Mediators Of Treatment Response Research Articles

Multilevel associations of emotion regulation strategy use during psychotherapy for depression: A longitudinal study

BackgroundPeople with depression select avoidant emotion regulation (ER) strategies more often than engagement strategies. While psychotherapy improves ER strategies, examining the week-to-week changes in ER and their relationship to clinical outcomes is warranted to understand how these interventions work. This study examined the changes in six ER strategies and depressive symptoms during virtual psychotherapy. MethodsTreatment-seeking adults (N = 56) with moderate depression severity completed a baseline diagnostic interview and questionnaires and were followed for up to 3 months as they completed virtual psychotherapy in an unrestricted format (e.g., individual) and orientation (e.g., cognitive-behavioral therapy; CBT). Participants completed weekly assessments of depression and six ER strategies along with assessments of CBT skills and participant-rated CBT components for each psychotherapy session. Multilevel modeling was used to examine associations between within-person changes in ER strategy use and weekly depression scores, controlling for between-person effects and time. ResultsDepressive symptoms, rumination, and experiential avoidance decreased non-linearly over time while cognitive reappraisal and acceptance increased non-linearly. Controlling for CBT skills, within-person increases in acceptance and cognitive reappraisal, as well as within-person decreases in experiential avoidance, were associated with fewer depressive symptoms over time. People who reported greater CBT components in their sessions also reported fewer depressive symptoms over time. LimitationsThe study was unable to make more causal inferences or standardize the type, baseline, or length of psychotherapy received. ConclusionsImprovements in ER strategies were associated with depression symptom reduction during psychotherapy. Future research to elucidate ER strategies as mediators of treatment response is warranted.

Problem-solving training as an active ingredient of treatment for youth depression: a scoping review and exploratory meta-analysis

BackgroundProblem-solving training is a common ingredient of evidence-based therapies for youth depression and has shown effectiveness as a versatile stand-alone intervention in adults. This scoping review provided a first overview of the evidence supporting problem solving as a mechanism for treating depression in youth aged 14 to 24 years.MethodsFive bibliographic databases (APA PsycINFO, CINAHL, Embase, MEDLINE, Web of Science) and the grey literature were systematically searched for controlled trials of stand-alone problem-solving therapy; secondary analyses of trial data exploring problem-solving-related concepts as predictors, moderators, or mediators of treatment response within broader therapies; and clinical practice guidelines for youth depression. Following the scoping review, an exploratory meta-analysis examined the overall effectiveness of stand-alone problem-solving therapy.ResultsInclusion criteria were met by four randomized trials of problem-solving therapy (524 participants); four secondary analyses of problem-solving-related concepts as predictors, moderators, or mediators; and 23 practice guidelines. The only clinical trial rated as having a low risk of bias found problem-solving training helped youth solve personal problems but was not significantly more effective than the control at reducing emotional symptoms. An exploratory meta-analysis showed a small and non-significant effect on self-reported depression or emotional symptoms (Hedges’ g = − 0.34; 95% CI: − 0.92 to 0.23) with high heterogeneity. Removing one study at high risk of bias led to a decrease in effect size and heterogeneity (g = − 0.08; 95% CI: − 0.26 to 0.10). A GRADE appraisal suggested a low overall quality of the evidence. Tentative evidence from secondary analyses suggested problem-solving training might enhance outcomes in cognitive-behavioural therapy and family therapy, but dedicated dismantling studies are needed to corroborate these findings. Clinical practice guidelines did not recommend problem-solving training as a stand-alone treatment for youth depression, but five mentioned it as a treatment ingredient.ConclusionsOn its own, problem-solving training may be beneficial for helping youth solve personal challenges, but it may not measurably reduce depressive symptoms. Youth experiencing elevated depressive symptoms may require more comprehensive psychotherapeutic support alongside problem-solving training. High-quality studies are needed to examine the effectiveness of problem-solving training as a stand-alone approach and as a treatment ingredient.

