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Terapias psicológicas versus fármacos antidepresivos, solos y en combinación para la depresión en niños y adolescentes

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Referencias

Referencias de los estudios incluidos en esta revisión

ADAPT 2007 {published data only}

Byford S, Barrett B, Roberts C, Wilkinson P, Dubicka B, Kelvin RG, et al. Cost‐effectiveness of selective serotonin reuptake inhibitors and routine specialist care with and without cognitive behavioural therapy in adolescents with major depression. British Journal of Psychiatry 2007;191:521‐7.
Goodyer I, Dubicka B, Wilkinson P, Kelvin R, Roberts C, Byford S, et al. Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial. BMJ 2007;335(7611):142‐5.
Goodyer I, Kutcher S. CBT plus an SSRI was as effective as an SSRI alone for adolescents with moderate to severe depression: Commentary. Evidence Based Medicine 2008;13(1):13.
Harrington R, Dubicka B, Leech A, Breen S, Roberts C, Goodyer I, et al. Randomised controlled trial of fluoxetine and cognitive‐behaviour therapy versus fluoxetine alone in adolescents with major depression (ADAPT Trial) [conference abstract]. Proceedings of the 30th Annual Conference of the British Association for Behavioural and Cognitive Psychotherapies; 2002 Jul 17‐20; Warwick, UK. 2002.
Wilkinson P, Dubicka B, Kelvin R, Roberts C, Goodyer I. Treated depression in adolescents: Predictors of outcome at 28 weeks. British Journal of Psychiatry 2009;194(4):334‐41.
Wilkinson P, Kelvin R, Roberts C, Dubicka B, Goodyer I. Clinical and psychosocial predictors of suicide attempts and nonsuicidal self‐injury in the Adolescent Depression Antidepressants and Psychotherapy Trial (ADAPT). The American Journal of Psychiatry 2011;168(5):495‐501.
Wilkinson PO, Goodyer IM. The effects of cognitive‐behavioural therapy on mood‐related ruminative response style in depressed adolescents. Child and Adolescent Psychiatry and Mental Health 2008;2(1):3‐13.

Bernstein 2000 {published data only}

Bernstein GA, Anderson LK, Hektner JM, Realmuto GM. Imipramine compliance in adolescents. Journal of the American Academy of Child and Adolescent Psychiatry 2000;39(3):284‐91.
Bernstein GA, Borchardt CM, Perwien AR, Crosby RD, Kushner MG, Thuras PD, et al. Imipramine plus cognitive‐behavioral therapy in the treatment of school refusal. Journal of the American Academy of Child and Adolescent Psychiatry 2000;39(3):276‐83.
Bernstein GA, Hektner JM, Borchardt CM, McMillan MH. Treatment of school refusal: One‐year follow‐up. Journal of the American Academy of Child and Adolescent Psychiatry 2001;40(2):206‐13.
Bernstein GA, Warren SL, Massie ED, Thuras PD. Family dimensions in anxious‐depressed school refusers. Journal of Anxiety Disorders 1999;13(5):513‐28.
Layne AE, Bernstein GA, Egan EA, Kushner MG. Predictors of treatment response in anxious‐depressed adolescents with school refusal. Journal of the American Academy of Child and Adolescent Psychiatry 2003;42(3):319‐26.

Clarke 2005 {published data only}

Clarke G, DeBar L, Lynch F, Powell J, Gale J, O'Connor E, et al. A randomized effectiveness trial of brief cognitive‐behavioral therapy for depressed adolescents receiving antidepressant medication. Journal of the American Academy of Child and Adolescent Psychiatry 2005;44(9):888‐98.

Cornelius 2009 {published data only}

Cornelius J, Douaihy A, Chung T, Kelly T, Daley D, Hayes J, et al. Four‐year follow‐up of double‐blind fluoxetine trial in comorbid MDDAUD adolescents. Alcoholism, Clinical and Experimental Research [abstracts from the 34th Annual Scientific Meeting of the Research Society on Alcoholism, RSA. 25‐29 Jun 2011; Atlanta, GA United States] 2011;35:20A.
Cornelius JR, Bukstein OG, Wood DS, Kirisci L, Douaihy A, Clark DB. Double‐blind placebo‐controlled trial of fluoxetine in adolescents with comorbid major depression and an alcohol use disorder. Addictive Behaviors 2009;34(10):905‐9.
Cornelius JR, Douaihy A, Bukstein OG, Daley DC, Wood SD, Kelly TM, et al. Evaluation of cognitive behavioral therapy/motivational enhancement therapy (CBT/MET) in a treatment trial of comorbid MDD/AUD adolescents. Addictive Behaviors 2011;36(8):843‐8.

Deas 2000 {published data only}

Deas D, Randall CL, Roberts JS, Anton RF. A double‐blind, placebo‐controlled trial of sertraline in depressed adolescent alcoholics: a pilot study. Human Psychopharmacology 2000;15:461‐9.

Kim 2012 {published data only}

Kim SM, Han DH, Lee YS, Renshaw PF. Combined cognitive behavioral therapy and bupropion for the treatment of problematic on‐line game play in adolescents with major depressive disorder. Computers in Human Behavior 2012;28(5):1954‐9.

Mandoki 1997 {published data only}

Mandoki MW, Tapia MR, Tapia MA, Sumner GS, Parker JL. Venlafaxine in the treatment of children and adolescents with major depression. Psychopharmacology Bulletin 1997;33(1):149‐54.

Melvin 2006 {published data only}

Dudley AL, Melvin GA, Williams NJ, Tonge BJ, King NJ. Investigation of consumer satisfaction with cognitive‐behaviour therapy and sertraline in the treatment of adolescent depression. Australian and New Zealand Journal of Psychiatry 2005;39(6):500‐6.
Gordon MS, Tonge B, Melvin GA. Outcome of adolescent depression: 6 Months after treatment. Australian and New Zealand Journal of Psychiatry 2011;45(3):232‐9.
Melvin GA, Tonge BJ, King NJ, Heyne D, Gordon MS, Klimkeit E. A comparison of cognitive‐behavioral therapy, sertraline, and their combination for adolescent depression. Journal of the American Academy of Child and Adolescent Psychiatry 2006;45(10):1151‐61.

Riggs 2007 {published data only}

Riggs PD, Mikulich‐Gilbertson SK, Davies RD, Lohman M, Klein C, Stover SK. A randomized controlled trial of fluoxetine and cognitive behavioral therapy in adolescents with major depression, behavior problems, and substance use disorders. Archives of Pediatrics and Adolescent Medicine 2007;161(11):1026‐34.

TADS 2004 {published data only}

Brent DA. Glad for what TADS adds, but many TADS grads still sad. Journal of the American Academy of Child and Adolescent Psychiatry 2006;45(12):1461‐4.
Curry J, Rohde P, Simons A, Silva S, Vitiello B, Kratochvil C, et al. Predictors and moderators of acute outcome in the Treatment for Adolescents with Depression Study (TADS). Journal of the American Academy of Child and Adolescent Psychiatry 2006;45(12):1427‐39.
Domino ME, Burns BJ, Silva SG, Kratochvil CJ, Vitiello B, Reinecke MA, et al. Cost‐effectiveness of treatments for adolescent depression: Results from TADS. The American Journal of Psychiatry 2008;165(5):588‐96.
Domino ME, Foster E, Vitiello B, Kratochvil CJ, Burns BJ, Silva SG, et al. Relative cost‐effectiveness of treatments for adolescent depression: 36‐week results from the TADS randomized trial. Journal of the American Academy of Child and Adolescent Psychiatry 2009;48(7):711‐20.
Feeny NC, Silva SG, Reinecke MA, McNulty S, Findling RL, Rohde P, et al. An exploratory analysis of the impact of family functioning on treatment for depression in adolescents. Journal of Clinical Child and Adolescent Psychology 2009;38(6):814‐25.
Glass RM. Fluoxetine, cognitive‐behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents with Depression Study (TADS) randomized controlled trial. Journal of Pediatrics 2005;146:145.
Goodyer I, Kutcher S. CBT plus an SSRI was as effective as an SSRI alone for adolescents with moderate to severe depression: Commentary. Evidence Based Medicine 2008;13(1):13.
Jacobs RH, Becker‐Weidman EG, Reinecke MA, Jordan N, Silva SG, Rohde P, et al. Treating depression and oppositional behavior in adolescents. Journal of Clinical Child and Adolescent Psychology 2010;39(4):559‐67.
Jensen PS. After TADS, can we measure up, catch up, and ante up?. Journal of the American Academy of Child and Adolescent Psychiatry 2006;45(12):1456‐60.
Jensen PS. NIMH's TADS: More than just a tad of progress?. Cognitive and Behavioral Practice 2005;12:156‐8.
Kratochvil C, Emslie G, Silva S, McNulty S, Walkup J, Curry J, et al. Acute time to response in the Treatment for Adolescents with Depression Study (TADS). Journal of the American Academy of Child and Adolescent Psychiatry 2006;45(12):1412‐8.
March J, Albano AM, Rosenberg D, Casat C, Emslie G, Kratochvil, et al. Treatment for Adolescents With Depression Study (TADS). www.clinicaltrials.gov/ct/show/NCT00006286 (accessed 17 January 2012).
March J, Silva S, Curry J, Wells K, Fairbank J, Burns B, et al. The Treatment for Adolescents With Depression Study (TADS): outcomes over 1 year of naturalistic follow‐up. American Journal of Psychiatry 2009;166(10):1141‐9.
March J, Silva S, Petrycki S, Curry J, Wells K, Fairbank J, et al. Fluoxetine, cognitive‐behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents with Depression Study (TADS) randomized controlled trial. JAMA 2004;292(7):807‐820.
March J, Silva S, Vitiello B, Team Tads. The Treatment for Adolescents with Depression Study (TADS): methods and message at 12 weeks. Journal of the American Academy of Child and Adolescent Psychiatry 2006;45(12):1393‐403.
March JS, Silva S, Petrycki S, Dubicka B, Ramchandani P. Fluoxetine plus cognitive behavioural therapy was most effective for adolescents with major depressive disorder. Evidence Based Medicine 2005;10:46.
May DE, Kratochvil CJ, Puumala SE, Silva SG, Rezac AJ, Hallin MJ, et al. A manual‐based intervention to address clinical crises and retain patients in the Treatment of Adolescents With Depression Study (TADS). Journal of the American Academy of Child and Adolescent Psychiatry 2007;46:573‐81.
The TADS Team. The Treatment for Adolescents with Depression Study (TADS): Long Term Effectiveness and Safety Outcomes. Archives of General Psychiatry 2007;64(10):1132‐44.

TASA 2009 {published data only}

Brent DA, Greenhill LI, Compton S, Emslie G, Wells K, Walkup JT, et al. The Treatment of Adolescent Suicide Attempters Study (TASA): predictors of suicidal events in an open treatment trial. Journal of the American Academy of Child and Adolescent Psychiatry 2009;48(10):987‐86.
Stanley B, Brown G, Brent DA, Wells K, Poling K, Curry J, et al. Cognitive‐behavioral therapy for suicide prevention (CBT‐SP): treatment model, feasibility, and acceptability. Journal of the American Academy of Child and Adolescent Psychiatry 2009;48(10):1005‐13.
Vitiello B, Brent DA, Greenhill Ll, Emslie G, Wells K, Walkup JT, et al. Depressive symptoms and clinical status during the Treatment of Adolescent Suicide Attempters (TASA) Study. Journal of the American Academy of Child and Adolescent Psychiatry 2009;48(10):997‐1004.

Referencias de los estudios excluidos de esta revisión

Cheung 2008 {published data only}

Cheung A, Kusumakar V, Kutcher S, Dubo E, Garland J, Weiss M, et al. Maintenance study for adolescent depression. Journal of Child and Adolescent Psychopharmacology 2008;18(4):389‐94.

Cornelius 2010 {published data only}

Cornelius JR, Bukstein OG, Douaihy AB, Clark DB, Chung TA, Daley DC, et al. Double‐blind fluoxetine trial in comorbid MDD–CUD youth and young adults. Drug and Alcohol Dependence 2010;112(1‐2):39‐45.
Douaihy A, Cornelius J, Chung RT, Daley D, Wood D, Kirisci L, et al. One‐year follow‐up of double‐blind fluoxetine trial in comorbid MDD‐CUD youth [abstract]. Alcoholism: clinical and experimental research [abstracts from the 34th annual scientific meeting of the research society on alcoholism, RSA. 25‐29 jun 2011; atlanta, GA united states] 2011;35:20A.

Dujovne 1994 {published data only}

Dujovne VF. Comparison of cognitive‐behavioral to pharmacological treatment of depression in prepubertal children. Dissertation Abstracts International 1994;54(10‐B):5384.

Emslie 2002 (Eli 2002) {published data only}

Emslie GJ, Heiligenstein JH, Wagner KD, Hoog SL, Ernest DE, Brown E, et al. Fluoxetine for acute treatment of depression in children and adolescents: a placebo‐controlled, randomized clinical trial. Journal of American Child and Adolescent Psychiatry 2002;41(10):1205‐15.

Emslie 2004 {published data only}

Emslie GJ, Hughes CW, Crismon ML, Lopez M, Pliszka S, Toprac MG, et al. A feasibility study of the childhood depression medication algorithm: the Texas Children's Medication Algorithm Project (CMAP). Journal of the American Academy of Child and Adolescent Psychiatry 2004;43(5):519‐27.

Emslie 2013 {published data only}

Emslie, G. Pediatric MDD: Sequential treatment with fluoxetine and relapse prevention CBT [abstract]. European child & adolescent psychiatry [abstracts of the 15th International Congress of European Society for Child and Adolescent Psychiatry, ESCAP; 2013 Jul 6‐10; Dublin Ireland] 2013;22:S112‐‐S113.

Findling 2008 {published data only}

Findling RL, Lingler J, Rowles BM, McNamara NK, Calabrese JR. A pilot pharmacotherapy trial for depressed youths at high genetic risk for bipolarity. Journal of Child and Adolescent Psychopharmacology 2008;18(6):615‐21.

Forbes 2012 {published data only}

Real‐world affect and social context as predictors of treatment response in child and adolescent depression and anxiety: an ecological momentary assessment study. Journal of Child and Adolescent Psychopharmacology 2012;22(1):37‐47.

Fristad 2009 {published data only}

Fristad MA, Verducci JS, Walters K, Young ME. Impact of multifamily psychoeducational psychotherapy in treating children aged 8 to 12 years with mood disorders. Archives of General Psychiatry 2009;66(9):1013‐21.

Goodyer 2011 {published data only}

Goodyer IM, Tsancheva S, Byford S, Dubicka B, Hill J, Kelvin R, et al. Improving mood with psychoanalytic and cognitive therapies (IMPACT): a pragmatic effectiveness superiority trial to investigate whether specialised psychological treatment reduces the risk for relapse in adolescents with moderate to severe unipolar depression: study protocol for a randomised controlled trial. Trials 2011;12:175.
Hagan CC, Graham JME, Widmer B, Holt RJ, Ooi C, van Nieuwenhuizen AO, et al. Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: Study protocol for Magnetic Resonance‐Improving Mood with Psychoanalytic and Cognitive Therapies [MR‐IMPACT]. BMC psychiatry 2013;13:247.
Midgley N, Ansaldo F, Target M. The meaningful assessment of therapy outcomes: Incorporating a qualitative study into a randomized controlled trial evaluating the treatment of adolescent depression [IMPACT‐ME]. Psychotherapy 2014;51(1):128‐37.

King 2009 {published data only}

King CA, Klaus N, Kramer A, Venkataraman S, Quinlan P, Gillespie B. The Youth‐Nominated Support Team‐Version II for suicidal adolescents: A randomized controlled intervention trial. Journal of Consulting and Clinical Psychology 2009;77(5):880‐93.

Lubman 2005 {published data only}

Hides L, Lubman D, Wong L, Carroll S, Kay‐Lambkin F, Allen N, et al. Treating coexisting depression and alcohol/other drug misuse in young people. 29th Australian Association for Cognitive and Behaviour Therapy Annual Conference; 2006 October 18 ‐ 23; Manly 2006 2005:50.
Lubman D. n Integrated Pharmacological and Psychological Approach to Young People With Comorbid Depression and Substance Abuse [Treatment of Comorbid Depression and Substance Abuse in Young People]. https://clinicaltrials.gov/ct2/show/NCT00232284 2005 (accessed 20 June 2014).

