John R. Keefe

Psychodynamic therapy meets evidence-based medicine: a systematic review using updated criteria

Psychodynamic therapy (PDT) is an umbrella concept for treatments that operate on an interpretive-supportive continuum and is frequently used in clinical practice. The use of any form of psychotherapy should be supported by sufficient evidence. Efficacy research has been neglected in PDT for a long time. In this review, we describe methodological requirements for proofs of efficacy and summarise the evidence for use of PDT to treat mental health disorders. After specifying the requirements for superiority, non-inferiority, and equivalence trials, we did a systematic search using the following criteria: randomised controlled trial of PDT; use of treatment manuals or manual-like guidelines; use of reliable and valid measures for diagnosis and outcome; adults treated for specific mental problems. We identified 64 randomised controlled trials that provide evidence for the efficacy of PDT in common mental health disorders. Studies sufficiently powered to test for equivalence to established treatments did not find substantial differences in efficacy. These results were corroborated by several meta-analyses that suggest PDT is as efficacious as treatments established in efficacy. More randomised controlled trials are needed for some mental health disorders such as obsessive-compulsive disorder and post-traumatic stress disorder. Furthermore, more adequately powered equivalence trials are needed.

A meta-analytic review of psychodynamic therapies for anxiety disorders

Recent randomized controlled trials (RCTs) suggest that psychodynamic therapy (PDT) may be useful in the treatment of anxiety disorders. This paper presents the most comprehensive meta-analysis to date examining the controlled effects of PDT for anxiety disorders. 14 RCTs totaling 1073 patients were included. PDT was found to be significantly more effective than control conditions (g=0.64). PDT did not differ significantly from alternative treatments at post-treatment (g=0.02), follow-up (FU) up to a year (g=-0.11), and FU past a year (g=-0.26). Medium-to-high levels of heterogeneity were detected, indicating significant differences between studies. Nevertheless, our findings remained unchanged when heterogeneity outliers were removed (termination g=-0.06/short FU g=-0.01/long FU g=-0.10). Power analyses indicated that large or medium effect size differences between PDT and other active treatments could be detected even with high heterogeneity. Exploratory moderator analyses found few significant predictors of effect (e.g., relative risk of dropout). No differences were found examining remission rates or relative risk of dropout. Overall, PDT was shown to be as efficacious as other active treatments that have been studied for anxiety disorders.

Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial.

BACKGROUND Generalized Anxiety Disorder (GAD) is one of the most common anxiety disorders treated in primary care, yet current therapies have limited efficacy and substantial side effects. PURPOSE To evaluate long-term chamomile (Matricaria chamomilla L.) use for prevention of GAD symptom relapse. METHODS Outpatients from primary care practices and local communities with a primary diagnosis of moderate-to-severe GAD were enrolled for this two-phase study at a large US academic medical center. During Phase 1, eligible participants received 12 weeks of open-label therapy with chamomile pharmaceutical grade extract 1500mg (500mg capsule 3 times daily). During Phase 2, treatment responders were randomized to either 26 weeks of continuation chamomile therapy or placebo in a double-blinded, placebo-substitution design. The primary outcome was time to relapse during continuation therapy, analyzed using Cox proportional hazards. Secondary outcomes included the proportion who relapsed, treatment-emergent adverse events, and vital sign changes. This study is registered at ClinicalTrials.gov, identifier NCT01072344. RESULTS Between March 1, 2010, and June 30, 2015, we enrolled 179 participants. Of those, 93 (51.9%) were responders and agreed to continue in the double-blind randomized controlled trial. A numerically greater number of placebo-switched (n=12/47; 25.5%) versus chamomile-continuation (n = 7/46; 15.2%) participants relapsed during follow-up. Mean time to relapse was 11.4 ± 8.4 weeks for chamomile and 6.3 ± 3.9 weeks for placebo. Hazard of relapse was non-significantly lower for chamomile (hazard ratio, 0.52; 95% CI, 0.20-1.33; P = 0.16). During follow-up, chamomile participants maintained significantly lower GAD symptoms than placebo (P = 0.0032), with significant reductions in body weight (P = 0.046) and mean arterial blood pressure (P = 0.0063). Both treatments had similar low adverse event rates. CONCLUSIONS Long-term chamomile was safe and significantly reduced moderate-to-severe GAD symptoms, but did not significantly reduce rate of relapse. Our limited sample size and lower than expected rate of placebo group relapse likely contributed to the non-significant primary outcome finding. Possible chamomile superiority over placebo requires further examination in large-scale studies.

