Does a lack of emotions make chatbots unfit to be psychotherapists?

Mental health chatbots (MHCBs) designed to support individuals in coping with mental health issues are rapidly advancing. Currently, these MHCBs are predominantly used in commercial rather than clinical contexts, but this might change soon. The question is whether this use is ethically desirable. This paper addresses a critical yet understudied concern: assuming that MHCBs cannot have genuine emotions, how this assumption may affect psychotherapy, and consequently the quality of treatment outcomes. We argue that if MHCBs lack emotions, they cannot have genuine (affective) empathy or utilise countertransference. Consequently, this gives reason to worry that MHCBs are (a) more liable to harm and (b) less likely to benefit patients than human therapists. We discuss some responses to this worry and conclude that further empirical research is necessary to determine whether these worries are valid. We conclude that, even if these worries are valid, it does not mean that we should never use MHCBs. By discussing the broader ethical debate on the clinical use of chatbots, we point towards how further research can help us establish ethical boundaries for how we should use mental health chatbots.

Patient Perceptions of Illness Causes and Treatment Preferences for Obsessive-Compulsive Disorder: A Mixed-Methods Study.

Obsessive-compulsive disorder (OCD) is a condition with high patient morbidity and mortality. Research shows that eliciting patient explanations about illness causes and treatment preferences promotes cross-cultural work and engagement in health services. These topics are in the Cultural Formulation Interview (CFI), a semi-structured interview first published in DSM-5 that applies anthropological approaches within mental health services to promote person-centered care. This study focuses on the New York City site of an international multi-site study that used qualitative-quantitative mixed methods to: (1) analyze CFI transcripts with 55 adults with OCD to explore perceived illness causes and treatment preferences, and (2) explore whether past treatment experiences are related to perceptions about causes of current symptoms. The most commonly named causes were circumstantial stressors (n = 16), genetics (n = 12), personal psychological traits (n = 9), an interaction between circumstantial stressors and participants' brains (n = 6), and a non-specific brain problem (n = 6). The most common treatment preferences were psychotherapy (n = 42), anything (n = 4), nothing (n = 4), and medications (n = 2). Those with a prior medication history had twice the odds of reporting a biological cause, though this was not a statistically significant difference. Our findings suggest that providers should ask patients about illness causes and treatment preferences to guide treatment choice.

Which psychotherapy is most effective and acceptable in the treatment of adults with a (sub)clinical borderline personality disorder? A systematic review and network meta-analysis.

A broad range of psychotherapies have been proposed and evaluated in the treatment of borderline personality disorder (BPD), but the question which specific type of psychotherapy is most effective remains unanswered. In this study, two network meta-analyses (NMAs) were conducted investigating the comparative effectiveness of psychotherapies on (1) BPD severity and (2) suicidal behaviour (combined rate). Study drop-out was included as a secondary outcome. Six databases were searched until 21 January 2022, including RCTs on the efficacy of any psychotherapy in adults (⩾18 years) with a diagnosis of (sub)clinical BPD. Data were extracted using a predefined table format. PROSPERO ID:CRD42020175411. In our study, a total of 43 studies (N = 3273) were included. We found significant differences between several active comparisons in the treatment of (sub)clinical BPD, however, these findings were based on very few trials and should therefore be interpreted with caution. Some therapies were more efficacious compared to GT or TAU. Furthermore, some treatments more than halved the risk of attempted suicide and committed suicide (combined rate), reporting RRs around 0.5 or lower, however, these RRs were not statistically significantly better compared to other therapies or to TAU. Study drop-out significantly differed between some treatments. In conclusion, no single treatment seems to be the best choice to treat people with BPD compared to other treatments. Nevertheless, psychotherapies for BPD are perceived as first-line treatments, and should therefore be investigated further on their long-term effectiveness, preferably in head-to-head trials. DBT was the best connected treatment, providing solid evidence of its effectiveness.

Risk factors of chronic course of anxiety and depressive disorders: a 3-year longitudinal study in the general population.