Pallavi 2014 {published data only}

Pallavi, P. A randomized, single‐blind, trial of yoga therapy as an adjunct to SSRI treatment for adolescent depression patients: Variations in serum cytokine and neurotrophin levels abstract. Biological psychiatry [abstracts of the 69th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry, SOBP; 2014 May 5‐10; New York, NY United States] 2014;75(9 Suppl 1):118S.

Siddique 2012 {published data only}

Siddique J, Chung JY, Brown C, Hendricks MJ. Comparative effectiveness of medication versus cognitive‐behavioral therapy in a randomized controlled trial of low‐income young minority women with depression. Journal of Consulting and Clinical Psychology 2012;80(6):995‐1006.

Tang 2009 {published data only}

Tang TC, Jou SH, Ko CH, Huang SY, Yen CF. Randomized study of school‐based intensive interpersonal psychotherapy for depressed adolescents with suicidal risk and parasuicide behaviors. Psychiatry and Clinical Neurosciences 2009;63(4):463‐70.

TORDIA 2008 {published data only}

Asarnow JR, Emslie G, Clarke G, Wagner KD, Spirito A, Vitiello B, et al. Treatment of selective serotonin reuptake inhibitor‐resistant depression in adolescents: predictors and moderators of treatment response. Journal of the American Academy of Child and Adolescent Psychiatry 2009;48(3):330‐9.
Brent D, Emslie G, Clarke G, Wagner KD, Asarnow JR, Keller M, et al. 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;299(8):901‐13.
Brent DA. The treatment of SSRI‐resistant depression in adolescents (TORDIA): In search of the best next step. Depression and Anxiety 2009;26(10):871‐4.
Brent DA, Emslie GJ, Clarke GN, Asarnow J, Spirito A, Ritz L, et al. Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI‐resistant depression in adolescents (TORDIA) study. The American Journal of Psychiatry 2009;166(4):418‐26.
Emslie GJ, Mayes T, Porta G, Vitiello B, Clarke G, Wagner KD, et al. Treatment of Resistant Depression in Adolescents (TORDIA): Week 24 outcomes. American Journal of Psychiatry 2010;167(7):782‐91.
Kennard BD, Clarke GN, Weersing V, Asarnow JR, Shamseddeen W, Porta G, et al. Effective components of TORDIA cognitive‐behavioral therapy for adolescent depression: Preliminary findings. Journal of Consulting and Clinical Psychology 2009;77(6):1033‐41.
Kennard BD, Emslie GJ, Mayes TL, Nightingale‐Teresi J, Nakonezny PA, Hughes JL, et al. Cognitive‐behavioral therapy to prevent relapse in pediatric responders to pharmacotherapy for major depressive disorder. Journal of the American Academy of Child and Adolescent Psychiatry 2008;47(12):1395‐404.

Wagner 2003 {published data only}

Wagner KD, Ambrosini P, Rynn M, Wohlberg C, Yang R, Greenbaum MS, et al. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA 2003;290(8):1033‐41.

Warden 2012 {published data only}

Warden D, Riggs PD, Min SJ, Mikulich‐Gilbertson SK, Tamm L, Trello‐Rishel K, et al. Major depression and treatment response in adolescents with ADHD and substance use disorder. Drug and Alcohol Dependence 2012;120(1‐3):214‐9.

Wu 2013 {published data only}

Wu X, Liu F, Cai H, Huang L, Li Y, Mo Z, et al. Cognitive behaviour therapy combined fluoxetine treatment superior to cognitive behaviour therapy alone for school refusal. International Journal of Pharmacology 2013;9(3):197‐203.

Referencias de los estudios en curso

Craighead 2012 {published data only}

Craighead E. Randomized Trial of Behavioral Activation and Antidepressant Medication in the Treatment of Adolescents With Major Depression [Comparison of Behavioral Activation and Antidepressant Medication in the Treatment of Adolescents With Depression]. https://clinicaltrials.gov/ct2/show/study/NCT01740726 2012 (accessed 20 June 2014).

Davey 2012 {published data only}

Davey C. Youth Depression Alleviation: A Randomised Controlled Trial of Cognitive Behavioural Therapy with Fluoxetine or Placebo (YoDA‐C). http://www.anzctr.org.au/ACTRN12612001281886.aspx 2012 (accessed 4 September 2014).

Gunlicks‐Stoessel 2013 a {published data only}

Gunlicks‐Stoessel M. An Adaptive Treatment Strategy for Adolescent Depression (PTAD). http://clinicaltrials.gov/ct2/show/NCT01802437 2013 (Accessed 20 June 2014).

Gunlicks‐Stoessel 2013 b {published data only}

Gunlicks‐Stoessel M. A Personalized Approach to Achieving a Sustained Response to Treatment for Adolescent Depression [An Adaptive Treatment Strategy for Adolescent Depression‐Continuation (PTAD GIA)]. http://clinicaltrials.gov/ct2/show/NCT02017535 2013 (Accessed 20 June 2014).

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Goodyer 2010

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Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Archives of General Psychiatry 2006;63(3):332‐9.

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Harrington R, Dubicka B, Leech A, et al. Randomised controlled trial of fluoxetine and cognitive‐behaviour therapy versus fluoxetine alone in adolescents with major depression (ADAPT Trial). Proceedings of the 30th Annual Conference of the British Association for Behavioural and Cognitive Psychotherapies; 2002 July 17‐20, Warwick, UK. 2002.

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Hatcher‐Kay C, King CA. Depression and suicide. Pediatrics in Review 2003;24(11):363‐71.

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Hazell P, O'Connell D, Heathcote D, Henry D. Tricyclic drugs for depression in children and adolescents. Cochrane Database of Systematic Reviews 2002, Issue 2. [DOI: 10.1002/14651858.CD002317]

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

ADAPT 2007

Methods

Duration: 12 weeks

Follow‐up assessment points: Post‐intervention, 28 weeks

Funded by: NHS Health Technology Assessment (HTA) Programme, Central Manchester and Manchester Children’s University Hospitals

Participants

N = 208

Adolescents only (11 to 17 years)

Depression diagnoses included: DSM‐IV; criteria for major or probable major depression (four symptoms with psychosocial impairment). Participants also had to obtain a score of 7 or more on the Health of the Nation Outcome scales for children and adolescents (HoNOSCA; Gowers 1999)

Baseline risk of suicide: Measured using the suicidality items from the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K‐SADS‐PL; Kaufman 1997). Patients with active suicidal intent were included in the study

Baseline               Fluoxetine + CBT n = 105 (%)           Fluoxetine  n = 103 (%)

Thoughts                             50 (47.6)                               48 (46.6)

Ideation                               40 (38.1)                               44 (42.7)

Acts                                     13 (12.4)                               21 (20.4)

Medical lethality               3 (2.9)                                   4 (3.9)

Self harm                            30 (28.6)                               23 (22.3)

Baseline severity of depression: Children’s Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1996). Mean t‐score (SD):  Fluoxetine + CBT = 75.1 (6.7)  Fluoxetine = 75.3 (6.7)

Comorbidity included:

Comorbidity                                      Fluoxetine + CBT (n = 105)               Fluoxetine (n = 103)

Social Phobia                                                 43                                                  49

Obsessive compulsive disorder                 42                                                           37

Post‐traumatic stress disorder                    42                                                           36

Agorophobia                                                 36                                                           29

Separation anxiety disorder                        31                                                           28

Specific phobia                                              25                                                           22

Conduct disorder                                          18                                                           17

Panic disorder                                                21                                                          14

Oppositional defiance disorder                  17                                                           13

Generalised anxiety disorder                     19                                                           13

Panic disorder (with agoraphobia)            20                                                           13

ADHD                                                                 5                                                             6

Bulemia Nervosa                                               8                                                             4

Alcohol abuse                                                   1                                                             4

Transient tic disorder                                     2                                                             3

Tourettes syndrome                                      2                                                             2

Alcohol dependence                                      1                                                             2

Encopresis                                                         1                                                             0

Enuresis                                                             1                                                             0

Dysthymia                                                          1                                                             0

Age: Range = 11 to 17 years  

Fluoxetine + CBT (median) = 14

Fluoxetine (median) = 14                        

Sex (M:F):

Total: 54:154

Fluoxetine + CBT = 26:79

Fluoxetine = 28:75                   

Setting: Outpatient setting

Excluded psychiatric diagnoses: Schizophrenia or bipolar disorder; global learning disability (formal testing not undertaken)

Country: UK

Interventions

Combination (Fluoxetine+CBT)

N = 105

Name: CBT with core interventions including engagement and goal setting, emotional recognition, self monitoring, self reinforcement and activity scheduling, challenging negative thinking and cognitive restructuring, social problem‐solving and communication skills

 # sessions/length: 19 sessions over 28 weeks. (1 session per week for 12 weeks, 1 session per fortnight for 12 weeks, 1 final session at 28 weeks)

Manualised (Y/N): Yes

Individual or group: Individual

Parent involvement: Encouraged at the end of each session by therapist

Fidelity check: Yes. Audiotapes of the session were rated with a modified version of the cognitive therapy scale (Vallis 1986) Inter‐rater reliability k = 0.8

Delivered by: 4 Psychiatrists who either had previous CBT training or attended a 3‐day training course on CBT for depression, and 10 CBT therapists (mostly Psychologists)

Name (class & type): SSRI (Fluoxetine). However, 26 participants were taking a different SSRI when admitted to the trial; 3 switched to fluoxetine and 11 changed from fluoxetine to another SSRI

Dose (mg/day)/length: 10 mg daily for 1 week, increasing to 20 mg for 5 weeks. If no response, increase considered to 40 mg on alternate days for one week followed by 5 weeks of 40 mg. Option to increase dose to 60 mg on alternate days for 1 week followed by 60 mg daily for 5 weeks if participant did not respond by 12 weeks. Overall, there was a mean dose of 30 mg for both groups, and 2 patients received 60 mg

Delivered by: psychiatrists in the context of ongoing clinical care. The content of contact was an explanation of depression and attention to recent family or peer group conflicts. Liaison with schools and other agencies undertaken when appropriate. Participants offered 9 outpatient sessions of usual care over 28 weeks, with the option of more if needed

Medication Only

N = 103

Medication details as above Y/N: Yes

Outcomes

Clinician reported

The Children’s Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1996)

Children’s Global Assessment Scale (C‐GAS; Shaffer 1983)

Suicidality items from the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K‐SADS‐PL; Kaufman 1997)

Self reported

The Mood and Feelings Questionnaire (MFQ; Wood 1995)

Parent reported

The Clinical Global Impression Improvement Scale (CGI‐I; Guy 1976)

Additional Measures

The Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA; Gowers 1999)

The Clinical Global Impression Improvement Scale (CGI‐I; Guy 1976)

Notes

Dropouts during treatment to any or at least 1 adverse reaction: 1 participant experienced a fit possibly related to SSRI and 1 had an allergic reaction (possibly secondary to medication)

Suicide‐related outcome as an adverse event of treatment: 4 required admission for suicidality or self harm and were withdrawn from the study

Authors only report median age

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

“Participants were randomised to SSRI alone or SSRI plus CBT by an equal allocation ratio using stochastic minimisation balancing for severity (Childrens Global Assessment Scale <40), centre, sex, concurrent comorbidity disorder, and age”

pg. 2/8 (Under heading Assignment)

Allocation concealment (selection bias)

Low risk

“Research staff from the clinical sites enrolled patients, and an independent telephone randomisation centre allocated treatment”

pg. 2 /8 (Under heading Assignment)

Blinding (performance bias and detection bias)
Assessors

Low risk

 “...research assistants blind to treatment assignment assessed outcome”

pg. 4/8 (Under heading Outcomes)

Blinding (performance bias and detection bias)
Participants

High risk

No placebo or control psychotherapy was used. As such, participants would be aware that the medication was active and the therapy was CBT

Incomplete outcome data (attrition bias)

Low risk

ITT analysis: “Analysis was by intention to treat subject to the availability of the data”

pg. 4/8 (Under heading Statistical Analysis)

Number randomised:

Fluoxetine + CBT: 105          Fluoxetine:  103     Total: 208

Number of dropouts during intervention:

Fluoxetine + CBT: 11             Fluoxetine:6            Total: 17

Number dropouts in follow‐up:

Fluoxetine + CBT: 7              Fluoxetine: 7           Total: 14

Number analysed post‐intervention:

Fluoxetine + CBT: 105         Fluoxetine: 103      Total:  208

Number analysed follow‐up 1:  

Fluoxetine + CBT: 105         Fluoxetine: 103      Total:  208

Reasons for dropout in each group:

12 patients were formally withdrawn from the study for the following reasons: 4 required admission to hospital for suicidality or self harm, 5 failed to improve, 1 had a fit, 1 had an allergic reaction, 1 was prescribed paroxetine by a GP

18 families withdrew participants from the study: 6 were improving and did not want further treatment, 5 did not want more treatment, 2 wanted CBT, 2 did not want CBT, 1 wanted a female therapist, 1 was getting worse, 1 moved

Selective reporting (reporting bias)

Unclear risk

Authors reported data for all outcomes specified in their methods. Do not have access to trial protocol

Other bias

Low risk

Bernstein 2000

Methods

Duration: 8 weeks

Follow‐up assessment points: Post‐intervention, 12 months

Funded by: National Institute of Mental Health (NIMH)

Participants

N = 63

Adolescent only (12 to 18 years)

Depression diagnoses included: DSM‐III‐R Major Depressive Disorder (MDD). Participants also had to obtain a score of 35 or more on the CDRS‐R (Poznanski 1996)

Baseline risk of suicide: Not measured

Baseline severity of depression: Chidren’s Depression Rating Scale (CDRS‐R; Poznanski 1985). Mean score (SD):

Imipramine + CBT = 46.8 (9.5)

Placebo + CBT = 52.5 (10.8)

Comorbidity included: All 63 subjects met criteria for at least 1 anxiety disorder based on either adolescent or parental interviews

Age mean (SD):

Total = 13.9 (3.6)        

Sex (M:F): 25:38                

Setting: Unclear. Likely an outpatient setting based on information regarding medication monitoring throughout the trial.

Excluded psychiatric diagnoses: ADHD, conduct disorder, bipolar disorder, eating disorder, alcohol or drug abuse on the Diagnostic Interview for Children and Adolescents‐Revised‐Adolescent Version (DICA‐R‐A) or Parent Version (DICA‐R‐P; Reich 1990), or both, mental retardation by history, bipolar affective disorder in first degree relative

Country: USA

Interventions

Combination (Imipramine + CBT)

N = 31

Name: CBT. Based on school refusal treatment by Last 1998. Included the identification of negative thoughts surrounding school attendance and teaching adaptive coping strategies.

