Individual psychotherapy for cluster-C personality disorders: protocol of a pragmatic RCT comparing short-term psychodynamic supportive psychotherapy, affect phobia therapy and schema therapy (I-FORCE).

BACKGROUND: Cluster-C personality disorders (PDs) are highly prevalent in clinical practice and are associated with unfavourable outcome and chronicity of all common mental health disorders (e.g. depression and anxiety disorders). Although several forms of individual psychotherapy are commonly offered in clinical practice for this population, evidence for differential effectiveness of different forms of psychotherapy is lacking. Also, very little is known about the underlying working mechanisms of these psychotherapies. Finding evidence on the differential (cost)-effectiveness for this group of patients and the working mechanisms of change is important to improve the quality of care for this vulnerable group of patients. OBJECTIVE: In this study, we will compare the differential (cost)-effectiveness of three individual psychotherapies: short-term psychodynamic supportive psychotherapy (SPSP), affect phobia therapy (APT) and schema therapy (ST). Although these psychotherapies are commonly used in clinical practice, evidence for the Cluster-C PDs is limited. Additionally, we will investigate predictive factors, non-specific and therapy-specific mediators. METHODS: This is a mono-centre randomized clinical trial with three parallel groups: (1) SPSP, (2) APT, (3) ST. Randomization on patient level will be pre-stratified according to type of PD. The total study population to be included consists of 264 patients with Cluster-C PDs or other specified PD with mainly Cluster-C traits, aged 18-65 years, seeking treatment at NPI, a Dutch mental health care institute specialized in PDs. SPSP, APT and ST (50 sessions per treatment) are offered twice a week in sessions of 50 min for the first 4 to 5 months. After that, session frequency decreases to once a week. All treatments have a maximum duration of 1 year. Change in the severity of the PD (ADP-IV) will be the primary outcome measure. Secondary outcome measures are personality functioning, psychiatric symptoms and quality of life. Several potential mediators, predictors and moderators of outcome are also assessed. The effectiveness study is complemented with a cost-effectiveness/utility study, using both clinical effects and quality-adjusted life-years, and primarily based on a societal approach. Assessments will take place at baseline, start of treatment and at 1, 3, 6, 9, 12, 18, 24 and 36 months. DISCUSSION: This is the first study comparing psychodynamic treatment to schema therapy for Cluster-C PDs. The naturalistic design enhances the clinical validity of the outcome. A limitation is the lack of a control group for ethical reasons. TRIAL REGISTRATION: NL72823.029.20 [Registry ID: CCMO]. Registered on 31 August 2020. First participant included on 23 October 2020.

G-FORCE: the effectiveness of group psychotherapy for Cluster-C personality disorders: protocol of a pragmatic RCT comparing psychodynamic and two forms of schema group therapy.

BACKGROUND: Cluster-C personality disorders (PDs), characterized by a high level of fear and anxiety, are related to high levels of distress, societal dysfunctioning and chronicity of various mental health disorders. Evidence for the optimal treatment is extremely scarce. Nevertheless, the need to treat these patients is eminent. In clinical practice, group therapy is one of the frequently offered approaches, with two important frameworks: schema therapy and psychodynamic therapy. These two frameworks suggest different mechanisms of change, but until now, this has not yet been explored. The purpose of the present G-FORCE trial is to find evidence on the differential (cost)effectiveness of two forms of schema group therapy and psychodynamic group therapy in the routine clinical setting of an outpatient clinic and to investigate the underlying working mechanisms and predictors of outcome of these therapies. METHODS: In this mono-centre pragmatic randomized clinical trial, 290 patients with Cluster-C PDs or other specified PD with predominantly Cluster-C traits, will be randomized to one of three treatment conditions: group schema therapy for Cluster-C (GST-C, 1 year), schema-focused group therapy (SFGT, 1.5 year) or psychodynamic group therapy (PG, 2 years). Randomization will be pre-stratified on the type of PD. Change in severity of PD (APD-IV) over 24 months will be the primary outcome measure. Secondary outcome measures are personality functioning, psychiatric symptoms and quality of life. Potential predictors and mediators are selected and measured repeatedly. Also, a cost-effectiveness study will be performed, primarily based on a societal perspective, using both clinical effects and quality-adjusted life years. The time-points of assessment are at baseline, start of treatment and after 1, 3, 6, 9, 12, 18, 24 and 36 months. DISCUSSION: This study is designed to evaluate the effectiveness and cost-effectiveness of three formats of group psychotherapy for Cluster-C PDs. Additionally, predictors, procedure and process variables are analysed to investigate the working mechanisms of the therapies. This is the first large RCT on group therapy for Cluster-C PDs and will contribute improving the care of this neglected patient group. The absence of a control group can be considered as a limitation. TRIAL REGISTRATION: CCMO, NL72826.029.20 . Registered on 31 August 2020, first participant included on 18 October 2020.

