Table A2:
Characteristics of Systematic Reviews
| Author, Year | Objective | Study Design and Methods | Results | Limitations/Comments |
|---|---|---|---|---|
| Cognitive Behavioural Therapy Versus Usual Care for Major Depressive Disorder | ||||
| Cuijpers et al, 201620 | To conduct a meta-analysis of RCTs to determine the efficacy of CBT for the acute treatment of MDD compared with control (wait list, usual care, or pill placebo). |
Treatment Provider No details reported Inclusion Criteria RCTs Recruited patients met diagnostic criteria (e.g., DSM) Therapies that used individual, group, or guided self-help formats Exclusion Criteria Self-guided therapies without any professional support To calculate effect sizes, all measures examining depressive symptoms (e.g., BDI, HDRS) were used. |
Pooled Effect Size 63 comparisons g = 0.75 (95% CI: 0.64–0.87) NNT = 3.86 Egger's test found considerable asymmetry of the funnel plot (intercept: 1.54; 95% CI 0.59–2.50, P = .001), which indicated publication bias Waitlist Control g = 0.98 (95% CI: 0.80–1.17) NNT = 2.85 Usual Care g = 0.60 (95% CI: 0.45–0.75) NNT = 4.99 Pill Placebo g = 0.55 (95% CI: 0.28–0.81) NNT = 5.51 |
The authors assessed the methodological quality of most studies as low or unknown, according to the Cochrane risk-of-bias assessment tool. Eleven of the 63 studies were rated as high quality. The duration of treatment and follow-up was not reported. The number of treatment sessions varied from 1 to 25. For publication bias with regard to MDD, 14% of the studies were missing, and the pooled effect size dropped from g = 0.75 to g = 0.65 (95% CI: 0.53–0.78). |
| Guidi et al, 201631 | To determine the efficacy of the sequential use of psychotherapy after pharmacotherapy in the treatment of patients with MDD. |
Treatment Provider No details reported Inclusion Criteria RCTs examining the efficacy of the sequential use of psychotherapy following response to acute-phase pharmacotherapy in adults with MDD Exclusion Criteria Studies that did not report on the face-to-face delivery of psychotherapy Studies of continuation and maintenance treatments for MDD in which psychotherapy was also given during the acute phase ≤18 years of age Patients with bipolar disorder, dysthymia, minor depressive disorder, seasonal affective disorder, psychotic disorders, or active medical illness |
13 studies (N = 1,410) Follow-up ranged from 12 months to 52 months after treatment. Length of maintenance treatment ranged from 8 to 32 weeks. Primary outcome measure = relapse or recurrence rates of MDD as defined by study investigators (reaching cut-off on any depression rating scale and/or the occurrence of a defined MDE after remission/recovery in acute-phase treatment) at the longest available follow-up. All studies used CBT as psychotherapy. Three studies compared a sequential treatment arm with antidepressant medication and clinical management, 6 with usual care, 1 with psychoeducation and usual care, and 3 with clinical management only. Overall, the pooled risk ratio for relapse/recurrence was 0.78 (95% CI: 0.67–0.91); NNT = 8. Sequential Use of Psychotherapy During Continuation of Antidepressant Medication 9 studies Pooled risk ratio for relapse: 0.71 (95% CI: 0.68–0.96) NNT = 10 Sequential Use of Psychotherapy After Discontinuation of Antidepressant Medication 4 studies Pooled risk ratio for relapse: 0.67 (95% CI: 0.48–0.94) NNT = 5 |
The methodological quality of the studies was reported as high by the authors; however, the method of rating quality was not reported. Usual care involved standard care as typically provided by the referring agencies with no restriction on the use of pharmacotherapy. |
| Clarke et al, 201530 | To determine the effectiveness of nonpharmacological interventions compared with control in patients who have recovered from MDD. A subset analysis was conducted for CBT. |
Treatment Provider No details reported Inclusion Criteria Adults in full or partial remission from MDD were randomized to either a nonpharmacological intervention or a control condition (usual care, clinical management, or pharmacotherapy) Followed up for a minimum of 1 year after randomization Remission was any reduction in symptoms to below a diagnostic threshold or other threshold on a validated assessment tool Exclusion Criteria Studies that randomized patients to acute treatment even if they then followed them up after recovery |
Compared with control, the average risk of developing a new MDE by 12 months was reduced by 25% for CBT (RR = 0.75, 95% CI: 0.64–0.89). Data for relapse at 24 months were available for 7 of the 10 CBT studies. The effect for CBT at 24 months was similar to the effect at 12 months (RR = 0.72, 95% CI: 0.57–0.91). There was considerable variation among the trials in terms of the nature and duration of the intervention and the inclusion of patients who had undergone previous psychological or pharmacological treatments. Generally, the authors of the CBT trials had adapted CBT for relapse, produced their own manuals, and used this modified version in their own trials. Sessions were between 30 and 90 minutes and spanned periods of 8 to 35 weeks. Most trials treated patients individually. |
There was considerable overlap in the content of the controls; e.g., antidepressant drugs were used in control groups described as “usual care” and as “clinical management,” as well as those described as “medication” arms. There was a large difference in the control event rate for relapse across trials (for 12-month data, range = 0.2–0.79). Overall, the authors reported that half the studies in the meta-analysis were unclear or were at high risk of bias for attrition because of uncertainty about dropout or because of high levels of attrition. The authors used GRADE for each intervention. The evidence was generally of low quality; reasons for downgrading were inconsistency of results, indirectness of evidence, imprecision, and reporting bias. |