# sessions/length: 8 (45 to 60 minutes) sessions over 8 weeks

Manualised (Y/N): Yes

Individual or group: Individual

Parent involvement: Yes. Parents joined each session for 10 to 15 minutes at the end

Fidelity check: No formal check. Weekly discussions with all therapists and principal investigators, and a fortnightly telephone consultation with an expert on CBT for school refusal

Delivered by: 3 therapists (1 behaviorally trained Clinical Psychologist, 1 Doctoral level therapist and 1 Masters level therapist)

Name (class & type): TCA  (Imipramine)

Dose (mg/day)/length: Dose based on body weight. A gradual increase every 3 to 5 days to 3 mg/kg per day by the end of week 2 Mean dose at week 3 was 184.6mg + 33.3

Delivered how: Weekly appointments monitoring side effects, and compliance were undertaken with a psychiatrist. Blood imipramine levels were monitored at 3 and 8 weeks

Combination (Placebo medication + CBT)

N = 32

Details as above (Y/N): Yes

Outcomes

Clinician reported

Children’s Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1985) with a score of ≤ 35

Children’s Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1985)

Self reported

The Beck Depression Inventory (BDI; Beck 1979)

Additional Measures

Anxiety Rating for Children‐Revised (ARC‐R; Bernstein 1996)

The Revised Children’s Manifest Anxiety Scale (RCMAS; Reynolds 1978)

Weekly school attendance rates

Notes

Dropouts during treatment to any or at least 1 adverse reaction: 1 participant developed manic symptoms and 1 developed psychiatric symptoms and required hospitalisation

Suicide‐related outcome as an adverse event of treatment: No

Denominator and numerator for remission rates calculated from percentages reported in the publication

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

“Random assignment to treatment was blocked on gender and whether subjects had a school vacation that lasted 5 or more days during the 8 week treatment period”. (Under heading Procedure)

Allocation concealment (selection bias)

Unclear risk

No information contained in paper to make a judgement

Blinding (performance bias and detection bias)
Assessors

Low risk

“All project personnel...were blind to medication assignment”. (Under heading Procedure)

Blinding (performance bias and detection bias)
Participants

Low risk

"...imipramine pills and matching placebo"

“To preserve the blind, increases and decreases were also suggested for randomly selected patients on placebo”. (Under heading Medication Management)

Incomplete outcome data (attrition bias)

Low risk

ITT analysis: “All randomized subjects were included in analyses based on intent to treat”. (Under heading Statistical Analyses)

Number randomised:

Imipramine + CBT: 31        Placebo + CBT:  32          Total: 63

Number of dropouts during intervention

Imipramine + CBT: 7           Placebo + CBT: 9            Total: 16

Number analysed post‐intervention:

Imipramine + CBT:  31        Placebo + CBT:32           Total: 63

Reasons for dropout in each group: 1 missed 22 does of medication, 1 missed 2 therapy appointments, 1 developed manic symptoms on study medication, 1 required hospitalisation for psychiatric symptoms, and 12 declined further participation

Selective reporting (reporting bias)

Unclear risk

Authors report data for all outcomes post‐intervention. Do not have access to trial protocol

Other bias

High risk

Authors note that placebo group significantly more symptomatic at baseline compared with imipramine group despite randomisation

Clarke 2005

Methods

Duration: 6 weeks

Follow‐up assessment points: Post‐intervention, 12, 26 and 52 weeks

Funded by: The Agency for Healthcare Research and Quality and the Garfield Memorial Fund

Participants

N = 152

Adolescent only (12 to 18 years)

Depression diagnoses included: DSM‐IV episode of major depression

Baseline risk of suicide: 73.7% (112/152) of participants reported significant levels of suicidal behaviour; assessment tool not explicitly referenced

Baseline severity of depression: Centre for Epidemiological Studies ‐ Depression Scale (CES‐D; Radloff 1977):

TAU + CBT = 35.4 (11.8)

TAU = 33.7 (9.3)

Comorbidity included: Not reported

Age mean (SD):

Total = 15.30 (1.61)    

TAU + CBT = 15.29 (1.62)

TAU = 15.32 (1.60)                                          

Sex (M:F): 34:118               

TAU + CBT = 17:60          

TAU = 17:58                                        

Setting: Primary care health maintenance organization (HMO)

Excluded psychiatric diagnoses: Schizophrenia or a significant developmental/intellectual disability

Country: USA

Interventions

TAU (SSRI) + CBT

N = 77

Name: CBT employing cognitive restructuring, or behavioural training, or both. Participants able to choose which type to try first. After completion of first module (2 to 5 sessions), therapist and youth reviewed recovery and decided whether to proceed with the second module (sessions 6 to 9), focusing on skills training

 # sessions/length: Between 0 and 9, mean 5.3 sessions. Each session 1 hour. Weekly in frequency

Manualised (Y/N): No information 

Individual or group: Individual

Parent involvement: Clinicians organised separate parent meetings, however "parents' attendance was "sparse"

Fidelity check: Yes. All sessions audio taped. 57 sessions selected at random and rated by a senior supervisor. 87.2% adherence to protocol

Delivered by: Masters level Psychologists

Name (class & type): SSRI (varied). All trial participants were able to receive any medications provided by either the HMO or outside providers

Dose (mg/day)/length: Varied

Delivered by: No information

TAU (SSRI)

N = 75

Details as above (Y/N): Yes

Outcomes

Clinician reported

Mood disorders module of the Schedule for Affective Disorders and Schizophrenia for School‐age Children‐Present and Lifetime version (K‐SADS‐PL; Kaufman 1997) and the Longitudinal Interview Follow‐Up Evaluation (Keller 1982).

This was used to define remission i.e. those who had did not have a continuing or new mood disorder since the last interview according to the K‐SADS‐PL). It was unclear if DSM‐IV or ICD time criteria were employed

Centre for Epidemiological Studies‐Depression Scale (CES‐D; Radloff 1977), cut‐off of ≤ 15

Children’s Global Adjustment Scale (C‐GAS; Shaffer 1983)

Self reported

Centre for Epidemiological Studies‐Depression Scale (CES‐D; Radloff 1977)

Parent reported

The Child Behaviour Checklist (CBCL; Achenbach 1978)

Additional Measures

Hamilton Rating Scale for Depression (HAM‐D; Hamilton 1960)

Youth Self Report (YSR; Achenbach 1991)

Internalising and Externalising subscales and an extracted depression subscale created to match DSM criteria for major depression (Clarke 1992)

Social Adjustment Scale Self Report for Youth (Weissman 1980)

Short Form‐12 (Ware 1998)

Notes

Authors do not report reasons for dropout

Dropouts during treatment to any or at least 1 adverse reaction: Not reported

Suicide‐related outcome as an adverse event of treatment: Not reported

Numbers who reached remission by interview were calculated by review authors using percentages based on depressive episodes (Table 3). Data from Table 3 were based on observed cases not ITT following advice from statistician

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“Youths were randomized using a blocked procedure to minimize study arm imbalance”. pg. 889

Allocation concealment (selection bias)

Unclear risk

No information contained in paper to make a judgement

Blinding (performance bias and detection bias)
Assessors

Low risk

”Blinded interviewers assessed each adolescent and a participating parent by telephone at baseline and at 6, 12, 26 and 52 weeks post‐randomization”. pg. 890

Blinding (performance bias and detection bias)
Participants

High risk

No placebo or therapy control arm. As such, participants were aware if they were receiving CBT in the trial or not

Incomplete outcome data (attrition bias)

Unclear risk

ITT analysis: "...all subjects were considered part of the study from the point of randomisation (an intent‐to‐treat design)" pg.890

“We examined continuous depression and functioning outcome measures using random effect regression analysis”. pg. 892

Number randomised:

TAU + CBT: 77                       TAU: 75                      Total: 152

Number completing post‐intervention: (dropouts)

TAU + CBT: 67 (10)                TAU: 65 (10)              Total: 132 (20)

Number completing follow‐up 12 weeks:

TAU + CBT: 61 (16)                 TAU: 61 (14)              Total: 122 (30)

Number completing follow‐up 26 weeks:

TAU + CBT: 65 (12)                  TAU: 62 (13)             Total: 127 (25)

Number completing follow‐up 52 weeks:

TAU + CBT: 56 (21)                   TAU: 58 (17)             Total: 114 (38)

*Data obtained from Fig 1. Summary of study procedures. Number analysed not clearly stated in paper

Reasons for dropout in each group: Not reported

Selective reporting (reporting bias)

Unclear risk

Remission rates only reported at 52 weeks. Do not have access to trial protocol

Other bias

High risk

Authors note that telephone administration of self report measures may have created bias

Cornelius 2009

Methods

Duration: 12 weeks

Follow‐up assessment points: Post‐intervention (12 weeks)

Funded by: National Institute on Alcohol Abuse and Alcoholism

Participants

N = 50

Adolescent only (15 to 20 years)

Depression diagnoses included: DSM‐IV diagnosis of major depressive disorder (MDD) 

Baseline risk of suicide: Not measured and suicidality not stated as an exclusion criteria

Baseline severity of depression: Hamilton Rating Scale for Depression (HAM‐D; Hamilton 1960) Mean (SD):

CBT + fluoxetine = 16.88 (7.09)

CBT + placebo = 22.88 (8.79)

Comorbidity included: All participants were required to have a DSM‐IV diagnosis of an alcohol use disorder (AUD) confirmed using the Substance Use Disorders Section of the Structured Clinical Interview for the DSM (SCID)

Age mean: Not reported            

Sex (M:F):          

Total = 28:22 

CBT + fluoxetine = 12:12   

CBT + placebo = 16:10                       

Setting: Outpatient?

Psychiatric diagnoses excluded: DSM‐IV diagnosis of bipolar disorder, schizoaffective disorder, or schizophrenia, persons with and substance abuse or dependence other than nicotine dependence or cannabis use and dependence, persons with a history of intravenous drug use, persons who had received antipsychotic or antidepressant medication within 1 month prior to baseline assessment also excluded

Country: USA

Interventions

Combination: Psychotherapy + Medication

N = 24

Name (description): CBT for depressive disorder and the treatment of alcohol use disorder combined with Motivation Enhancement Therapy (MET) for the treatment of alcohol use disorder

 # sessions/length: 9 sessions over 12 weeks

Manualised (Y/N): Yes

Individual or group: Not reported

Parent involvement: Not reported

Fidelity check: No fidelity check reported

Delivered by: Not reported

Medication

Name (class & type): SSRI; fluoxetine

Dose (mg/day)/length: initiated at 10 mg, increased to 20 mg after week 2 until the end of the study, as 20 mg was target dose of the study

Delivered how: Study physicians prescribed all medication 

Combination: Psychotherapy + Placebo

N = 26

Delivered how: Pill placebo delivered in the same context as above

Outcomes

Clinician reported

Hamilton Rating Scale for Depression (HAM‐D; Hamilton 1960)

Self reported

Beck Depression Inventory (BDI; Beck 1988)

Additional Measures

Drinking behaviour measured using the Timeline Follow‐back Method (TLFB; Sobell 1988)

Notes

Dropouts during treatment to any or at least 1 adverse reaction: 0

Suicide‐related outcome as an adverse event of treatment: 0

Suicidality was not measured with a formalised tool

3 dropouts during study from placebo group due to persistent depressive symptoms

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“Patient randomisation was conducted by urn randomisation stratified by gender” pg. 906 (Treatment and assessment)

Allocation concealment (selection bias)

Low risk

“Active medication and matching placebo were prepared by the research pharmacy” pg. 906 (Treatment and assessment)

Blinding (performance bias and detection bias)
Assessors

High risk

“The study was conducted in a double blind fashion, though one study physician remained non‐blinded in order to handle any problems which may have arisen” pg. 906 (Assessment and treatment)

Blinding (performance bias and detection bias)
Participants

Low risk

”...participants were randomly assigned to receive fluoxetine or placebo administered in identical‐looking opaque capsules” pg. 906 (Assessment and treatment)

Incomplete outcome data (attrition bias)

Unclear risk

“Statistical analyses were completed on an intent‐to‐treat study group” pg. 907 (Statistical Analyses)

Number randomised:

CBT + fluoxetine: 24 CBT + placebo: 26

Number dropped out during intervention:

CBT + fluoxetine: 0 CBT + placebo: 3

Number analysed post‐intervention:

CBT + fluoxetine: 24 CBT + placebo: 26

Selective reporting (reporting bias)

Unclear risk

Do not have access to trial protocol

Other bias

Low risk

Baseline imbalance of HAM‐D and BDI scores with fluoxetine group have significantly lower baseline depression scores

Deas 2000

Methods

Duration:12 weeks

Follow‐up assessment points: Post‐intervention

Funded by: National Institute of Alcohol and Alcoholism (NIAAA)

Participants

N = 10

Adolescent only (15 to 18 years)

Depression diagnoses included: Not clearly stated. The Child Schedule for Affective Disorders and Schizophrenia (K‐SADS; Chambers 1985) was used to assess psychiatric disorders

Baseline risk of suicide: Not measured

Baseline severity of depression: measured using the Hamilton Rating Scale for Depression (HAM‐D; Hamilton 1960)

Sertraline + CBT = 20.40 (5.55)

Placebo + CBT = 20.80 (5.45)

Comorbidity included: All participants presented with an alcohol use disorder

Age mean (SD): Total = 16.6 (0.52)

Sertraline + CBT = 16.4 (0.55)

Placebo + CBT = 16.8 (0.45)     

Sex (M:F): 8:2 

Sertraline + CBT = 4:1   

Placebo + CBT = 4:1

Setting: Outpatient

Excluded psychiatric diagnoses: Not reported

Country: USA

Interventions

Combination (Sertraline+CBT)

N = 5

Name (description): CBT focusing on relapse prevention, coping skills, anger management, modelling and role playing

 # sessions/length: 12, average attendance was 8.2 sessions and 10.6 sessions for the placebo and sertraline groups respectively

Manualised (Y/N): No

Individual or group: Group

Parent involvement: Not reported

Fidelity check: Not reported

Delivered by: A psychiatrist, on a weekly basis

Name (class & type): SSRI (Sertraline)

Dose (mg/day)/length: 25 mg/day, increased to 25 mg weekly, to a maximum dose of 100 mg in about 4 weeks

Delivered by: A psychiatrist monitored side effects, made medication adjustments, and supplied participants with additional medication on a weekly basis

Combination (Placebo medication + CBT)

N = 5

Details as above (Y/N): Yes

Outcomes

Self reported

Outcome 4: Hamilton Rating Scale for Depression (HAM‐D; Hamilton 1960)

Additional Measures

The Time Line Follow Back (TLFB; Sobell 1988) assessed alcohol use

Notes

Dropouts during treatment to any or at least 1 adverse reaction: No. Authors note that all the side effects of sertraline were transient and did not lead to any dropouts

Suicide‐related outcome as an adverse event of treatment: No

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“Following the baseline assessments, subjects were randomized using a computer‐generated randomisation table into sertraline or placebo groups” pg. 462

Allocation concealment (selection bias)

Low risk

All of the medication supplied by the study pharmacist were identical in appearance" pg. 462

Blinding (performance bias and detection bias)
Assessors

Unclear risk

“This study was a 12 week double blind, placebo‐controlled trial” pg. 462

Blinding (performance bias and detection bias)
Participants

Low risk

Participants in both arms were blind to medication. Both received CBT

“This study was a 12 week double blind, placebo‐controlled trial” pg. 462

Incomplete outcome data (attrition bias)

Unclear risk

ITT analysis: All subjects randomised were included in the final analysis. No information is reported regarding imputation method for missing data

Number randomised:

SSRI + CBT: 5            Placebo + CBT: 5                 Total: 10

Number of dropouts during intervention:*

SSRI + CBT: 2            Placebo + CBT: 0                 Total: 2

Number analysed post‐intervention:

SSRI + CBT: 5            Placebo + CBT:5                 Total: 10

Treatment completion was defined a priori as 8 sessions

Selective reporting (reporting bias)

Unclear risk

All outcome data specified in methods was reported. Do not have access to trial protocol

Other bias

High risk

Small study sample, and no follow‐up

Kim 2012

Methods

Duration: 8 weeks

Follow‐up assessment points: postintervention; 4 weeks post intervention

Funded by: Korean Game Culture Foundation

Participants

N = 72

Adolescent only (13 to 18 years)

Depression diagnoses included: Major Depressive Disorder diagnosed using The Korean Child Schedule for Affective Disorders and Schizophrenia (K‐SADS; Chambers 1985); score of 19 or more on the BDI

Baseline risk of suicide: Not measured

Baseline severity of depression: measured using the Beck Depression Inventory (Beck 1961)

Buproion + CBT = 32.7 (SD 8.8)

Bupropion = 33.3 (SD 8.7)

Comorbidity included: Excluded other psychiatric disorders

Age mean (SD): Total = 16

Bupropion + CBT = 16.2 (1.4)

Bupropion = 15.9 ± 1.6

Sex (M:F): 72:0

Sertraline + CBT = 35:0

Placebo + CBT = 37:0

Setting: University clinic

Excluded psychiatric diagnoses: all other psychiatric disorders excluded

Country: South Korean

Interventions

Medication (Bupropion)

N = 37

Name (class & type): NDRI (Bupropion)

Dose (mg/day)/length: 150 mg/day for first week, increased to 300 mg daily for 7 weeks

Delivered by: A psychiatrist who meet with the participant on a weekly basis for 10 minutes to monitor progress with regard to online gaming

Combination (Bupropion+CBT)

N = 35

Name (description): CBT includes focus on negative consequences of online gaming and irrational beliefs about on‐line gamiing, problem solving and decision making, communication skills trianing, self control training, family therapy, planning for the future

# sessions/length: 8 one‐hour sessions delivered weekly, no details provided regarding actual attendance rates

Manualised (Y/N): No

Individual or group: Group

Parent involvement: One of the 8 CBT sessions was described as family therapy

Fidelity check: No

Delivered by: a multidisciplinary treatment team including a psychiatrist, nurse, psychologist, and social worker

Name (class & type): NDRI (Bupropion)

Dose (mg/day)/length: 150 mg/day for first week, increased to 300 mg daily for 7 weeks

Delivered by: A psychiatrist who meet with the participant on a weekly basis for 10 minutes to monitor progress with regard to online gaming

Outcomes

Self reported

Beck Depression Inventory (Beck 1961)

Additional Measures

Young Internet Addiction Scale (YIAS) (Young 1996)

Beck Anxiety Inventory (BAI) (Beck 1988).

