Whats 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 ID: 931755
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Slide1
Four decades of outcome research on psychotherapies for adult depression:
What's next?
Norwegian Psychological Association,
Oslo, September 2
nd 2016
Pim
Cuijpers
Slide2Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons between psychotherapiesComparisons with ADMCharacteristics of patientsCharacteristics of therapiesOther outcomes
Causes of overestimation of the effectsThe need for new treatmentsNew directionsConclusions
Slide3Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons with other psychotherapiesComparisons with ADMCharacteristics of patients
Characteristics of therapiesOther outcomesCauses of overestimation of the effects
The need for new treatments
New directionsConclusions
Slide4Methods
Database RCTs on therapies for depression>60 published meta-analysesMethods: 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 2011Not only significance, but also size of effect:Small: d=0.20 NNT=8.93
Moderate: d=0.50 NNT=3.62Large: d=0.80 NNT=2.34
Threshold for clinical relevance: d=0.24 (Cuijpers et al., Depr Anx, 2014)
Slide5Freely available at:
http://bit.do/meta-analysis
Slide6Randomized trials on psychotherapies for adult depression (N=400)
Cuijpers et al., Curr Opin Psychiatry 2015
Slide7440 randomized trials
Effects of different psychotherapies versus control groupsDirect comparisons between major types of psychotherapy with other psychotherapiesDirect comparisons of psychotherapy with pharmacotherapyComparisons of psychotherapy with combined treatment
Comparisons of pharmacotherapy with combined treatmentRandomized trials on psychotherapy for inpatientsDirect comparisons of individual and group therapy
Direct comparisons of face-to-face therapy with guided self-helpRandomized trials on self-guided therapy for depression
Slide8Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons between psychotherapiesComparisons with ADMCharacteristics of patients
Characteristics of therapiesOther outcomesCauses of overestimation of the effects
The need for new treatments
New directionsConclusions
Slide9440 randomized trials
Effects of different psychotherapies versus control groupsDirect comparisons between major types of psychotherapy with other psychotherapiesDirect comparisons of psychotherapy with pharmacotherapyComparisons of psychotherapy with combined treatment
Comparisons of pharmacotherapy with combined treatmentRandomized trials on psychotherapy for inpatientsDirect comparisons of individual and group therapy
Direct comparisons of face-to-face therapy with guided self-helpRandomized trials on self-guided therapy for depression
Slide10Effects of psychotherapies compared to control groups
N
d
NNT
CBT
159
0.60
3
Behavioral activation
11
0.82
2
Interpersonal Psychother.
22
0.67
3
Problem-solving therapy
21
0.48
4
Supportive therapy
17
0.52
4
Psychodynamic therapy
8
0.44
4
MBCT
6
0.733Other510.703
p for difference is 0.71
Slide11Different types of control groups (only CBT)
N
d
NNT
Waiting list
55
0.83
2
Care as usual
26
0.59
3
Pill placebo and others
13
0.51
4
p for difference is 0.003
Slide12Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons between psychotherapiesComparisons with ADMCharacteristics of patients
Characteristics of therapiesOther outcomesCauses of overestimation of the effects
The need for new treatments
New directionsConclusions
Slide13Main psychotherapies for adult depression
Cognitive behavior therapyBehavioral activation therapyInterpersonal psychotherapyProblem solving therapyPsychodynamic therapyNon-directive supportive counselingSocial 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
Slide14Differences 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
0.0536Cuijpers et al., J Consult Clin Psychol 2008;Barth et al., Plos Med 2013
Slide15Slide16Comparative effects of psychotherapies
Barth et al., Plos Med 2013
Slide17EFFECTIVE 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 thatSo many possible mediators/moderators that there are therapy specific mechanisms but they are not seenIf effects are comparable that is not automatically evidence for universal mechanismsThe evidence for causal mechanisms is very weak
Safe choice is evidence based therapies: CBT, IPT, but also BA
Cuijpers et al., Depress Anx 2013
Slide18Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons between psychotherapiesComparisons with ADMCharacteristics of patients
Characteristics of therapiesOther outcomesCauses of overestimation of the effects
