Within-patient Effects Research Articles

Disentangling between- and within-patients effects of emotion regulation on outcome in naturalistic psychotherapy.

The aim of this study was to disaggregate the between-patient and within-patient effects of emotion regulation (ER) on treatment outcome and explore relevant trait-like moderators of the within-patient effects. Three hundred thirty-nine patients with heterogenous clinical conditions were admitted to psychotherapy at a clinical center. During the intake evaluation, patients completed the Inventory of Interpersonal Problems, the Outcome Questionnaire 30, and the State Difficulties of Emotion Regulation Scale. Subsequently, patients responded to the Outcome Questionnaire 30 and State Difficulties of Emotion Regulation Scale every session for the initial five sessions, followed by assessments every two sessions until the 15th session and then every four sessions until the end of treatment. Multilevel models revealed significant between- and within-patient effects of ER on clinical distress. That is, patients with lower average levels of ER difficulties showed greater benefit from treatment, and lower ER difficulties over the course of treatment were associated with lower clinical distress. Furthermore, interactive models demonstrated that lower average levels of ER throughout treatment and fewer interpersonal problems at the beginning of treatment were associated with better treatment outcome. These findings provide evidence supporting the role of ER as a mechanism of change. The interaction between trait-like components and state-like fluctuations of ER suggests a capitalization model for the role of ER in psychotherapy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Identifying who benefits most from supportive versus expressive techniques in psychotherapy for depression: Moderators of within- versus between-individual effects.

A recent randomized controlled trial (RCT) indicated that individuals with higher levels of attachment anxiety exhibited better treatment outcomes in supportive-expressive therapy (SET) relative to supportive therapy (ST). But to gain insight into within-patient therapeutic changes, a within-individual design is required. The present study contrasts previous findings based on theory-driven between-patient moderators with data-driven moderators of within-patient processes to investigate whether findings converge or diverge across these two approaches. We used data of 118 patients from the pilot and active phases of a recent RCT for patients with major depressive disorder, comparing ST with SET, a time-limited psychodynamic therapy. The predefined primary outcome measure was the Hamilton Rating Scale for Depression. Supportive versus expressive techniques were rated based on patients' end-of-session perspective. We compared previous findings based on moderators of between-patient effects with a data-driven approach for identifying moderators of within-patient effects of techniques on subsequent outcome. After false discovery rate corrections, of 10 preselected moderators, patients' attachment anxiety and domineering style remained significant. Of these, bootstrap resampling revealed significant differences between ST and SET techniques for the attachment anxiety moderator: Those with higher attachment anxiety benefited more from greater use of ST than SET techniques in a particular session, as evidenced by lower levels of symptoms at the subsequent session. Our within-individual findings diverge from previously published between-individual analyses. This proof-of-concept study demonstrates the importance of complementing between-individuals with within-individual analyses to achieve better understanding of who benefits most from specific treatment techniques. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Using machine learning algorithms to predict the effects of change processes in psychotherapy: Toward process-level treatment personalization.

This study aimed to develop and test algorithms to determine the individual relevance of two psychotherapeutic change processes (i.e., mastery and clarification) for outcome prediction. We measured process and outcome variables in a naturalistic outpatient sample treated with an integrative treatment for a variety of diagnoses (n = 608) during the first 10 sessions. We estimated individual within-patient effects of each therapist-evaluated process of change on patient-evaluated subsequent outcomes on a session-by-session basis. Using patients' baseline characteristics, we trained machine learning algorithms on a randomly selected subsample (n = 407) to predict the effects of patients' process variables on outcome. We subsequently tested the predictive capacity of the best algorithm for each process on a holdout subsample (n = 201). We found significant within-patient effects of therapist perceived mastery and clarification on subsequent outcome. In the holdout subsample, the best-performing algorithms resulted in significant but small-to-medium correlations between the predicted and observed relevance of therapist perceived mastery (r = .18) and clarification (r = .16). Using the algorithms to create criteria for individual recommendations, in the holdout sample, we identified patients for whom mastery (14%) or clarification (18%) were indicated. In the mastery-indicated group, a greater focus on mastery was moderately associated with better outcome (r = .33, d = .70), while in the clarification-indicated group, the focus was not related to outcome (r = -.05, d = .10). Results support the feasibility of performing individual predictions regarding mastery process relevance that can be useful for therapist feedback and treatment recommendations. However, results will need to be replicated with prospective experimental designs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Emotional and cognitive processes in psychotherapy are associated with different aspects of the therapeutic relationship.