| Biesheuvel-Leliefeld et al, 201529 | To determine the effectiveness of psychological interventions in reducing the relapse or recurrence rates of MDD. A subset analysis was reported for CBT. |
Treatment Provider No details reported Inclusion Criteria RCTs Adults with recurrent MDD who were in remission (according to their own definition in the individual trial paper) at randomization Patients received a psychological intervention to reduce the risk of relapse or recurrence Control condition (usual care [routine clinical management, assessment only, no treatment, or waitlist control with unrestricted access to usual care] or antidepressant drugs) Studies reported relapse or recurrence rates using established screeners with a predefined cut-off point for MDD (HRSD, BDI, or diagnostic interview) All modes of delivery were included (face-to-face, group, follow-up booster sessions, Internet) Exclusion Criteria None reported |
16 trials (17 contrasts) CBT after remission was delivered by various modes: weekly group sessions, individual sessions, over the Internet, and as booster sessions (various numbers of sessions during various duration of periods with a minimum of 3 sessions). Duration of follow-up ranged from 22 to 332 weeks. In total, 529 patients received CBT. CBT vs. Usual Care Risk ratio: 0.68 (95% CI: 0.65–0.87) Risk difference: −0.196 (95% CI: −0.28 to −0.11) NNT = 5 CBT vs. Antidepressant Drugs Risk ratio: 0.79 (95% CI: 0.61–1.02) Risk difference: −0.16 (95% CI: −0.30 to −0.016) NNT = 6 |
The authors classified the overall quality of evidence as low according to the GRADE criteria. There were differences in the methodological design of the trials, including the definitions of remission, recovery, relapse, and recurrence; the type and duration of interventions; and whether there was a preceding acute intervention in the same trial (e.g., usual care was often described inadequately, and information on the exact method of determining recurrence [interview vs. questionnaire] was sometimes not provided. Owing to nature of psychological interventions, and the difficulty of comparing these with placebo interventions, the highest-quality evidence may not be possible in such studies. Factors that lower quality of evidence, such as differences in interventions (e.g., owing to differences in client–therapist relations) and difficulties blinding patients, outcome reporters, and personnel, will likely remain in studies investigating the effects of psychological interventions. |
| Linde et al, 201521 | To determine the effectiveness of psychological treatments compared with usual care or placebo in the treatment of primary care patients with MDD. A subset analysis was conducted for face-to-face CBT. |
Treatment Provider Varied (i.e., counsellors, nurses, psychiatrists, psychologists, psychotherapists, therapists) Inclusion Criteria Adults with unipolar MDD Patients had to be recruited through direct referral from a GP or other primary care physician not specialized in mental health care or through screening of patients in the waiting room or from a list in a primary care physician's practice Exclusion Criteria Studies that recruited patients from community-based centres specializing in mental health care |
Face-to-Face CBT Standardized Mean Differences for Posttreatment Depression Scores Compared With Control 7 studies WMD = −0.30 (95% CI: −0.48 to −0.13) Response (defined as at least a 50% score reduction on a depression rating scale) OR = 1.58 (95% CI: 1.11–2.26) NNT = 10 (95% CI: 5–47) Remission (defined as having a symptom score below a fixed threshold) OR = 1.49 (95% CI: 0.90–2.46) |
The reporting of intervention details in usual care groups and of co-interventions (e.g., pharmacotherapy) in the groups receiving psychological treatment was often insufficient. One-third of trials were considered to have a low risk of bias. The reporting of treatment discontinuation, dropout from the study, and loss to follow-up rarely provided sufficient detail to assess whether attrition was a result of acceptability of the treatment or organizational problems. No study reported adverse events or adverse effects for psychological treatments (not even studies including a pharmacotherapy treatment group). The authors reported that given the limited number, rather low quality, and considerable heterogeneity of the available studies, the findings of their review must be interpreted carefully. |
| Churchill et al, 200122 | To conduct a systematic review of all controlled clinical trials in which brief (completed within a time limited framework of ≤ 20 sessions) psychological treatments were compared with one another or with usual care in the treatment of MDD. Therapies included CBT (and variants), interpersonal therapy, and supportive therapy. |
Treatment Provider No details reported Inclusion Criteria Adults aged 16–65 years of age Primary diagnosis of MDD (according to Research Diagnostic Criteria, DSM-3/4 criteria, ICD criteria, or other validated diagnostic instruments, or based on assessment of levels of depressive symptomatology through self-rated or clinician-rated validated instruments) Compared with each other or usual care Exclusion Criteria Marital/couples therapy |
