Long-term outcomes of once weekly v. twice weekly sessions of cognitive behavioral therapy and interpersonal psychotherapy for depression.

BACKGROUND: Twice weekly sessions of cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for major depressive disorder (MDD) lead to less drop-out and quicker and better response compared to once weekly sessions at posttreatment, but it is unclear whether these effects hold over the long run. AIMS: Compare the effects of twice weekly v. weekly sessions of CBT and IPT for depression up to 24 months since the start of treatment. METHODS: Using a 2 × 2 factorial design, this multicentre study randomized 200 adults with MDD to once or twice weekly sessions of CBT or IPT over 16-24 weeks, up to a maximum of 20 sessions. Main outcome measures were depression severity, measured with the Beck Depression Inventory-II and the Longitudinal Interval Follow-up Evaluation. Intention-to-treat analyses were conducted. RESULTS: Compared with patients who received once weekly sessions, patients who received twice weekly sessions showed a significant decrease in depressive symptoms up through month 9, but this effect was no longer apparent at month 24. Patients who received CBT showed a significantly larger decrease in depressive symptoms up to month 24 compared to patients who received IPT, but the between-group effect size at month 24 was small. No differential effects between session frequencies or treatment modalities were found in response or relapse rates. CONCLUSIONS: Although a higher session frequency leads to better outcomes in the acute phase of treatment, the difference in depression severity dissipated over time and there was no significant difference in relapse.

Cost-effectiveness of twice-weekly versus once-weekly sessions of cognitive-behavioural therapy and interpersonal psychotherapy for depression at 12 months after start of treatment: randomised controlled trial.

BACKGROUND: Cost-effective treatments are needed to reduce the burden of depression. One way to improve the cost-effectiveness of psychotherapy might be to increase session frequency, but keep the total number of sessions constant. AIM: To evaluate the cost-effectiveness of twice-weekly compared with once-weekly psychotherapy sessions after 12 months, from a societal perspective. METHOD: An economic evaluation was conducted alongside a randomised controlled trial comparing twice-weekly versus once-weekly sessions of psychotherapy (cognitive-behavioural therapy or interpersonal psychotherapy) for depression. Missing data were handled by multiple imputation. Statistical uncertainty was estimated with bootstrapping and presented with cost-effectiveness acceptability curves. RESULTS: Differences between the two groups in depressive symptoms, physical and social functioning, and quality-adjusted life-years (QALY) at 12-month follow-up were small and not statistically significant. Total societal costs in the twice-weekly session group were higher, albeit not statistically significantly so, than in the once-weekly session group (mean difference €2065, 95% CI -686 to 5146). The probability that twice-weekly sessions are cost-effective compared with once-weekly sessions was 0.40 at a ceiling ratio of €1000 per point improvement in Beck Depression Inventory-II score, 0.32 at a ceiling ratio of €50 000 per QALY gained, 0.23 at a ceiling ratio of €1000 per point improvement in physical functioning score and 0.62 at a ceiling ratio of €1000 per point improvement in social functioning score. CONCLUSIONS: Based on the current results, twice-weekly sessions of psychotherapy for depression are not cost-effective over the long term compared with once-weekly sessions.

Skill Improvement Through Learning in Therapy (SKILT): A Study Protocol for a Randomized Trial Testing the Direct Effects of Cognitive Behavioral Therapy Skill Acquisition and Role of Learning Capacity in Depression.