In this naturalistic study we aimed to investigate the relationships between two central change processes (affective and cognitive) and two common relationship factors ("Confidence in the therapist" and "Confidence in the treatment"), which have been shown to impact outcomes in a clinical context. We also investigated whether these interrelationships varied across treatment orientations (i.e., cognitive or psychodynamic focused). The sample consisted of 631 patients with a primary anxiety or depressive disorder who were admitted to an inpatient program and treated with psychotherapy. The data consisted of weekly measures of cognitive (i.e., "rumination") and affective (i.e., "problems with emotional clarity") change processes as well as scores on Confidence in the therapist and Confidence in the treatment and symptom distress. A multivariate version of the latent curve model with structured residuals was used to investigate the within-patient effects of week-to-week changes in all variables. Initial analyses established that both problems with emotional clarity and rumination predicted symptom distress. Further, we found that higher Confidence in the therapist predicted higher emotional clarity (but not lower rumination) whereas higher Confidence in the treatment predicted lower rumination (but did not affect emotional clarity). Post hoc analyses found that these interrelationships varied across treatment orientation (i.e., cognitive vs. psychodynamic). The results indicate that patients' experience of the therapist is associated with emotional change processes, and that patients' experience of the coherence and meaningfulness of treatment, on the other hand, is associated with cognitive change processes. Implications for clinical practice are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Problem mastery and motivational clarification as mechanisms of change in cognitive-behavioral therapy for depression: Secondary analysis of a randomized controlled trial

ObjectiveIn process-outcome research, there is a growing body of literature investigating the therapeutic mechanisms underlying the promotion of positive change. This study investigated the between- and within-patient effects of problem mastery and motivational clarification on outcome in patients receiving two variations of cognitive therapies for depression. MethodsThis study drew on data of a randomized controlled trial conducted at an outpatient clinic and included 140 patients randomly assigned to 22 sessions of either cognitive-behavioral therapy or exposure-based cognitive therapy. To address the nested structure of the data and analyze mechanism effects, we used multilevel dynamic structural equations models. ResultsWe found significant within-patient effects of both problem mastery and motivational clarification on subsequent outcome. ConclusionThe results suggest that changes in problem mastery and motivational clarification precede symptom improvement during cognitive therapy for depressed patients and thus there may be benefit in fostering these putative mechanisms during psychotherapy.

A prospective single-arm study on the efficacy and safety of short-course oral corticosteroids followed by topical corticosteroids in patients with severe chronic rhinosinusitis with nasal polyps

ABSTRACT Background Little evidence exists regarding an integrated multidimensional evaluation methodology to analyze the within-patient effects of medical treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to use an integrated evaluation model to analyze the effects of short-course oral corticosteroid (OCS) followed by intranasal corticosteroid spray (INCS) therapy in patients with severe CRSwNP. Methods In all, 32 patients with severe CRSwNP received oral methylprednisolone for three weeks followed by intranasal budesonide spray for nine weeks in this prospective single-arm study. An evaluation model integrating the concepts of the core outcome set (COS), clinical control and minimum clinically important difference (MCID) was longitudinally evaluated. Results All uncontrolled patients at baseline showed similar progressive improvements from baseline and more than 1 MCID response across core outcomes during the OCS period, with severe CRSwNP being partly controlled in 31 (96.9%) patients and uncontrolled in 1 (3.1%) patient at 3 weeks. During the subsequent INCS period, 14 (43.8%) patients gradually deteriorated to an uncontrolled status at 12 weeks, whereas 18 (56.2%) exhibited partly controlled CRSwNP until 12 weeks. Conclusions In more than half of the patients, severe CRSwNP was partly controlled with the initial OCS followed by INCS therapy. An integrated evaluation model was used to facilitate the comprehensive evaluation of within-patient response, especially in patients with different responses to the same treatment. Trial registration ChiCTR1900024287.