CBT (and variants) vs. Usual Care/Wait List Control Posttreatment Recovery 12 trials (N = 654) OR = 3.42 (95% CI: 1.98–5.93) Mean Differences (Symptoms): Posttreatment 20 studies (N = 748) SMD = −1.0 (95% CI: −1.35 to −0.64) Mean Change in Symptoms from Baseline: Posttreatment 5 studies (N = 172) WMD = 2.38 (95% CI: 0.05–4.71) No Symptoms at Follow-Up 3 months 4 studies (N = 310) OR = 1.59 (95% CI: 0.65–3.90) Mean Differences (Symptoms): Follow-Up 1 month 4 studies (N = 152) SMD = −1.20 (95% CI: −2.10 to −0.31) 2 months 2 studies (N = 44) SMD = −0.73 (95% CI: −1.80 to 0.33) 3 months 2 studies (N = 155) SMD = −0.36 (95% CI: −0.68 to −0.04) 6 months 3 studies (N = 160) SMD = −0.73 (95% CI: −1.50 to 0.03) Mean Change in Symptom Levels From Baseline: Follow-Up 3 months 2 studies (N = 155) WMD = 7.11 (95% CI: 3.25–10.98) 6 months 2 studies (N = 144) WMD = 6.41 (95% CI: 2.48–10.34) Individual CBT vs. Group CBT Posttreatment Recovery 6 studies (N = 231) OR = 1.98 (95% CI: 1.11–3.54) Mean Difference (Symptoms) 8 studies (N = 283) WMD = −3.07 (95% CI: −4.69 to −1.45) Mean Change (Symptoms) No studies reported data No Symptoms at Follow-Up 6 months 2 studies (N = 113) OR = 1.28 (95% CI: 0.52–3.20) Mean Differences (Symptoms): Follow-Up 1 month 2 studies (N = 74) WMD = 5.20 (95% CI: 0.21–10.19) 2 months 3 studies (N = 84) WMD = 0.21 (95% CI: −3.53 to 3.96) 3 months 2 studies (N = 65) WMD = 0.25 (95% CI: −4.61 to 5.11) 6 months 4 studies (N = 155) WMD = 3.21 (95% CI: −2.18 to 8.60) Mean Change in Symptom Levels From Baseline: Follow-Up No studies reported data |
Low scores on internal-validity items were recorded for all but a small number of trials in the review. This, coupled with the inadequate reporting of methodology, resulted in low overall quality scores. Evaluation of psychotherapy poses methodological challenges that are not easily addressed within the context of RCTs. Blinding of therapists in RCTs of psychological treatments cannot be achieved by the inclusion of an inactive placebo psychotherapy arm. Individual therapist characteristics cannot be controlled, nor can the nature of the therapeutic encounter be predetermined or measured with absolute precision. The nature of psychotherapy requires active participation by patients, and it is possible that at least some would be able to identify prominent theoretical constructs during therapy thereby introducing potential bias on the part of the patient. The use of antidepressants in the studies was variable. More than half the studies included in the entire review excluded randomized patients who did not commence treatment or who later dropped out. The majority of the trials used the BDI to measure outcomes in terms of recovery from depressive symptoms. The BDI is a widely used self-rated instrument; however, it is limited to the measurements of symptomatic clinical outcomes. Patients with MDD are affected in many other aspects, and broader measures of levels of functioning, such as quality-of-life scales, might be more meaningful and sensitive to changes in patients. The use of quality-of-life measures was extremely rare in the included studies. Although many authors reported using manuals to standardize individual psychotherapy interventions, only 16% of all included studies monitored the psychological intervention through weekly supervision discussions with the therapists. Nearly 40% of all studies included in the review failed to monitor adherence to the psychotherapy interventions under evaluation. Funnel plots indicated that small negative trials might have been omitted in the literature. Publication bias and other reporting biases are very likely explanations for possible missing studies. The reporting of adverse effects resulting from psychological treatments was poor. Reasons for patient dropout were infrequently investigated or reported by the authors. More than half the studies used volunteer populations (through local radio and newspaper advertising and sometimes offering small cash payments to people who agreed to participate). Patients who volunteer to participate in intervention studies are a self-selected group who tend to experience generally lower morbidity rates than those who do not take part and whose motivation for treatment and attrition rates may differ from the experimental population and from the general patient population. |
| Cognitive Behavioural Therapy and Pharmacotherapy Versus Pharmacotherapy Only for Major Depressive Disorder | ||||
| Karyotaki et al, 201635 | To determine the effectiveness of combined pharmacotherapy and general psychotherapy vs. general psychotherapy or pharmacotherapy only in the treatment of patients with MDD at 6 months or longer postrandomization. Results for CBT were reported in subanalyses. |
Treatment Provider No details reported Inclusion Criteria RCTs Adults ≥ 18 years of age Acute- and maintenance-phase treatments Outcomes at 6 months or longer postrandomization Exclusion Criteria None reported |
Primary outcome = treatment response and sustained response Combined CBT and Antidepressants vs. CBT, Acute Phase Response ≥ 6 Months Postrandomization 5 comparisons OR = 1.51 (95% CI: 0.79–2.86) Response ≥ 1 Year Postrandomization 4 comparisons OR = 1.48 (95% CI: 0.59–3.71) Combined CBT and Antidepressants vs. Antidepressants, Acute Phase Response ≥ 6 Months Postrandomization 6 comparisons OR = 3.02 (95% CI: 1.74–5.25) Response ≥ 1 Year Postrandomization 4 comparisons OR = 3.37 (95% CI: 1.38–8.21) Maintenance CBT and Antidepressants vs. CBT No data reported Maintenance CBT and Antidepressants vs. Antidepressants Response ≥ 6 Months Postrandomization 4 comparisons OR = 1.79 (95% CI: 1.19–2.70) Response ≥ 1 Year Postrandomization No data reported |
For trials on acute-phase treatment, the duration of follow-up ranged from 6 to 48 months after randomization. For maintenance studies, patients entered into either a maintenance psychotherapy combined with antidepressants or maintenance antidepressants group and were followed for 6 to 24 months. Acute-phase treatment had a duration ranging from 6 to 29 sessions, while maintenance-phase psychotherapeutic interventions consisted of 6 to 20 sessions conducted either weekly, biweekly, or monthly. Both older and newer antidepressants were used, including amitriptyline, fluoxetine, fluvoxamine, imipramine, nortriptyline, and sertraline. Overall, there was a general high risk of bias in the RCTs, according to the Cochrane risk-of-bias tool. |
| Amick et al, 201536 | To compare the benefits and harms of second-generation antidepressants and CBT in the initial treatment of a current episode of MDD in adults. |
