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.

The Effects of Patient Preference on Clinical Outcome, Satisfaction and Adherence Within the Treatment of Anxiety and Depression: A Meta-Analysis.

BACKGROUND: Taking patient preference into consideration has received increased attention in the last decades. We conducted a meta-analysis to estimate the effects of patient preference on clinical outcome, satisfaction and adherence regarding treatment of depression and anxiety. METHODS: Pubmed, Embase, PsycINFO and Scopus were searched for (cluster) randomized controlled trials. Twenty-six randomized controlled clinical trials were included, comprising 3670 participants, examining the effect of patient preference regarding treatment of anxiety and depression on clinical outcome, satisfaction and/or adherence. RESULTS: No effect of patient preference was found on clinical outcome [d = 0.06, 95% CI = (-0.03, 0.15), p = 0.16, n = 23 studies]. A small effect of patient preference was found on treatment satisfaction [d = 0.33, 95% CI = (0.08, 0.59), p = 0.01, n = 6 studies] and on treatment adherence [OR = 1.55, 95% CI = (1.28, 1.87), p < 0.001, n = 22 studies]. LIMITATIONS: Patient preference is a heterogeneous concept, future studies should strive to equalize operationalization of preference. Subgroup analyses within this study should be interpreted with caution because the amount of studies per analysed subgroup was generally low. Most studies included in this meta-analysis focused on patients with depression. The small number of studies (n = 6) on satisfaction, prevents us from drawing firm conclusions. CONCLUSIONS: While this meta-analysis did not find a positive effect of considering patient preference on clinical outcome, it was associated with slightly better treatment satisfaction and adherence. Accommodating preference of patients with anxiety and depression can improve treatment. TRIAL REGISTRATION: PROSPERO: CRD42020172556.

Feasibility and Acceptability of Group Interpersonal and Social Rhythm Therapy for Recurrent Mood Disorders: A Pilot Study.

OBJECTIVE: Interpersonal and social rhythm therapy (IPSRT) was developed to empower patients with mood disorders by stabilizing underlying disturbances in circadian rhythms and by using strategies from interpersonal psychotherapy. Group IPSRT has not been studied with a transdiagnostic sample of patients across the life span with either major depressive disorder or bipolar disorder. METHODS: Thirty-eight outpatients, ages 26-80, with major depressive disorder or bipolar disorder in any mood state were recruited from clinics in the Netherlands and were treated with 20 sessions (two per week) of group IPSRT. Recruitment results, dropout rates, and session adherence were used to assess feasibility. The modified Client Satisfaction Questionnaire (CSQ) and a feedback session were used to measure treatment acceptability. Changes in mood symptoms, quality of life, and mastery were also measured. RESULTS: Participants' mean±SD age was 65.4±10.0 years. Participants were diagnosed as having major depressive disorder (N=14, 37%) or bipolar disorder (N=24, 63%). The dropout rate was relatively low (N=9, 24%). High CSQ scores (32.3±5.2 of 44.0 points) and low dropout rates indicated the acceptability and feasibility of group IPSRT for major depressive disorder and bipolar disorder. Quality of life 3 months after completion of treatment was significantly higher than at baseline (p<0.01, Cohen's d=-0.69). No significant differences were found between pre- and postintervention depressive symptom scores. CONCLUSIONS: Twice-weekly group IPSRT for older outpatients with major depressive disorder or bipolar disorder was feasible and acceptable. Future research should evaluate the short- and long-term efficacy of group IPSRT for major depressive disorder and bipolar disorder among patients of all ages.

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.

Predictors of the 6-year outcome of obsessive-compulsive disorder: Findings from the Netherlands Obsessive-Compulsive Disorder Association study.