Self-compassion as a mechanism of change in patients with eating disorders and childhood trauma receiving CFT-E; a study of within-person processes

Objective: This study examines the reciprocal relationship between self-compassion and eating disorder (ED) and trauma symptoms for patients receiving compassion- focused therapy for eating disorders (CFT-E). Method: A total of thirty-six patients with EDs and childhood trauma received inpatient treatment over 13 weeks. Levels of self-compassion and symptoms were assessed using repeated measures. A multilevel growth model was applied, and the effects of self-compassion and symptoms were separated into between- and within-patient effects. Results: The results show that ED symptoms did decrease significantly during treatment. Furthermore, the analyses demonstrated a reciprocal between-patient relationship between self-compassion and ED symptoms, and between self-compassion and trauma symptoms. However, regarding within-patient effects, only self-compassion predicted trauma symptoms. Discussion: The outcome of the current study demonstrates a favourable course for patients with EDs and childhood trauma receiving CFT-E in an inpatient facility. While there is a reciprocal relationship between the variables, the within-patient analyses imply the role of self-compassion in the therapy process for trauma symptoms.

Disaggregating between- and within-patient effects of ruptures and resolutions on the therapeutic alliance and symptom severity.

The therapeutic alliance is considered a robust predictor of psychotherapy outcome. Ruptures and resolutions in the alliance have been the focus of recent alliance literature. Most previous studies investigated their between-patient effects. We used hierarchical linear models to disaggregate the between- and within-patient effects of ruptures on the alliance from patient- and therapist perspective and symptom severity. Further, the moderating effects of rupture resolutions were analyzed. The sample consisted of 56 patients diagnosed with depressive or anxiety disorders who received 25 ± 3 sessions of integrative cognitive behavioral therapy in the outpatient setting. The observer-rated rupture resolution rating system was applied to all 1st, 8th, 16th and 24th therapy sessions. The alliance quality and symptom severity were assessed using self-report questionnaires after these four sessions. Results showed that a higher intensity of ruptures across treatment was associated with lower alliance ratings from both patient- and therapist perspectives during treatment. After sessions with more intense confrontation ruptures, both reported a weaker alliance. Rupture resolutions significantly moderated the withdrawal rupture effect on the alliance. The results provide meaningful practical implications for therapist feedback and training. They further underline the importance of using appropriate statistical analyses to the data structure and nature of psychotherapy to better understand the role of the alliance, rupture, and repair during therapy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Confidence in the therapist and confidence in the treatment predict symptomatic improvement week by week in therapy: A latent curve modeling approach.

Previous research suggests that common relationship factors are composed of two overarching factors, "Confidence in the therapist" and "Confidence in the treatment." The aim of this naturalistic process-outcome study was to investigate the reciprocal relationships between these two constructs and patients' symptom level across treatment. The sample consisted of 587 patients who were admitted to an inpatient program and treated with psychotherapy for a range of mental health disorders, such as chronic depression, anxiety disorders, and eating disorders. Our data consisted of weekly measures of symptomatic distress (Patient Health Questionnaire) and the common relationship factors were measured weekly using a newly developed scale. Latent curve modeling with structured residuals was used to investigate the between- and within effects of week-to-week changes in the two components as predictors of subsequent symptom level. An increase in both relationship factors predicted a decrease in subsequent levels of symptoms at the within-patient level, and the other way around, but the two relationship factors did not systematically relate to one another at the within-patient level over the course of treatment. Our findings indicate that patients' perceptions of the therapist as a person and their appraisal of the treatment, are important, different predictors of therapeutic change. Furthermore, they support prior research demonstrating a reciprocal relationship between common relationship factors and symptomatic distress and add to existing common factor theory by exploring the role of two central relationship dimensions and using a method which examines reciprocal relationships and within-patient effects simultaneously. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

It matters not only where you come from but also where you are going, and the interplay between the two: Reply to Huppert (2022).