Treatment Provider No details reported Inclusion Criteria RCTs Adults ≥ 18 years of age Acute-phase MDD Exclusion Criteria ≤ 18 years of age Patients with perinatal depression, seasonal affective disorder, psychotic depression, or treatment-resistant depression |
Second-Generation Antidepressants vs. CBT Monotherapy Remission: 3 trials (N = 432); risk ratio: 0.98 (95% CI 0.73–1.32) Response: 5 trials (N = 660); risk ratio: 0.91 (95% CI: 0.77–1.07) Overall discontinuation of treatment: 4 trials (N = 646); risk ratio: 1.00 (95% CI: 0.55–1.81) Discontinuation of treatment because of adverse effects: 3 trials (N = 632); risk ratio: 2.54 (95% CI: 0.39–16.47) Second-Generation Antidepressants vs. Combination of Second-Generation Antidepressants and CBT Remission: 2 trials (N = 376); risk ratio: 1.06 (95% CI: 0.82–1.38) Response: 2 trials (N = 376); risk ratio: 1.03 (95% CI: 0.85–1.26) Overall discontinuation of treatment: 2 trials (N = 256); risk ratio: 0.77 (95% CI: 0.37–1.60) Discontinuation of treatment because of adverse effects: 2 trials (N = 256); risk ratio: 2.93 (95% CI: 0.72–11.91) |
According to the authors, the type, training, and experience of the clinicians who provided the interventions were quite diverse. The authors reported that the overall strength of evidence was low, based on methods guidance for the Evidence-Based Practice Centers Program of the Agency for Healthcare Research and Quality. |
| Cognitive Behavioural Therapy Versus Pharmacotherapy Only for Major Depressive Disorder | ||||
| Cuijpers et al, 201337 | To compare the effects of acute-phase CBT without any subsequent continuation treatment with the effects of pharmacotherapy that either were continued or discontinued across 6 to 18 months of follow-up. |
Treatment Provider No details reported Inclusion Criteria RCTs Adults ≥ 18 years of age Acute-phase MDD Follow-up of 6–18 months Exclusion Criteria Studies in which CBT was continued during follow-up (although a maximum of 5 booster sessions during follow-up was allows as long as these were not regularly planned) Depression not diagnosed with a standardized diagnostic interview (e.g., structured clinical interview for DSM disorders) Studies in inpatients Studies in adolescents |
9 studies N = 506 patients (CBT n = 271; pharmacotherapy n = 235) Number of CBT treatment sessions ranged from 18 to 24. During the follow-up phase, 3 studies offered up to 4 CBT booster sessions, whereas the other 6 did not offer any additional treatment. The overall quality of the studies was relatively high, compared with the quality of studies on psychotherapy for adult depression in general. Outcome = number of patients who responded to treatment and remained well. Although at least some of the follow-ups were long enough for patients free from relapse to have met the criteria for recovery, the authors used the term “relapse” to refer to all instances of symptom return. Acute-Phase CBT vs. Continuation Pharmacotherapy 5 studies compared 1-year outcomes OR = 1.62 (95% CI: 0.97–2.72) Heterogeneity was zero (95% CI: 0%–79%) NNT = 10 (95% CI not reported) Acute-Phase CBT vs. Pharmacotherapy Discontinuation 8 studies compared 1-year outcomes OR = 2.61 (95% CI: 1.58–4.31) Heterogeneity was zero (95% CI: 0%–68%) NNT = 5 (95% CI: 4–11) |
Small number of studies. Small number of patients within the studies. Variation in the methods used between the studies in terms of drugs, measures and other characteristics. Variability in when pharmacotherapy was discontinued across the studies. |
| Cognitive Behavioural Therapy Versus Usual Care for Generalized Anxiety Disorder | ||||
| Cuijpers et al, 201620 | To meta-analyze RCTs to determine the efficacy of CBT for the acute treatment of GAD compared with control (wait list, usual care, or pill placebo). A subset analysis was conducted for GAD (the study included GAD, social anxiety disorder, and panic disorder). The purpose of the overall study was to report the current best evidence of the effects of CBT in the treatment of GAD, panic disorder, social anxiety disorder, and MDD. |
Treatment Provider No details reported Inclusion Criteria RCTs Recruited patients met diagnostic criteria (e.g., DSM) Therapies that used individual, group, or guided self-help formats Exclusion Criteria Self-guided therapies without any professional support To calculate effect sizes, all measures examining anxiety symptoms (e.g., Beck Anxiety Inventory, PSWQ) were used |
31 studies on GAD were identified. Pooled Effect Size 31 comparisons SMD = 0.80 (95% CI: 0.67–0.93) NNT = 3.58 The Eggers test for publication bias was significant (intercept: 1.60 [95% CI: 0.38–2.83], P = .006). Waitlist Control SMD = 0.85 (95% CI: 0.72–0.99) NNT = 3.35 Usual Care SMD = 0.45 (95% CI: 0.26–0.64) NNT = 6.93 Pill Placebo SMD = 1.32 (95% CI: 0.83–1.81) NNT = 2.08 |
The methodological quality of most studies was low or unknown, according to the Cochrane risk-of-bias tool. Nine of the 31 studies were rated as high quality. The number of treatment sessions varied from 1 to 25. The deadline for the literature search was August 14, 2015. For publication bias with regard to GAD, it was estimated that about one-quarter of the studies were missing; after adjusting for these missing studies, the effect size dropped from g = 0.80 to g = 0.59 (95% CI: 0.44–0.75). |
| Cuijpers et al, 201438 | To meta-analyze RCTs of psychological treatments for GAD. A subset analysis was conducted for CBT. |
Treatment Provider No details reported Inclusion Criteria RCTs of psychological treatments compared with control (wait list, usual care, or placebo) Adults ≥ 18 years of age Patients meeting diagnostic criteria for GAD according to a formal diagnostic interview Exclusion Criteria Patients ≤ 18 years of age |
CBT vs. Control Post-Test 28 comparisons SMD = 0.90 (95% CI: 0.75–1.05) NNT = 2.10 |