Biases in research: risk factors for non-replicability in psychotherapy and pharmacotherapy research

Replicability of findings is an essential prerequisite of research. For both basic and clinical research, however, low replicability of findings has recently been reported. Replicability may be affected by research biases not sufficiently controlled for by the existing research standards. Several biases such as researcher allegiance or selective reporting are well-known for affecting results. For psychotherapy and pharmacotherapy research, specific additional biases may affect outcome (e.g. therapist allegiance, therapist effects or impairments in treatment implementation). For meta-analyses further specific biases are relevant. In psychotherapy and pharmacotherapy research these biases have not yet been systematically discussed in the context of replicability. Using a list of 13 biases as a starting point, we discuss each biass impact on replicability. We illustrate each bias by selective findings of recent research, showing that (1) several biases are not yet sufficiently controlled for by the presently applied research standards, (2) these biases have a pernicious effect on replicability of findings. For the sake of research credibility, it is critical to avoid these biases in future research. To control for biases and to improve replicability, we propose to systematically implement several measures in psychotherapy and pharmacotherapy research, such as adversarial collaboration (inviting academic rivals to collaborate), reviewing study design prior to knowing the results, triple-blind data analysis (including subjects, investigators and data managers/statisticians), data analysis by other research teams (crowdsourcing), and, last not least, updating reporting standards such as CONSORT or the Template for Intervention Description and Replication (TIDieR).

Goldilocks on the couch: Moderate levels of psychodynamic and process-experiential technique predict outcome in psychodynamic therapy

Abstract Objectives: Greater symptom change is often assumed to follow greater technique use, a “more is better” approach. We tested whether psychodynamic techniques, as well as common factors and techniques from other orientations, had a curvilinear relation to outcome (i.e., whether moderate or “just right” intervention levels predict better outcome than lower or higher levels). Methods: For 33 patients receiving supportive-expressive psychodynamic psychotherapy for depression, interventions were assessed at Week 4 using the multitheoretical list of therapeutic interventions and symptoms were rated with the Hamilton Rating Scale for Depression. Results: Moderate psychodynamic and experiential techniques predicted greater symptom change compared to lower or higher levels. Conclusion: This “Goldilocks effect” suggests a more complex relation of intervention use to outcome might exist.

Short-term open-label chamomile (Matricaria chamomilla L.) therapy of moderate to severe generalized anxiety disorder

BACKGROUND Conventional drug treatments for Generalized Anxiety Disorder (GAD) are often accompanied by substantial side effects, dependence, and/or withdrawal syndrome. A prior controlled study of oral chamomile (Matricaria chamomilla L.) extract showed significant efficacy versus placebo, and suggested that chamomile may have anxiolytic activity for individuals with GAD. HYPOTHESIS We hypothesized that treatment with chamomile extract would result in a significant reduction in GAD severity ratings, and would be associated with a favorable adverse event and tolerability profile. STUDY DESIGN We report on the open-label phase of a two-phase randomized controlled trial of chamomile versus placebo for relapse-prevention of recurrent GAD. METHODS Subjects with moderate to severe GAD received open-label treatment with pharmaceutical-grade chamomile extract 1500mg/day for up to 8 weeks. Primary outcomes were the frequency of clinical response and change in GAD-7 symptom scores by week 8. Secondary outcomes included the change over time on the Hamilton Rating Scale for Anxiety, the Beck Anxiety Inventory, and the Psychological General Well Being Index. Frequency of treatment-emergent adverse events and premature treatment discontinuation were also examined. RESULTS Of 179 subjects, 58.1% (95% CI: 50.9% to 65.5%) met criteria for response, while 15.6% prematurely discontinued treatment. Significant improvement over time was also observed on the GAD-7 rating (β=-8.4 [95% CI=-9.1 to -7.7]). A similar proportion of subjects demonstrated statistically significant and clinically meaningful reductions in secondary outcome ratings of anxiety and well-being. Adverse events occurred in 11.7% of subjects, although no serious adverse events occurred. CONCLUSION Chamomile extract produced a clinically meaningful reduction in GAD symptoms over 8 weeks, with a response rate comparable to those observed during conventional anxiolytic drug therapy and a favorable adverse event profile. Future comparative effectiveness trials between chamomile and conventional drugs may help determine the optimal risk/benefit of these therapies for patients suffering from GAD.

