Four decades of outcome research on psychotherapies for
- Slides: 56
Four decades of outcome research on psychotherapies for adult depression: What's next? Norwegian Psychological Association, Oslo, September 2 nd 2016 Pim Cuijpers
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons between psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 2
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons with other psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 3
METHODS • • Database RCTs on therapies for depression >60 published meta-analyses Methods: Cuijpers et al. , BMC Psychiatry 2008; 8: 36. Data can be downloaded by other researchers: www. evidencebasedpsychotherapies. org • Overview: Cuijpers et al. , Nord J Psychiatry 2011 • Not only significance, but also size of effect: – Small: – Moderate: – Large: d=0. 20 d=0. 50 d=0. 80 NNT=8. 93 NNT=3. 62 NNT=2. 34 • Threshold for clinical relevance: d=0. 24 (Cuijpers et al. , Depr Anx, 2014) 4
Freely available at: http: //bit. do/meta-analysis
RANDOMIZED TRIALS ON PSYCHOTHERAPIES FOR ADULT DEPRESSION (N=400) Cuijpers et al. , Curr Opin Psychiatry 2015 6
440 RANDOMIZED TRIALS • Effects of different psychotherapies versus control groups • Direct comparisons between major types of psychotherapy with other psychotherapies • Direct comparisons of psychotherapy with pharmacotherapy • Comparisons of psychotherapy with combined treatment • Comparisons of pharmacotherapy with combined treatment • Randomized trials on psychotherapy for inpatients • Direct comparisons of individual and group therapy • Direct comparisons of face-to-face therapy with guided self-help • Randomized trials on self-guided therapy for depression 7
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons between psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 8
440 RANDOMIZED TRIALS • Effects of different psychotherapies versus control groups • Direct comparisons between major types of psychotherapy with other psychotherapies • Direct comparisons of psychotherapy with pharmacotherapy • Comparisons of psychotherapy with combined treatment • Comparisons of pharmacotherapy with combined treatment • Randomized trials on psychotherapy for inpatients • Direct comparisons of individual and group therapy • Direct comparisons of face-to-face therapy with guided self-help • Randomized trials on self-guided therapy for depression 9
EFFECTS OF PSYCHOTHERAPIES COMPARED TO CONTROL GROUPS CBT N 159 d 0. 60 NNT 3 Behavioral activation Interpersonal Psychother. Problem-solving therapy Supportive therapy Psychodynamic therapy MBCT Other 11 22 21 17 8 6 51 0. 82 0. 67 0. 48 0. 52 0. 44 0. 73 0. 70 2 3 4 4 4 3 3 p for difference is 0. 71 10
DIFFERENT TYPES OF CONTROL GROUPS (ONLY CBT) Waiting list Care as usual Pill placebo and others p for difference is 0. 003 11 N 55 26 13 d 0. 83 0. 59 0. 51 NNT 2 3 4
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons between psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 12
MAIN PSYCHOTHERAPIES FOR ADULT DEPRESSION • • Cognitive behavior therapy Behavioral activation therapy Interpersonal psychotherapy Problem solving therapy Psychodynamic therapy Non-directive supportive counseling Social skills training • Families or types of therapy? • Difficult to assess from papers which type of therapy is used Cuijpers et al. , J Consult Clin Psychol 2008 13 Faculty of Psychology and Education
DIFFERENCES BETWEEN PSYCHOTHERAPIES? N d NNT CBT vs all other 56 0. 03 167 Supportive vs all other 30 -0. 17 * 10 Behavioral Activ. vs all other 21 0. 14 13 Psychodynamic vs all other 16 -0. 07 25 PST vs all other 7 0. 40 5 IPT vs all other 8 0. 21 * 8 Social Skills vs all other 7 0. 05 36 Cuijpers et al. , J Consult Clin Psychol 2008; Barth et al. , Plos Med 2013 14
COMPARATIVE EFFECTS OF PSYCHOTHERAPIES Barth et al. , Plos Med 2013 16