Which patients benefit from adding short-term psychodynamic psychotherapy to antidepressants in the treatment of depression? A systematic review and meta-analysis of individual participant data.

BACKGROUND: Adding short-term psychodynamic psychotherapy (STPP) to antidepressants increases treatment efficacy, but it is unclear which patients benefit specifically. This study examined efficacy moderators of combined treatment (STPP + antidepressants) v. antidepressants for adults with depression. METHODS: For this systematic review and meta-analysis (PROSPERO registration number: CRD42017056029), we searched PubMed, PsycINFO, Embase.com, and the Cochrane Library from inception to 1 January 2022. We included randomized clinical trials comparing combined treatment (antidepressants + individual outpatient STPP) v. antidepressants in the acute-phase treatment of depression in adults. Individual participant data were requested and analyzed combinedly using mixed-effects models (adding Cochrane risk of bias items as covariates) and an exploratory machine learning technique. The primary outcome was post-treatment depression symptom level. RESULTS: Data were obtained for all seven trials identified (100%, n = 482, combined: n = 238, antidepressants: n = 244). Adding STPP to antidepressants was more efficacious for patients with high rather than low baseline depression levels [B = -0.49, 95% confidence interval (CI) -0.61 to -0.37, p < 0.0001] and for patients with a depressive episode duration of >2 years rather than <1 year (B = -0.68, 95% CI -1.31 to -0.05, p = 0.03) and than 1-2 years (B = -0.86, 95% CI -1.66 to -0.06, p = 0.04). Heterogeneity was low. Effects were replicated in analyses controlling for risk of bias. CONCLUSIONS: To our knowledge, this is the first study that examines moderators across trials assessing the addition of STPP to antidepressants. These findings need validation but suggest that depression severity and episode duration are factors to consider when adding STPP to antidepressants and might contribute to personalizing treatment selection for depression.

Exploring the effect of group schema therapy and comorbidity on the treatment course of personality disorders.

PURPOSE OF REVIEW: To provide an update of outcome studies of schema group therapy for personality disorders and the effect of comorbidity in order to explore whether schema group therapy might be effective for this patient group and what dosage is required. RECENT FINDINGS: Studies of short-term schema group therapy for personality disorders with or without comorbidity show moderately effective results but the majority of patients fail to achieve full remission from global psychological symptom distress. Preliminary findings revealed that those unremitted patients might benefit from 40 to 60 sessions. Patients with severe personality disorders (such as borderline personality disorders) seem to need longer and/or more intensive treatment dosage to recover. SUMMARY: We advocate short-term schema therapy in groups as a valuable first step in a stepped-care programme for patients with moderate personality disorders and comorbidity.Treatment extension or treatment intensification may be indicated in patients who do not recover. Patients with severe personality disorders seem to require long-term outpatient group treatment, with a combination of group and individual treatment being preferable. High-quality randomized controlled trials are needed in order to determine which treatment dosage is necessary for whom.

Exploration of symptom dimensions and duration of untreated psychosis within a staging model of schizophrenia spectrum disorders.

AIM: Clinical staging of schizophrenia entails a new method that identifies clusters of symptoms and variation in level of remission, with the goal to create a framework for early intervention. Additionally, duration of untreated psychosis (DUP) may influence symptom severity in the first episode of psychosis (FEP) and could necessitate refining of the staging model. However, consistent evidence concerning variation in symptom severity and DUP between stages is missing. Therefore, we evaluated the clinical validity of the staging model by investigating differences in symptom severity across stages in schizophrenia spectrum disorders. Second, we assessed if a prolonged DUP is associated with higher symptom severity in FEP. METHODS: We performed a cross-sectional study of 291 acutely admitted patients with a schizophrenia spectrum disorder. Patients were assigned to clinical stages following the definition of McGorry. Symptom severity was evaluated with the new DSM-5 Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS). In FEP, we determined the DUP. RESULTS: Significantly higher severity scores of CRDPSS items hallucinations (H = 14.34, df = 4, P-value = .006), negative symptoms (H = 19.678, df = 4, P-value = .001) and impaired cognition (H = 26.294, df = 4, P-value = <.001) were found in more advanced stages of disease. Moreover, patients with FEP and a DUP longer than 1 year showed significantly more severe negative symptoms (U = 314 000, P = .015) compared to patients with a DUP shorter than 1 year. CONCLUSIONS: The present study found supporting evidence for the clinical validity of the staging model in schizophrenia spectrum disorders. In addition, we found support for refining the stage "first episode" with information concerning the DUP.