Background: To improve psychological treatments for major depressive disorder (MDD), a better understanding on how symptoms ameliorate during treatment is essential. In cognitive behavioral therapy (CBT), it is unclear whether procedures focused on the acquisition of CBT skills play a causal role in the improvement of CBT skills. In this randomized trial, we isolate a single CBT Skill Acquisition Procedure (CBTSAP) and test its direct effects on CBT skills and related therapy processes (i.e., change in (idiosyncratic) dysfunctional thinking and reward processing). We hypothesize that the CBTSAP causes improvements in CBT skills and related therapy processes compared to an active control condition. In addition, we hypothesize that individual differences in attentional bias and memory functioning (defined as learning capacity) moderate the effects of CBTSAP on outcomes and that using mental imagery as a cognitive support strategy to strengthen the effects of the CBTSAP will be most beneficial for patients with low learning capacity. Method: 150 patients with MDD will be randomized to one of three conditions: 1. an active control condition, 2. CBTSAP, 2. CBTSAP plus mental imagery, all consisting of three sessions. Primary outcomes will be change in CBT skills, changes in (idiosyncratic) dysfunctional thoughts and behaviors, reward processing. Depressive symptoms are a secondary outcome. Measures of learning capacity will be conducted at baseline and tested as a potential moderator. Discussion: Knowing whether and for whom the acquisition of CBT skills leads to change in therapy processes and a subsequent reduction of depressive symptoms will inform on how to personalize and optimize psychotherapy outcomes for depression. Trial registration: The trial is registered at the German Clinical Trial Register (DKTR; registration number: DRKS00024116).

Temporal and specific pathways of change in cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for depression.

BACKGROUND: The present study investigated the specific and temporal role of putative mechanisms of change in cognitive-behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for major depressive disorder (MDD). METHOD: 200 patients were randomized to CBT weekly, CBT twice weekly, IPT weekly or IPT twice weekly. Outcome and putative mechanisms of change (i.e., dysfunctional thinking, behavioral activation, CBT skills, IPT skills, therapeutic alliance, compliance, motivation) were measured multiple times up to six months after the start of treatment. Latent change score models were used to investigate temporal relations and test mediation. Explorative analyses tested whether baseline working memory moderated the effect of mechanism change on outcome change. RESULTS: CBT skills and dysfunctional thinking mediated the relation between treatment modality and changes in depression. In both treatments, IPT skills and behavioral activation were related to subsequent change in depression while a decrease in depression led to subsequent improvement in therapeutic alliance and a decrease in autonomous motivation. Change in compliance was unrelated to change in depression. Baseline working memory was related to therapy skill improvement. CONCLUSION: CBT skill improvement seems a specific mechanism of change leading to subsequent decrease in depression in CBT. Changes in IPT skills acted as a non-specific mechanism, subsequently reducing depression regardless of treatment modality. The specific role of cognitive change and behavioral activation remains unclear. Future studies should investigate the specificity and direction of the potential mechanisms of change throughout the course of therapy and investigate whether these mechanistic pathways differ between individuals.

Mechanistic pathways of change in twice weekly versus once weekly sessions of psychotherapy for depression.

BACKGROUND: Recently, we showed that twice weekly sessions of cognitive-behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for depression lead to better and faster treatment outcomes compared to once weekly sessions (Bruijniks et al., 2020). The present study investigated which pathways of change may account for the effects of different session frequencies. METHOD: The sample consisted of 200 patients who were randomized to CBT weekly, CBT twice weekly, IPT weekly, or IPT twice weekly. Outcome and therapy processes were measured at baseline, two weeks and monthly up to month 6 after the start of treatment. Latent change score models investigated temporal relations between change in therapy processes and change in depression and tested whether change in the therapy processes mediated the effect of session frequency on change in depression. RESULTS: IPT skills mediated the relation between session frequency and change in depression. A decrease in depression was related to subsequent improvement in CBT skills and subsequent decrease in motivation for therapy. CONCLUSION: The development of IPT skills may explain why a twice weekly higher session frequency is more effective in reducing depression compared to a once-weekly session frequency. Future studies should disentangle the causal effects of therapy process change throughout the course of therapy.

Individual differences in response to once versus twice weekly sessions of CBT and IPT for depression.