OBJECTIVE: Obsessive-compulsive disorder is characterized by a chronic course that can vary between patients. The knowledge on the naturalistic long-term outcome of obsessive-compulsive disorder and its predictors is surprisingly limited. The present research was designed to identify clinical and psychosocial predictors of the long-term outcome of obsessive-compulsive disorder. METHODS: We included 377 individuals with a current diagnosis of obsessive-compulsive disorder, who participated in the Netherlands Obsessive Compulsive Disorder Association study, a multicenter naturalistic cohort study. Predictors were measured at baseline using self-report questionnaires and clinical interviews. Outcome was assessed using the Yale-Brown Obsessive Compulsive Scale at 2-, 4- and 6-year follow-up. RESULTS: The overall course of obsessive-compulsive disorder was characterized by two prominent trends: the first reflected an improvement in symptom severity, which was mitigated by the second, worsening trend in the long term. Several determinants affected the course variations of obsessive-compulsive disorder, namely, increased baseline symptom severity, late age of onset, history of childhood trauma and autism traits. CONCLUSION: The long-term outcome of obsessive-compulsive disorder in naturalistic settings was characterized by an overall improvement in symptom severity, which was gradually halted to the point of increased worsening. However, after 6 years, the severity of symptoms remained below the baseline level. While certain determinants predicted a more favorable course, their effect diminished over time in correspondence to the general worsening trend. The results highlight the importance of a regular and continuous monitoring for symptom exacerbations as part of the management of the obsessive-compulsive disorder, regardless of the presence of putative predictors.

Associations of three major physiological stress systems with suicidal ideation and suicide attempts in patients with a depressive and/or anxiety disorder.

BACKGROUND: People with depressive and/or anxiety disorders are at increased risk of suicidal ideation and suicide attempts, but biological correlates signaling such risk remain unclear. Independent and cumulative dysregulations in physiological stress systems, in particular the hypothalamic-pituitaryadrenal axis (HPA-axis), immune-inflammatory system, and autonomous nervous system (ANS), may contribute to this risk. However, findings have either been heterogeneous or absent thus far. METHODS: Associations between individual markers and cumulative indices of the HPA-axis (cortisol awakening response and evening cortisol), immune-inflammatory system (C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-α), and the ANS (heart rate, respiratory sinus arrhythmia, and pre-ejection period) and the outcomes no suicide ideation with suicide attempt (SI-SA+), suicide ideation without suicide attempt (SI+SA-) and suicide ideation with suicide attempt (SI+SA+) were investigated in 1749 persons with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA). RESULTS: High levels of CRP and IL-6 were associated with SI-SA+ and SI+SA+ respectively when compared to non-suicidal patients after adjusting for confounders and multiple testing. Also, cumulative immune-inflammatory dysregulations were positively associated with SI+SA+, suggesting a dose-response effect. No significant associations were found between HPA-axis or ANS indicators and suicide-outcomes and between immune-inflammatory system markers or cumulative stress system dysregulations and SI+SA-. CONCLUSION: Although stress system markers could not differentiate between SI+SA- and non-suicidal patients, findings indicate that dysregulations of individual and cumulative immune-inflammatory markers are associated with suicide attempts in depressive and/or anxiety patients. Thus, immune-inflammatory system dysregulation may be involved in the pathophysiology of suicidal behavior, supporting further examination of the effects of anti-inflammatory interventions on suicidality.

Is social functioning in older age patients with bipolar disorder associated with affective and/or non-affective cognition?

OBJECTIVES: Previous research showed impairments in non-affective cognition, affective cognition, and social functioning in adult patients with bipolar disorder (BD). Only 37% of adult BD patients recovers in social functioning, and both aspects of cognition are important constructs of influence. The role of affective cognition in older age bipolar disorder (OABD) patients is still unclear. Therefore, the aim of our study was to examine the separate and combined effects of affective cognition and non-affective cognition on social functioning. METHODS: The current study included 60 euthymic patients (aged >60) of the Dutch Older Bipolar Study. Affective cognition was measured by Theory of Mind and Emotion Recognition. Non-affective cognition was assessed through the measurements of attention, learning and memory, and executive functioning. Social functioning was examined through global social functioning, social participation, and meaningful contacts. The research questions were tested with linear and ordinal regression analyses. RESULTS: Results showed a positive association of all non-affective cognitive domains with global social functioning. Associations between affective cognition and social functioning were non-significant. Results did show an interaction between non-affective and affective cognition. CONCLUSIONS: Associations between non-affective cognition and social functioning were confirmed, associations between affective cognition and social function were not found. For generalizability, studies with a greater sample size are needed. Conducting additional research about OABD patients and affective cognition is important. It may lead to more insight in impairment and guide tailored treatment that focusses more on all aspects of recovery and the needs of OABD patients.