EFFECTIVE THERAPIES OR EFFECTIVE MECHANISMSIN TREATMENT GUIDELINES FOR DEPRESSION? • If all therapies are (about) equally effective, why not focus on effective mechanisms? • Universal / non-specific mechanisms may explain that • So many possible mediators/moderators that there are therapy specific mechanisms but they are not seen • If effects are comparable that is not automatically evidence for universal mechanisms • The evidence for causal mechanisms is very weak • Safe choice is evidence based therapies: CBT, IPT, but also BA Cuijpers et al. , Depress Anx 2013 17 Faculty of Psychology and Education
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons between psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 18
COMPARISONS WITH PHARMACOTHERAPY N d Psychotherapy vs pharmacotherapy 37 -0. 07 25 Psychotherapy vs combined treatment 19 0. 35 5 22 0. 30 6 16 0. 25 7 Pharmacotherapy vs combined treatment Psychotherapy + pharmacotherapy vs PSY+ placebo Cuijpers et al. , J Clin Psychiatry 2008; 2009; 2010; Depress Anx 2008; Acta Psychiatrica Scand 2009; World Psychiatry 2013; 2014 19 NNT
PSYCHOTHERAPY VS ADM IN MOOD ANXIETY • 67 trials (40 depression; 27 anxiety disorders) • In mood anxiety disorders • Psychotherapy less effective in dysthymia (g=-0. 30) • Psychotherapy more effective in OCD (g=0. 64) • Counseling less effective than pharmacotherapy (g=-0. 33) • TCAs less effective than psychotherapies (g=0. 21) • Remains significant in multivariate metaregression analyses, except for dysthymia Cuijpers et al. , World Psychiatry, 2013 20
ARE TREATMENTS OF DEPRESSION EFFECTIVE? A) Pharmacotherapy b) Psychotherapy c) Combined therapyd) Cohen’s d 0. 31 0. 25 0. 52 NNT 5. 75 7. 14 3. 50 Only comparisons with pill placebo b) Based on Turner et al. , Nw Engl J Med 2008; adjusted for publication bias c) Cuijpers et al. , Psychol Med 2013 (N=12) d) Data from our database, not (yet) published; only combined versus placebo (N=6) a) 21
11 STUDIES WITH PLA - PSY – PHA COMB vs placebo PHA vs COMB PHA vs placebo PSY vs COMB PSY vs placebo N 11 11 11 g 0. 74 0. 37 0. 35 0. 38 0. 37 95% CI 0. 48~1. 01 0. 12~0. 63 0. 21~0. 49 0. 16~0. 59 0. 11~0. 64 Cuijpers et al. , World Psychiatry 2013 22 NNT 3 5 5
LONG TERM OUTCOMES (POSTRANDOMIZATION) N Therapy vs control (acute) • response at >6 mn • response at >12 mn Therapy vs contr. (respnd) • Sustained resp. >6 mn • Sustained resp. >2 yr • No relapse >6 mn • No relapse >12 mn 22 1. 96 1. 50~2. 55 11 1. 59 1. 14~2. 21 16 6 11 5 Karyotaki et al. , 2014 23 OR 2. 37 2. 19 3. 34 2. 46 1. 78~3. 14 1. 17~4. 09 1. 60~3. 41 1. 26~4. 82
LONG-TERM EFFECTS • Acute CBT with (almost) no maintenance vs discontinued pharmacotherapy, at 12 months follow-up (N=8): – OR = 2. 61 (95% CI: 1. 58~4. 31), p<0. 001 • Acute CBT with (almost) no maintenance vs maintenance pharmacotherapy, at 12 months follow-up (N=5): – OR = 1. 62 (95% CI: 0. 97~2. 72), p=0. 07 – NNT = 9. 5 Cuijpers et al. , BMJ open 2013 24
LONG TERM OUTCOMES (POSTRANDOMIZATION) N OR Combined vs ADM • response at >6 months 12 2. 72 1. 83~4. 04 • response at >12 months 8 2. 72 1. 50~4. 96 Combined vs PSY • response at >6 months 7 Karyotaki et al. , 2014 25 1. 30 0. 76~2. 22
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons between psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 26
EFFECT SIZES PER TARGET GROUP (N=295) Adults in general Older adults Students N 144 40 17 g 0. 76 0. 70 0. 95 95% CI 0. 67~0. 84 0. 54~0. 85 0. 67~1. 23 Women with PPD General medical Other 23 37 34 0. 64 0. 60 0. 43~0. 85 3 0. 49~0. 80 3 0. 43~0. 77 3 p for difference: 0. 26 Cuijpers et al. , 2006; 2008; 2009; 2014; Van Straten et al. , 2011 27 NNT 2 3 2
SETTINGS Primary care • referral • systematic screening Inpatients Cuijpers et al. , Br J Gen Pract 2009; Cuijpers et al. , Clin Psychol Rev 2010 28 N g NNT 20 11 7 15 0. 31 0. 43 0. 13 0. 29 6 4 14 6