BACKGROUND: Risk factors of a chronic course of anxiety and depressive disorders were previously studied using a limited definition of recovery, i.e. remission of the index disorder. However, frequently, other mental disorders are present at follow-up. Thus, the course of anxiety and depressive disorders was represented too rosy and the identified determinants may not apply when using a broader, more realistic definition. Additionally, physical health risk factors have often been ignored. METHODS: Data were used from two waves of the Netherlands Mental Health Survey and Incidence Study-2 including 509 respondents with 12-month anxiety disorder (panic disorder, social phobia, agoraphobia or generalized anxiety disorder) or/and major depressive disorder at baseline. Chronic course was defined as (1) presence of index disorder; and (2) presence of any anxiety, mood or substance use disorder (overall course) during the subsequent three years. Regression models were built with sociodemographic, clinical, and lifestyle/physical health indicators. Predictive accuracy was evaluated with area under the curve (AUC). RESULTS: Chronic course of the index disorder was present among 24.8% of cases, whereas 38.7% had a chronic overall course. The accuracy of prediction of chronic course of the index disorder was suboptimal (AUC = 0.68) compared to prediction of overall course (AUC = 0.75). The main risk factors were baseline number of mental disorders, neuroticism, childhood abuse, parental psychopathology and alcohol use. Lifestyle and physical health indicators were marginally relevant. CONCLUSION: Transdiagnostic risk factors are important in predicting overall course of anxiety and depressive disorders but cannot accurately predict chronic course of the index disorder.

Schema therapy with cognitive behaviour day-treatment in patients with treatment-resistant anxiety disorders and obsessive-compulsive disorder: an uncontrolled pilot study.

BACKGROUND: Treatment resistance in patients with anxiety disorders and obsessive-compulsive disorder (OCD) might be caused by dysfunctional personality traits or, more specifically, early maladaptive schemas (EMSs) and schema modes, that can be treated with schema therapy (ST). AIM: To explore possible effectiveness of ST-CBT day-treatment in patients with treatment-resistant anxiety disorders and OCD in an uncontrolled pilot study. METHOD: Treatment-resistant patients with anxiety disorders or OCD (n = 27) were treated with ST-CBT day-treatment for 37 weeks on average including 11.5 therapy hours per week. The Symptom Questionnaire-48, Young Schema Questionnaire-2 and Schema Mode Inventory were completed before and after treatment. RESULTS: General psychopathology, EMSs and schema modes significantly improved after treatment. Spearman's correlations between pre- to post-treatment difference scores of general psychopathology, EMSs and schema modes were significant and high. The level of pre-treatment EMSs and schema modes did not predict post-treatment general psychopathology. CONCLUSIONS: Symptom reduction was strongly correlated with improvement of EMSs and schema modes. Stronger pre-treatment EMSs and schema modes did not hinder improvement of symptoms. ST-CBT day-treatment is promising for patients with treatment-resistant anxiety disorders and OCD. Further controlled research is needed to substantiate evidence for schema therapy in patients with treatment-resistant anxiety disorders and OCD.

Group autonomy enhancing treatment versus cognitive behavioral therapy for anxiety disorders: A cluster-randomized clinical trial.

BACKGROUND: Although cognitive behavioral therapy (CBT) is effective in the treatment of anxiety disorders, few evidence-based alternatives exist. Autonomy enhancing treatment (AET) aims to decrease the vulnerability for anxiety disorders by targeting underlying autonomy deficits and may therefore have similar effects on anxiety as CBT, but yield broader effects. METHODS: A multicenter cluster-randomized clinical trial was conducted including 129 patients with DSM-5 anxiety disorders, on average 33.66 years of age (SD = 12.57), 91 (70.5%) female, and most (92.2%) born in the Netherlands. Participants were randomized over 15-week groupwise AET or groupwise CBT and completed questionnaires on anxiety, general psychopathology, depression, quality of life, autonomy-connectedness and self-esteem, pre-, mid-, and posttreatment, and after 3, 6, and 12 months (six measurements). RESULTS: Contrary to the hypotheses, effects on the broader outcome measures did not differ between AET and CBT (d = .16 or smaller at post-test). Anxiety reduction was similar across conditions (d = .059 at post-test) and neither therapy was superior on long term. CONCLUSION: This was the first clinical randomized trial comparing AET to CBT. The added value of AET does not seem to lie in enhanced effectiveness on broader outcome measures or on long term compared to CBT. However, the study supports the effectiveness of AET and thereby contributes to extended treatment options for anxiety disorders.

The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression.

This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion-this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Barriers and facilitators for treatment-seeking in adults with a depressive or anxiety disorder in a Western-European health care setting: a qualitative study.