A randomized controlled trial comparing the clinical efficacy and cost-effectiveness of eye movement desensitization and reprocessing (EMDR) and integrated EMDR-Dialectical Behavioural Therapy (DBT) in the treatment of patients with post-traumatic stress disorder and comorbid (Sub)clinical borderline personality disorder: study design

BackgroundComorbidity between Posttraumatic Stress Disorder (PTSD) and Borderline Personality Disorder (BPD) is high. There is growing motivation among clinicians to offer PTSD treatments – such as Eye Movement Desensitization and Reprocessing (EMDR) - to patients with PTSD and comorbid BPD. However, a large subgroup with comorbid BPD does not sufficiently respond to PTSD treatment and is more likely to be excluded or to dropout from treatment. Dialectical Behaviour Therapy (DBT) for BPD is well established and although there is some evidence that DBT combined with DBT Prolonged Exposure (DBT + DBT PE) is twice as effective in reducing PTSD symptoms than DBT alone, the comparative efficacy of integrated PTSD-DBT and PTSD-only treatment has not been investigated yet. The current study will therefore evaluate the comparative clinical efficacy and cost-effectiveness of EMDR-DBT and EMDR-only in patients with PTSD and comorbid (sub)clinical BPD. Moreover, it is not clear yet what treatment works best for which individual patient. The current study will therefore evaluate neurobiological predictors and mediators of the individual response to treatment.MethodA randomized controlled trial comparing the clinical efficacy and cost-effectiveness of integrated EMDR-DBT (n = 63) and EMDR-only (n = 63) in treatment-seeking adult patients with PTSD and comorbid (sub)clinical BPD. In addition, neurobiological predictors and mediators of treatment outcome, such as hair cortisol, FKBP5 and BDNF protein levels and FKBP5 and BDNF methylation status, are measured through hair and blood samples.DiscussionThis is the first study to compare the clinical efficacy and cost-effectiveness of integrated EMDR-DBT and EMDR-only in patients with PTSD and comorbid (sub)clinical BPD, while simultaneously identifying individual predictors and mediators of treatment response. Results will reveal which treatment works best for which individual patient, thereby guiding individual treatment choices and personalizing psychiatry.Trial registrationClinical Trials, NCT03833453. Retrospectively registered, 15 March 2019.

Auditory-perceptual acuity in rhotic misarticulation: baseline characteristics and treatment response

ABSTRACT The rhotic sound /r/ is one of the latest-emerging sounds in English, and many children receive treatment for residual errors affecting /r/ that persist past the age of 9. Auditory-perceptual abilities of children with residual speech errors are thought to be different from their typically developing peers. This study examined auditory-perceptual acuity in children with residual speech errors affecting /r/ and the relation of these skills to production accuracy, both before and after a period of treatment incorporating visual biofeedback. Identification of items along an /r/-/w/ continuum was assessed prior to treatment. Production accuracy for /r/ was acoustically measured from standard/r/stimulability probes elicited before and after treatment. Fifty-nine children aged 9–15 with residual speech errors (RSE) affecting /r/ completed treatment, and forty-eight age-matched controls who completed the same auditory-perceptual task served as a comparison group. It was hypothesized that children with RSE would show lower auditory-perceptual acuity than typically developing speakers and that higher auditory-perceptual acuity would be associated with more accurate production before treatment. It was also hypothesized that auditory-perceptual acuity would serve as a mediator of treatment response. Results indicated that typically developing children have more acute perception of the /r/-/w/ contrast than children with RSE. Contrary to hypothesis, baseline auditory-perceptual acuity for /r/ did not predict baseline production severity. For baseline auditory-perceptual acuity in relation to biofeedback efficacy, there was an interaction between auditory-perceptual acuity and gender, such that higher auditory-perceptual acuity was associated with greater treatment response in female, but not male, participants.

Targeting hyperarousal: Mantram Repetition Program for PTSD in US veterans

ABSTRACT Background: Hyperarousal appears to play an important role in the development and maintenance of posttraumatic stress disorder (PTSD) symptoms, but current evidence-based treatments appear to address this symptom type less effectively than the other symptom clusters. The Mantram Repetition Program (MRP) is a meditation-based intervention that has previously been shown to improve symptoms of posttraumatic stress disorder (PTSD) and may be especially helpful for hyperarousal. If MRP is an effective tool for decreasing this often treatment-resistant symptom cluster, it may become an important clinical tool. Objective: The goal of this secondary analysis was to examine the effect of the MRP on hyperarousal and other PTSD symptom clusters and to examine hyperarousal as a mediator of treatment response. Method: Secondary analyses were conducted on data from a randomized controlled trial in which Veterans with PTSD (n = 173) were assigned to the MRP or a non-specific psychotherapy control and assessed pre-treatment, post-treatment and 8 weeks after treatment completion. The impact of the interventions on PTSD symptom clusters was examined, and time-lagged hierarchical linear modelling was applied to examine alternative mediation models. Results: All PTSD symptom clusters improved in both treatments. MRP led to greater reductions in hyperarousal at post-treatment (Hedge’s g = 0.57) and follow-up (Hedge’s g = 0.52), and in numbing at post-treatment (Hedge’s g = 0.47). Hyperarousal mediated reductions in the composite of the other PTSD symptom clusters. Although the reverse model was significant as well, the effect was weaker in this direction. Conclusion: Interventions focused on the management of hyperarousal may play an important role in recovery from PTSD. The MRP appears efficacious in reducing hyperarousal, and thereby impacting other PTSD symptom clusters, as one pathway to facilitating recovery.