Associations between personality traits and suicidal ideation and suicide attempts in patients with personality disorders.

INTRODUCTION: People with personality disorders (PDs) have an elevated suicide risk. However, correlates of suicidal ideation (SI) and suicide attempts (SA) remain largely unknown in this population. A growing body of literature highlights the contribution of the Big Five personality traits in suicide-outcomes. Therefore, the present study investigates the association between the Big Five personality traits and SI and SA in people with PDs while applying the ideation-to-action framework. METHOD: Data were obtained from 105 treatment-seeking individuals diagnosed with PDs participating in the Trauma tO Personality Spectrum Study (TOPSS). Multinomial logistic regression analyses were used to analyze the association between the NEO Five-Factor Inventory and the three category suicide-outcome: non-suicidal, SI, and SA. RESULTS: After controlling for age, gender, a comorbid depressive disorder, the severity of borderline manifestations, and other personality traits from the Big Five taxonomy, significantly lower levels of extraversion were observed in participants with SI compared to non-suicidal participants (OR = 0.27, 95% CI 0.10-0.72) but not in SA participants. In contrast, higher levels of extraversion were associated with SA when compared to SI (OR = 3.52, 95% CI 1.33-9.32). Other Big Five traits were not independently associated with suicide-outcomes. CONCLUSIONS: Of the Big Five traits, the introversion-extraversion dimension most clearly distinguishes individuals with SI from non-suicidal individuals, as well as those with a SA in the past from those with SI only. Prospective studies are required to investigate if this personality trait can predict the progression from being non-suicidal to having SI and from having SI to performing an attempt.

Psychiatric symptoms during the COVID-19 outbreak in older adults with bipolar disorder.

OBJECTIVES: Older adults with bipolar disorder (OABD) are vulnerable for a COVID-19 infection via multiple pathways. It is essential for OABD to adhere to the COVID-19 measures, with potential consequences for the psychiatric symptoms. This situation offers the unique opportunity to investigate factors of vulnerability and resilience that are associated with psychiatric symptoms in OABD. METHODS: This study included 81 OABD patients aged over 50 years. Factors measured at baseline in patients that participated in 2017/2018 were compared with factors measured during the COVID-19 outbreak. RESULTS: Participants experienced less psychiatric symptoms during COVID-19 than (67.9% euthymic) than at baseline (40.7% euthymic). There was no difference in loneliness between COVID-19 and baseline. Not having children, more feelings of loneliness, lower mastery, passive coping style and neuroticism were associated with more psychiatric symptoms during COVID-19 measures. CONCLUSIONS: Participants experienced less psychiatric symptoms during COVID-19 measures when compared to baseline. Our results indicate promising targets for psychological interventions aimed at curing and preventing recurrence in OABD and improving quality of life in this growing vulnerable group.

The influence of social, psychological, and cognitive factors on the clinical course in older patients with bipolar disorder.

OBJECTIVES: Research on factors that contribute to recurrence in older adults with bipolar disorder (OABD) is sparse. Previous research showed that clinical factors (e.g., age of onset, lifetime psychotic features, and suicide risk) were not associated with the recurrence in OABD. In younger adults, worse social functioning, coping style, and worse cognitive functioning are found to be associated with an unfavorable course of bipolar disorder. Therefore, this study is focusing on social, psychological, and cognitive factors in OABD. More insight in these factors is essential in order to develop and further specify preventive and treatment interventions. METHODS: Data were used from the Dutch Older Bipolars (DOBi) cohort study. We included 64 patients for 3-year follow-up measurements, who were divided in a recurrent group and a nonrecurrent group. Logistic regression analyses were conducted to assess associations between social, psychological, and cognitive factors, and nonrecurrence. RESULTS: 39.1% reported at least one recurrence during the 3-year follow-up period. No significant associations were found between the social, psychological, and cognitive factors and having a recurrence during the follow-up period. DISCUSSION: Participants in the recurrent group were younger, more often female and less likely to have children. Our results suggest that results from the adult bipolar disorder population cannot be extrapolated to OABD patients, underlining the need for longitudinal studies in OABD.