BACKGROUND: Previous research on barriers and facilitators regarding treatment-seeking of adults with depressive and anxiety disorders has been primarily conducted in the Anglosphere. This study aims to gain insight into treatment-seeking behaviour of adults with depressive and anxiety disorders in a European healthcare system. METHODS: In-depth semi-structured interviews were conducted with 24 participants, aged ≥18 years and diagnosed with an anxiety disorder and/or depressive disorder according to DSM-IV. Participants were purposively sampled from an outpatient department for mental health care in the Netherlands. The seven steps of framework analysis were used to identify relevant themes emerging from the interviews. RESULTS: Data analysis suggested an interplay between individual aspects, personal social system, healthcare system and sociocultural context influences. Amongst the most relevant themes were mental health illiteracy, stigma, a negative attitude toward professional help, the influence of significant others and general practitioner, and waiting time. Financial barriers were not of relevance. CONCLUSIONS: Even in a country with a well-developed mental health care system and in absence of financial barriers, there are many barriers to treatment-seeking in adult patients with depressive and anxiety disorders. National campaigns to increase awareness and decrease stigma in the general population, and to empower the social environment might reduce the treatment gap.

Guidelines improve patient outcomes in specialised mental health care: A systematic review and meta-analysis.

OBJECTIVE: The uptake of evidence-based guideline recommendations appears to be challenging. In the midst of the discussion on how to overcome these barriers, the question of whether the use of guidelines leads to improved patient outcomes threatens to be overlooked. This study examined the effectiveness of evidence-based guidelines for all psychiatric disorders on patient health outcomes in specialist mental health care. All types of evidence-based guidelines, such as psychological and medication-focused guidelines, were eligible for inclusion. Provider performance was measured as a secondary outcome. Time to remission when treated with the guidelines was also examined. METHOD: Six databases were searched until 10 August 2020. Studies were selected, and data were extracted independently according to the PRISMA guidelines. Random effects meta-analyses were used to pool estimates across studies. Risk of bias was assessed according to the Cochrane Effective Practice and Organization of Care Review Group criteria. PROSPERO: CRD42020171311. RESULTS: The meta-analysis included 18 studies (N = 5380). Guidelines showed a positive significant effect size on the severity of psychopathological symptoms at the patient level when compared to treatment-as-usual (TAU) (d = 0.29, 95%-CI = (0.19, 0.40), p < 0.001). Removal of a potential outlier gave globally the same results with Cohen's d = 0.26. Time to remission was shorter in the guideline treatment compared with TAU (HR = 1.54, 95%-CI = (1.29, 1.84), p = 0.001, n = 3). CONCLUSIONS: Patients cared for with guideline-adherent treatments improve to a greater degree and more quickly than patients treated with TAU. Knowledge on the mechanisms of change during guideline-adherent treatment needs to be developed further such that we can provide the best possible treatment to patients in routine care.

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature.

OBJECTIVE: In the last decade, repetitive transcranial magnetic stimulation (rTMS) has been introduced as a non-invasive neuromodulation therapy for depression. Little is known, however, about (serious) adverse events (AE) of rTMS in older adults with a depression. In this article, we want to study what is known about (serious) AE of rTMS in older adults (>60 years) with late-life depression (LLD). METHODS: A systematic search has been performed according to the PRISMA guidelines in PubMed, EMBase and PsycInfo. We have screened 622 articles for eligibility. Eleven studies, evaluating 353 patients in total, were included in this review. RESULTS: AE were reported in 12.4% of the older adults with a LLD treated with rTMS, serious AE in 1.5%. Headache (6.9%) and discomfort at the stimulation site (2.7%) are the most commonly reported AE. Serious AE reported are: psychiatric hospitalization (three times), a combination of posterior vitreous detachment and retinal tear, and increased suicide ideation (both once). CONCLUSIONS: rTMS in older adults with LLD was concluded overall to be safe due to the low frequency of AE reported in trials and observational studies. In case-reports, however, more serious AE have been described. To tailor use of rTMS in older adults with LLD, more research is needed in larger samples to optimize tolerance.

Specific Phobia: Risk Factor of Other Psychiatric Disorders.

ABSTRACT: Predicting the onset and persistence of psychopathology and limited functioning might enable personalized care. Specific phobia (SP) might serve as a predictor, but this needs further evaluation. Participants of the Netherlands Mental Health Survey and Incidence Study-2 were divided into three groups: no-SP (n = 6094), history of SP (n = 204), and current SP (n = 348). Results showed that current SP was associated with a higher prevalence of other anxiety disorders, mood and substance use disorders, and lower levels of functioning. The 6-year onset of other anxiety disorders was associated with history and current SP. Current-SP was also associated with the onset of mood disorders. Neuroticism and childhood trauma only partly accounted for these associations. To conclude, SP was independently associated with presence and onset of other disorders and with limited functioning over time. The presence of SP may serve as an identifier of persons vulnerable to the development of other psychopathologies.