Modified‐School Problematic Behavior Scale (Baker 1984).

Modified Student’s Life Satisfaction Scale (Huebner 1991)

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No description

Allocation concealment (selection bias)

Unclear risk

No description

Blinding (performance bias and detection bias)
Assessors

Unclear risk

No assessor rated outcomes

Blinding (performance bias and detection bias)
Participants

High risk

Participants not blinded (no placebo CBT condition)

Incomplete outcome data (attrition bias)

High risk

10% missing data; observed case data used in analysis

Selective reporting (reporting bias)

Unclear risk

Authors report on all outcomes specified in their methods section. No access to trial protocol.

Other bias

Unclear risk

No rating of fidelity; very short follow‐up period

Mandoki 1997

Methods

Duration: 6 weeks

Follow‐up assessment points: Post‐intervention

Funded by: Not specified

Participants

N = 33

Child and adolescent (8 to 17 years)

Depression diagnoses included: DSM‐IV Major Depression

Baseline risk of suicide: Participants who were acutely suicidal were excluded form the study. No other specific suicide measurements were administered

Baseline severity of depression: Not reported

Comorbidity included: Not reported

Age mean (SD): Total based on completed participants: 12.7 (2.88)

Sex (M:F): 25:8

Setting: Outpatient

Excluded psychiatric diagnoses: Schizophrenia, mental retardation and Gilles de la Tourette’s syndrome

Country: USA

Interventions

Combination (SNRI + Psychotherapy)

N = 20

Name: Predominantly behavioural/cognitive in nature

 # sessions/length: One weekly session over 6 weeks

Manualised (Y/N): Not reported

Individual or group: Individual sessions of 60 minutes (45 minutes plus 15 minutes "collateral")

Parent involvement: 15 minutes at the end of each session was "collateral" with parents and participants

Fidelity check: Not reported

Delivered by: Masters level therapists, trained in the procedural aspects of the study

 

Name (class & type): SNRI (Venlafaxine)

Dose (mg/day)/length: Children (8 to 12 yrs) began at 12.5 mg q.d for 3 days, increasing to 12.5 mg b.i.d for 3 days, and further increased to 12.5 mg t.i.d for the remainder of the study. Adolescents (13‐17yrs) began at 25mg q.d. for 3 days, increased to 25mg b.i.d for 3 days and then 25mg t.i.d. for the remainder of the study

Delivered how: Weekly clinic supplied medication/placebo and monitored vital signs and side effects

Combination (Placebo+Psychotherapy)

N = 20

Details as above (Y/N): Yes

Outcomes

Clinician reported

The Child Depression Rating Scale (CDRS; Poznanski 1979)

Self reported

Children’s Depression Inventory (CDI; Kovacs 1992)

Parent reported

The Child Behaviour Checklist (CBCL; Achenbach 1993)

Additional Measures

The Hamilton Rating Scale for Depression (Hamilton 1960)

Notes

Age and gender calculated manually from Figure 1 (pg 151 of the Mandoki 1997 publication)

Dropouts during treatment to any or at least 1 adverse reaction: One participant developed a manic episode, was hospitalised and subsequently put on lithium. Authors note in discussion that "There are specific side effects associated with venlafaxine treatment....However, these side effects were not severe enough to discontinue the medication"

Suicide‐related outcome as an adverse event of treatment: None reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information contained in paper to make a judgement

Allocation concealment (selection bias)

Unclear risk

As authors quote study as being 'double blind'

Blinding (performance bias and detection bias)
Assessors

Low risk

"After the 6‐week treatment, the study ended. The blind was broken...”. pg. 151 Under heading Procedures, Measurements, and Medication Dose

Blinding (performance bias and detection bias)
Participants

Low risk

“The patients were randomly assigned, in a double blind fashion, to either the venlafaxine and psychotherapy or the placebo and psychotherapy treatment group”. pg. 151 Under heading Procedures, Measurements, and Medication Dose

Incomplete outcome data (attrition bias)

High risk

ITT analysis: No. Figure 1 (pg 151 of the Mandoki 1997 publication) shows the age and sex composition of the final sample on which the statistical analysis was based”. Manual calculation shows the analysis was conducted only on participants completing the trial. pg. 150 Under heading Subjects

Number randomised:

SNRI + Psychotherapy: 20                Placebo + Psychotherapy: 20            Total: 40

Number of dropouts during intervention:

SNRI + Psychotherapy: 4                   Placebo + Psychotherapy:  3             Total: 7

Number analysed post‐intervention:

SNRI + Psychotherapy: 16                Placebo + Psychotherapy: 17             Total: 33

Reasons for dropouts: 6 did not continue coming to the clinic by week 2 for unknown reasons, and 1 patient (in the venlafaxine group) developed a manic episode and was hospitalised

Selective reporting (reporting bias)

High risk

No numerical outcome data was reported in the article, all data was presented in graphs only. Do not have access to trial protocol

Other bias

Low risk

Melvin 2006

Methods

Duration: 12 weeks

Follow‐up assessment points: Post‐intervention, 6 months.

Funded by: Beyond Blue, Premiers Youth Suicide Taskforce, Department of Human Services Victoria and Australian Rotary Health Research Fund.

Participants

N = 73

Adolescents only (12 to 18 years)

Depression diagnoses included: DSM‐IV major depressive disorder (MDD), dysthymic disorder (DD) and depressive disorder not otherwise specified (DDNOS)

Baseline risk of suicide: Participants who were 'actively suicidal' were excluded from the study, however 'suicidally depressed teenagers (who did not require hospitalisation) were included. Measured using the Suicidal Ideation Questionnaire‐Junior High School Version (SIQ‐JR; Reynolds 1987)

CBT = 26.05 (19.93)

Sertraline = 29.42 (27.24)

Sertraline + CBT = 30.64 (24.42)

Participants exhibiting active suicidality that required acute hospital admission were excluded from the study

Baseline severity of depression:

CBT = 83.77 (13.8)

Sertraline = 84.92 (11.20)

Sertraline + CBT = 83.96 (15.01)

Comorbidity included: 69% were diagnosed with at least 1 comorbid disorder, 22% were diagnosed with 2 or more

Comorbid disorder (n)                               CBT             Sertraline           Sertraline + CBT

Anxiety disorders                                             8                           9                             10

Dysthymic disorder                                         1                           2                              3

Conduct Disorder/ODD                                 2                           3                              1

Body dysmorphic disorder                           1                           0                              0

Adjustment disorder with anxiety            0                           1                              0

Enuresis                                                            1                           0                              0

Reading Disorder                                              0                           1                              0

Cannabis‐related disorder NOS                 0                           1                              0

Parent‐child relational problem                 5                            6                              8

Sibling relational problem                              1                             2                              3

Age mean (SD): 15.3 (1.5)    

CBT= 15.0                   

Sertraline = 15.5         

CBT + Sertraline = 15.3             

Sex (M:F): 25:48        

CBT = 7:15

Sertraline = 7:19

CBT + Sertraline = 11:14

Setting: 3 clinics collocated with public child and adolescent mental health services

Excluded psychiatric diagnoses: Bipolar disorder, psychotic disorder, primary diagnosis of substance abuse disorder, severe psychiatric disturbance that required acute hospital admission, and intellectual disability of sufficient severity to preclude participation in the study

Country: Australia

Interventions

Psychotherapy (CBT)

N = 22

Name: CBT course based in the Adolescent Coping with Depression Course (Clarke 1990). Modules included; goal setting, psycho education, affective education, self monitoring, relaxation training, social skills training, pleasant events scheduling, cognitive therapy and life goals planning

 # sessions/length: Twelve 50 minute sessions over 12 weeks. Three ‘booster’ sessions were also delivered over 3 months

Manualised (Y/N): Yes

Individual or group: Individual

Parent involvement: Parents who chose to participate received concurrent CBT sessions, with 2 family sessions

Fidelity check: No formal check. Clinicians received weekly to twice weekly supervision with an expert therapist. Peer supervision held weekly

Delivered by: 7 registered psychologists, a supervised probationary psychologist, 2 general medical practitioners, and a social worker with experience in providing CBT for adolescent depression. Training provided by chief investigators

Medication (Sertraline)

N = 26

Name (class & type): SSRI (Sertraline)

Dose (mg/day)/length: 25 mg/day for 1 week, increased to 50 mg/day at week 2 depending on response and adverse events. Maximum dose of 100 mg/day administered depending on clinical response and tolerability

Delivered how: Review sessions occurred every 2 to 3 weeks to monitor adverse effects, and included  education about depression but no CBT strategies

Combination (Sertraline + CBT)

N = 25

Details as above (Y/N): Yes

Outcomes

Clinician reported

The Schedule for Affective Disorders and Schizophrenia for School‐Age Children‐Lifetime Version (KSADS‐PL; Kaufman 1997) was used to assess for disorder or remission, which was based on DSM‐IV criteria for full remission (i.e. 8 weeks asymptomatic).

The Global Assessment of Functioning Scale (GAF; APA 1994)

Dropouts:

Post‐intervention:

CBT: 21/22 completed (1 dropout)

Sertraline: 21/26 completed treatment (5 dropouts)

Sertraline + CBT: 20/25 completed treatment (5 dropouts)

6 month follow‐up:

CBT: 19/22 completed assessment (3 dropouts)

Sertraline: 23/26 completed assessment (3 dropouts)

Sertraline + CBT: 24/25 completed assessment (1 dropout)

Self reported

Reynolds Adolescent Depression Scale (RADS; Reynolds 1986)

The Suicidal Ideation Questionnaire‐Junior High School Version (SIQ‐JR; Reynolds 1987)

Parent reported

The Child Behaviour Checklist (CBCL; Achenbach 1991)

Additional Measures

The Global Assessment of Relational Functioning Scale (APA 1994)

Revised Children’s Manifest Anxiety Scale (RCMAS; Reynolds 1978)

The Self Efficacy Questionnaire for Depressed Adolescents (SEQ‐DA; Tonge 2005)

Family Assessment Device General Functioning Scale (Epstein 1983)

Notes

Dropouts during treatment to any or at least 1 adverse reaction: 6% discontinued medication due to adverse affects. These effects included slurred speech and dizziness, feeling agitated and restless, and diarrhoea

Suicide‐related outcome as an adverse event of treatment: 11.1% (n = 45) of participants taking sertraline either alone or with CBT reported suicidal ideation. 1 participant in the sertraline + CBT received an inpatient admission for several hours, however treatment according to protocol was subsequently continued

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“...subjects were randomly allocated by an independent statistician using a computer generated assignment to CBT, MED or COMB”. pg. 1154

Allocation concealment (selection bias)

Low risk

”...allocated by an independent statistician...Allocation for those eligible for the trial was concealed to all until after pre‐treatment assessment”. pg. 1154

Blinding (performance bias and detection bias)
Assessors

High risk

“Independent raters blind to treatment allocation were not used because of resource limitations but may have reduced the risk of experimenter bias in assessments”. pg. 1160

Blinding (performance bias and detection bias)
Participants

High risk

Psychotherapy administered in both groups and no placebo control used for medication

Incomplete outcome data (attrition bias)

Unclear risk

ITT analysis: “data were analysed using an intent‐to‐treat strategy to counter any possible overestimation of treatment outcomes, using the last observation carried forward method (Nelson 1996)”. pg. 1155

Number randomised:

CBT: 22      Sertraline: 26               CBT + Sertraline: 25        Total: 73

Number of dropouts during intervention

CBT: 1          Sertraline: 5               CBT + Sertraline: 5          Total: 11

Number dropouts in follow‐up:

CBT: 3          Sertraline: 3               CBT + Sertraline: 1          Total:7

Number analysed post‐intervention:

CBT: 22          Sertraline: 26           CBT + Sertraline: 25    Total: 73

Number analysed follow‐up 1:

CBT: 22          Sertraline: 26           CBT + Sertraline: 25     Total: 73

Reasons for dropouts:

CBT: At post‐intervention, 1 participant reported symptoms had improved. At 6‐month follow‐up, 2 refused to attend and 1 was unable to be located

Sertraline: At post‐intervention, 2 participants reported symptoms had improved, 1 reported side effects, 1 dissatisfied with programme and 1 did not pursue treatment. At 6‐month follow‐up, 1 participant refused to attend, 1 was unable to be located and 1 'trial closure'

CBT + sertraline: At post‐intervention: 2 reported side effects, 1 symptoms improved, 1 dissatisfied with programme, and 1 did not respond. At 6‐month follow‐up, 1 refused to attend

Selective reporting (reporting bias)

Unclear risk

Remission data not reported by group and functioning data not reported in a useable format. All other outcomes were reported. Do not have access to trial protocol

Other bias

Low risk

Riggs 2007

Methods

Duration:16 weeks

Follow‐up assessment points: Post‐intervention

Funded by: National Institute on Drug Abuse, National Institutes of Health

Participants

N = 126

Adolescent only (13 to 19 years)

Depression diagnoses included: DSM‐IV current MDD episode

Baseline risk of suicide:Primary measure of suicidality was question 13 on the Childhood Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1996)

Baseline suicidality data: Fluoxetine + CBT = 25/63 (39.7%) CBT + placebo = 24/63 (38.1%). N = 13 displayed severe suicidal ideation (> 5 on CDRS‐R Q13)

“Adolescents with past, current or intermittent suicidal ideation (39% at baseline) were not excluded from study participation unless suicidal ideation  were severe or they were otherwise considered by the study physician and according to baseline CDRS‐R ratings (question 13) to be at high risk for a suicide attempt during the trial”

Baseline severity of depression: Children’s Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1996) mean t‐score (SD):

Fluoxetine + CBT: 73.74 (8.51)

Placebo + CBT: 73.03 (7.70)

Comorbidity included: All participants had at least 1 non‐tobacco Substance Use Disorder (SUD), and lifetime Conduct Disorder (CD)

Age mean (SD): Total = 17.16 (1.66)                         

Sex (M:F):  Total = 85:41         

Setting: Outpatient

Excluded psychiatric disorders: Current or past diagnosis of a psychotic disorder or of bipolar disorder (type I or II)

Country: USA

Interventions

Combination (Fluoxetine + CBT)

N = 63

Name: CBT approach using behavioural, cognitive behavioural and motivational enhancement techniques to help adolescents reduce their drug use. The programme contains 1 session specifically on depression, helping adolescents to identify, manage and regulate mood states that often trigger substance use.

 # sessions/length: 1 hour, 16 weekly sessions

Manualised (Y/N): Yes

Individual or group: Individual

Parent involvement: Not specifically but could include up to 2 parent sessions

Fidelity check: Yes. All sessions videotaped and self rated by therapists. 32 videotapes randomly selected and independently rated for adherence and fidelity. “...neither therapist fell below present fidelity/adherence standards during any point of the study”

Delivered by: Study therapists (MD) who were trained and certified by one of the manuals developers. The developer provided ongoing supervision and quality monitoring

Name (class and type): SSRI (Fluoxetine)

Dose (mg/day)/length: 20 mg fixed daily dose

Delivered how: Monitoring of adverse effects and medication adherence was undertaken by research nurses, and occurred either immediately before or after the weekly CBT session

Combination (Placebo + CBT)

Details as above (Y/N): Yes

Outcomes

Clinician reported

Remission of depression defined as as post‐intervention Children’s Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1996) score of ≤ 28

Children’s Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1996)

The Clinical Global Impression Improvement rating (CGI‐I; Guy 1976)

Self reported

Question 13 on the Children’s Depression Rating Scale (CDRS‐R; Poznanski 1996)

Additional Measures

Self reported number of non‐tobacco drugs used in the past 30 days

Urine samples for substance use

Conduct Disorder: Number of self reported DSM‐IV symptoms in the past 30 days

Notes

Group means for age and gender not reported

Dropouts during treatment to any or at least 1 adverse reaction: Authors list 6 as ‘lost to follow‐up’ and 2 to ‘withdrew consent’ but do not disclose if this was due to an adverse reaction

Suicide‐related outcome as an adverse event of treatment: 5 participants (4 in the fluoxetine + CBT group and 1 in the Placebo + CBT group were evaluated in an emergency department or hospitalised for concerns of worsening suicidality during the study.