Suicide ideation versus suicide attempt: Examining overlapping and differential determinants in a large cohort of patients with depression and/or anxiety.

OBJECTIVE: Individuals with a depressive and/or anxiety disorder are known to have an elevated risk of suicide. However, these diagnoses alone are insufficient at differentiating patients with suicide ideation that attempt suicide from those that do not. Few studies examined such differences in an ideation-to-action framework. Using this framework, extensive multivariate testing was performed to examine differences between suicidal patients with and without a suicide attempt. METHOD: Data were from 1576 respondents with a depressive and/or anxiety disorder, participating in the Netherlands Study of Depression and Anxiety. Logistic regression analyses were used to analyze associations between sociodemographic, clinical, personality, and psychosocial risk factors and suicide ideation and attempt. RESULTS: Patients with suicide ideation could be uniquely distinguished from non-suicidal patients by more years of education, presence of a depressive disorder (vs anxiety disorder) and higher introversion. Patients with suicide ideation and a past suicide attempt could be uniquely distinguished from non-suicidal patients by a younger age of onset, a lifetime alcohol use disorder, more external locus of control and lower levels of social support. Within the group of patients with suicide ideation, patients with a suicide attempt were more likely to have childhood trauma and lower education, and be of non-Western descent than patients with suicide ideation and no past attempt. CONCLUSION: This study found that although various clinical, personality and psychosocial characteristics distinguish patients with suicide ideation from non-suicidal patients, many of these often-cited factors do not distinguish patients with a suicide attempt from those who only think about suicide. However, childhood trauma, lower education and non-Western descent could aid in detecting suicide attempt risk among patients with suicide ideation.

The correlates of social phobia in OCD: Findings from a large clinical sample.

OBJECTIVES: Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder, often complicated with comorbidities. Social phobia (SP) is the most frequent co-occurring anxiety disorder in OCD, associated with increased clinical severity. However, no study had examined the relevance of interpersonal processes in this comorbidity, which are at the core of SP. This study characterized the clinical (i.e., symptom profile, age of onset, chronicity, and comorbidity), vulnerability (i.e., childhood trauma, negative life events), and interpersonal (attachment style, expressed emotion, and social support) correlates of comorbid SP in a large sample of OCD patients. METHODS: We analysed the data of 382 OCD patients participating in the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study. We examined the correlates of SP in OCD using self-report questionnaires and structured clinical interviews. In addition, data of 312 non-OCD SP patients were drawn from the Netherlands Study of Depression and Anxiety (NESDA), to compare the age of onset of SP between groups. Descriptive univariate analyses were followed by backward stepwise logistic regression analyses. RESULTS: Social phobia was present among approximately 20% of OCD patients. Social phobia in OCD was associated with increased depression severity and decreased ratings of secure attachment style. Among OCD patients, SP had a significantly earlier age onset as compared to SP in non-OCD patients. CONCLUSION: Social phobia in OCD might render a vulnerable clinical picture, characterized with early onset of SP symptoms, insecure attachment style, and increased depressive symptoms. Future studies should use prospective designs to better understand the nature of comorbid SP in OCD. PRACTITIONER POINTS: Approximately one fifth of OCD patients were diagnosed with comorbid social phobia in a large representative clinical sample. OCD patients with comorbid social phobia presented with a vulnerable clinical picture, characterized with increased depression severity and decreased ratings of secure attachment style. Social phobia in OCD was associated with an earlier AOO as compared to the AOO of social phobia without OCD. The findings are limited by a cross-sectional design; thus, causality could not be assessed. Research is needed to further examine the mechanisms of comorbid social phobia in OCD.

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.

Four-year course of quality of life and obsessive-compulsive disorder.