OBJECTIVE: The Personalized Advantage Index (PAI) is a method to guide treatment selection by investigating which of two or more treatments is optimal for a given individual. Recently, it was shown that, on average, twice-weekly sessions of psychotherapy for depression lead to better outcomes compared to once-weekly sessions. The present study applied the PAI method to assess if subgroups of patients may have a differential response to psychotherapy frequency. METHOD: Data came from a clinical trial (n = 200) randomizing depressed patients into different session frequencies: weekly sessions versus twice-weekly sessions. Machine-learning techniques were used to select pretreatment variables and develop a multivariable prediction model that calculated each patient's PAI. Differences in observed depression post-treatment scores (Beck Depression Inventory-II [BDI-II]) were tested between patients that received their PAI-indicated versus non-indicated session frequency. Between-group effect sizes (Cohen's d) were reported. RESULTS: We identified prognostic indicators generally associated with lower post-treatment BDI-II regardless of treatment assignment. In addition, we identified specific demographic and psychometric features associated with differential response to weekly- versus twice-weekly therapy sessions. Observed post-treatment BDI-II scores were significantly different between individuals receiving the PAI-indicated versus non-indicated session frequency (d = .37). CONCLUSIONS: Although a higher session frequency is more effective on average, different session frequencies seem beneficial for different patients. Future studies should externally validate these findings before they can be generalized to other settings. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The relation between therapy quality, therapy processes and outcomes and identifying for whom therapy quality matters in CBT and IPT for depression.

BACKGROUND: Research on which therapy processes are crucial for whom is necessary to optimize treatment outcomes for major depressive disorder (MDD) but may be impeded by a lack of variation in therapy quality and because of individual differences in therapy response. The present study used a dataset with large variation in therapy quality to investigate the impact of therapy quality on change in therapy processes and outcome. Machine-learning techniques were used to explore individual differences in these relationships. METHOD: Data come from a multicenter trial that randomized patients with MDD into weekly versus twice weekly sessions of cognitive behavioral therapy (CBT) or interpersonal psychotherapy (IPT). Correlations between quality of therapy, change in therapy processes and depressive symptoms were calculated. Using elastic net regression, a prognostic model was developed that investigated individual differences. RESULTS: There were no significant correlations between therapy quality and change in therapy process variables or between therapy quality and therapy outcome, except between therapy quality and dysfunctional thinking and IPT skills. Improvement in therapy processes played a larger role in patients whose therapy outcome was poorly predicted by their baseline characteristics. CONCLUSIONS: In this study, in which therapy quality varied considerably, we found that therapy quality was not related to change in therapy processes or outcome. In addition, this study provides a first demonstration of proposed methods to identify individual responses to change in therapy processes. Results suggested that the importance of certain therapy processes might differ between patients. Future research into the relation between therapy quality, change in therapy processes and outcome should take into account the variation of therapy quality, focus on improved measurement of therapy quality and use a combination of machine learning techniques and experimental lab studies to determine to which extent and for whom therapy quality and change in therapy processes matter.

Prospective Mental Imagery in Depression: Impact on Reward Processing and Reward-Motivated Behaviour.

Background: Mental imagery has long been part of cognitive behavioural therapies. More recently, a resurgence of interest has emerged for prospective mental imagery, i.e. future-directed imagery-based thought, and its relation to reward processing, motivation and behaviour in the context of depression. Method: We conducted a selective review on the role of prospective mental imagery and its impact on reward processing and reward-motivated behaviour in depression. Results: Based on the current literature, we propose a conceptual mechanistic model of prospective mental imagery. Prospective mental imagery of engaging in positive activities can increase reward anticipation and reward motivation, which can transfer to increased engagement in reward-motivated behaviour and more experiences of reward, thereby decreasing depressive symptoms. We suggest directions for future research using multimodal assessments to measure the impact of prospective mental imagery from its basic functioning in the lab to real-world and clinical implementation. Conclusion: Prospective mental imagery has the potential to improve treatment for depression where the aim is to increase reward-motivated behaviours. Future research should investigate how exactly and for whom prospective mental imagery works.

Cross-trial prediction in psychotherapy: External validation of the Personalized Advantage Index using machine learning in two Dutch randomized trials comparing CBT versus IPT for depression.