CLINICAL CHARACTERISTICS N g NNT 15 0. 27 7 15 0. 17 10 8 0. 26 7 9 0. 31 6 • versus control 8 0. 23 8 • versus ADM 10 -0. 31 6 • COMB vs ADM 9 0. 23 8 • COMB vs psychotherapy 4 0. 45 4 18 0. 35 5 Comorbid alcohol • depression • alcohol • 6 -12 months depression • 6 -12 months alcohol Chronic depression/dysthymia Subclinical depression Riper et al. , Addiction 2014; Cuijpers et al. , Clin Psychol Rev 2010; Br J Psychiatry 2014 29
OTHER CHARACTERISTICS • Proportion ethnic minorities: no association • No association between outcome and baseline severity • In low- and middle income countries (depression & anxiety) • 17 studies • Brazil, Uganda (4), Turkey, Pakistan, China (2), Cambodia, India, Iran (1) • g: 1. 02 (95% CI: 0. 76~1. 28); NNT=1. 89 • Depression (8 studies): ES=1. 07 (95% CI: 0. 71~1. 43): NNT=1. 82 Ünlü et al. , Psychiatr Serv 2014; Driessen et al. , J Consult Clin Psychol 2010; Van ‘t Hof et al. , 2011 30
INDIVIDUAL PATIENT DATA META-ANALYSES • 16 trials comparing CBT with ADM and pill placebo • N>1800 patients • Moderators: • No difference between men and women • No association between baseline severity and outcome • No association between other sociodemographics and outcome • No difference between ADM and CBT in melancholia or atypical depression • Sleep is not a predictor or moderator of outcome Cuijpers et al. , Depress Anx 2014; Weitz et al. , JAMA Psychiatry 2015 31
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons between psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 32
TREATMENT FORMAT (N=295) Individual Group Guided self-help Mixed/other p for difference: 0. 92 33 N g NNT 133 108 41 13 0. 71 0. 73 0. 71 0. 62 3 3
DIFFERENCES BETWEEN FORMATS? • Direct comparisons Individual vs group : • N= 19; d = 0. 20; p<0. 01; NNT = 9 (individual is superior) • Drop-out is higher in group: OR=0. 56; p<0. 01 • Internet-based therapies is effective compared to control groups (12 studies) • With support: large effects (d=0. 61) • Without support: small effects (d=0. 25) • • Effects of self-guided therapy are smaller: 7 large trials d=0. 28, NNT=6 Direct comparisons between GSH and FTF therapies for depression/anxiety (21 studies): no difference Cuijpers et al. , Eur J Psychiatry 2008; Psychol Med, 2010; Plos One 2011; Spek et al. , Psychol Med 2007; Andersson & Cuijpers, 2009; Andrews et al. , Plos One 2010; 34
TREATMENT INTENSITY • 70 studies on individual therapies • Only small association between number of sessions and treatment effect • Negative association between length of treatment and outcome • Strong positive association between number of sessions per week and outcome • Two in stead of 1 session per week would increase effect size with 0. 45 • Sessions per week remained significant in multivariate metaregression analysis Cuijpers et al. , JAD 2013 35
NUMBER OF SESSIONS 36
NUMBER OF SESSIONS PER WEEK 37
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons between psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 38
OTHER OUTCOMES N d NNT Quality of life 31 0. 33 6 Suicidality 4 0. 12 n. s. 15 Hopelessness 18 1. 10 2 Social functioning 31 0. 46 4 Social support 15 0. 38 5 Mental health children 7 0. 40 5 Mother-child interaction 8 0. 35 5 Parental functioning 5 0. 67 3 Cuijpers et al. , Ment H Phys Act 2014; EACP 2015; Renner et al. , Psychol Med 2013; Park et al. , COTR 2015; Kolovos, Br J Psychiatry, in press 39
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons with other psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 40
RISK OF BIAS Risk of bias N 0 (high) 1 2 3 4 (low) g 15 1. 06 118 0. 88 45 0. 81 33 0. 69 84 0. 47 p for difference: <0. 001 See also: Cuijpers et al. , Psychol Med 2010 41 NNT 2 2 2 3 4
