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.

Design and rationale of the REStoring mood after early life trauma with psychotherapy (RESET-psychotherapy) study: a multicenter randomized controlled trial on the efficacy of adjunctive trauma-focused therapy (TFT) versus treatment as usual (TAU) for adult patients with major depressive disorder (MDD) and childhood trauma.

BACKGROUND: Major depressive disorder (MDD) is a common, recurrent mental disorder and a leading cause of disability worldwide. A large part of adult MDD patients report a history of childhood trauma (CT). Patients with MDD and CT are assumed to represent a clinically and neurobiologically distinct MDD subtype with an earlier onset, unfavorable disease course, stress systems' dysregulations and brain alterations. Currently, there is no evidence-based treatment strategy for MDD that specifically targets CT. Given the central role of trauma in MDD patients with CT, trauma-focused therapy (TFT), adjunctive to treatment as usual (TAU), may be efficacious to alleviate depressive symptoms in this patient population. METHODS: The RESET-psychotherapy study is a 12-week, single-blind, randomized controlled trial testing the efficacy of TFT in 158 adults with moderate to severe MDD, as a 'stand-alone' depression diagnosis or superimposed on a persistent depressive disorder (PDD), and CT. TFT (6-10 sessions of Eye Movement Desensitization and Reprocessing and/or imagery rescripting) + TAU is compared to TAU only. Assessments, including a wide range of psychological/psychiatric and biological characteristics, take place before randomization (T0), during treatment (T1), at post-treatment (T2) and at 6-month follow-up (T3). Pre-post treatment stress-related biomarkers in hair (cortisol) and blood (epigenetics and inflammation) will be assessed to better understand working mechanisms of TFT. A subgroup of 60 participants will undergo structural and functional Magnetic Resonance Imaging (MRI) assessments to determine pre-post treatment brain activity. The primary outcome is self-reported depression symptom severity at post-treatment, measured with the 30-item Inventory of Depressive Symptomatology - Self Report (IDS-SR). DISCUSSION: If adjunctive TFT efficaciously alleviates depressive symptoms in MDD patients with CT, this novel treatment strategy could pave the way for a more personalized and targeted MDD treatment. TRIAL REGISTRATION: ClinicalTrials.gov, registered at 08-12-2021, number of identification: NCT05149352.

Do high-risk couples profit more or less from couple relationship education programs than low-risk couples? Room for improvement and vulnerability effects.

In recent years it has been discussed whether high-risk couples benefit more from Couple Relationship Education programs (CREs) than low-risk couples due to larger room for improvement, or profit less due to greater vulnerability. Pertinent response prediction studies yielded inconclusive results. Careful review suggests this may be due to: statistical handling (not disentangling room for improvement and vulnerability effects), time frame analyzed (not disentangling opposing effects during intervention and follow-up), sampling, and selection of risk factors. We used an analytic strategy that maximized odds for replicability and tested two hypotheses: (1) room for improvement: pre-intervention relationship dissatisfaction predicts gain in satisfaction during intervention, and decline during follow up, and (2) vulnerability: when adjusted for room for improvement (pre-intervention relationship dissatisfaction), risk factors show negative or negligible, but no positive associations with gain in satisfaction. Actor-Partner Interdependence Modeling (APIM) was employed in 79 self-referred (SR) couples and 50 clinician-referred (CR) couples who had completed the 'Hold me Tight' program, a CRE based on Emotionally Focused Couple Therapy. Our findings supported both the room for improvement hypothesis, with pre-intervention dissatisfaction predicting more gain during intervention (both samples) and decline during follow-up (SR sample, for the CR sample the effect was negligible), and the vulnerability hypothesis, as several negative, but no positive effects of risk factors were observed during intervention and follow-up. Specific risk factors did not replicate between samples. To promote replicable results in future research, we advocate disentangling room for improvement and vulnerability effects, separately testing effects during intervention and follow-up, purposeful sampling, and studying a large set of risk factors including partner variables.

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.

Effectiveness of the 'Hold me Tight' Relationship Enhancement Program in a Self-referred and a Clinician-referred Sample: An Emotionally Focused Couples Therapy-Based Approach.

While evidence-based couple therapies are available, only a minority of troubled couples seek help and they often do this too late. To reach more couples earlier, the couple relationship education (CRE) group program "Hold me Tight" (HmT) based on Emotionally Focused Couples Therapy (EFCT) was developed. This study is the first to examine the effectiveness of HmT. Using a three-wave (waiting period, treatment, and follow-up) within-subject design, HmT was delivered to 79 self-referred couples and 50 clinician-referred couples. We applied a comprehensive outcome measure battery. Our main findings were that (1) self-referred couples significantly improved during HmT on all measures, that is relationship satisfaction, security of partner-bond, forgiveness, daily coordination, maintenance behavior, and psychological complaints, with a moderate-to-large mean effect size (d = .63), which was maintained (d = .57) during the 3.5 month follow-up; (2) in clinician-referred couples, who were vulnerable in terms of insecure attachment status and psychopathology, the improvement during HmT was moderate (d = .42), but this was reduced during the 3.5-month follow-up to a small effect (d = .22); (3) emotional functioning (typical HmT target) as well as behavioral functioning (typical Behavioral Couples Therapy-based CRE target) improved during HmT; and (4) individual psychological complaints, although not specifically targeted, were reduced during HmT. These findings suggest that HmT is a promising intervention for enhancement of relationship functioning. Clinical implications are discussed.

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 ).

Reducing intrusive suicidal mental images in patients with depressive symptoms through a dual-task add-on module: Results of a multicenter randomized clinical trial.