Standard error and sample size was used to calculate standard deviations for group means

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

“A non‐blinded research pharmacist assigned eligible participants to receive 20 mg of fluoxetine hydrochloride or matching placebo using a small block (6) randomisation scheme of 20 blocks to achieve balance in the treatment assignment”. pg. 1027

Allocation concealment (selection bias)

Low risk

“Active medication and matching placebo were prepared by the research pharmacy at the University of Colorado at Denver and Health Sciences Centre and then provided to clinical research staff in pre‐randomized and pre‐blinded medication bottles”. pg. 1027

Blinding (performance bias and detection bias)
Assessors

Low risk

“Research staff....remained blinded to medication status throughout the trial”. pg.1027

Blinding (performance bias and detection bias)
Participants

Low risk

: “.....participants remained blinded to medication status throughout the trial”. pg.1027

Incomplete outcome data (attrition bias)

Low risk

ITT analysis: “All analyses were intent‐to‐treat (including all randomized study participants)”. pg. 1028.

Impulation method used: “Analyses of dichotomous and continuous primary outcome measures over time used generalized estimating equation (GEE) and likelihood based methods, respectively. Both allow for estimates of changes in repeated measures in the presence of missing data, assuming those data were missing at random”. pg. 1028

Number randomised:

Combination (Fluoxetine + CBT): 63  Combination (Placebo + CBT): 63       Total: 126

Number of dropouts during intervention:

Combination (Fluoxetine+CBT): 11  Combination (Placebo + CBT):9          Total:20

Number analysed post‐intervention:

Combination (Fluoxetine + CBT): 63    Combination (Placebo + CBT): 63       Total:126

Reasons for dropouts: Fluoxetine + CBT: 4 participants went to jail/detention, 3 went to residential treatment at facility and were unable to continue the study, 3 were lost to follow‐up and 1 moved out of area.

Placebo + CBT: 1 participant went to jail/detention, 3 were lost to follow‐up, 3 moved out of area and 2 withdrew consent

Selective reporting (reporting bias)

Unclear risk

No group data on suicide outcomes reported. All other outcomes specified in methods reported. Do not have access to trial protocol

Other bias

Low risk

TADS 2004

Methods

Duration: 12 weeks acute treatment, 6 weeks continuation treatment and 18 weeks maintenance treatment

Follow‐up assessment points: Post‐intervention (12 weeks), 18 weeks (after continuation), 36 weeks (after maintenance)

Funded by: National Institution of Mental Health to Duke University Medical Centre

Participants

N = 439

Adolescent only (12 to 17 years)

Depression diagnoses included: DSM‐IV Major Depressive Disorder (MDD) and a score of 45 or more on the CDRS‐R (Poznanski 1996)

Baseline risk of suicide:

*data obtained from Table 2, 2004 paper

Measured using the Suicidal ideation Questionnaire‐Junior High School Version (SIQ‐JR; Reynolds 1987)

Adjusted mean (SD):

CBT: 21.91 (16.28)

Fluoxetine: 21.81 (15.68)

Fluoxetine + CBT: 27.33 (18.51)

Placebo: 24.20 (16.46)

Analysed according to a cut‐off score of ≤ 31

CBT: 27/107 (25.2%)

Fluoxetine: 28/107 (26.2%)

Fluoxetine + CBT: 42/106 (39.6%)

Participants excluded if deemed ‘high risk’ because of a suicide attempt requiring medical attention within 6 months. Also excluded on the basis of having a clear intent or active plan to attempt suicide, or suicidal ideation accompanied by a disorganised family unable to guarantee adequate safety monitoring

 Baseline severity of depression:

*data obtained from Table 1, 2004 paper, t‐scores presented

Children’s Depression Rating Score (CDRS‐R; Poznanski 1996):

CBT: 75.37 (6.32)

Fluoxetine: 74.73 (6.74)

Fluoxetine + CBT: 75.67 (6.53)

Placebo: 76.14 (6.11)

 

Comorbidity included:

Comorbidity (%)                              CBT        Fluoxetine          Fluoxetine+CBT       Placebo

Any psychiatric comorbidity         58.18                  43.12                     55.66                     51.35

Dysthymia                                         15.45                    5.5                       10.28                     10.71

Anxiety                                               32.43                  23.85                     28.4                       25.23

Disruptive behaviour                       24.32                  22.94                    21.50                     25.00

Obsessive compulsive/tic              1.80                     1.83                      3.74                       3.57

Substance use                                    0.90                     2.75                     2.80                        0

Attention‐deficit/hyperactivity  12.61                   11.93                   13.08                     16.96

Taking medications                          3.60                     2.75                      3.74                      8.93

Age mean (SD): Total = 14.6 (1.54)     

CBT = 14.62 (1.50)                 

Fluoxetine = 14.50 (1.57)                    

CBT + Fluoxetine = 14.6 (1.48)

Placebo = 14.51 (1.62)            

Sex (M:F): 200:239                 

CBT= 50:61                

Fluoxetine = 50:59                  

CBT + Fluoxetine =  47:60

Placebo = 53:59                                  

Setting: Outpatient

Excluded psychiatric disorders: Current or past diagnosis of bipolar disorder, severe conduct disorder, current substance abuse or dependence, pervasive developmental disorder(s), thought disorder or psychiatric disorders requiring out of protocol treatments

Country: USA

Interventions

Psychotherapy (CBT)

N = 111

Name: CBT modules included psycho education about depression and it’s causes, goal‐setting, mood monitoring, increasing pleasant activities, social problem‐solving, and cognitive restructuring

 # sessions/length: Fifteen 1 hour sessions during stage 1, 6 additional sessions for partial responders and bi‐weekly sessions for full responders in stage 2, and 3 sessions (1 every 6 weeks) in stage 3

Manualised (Y/N): Yes

Individual or group: Individual

Parent involvement: 1 to 3 conjoint parent and adolescent sessions took place

Fidelity check: Not reported

Delivered by: Not reported

Medication (Fluoxetine)

N = 109

Name (class and type): Fluoxetine (SSRI)

Dose (mg/day)/length: 10 mg/day and increased up to 40 mg/day by week 8. At week 12, dose raised to 50 to 60mg/day for ‘partial responders’ and ‘full responders’ remained on same fluoxetine dose

Delivered how: Monitoring and status and medication effects occurred during 20 to 30 minute visits. Clinician also offered general encouragement about the effectiveness of pharmacotherapy for MDD

Combination (Fluoxetine+CBT)

N = 107

Details as above (Y/N): Yes

Placebo

N = 112

Outcomes

Clinician reported

Schedule for Affective Disorder and Schizophrenia for School‐Age Children‐Present and Lifetime Version (K‐SADS‐P‐L; Kaufman 1997)

This was used to define remission i.e. those who had did not have a continuing or new mood disorder since the last interview according to the K‐SADS‐PL).It was unclear if DSM‐IV or ICD time criteria were employed

Children’s Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1996)

Self reported

Reynolds Adolescent Depression Scale (RADS; Reynolds 1986).

Suicidal ideation Questionnaire‐Junior High School Version (SIQ‐JR; Reynolds 1987)

Additional Measures

Clinical Global Impression Improvement (CGI‐I; Guy 1976)

Child and Adolescent Impact Assessment (Angold 1998)

Columbia University classification scheme of the US Food and Drug Administration analyses of antidepressant‐associated suicidal events

Notes

Dropouts during treatment to any or at least 1 adverse reaction:

Suicide‐related outcome as an adverse event of treatment: 24 (5.5%) of participants experienced a suicide‐related adverse event Total number (%): *data obtained from 2006 paper

CBT: 5 (4.5)

Fluoxetine: 10 (9.2)

CBT + Fluoxetine: 5 (4.7)

Placebo: 3 (2.7)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“Eligible participants were randomly assigned...using a computerized stratified randomisation, a 1:1:1:1 treatment allocation ratio, permuted blocking (first block size = 4, with subsequent random block sizes of 4 and 8) within each striatum, and site and sex stratification variables”. pg. 808

Allocation concealment (selection bias)

Low risk

“Participants were randomly assigned...at the coordinating centre”. pg. 449

Blinding (performance bias and detection bias)
Assessors

Low risk

“TADS used 2 primary measures of depression status assessed...by an independent evaluator blind to condition”. pg. 448

Blinding (performance bias and detection bias)
Participants

High risk

“Participants and all study staff remained masked in the ‘pills only’ condition (fluoxetine therapy and placebo) until the end of stage 1 (week 12). Patients and treatment providers in the combination and CBT conditions were aware of treatment assignment”. pg. 1133

Incomplete outcome data (attrition bias)

Unclear risk

“The primary analyses of remission rates...were conducted using an “intention to treat” (ITT) approach in which the analysis included all participants randomized to treatment regardless of protocol adherence and/or treatment completion”. pg. Under heading Data Analysis, 2009

Imputation method: LOCF

Number randomised:

CBT: 111      Fluoxetine: 109      Fluoxetine + CBT: 107     Placebo:  112     Total: 439

Number of dropouts during intervention

CBT: 41       Fluoxetine: 38        Fluoxetine + CBT: 23       Placebo: 14         Total: 116

Number of dropouts in follow‐up (18 weeks):

CBT: 21        Fluoxetine: 37      Fluoxetine + CBT: 15      Placebo: 8           Total: 81

Number of dropouts in follow‐up (36 weeks):

CBT: 25        Fluoxetine: 21         Fluoxetine+CBT:23    Placebo: 15        Total: 84

Number analysed post‐intervention:

CBT: 111     Fluoxetine: 109      Fluoxetine + CBT:107     Placebo: 112     Total: 439

Number analysed follow‐up 1 (18 weeks):

CBT: 111      Fluoxetine: 109      Fluoxetine + CBT:107    Total: 327

Number analysed follow‐up 2 (36 weeks):

CBT: 111      Fluoxetine: 109      Fluoxetine + CBT: 107     Total: 327

For active treatment arms: 84/327 exited the study because of loss of follow‐up or withdrawal of consent (n = 21 for CBT + fluoxetine, n = 32 for fluoxetine, n = 31 for CBT). 96/327 discontinued treatment before week 36 due to premature termination or non‐response at the end of stage 1 (n = 25 for CBT + fluoxetine, n = 39 for fluoxetine, n = 32 for CBT), and this discontinuation was decided by the study physician

For placebo: 13/112 participants were terminated prematurely from the study by week 12 due to clinical worsening

Selective reporting (reporting bias)

Unclear risk

Trial protocol located

Other bias

High risk

Combination therapy group had an excess of suicidal ideation at baseline relative to fluoxetine or CBT

TASA 2009

Methods

Duration: 6 months

Follow‐up assessment points: Post‐intervention (24 weeks)

Funded by: National Institute of Mental Health (NIMH)

Participants

N = 124

Adolescent only (12 to 18 years)

Depression diagnoses included: DSM‐IV Major Depressive Disorder (MDD), Dysthymic Disorder (DD) or Depressive Disorder not otherwise specified (DD‐NOS). Participants also had to obtain a score of 36 or more on the CDRS‐R (Poznanski 1996)

Baseline risk of suicide: Participants were only eligible for participation if they had made a suicide attempt in the last 90 days. Beck Scale for Suicidal Ideation (SSI; Beck et al 1979). Mean (SD):

Total = 6.3 (7.7)

CBT‐SP = 5.0 (6.0)

SSRI = 3.9 (6.0)

SSRI+CBT‐SP = 6.9 (8.2)

Baseline severity of depression: 96% met criteria for MDD and 10.5% had DD and DD. Children’s Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1996). Mean (SD):

Total =  50.4 (12.6)

CBT‐SP =  46.9 (14.7)

SSRI = 43.4 (11.1)

SSRI+CBT‐SP= 52.1 (12.0)

Comorbidity included:

Comorbidity (%)               CBT‐SP  SSRI       SSRI+CBT‐SP

Anxiety                                   23.5        28.6        63.4

ADHD                                    11.8        14.3        23.7

ODD/CD                                0.0          35.7        15.1

Age mean (SD):

Total =  15.7 (1.5)

CBT‐SP = 15.7 (1.5)

SSRI = 15.6 (1.4)

SSRI + CBT‐SP = 15.7 (1.6)

Sex (M:F): 28:96            

CBT‐SP = 1:16

SSRI = 1:13

SSRI + CBT‐SP = 26:67   

Setting: Academic sites

Excluded psychiatric diagnoses: Substance dependence, bipolar disorder, psychosis and pervasive developmental disorders (PDD)

Country: USA

Interventions

Psychotherapy (CBT‐SP)

N = 17

Name: CBT + Suicide prevention (CBT‐SP). Modules included; chain analysis of the suicide attempt, safety planning, formulation of the participants cognitive, behavioural, affective and contextual problems, behavioural activation, cognitive restructuring, problem‐solving, and relapse prevention

# sessions/length: Up to 22 sessions, length not specified

Manualised (Y/N): Yes

Individual or group: Individual

Parent involvement: Parent‐youth sessions were included

Fidelity check: No formal check. Weekly telephone conferences were held to review cases

Delivered by: Trained psychotherapists under the supervision of senior experts

Medication (SSRI)

N = 14

Name (class and type): SSRI. Step 1: Monotherapy with an SSRI. Step 2: In the case of non‐response changed to a different SSRI. Stage 3: Medication changed to an alternative class (venlafaxine, duloxetine, mirtazapine, or bupropion) with option of augmenting with lithium or another SSRI

Dose (mg/day)/length: Not specified

Delivered how: By psychopharmacologists

Combination (SSRI + CBT‐SP)

N = 93

Details as above (Y/N): Yes

Outcomes

Clinician reported

Children’s Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1996)

Children’s Global Assessment Scale (C‐GAS; Shaffer 1983)

Self reported

Beck Depression Inventory (BDI; Beck 1988)

Beck Scale for Suicidal Ideation (SSI; Beck 1979a)

Recurrence of a suicidal event

Additional Measures

The Montgomery‐Asberg Depression Rating Scale (MADRS; Montgomery 1979)

The Multidimensional Anxiety Scale for Children (MASC; March 1997)

The Clinical Global Impressions‐Severity (CGI‐S) and Improvement scales (CGI‐I; Guy 1976)

Notes

Dropouts during treatment to any or at least 1 adverse reaction:

Suicide‐related outcome as an adverse event of treatment: 19.5% of participants experienced a suicide event and 12% made a suicide attempt. 1 participant died of suicide 20 days after completing the 24 week SSRI + CBT ‐ SP treatment

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

“The study started as a randomized controlled trial; however; after approximately 9 months of low enrolment despite intensive recruitment efforts, the design was changed so that patients and their families could accept randomisation or choose which treatment to receive”. pg. 998

Allocation concealment (selection bias)

High risk

As participants chose their treatment condition, allocation concealment is not applicable

Blinding (performance bias and detection bias)
Assessors

Low risk

“Independent evaluators were trained to ensure interrater reliability and remained blind to patient treatment assignment”. pg. 999

Blinding (performance bias and detection bias)
Participants

High risk

“Most (n = 104) chose their treatment rather than being randomized”. pg. 1000

Incomplete outcome data (attrition bias)

Unclear risk

“The data were analysed with an intent‐to‐treat approach”. pg. 999

Imputation method: LOCF

Number enrolled (included non‐randomised participants):

CBT‐SI: 17                  SSRI: 14              SSRI + CBT‐SP: 93                Total: 124

Number of dropouts during intervention

CBT‐SI: 6                     SSRI: 6                 SSRI + CBT‐SP: 26               Total: 36

Number analysed post‐intervention:

CBT‐SI: 17                  SSRI: 14               SSRI+ CBT‐SP: 93                Total: 124

Reasons for dropout: 2 participants reported suicidal intent with inability to commit to safety plan, 5 showed lack of adherence to treatment, 9 had a need for different treatments and services and 23 withdrew consent or failed to return for visits for unspecified reasons

Selective reporting (reporting bias)

High risk

Only total and combination treatment outcomes reported. Do not have access to trial protocol

Other bias

High risk

The SSRI + CBT ‐ SP group had higher levels of depression severity at baseline compared with the SSRI or CBT alone group. The SSRI + CBT ‐ SP group also had a higher prevalence of comorbid anxiety and more functional impairment than the other 2 groups

Only 20/124 participants were randomised, the remaining 104/124 chose their treatment option

ADHD: Attention Deficit Hyperactvity Disorder; b.i.d: twice daily; CDI: Children's Depression Inventory; CDRS‐R; Childrens Depression Rating Scale‐Revised; DSM‐III: Diagnostic and Statistical Manual of Mental Disorders, Third Edition; DSM‐IV: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; HMO: Health Maintenance Organisation; ICD: Internation Classification of Diseases; ITT: Intention to Treat; NHS: National Health Service; NOS: Not Otherwise Specified; ODD; Oppositional Definant Disorder; q.i.d: four times daily; SD: Standard Deviation; SSRI: Selective Serotonin REuptake Inhibitor; TAU: Treatment As Usual; t.i.d: three times daily.