PUBLICATION BIAS? • Duvall & Tweedie’s trim & fill procedure: – Unadjusted effect size: d=0. 67 – Adjusted effect size: d=0. 42 (p<0. 001) – Imputed studies: 51 • Other tests: Begg & Mazumdar; Egger’s test • Very significant results (p<0. 001) • No indication for publication bias in IPT Cuijpers et al. , Br J Psychiatry 2010 42
PUBLICATION BIAS? UNADJUSTED 43
PUBLICATION BIAS? ADJUSTED 44
A BETTER ESTIMATE OF THE EFFECTS (ALL THERAPIES) N 45 g NNT All studies 295 0. 71 3 No waiting list 161 0. 58 3 Low risk of bias 62 0. 39 5 Adjusted for publ. bias 74 0. 31 6
A BETTER ESTIMATE OF THE EFFECTS (CBT) N 46 g NNT All studies 159 0. 71 3 No waiting list 77 0. 54 3 Low risk of bias 34 0. 39 5 Adjusted for publ. bias 38 0. 34 5
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons between psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 47
EFFECTIVE TREATMENTS ARE AVAILABLE • Evidence-based treatments are available: CBT and other psychotherapies, pharmacotherapy, others • Considerable improvements in treatment • Comparable effects in mental health as in general medical field (Leucht, Br J Psychiatry 2012) 48 Faculty of Psychology and Education
BUT • Only 1/3 of disease burden reduced by treatments (Andrews et al. , 2004) • High relapse (~50% in 2 years, ~80% in 5 years) • Treatments not more effective then 40 years ago • Most progress: how to apply the treatments • Prevalence does not go down with more treatment • Treatment effects are overestimated • Publication bias • Low quality of studies • Researcher allegiance • Underserved populations and access 49 Faculty of Psychology and Education
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons between psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 50
RESEARCH PRIORITIES • Better understanding of depression (heterogeneity, comorbidity, aetiology, staging) • Better diagnostic tools • Better treatments: but how? 51 Faculty of Psychology and Education
WE DO NOT NEED • No new therapies for acute treatment Ø To examine superiority: trials of ~1000 patients 52 • No trials examining different treatment formats • No trials comparing different therapies • No trials examing therapies in specific target groups • Unless there is a convincing reason Faculty of Psychology and Education
WE DO NEED Prevention of depression (reduction of incidence 20 -25%) Improvement of treatments: • • o o • Focus on chronic, treatment resistant depression (e. g. , CBASP) Focus on relapse Who benefits from which treatment? How do treatments work? But also how does natural recovery work and how can that be stimulated? Scaling up and simplifying treatments • • • Lay health counselors Group therapies Guided self-help/Internet-based/telephone therapies are equally effective Cuijpers et al. , Am J Psychiatry, Van Zoonen et al. , J Clin Epidem 2014; Cuijpers, Curr Opin Psychiatry 2015; World Psychiatry in press 53 Faculty of Psychology and Education
OVERVIEW • What have we learned about psychotherapies for adult depression? • • The effects Comparisons between psychotherapies Comparisons with ADM Characteristics of patients Characteristics of therapies Other outcomes Causes of overestimation of the effects • The need for new treatments • New directions • Conclusions 54
OVERALL CONCLUSIONS • 40 years of research on psychotherapy for depression has resulted in a huge body of knowledge • Psychotherapies are effective, but less effective than we thought for a long time • Better at the longer term • It is effective in many target groups and settings • But we need to improve treatments, not by developing new ones, but by • focusing on prevention, chronic depression and relapse • scaling up and simplifying treatments 55
Ø Thank you for your attention! Contact: p. cuijpers@vu. nl 56
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