There is large overlap in the studies included in this meta-analysis and the 2016 analysis by Cuijpers et al.20 The authors stated that the effects of psychotherapies may also have been overestimated because of publication bias. Publication bias was assessed for all psychotherapies together and not broken down specifically for CBT. Many studies did not provide follow-up assessments. According to the authors:
|
| Hunot et al, 200711 | To examine the efficacy of psychological treatments compared with treatments as usual/wait list for patients with GAD. |
Treatment Provider Varied (i.e., clinical psychologists; doctoral-, senior-, or advanced-level CBT therapists; “experienced therapists”; “therapists”) Inclusion Criteria RCTs Adults 18–75 years of age treated in a primary, secondary, or community setting Use a formal standardized interview to diagnose GAD based on ICD or DSM criteria Any comorbidity in patients must be secondary to the diagnosis of GAD (however, studies involving patients with a comorbid psychiatric diagnosis of substance-related disorder, schizophrenia, or psychotic disorder were excluded) Exclusion Criteria Inpatients |
CBT vs. Usual Care/Wait List 13 studies Primary Outcomes Clinical Response Posttreatment 8 studies (N = 334) 3 studies used clinician-rated composite measure of anxiety severity to assess clinical response; 5 used structured diagnostic interviews RR = 0.64 (95% CI: 0.55–0.74) Reduction in Anxiety Symptoms Posttreatment 12 studies (N = 350) Measures to assess anxiety symptoms comprised the SCID (3 studies), ADIS (2 studies), HAM-A (5 studies), and Zung Anxiety Inventory (2 studies) SMD = −1.00 (95% CI: −1.24 to −0.77) Secondary Outcomes: Posttreatment Reduction in Worry/Fear Symptoms 9 studies (N = 256) Measures included the STAI-T (3 studies), PSWQ (5 studies), and Fear Survey Questionnaire (1 study) SMD = −0.90 (95% CI: −1.16 to −0.64) Reduction in Depressive Symptoms 11 studies (N = 317) Measures included the HDRS (1 study), BDI (9 studies), and the depression subscale of the GHQ-28 (1 study) SMD = −0.96 (95% CI: −1.20 to −0.72) Improvement in Social Functioning 3 studies (N = 69) Measures included the social functioning subscale of the SF-36 (2 studies) and the extraversion subscale of the Eysenck Personality Inventory SMD = 1.01 (95% CI: 0.00–2.03) Improvement in Quality of Life 3 studies (N = 112) Measures included the SF-36 (2 studies) and the Quality-of-Life Inventory (1 study) SMD = 0.44 (95% CI: 0.06–0.82) Adverse Effects No studies reported data Individual or Group Therapy (Subgroup Analysis) 9 studies used individual therapy, and 4 studies used group therapy Clinical Response Ind: RR = 0.63 (95% CI: 0.51–0.76) Grp: RR = 0.66 (95% CI: 0.54–0.82) Anxiety Symptoms Ind: SMD = −0.98 (95% CI: −1.32 to −0.65) Grp: SMD = −1.02 (95% CI: −1.35 to −0.69) Worry Symptoms Ind: SMD = −0.92 (95% CI: −1.37 to −0.48) Grp: SMD = −0.66 (95% CI: −1.03 to −0.29) Depression Symptoms Ind: SMD = −1.06 (95% CI: −1.39 to −0.72) Grp: SMD = −0.86 (95% CI: −1.20 to −0.53) ≤ 8 or > 8 Sessions (Subgroup Analysis) 4 studies used ≤ 8 sessions, and 9 studies used > 8 sessions Clinical Response ≤ 8: RR = 0.49 (95% CI: 0.26–0.91) >8: RR = 0.66 (95% CI: 0.57–0.76) Anxiety Symptoms ≤ 8: SMD = −1.00 (95% CI: −1.56 to −0.44) > 8: SMD = −1.00 (95% CI: −1.26 to −0.74) Worry Symptoms ≤ 8: SMD = −0.62 (95% CI: −1.50 to 0.27) > 8: SMD = −0.93 (95% CI: −1.20 to −0.65) Depression Symptoms ≤ 8: SMD = −1.35 (95% CI: −2.03 to −0.66) > 8: SMD = −0.91 (95% CI: −1.16 to −0.65) |
Study quality was assessed according to the criteria set out in the Cochrane Handbook. Overall, there was a moderate risk of bias in the studies based on unclear allocation concealment. All studies were randomized; however, none provided information on the methods used. Allocation concealment in most studies remains unknown. 72% of all studies in the review used blind assessors. No studies reported whether integrity of blinding was assessed. Studies were mostly small, with a mean sample size of 54 patients. One study included a sample size calculation. 76% of studies used manuals or protocols to standardize treatment approaches for CBT together with the employment of therapists who were experienced in the psychological model under examination. Testing therapists’ fidelity to treatment manuals through the systematic or random checking of audiotapes by independent clinicians is an additional key methodological aspect of assessing psychological studies to ensure that any observed treatment effect can be attributed to specific components and characteristics of the model. 52% of the included studies tested therapists’ treatment fidelity; therefore, there is no certainty in many studies that therapists were adhering to the required psychological model. 66% of studies allowed for the concurrent use of benzodiazepines or antidepressants either in ongoing use, as new courses during the trial period, or in follow-up. Adherence to ongoing treatment was reported in 4 studies that presented mean attendance rates at therapy sessions or adherence to homework assignments. Publication bias was assessed for the two primary outcomes. For clinical response, the funnel plot showed possible asymmetry, which might suggest that small trials with negative outcomes were not included in the review. For reduction in anxiety symptoms, the funnel plot showed a more symmetrical spread. |
| Interpersonal Therapy Versus Usual Care for Major Depressive Disorder | ||||
| Jakobsen et al, 201146 | To systematically review RCTs to determine beneficial and harmful effects of interpersonal therapy versus usual care. |
Provider of Treatment No details reported Inclusion Criteria Adults ≥ 17 years of age Primary diagnosis of MDD based on standardized criteria (e.g., DSM or ICD) Exclusion Criteria Comorbid serious somatic illness Late-life depression (≥ 65 years of age) Pregnancy-related depression Drug or alcohol dependence–related depression |