The need for new treatments
New directionsConclusions
Slide19Comparisons with pharmacotherapy
N
d
NNT
Psychotherapy vs pharmacotherapy
37
-0.07
25
Psychotherapy vs combined treatment
19
0.35
5
Pharmacotherapy vs combined treatment
22
0.30
6
Psychotherapy + pharmaco-therapy vs PSY+ placebo
16
0.25
7
Cuijpers et al., J Clin Psychiatry 2008; 2009; 2010; Depress Anx 2008; Acta Psychiatrica Scand 2009; World Psychiatry 2013; 2014
Slide20PSYchotherapy vs adm in mood and anxiety
67 trials (40 depression; 27 anxiety disorders)In mood and anxiety disordersPsychotherapy 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
Slide21Are treatments of depression effective? a)
Cohen’s dNNTPharmacotherapy b)
0.315.75Psychotherapy c)0.257.14
Combined therapyd)0.523.50
a) Only comparisons with pill placebob) Based on Turner et al., Nw Engl J Med 2008; adjusted for publication biasc) Cuijpers et al., Psychol Med 2013 (N=12)d) Data from our database, not (yet) published; only combined versus placebo (N=6)
Slide2211 studies with PLA - PSY – PHA - COMB
Ng95% CINNTCOMB vs placebo110.74
0.48~1.013PHA vs COMB110.370.12~0.63
5PHA vs placebo110.35
0.21~0.495PSY vs COMB110.380.16~0.595PSY vs placebo110.370.11~0.645
Cuijpers et al., World Psychiatry 2013
Slide23Long term outcomes (post-randomization)
NORTherapy vs control (acute)
response at >6 mn221.96
1.50~2.55response at >12
mn111.591.14~2.21Therapy vs contr. (respnd)
Sustained
resp. >6 mn
16
2.37
1.78~3.14
Sustained
resp. >2 yr
6
2.19
1.17~4.09
No relapse >6 mn
11
3.34
1.60~3.41
No relapse >12 mn
5
2.46
1.26~4.82
Karyotaki et al., 2014
Slide24Long-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<0.001Acute 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=0.07NNT = 9.5
Cuijpers et al., BMJ open 2013
Slide25Long term outcomes (post-randomization)
NORCombined vs ADM
response at >6 months122.72
1.83~4.04response at >12 months
82.721.50~4.96Combined vs PSYresponse at >6 months
7
1.30
0.76~2.22
Karyotaki et al., 2014
Slide26Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons between psychotherapiesComparisons with ADMCharacteristics of patients
Characteristics of therapiesOther outcomesCauses of overestimation of the effects
The need for new treatments
New directionsConclusions
Slide27Effect sizes per target group (N=295)
Ng95% CINNTAdults in general144
0.760.67~0.842Older adults400.700.54~0.85
3Students170.95
0.67~1.232Women with PPD230.640.43~0.853General medical
37
0.64
0.49~0.80
3
Other
34
0.60
0.43~0.77
3
p for difference: 0.26
Cuijpers et al., 2006; 2008; 2009; 2014;
Van Straten et al., 2011
Slide28Settings
NgNNTPrimary care20
0.316referral11
0.434systematic screening
70.1314Inpatients150.296
Cuijpers et al., Br J Gen Pract 2009;
Cuijpers et al., Clin Psychol Rev 2010
Slide29Clinical characteristics
NgNNTComorbid alcohol
depression150.27
7alcohol
150.17106-12 months depression80.26
7
6-12 months alcohol
9
0.31
6
Chronic depression/dysthymia
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
Subclinical depression
18
0.35
5Riper et al., Addiction 2014; Cuijpers et al., Clin Psychol Rev 2010; Br J Psychiatry 2014
Slide30Other characteristics
Proportion ethnic minorities: no associationNo association between outcome and baseline severityIn low- and middle income countries (depression & anxiety)17 studiesBrazil, 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
Slide31Individual patient data meta-analyses
16 trials comparing CBT with ADM and pill placeboN>1800 patientsModerators:No difference between men and womenNo association between baseline severity and outcomeNo association between other sociodemographics and outcome
No difference between ADM and CBT in melancholia or atypical depressionSleep is not a predictor or moderator of outcome
Cuijpers et al., Depress Anx 2014; Weitz et al., JAMA Psychiatry 2015
Slide32Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons between psychotherapiesComparisons with ADMCharacteristics of patients
Characteristics of therapiesOther outcomesCauses of overestimation of the effects
The need for new treatments
New directionsConclusions
Slide33Treatment format (N=295)
NgNNTIndividual133
0.713Group108
0.733Guided self-help
410.713Mixed/other130.623
p for difference: 0.92
Slide34Differences 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<0.01Internet-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=6Direct 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;
Slide35Treatment intensity