OBJECTIVE: Patients with obsessive compulsive disorder (OCD) have high disease burden. It is important to restore quality of life (QoL) in treatment, so that patients become able to live a fulfilling life. Little is known about the longitudinal course of QoL in patients with OCD, its association with remission from OCD, and about factors that contribute to an unfavourable course of QoL in remitting patients. METHODS: Study on the 4-year course of QoL of patients with chronic (n = 144), intermittent (n = 22), and remitting OCD (n = 73) using longitudinal data of the Netherlands Obsessive Compulsive Disorder Association (NOCDA; complete data: n = 239; imputed data n = 382). The EuroQol five-dimensional questionnaire (EQ-5D) utility score was used to assess QoL. In patients with remitting OCD, we examined patient characteristics that contributed to an unfavourable course of QoL, including sociodemographics, OCD characteristics, psychiatric comorbidity, and personality traits. RESULTS: Course of QoL was associated with course of OCD. QoL improved in those who remitted from OCD; however, even in these patients, QoL remained significantly below the population norms. The correlation between QoL and severity of OCD was only moderate: r = - 0.40 indicating that other factors besides OCD severity contribute to QoL. In remitters, more severe anxiety and depression symptoms were related to a lower QoL. Results were similar in complete and imputed data sets. CONCLUSIONS: Remission from OCD is associated with improvement of QoL, but comorbid anxiety and depression symptoms hamper the improvement of QoL. QoL could be improved by reducing OCD symptoms in patients with OCD and by treating comorbid anxiety and depression symptoms in remitting patients.

Fronto-limbic disconnection in patients with multiple sclerosis and depression.

BACKGROUND: The biological mechanism of depression in multiple sclerosis (MS) is not well understood. Based on work in major depressive disorder, fronto-limbic disconnection might be important. OBJECTIVE: To investigate structural and functional fronto-limbic changes in depressed MS (DMS) and non-depressed MS (nDMS) patients. METHODS: In this retrospective study, 22 moderate-to-severe DMS patients (disease duration 8.2 ± 7.7 years), 21 nDMS patients (disease duration 15.3 ± 8.3 years), and 12 healthy controls underwent neuropsychological testing and magnetic resonance imaging (MRI; 1.5 T). Brain volumes (white matter (WM), gray matter, amygdala, hippocampus, thalamus), lesion load, fractional anisotropy (FA) of fronto-limbic tracts, and resting-state functional connectivity (FC) between limbic and frontal areas were measured and compared between groups. Regression analysis was performed to relate MRI measures to the severity of depression. RESULTS: Compared to nDMS patients, DMS patients (shorter disease duration) had lower WM volume ( p < 0.01), decreased FA of the uncinate fasciculus ( p < 0.05), and lower FC between the amygdala and frontal regions ( p < 0.05). Disease duration, FA of the uncinate fasciculus, and FC of the amygdala could explain 48% of variance in the severity of depression. No differences in cognition were found. CONCLUSION: DMS patients showed more pronounced (MS) damage, that is, structural and functional changes in temporo-frontal regions, compared to nDMS patients, suggestive of fronto-limbic disconnection.

The (cost) effectiveness of guided internet-based self-help CBT for dialysis patients with symptoms of depression: study protocol of a randomised controlled trial.