Objective: Optimizing treatment selection may improve treatment outcomes in depression. A promising approach is the Personalized Advantage Index (PAI), which predicts the optimal treatment for a given individual. To determine the generalizability of the PAI, models needs to be externally validated, which has rarely been done. Method: PAI models were developed within each of two independent trials, with substantial between-study differences, that both compared CBT and IPT for depression (STEPd: n = 151 and FreqMech: n = 200). Subsequently, both PAI models were tested in the other dataset. Results: In the STEPd study, post-treatment depression was significantly different between individuals assigned to their PAI-indicated treatment versus those assigned to their non-indicated treatment (d = .57). In the FreqMech study, post-treatment depression was not significantly different between patients receiving their indicated treatment versus those receiving their non-indicated treatment (d = .20). Cross-trial predictions indicated that post-treatment depression was not significantly different between those receiving their indicated treatment and those receiving their non-indicated treatment (d = .16 and d = .27). Sensitivity analyses indicated that cross-trial prediction based on only overlapping variables didn't improve the results. Conclusion: External validation of the PAI has modest results and emphasizes between-study differences and many other challenges.

Working memory moderates the relation between the brain-derived neurotropic factor (BDNF) and psychotherapy outcome for depression.

BACKGROUND: Insight into patient characteristics that predict response to treatment for major depressive disorder (MDD) may help to personalize treatment and improve outcomes. One mechanism that has been linked to the success of treatment for MDD is brain-derived neurotropic factor (BDNF). BDNF is implicated in learning and memory and may play a role in the effects of psychotherapy that involves changing cognitions and behaviors. In addition, only in individuals with low BDNF, low working memory capacity has been associated with increased symptoms of depression. However, the role of BDNF and working memory capacity in psychotherapy outcome is unclear. The aim of this study was to investigate the role of BDNF and its interaction with working memory capacity in psychotherapy outcomes for MDD. METHOD: Adult patients with MDD were randomized to weekly or twice weekly sessions of cognitive behavioral therapy or interpersonal psychotherapy. BDNF Val66Met polymorphism (rs6265) (n = 138) was defined and serum BDNF was quantified before (n = 138) and after psychotherapy (n = 82). RESULTS: Baseline serum BDNF and the Val66Met polymorphism were not associated with outcome and associations did not differ between treatment conditions. Working memory capacity significantly moderated the relation between baseline serum BDNF and outcome: high serum BDNF at baseline was related to less depressive symptoms following psychotherapy in the presence of high working memory capacity, but not low working memory capacity. DISCUSSION: These findings, if replicated, might indicate that while BDNF may not be related to psychotherapy outcomes in general, they may play a role in the presence of specific learning processes such as working memory capacity.

The effects of once- versus twice-weekly sessions on psychotherapy outcomes in depressed patients.

BACKGROUND: It is unclear what session frequency is most effective in cognitive-behavioural therapy (CBT) and interpersonal psychotherapy (IPT) for depression. AIMS: Compare the effects of once weekly and twice weekly sessions of CBT and IPT for depression. METHOD: We conducted a multicentre randomised trial from November 2014 through December 2017. We recruited 200 adults with depression across nine specialised mental health centres in the Netherlands. This study used a 2 × 2 factorial design, randomising patients to once or twice weekly sessions of CBT or IPT over 16-24 weeks, up to a maximum of 20 sessions. Main outcome measures were depression severity, measured with the Beck Depression Inventory-II at baseline, before session 1, and 2 weeks, 1, 2, 3, 4, 5 and 6 months after start of the intervention. Intention-to-treat analyses were conducted. RESULTS: Compared with patients who received weekly sessions, patients who received twice weekly sessions showed a statistically significant decrease in depressive symptoms (estimated mean difference between weekly and twice weekly sessions at month 6: 3.85 points, difference in effect size d = 0.55), lower attrition rates (n = 16 compared with n = 32) and an increased rate of response (hazard ratio 1.48, 95% CI 1.00-2.18). CONCLUSIONS: In clinical practice settings, delivery of twice weekly sessions of CBT and IPT for depression is a way to improve depression treatment outcomes.

