.
• Background Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T, Stokes J, Handelsman L, Medrano M, Desmond D, Zule W. Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse Negl. 2003 Feb;27(2):169-90. doi: 10.1016/s0145-2134(02)00541-0.
• Background Li TJ, Sun YC, Ma QY, Wu Y, Yang C, Zhang N, Yang Y, Yang YX. Clinical observation of Dan-Hong Hua-Yu oral solution in treating retinal vein occlusion. Medicine (Baltimore). 2020 May 22;99(21):e20173. doi: 10.1097/MD.0000000000020173.
• He Y, Gan X, Li X, Wang T, Li J, Lei T, Huang Y, Liu R, Chen F, Teng T, Xie Y, Ouyang X, Zhou X. Sequenced treatment alternatives to relieve adolescent depression (STAR-AD): a multicentre open-label randomized controlled trial protocol. BMC Psychiatry. 2023 Oct 27;23(1):789. doi: 10.1186/s12888-023-05221-w.

Drugs

Indications