Depressive Symptoms 4 trials (N = 553) HDRS: WMD = −3.53 (95% CI: −4.91 to −2.16), P < .0001 BDI: WMD = −3.09 (95% CI: −5.35 to −0.83), P = .007 Remission (HDRS < 8) (event = patient not remitting) 3 trials (N = 430) OR = 0.36 (95% CI: 0.24–0.55), P = .00001 Adverse Events Adverse events were reported narratively; no statistics provided Quality of Life None of the RCTs reported this outcome |
All trials had a high risk of bias. Adverse events were not thoroughly reported. The duration of treatment ranged from 5 weeks of treatment to 16 weekly sessions followed by 4 monthly sessions. Four studies used individual treatment, and one study used both individual and group therapy. The length of follow-up was not reported. The extent and form of usual care varied greatly across studies. |
| Clarke et al, 201530 | To determine the effectiveness of nonpharmacological interventions compared with control in patients who have recovered from MDD. A subset analysis was conducted for interpersonal therapy. |
Treatment Provider No details reported Inclusion Criteria Adults in full or partial remission from MDD were randomized to either a nonpharmacological intervention or a control condition (usual care, clinical management, or pharmacotherapy) Followed up for a minimum of 1 year after randomization Remission was any reduction in symptoms to below a diagnostic threshold or other threshold on a validated assessment tool Exclusion Criteria Studies that randomized patients to acute treatment even if they then followed them up after recovery |
6 trials Compared with controls, the average risk of developing a new MDE by 12 months was reduced by 22% for interpersonal therapy (RR = 0.78, 95% CI: 0.65–0.95) Data for relapse at 24 months were available for all 6 of the interpersonal therapy trials. The effect of interpersonal therapy was not sustained (RR = 0.92, 95% CI: 0.81–1.05) |
Considerable overlap in the content of the controls; e.g., antidepressant drugs were used in control groups described as “usual care” and as “clinical management,” as well as those described as “medication” arms. There was a large difference in the control event rate for relapse across trials (for 12-month data, range = 0.2–0.79). Overall, the authors reported that half the studies in the meta-analysis were unclear or at high risk of bias for attrition because of uncertainty about dropouts or because of high levels of attrition. The authors used GRADE for each intervention. Evidence was generally of low quality; reasons for downgrading were inconsistency of results, indirectness of evidence, imprecision, and reporting bias. All interpersonal therapy trials were conducted by related research groups from the University of Pittsburgh. All trials provided monthly sessions for the duration of follow-up. |
| Biesheuvel-Leliefeld et al, 201529 | To determine the effectiveness of psychological interventions in reducing relapse or recurrence rates of MDD. A subset analysis was reported for interpersonal therapy. |
Treatment Provider No details reported Inclusion Criteria RCTs Adults with recurrent MDD who were in remission (according to their own definition in the individual trial paper) at randomization Patients received a psychological intervention to reduce the risk of relapse or recurrence Control condition (usual care [routine clinical management, assessment only, no treatment, or waitlist control with unrestricted access to usual care] or antidepressant drugs) Studies reported relapse or recurrence rates using established screeners with a predefined cut-off point for MDD (HDRS, BDI, or diagnostic interview) All modes of delivery were included (face-to-face, group, follow-up booster sessions, Internet) Exclusion Criteria None reported |
3 trials (6 contrasts) Interpersonal therapy was delivered in individual sessions (varying from monthly maintenance sessions over 8 months to weekly maintenance sessions over 4 months) Duration of follow-up ranged from 17 to 156 weeks In total, 142 patients received interpersonal therapy Interpersonal Therapy vs. Usual Care Risk ratio: 0.41 (95% CI: 0.27–0.63) NNT = 6 Interpersonal Therapy vs. Antidepressant Drugs Risk ratio: 0.83 (95% CI: 0.50–1.38) NNT = not reported |
The authors classified the overall quality of evidence as low according to the GRADE criteria. There were differences in the methodological design of the trials, including the definitions of remission, recovery, relapse, and recurrence; the type and duration of interventions; and whether there was a preceding acute intervention in the same trial (e.g., usual care was often described inadequately, and information on the exact method of determining recurrence [interview vs. questionnaire] was sometimes not provided. Owing to nature of psychological interventions, and the difficulty of comparing these with placebo interventions, the highest-quality evidence may not be possible in such studies. Factors that lower quality of evidence, such as differences in interventions (e.g., owing to differences in client–therapist relations) and difficulties blinding patients, outcome reporters, and personnel, will likely remain in studies investigating the effects of psychological interventions. |
| Linde et al, 201521 | To determine the effectiveness of psychological treatments compared with usual care or placebo in the treatment of primary care patients with MDD. A subset analysis was conducted for face-to-face interpersonal therapy. |
Treatment Provider Varied (i.e., counsellors, nurses, psychiatrists, psychologists, psychotherapists, therapists) Inclusion Criteria Adults with unipolar MDD Patients had to be recruited through direct referral from a GP or other primary care physician not specialized in mental health care or through screening of patients in the waiting room or from a list in a primary care physician's practice Exclusion Criteria Studies that recruited patients from community-based centres specializing in mental health care |