Weight gain trajectories in hospital-based treatment of anorexia nervosa.

Weight gain is a primary treatment goal for anorexia nervosa (AN); however little is known about heterogeneity in weight gain pattern during treatment. Preliminary evidence suggests weight gain trajectory is associated with treatment outcome. This study grouped patients using mixture modeling into weight gain trajectories, and compared predictors and treatment outcomes between trajectory groups. Women diagnosed with AN or subthreshold AN (N = 211) completed self-report measures at admission and six-months after discharge from an integrated inpatient (IP)-partial hospitalization (PH) behavioral specialty eating disorders program. Gowned weights were measured daily. Three distinct trajectories emerged: negative quadratic (Optimal), negative quadratic with fast weight gain (Fast), and positive linear with slower weight gain (Slow). The majority of patients were assigned to the Optimal group. Trajectory groups differed on admission, discharge, and follow-up variables. The Fast group emerged as most distinct. Women in this group were more than twice as likely to binge and or vomit regularly compared with the other two groups and were most likely to achieve weight restoration by discharge and to have more positive weight outcomes at short-term follow-up. There were no group differences in eating disorder behavioral frequencies at follow-up when adjusting for behavioral severity at admission. Weight gain trajectory may serve as a personalized in-treatment marker of outcome and could inform research on moderators and mediators of treatment response. Randomized controlled treatment studies, utilizing weight gain trajectories to determine group membership, may help identify subgroups of patients with differential responses to treatment interventions.

The Treatment of Anxiety in Autism Spectrum Disorder (TAASD) Study: Rationale, Design and Methods.

This paper describes the rationale, design, and methods of the Treatment for Anxiety in Autism Spectrum Disorders study, a three-site randomized controlled trial investigating the relative efficacy of a modular CBT protocol for anxiety in ASD (Behavioral Interventions for Anxiety in Children with Autism) versus standard CBT for pediatric anxiety (the Coping Cat program) and a treatment-as-usual control. The trial is distinct in its scope, its direct comparison of active treatments for anxiety in ASD, and its comprehensive approach to assessing anxiety difficulties in youth with ASD. The trial will evaluate the relative benefits of CBT for children with ASD and investigate potential moderators (ASD severity, anxiety presentation, comorbidity) and mediators of treatment response, essential steps for future dissemination and implementation.

Identifying predictors, moderators, and mediators of antidepressant response in major depressive disorder: neuroimaging approaches.

Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes.

Motivational Enhancement to Improve Adherence to Positive Airway Pressure in Patients with Obstructive Sleep Apnea: A Randomized Controlled Trial

Obstructive sleep apnea (OSA) is associated with a variety of medical conditions. Positive airway pressure (PAP) is an effective treatment for improving sleep, yet adherence rates are low. The aim of the current study is to test two treatments versus standard care in improving adherence to PAP. Two hundred twenty-seven patients with OSA were randomized to standard care (SC), education (ED) and motivational enhancement therapy (MET). Adherence was measured objectively and the first week of adherence (prior to the intervention) was used as an a priori moderator of the effect of the various interventions. Mediators of treatment response were also examined using theory-based measures of decisional balance and self-efficacy. Adherence declined over time for all three groups. There was a significant interaction between level of adherence during the first week of treatment and treatment group. Those who had moderate levels of adherence during their first week of PAP were more likely to adhere to treatment at follow-up if they had MET; those who had high levels of adherence during their first week of PAP were more likely to adhere to treatment at follow-up if they had ED. MET treatment increased the perception of the positive aspects of PAP, but ED did not. Initial adherence to positive airway pressure could help guide subsequent treatment plans. The results also support social cognitive theory in that educational approaches might be best suited for those who are ready for change whereas more motivational approaches might be best for those who are ambivalent about change.