An old but still burning problem: Inter-rater reliability in clinical trials with antidepressant medication.

BACKGROUND: Antidepressant trials are criticized due to potential methodological flaws. Root causes of failing methodology can be found in insufficient inter-rater reliability (IRR) and training practices, leading to higher placebo response and reduced study-power. However, it is unknown to what extent reliability estimates or training procedures are currently included in antidepressant reports. Therefore, we aimed to determine the proportion of publications concerning double-blind randomized controlled antidepressant trials that report on IRR coefficients and training procedures. METHODS: We extracted all double-blind randomized clinical trials (RCTs) from the meta-analysis of Cipriani et al. (2018) concerning the period from 2000 until January 2016. Further, we conducted a Medline-search for double-blind RCTs from January 2016 until January 2020 for additional reports. We identified IRR coefficients and training procedures in these publications. RESULTS: In total we identified 179 double-blind RCTs. Only 4.5% reported an IRR coefficient whereas 27.9% reported training procedures. LIMITATIONS: We did not contact individual authors for additional information regarding implementation of training procedures or inter-rater reliability assessment. CONCLUSIONS: There is a substantial lack of reporting IRR coefficients and training procedures in RCTs with antidepressant medication. Considering the large implications of insufficient reliability, we urge researchers to conduct and report training procedures and reliability estimations.

The efficacy of adding short-term psychodynamic psychotherapy to antidepressants in the treatment of depression: A systematic review and meta-analysis of individual participant data.

PURPOSE: We examined the efficacy of adding short-term psychodynamic psychotherapy (STPP) to antidepressants in the treatment of depression by means of a systematic review and meta-analysis of individual participant data, which is currently considered the most reliable method for evidence synthesis. RESULTS: A thorough systematic literature search resulted in 7 studies comparing combined treatment of antidepressants and STPP versus antidepressant mono-therapy (n = 3) or versus antidepressants and brief supportive psychotherapy (n = 4). Individual participant data were obtained for all these studies and totaled 482 participants. Across the total sample of studies, combined treatment of antidepressants and STPP was found significantly more efficacious in terms of depressive symptom levels at both post-treatment (Cohen's d = 0.26, SE = 0.10, p = .01) and follow-up (d = 0.50, SE = 0.10, p < .001). This effect was most apparent at follow-up and in studies examining STPP's specific treatment efficacy. Effects were still apparent in analyses that controlled for risk of bias and STPP quality in the primary studies. CONCLUSIONS: These findings support the evidence-base of adding STPP to antidepressants in the treatment of depression. However, further studies are needed, particularly assessing outcome measures other than depression and cost-effectiveness, as well as examining the relative merits of STPP versus other psychotherapies as added to antidepressants.

Staging and profiling for schizophrenia spectrum disorders: Inter-rater reliability after a short training course.

OBJECTIVE: Clinical staging and profiling have been proposed as a new approach in order to refine the diagnostic assessment of schizophrenia spectrum disorders. However, only limited evidence is available for the inter-rater reliability of the clinical staging and profiling model. The aim of the present study was therefore to determine the inter-rater reliability of the clinical staging and profiling model for schizophrenia spectrum disorders, and to investigate whether a short course can improve inter-rater reliability. METHODS: Consecutively recruited inpatients with schizophrenia spectrum disorders were included between January 2015 and January 2016 (study 1), and between March 2018 and October 2018 (study 2). By contrast with the assessors in study 1, all the assessors in study 2 were trained in clinical staging and profiling. We used the clinical staging model proposed by McGorry and identified profile characteristics. Inter-rater reliability was measured using the Intraclass Correlation Coefficient (ICC). RESULTS: The ICC score for clinical staging in study 1 was moderate (0.578). It improved considerably in study 2 (0.757). In general, the ICC scores for the profile characteristics in studies 1 and 2 ranged from poor to sufficient (0.123-0.781). CONCLUSION: This study demonstrated that inter-rater reliability in clinical staging was sufficient after training. However, inter-rater reliability for clinical profile characteristics was highly variable. The general implementation of the clinical staging model for schizophrenia spectrum disorders is therefore feasible but clinical profile characteristics should be used with caution.