BACKGROUND: Only a minority of dialysis patients with depressive symptoms are diagnosed and receive treatment. Depressive symptoms are highly prevalent in this population and are associated with adverse clinical outcomes. Underlying factors for this undertreatment may be the lack of evidence for the safety and effectivity of antidepressant medication, the reluctance of patients to adhere to antidepressant medication, the lack of mental healthcare provision in somatic healthcare environments and end-stage renal disease (ESRD) related physical limitations that complicate face-to-face psychotherapy. Guided Internet-based self-help treatment has demonstrated to be effective for depressive symptoms in other chronic patient populations and may overcome these barriers. The aim of this study is to investigate the (cost) effectiveness of a guided Internet-based self-help intervention for symptoms of depression in dialysis patients. METHODS: This study is a cluster randomized controlled trial (RCT) that investigates the effectiveness of a 5-week Internet-based self-help Problem Solving Therapy (PST) for depressive symptoms in dialysis patients. Depressive symptoms will be measured using the Beck Depression Inventory - second edition (BDI-II), with a cut-off score of ≥10. We aim to include 206 dialysis patients with depressive symptoms who will be cluster randomized to the intervention or the Care as Usual (CAU) control group. Secondary outcomes will include anxiety symptoms, quality of life, economic costs and clinical outcomes, such as inflammatory factors and hair cortisol levels. Assessments will take place at baseline (T0), 2 weeks after intervention (T1) and 6 months (T2), 12 months (T3) and 18 months (T4) after intervention. The control group will be measured at the same time points. Analysis will be based on the intention-to-treat principle. Mixed models will be used to assess the changes within each condition between pre-treatment and post-treatment. DISCUSSION: If demonstrated to be (cost) effective, Internet-based PST will offer new possibilities to treat dialysis patients with depressive symptoms and to improve their quality of care. TRIAL REGISTRATION: Dutch Trial Register: Trial NL6648 (NTR6834) (prospectively registered 13th November 2017).

The impact of depression and anxiety treatment on biological aging and metabolic stress: study protocol of the MOod treatment with antidepressants or running (MOTAR) study.

BACKGROUND: Depressive and anxiety disorders have shown to be associated to premature or advanced biological aging and consequently to adversely impact somatic health. Treatments with antidepressant medication or running therapy are both found to be effective for many but not all patients with mood and anxiety disorders. These interventions may, however, work through different pathophysiological mechanisms and could differ in their impact on biological aging and somatic health. This study protocol describes the design of an unique intervention study that examines whether both treatments are similarly effective in reducing or reversing biological aging (primary outcome), psychiatric status, metabolic stress and neurobiological indicators (secondary outcomes). METHODS: The MOod Treatment with Antidepressants or Running (MOTAR) study will recruit a total of 160 patients with a current major depressive and/or anxiety disorder in a mental health care setting. Patients will receive a 16-week treatment with either antidepressant medication or running therapy (3 times/week). Patients will undergo the treatment of their preference and a subsample will be randomized (1:1) to overcome preference bias. An additional no-disease-no-treatment group of 60 healthy controls without lifetime psychopathology, will be included as comparison group for primary and secondary outcomes at baseline. Assessments are done at week 0 for patients and controls, and at week 16 and week 52 for patients only, including written questionnaires, a psychiatric and medical examination, blood, urine and saliva collection and a cycle ergometer test, to gather information about biological aging (telomere length and telomerase activity), mental health (depression and anxiety disorder characteristics), general fitness, metabolic stress-related biomarkers (inflammation, metabolic syndrome, cortisol) and genetic determinants. In addition, neurobiological alterations in brain processes will be assessed using structural and functional Magnetic Resonance Imaging (MRI) in a subsample of at least 25 patients per treatment arm and in all controls. DISCUSSION: This intervention study aims to provide a better understanding of the impact of antidepressant medication and running therapy on biological aging, metabolic stress and neurobiological indicators in patients with depressive and anxiety disorders in order to guide a more personalized medicine treatment. TRIAL REGISTRATION: Trialregister.nl Number of identification: NTR3460, May 2012.

The decision tool unipolar depression (DTUD): a new measure to facilitate the early identification of patients with major depressive disorder in need of highly specialized care.