Two main sources of confusion dominate research on trait-like (between-patients) and state-like (within-patient) effects in psychotherapy. The first is that being higher than another person on a given construct (between-individuals differences) has the same statistical and clinical implications as showing increases from one time point to the next on that construct (within-individual changes). However, research shows that it is a mistake to mix together the two effects. The second is overlooking the interplay between trait-like (between-individuals) differences and state-like (within-individual) changes in the same construct, although such interactive effects between the two may reveal critical information for guiding clinical decision-making. Two types of such interplays are briefly discussed, as well as their distinct clinical implications. The first refers to a compensatory effect according to which those with the lowest trait-like levels on a mechanism of change are the ones benefiting most from state-like improvements in that mechanism, so that where you start from need not have a deterministic effect if you are going in a promising new direction; on the contrary, it may point to the most critical state-like change required to return to healthy homeostasis. The second refers to a complementary effect, according to which treatment should focus on identifying individuals' trait-like strengths and capitalizing on them in treatment planning to drive state-like improvement. Differentiating between the two types of interplay is critical for basing treatment planning (determining the required state-like changes) on the individual's case conceptualization (trait-like characteristics). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Supplemental Material for Disaggregating Between- and Within-Patient Effects of Ruptures and Resolutions on the Therapeutic Alliance and Symptom Severity

Supplemental Material for Disaggregating Between- and Within-Patient Effects of Ruptures and Resolutions on the Therapeutic Alliance and Symptom Severity

Negative mood regulation as a mechanism of change in cognitive therapy for depression.

The present study investigates the effects of negative mood regulation expectancies (NMRE) on symptom severity of depression in 2 cognitive therapies for depression. The sample included the first 146 consecutively recruited patients from a randomized controlled trial. Patients received 22 sessions of either cognitive-behavioral therapy or exposure-based cognitive therapy. They completed the Beck Depression Inventory and Negative Mood Regulation Scale at baseline and treatment termination, as well as after Sessions 7 and 14. Multilevel modeling was applied. We found a significant between-patient effect of NMRE on symptom severity of depression, when NMRE within-patient effects were set to random. There was no significant interactive effect of the between-patient NMRE with type of treatment. However, a significant moderation effect of the within-patient NMRE effect by treatment condition on depression severity was detected, with patients receiving cognitive-behavioral therapy benefiting more from improvements in NMRE. Together, these results empirically support NMRE as a relevant mechanism of change in cognitive therapy for depression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Interpersonal cognitions as a mechanism of change in cognitive behavioral therapy for generalized anxiety disorder? A multilevel dynamic structural equation model approach.

This study aimed to investigate the effects of changes in interpersonal cognitions on outcome during cognitive behavioral therapy (CBT) for generalized anxiety disorder (GAD) and how these effects are moderated by patients' interpersonal problems at intake. A sample of 80 adult patients diagnosed with GAD who were undergoing CBT within a randomized controlled trial completed a questionnaire concerning interpersonal problems at baseline as well as measures of changes in interpersonal and self-related cognitions and in worry severity session by session. We conducted dynamic structural equation modeling to estimate cross-lagged within-patient effects of changes in interpersonal cognitions on worry, adjusting for the effects of self-related cognitions. Furthermore, we included interpersonal problems as a moderator of the effects of changes in interpersonal cognitions. We found significant cross-lagged effects of changes in both interpersonal cognitions and self-related cognitions on subsequent worry levels. Greater changes in interpersonal cognitions and self-related cognitions in a given session were associated with lower worry levels at the beginning of the next session. When adjusting for self-related cognitions, the effects of changes in interpersonal cognitions on subsequent worry remained significant. However, there were no interactive effects of changes in interpersonal cognitions by patients' interpersonal problems on worry severity. The results present evidence supporting changes in interpersonal cognitions and self-related cognitions as relevant change mechanisms in CBT for GAD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Interpersonal clarification effects in Cognitive-Behavioral Therapy for depression and how they are moderated by the therapeutic alliance