A demonstration of a multi-method variable selection approach for treatment selection: Recommending cognitive-behavioral versus psychodynamic therapy for mild to moderate adult depression.

Objective: We use a new variable selection procedure for treatment selection which generates treatment recommendations based on pre-treatment characteristics for adults with mild-to-moderate depression deciding between cognitive behavioral (CBT) versus psychodynamic therapy (PDT). Method: Data are drawn from a randomized comparison of CBT versus PDT for depression (N = 167, 71% female, mean-age = 39.6). The approach combines four different statistical techniques to identify patient characteristics associated consistently with differential treatment response. Variables are combined to generate predictions indicating each individual's optimal-treatment. The average outcomes for patients who received their indicated treatment versus those who did not were compared retrospectively to estimate model utility. Results: Of 49 predictors examined, depression severity, anxiety sensitivity, extraversion, and psychological treatment-needs were included in the final model. The average post-treatment Hamilton-Depression-Rating-Scale score was 1.6 points lower (95%CI = [0.5:2.8]; d = 0.21) for those who received their indicated-treatment compared to non-indicated. Among the 60% of patients with the strongest treatment recommendations, that advantage grew to 2.6 (95%CI = [1.4:3.7]; d = 0.37). Conclusions: Variable selection procedures differ in their characterization of the importance of predictive variables. Attending to consistently-indicated predictors may be sensible when constructing treatment selection models. The small N and lack of separate validation sample indicate a need for prospective tests before this model is used.

Dying Too Soon: Excess Mortality in Severe Mental Illness.

Aims: We aimed to identify baseline predictors of mortality in patients with a severe mental illness (SMI) over a 6-year period and to describe mortality rates as standardised mortality ratios (SMRs). We hypothesised that cardiovascular diseases, older age, cigarette smoking, more severe psychiatric symptoms and more severe psychotropic side effects, and alcohol or drug use were independent risk factors for mortality. Method: Medical examinations were conducted at baseline in a cohort of 322 SMI patients. SMRs were estimated after 6 years and an evaluation was made of the impact of a wide range of variables on survival time. Results: Almost 11% of the SMI patients had died at the end of the study period. All-cause SMRs were 4.51 (95% CI 3.07-5.95) for all SMI patients (4.89, 95% CI 2.97-6.80 for men, and 3.94, 95% CI 1.78-6.10 for women). Natural causes accounted for 86% of excess mortality and unnatural causes for 14%. Cardiovascular disease was a major contributor to this excess mortality. Multivariate Cox regression analyses showed that premature death was associated with a longer history of tobacco use (HR: 1.03, 95% CI 1.02-1.03) and more severe symptoms of disorganisation (HR: 2.36, 95% CI 2.21-2.52). Conclusions: The high SMR and the incidence of cardiovascular disease-related death in SMI patients in our study justify concern. This study underscores the urgent need for interventions to reduce excess mortality in patients with SMI.

The association between the number of previous episodes and modifiable vulnerability factors in remitted patients with recurrent depression.

OBJECTIVE: Remitted patients with a history of several previous major depressive episodes have a higher risk of relapse/recurrence than patients with fewer previous episodes, and the probability of another episode increases progressively with each successive episode. This study examines the association between the number of previous episodes and modifiable vulnerability factors in remitted patients with recurrent depression. METHODS: Patients with recurrent depression (DSM-IV-diagnosed) who were in remission (N = 214) were recruited between September 2011 and July 2016. The association was examined between the number of previous episodes and the following factors: i.e. interpersonal functioning, daily stress, sense of mastery, coping and dysfunctional beliefs. RESULTS: A history of more previous episodes was associated with higher levels of interpersonal problems (P < .001), daily stress (P = .04) and a lower sense of mastery (P = .05). Interpersonal problems were most strongly associated with more previous episodes in a Generalized Linear Regression model. In the domain of interpersonal problems, the subscales that showed the strongest relationship were domineering/controlling, vindictive/self-centred, socially inhibited and self-sacrificing. CONCLUSIONS: Patients with a history of more depressive episodes reported higher levels of interpersonal problems, daily stress and a lower sense of mastery. Future studies should examine these factors in a longitudinal cohort and look at whether the effect of interventions to prevent relapse can be explained by targeting these psychological factors. TRIAL REGISTRATION: Netherlands Trial Register: 2599.