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.

Long-term disability in major depressive disorder: a 6-year follow-up study.

BACKGROUND: Major depressive disorder (MDD) represents a leading cause of disability. This study examines the course of disability in patients with chronic, recurrent and remitting MDD compared to healthy controls and identifies predictors of disability in remitting MDD. METHODS: We included 914 participants from the Netherlands Study of Depression and Anxiety (NESDA). DSM-IV MDD and WHO DAS II disability were assessed at baseline and at 2, 4 and 6 years. Six-year total and domain-specific disability were analysed and compared in participants with chronic (n = 57), recurrent (n = 120), remitting (n = 127) MDD and in healthy controls (n = 430). Predictors of residual disability were identified using linear regression analysis. RESULTS: At baseline, most disability was found in chronic MDD, followed by recurrent MDD, remitting MDD and healthy controls. Across diagnostic groups, most disability was found in household activities, interpersonal functioning, participation in society and cognition. A chronic course was associated with chronic disability. Symptom remission was associated with a decrease in disability, but some disability remained. In remitting MDD, higher residual disability was predicted by older age, more severe avoidance symptoms, higher disability at baseline and late symptom remission. Severity of residual disability correlated with the severity of residual depressive symptoms. CONCLUSIONS: Symptomatic remission is a prerequisite for improvements in disability. However, disability persists despite symptom remission. Therefore, treatment of MDD should include an explicit focus on disability, especially on the more complex domains. To this end, treatments should promote behavioural activation and address subthreshold depressive symptoms in patients with remitted MDD.

Prioritizing suicide prevention guideline recommendations in specialist mental healthcare: a Delphi study.

BACKGROUND: The Delphi technique is a proven and reliable method to create common definitions and to achieve convergence of opinion. This study aimed to prioritize suicide prevention guideline recommendations and to develop a set of quality indicators (QIs) for suicide prevention in specialist mental healthcare. METHODS: This study selected 12 key recommendations from the guideline to modify them into QIs. After feedback from two face-to-face workgroup sessions, 11 recommendations were rephrased and selected to serve as QIs. Next, a Delphi study with the 11 QIs was performed to achieve convergence of opinion among a panel of 90 participants (23 suicide experts, 23 members of patients' advisory boards or experts with experiences in suicidal behavior and 44 mental healthcare professionals). The participants scored the 11 QIs on two selection criteria: relevance (it affects the number of suicides in the institution) and action orientation (institutions or professionals themselves can influence it) using a 5-point Likert scale. Also, data analysts working in mental healthcare institutions (MHIs) rated each QI on feasibility (is it feasible to monitor and extract from existing systems). Consensus was defined as 70% agreement with priority scores of four or five. RESULTS: Out of the 11 recommendations, participants prioritized five recommendations as relevant and action-oriented in optimizing the quality of care for suicide prevention: 1) screening for suicidal thoughts and behavior, 2) safety plan, 3) early follow-up on discharge, 4) continuity of care and 5) involving family or significant others. Only one of the 11 recommendations early follow-up on discharge reached consensus on all three selection criteria (relevance, action orientation, and feasibility). CONCLUSIONS: The prioritization of relevant and action-oriented suicide prevention guideline recommendations is an important step towards the improvement of quality of care in specialist mental healthcare.

Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative.

BACKGROUND: Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2-3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. METHODS: We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. DISCUSSION: Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.

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.

The GET READY relapse prevention programme for anxiety and depression: a mixed-methods study protocol.