BackgroundAlthough a wide body of research links depression to interpersonal deficits, Cognitive-Behavioral Therapy (CBT), considered the gold standard in the treatment of this condition, has not been developed to specifically address interpersonal difficulties. However, cognitive changes on a relational level occurring during CBT might play an important role in the treatment of depression. Interpersonal clarification refers to the process of better understanding the nature of one's interpersonal patterns during therapy. The aim of this study is to analyze the effects of interpersonal clarification in CBT and how they are moderated by the therapeutic alliance. MethodsA sample of 621 patients diagnosed with depression were treated with CBT by 126 therapists in a university outpatient clinic. Patients completed measures of interpersonal problems and depression severity at baseline, measures of symptomatic evolution before each session and process measures (assessing interpersonal clarification and alliance) after each session. Multilevel models separating between-patient (BP) and within-patient (WP) effects of interpersonal clarification, and including BP and WP alliance effects as covariates and moderators of the interpersonal clarification effects were conducted. ResultsAnalyses showed both significant BP and WP effects interpersonal clarification, even when adjusting for alliance effects. Furthermore, significant interactive effects were found between outcome of WP interpersonal clarification with both BP alliance and WP alliance. LimitationsInterpersonal clarification was measured with one single-item and adherence to CBT was not explicitly measured. ConclusionsThe results present preliminary evidence for considering interpersonal clarification a meaningful change process in CBT for depression, especially in the context of a stronger therapeutic alliance.

The reciprocal relationship between alliance and early treatment symptoms: A two-stage individual participant data meta-analysis.

Even though the early alliance has been shown to robustly predict posttreatment outcomes, the question whether alliance leads to symptom reduction or symptom reduction leads to a better alliance remains unresolved. To better understand the relation between alliance and symptoms early in therapy, we meta-analyzed the lagged session-by-session within-patient effects of alliance and symptoms from Sessions 1 to 7. We applied a 2-stage individual participant data meta-analytic approach. Based on the data sets of 17 primary studies from 9 countries that comprised 5,350 participants, we first calculated standardized session-by-session within-patient coefficients. Second, we meta-analyzed these coefficients by using random-effects models to calculate omnibus effects across the studies. In line with previous meta-analyses, we found that early alliance predicted posttreatment outcome. We identified significant reciprocal within-patient effects between alliance and symptoms within the first 7 sessions. Cross-level interactions indicated that higher alliances and lower symptoms positively impacted the relation between alliance and symptoms in the subsequent session. The findings provide empirical evidence that in the early phase of therapy, symptoms and alliance were reciprocally related to one other, often resulting in a positive upward spiral of higher alliance/lower symptoms that predicted higher alliances/lower symptoms in the subsequent sessions. Two-stage individual participant data meta-analyses have the potential to move the field forward by generating and interlinking well-replicable process-based knowledge. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Do therapist effects really impact estimates of within-patient mechanisms of change? A Monte Carlo simulation study

ABSTRACT Objective: Existing evidence highlights the importance of modeling differential therapist effectiveness when studying psychotherapy outcome. However, no study to date examined whether this assertion applies to the study of within-patient effects in mechanisms of change. The study investigated whether therapist effects should be modeled when studying mechanisms of change on a within-patient level. Methods: We conducted a Monte Carlo simulation study, varying patient- and therapist level sample sizes, degree of therapist-level nesting (intra-class correlation), balanced vs. unbalanced assignment of patients to therapists, and fixed vs random within-patient coefficients. We estimated all models using longitudinal multilevel and structural equation models that ignored (2-level model) or modeled therapist effects (3-level model). Results: Across all conditions, 2-level models performed equally or were superior to 3-level models. Within-patient coefficients were unbiased in both 2- and 3-level models. In 3-level models, standard errors were biased when number of therapists was small, and this bias increased in unbalanced designs. Ignoring random slopes led to biased standard errors when slope variance was large; but 2-level models still outperformed 3-level models. Conclusions: In contrast to treatment outcome research, when studying mechanisms of change on a within-patient level, modeling therapist effects may even reduce model performance and increase bias.

Interpersonal agency as predictor of the within-patient alliance effects on depression severity.