The effects of retrieval versus rehearsal of online problem-solving therapy sessions on recall, problem-solving skills and distress in distressed individuals: An experimental study.

BACKGROUND AND OBJECTIVES: Improving memory for the content of therapy sessions might increase the effects of psychological interventions. Previous studies showed that healthy individuals who took a memory test (retrieval) of studied material showed better long-term memory retention than individuals who restudied (rehearsal) the material. The aim of the current study was to find out whether we can translate these findings to a subclinical setting. METHODS: Individuals with moderate levels of distress were randomized into retrieving (n = 46) or rehearsing (n = 49) four weekly sessions of online Problem-Solving Therapy (PST). Session recall, problem-solving skills and distress were measured at baseline, three days after each session and at one-week follow-up. RESULTS: Retrieval led to overall higher recall, but this difference disappeared when controlling for the time spent on retrieval versus rehearsal. Retrieval did not lead to better problem-solving skills or less distress, compared to rehearsal. Baseline working memory performance moderated the effect of condition on recall after controlling for the time spent on retrieval versus rehearsal: the effect of retrieval compared to rehearsal on recall was larger for individuals with lower working memory performance. LIMITATIONS: The sample mostly consisted of university students with overall high working memory scores. CONCLUSIONS: This study provided the first evidence that retrieval of the content of PST sessions may lead to better session recall compared to rehearsal of the PST sessions in individuals with a low working memory score. Implications for the use of cognitive support strategies within a therapeutic setting are discussed.

Direct effects of cognitive therapy skill acquisition on cognitive therapy skill use, idiosyncratic dysfunctional beliefs and emotions in distressed individuals: An experimental study.

Experimental studies that manipulate treatment procedures to investigate their direct effects on treatment processes and outcomes are necessary to find out the effective elements and improve the effects of cognitive behavioral therapy (CBT) for depression. The present study randomized mildly to severely depressed participants into a procedure focused on cognitive therapy skill acquisition (CTSA; n = 27) or a control procedure focused on being exposed to theories of automatic thinking (n = 25) and investigated the direct effects on cognitive therapy (CT) skill use, credibility of idiosyncratic dysfunctional beliefs and strength of emotions. After the procedure, participants were exposed to a sad mood induction and given an assignment to test their CT skills. Participants who received the CTSA procedure used more CT skills compared to participants that received the control procedure, but there were no differences between conditions in the decrease of the credibility of idiosyncratic dysfunctional beliefs and strength of emotions. However, in participants with mild levels of depression, those who underwent the CTSA procedure showed larger decrease in the credibility of their most malleable belief (i.e. mostly automatic negative thoughts) compared to those who received the control procedure, but the significance of these findings disappeared when controlling for differences in ratings of the procedures. Future experimental studies should focus on the effects of CT skill training in the long term, the dose of the procedure and individual patient differences to find out under what circumstances the use of CT skills can lead to a reduction in dysfunctional thinking and subsequent symptoms of depression.

Measuring Patients' Acquisition of Therapy Skills in Psychotherapy for Depression: Assessing the CCTS-SR and the IPSS-SR.

Using data from 202 patients with depression, the authors conducted a psychometric evaluation of the Dutch translation of the Competencies of Cognitive Therapy Scale-Self-Report and an initial psychometric evaluation of the newly developed Interpersonal Psychotherapy Skills Scale-Self-Report.

The implementation and adherence to evidence-based protocols for psychotherapy for depression: the perspective of therapists in Dutch specialized mental healthcare.