Face-to-Face Interpersonal Therapy Standardized Mean Differences for Posttreatment MDD Scores Compared With Control 2 studies WMD = −0.24 (95% CI: −0.47 to −0.02) Response (defined as at least a 50% score reduction on a depression rating scale) OR = 1.28 (0.80–2.05) Remission (defined as having a symptom score below a fixed threshold) OR = 1.37 (0.81–2.34) |
The reporting of intervention details in usual care groups and of co-interventions (e.g., pharmacotherapy) in the groups receiving psychological treatment was often insufficient. One-third of trials were considered to have a low risk of bias. The reporting of treatment discontinuation, dropout from the study, and loss to follow-up rarely provided sufficient detail to assess whether attrition was a result of acceptability of the treatment or organizational problems. No study reported adverse events or adverse effects for psychological treatments (not even studies including a pharmacotherapy treatment group). The authors reported that given the limited number, rather low quality, and considerable heterogeneity of the available studies, the findings of their review must be interpreted carefully. |
| Churchill et al, 200122 | To conduct a systematic review of all controlled clinical trials in which brief (completed within a time-limited framework of ≤ 20 sessions) psychological treatments were compared with one another or with usual care in the treatment of MDD. Therapies included CBT (and variants), interpersonal therapy, and supportive therapy. |
Treatment Provider No details reported Inclusion Criteria Adults aged 16–65 years of age Primary diagnosis of MDD (according to Research Diagnostic Criteria, DSM-3/4 criteria, ICD criteria, or other validated diagnostic instruments, or based on assessment of levels of depressive symptomatology through self-rated or clinician-rated validated instruments) Compared with each other or usual care Exclusion Criteria Marital/couples therapy |
Interpersonal Therapy vs. Usual Care/Waitlist Control Posttreatment Recovery 1 study (N = 185) OR = 3.52 (95% CI: 1.91–6.51) Mean Differences (Symptoms): Posttreatment 1 study (N = 185) WMD = −3.21 (95% CI: −5.18 to −1.24) Mean Change in Symptoms From Baseline: Posttreatment 1 study (N = 185) WMD = 2.09 (95% CI: 0.04–4.14) No Symptoms at Follow-Up 8 months 1 study (N = 185) OR = 3.72 (95% CI: 2.03–6.81) Mean Differences (Symptoms): Follow-Up 8 months 1 study (N = 185) WMD = −3.77 (95% CI: −5.66 to −1.88) Mean Change in Symptom Levels From Baseline: Follow-Up 8 months 1 study (N = 185) WMD = 2.64 (95% CI: 0.56–4.72) |
Low scores on internal-validity items were recorded for all but a small number of trials in the review. This, coupled with the inadequate reporting of methodology, resulted in low overall quality scores. Evaluation of psychotherapy poses methodological challenges that are not easily addressed within the context of RCTs. Blinding of therapists in RCTs of psychological treatments cannot be achieved by the inclusion of an inactive placebo psychotherapy arm. Individual therapist characteristics cannot be controlled, nor can the nature of the therapeutic encounter be predetermined or measured with absolute precision. The nature of psychotherapy requires active participation by patients, and it is possible that at least some would be able to identify prominent theoretical constructs during therapy thereby introducing potential bias on the part of the patient. The use of antidepressants in the studies was variable. More than half the studies included in the entire review excluded randomized patients who did not commence treatment or who later dropped out. The majority of the trials used the BDI to measure outcomes in terms of recovery from depressive symptoms. (The BDI is a widely used self-rated instrument; however, it is limited to the measurements of symptomatic clinical outcomes. Patients with MDD are affected in many other aspects, and broader measures of levels of functioning, such as quality-of-life scales, might be more meaningful and sensitive to changes in patients. The use of quality-of-life measures was extremely rare in the included studies. Although many authors reported using manuals to standardize individual psychotherapy interventions, only 16% of all included studies monitored the psychological intervention through weekly supervision discussions with the therapists. Nearly 40% of all studies included in the review failed to monitor adherence to the psychotherapy interventions under evaluation. Funnel plots indicated that small negative trials might have been omitted in the literature. Publication bias and other reporting biases are very likely explanations for possible missing studies. The reporting of adverse effects resulting from psychological treatments was poor. Reasons for patient dropout were infrequently investigated or reported by the authors. More than half the studies used volunteer populations (through local radio and newspaper advertising and sometimes offering small cash payments to people who agreed to participate). Patients who volunteer to participate in intervention studies are a self-selected group who tend to experience generally lower morbidity rates than those who do not take part and whose motivation for treatment and attrition rates may differ from the experimental population and from the general patient population. |
| Supportive Therapy Versus Usual Care for Major Depressive Disorder | ||||
| Churchill et al, 200122 | To conduct a systematic review of all controlled clinical trials in which brief (completed within a time-limited framework of ≤ 20 sessions) psychological treatments were compared with one another or with usual care in the treatment of MDD. Therapies included CBT (and variants), interpersonal therapy, and supportive therapy. |
Treatment Provider No details reported Inclusion Criteria Adults aged 16–65 years of age Primary diagnosis of MDD (according to Research Diagnostic Criteria, DSM-3/4 criteria, ICD criteria, or other validated diagnostic instruments, or based on assessment of levels of depressive symptomatology through self-rated or clinician-rated validated instruments) Compared with each other or usual care Exclusion Criteria Marital/couples therapy |