Several studies have reported significant within-patient effects of the therapeutic alliance on outcome. However, it remains uncertain whether there are specific patient groups for whom an improved alliance might be particularly beneficial. The relational nature of the alliance makes patients' interpersonal problems a promising candidate for examining such differential effects. This study aims to analyze (i) between- and within-patient effects of the alliance on depression severity, (ii) the effects of patients' baseline interpersonal problems on the within-patient alliance-outcome association, and (iii) whether within-patient effects of the alliance remain significant when adjusting for patients' initial interpersonal problems. A sample of 141 patients with depression and undergoing outpatient psychotherapy completed the Inventory of Interpersonal Problems at baseline as well as a brief version of the Working Alliance Inventory and the Well-Being Index (as a proxy of depression severity) session by session. Multilevel models revealed both significant between- and within-patient effects of the alliance on improvements in depression severity. Patients' problems relating to agency had a significant effect on the within-patient effect of alliance, with more submissive patients benefiting more from an improved therapeutic alliance. Finally, the between- and within-patient effects of the alliance remained significant when adjusting for the patients' agentic interpersonal problems and treatment condition. The results provide evidence on which types of patients would particularly benefit from an improved therapeutic alliance. For patients suffering from low interpersonal agency and reporting problems with submissiveness, an enhanced alliance during the therapy process might improve treatment outcome. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Phase II double-blind randomised controlled trial of exogenous administration of melatonin in chronic pain (DREAM—CP): a study protocol

IntroductionChronic pain is prevalent, and approximately half of patients with chronic pain experience sleep disturbance. Exogenous melatonin is licensed to treat primary insomnia and there is some evidence for analgesic...

Clinical Usefulness of Bright White Light Therapy for Depressive Symptoms in Cancer Survivors: Results from a Series of Personalized (N-of-1) Trials.

Purpose: Little is known about the effectiveness of bright white light therapy (BWL) for depressive symptoms in cancer survivors, many of whom prefer non-pharmacological treatments. The purpose of this study was to compare the effectiveness of BWL versus dim red light therapy (DRL) on depressive symptoms within individual cancer survivors using personalized (N-of-1) trials. Methods: Cancer survivors with at least mild depressive symptoms were randomized to one of two treatment sequences consisting of counterbalanced crossover comparisons of three-weeks of lightbox-delivered BWL (intervention) or DRL (sham) for 30 min each morning across 12 weeks. A smartphone application guided cancer survivors through the treatment sequence and facilitated data collection. Cancer survivors tracked end-of-day depressive symptoms (primary outcome) and fatigue using visual analog scales. Within-patient effects of BWL were assessed using an autoregressive model with adjustment for linear time trends. Results: Eight of nine cancer survivors completed the 12-week protocol. Two survivors reported significantly (i.e., p < 0.05) lower depressive symptoms (−1.3 ± 0.5 and −1.30 ± 0.9 points on a 10-point scale), five reported no difference in depressive symptoms, and one reported higher depressive symptoms (+1.7 ± 0.6 points) with BWL versus DRL. Eight of nine cancer survivors recommended personalized trials of BWL to others. Conclusions: There were heterogeneous effects of three-week BWL on self-reported depressive symptoms among cancer survivors, with some finding a benefit but others finding no benefit or even harm. Implications for Cancer Survivors: Personalized trials can help cancer survivors learn if BWL is helpful for improving their depressive symptoms.

The working alliance in manualized CBT for generalized anxiety disorder: Does it lead to change and does the effect vary depending on manual implementation flexibility?

The investigation of session-to-session effects of working alliance on symptoms and coping experiences in patients diagnosed with generalized anxiety disorder. In addition, investigating these effects dependent on whether therapists are primed to work with patients strength (resource priming) or to adhere to the treatment manual (adherence priming). Data was drawn from a randomized controlled trial in which 57 patients were randomly assigned to either the resource priming condition or the adherence priming condition. Within- and between patient associations were disentangled using dynamic structural equation modeling. The total score of the working alliance, as well as all its overlapping components (i.e., goal agreement, task consensus, bond) showed significant within-patient effects on next session coping experiences. More specifically, better alliance scores in one session were followed by more coping experiences in the subsequent session. With regard to anxiety symptoms, an association was found only with the working alliance total score as well as for the bonds component, but not for the goals and task components of the working alliance. The priming condition (resource priming vs. adherence priming) had no influence on the within-patient alliance-outcome association. Between-patient alliance associations were only present with coping experiences, but not with anxiety symptoms. The findings provide further empirical evidence for the hypothesis that the working alliance may be a robust facilitative factor for change in CBT treatments for generalized anxiety disorder, which evolves irrespective of the strictness with which therapists adhere to the treatment manual. (PsycINFO Database Record (c) 2019 APA, all rights reserved).