BACKGROUND: Although psychotherapy is an effective treatment for depression, a large number of patients still do not receive care according to the protocols that are used in clinical trials. Instead, patients often receive a modified version of the original intervention. It is not clear how and when treatment protocols are used or modified in the Dutch specialized mental health care and whether these changes lead to suboptimal adherence to treatment protocols. METHODS: In the context of an ongoing multicenter trial that investigates whether twice-weekly sessions of protocolized interpersonal psychotherapy (IPT) and cognitive behavioral therapy (CBT) for depression lead to better treatment outcomes compared to once-weekly sessions, two focus groups using semi-structured interviews were organized. Aims were to increase insight in the adherence to and modifications of CBT and IPT protocols in the Dutch specialized mental health care for depression. Participants were fifteen therapists from seven mental health locations part of five mental health organizations. Verbatim transcripts were coded and analyzed using qualitative software. RESULTS: Three themes emerged: modification as the common practice, professional and patient factors influencing the adherence to protocols and organizational boundaries and flexibility. Treatment modification appeared to happen on a frequent basis, even in the context of a trial. Definitions of treatment modifications were multiple and varied from using intuition to flexible use of the same protocol. Therapist training and supervision, the years of work experience and individual characteristics of the therapist and the patient were mentioned to influence the adherence to protocols. Modifications of the therapists depended very much on the culture within the mental health locations, who differed in terms of the flexibility offered to therapists to choose and modify treatment protocols. CONCLUSIONS: Not all treatment modifications were in line with existing evidence or guidelines. Regular supervision, team meetings and a shared vision were identified as crucial factors to increase adherence to treatment protocols, whereas additional organizational factors, among which a change of mindset, may facilitate adequate implementation.

Frequency and change mechanisms of psychotherapy among depressed patients: study protocol for a multicenter randomized trial comparing twice-weekly versus once-weekly sessions of CBT and IPT.

BACKGROUND: Cognitive behavioral therapy (CBT) and interpersonal therapy (IPT) are among the most well established therapies for the treatment of depression. However, some major questions remain unanswered. First, it is unknown what session frequency results in the most optimal (cost) effectiveness in psychotherapy. Second, the debate as to what mechanisms underlie the effect of psychotherapy has not yet been resolved. Enhancing knowledge about the optimal session frequency and mechanisms of change seems crucial in order to optimize the (cost) effectiveness of psychotherapy for depression. This study aims to compare treatment outcome of twice-weekly versus once-weekly sessions of CBT and IPT. We expect twice-weekly sessions to be more effective and lead to more rapid recovery of depressive symptoms in comparison to once-weekly sessions. Both therapy-specific and non-specific process measures will be included to unravel the mechanisms of change in psychotherapy for depression. Besides the use of self-reports and behavioral observations, this study will also examine underlying biological processes by collecting blood samples. METHOD: In a multicenter randomized trial, two hundred depressed patients will be recruited from Dutch specialized mental healthcare centers and randomized into one of the following groups, all receiving a maximum of 20 sessions in different frequencies: a) twice-weekly sessions at the start of CBT, b) twice-weekly sessions at the start of IPT, c) once-weekly sessions at the start of CBT, d) once-weekly sessions at the start of IPT. Primary outcome measures are depression severity, cost-effectiveness and quality of life. Process measures include therapeutic alliance, recall, therapy-specific skills, motivation and compliance. Assessments will take place during baseline, monthly during treatment and follow-up at month 9, 12 and 24. In addition, at 12 and 24 months, the frequency of depressive episodes in the previous year will be assessed. Blood samples will be taken pre- and post-treatment. The study has been ethically approved and registered. DISCUSSION: Finding that twice-weekly sessions are more effective or lead to more rapid recovery of depressive symptoms could lead to treatment adaptations that have the potential to reduce the personal and societal burden of depression. In addition, insight into the mechanisms of change and physiological processes in psychotherapy will enable us to optimize treatments and may help to understand human functioning beyond the context of treatment. TRIAL REGISTRATION: The study has been registered on October 21th, 2014 at the Netherlands Trial Register, part of the Dutch Cochrane Centre ( NTR4856 ).