Cognitive-Behavioral Therapy: Nature and Relation to Non-Cognitive Behavioral Therapy

Since the introduction of Becks cognitive theory of emotional disorders, and their treatment with psychotherapy, cognitive-behavioral approaches have become the most extensively researched psychological treatment for a wide variety of disorders. Despite this, the relative contribution of cognitive to behavioral approaches to treatment are poorly understood and the mechanistic role of cognitive change in therapy is widely debated. We critically review this literature, focusing on the mechanistic role of cognitive change across cognitive and behavioral therapies for depressive and anxiety disorders.

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.

Reducing Dropout in Treatment for Depression: Translating Dropout Predictors Into Individualized Treatment Recommendations

OBJECTIVE Premature discontinuation of therapy is a widespread problem that hampers the delivery of mental health treatment. A high degree of variability has been found among rates of premature treatment discontinuation, suggesting that rates may differ depending on potential moderators. In the current study, our aim was to identify demographic and interpersonal variables that moderate the association between treatment assignment and dropout. METHODS Data from a randomized controlled trial conducted from November 2001 through June 2007 (N = 156) comparing supportive-expressive therapy, antidepressant medication, and placebo for the treatment of depression (based on DSM-IV criteria) were used. Twenty prerandomization variables were chosen based on previous literature. These variables were subjected to exploratory bootstrapped variable selection and included in the logistic regression models if they passed variable selection. RESULTS Three variables were found to moderate the association between treatment assignment and dropout: age, pretreatment therapeutic alliance expectations, and the presence of vindictive tendencies in interpersonal relationships. When patients were divided into those randomly assigned to their optimal treatment and those assigned to their least optimal treatment, dropout rates in the optimal treatment group (24.4%) were significantly lower than those in the least optimal treatment group (47.4%; P = .03). CONCLUSIONS Present findings suggest that a patients age and pretreatment interpersonal characteristics predict the association between common depression treatments and dropout rate. If validated by further studies, these characteristics can assist in reducing dropout through targeted treatment assignment. TRIAL REGISTRATION Secondary analysis of data from ClinicalTrials.gov identifier: NCT00043550.

Heightened risk of false positives in a network meta-analysis of social anxiety.

In their critical analysis of the brain disease model of addiction (BDMA), Wayne Hall and colleagues have elegantly shown that the BDMA is insuf f iciently suppor ted by animal-model and neuroimaging evidence; has not contributed to the development of more effective treatments; and has had a modest effect on public policies toward drugs and drug addiction. However, one of the key aspirational claims of advocates for the BDMA is left unaddressed—even though alluded to—by Hall and colleagues: the BDMA’s potential to undermine the stigmatisation of addiction and people with drug addiction. Together with a few theoretical papers, a paucity of empirical studies has explored this issue. Recently, an Australian survey on public attitudes has shown that considering addiction as a so-called brain disease is not associated with a reduced stigmatisation or with reduced support for coerced-treatment or punishment for addiction. In this line, a newly published experimental study has concluded that strengthening belief in a BDMA does not reduce feelings of stigma and shame in mildto-moderate alcohol-dependent individuals, but even weakens some of their perceptions of agency over addiction-related behaviours (eg, locus of control, coping style, and controlled drinking self-efficacy). The more extensive literature linking stigma and the conceptualisation of psychiatric diagnoses in terms of brain disease seems to point in the same direction. Therefore, as Hall and colleagues have questioned the evidence base for—and potential benefi ts from—the BDMA, it would have been desirable that their critical analysis has also addressed BDMA’s stigma-related issues. In any case, so far, the claim that framing addiction as a brain disease will lead to stigma reduction seems to be an unrealistically rosy picture or at least an unsubstantiated desideratum of BDMA’s advocates.