The Developmental Profile Inventory: Constructing a Clinically Useful Self-Report for Levels of Psychodynamic Personality Functioning.

OBJECTIVE: The Developmental Profile Inventory (DPI) was constructed to assess psychodynamic personality functioning by self-report. METHOD: On the basis of the frame of reference of the Development Profile interview method, a self-report was developed covering 3 domains, self, interpersonal functioning, and problem-solving strategies, which represent 6 maladaptive and 3 adaptive developmental levels of psychodynamic functioning. The DPI was administered to patients with personality disorders who were receiving psychotherapy (N=179) and to normal controls (N=228). RESULTS: The internal reliabilities of the subscales were in general in the fair to good range in the patient sample, (α=0.67 to 0.88, ωh=0.52 to 0.87) and adequate to good in the healthy controls (α=0.71 to 0.91, ωh=0.71 to 0.90). Mean item-rest correlations were adequate (0.30 to 0.50). Test-retest reliability was good (intraclass correlation=0.73 to 0.91). The hypothesized factorial structure of the DPI with 9 subscales organized in 3 clusters was partly confirmed by confirmatory factor analysis χ/df=2.37, root mean square error of approximation=0.060, root mean residual square=0.078, and comparative fit index=0.630, with each factor showing over 80% standardized loadings >0.30, and at least 75% loadings >0.40. The DPI discriminated patients and healthy controls in a meaningful way. Correlations among the DPI and other self-report measures of global personality pathology and psychological complaints showed satisfactory convergent and discriminant validity. CONCLUSIONS: The DPI is a promising self-report measure for assessing both adaptive and maladaptive patterns of psychodynamic personality functioning. The appropriate initial psychometric properties justify proceeding with more formal tests of construct validity and predictive performance in broader mental health settings.

Optimizing psychotherapy dosage for comorbid depression and personality disorders (PsyDos): a pragmatic randomized factorial trial using schema therapy and short-term psychodynamic psychotherapy.

BACKGROUND: Patients with comorbid depression and personality disorders suffer from a heavy disease burden while tailored treatment options are limited, accounting for a high psychological and economic burden. Little is known about the effect of treatment dosage and type of psychotherapy for this specific co-morbid patient population, in terms of treatment-effect and cost-effectiveness. This study aims to compare treatment outcome of 25 versus 50 individual therapy sessions in a year. We expect the 50-session condition to be more effective in treating depression and maintaining the effect. Secondary objectives will be addressed in order to find therapy-specific and non-specific mechanisms of change. METHODS: In a mono-center pragmatic randomized controlled trial with a 2 × 2 factorial design, 200 patients with a depressive disorder and personality disorder(s) will be included. Patients will be recruited from a Dutch mental health care institute for personality disorders. They will be randomized over therapy dosage (25 vs 50 sessions in a year) and type of therapy (schema therapy vs short-term psychodynamic supportive psychotherapy). The primary clinical outcome measure will be depression severity and remission. Changes in personality functioning and quality of life will be investigated as secondary outcomes. A priori postulated effect moderators and mediators will be collected as well. All patients are assessed at baseline and at 1, 2, 3, 6, 9-12 months (end of therapy) and at follow up (6 and 12 months after end of treatment). Alongside the trial, an economic evaluation will be conducted. Costs will be collected from a societal perspective. DISCUSSION: This trial will be the first to compare two psychotherapy dosages in patients with both depression and personality disorders. Insight in the effect of treatment dosage for this patient group will contribute to both higher treatment effectiveness and lower costs. In addition, this study will contribute to the limited evidence base on treating patients with both depression and personality disorders. Understanding the processes that account for the therapeutic changes could help to gain insight in what works for whom. TRIAL REGISTRATION: This trial has been registered on July 20th 2016, Netherlands Trial Register, part of the Dutch Cochrane Centre ( NTR5941 ).

Which patients benefit specifically from short-term psychodynamic psychotherapy (STPP) for depression? Study protocol of a systematic review and meta-analysis of individual participant data.