OBJECTIVE: To examine the safety and efficacy of a brief cognitive dual-task (using eye movements) add-on module to treatment as usual (TAU) in reducing the severity and frequency of intrusive suicidal mental images and suicidal ideation. METHOD: We conducted a single-blind, parallel multicenter randomized trial (No. NTR7563) among adult psychiatric outpatients (N = 91; Mage = 34.4, SD = 13.54; 68% female) with elevated depressive symptoms and experiencing distressing suicidal intrusions in the Netherlands. Primary outcome was the severity (Suicidal Intrusions Attributes Scale) and frequency (Clinical Interview for Suicidal Intrusions) of suicidal mental imagery intrusions at 1-week posttreatment and 3-month follow-up. Primary analysis was intention-to-treat. RESULTS: Between November 27, 2018 and September 13, 2021, 91 patients were included and randomly assigned to intervention group (Cognitive Dual Task Add-on + TAU) (n = 46) or TAU-only (n = 45). Cognitive Dual Task Add-on + TAU had greater reductions in severity (mean difference, -15.50, 95% CI [23.81, -7.19]; p < .001, d = 0.60), and frequency (geometric mean difference, 0.47, 95% CI [0.29, 0.79]; p = .004) of suicidal intrusions over time than TAU-alone. Cognitive Dual Task Add-on + TAU patients also showed lower suicidal ideation over time (p = .008, d = 0.42). There were no significant group differences in reductions in depressive symptoms, rumination, or hopelessness. Four serious adverse events occurred (three Cognitive Dual Task Add-on + TAU; one TAU-only); all unlikely attributable to intervention/trial. CONCLUSIONS: Findings provide support for the effectiveness of adding a cognitive dual-task module to the treatment of psychiatric outpatients with elevated depressive symptoms in reducing suicidal intrusions and ideation and can be executed safely. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effectiveness and feasibility of structured emotionally focused family therapy for parents and adolescents: Protocol of a within-subjects pilot study.

Mental health issues are widespread among children and adolescents worldwide. Although mental health difficulties may manifest themselves in many different diagnoses, there is growing support for a limited number of underlying transdiagnostic processes. Attachment encompasses a key transdiagnostic mechanism, namely emotional regulation. This study protocol aims to evaluate the feasibility and potential effectiveness of structured emotionally focused family therapy (EFFT), the goal of which is to develop secure attachment between parents and their children to reduce children's vulnerability to mental health problems. A within-subjects design with three waves, a waiting period, treatment, and follow-up, will be conducted. Families will serve as their own controls. Approximately 15 to 20 families with adolescents (aged 12-18 years) as the 'identified patients' will be included. They will participate in 16-21 sessions of EFFT. The study will use a multi-method approach. Self-report questionnaires will be administered repeatedly (i.e., pre-waiting period, pre-treatment, halfway treatment, post-treatment, and follow-up), measuring parent-adolescent attachment, partner-partner attachment, negative interactions, and adolescent psychological complaints. Multi-level analyses will be conducted. Semi-structured interviews will be administered at follow-up to evaluate feasibility and acceptability of EFFT. Treatment integrity will be assessed. The present study is the first to evaluate feasibility of structured EFFT and obtain a first impression of its effectiveness. This information will help us to improve EFFT. Limitations are discussed. Trial registration: Recruitment commenced in June 2022. The approximate trial duration is 36 months. The trial was registered at ClinicalTrials.gov (NCT05657067) on December 9, 2022, and Open Science Framework (https://osf.io/39dt2/) on June 14, 2022.

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.

Actor and Partner Effects of Attachment on Relationship Satisfaction and Sexual Satisfaction Across the Genders: An APIM Approach.

Previous studies found gender differences in relationship satisfaction and sexuality. We tested gender differences in associations between attachment, a lasting relationship determinant, and two outcomes, relationship and sexual satisfaction. This study improves on earlier research by examining these associations in one Actor-Partner-Interdependence-Model, making direct statistical testing between outcomes possible. Furthermore, a community and a distressed sample (N = 113 heterosexual couples each) were included to attempt replication across samples and to examine clinical implications. In both genders, actor attachment avoidance negatively affected relationship satisfaction and (with one exception) sexual satisfaction. Also in both genders, partner attachment avoidance negatively affected sexual satisfaction. However, whereas partner attachment avoidance influenced female relationship satisfaction, it did not affect male relationship satisfaction. The findings replicated across samples. Clinical implications are discussed.

High-performance anion-exchange chromatography combined with intrinsic fluorescence detection to determine erythropoietin in pharmaceutical products.

A high-performance anion-exchange chromatography (HPAEC) method was developed for determination of recombinant human erythropoietin (EPO) in pharmaceutical products. A fluorescence detector was added to the HPLC system as intrinsic fluorescence detection compared favourably to UV detection regarding sensitivity and selectivity. The HPLC method has been successfully applied to analyse erythropoietin products even in the presence of albumin as excipient. The intrinsic fluorescence chromatograms of both proteins revealed various peaks attributed to either micro-heterogeneous erythropoietin or albumin variants. The intrinsic fluorescence signal was linear over the range 10-200 microg/ml erythropoietin corresponding to pharmaceutically relevant concentrations. The HPLC method appeared to be a suitable method for differentation between recombinant human erythropoietin epoetin-alpha and -beta as they revealed different intrinsic fluorescence elution profiles. In conclusion, this study contributes to the development of a straightforward physicochemical method for specific quantification of recombinant human erythropoietin in pharmaceutical preparations.