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Cheung 2008

Antidepressant versus placebo only, no psychological intervention

Cornelius 2010

Mean age of participants was 21 (too old for inclusion in this review)

Dujovne 1994

Randomised cross‐over trial, which is an exclusion criteria

Emslie 2002 (Eli 2002)

Trial did not include a suitable comparison condition

Emslie 2004

Medical algorithm

Emslie 2013

Relapse prevention study

Findling 2008

Trial did not include a suitable comparison condition

Forbes 2012

Not an RCT (parents chose the treatment condition)

Fristad 2009

Trial did not include a suitable comparison condition.

Goodyer 2011

Relapse prevention study, plus trial did not include a suitable comparison condition (participants in any arm could receive fluoxetine)

King 2009

Trial did not include a suitable comparison condition

Lubman 2005

Participants outside the age range for inclusion in this review, plus it was a treatment resistant trial (sertraline in addition to CBT vs CBT alone in young people who have failed to respond to acute treatment)

Pallavi 2014

Trial did not include a suitable comparison condition

Siddique 2012

Mean age of participants was 29 (too old for inclusion in this review)

Tang 2009

Trial did not include a suitable comparison condition

TORDIA 2008

Treatment of resistant depression

Wagner 2003

Antidepressant versus placebo only, no psychological intervention

Warden 2012

Participants did not have a primary diagnosis of depressive disorder

Wu 2013

Participants did not have a primary diagnosis of depressive disorder

Characteristics of ongoing studies [ordered by study ID]

Craighead 2012

Trial name or title

NCT01740726

Methods

Randomized, treatment efficacy study

Parallel assignment, single blind (outcomes assessor)

Participants

  • Male and female adolescents ages 13‐17

  • Current diagnosis of Major Depressive Disorder as determined by the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS‐PL), Children's Depression Rating Scale (CDRS‐R) raw score > 45 (T‐score > 65) at baseline

  • Estimated full scale IQ > 80 as determined by the Wechsler Intelligence Scale for Children (WISC)

  • Able to receive outpatient care

  • Willing to discontinue other psychosocial treatments

  • Not taking psychotropic medications in the one month prior to consent, with the exception of psychostimulant medication prescribed for the treatment of attention‐deficit/hyperactivity disorder (ADHD)

Interventions

Behavioral Activation: 18 weeks of 1‐hour individual therapy focused on increasing rewarding behaviors, (BA intervention includes monthly booster sessions offered throughout 6‐month follow up)

Drug Therapy: Fluoxetine ‐ initial 10mg dose titrated as necessary to 40mg daily (therapists will be available between sessions and throughout the follow‐up interval to manage clinical concerns or emergencies)

Outcomes

Children's Depression Rating Scale ‐ Revised (CDRS‐R)

Beck Depression Inventory, 2nd Edition (BDI‐II) (self‐report depressive symptom severity)

Starting date

2013

Contact information

Notes

Davey 2012

Trial name or title

YoDA‐C

Methods

Randomised controlled treatment trial

Parallel assignment, double blind

Participants

  • Aged between 15 and 25 years inclusive

  • Diagnosis of Major Depressive Disorder (MDD) using Structured Clinical Interview for DSM‐IV Axis I Disorders, patient version (SCID)

  • Score on the MADRS of 20 or greater, indicating depression of at least moderate severity

Exclusion criteria

  • lifetime or current SCID‐I/P diagnosis of a psychotic disorder

  • lifetime or current SCID‐I/P diagnosis of bipolar I or II disorder

  • acute or unstable medical disorder that would interfere with treatment

  • current pregnancy

  • severe disturbance such that the young person would be unable to comply with the requirements of informed consent orcomply with the study protocol

  • current treatment with an antidepressant medication taken for at least 2 weeks

  • previous treatment with fluoxetine that was either ineffective or poorly tolerated

Interventions

Antidepressant fluoxetine hydrochloride or a placebo tablet will be administered in conjunction with CBT over a period of 12 weeks. The starting dose of fluoxetine or placebo will be 1 capsule or 20mg, administered orally. The dose may be increased any time after the first four weeks to a maximum dose of 2 capsules or 40 mg.

CBT is delivered weekly in 50 minute sessions; where possible clinicians will rescheduled missed appointments. CBT is being delivered according to a newly devised manual that is modular and flexible in its approach and targets the the age group specifically. Each session is being recorded and random sessions will be selected for coding for fidelity.

Outcomes

Primary outcome: change in the Montgomery‐Asberg Depression Rating Scale (MADRS) at week 12

Quick Inventory of Depression Symptomatology–Self Report (QIDS)

CGI Scale severity score

CGI Scale improvement score

Patient Global Impression improvement score

Social and Occupational Functioning Scale

Social Adjustment Scale–Self‐Report

Quality of Life Enjoyment and Satisfaction Questionnaire–Short Form

Suicidal Ideation Questionnaire

Columbia Suicide Severity Rating Scale

Starting date

2013

Contact information

[email protected]

Notes

Gunlicks‐Stoessel 2013 a

Trial name or title

NCT01802437

Methods

Randomized, single blind, defficacy study,

Participants

  • Male and female adolescents ages 12‐17

  • DSM‐IV‐TR criteria for a diagnosis of Major Depressive Disorder, Dysthymia, or Depressive Disorder NOS; demonstrate symptoms of depression (CDRS‐R > 35); and demonstrate impairment in general functioning (CGAS < 65)

  • Adolescents and parents must be English‐speaking

Interventions

Interpersonal psychotherapy ‐ adolescent randomized to an increase in therapy (4 extra therapy sessions)

Fluoxetine ‐ adolescents randomized to an increase in therapy (4 extra therapy sessions)

(Adolescents who receive pharmacotherapy will be prescribed fluoxetine for 12 weeks. The dosage schedule will be 10 mg per day for the first week and 20 mg per day for the following 5 weeks. If no treatment response is observed by week 6, the dosage can be increased to 40 mg per day. Pharmacotherapy sessions will be scheduled weekly for the first 4 weeks and every other week thereafter)

Outcomes

KSADS at week 16 and 32

BDI‐II at weeks 4/8/12/16/24/32

HRSD at weeks 4/8/12/16/24/32

CSSR‐S at weeks 4/8/12/16/24/32

Starting date

2010

Contact information

Notes

Gunlicks‐Stoessel 2013 b

Trial name or title

NCT02017535

Methods

Randomized, single blind, continuation study of NCT01802437 (Gunlicks‐Stoessel 2013 a)

Participants

  • Male and female adolescents ages 12‐17

  • DSM‐IV‐TR criteria for a diagnosis of Major Depressive Disorder, Dysthymia, or Depressive Disorder NOS; demonstrate symptoms of depression (CDRS‐R > 35); and demonstrate impairment in general functioning (CGAS < 65)

  • Adolescents and parents must be English‐speaking

Interventions

Interpersonal Psychotherapy ‐ adolescents randomized to an increase in therapy (4 extra therapy sessions)

Fluoxetine ‐ adolescents randomized to an increase in therapy (4 extra therapy sessions)

(Adolescents who receive pharmacotherapy will be prescribed fluoxetine for 12 weeks. The dosage schedule will be 10 mg per day for the first week and 20 mg per day for the following 5 weeks. If no treatment response is observed by week 6, the dosage can be increased to 40 mg per day. Pharmacotherapy sessions will be scheduled weekly for the first 4 weeks and every other week thereafter)

Outcomes

KSADS at week 16 and 32

BDI‐II at weeks 4/8/12/16/24/32

HRSD at weeks 4/8/12/16/24/32

CSSR‐S at weeks 4/8/12/16/24/32

Starting date

2012

Contact information

Notes

Data and analyses

Open in table viewer
Comparison 1. Psychological therapy versus antidepressant medication

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission by clinical interview (post‐intervention) ITT Show forest plot

2

268

Odds Ratio (M‐H, Random, 95% CI)

0.62 [0.28, 1.35]

Analysis 1.1

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 1 Remission by clinical interview (post‐intervention) ITT.

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 1 Remission by clinical interview (post‐intervention) ITT.

2 Remission by clinical interview (post‐intervention) OC Show forest plot

2

220

Odds Ratio (M‐H, Random, 95% CI)

0.52 [0.27, 0.98]

Analysis 1.2

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 2 Remission by clinical interview (post‐intervention) OC.

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 2 Remission by clinical interview (post‐intervention) OC.

3 Remission by clinical interview (six to nine months follow‐up) ITT Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 1.3

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.

4 Remission by clinical interview (six to nine months follow‐up) OC Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 1.4

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.

5 Dropouts (post‐intervention) Show forest plot

2

271

Odds Ratio (M‐H, Random, 95% CI)

0.61 [0.11, 3.28]

Analysis 1.5

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 5 Dropouts (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 5 Dropouts (post‐intervention).

6 Dropouts (six to nine months follow‐up) Show forest plot

2

223

Odds Ratio (M‐H, Random, 95% CI)

1.17 [0.63, 2.19]

Analysis 1.6

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 6 Dropouts (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 6 Dropouts (six to nine months follow‐up).

7 Suicidal ideation (post‐intervention) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 1.7

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 7 Suicidal ideation (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 7 Suicidal ideation (post‐intervention).

8 Suicidal ideation (six to nine months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 1.8

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 8 Suicidal ideation (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 8 Suicidal ideation (six to nine months follow‐up).

9 Suicidal ideation (post‐intervention) Show forest plot

2

268

Mean Difference (IV, Random, 95% CI)

‐3.12 [‐5.91, ‐0.33]

Analysis 1.9

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 9 Suicidal ideation (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 9 Suicidal ideation (post‐intervention).

10 Suicidal ideation (six to nine months follow‐up) Show forest plot

2

268

Mean Difference (IV, Random, 95% CI)

‐2.89 [‐5.49, ‐0.28]

Analysis 1.10

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 10 Suicidal ideation (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 10 Suicidal ideation (six to nine months follow‐up).

11 Suicidal ideation (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 1.11

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 11 Suicidal ideation (12 months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 11 Suicidal ideation (12 months follow‐up).

12 Remission by cut‐off (post‐intervention) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 1.12

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 12 Remission by cut‐off (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 12 Remission by cut‐off (post‐intervention).

13 Remission by cut‐off (six to nine months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 1.13

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 13 Remission by cut‐off (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 13 Remission by cut‐off (six to nine months follow‐up).

14 Remission by cut‐off (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 1.14

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 14 Remission by cut‐off (12 months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 14 Remission by cut‐off (12 months follow‐up).

15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 1.15

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 1.16

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).

17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 1.17

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).

18 Depression symptoms self rated (post‐intervention) Show forest plot

2

255

Std. Mean Difference (IV, Random, 95% CI)

0.16 [‐0.69, 1.01]

Analysis 1.18

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 18 Depression symptoms self rated (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 18 Depression symptoms self rated (post‐intervention).

19 Depression symptoms self rated (six to nine months follow‐up) Show forest plot

2

268

Std. Mean Difference (IV, Random, 95% CI)

‐0.04 [‐0.51, 0.42]

Analysis 1.19

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 19 Depression symptoms self rated (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 19 Depression symptoms self rated (six to nine months follow‐up).

20 Depression symptoms self rated (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 1.20

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 20 Depression symptoms self rated (12 months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 20 Depression symptoms self rated (12 months follow‐up).

21 Functioning (post‐intervention) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 1.21

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 21 Functioning (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 21 Functioning (post‐intervention).

22 Functioning (six to nine months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 1.22

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 22 Functioning (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 22 Functioning (six to nine months follow‐up).

Open in table viewer
Comparison 2. Combination therapy versus antidepressant medication

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission by clinical interview (post‐intervention) ITT Show forest plot

3

419

Odds Ratio (M‐H, Random, 95% CI)

1.50 [0.99, 2.27]

Analysis 2.1

Comparison 2 Combination therapy versus antidepressant medication, Outcome 1 Remission by clinical interview (post‐intervention) ITT.

Comparison 2 Combination therapy versus antidepressant medication, Outcome 1 Remission by clinical interview (post‐intervention) ITT.

2 Remission by clinical interview (post‐intervention) OC Show forest plot

3

378

Odds Ratio (M‐H, Random, 95% CI)

1.56 [0.98, 2.47]

Analysis 2.2

Comparison 2 Combination therapy versus antidepressant medication, Outcome 2 Remission by clinical interview (post‐intervention) OC.

Comparison 2 Combination therapy versus antidepressant medication, Outcome 2 Remission by clinical interview (post‐intervention) OC.

3 Remission by clinical interview (six to nine months follow‐up) ITT Show forest plot

2

203

Odds Ratio (M‐H, Random, 95% CI)

1.93 [0.93, 4.00]

Analysis 2.3

Comparison 2 Combination therapy versus antidepressant medication, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.

Comparison 2 Combination therapy versus antidepressant medication, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.

4 Remission by clinical interview (six to nine months follow‐up) OC Show forest plot

2

193

Odds Ratio (M‐H, Random, 95% CI)

1.94 [0.88, 4.27]

Analysis 2.4

Comparison 2 Combination therapy versus antidepressant medication, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.

Comparison 2 Combination therapy versus antidepressant medication, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.

5 Remission by clinical interview (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 2.5

Comparison 2 Combination therapy versus antidepressant medication, Outcome 5 Remission by clinical interview (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 5 Remission by clinical interview (12 months follow‐up).

6 Dropouts (post‐intervention) Show forest plot

5

699

Odds Ratio (M‐H, Random, 95% CI)

0.84 [0.51, 1.39]

Analysis 2.6

Comparison 2 Combination therapy versus antidepressant medication, Outcome 6 Dropouts (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 6 Dropouts (post‐intervention).

7 Dropouts (six to nine months follow‐up) Show forest plot

3

420

Odds Ratio (M‐H, Random, 95% CI)

0.94 [0.54, 1.64]

Analysis 2.7

Comparison 2 Combination therapy versus antidepressant medication, Outcome 7 Dropouts (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 7 Dropouts (six to nine months follow‐up).

8 Dropouts (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 2.8

Comparison 2 Combination therapy versus antidepressant medication, Outcome 8 Dropouts (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 8 Dropouts (12 months follow‐up).

9 Suicidal ideation (post‐intervention) Show forest plot

2

388

Odds Ratio (M‐H, Random, 95% CI)

0.75 [0.26, 2.16]

Analysis 2.9

Comparison 2 Combination therapy versus antidepressant medication, Outcome 9 Suicidal ideation (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 9 Suicidal ideation (post‐intervention).

10 Suicidal ideation (six to nine months follow‐up) Show forest plot

2

344

Odds Ratio (M‐H, Random, 95% CI)

0.53 [0.06, 4.58]

Analysis 2.10

Comparison 2 Combination therapy versus antidepressant medication, Outcome 10 Suicidal ideation (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 10 Suicidal ideation (six to nine months follow‐up).

11 Suicidal ideation (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 2.11

Comparison 2 Combination therapy versus antidepressant medication, Outcome 11 Suicidal ideation (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 11 Suicidal ideation (12 months follow‐up).

12 Suicidal ideation (post‐intervention) Show forest plot

2

267

Mean Difference (IV, Random, 95% CI)

‐2.57 [‐5.53, 0.40]

Analysis 2.12

Comparison 2 Combination therapy versus antidepressant medication, Outcome 12 Suicidal ideation (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 12 Suicidal ideation (post‐intervention).

13 Suicidal ideation (six to nine months follow‐up) Show forest plot

2

267

Mean Difference (IV, Random, 95% CI)

‐1.89 [‐4.50, 0.72]

Analysis 2.13

Comparison 2 Combination therapy versus antidepressant medication, Outcome 13 Suicidal ideation (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 13 Suicidal ideation (six to nine months follow‐up).