Supportive Therapy vs. Usual Care/Waitlist Control Posttreatment Recovery 4 studies (N = 118) OR = 2.71 (95% CI: 1.19–6.16) Mean Differences (Symptoms): Posttreatment 4 studies (N = 123) SMD = −0.42 (95% CI: −0.78 to −0.06) Mean Change in Symptoms From Baseline Posttreatment 2 studies (N = 79) SMD = −0.01 (95% CI: −0.45 to 0.43) No Symptoms at Follow-Up No data available Mean Differences (Symptoms): Follow-Up 2 months 1 study (N = 22) SMD = −0.27 (95% CI: −1.11 to 0.57) 6 months 1 study (N = 17) SMD = −2.01 (95% CI: −3.27 to −0.75) Mean Change in Symptom Levels From Baseline: Follow-Up 2 months 1 study (N = 22) WMD = −4.30 (95% CI: −17.05 to 8.45) |
Low scores on internal-validity items were recorded for all but a small number of trials in the review. This, coupled with the inadequate reporting of methodology, resulted in low overall quality scores. Evaluation of psychotherapy poses methodological challenges that are not easily addressed within the context of RCTs. Blinding of therapists in RCTs of psychological treatments cannot be achieved by the inclusion of an inactive placebo psychotherapy arm. Individual therapist characteristics cannot be controlled, nor can the nature of the therapeutic encounter be predetermined or measured with absolute precision. The nature of psychotherapy requires active participation by patients, and it is possible that at least some would be able to identify prominent theoretical constructs during therapy thereby introducing potential bias on the part of the patient. The use of antidepressants in the studies was variable. More than half the studies included in the entire review excluded randomized patients who did not commence treatment or who later dropped out. The majority of the trials used the BDI to measure outcomes in terms of recovery from depressive symptoms. The BDI is a widely used self-rated instrument; however, it is limited to the measurements of symptomatic clinical outcomes. Patients with MDD are affected in many other aspects, and broader measures of levels of functioning, such as quality-of-life scales, might be more meaningful and sensitive to changes in patients. The use of quality-of-life measures was extremely rare in the included studies. Although many authors reported using manuals to standardize individual psychotherapy interventions, only 16% of all included studies monitored the psychological intervention through weekly supervision discussions with the therapists. Nearly 40% of all studies included in the review failed to monitor adherence to the psychotherapy interventions under evaluation. Funnel plots indicated that small negative trials might have been omitted in the literature. Publication bias and other reporting biases are very likely explanations for possible missing studies. The reporting of adverse effects resulting from psychological treatments was poor. Reasons for patient dropout were infrequently investigated or reported by the authors. More than half the studies used volunteer populations (through local radio and newspaper advertising and sometimes offering small cash payments to people who agreed to participate). Patients who volunteer to participate in intervention studies are a self-selected group who tend to experience generally lower morbidity rates than those who do not take part and whose motivation for treatment and attrition rates may differ from the experimental population and from the general patient population. |
| Cuijpers et al, 201214 | To conduct a meta-analysis of RCTs to determine the efficacy of supportive therapy compared with control (waitlist or usual care) or pharmacotherapy for the treatment of MDD. |
Treatment Provider Varied (i.e., nurses, psychiatrists, psychologists, social workers, specialists in counselling, and trained nonspecialists) Inclusion Criteria RCTs Adults with MDD assessed via diagnostic interview Exclusion Criteria Studies in which nonprofessional therapists were used Patients ≤ 18 years of age Patients who did not have MDD |
Supportive Therapy vs. Control Overall Mean Effect Size 18 comparisons g = 0.58 (95% CI: 0.45–0.72), P < .001 NNT = 3.14 HDRS Only 5 comparisons g = 0.46 (95% CI: 0.19–0.73), P < .001 NNT = 3.91 BDI Only 8 comparisons g = 0.52 (95% CI: 0.32–0.73), P < .001 NNT = 3.50 3–6 Months of Follow-Up 4 comparisons g = 0.22 (95% CI: −0.05 to 0.50) NNT = 8.06 9–12 Months of Follow-Up 4 comparisons g = 0.09 (95% CI: −0.12 to 0.31) NNT = 20.00 Supportive Therapy vs. Pharmacotherapy Overall Effect Size 4 comparisons g = −0.18 (95% CI −0.59 to 0.23) NNT: ns |
The majority of the studies did not examine long-term effects. Most studies focused on mild to moderate MDD The quality of the studies varied. Eight studies met all 4 quality criteria (the Cochrane Collaboration risk-of-bias criteria), while 12 studies met 3 of the 4 criteria. |
Abbreviations: ADIS, Anxiety Disorder Interview Schedule; BDI, Becks Depression Inventory; CBT, cognitive behavioural therapy; CI, confidence interval; DSM, Diagnostic and Statistical Manual; GAD, generalized anxiety disorder; GHQ-28, General Health Questionnaire-28; GP, general practitioner; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; HAM-A, Hamilton Anxiety Rating Scale; HDRS, Hamilton Depression Rating Scale; ICD, International Statistical Classification of Diseases and Related Health Problems; MDD, major depressive disorder; MDE, major depressive episode; NNT, number needed to treat; ns, not significant; OR, odds ratio; PSWQ, Penn State Worry Questionnaire; RCT, randomized controlled trial; RR, relative risk; SCID, Structured Clinical Interview for DSM-4; SF-36; 36-Item Short-Form Health Survey; SMD, standardized mean difference; STAI-T, State–Trait Anxiety Inventory; WMD, weighted mean difference.