70 studies on individual therapiesOnly small association between number of sessions and treatment effectNegative association between length of treatment and outcomeStrong positive association between number of sessions per week and outcomeTwo in stead of 1 session per week would increase effect size with 0.45Sessions per week remained significant in multivariate metaregression analysis
Cuijpers
et al., JAD 2013
Slide36Number of sessions
Slide37Number of sessions per week
Slide38Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons between psychotherapiesComparisons with ADMCharacteristics of patients
Characteristics of therapiesOther outcomesCauses of overestimation of the effects
The need for new treatments
New directionsConclusions
Slide39Other 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
0.355Parental functioning50.673Cuijpers 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
Slide40Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons with other psychotherapiesComparisons with ADMCharacteristics of patients
Characteristics of therapiesOther outcomesCauses of overestimation of the effects
The need for new treatments
New directionsConclusions
Slide41RISK of bias
p for difference: <0.001Risk of bias
NgNNT
0 (high)
151.0621
118
0.88
2
2
45
0.81
2
3
33
0.69
3
4 (low)
84
0.47
4
See also:
Cuijpers et al., Psychol Med 2010
Slide42Publication bias?
Duvall & Tweedie’s trim & fill procedure:Unadjusted effect size: d=0.67Adjusted effect size: d=0.42 (p<0.001)Imputed studies: 51Other tests: Begg & Mazumdar; Egger’s testVery significant results (p<0.001)No indication for publication bias in IPT
Cuijpers et al., Br J
Psychiatry 2010
Slide43Publication bias? Unadjusted
Slide44Publication bias? Adjusted
Slide45A better estimate of the effects (All therapies)
Ng
NNTAll studies
295
0.713No waiting list161
0.58
3
Low risk
of bias
62
0.39
5
Adjusted for publ. bias
74
0.31
6
Slide46A better estimate of the effects (CBT)
Ng
NNTAll studies
159
0.713No waiting list77
0.54
3
Low risk
of bias
34
0.39
5
Adjusted for publ. bias
38
0.34
5
Slide47Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons between psychotherapiesComparisons with ADMCharacteristics of patients
Characteristics of therapiesOther outcomes
Causes of overestimation of the effectsThe need for new treatments
New directionsConclusions
Slide48Effective treatments are available
Evidence-based treatments are available: CBT and other psychotherapies, pharmacotherapy, othersConsiderable improvements in treatmentComparable effects in mental health as in general medical field (Leucht, Br J Psychiatry 2012)
Slide49But
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 treatmentsPrevalence does not go down with more treatment
Treatment
effects are overestimatedPublication biasLow quality of studiesResearcher allegianceUnderserved populations and access
Slide50Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons between psychotherapiesComparisons with ADMCharacteristics of patients
Characteristics of therapiesOther outcomes
Causes of overestimation of the effectsThe need for new treatments
New directionsConclusions
Slide51Research priorities
Better understanding of depression (heterogeneity, comorbidity, aetiology, staging)Better diagnostic toolsBetter treatments: but how?
Slide52We do not need
No new therapies for acute treatmentTo examine superiority: trials of ~1000 patientsNo trials examining different treatment formatsNo trials comparing different therapies
No trials examing therapies in specific target groupsUnless there is a convincing reason
Slide53We DO need
Prevention of depression (reduction of incidence 20-25%)Improvement of treatments:Focus on chronic, treatment resistant depression (e.g., CBASP)Focus on relapseWho 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 treatmentsLay health counselors
Group therapiesGuided 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
Slide54Overview
What have we learned about psychotherapies for adult depression?The effectsComparisons between psychotherapiesComparisons with ADMCharacteristics of patients
Characteristics of therapiesOther outcomes
Causes of overestimation of the effectsThe need for new treatments
New directionsConclusions
Slide55Overall conclusions
40 years of research on psychotherapy for depression has resulted in a huge body of knowledgePsychotherapies are effective, but less effective than we thought for a long timeBetter at the longer termIt is effective in many target groups and settingsBut we need to improve treatments, not by developing new ones, but by
focusing on prevention, chronic depression and relapsescaling up and simplifying treatments
Slide56Thank you for your attention!
Contact: p.cuijpers@vu.nl