14 Suicidal ideation (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 2.14

Comparison 2 Combination therapy versus antidepressant medication, Outcome 14 Suicidal ideation (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 14 Suicidal ideation (12 months follow‐up).

15 Remission by cut‐off (post‐intervention) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 2.15

Comparison 2 Combination therapy versus antidepressant medication, Outcome 15 Remission by cut‐off (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 15 Remission by cut‐off (post‐intervention).

16 Remission by cut‐off (six to nine months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 2.16

Comparison 2 Combination therapy versus antidepressant medication, Outcome 16 Remission by cut‐off (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 16 Remission by cut‐off (six to nine months follow‐up).

17 Remission by cut‐off (12 months follow‐up) Show forest plot

2

319

Odds Ratio (M‐H, Random, 95% CI)

1.45 [0.60, 3.52]

Analysis 2.17

Comparison 2 Combination therapy versus antidepressant medication, Outcome 17 Remission by cut‐off (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 17 Remission by cut‐off (12 months follow‐up).

18 Depression symptoms clinician rated (CDRS‐R) (post‐intervention) Show forest plot

2

415

Mean Difference (IV, Random, 95% CI)

‐0.27 [‐4.95, 4.41]

Analysis 2.18

Comparison 2 Combination therapy versus antidepressant medication, Outcome 18 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 18 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

19 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up) Show forest plot

2

408

Mean Difference (IV, Random, 95% CI)

‐0.27 [‐2.26, 1.72]

Analysis 2.19

Comparison 2 Combination therapy versus antidepressant medication, Outcome 19 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 19 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).

20 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 2.20

Comparison 2 Combination therapy versus antidepressant medication, Outcome 20 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 20 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).

21 Depression symptoms self rated (post‐intervention) Show forest plot

5

683

Std. Mean Difference (IV, Random, 95% CI)

‐0.14 [‐0.36, 0.09]

Analysis 2.21

Comparison 2 Combination therapy versus antidepressant medication, Outcome 21 Depression symptoms self rated (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 21 Depression symptoms self rated (post‐intervention).

22 Depression symptoms self rated (six to nine months follow‐up) Show forest plot

4

610

Std. Mean Difference (IV, Random, 95% CI)

‐0.06 [‐0.28, 0.17]

Analysis 2.22

Comparison 2 Combination therapy versus antidepressant medication, Outcome 22 Depression symptoms self rated (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 22 Depression symptoms self rated (six to nine months follow‐up).

23 Depression symptoms self rated (12 months follow‐up) Show forest plot

2

368

Std. Mean Difference (IV, Random, 95% CI)

‐0.26 [‐0.46, ‐0.05]

Analysis 2.23

Comparison 2 Combination therapy versus antidepressant medication, Outcome 23 Depression symptoms self rated (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 23 Depression symptoms self rated (12 months follow‐up).

24 Functioning (post‐intervention) Show forest plot

3

396

Std. Mean Difference (IV, Random, 95% CI)

0.09 [‐0.11, 0.28]

Analysis 2.24

Comparison 2 Combination therapy versus antidepressant medication, Outcome 24 Functioning (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 24 Functioning (post‐intervention).

25 Functioning (six to nine months follow‐up) Show forest plot

3

385

Std. Mean Difference (IV, Random, 95% CI)

0.08 [‐0.12, 0.28]

Analysis 2.25

Comparison 2 Combination therapy versus antidepressant medication, Outcome 25 Functioning (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 25 Functioning (six to nine months follow‐up).

26 Functioning (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 2.26

Comparison 2 Combination therapy versus antidepressant medication, Outcome 26 Functioning (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 26 Functioning (12 months follow‐up).

Open in table viewer
Comparison 3. Combination therapy versus psychological therapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission by clinical interview (post‐intervention) ITT Show forest plot

2

265

Odds Ratio (M‐H, Random, 95% CI)

1.61 [0.38, 6.90]

Analysis 3.1

Comparison 3 Combination therapy versus psychological therapy, Outcome 1 Remission by clinical interview (post‐intervention) ITT.

Comparison 3 Combination therapy versus psychological therapy, Outcome 1 Remission by clinical interview (post‐intervention) ITT.

2 Remission by clinical interview (post‐intervention) OC Show forest plot

2

222

Odds Ratio (M‐H, Random, 95% CI)

1.82 [0.38, 8.68]

Analysis 3.2

Comparison 3 Combination therapy versus psychological therapy, Outcome 2 Remission by clinical interview (post‐intervention) OC.

Comparison 3 Combination therapy versus psychological therapy, Outcome 2 Remission by clinical interview (post‐intervention) OC.

3 Remission by clinical interview (six to nine months follow‐up) ITT Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 3.3

Comparison 3 Combination therapy versus psychological therapy, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.

Comparison 3 Combination therapy versus psychological therapy, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.

4 Remission by clinical interview (six to nine months follow‐up) OC Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 3.4

Comparison 3 Combination therapy versus psychological therapy, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.

Comparison 3 Combination therapy versus psychological therapy, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.

5 Dropouts (post‐intervention) Show forest plot

2

265

Odds Ratio (M‐H, Random, 95% CI)

1.23 [0.12, 12.71]

Analysis 3.5

Comparison 3 Combination therapy versus psychological therapy, Outcome 5 Dropouts (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 5 Dropouts (post‐intervention).

6 Dropouts (six to nine months follow‐up) Show forest plot

2

231

Odds Ratio (M‐H, Random, 95% CI)

0.75 [0.40, 1.42]

Analysis 3.6

Comparison 3 Combination therapy versus psychological therapy, Outcome 6 Dropouts (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 6 Dropouts (six to nine months follow‐up).

7 Suicidal ideation (post‐intervention) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 3.7

Comparison 3 Combination therapy versus psychological therapy, Outcome 7 Suicidal ideation (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 7 Suicidal ideation (post‐intervention).

8 Suicidal ideation (six to nine months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 3.8

Comparison 3 Combination therapy versus psychological therapy, Outcome 8 Suicidal ideation (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 8 Suicidal ideation (six to nine months follow‐up).

9 Suicidal ideation (post‐intervention) Show forest plot

2

265

Mean Difference (IV, Random, 95% CI)

0.60 [‐2.25, 3.45]

Analysis 3.9

Comparison 3 Combination therapy versus psychological therapy, Outcome 9 Suicidal ideation (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 9 Suicidal ideation (post‐intervention).

10 Suicidal ideation (six to nine months follow‐up) Show forest plot

2

265

Mean Difference (IV, Random, 95% CI)

1.78 [‐2.29, 5.85]

Analysis 3.10

Comparison 3 Combination therapy versus psychological therapy, Outcome 10 Suicidal ideation (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 10 Suicidal ideation (six to nine months follow‐up).

11 Suicidal ideation (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 3.11

Comparison 3 Combination therapy versus psychological therapy, Outcome 11 Suicidal ideation (12 months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 11 Suicidal ideation (12 months follow‐up).

12 Remission by cut‐off (post‐intervention) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 3.12

Comparison 3 Combination therapy versus psychological therapy, Outcome 12 Remission by cut‐off (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 12 Remission by cut‐off (post‐intervention).

13 Remission by cut‐off (six to nine months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 3.13

Comparison 3 Combination therapy versus psychological therapy, Outcome 13 Remission by cut‐off (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 13 Remission by cut‐off (six to nine months follow‐up).

14 Remission by cut‐off (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 3.14

Comparison 3 Combination therapy versus psychological therapy, Outcome 14 Remission by cut‐off (12 months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 14 Remission by cut‐off (12 months follow‐up).

15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 3.15

Comparison 3 Combination therapy versus psychological therapy, Outcome 15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 3.16

Comparison 3 Combination therapy versus psychological therapy, Outcome 16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).

17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 3.17

Comparison 3 Combination therapy versus psychological therapy, Outcome 17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).

18 Depression symptoms self rated (post‐intervention) Show forest plot

2

265

Std. Mean Difference (IV, Random, 95% CI)

‐0.28 [‐1.41, 0.84]

Analysis 3.18

Comparison 3 Combination therapy versus psychological therapy, Outcome 18 Depression symptoms self rated (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 18 Depression symptoms self rated (post‐intervention).

19 Depression symptoms self rated (six to nine months follow‐up) Show forest plot

2

265

Std. Mean Difference (IV, Random, 95% CI)

‐0.16 [‐0.63, 0.31]

Analysis 3.19

Comparison 3 Combination therapy versus psychological therapy, Outcome 19 Depression symptoms self rated (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 19 Depression symptoms self rated (six to nine months follow‐up).

20 Depression symptoms self rated (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 3.20

Comparison 3 Combination therapy versus psychological therapy, Outcome 20 Depression symptoms self rated (12 months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 20 Depression symptoms self rated (12 months follow‐up).

21 Functioning (post‐intervention) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 3.21

Comparison 3 Combination therapy versus psychological therapy, Outcome 21 Functioning (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 21 Functioning (post‐intervention).

22 Functioning (six to nine months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 3.22

Comparison 3 Combination therapy versus psychological therapy, Outcome 22 Functioning (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 22 Functioning (six to nine months follow‐up).

Open in table viewer
Comparison 4. Combination therapy versus psychological therapy plus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Dropouts (post‐intervention) Show forest plot

4

249

Odds Ratio (M‐H, Random, 95% CI)

0.98 [0.42, 2.28]

Analysis 4.1

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 1 Dropouts (post‐intervention).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 1 Dropouts (post‐intervention).

2 Suicidal ideation (post‐intervention) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Analysis 4.2

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 2 Suicidal ideation (post‐intervention).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 2 Suicidal ideation (post‐intervention).

3 Remission by cut‐off (post‐intervention) Show forest plot

2

173

Odds Ratio (M‐H, Random, 95% CI)

2.15 [1.15, 4.02]

Analysis 4.3

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 3 Remission by cut‐off (post‐intervention).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 3 Remission by cut‐off (post‐intervention).

4 Remission by cut‐off (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Analysis 4.4

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 4 Remission by cut‐off (12 months follow‐up).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 4 Remission by cut‐off (12 months follow‐up).

5 Depression symptoms clinician rated (CDRS‐R) (post‐intervention) Show forest plot

3

239

Std. Mean Difference (IV, Random, 95% CI)

‐0.52 [‐0.78, ‐0.26]

Analysis 4.5

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 5 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 5 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

6 Depression symptoms self rated (post‐intervention) Show forest plot

3

123

Std. Mean Difference (IV, Random, 95% CI)

‐0.34 [‐0.70, 0.02]

Analysis 4.6

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 6 Depression symptoms self rated (post‐intervention).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 6 Depression symptoms self rated (post‐intervention).

PRISMA flow diagram: CCDANCTR update search June 2014
Figuras y tablas -
Figure 1

PRISMA flow diagram: CCDANCTR update search June 2014

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 1 Remission by clinical interview (post‐intervention) ITT.
Figuras y tablas -
Analysis 1.1

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 1 Remission by clinical interview (post‐intervention) ITT.

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 2 Remission by clinical interview (post‐intervention) OC.
Figuras y tablas -
Analysis 1.2

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 2 Remission by clinical interview (post‐intervention) OC.

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.
Figuras y tablas -
Analysis 1.3

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.
Figuras y tablas -
Analysis 1.4

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 5 Dropouts (post‐intervention).
Figuras y tablas -
Analysis 1.5

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 5 Dropouts (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 6 Dropouts (six to nine months follow‐up).
Figuras y tablas -
Analysis 1.6

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 6 Dropouts (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 7 Suicidal ideation (post‐intervention).
Figuras y tablas -
Analysis 1.7

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 7 Suicidal ideation (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 8 Suicidal ideation (six to nine months follow‐up).
Figuras y tablas -
Analysis 1.8

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 8 Suicidal ideation (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 9 Suicidal ideation (post‐intervention).
Figuras y tablas -
Analysis 1.9

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 9 Suicidal ideation (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 10 Suicidal ideation (six to nine months follow‐up).
Figuras y tablas -
Analysis 1.10

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 10 Suicidal ideation (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 11 Suicidal ideation (12 months follow‐up).
Figuras y tablas -
Analysis 1.11

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 11 Suicidal ideation (12 months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 12 Remission by cut‐off (post‐intervention).
Figuras y tablas -
Analysis 1.12

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 12 Remission by cut‐off (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 13 Remission by cut‐off (six to nine months follow‐up).
Figuras y tablas -
Analysis 1.13

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 13 Remission by cut‐off (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 14 Remission by cut‐off (12 months follow‐up).
Figuras y tablas -
Analysis 1.14

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 14 Remission by cut‐off (12 months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).
Figuras y tablas -
Analysis 1.15

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).
Figuras y tablas -
Analysis 1.16

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).
Figuras y tablas -
Analysis 1.17

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 18 Depression symptoms self rated (post‐intervention).
Figuras y tablas -
Analysis 1.18

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 18 Depression symptoms self rated (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 19 Depression symptoms self rated (six to nine months follow‐up).
Figuras y tablas -
Analysis 1.19

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 19 Depression symptoms self rated (six to nine months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 20 Depression symptoms self rated (12 months follow‐up).
Figuras y tablas -
Analysis 1.20

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 20 Depression symptoms self rated (12 months follow‐up).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 21 Functioning (post‐intervention).
Figuras y tablas -
Analysis 1.21

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 21 Functioning (post‐intervention).

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 22 Functioning (six to nine months follow‐up).
Figuras y tablas -
Analysis 1.22

Comparison 1 Psychological therapy versus antidepressant medication, Outcome 22 Functioning (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 1 Remission by clinical interview (post‐intervention) ITT.
Figuras y tablas -
Analysis 2.1

Comparison 2 Combination therapy versus antidepressant medication, Outcome 1 Remission by clinical interview (post‐intervention) ITT.

Comparison 2 Combination therapy versus antidepressant medication, Outcome 2 Remission by clinical interview (post‐intervention) OC.
Figuras y tablas -
Analysis 2.2

Comparison 2 Combination therapy versus antidepressant medication, Outcome 2 Remission by clinical interview (post‐intervention) OC.

Comparison 2 Combination therapy versus antidepressant medication, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.
Figuras y tablas -
Analysis 2.3

Comparison 2 Combination therapy versus antidepressant medication, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.

Comparison 2 Combination therapy versus antidepressant medication, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.
Figuras y tablas -
Analysis 2.4

Comparison 2 Combination therapy versus antidepressant medication, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.

Comparison 2 Combination therapy versus antidepressant medication, Outcome 5 Remission by clinical interview (12 months follow‐up).
Figuras y tablas -
Analysis 2.5

Comparison 2 Combination therapy versus antidepressant medication, Outcome 5 Remission by clinical interview (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 6 Dropouts (post‐intervention).
Figuras y tablas -
Analysis 2.6

Comparison 2 Combination therapy versus antidepressant medication, Outcome 6 Dropouts (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 7 Dropouts (six to nine months follow‐up).
Figuras y tablas -
Analysis 2.7

Comparison 2 Combination therapy versus antidepressant medication, Outcome 7 Dropouts (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 8 Dropouts (12 months follow‐up).
Figuras y tablas -
Analysis 2.8

Comparison 2 Combination therapy versus antidepressant medication, Outcome 8 Dropouts (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 9 Suicidal ideation (post‐intervention).
Figuras y tablas -
Analysis 2.9

Comparison 2 Combination therapy versus antidepressant medication, Outcome 9 Suicidal ideation (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 10 Suicidal ideation (six to nine months follow‐up).
Figuras y tablas -
Analysis 2.10

Comparison 2 Combination therapy versus antidepressant medication, Outcome 10 Suicidal ideation (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 11 Suicidal ideation (12 months follow‐up).
Figuras y tablas -
Analysis 2.11

Comparison 2 Combination therapy versus antidepressant medication, Outcome 11 Suicidal ideation (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 12 Suicidal ideation (post‐intervention).
Figuras y tablas -
Analysis 2.12

Comparison 2 Combination therapy versus antidepressant medication, Outcome 12 Suicidal ideation (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 13 Suicidal ideation (six to nine months follow‐up).
Figuras y tablas -
Analysis 2.13

Comparison 2 Combination therapy versus antidepressant medication, Outcome 13 Suicidal ideation (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 14 Suicidal ideation (12 months follow‐up).
Figuras y tablas -
Analysis 2.14

Comparison 2 Combination therapy versus antidepressant medication, Outcome 14 Suicidal ideation (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 15 Remission by cut‐off (post‐intervention).
Figuras y tablas -
Analysis 2.15

Comparison 2 Combination therapy versus antidepressant medication, Outcome 15 Remission by cut‐off (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 16 Remission by cut‐off (six to nine months follow‐up).
Figuras y tablas -
Analysis 2.16

Comparison 2 Combination therapy versus antidepressant medication, Outcome 16 Remission by cut‐off (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 17 Remission by cut‐off (12 months follow‐up).
Figuras y tablas -
Analysis 2.17

Comparison 2 Combination therapy versus antidepressant medication, Outcome 17 Remission by cut‐off (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 18 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).
Figuras y tablas -
Analysis 2.18

Comparison 2 Combination therapy versus antidepressant medication, Outcome 18 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 19 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).
Figuras y tablas -
Analysis 2.19

Comparison 2 Combination therapy versus antidepressant medication, Outcome 19 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 20 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).
Figuras y tablas -
Analysis 2.20

Comparison 2 Combination therapy versus antidepressant medication, Outcome 20 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 21 Depression symptoms self rated (post‐intervention).
Figuras y tablas -
Analysis 2.21

Comparison 2 Combination therapy versus antidepressant medication, Outcome 21 Depression symptoms self rated (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 22 Depression symptoms self rated (six to nine months follow‐up).
Figuras y tablas -
Analysis 2.22

Comparison 2 Combination therapy versus antidepressant medication, Outcome 22 Depression symptoms self rated (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 23 Depression symptoms self rated (12 months follow‐up).
Figuras y tablas -
Analysis 2.23

Comparison 2 Combination therapy versus antidepressant medication, Outcome 23 Depression symptoms self rated (12 months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 24 Functioning (post‐intervention).
Figuras y tablas -
Analysis 2.24

Comparison 2 Combination therapy versus antidepressant medication, Outcome 24 Functioning (post‐intervention).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 25 Functioning (six to nine months follow‐up).
Figuras y tablas -
Analysis 2.25

Comparison 2 Combination therapy versus antidepressant medication, Outcome 25 Functioning (six to nine months follow‐up).