BACKGROUND: Selection of the optimal initial treatment in patients with major depressive disorder (MDD) in need of highly specialized care has the potential to benefit treatment outcomes and cost-effectiveness of treatment strategies. However, to date, there is a paucity of measures that could guide the selection of the initial treatment, in particular to indicate which patients with MDD are in need of highly specialized care. Recognizing this gap, this paper reports on the development and psychometric evaluation of the Decision Tool Unipolar Depression (DTUD), aimed to facilitate the early identification of patients with MDD in need of highly specialized care. METHODS: The DTUD was developed using a mixed-methods approach, consisting of a systematic review and a concept mapping study. To evaluate the psychometric features of the DTUD, a cross-sectional multicenter study was conducted. A total of 243 patients with MDD were evaluated with the DTUD. Feasibility was operationalized as the time required to complete the DTUD and the content clarity of the DTUD. Inter-rater reliability was evaluated using Krippendorf's alpha. The Maudsley Staging Method (MSM) and the Dutch Measure for quantification of Treatment Resistance in Depression (DM-TRD) were administered to assess the convergent validity. A receiver operator characteristic curve was generated to evaluate the criterion validity and establish the optimal cut-off value. RESULTS: The mean administration time was 4.49 min (SD = 2.71), and the content of the total DTUD was judged as clear in 94.7% of the evaluations. Inter-rater reliability values ranged from 0.69 to 0.91. Higher scores on the DTUD were associated with higher scores on the MSM (rs = 0.47) and DM-TRD (rs = 0.53). Based on the maximum Youden index (0.494), maximum discrimination was reached at a cut-off score of ≥5 (sensitivity 67%, specificity 83%). CONCLUSION: The DTUD demonstrated to be a tool with solid psychometric properties and, therefore, is a promising measure for the early identification of patients with MDD in need of highly specialized care. Use of the DTUD has the potential to facilitate the selection and initiation of the optimal initial treatment in patients with MDD, which in turn may improve the clinical effectiveness and cost-effectiveness of treatment strategies.

Cost and Effectiveness of Blended Versus Standard Cognitive Behavioral Therapy for Outpatients With Depression in Routine Specialized Mental Health Care: Pilot Randomized Controlled Trial.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective treatment, but access is often restricted due to costs and limited availability of trained therapists. Blending online and face-to-face CBT for depression might improve cost-effectiveness and treatment availability. OBJECTIVE: This pilot study aimed to examine the costs and effectiveness of blended CBT compared with standard CBT for depressed patients in specialized mental health care to guide further research and development of blended CBT. METHODS: Patients were randomly allocated to blended CBT (n=53) or standard CBT (n=49). Blended CBT consisted of 10 weekly face-to-face sessions and 9 Web-based sessions. Standard CBT consisted of 15 to 20 weekly face-to-face sessions. At baseline and 10, 20, and 30 weeks after start of treatment, self-assessed depression severity, quality-adjusted life-years (QALYs), and costs were measured. Clinicians, blinded to treatment allocation, assessed psychopathology at all time points. Data were analyzed using linear mixed models. Uncertainty intervals around cost and effect estimates were estimated with 5000 Monte Carlo simulations. RESULTS: Blended CBT treatment duration was mean 19.0 (SD 12.6) weeks versus mean 33.2 (SD 23.0) weeks in standard CBT (P<.001). No significant differences were found between groups for depressive episodes (risk difference [RD] 0.06, 95% CI -0.05 to 0.19), response to treatment (RD 0.03, 95% CI -0.10 to 0.15), and QALYs (mean difference 0.01, 95% CI -0.03 to 0.04). Mean societal costs for blended CBT were €1183 higher than standard CBT. This difference was not significant (95% CI -399 to 2765). Blended CBT had a probability of being cost-effective compared with standard CBT of 0.02 per extra QALY and 0.37 for an additional treatment response, at a ceiling ratio of €25,000. For health care providers, mean costs for blended CBT were €176 lower than standard CBT. This difference was not significant (95% CI -659 to 343). At €0 per additional unit of effect, the probability of blended CBT being cost-effective compared with standard CBT was 0.75. The probability increased to 0.88 at a ceiling ratio of €5000 for an added treatment response, and to 0.85 at €10,000 per QALY gained. For avoiding new depressive episodes, blended CBT was deemed not cost-effective compared with standard CBT because the increase in costs was associated with negative effects. CONCLUSIONS: This pilot study shows that blended CBT might be a promising way to engage depressed patients in specialized mental health care. Compared with standard CBT, blended CBT was not considered cost-effective from a societal perspective but had an acceptable probability of being cost-effective from the health care provider perspective. Results should be carefully interpreted due to the small sample size. Further research in larger replication studies focused on optimizing the clinical effects of blended CBT and its budget impact is warranted. TRIAL REGISTRATION: Netherlands Trial Register NTR4650; https://www.trialregister.nl/trial/4408. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12888-014-0290-z.