The Nordic long-term OCD treatment study (NordLOTS): rationale, design, and methods

BackgroundThis paper describes and discusses the methodology of the Nordic long-term OCD-treatment study (NordLOTS). The purpose of this effectiveness study was to study treatment outcome of CBT, to identify CBT non- or partial responders and to investigate whether an increased number of CBT-sessions or sertraline treatment gives the best outcome; to identify treatment refractory patients and to investigate the outcome of aripiprazole augmentation; to study the outcome over a three year period for each responder including the risk of relapse, and finally to study predictors, moderators and mediators of treatment response.MethodsStep 1 was an open and uncontrolled clinical trial with CBT, step 2 was a controlled, randomised non-blinded study of CBT non-responders from step 1. Patients were randomized to receive either sertraline plus CBT-support or continued and modified CBT. In step 3 patients who did not respond to either CBT or sertraline were treated with aripiprazole augmentation to sertraline.ConclusionsThis multicenter trial covering three Scandinavian countries is going to be the largest CBT-study for paediatric OCD to date. It is not funded by industry and tries in the short and long-term to answer the question whether further CBT or SSRI is better in CBT non-responders.

The pediatric obsessive compulsive disorder treatment study for young children (POTS Jr): Developmental considerations in the rationale, design, and methods

This paper presents the rationale, design, and methods of the pediatric obsessive compulsive disorder treatment study for young children (POTS Jr). The study is a multi-site randomized controlled trial (RCT) of family-based cognitive behavioral treatment (CBT) vs. family-based relaxation therapy for young children (ages 5–8) with obsessive compulsive disorder (OCD), which examines the effect of treatment on symptom reduction, functional impairment, and quality of life. Secondary aims evaluate: potential moderators and mediators of treatment response, differences in time course of response, retention rates, and maintenance of treatment gains over one year post-treatment. The sample included 127 children (53% female) and their parents. With regard to ethnicity, 89% of the sample described themselves as non-Hispanic, 5% Hispanic/Latino, and 6% did not endorse a category. In terms of race, the sample was predominantly (91%) white. Because the rationale and methods of the multi-site RCT have been well established, we emphasize here the methodological aspects of the study that were tailored to meet the developmental needs of young children with OCD. Aspects that are highlighted include: choice of control group, inclusion/exclusion criteria, assessment/measurement issues, treatment adaptations, training, and recruitment.

Obsessive-Compulsive Disorder and Tourette's Disorder: Where Are We Now?

Obsessive-Compulsive Disorder and Tourette's Disorder: Where Are We Now?

Moderators and Mediators of Treatment Outcome for Youth With ADHD: Understanding for Whom and How Interventions Work

To present data on moderators and mediators of treatment response from the Multimodal Treatment Study of Children With ADHD (MTA). Moderator variables (baseline factors that define subgroups with greater vs lesser intervention response) and mediator variables (factors occurring during treatment that explain how interventions "work") are described with specific application to the outcomes of the MTA Study. Key moderator variables (comorbid anxiety disorder, public assistance, severity of attention-deficit/hyperactivity disorder, parental depressive symptomatology, IQ) and mediator processes (negative/ineffective parental discipline) are reviewed. Treatment research in the future should explicitly consider the exploration of moderator and mediator variables, which can greatly aid the explanatory power of clinical trials and specify the critical next steps for intervention research.

Patient characteristics and treatment implications of marijuana abuse among bipolar alcoholics: Results from a double blind, placebo-controlled study

Objective Marijuana abuse, primarily a disorder of adolescents and young adults, is highly prevalent among patients with severely ill psychiatric population, especially those with bipolar disorder. Additional marijuana abuse may impact on the clinical presentation of bipolar illness and may potentially act as mediator of treatment response in this population. However, the characterization of bipolar disorder patients with additional marijuana abuse and the impact of such abuse on treatment outcome has been rarely examined. The aim of this study was to characterize bipolar alcoholic patients with comorbid marijuana abuse and test the impact of marijuana abuse on alcohol and mood outcome of patients with bipolar disorder and comorbid alcohol dependence. Method We conducted secondary analyses of a randomized, double blind, placebo-controlled trial testing valproate in 52 bipolar alcoholics. Subjects had a comprehensive assessment at baseline using structured diagnostic assessments, and they were then assessed every 2 weeks for 24 weeks. Results Twenty-five subjects (48%) reported marijuana abuse. Those with co-occurring marijuana abuse were younger, had fewer years of education, and had significantly higher number of additional psychiatric comorbidity. They also had more severe alcohol and other drug use and were significantly more likely to present in the manic phase. The mixed model indicated that the placebo-treated marijuana abuse group had the worst alcohol use outcome. Conclusions Marijuana abuse among patients with bipolar disorder and alcohol dependence is associated with higher degree of severity of alcohol and other drugs of abuse and may negatively impact on alcohol treatment outcome.