Comparison 2 Combination therapy versus antidepressant medication, Outcome 26 Functioning (12 months follow‐up).
Figuras y tablas -
Analysis 2.26

Comparison 2 Combination therapy versus antidepressant medication, Outcome 26 Functioning (12 months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 1 Remission by clinical interview (post‐intervention) ITT.
Figuras y tablas -
Analysis 3.1

Comparison 3 Combination therapy versus psychological therapy, Outcome 1 Remission by clinical interview (post‐intervention) ITT.

Comparison 3 Combination therapy versus psychological therapy, Outcome 2 Remission by clinical interview (post‐intervention) OC.
Figuras y tablas -
Analysis 3.2

Comparison 3 Combination therapy versus psychological therapy, Outcome 2 Remission by clinical interview (post‐intervention) OC.

Comparison 3 Combination therapy versus psychological therapy, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.
Figuras y tablas -
Analysis 3.3

Comparison 3 Combination therapy versus psychological therapy, Outcome 3 Remission by clinical interview (six to nine months follow‐up) ITT.

Comparison 3 Combination therapy versus psychological therapy, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.
Figuras y tablas -
Analysis 3.4

Comparison 3 Combination therapy versus psychological therapy, Outcome 4 Remission by clinical interview (six to nine months follow‐up) OC.

Comparison 3 Combination therapy versus psychological therapy, Outcome 5 Dropouts (post‐intervention).
Figuras y tablas -
Analysis 3.5

Comparison 3 Combination therapy versus psychological therapy, Outcome 5 Dropouts (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 6 Dropouts (six to nine months follow‐up).
Figuras y tablas -
Analysis 3.6

Comparison 3 Combination therapy versus psychological therapy, Outcome 6 Dropouts (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 7 Suicidal ideation (post‐intervention).
Figuras y tablas -
Analysis 3.7

Comparison 3 Combination therapy versus psychological therapy, Outcome 7 Suicidal ideation (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 8 Suicidal ideation (six to nine months follow‐up).
Figuras y tablas -
Analysis 3.8

Comparison 3 Combination therapy versus psychological therapy, Outcome 8 Suicidal ideation (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 9 Suicidal ideation (post‐intervention).
Figuras y tablas -
Analysis 3.9

Comparison 3 Combination therapy versus psychological therapy, Outcome 9 Suicidal ideation (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 10 Suicidal ideation (six to nine months follow‐up).
Figuras y tablas -
Analysis 3.10

Comparison 3 Combination therapy versus psychological therapy, Outcome 10 Suicidal ideation (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 11 Suicidal ideation (12 months follow‐up).
Figuras y tablas -
Analysis 3.11

Comparison 3 Combination therapy versus psychological therapy, Outcome 11 Suicidal ideation (12 months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 12 Remission by cut‐off (post‐intervention).
Figuras y tablas -
Analysis 3.12

Comparison 3 Combination therapy versus psychological therapy, Outcome 12 Remission by cut‐off (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 13 Remission by cut‐off (six to nine months follow‐up).
Figuras y tablas -
Analysis 3.13

Comparison 3 Combination therapy versus psychological therapy, Outcome 13 Remission by cut‐off (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 14 Remission by cut‐off (12 months follow‐up).
Figuras y tablas -
Analysis 3.14

Comparison 3 Combination therapy versus psychological therapy, Outcome 14 Remission by cut‐off (12 months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).
Figuras y tablas -
Analysis 3.15

Comparison 3 Combination therapy versus psychological therapy, Outcome 15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).
Figuras y tablas -
Analysis 3.16

Comparison 3 Combination therapy versus psychological therapy, Outcome 16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).
Figuras y tablas -
Analysis 3.17

Comparison 3 Combination therapy versus psychological therapy, Outcome 17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 18 Depression symptoms self rated (post‐intervention).
Figuras y tablas -
Analysis 3.18

Comparison 3 Combination therapy versus psychological therapy, Outcome 18 Depression symptoms self rated (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 19 Depression symptoms self rated (six to nine months follow‐up).
Figuras y tablas -
Analysis 3.19

Comparison 3 Combination therapy versus psychological therapy, Outcome 19 Depression symptoms self rated (six to nine months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 20 Depression symptoms self rated (12 months follow‐up).
Figuras y tablas -
Analysis 3.20

Comparison 3 Combination therapy versus psychological therapy, Outcome 20 Depression symptoms self rated (12 months follow‐up).

Comparison 3 Combination therapy versus psychological therapy, Outcome 21 Functioning (post‐intervention).
Figuras y tablas -
Analysis 3.21

Comparison 3 Combination therapy versus psychological therapy, Outcome 21 Functioning (post‐intervention).

Comparison 3 Combination therapy versus psychological therapy, Outcome 22 Functioning (six to nine months follow‐up).
Figuras y tablas -
Analysis 3.22

Comparison 3 Combination therapy versus psychological therapy, Outcome 22 Functioning (six to nine months follow‐up).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 1 Dropouts (post‐intervention).
Figuras y tablas -
Analysis 4.1

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 1 Dropouts (post‐intervention).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 2 Suicidal ideation (post‐intervention).
Figuras y tablas -
Analysis 4.2

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 2 Suicidal ideation (post‐intervention).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 3 Remission by cut‐off (post‐intervention).
Figuras y tablas -
Analysis 4.3

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 3 Remission by cut‐off (post‐intervention).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 4 Remission by cut‐off (12 months follow‐up).
Figuras y tablas -
Analysis 4.4

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 4 Remission by cut‐off (12 months follow‐up).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 5 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).
Figuras y tablas -
Analysis 4.5

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 5 Depression symptoms clinician rated (CDRS‐R) (post‐intervention).

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 6 Depression symptoms self rated (post‐intervention).
Figuras y tablas -
Analysis 4.6

Comparison 4 Combination therapy versus psychological therapy plus placebo, Outcome 6 Depression symptoms self rated (post‐intervention).

Comparison 1. Psychological therapy versus antidepressant medication

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission by clinical interview (post‐intervention) ITT Show forest plot

2

268

Odds Ratio (M‐H, Random, 95% CI)

0.62 [0.28, 1.35]

2 Remission by clinical interview (post‐intervention) OC Show forest plot

2

220

Odds Ratio (M‐H, Random, 95% CI)

0.52 [0.27, 0.98]

3 Remission by clinical interview (six to nine months follow‐up) ITT Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

4 Remission by clinical interview (six to nine months follow‐up) OC Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

5 Dropouts (post‐intervention) Show forest plot

2

271

Odds Ratio (M‐H, Random, 95% CI)

0.61 [0.11, 3.28]

6 Dropouts (six to nine months follow‐up) Show forest plot

2

223

Odds Ratio (M‐H, Random, 95% CI)

1.17 [0.63, 2.19]

7 Suicidal ideation (post‐intervention) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

8 Suicidal ideation (six to nine months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

9 Suicidal ideation (post‐intervention) Show forest plot

2

268

Mean Difference (IV, Random, 95% CI)

‐3.12 [‐5.91, ‐0.33]

10 Suicidal ideation (six to nine months follow‐up) Show forest plot

2

268

Mean Difference (IV, Random, 95% CI)

‐2.89 [‐5.49, ‐0.28]

11 Suicidal ideation (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

12 Remission by cut‐off (post‐intervention) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

13 Remission by cut‐off (six to nine months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

14 Remission by cut‐off (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

18 Depression symptoms self rated (post‐intervention) Show forest plot

2

255

Std. Mean Difference (IV, Random, 95% CI)

0.16 [‐0.69, 1.01]

19 Depression symptoms self rated (six to nine months follow‐up) Show forest plot

2

268

Std. Mean Difference (IV, Random, 95% CI)

‐0.04 [‐0.51, 0.42]

20 Depression symptoms self rated (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

21 Functioning (post‐intervention) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

22 Functioning (six to nine months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Figuras y tablas -
Comparison 1. Psychological therapy versus antidepressant medication
Comparison 2. Combination therapy versus antidepressant medication

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission by clinical interview (post‐intervention) ITT Show forest plot

3

419

Odds Ratio (M‐H, Random, 95% CI)

1.50 [0.99, 2.27]

2 Remission by clinical interview (post‐intervention) OC Show forest plot

3

378

Odds Ratio (M‐H, Random, 95% CI)

1.56 [0.98, 2.47]

3 Remission by clinical interview (six to nine months follow‐up) ITT Show forest plot

2

203

Odds Ratio (M‐H, Random, 95% CI)

1.93 [0.93, 4.00]

4 Remission by clinical interview (six to nine months follow‐up) OC Show forest plot

2

193

Odds Ratio (M‐H, Random, 95% CI)

1.94 [0.88, 4.27]

5 Remission by clinical interview (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

6 Dropouts (post‐intervention) Show forest plot

5

699

Odds Ratio (M‐H, Random, 95% CI)

0.84 [0.51, 1.39]

7 Dropouts (six to nine months follow‐up) Show forest plot

3

420

Odds Ratio (M‐H, Random, 95% CI)

0.94 [0.54, 1.64]

8 Dropouts (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

9 Suicidal ideation (post‐intervention) Show forest plot

2

388

Odds Ratio (M‐H, Random, 95% CI)

0.75 [0.26, 2.16]

10 Suicidal ideation (six to nine months follow‐up) Show forest plot

2

344

Odds Ratio (M‐H, Random, 95% CI)

0.53 [0.06, 4.58]

11 Suicidal ideation (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

12 Suicidal ideation (post‐intervention) Show forest plot

2

267

Mean Difference (IV, Random, 95% CI)

‐2.57 [‐5.53, 0.40]

13 Suicidal ideation (six to nine months follow‐up) Show forest plot

2

267

Mean Difference (IV, Random, 95% CI)

‐1.89 [‐4.50, 0.72]

14 Suicidal ideation (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

15 Remission by cut‐off (post‐intervention) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

16 Remission by cut‐off (six to nine months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

17 Remission by cut‐off (12 months follow‐up) Show forest plot

2

319

Odds Ratio (M‐H, Random, 95% CI)

1.45 [0.60, 3.52]

18 Depression symptoms clinician rated (CDRS‐R) (post‐intervention) Show forest plot

2

415

Mean Difference (IV, Random, 95% CI)

‐0.27 [‐4.95, 4.41]

19 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up) Show forest plot

2

408

Mean Difference (IV, Random, 95% CI)

‐0.27 [‐2.26, 1.72]

20 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

21 Depression symptoms self rated (post‐intervention) Show forest plot

5

683

Std. Mean Difference (IV, Random, 95% CI)

‐0.14 [‐0.36, 0.09]

22 Depression symptoms self rated (six to nine months follow‐up) Show forest plot

4

610

Std. Mean Difference (IV, Random, 95% CI)

‐0.06 [‐0.28, 0.17]

23 Depression symptoms self rated (12 months follow‐up) Show forest plot

2

368

Std. Mean Difference (IV, Random, 95% CI)

‐0.26 [‐0.46, ‐0.05]

24 Functioning (post‐intervention) Show forest plot

3

396

Std. Mean Difference (IV, Random, 95% CI)

0.09 [‐0.11, 0.28]

25 Functioning (six to nine months follow‐up) Show forest plot

3

385

Std. Mean Difference (IV, Random, 95% CI)

0.08 [‐0.12, 0.28]

26 Functioning (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Figuras y tablas -
Comparison 2. Combination therapy versus antidepressant medication
Comparison 3. Combination therapy versus psychological therapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission by clinical interview (post‐intervention) ITT Show forest plot

2

265

Odds Ratio (M‐H, Random, 95% CI)

1.61 [0.38, 6.90]

2 Remission by clinical interview (post‐intervention) OC Show forest plot

2

222

Odds Ratio (M‐H, Random, 95% CI)

1.82 [0.38, 8.68]

3 Remission by clinical interview (six to nine months follow‐up) ITT Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

4 Remission by clinical interview (six to nine months follow‐up) OC Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

5 Dropouts (post‐intervention) Show forest plot

2

265

Odds Ratio (M‐H, Random, 95% CI)

1.23 [0.12, 12.71]

6 Dropouts (six to nine months follow‐up) Show forest plot

2

231

Odds Ratio (M‐H, Random, 95% CI)

0.75 [0.40, 1.42]

7 Suicidal ideation (post‐intervention) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

8 Suicidal ideation (six to nine months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

9 Suicidal ideation (post‐intervention) Show forest plot

2

265

Mean Difference (IV, Random, 95% CI)

0.60 [‐2.25, 3.45]

10 Suicidal ideation (six to nine months follow‐up) Show forest plot

2

265

Mean Difference (IV, Random, 95% CI)

1.78 [‐2.29, 5.85]

11 Suicidal ideation (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

12 Remission by cut‐off (post‐intervention) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

13 Remission by cut‐off (six to nine months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

14 Remission by cut‐off (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

15 Depression symptoms clinician rated (CDRS‐R) (post‐intervention) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

16 Depression symptoms clinician rated (CDRS‐R) (six to nine months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

17 Depression symptoms clinician rated (CDRS‐R) (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

18 Depression symptoms self rated (post‐intervention) Show forest plot

2

265

Std. Mean Difference (IV, Random, 95% CI)

‐0.28 [‐1.41, 0.84]

19 Depression symptoms self rated (six to nine months follow‐up) Show forest plot

2

265

Std. Mean Difference (IV, Random, 95% CI)

‐0.16 [‐0.63, 0.31]

20 Depression symptoms self rated (12 months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

21 Functioning (post‐intervention) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

22 Functioning (six to nine months follow‐up) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Figuras y tablas -
Comparison 3. Combination therapy versus psychological therapy
Comparison 4. Combination therapy versus psychological therapy plus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Dropouts (post‐intervention) Show forest plot

4

249

Odds Ratio (M‐H, Random, 95% CI)

0.98 [0.42, 2.28]

2 Suicidal ideation (post‐intervention) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

3 Remission by cut‐off (post‐intervention) Show forest plot

2

173

Odds Ratio (M‐H, Random, 95% CI)

2.15 [1.15, 4.02]

4 Remission by cut‐off (12 months follow‐up) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

5 Depression symptoms clinician rated (CDRS‐R) (post‐intervention) Show forest plot

3

239

Std. Mean Difference (IV, Random, 95% CI)

‐0.52 [‐0.78, ‐0.26]

6 Depression symptoms self rated (post‐intervention) Show forest plot

3

123

Std. Mean Difference (IV, Random, 95% CI)

‐0.34 [‐0.70, 0.02]

Figuras y tablas -
Comparison 4. Combination therapy versus psychological therapy plus placebo