INTRODUCTION: Short-term psychodynamic psychotherapy (STPP) is an empirically supported treatment that is often used to treat depression. However, it is largely unclear if certain subgroups of depressed patients can benefit specifically from this treatment method. We describe the protocol for a systematic review and meta-analysis of individual participant data (IPD) aimed at identifying predictors and moderators of STPP for depression efficacy. METHOD AND ANALYSIS: We will conduct a systematic literature search in multiple bibliographic databases (PubMed, PsycINFO, Embase.com, Web of Science and Cochrane's Central Register of Controlled Trials), 'grey literature' databases (GLIN and UMI ProQuest) and a prospective trial register (http://www.controlled-trials.com). We will include studies reporting (a) outcomes on standardised measures of (b) depressed (c) adult patients (d) receiving STPP. We will next invite the authors of these studies to share the participant-level data of their trials and combine these data to conduct IPD meta-analyses. The primary outcome for this study is post-treatment efficacy as assessed by a continuous depression measure. Potential predictors and moderators include all sociodemographic variables, clinical variables and psychological patient characteristics that are measured before the start of treatment and are assessed consistently across studies. One-stage IPD meta-analyses will be conducted using mixed-effects models. ETHICS AND DISSEMINATION: Institutional review board approval is not required for this study. We intend to submit reports of the outcomes of this study for publication to international peer-reviewed journals in the fields of psychiatry or clinical psychology. We also intend to present the outcomes at international scientific conferences aimed at psychotherapy researchers and clinicians. The findings of this study can have important clinical implications, as they can inform expectations of STPP efficacy for individual patients, and help to make an informed choice concerning the best treatment option for a given patient. PROSPERO REGISTRATION NUMBER: CRD42017056029.

Moderation of the Alliance-Outcome Association by Prior Depressive Episodes: Differential Effects in Cognitive-Behavioral Therapy and Short-Term Psychodynamic Supportive Psychotherapy.

Prior studies have suggested that the association between the alliance and depression improvement varies as a function of prior history of depression. We sought to replicate these findings and extend them to short-term psychodynamic supportive psychotherapy (SPSP) in a sample of patients who were randomized to one of these treatments and were administered the Helping Alliance Questionnaire (N=282) at Week 5 of treatment. Overall, the alliance was a predictor of symptom change (d=0.33). In SPSP, the alliance was a modest but robust predictor of change, irrespective of prior episodes (d=0.25-0.33). By contrast, in CBT, the effects of the alliance on symptom change were large for patients with 0 prior episodes (d=0.86), moderate for those with 1 prior episode (d=0.49), and small for those with 2+ prior episodes (d=0.12). These findings suggest a complex interaction between patient features and common vs. specific therapy processes. In CBT, the alliance relates to change for patients with less recurrent depression whereas other CBT-specific processes may account for change for patients with more recurrent depression.

Cognitive-behavioral versus psychodynamic therapy for major depression: Secondary outcomes of a randomized clinical trial.

OBJECTIVE: In a randomized clinical trial, we compared the efficacy of cognitive-behavioral therapy (CBT) and psychodynamic therapy for adult outpatient depression on measures of psychopathology, interpersonal functioning, pain, and quality of life. METHOD: There were 341 Dutch adults (70.1% female, mean age = 38.9, SD = 10.3) meeting Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition (DSM-IV) criteria for a major depressive episode and with a Hamilton Depression Rating Scale (HAM-D) score ≥14, who were randomized to 16 sessions of individual manualized CBT or short-term psychodynamic supportive psychotherapy. Severely depressed patients (HAM-D >24) received additional antidepressant medication according to a protocol. Outcome measures included the Brief Symptom Inventory, Beck Anxiety Inventory, Outcome Questionnaire, a visual analogue scale for pain, and EuroQol. Data were analyzed with mixed model analyses using intention-to-treat samples. Noninferiority margins were prespecified as Cohen's d = -0.30. RESULTS: Across treatment conditions, 45-60% of the patients who completed posttreatment assessment showed clinically meaningful change for most outcome measures. We found no significant differences between the treatment conditions on any of the outcome measures at both posttreatment and follow-up. Noninferiority of psychodynamic therapy to CBT was shown for posttreatment and follow-up anxiety measures as well as for posttreatment pain and quality of life measures, but could not be consistently demonstrated for the other outcomes. CONCLUSIONS: This is the first study that shows that psychodynamic therapy can be at least as efficacious as CBT for depression on important aspects of patient functioning other than depressive symptom reduction. These findings extend the evidence-base of psychodynamic therapy for depression, but replication is needed by means of rigorously designed noninferiority trials. (PsycINFO Database Record