BACKGROUND: Since anxiety and depressive disorders often recur, self-management competencies are crucial for improving the long-term course of anxiety and depressive disorders. However, few relapse prevention programmes are available that focus on improving self-management. E-health combined with personal contact with a mental health professional in general practice might be a promising approach for relapse prevention. In this protocol, the GET READY (Guided E-healTh for RElapse prevention in Anxiety and Depression) study will be described in which a relapse prevention programme is developed, implemented and evaluated. The aim of the study is to determine patients' usage of the programme and the associated course of their symptoms, to examine barriers and facilitators of implementation, and to assess patients' satisfaction with the programme. METHODS: Participants are discharged from mental healthcare services, and are in complete or partial remission. They receive access to an E-health platform, combined with regular contact with a mental health professional in general practices. Online questionnaires will be completed at baseline and after 3, 6 and 9 months. Also, semi-structured qualitative individual interviews and focus group interviews will be conducted with patients and mental health professionals. DISCUSSION: This mixed-methods observational cohort study will provide insights into the use of a relapse prevention programme in relation to the occurrence of symptoms, as well as in its implementation and evaluation. Using the results of this study, the relapse prevention programme can be adapted in accordance with the needs of patients and mental health professionals. If this programme is shown to be acceptable, a randomized controlled trial may be conducted to test its efficacy. TRIAL REGISTRATION: Retrospectively registered in the Netherlands Trial Register ( NTR7574 ; 25 October 2018).

Effectiveness of a self-management training for patients with chronic and treatment resistant anxiety or depressive disorders on quality of life, symptoms, and empowerment: results of a randomized controlled trial.

BACKGROUND: Anxiety and depressive disorders are common mental disorders. A substantial part of patients does not achieve symptomatic remission after treatment in specialized services. Current care as usual (CAU) for these patients consists of long-term supportive contacts. Termination of CAU is often not considered to be an option due to persistent symptoms, a low level of functioning, and the absence of further treatment options. A new intervention, ZemCAD, offers a program focused on rehabilitation and self-management, followed by referral back to primary care. METHODS: This multicenter randomized controlled trial was carried out in twelve specialized outpatient mental health care services in the Netherlands. Consenting and eligible patients were invited for the MINI interview and the baseline questionnaire. Assessments were done at 6 (T1), 12 (T2) and 18 (T3) months post baseline. We used linear mixed model analysis (LMM) to ascertain the effectiveness of the ZemCAD group relative to the CAU group on quality of life, symptom severity and empowerment. RESULTS: In total 141 patients were included. The results at 18-month follow-up regarding to quality of life and symptom severity, showed no significant differences between the ZemCAD group and the CAU group, except on the 'social relationships'-domain (d = 0.37). With regard to empowerment a significant difference between both groups was observed in the total empowerment score and one empowerment dimension (d = 0.45 and d = 0.39, respectively). After the ZemCAD intervention, more patients went from specialized outpatient mental health services back to a less specialized health care setting with less intensive treatment, such as primary care. CONCLUSION: The findings in this study suggest that patients with chronic and treatment-resistant anxiety and depression using the ZemCAD intervention improve on empowerment but not on symptom severity or quality of life. Since little is known about the effects of rehabilitation and self-management in patients with chronic and treatment resistant anxiety and depressive disorders, this is a first attempt to provide a proof-of-concept study in this under-researched but important field. TRIAL REGISTRATION: Netherlands Trial Register: NTR3335 , registered 7 March 2012.

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.

Cannabidiol enhancement of exposure therapy in treatment refractory patients with phobias: study protocol of a randomized controlled trial.

BACKGROUND: Phobic anxiety disorders are among the most prevalent psychiatric disorders and are burdensome in terms of loss of quality of life and work productivity. Evidence-based treatments are relatively successful in the majority of patients, especially exposure therapy. However, a substantial subset of patients fails to achieve or stay in remission. Preclinical and genetic research have yielded evidence that the cannabinoid system is involved in the extinction of fear, presumed to underlie the beneficial effects of exposure therapy in phobic disorders. A cannabinoid constituent that may enhance endocannabinoid signaling is cannabidiol (CBD), a non-psychoactive component of cannabis. Hence, the addition of CBD to exposure therapy is expected to strengthen effects of treatment. To determine the added benefit of CBD on exposure therapy, we conduct a randomized controlled trial, in which patients in whom previous treatment as usual has not yielded sufficient response receive either CBD or placebo preceding 8 exposure sessions in a double-blind fashion. A subsidiary aim is to explore which (combination of) clinical, behavioral and genetic profiles of patients are related to treatment response. METHODS/DESIGN: This is an 8-week multicenter, randomized, double-blind, placebo-controlled trial. Seventy-two patients with social phobia or panic disorder with agoraphobia with incomplete response to earlier treatment will be included from outpatient clinics in the Netherlands. Patients are randomized to augmentation of exposure therapy with 300 mg CBD or placebo. The study medication is administered orally, 2 h preceding each of the eight 90 min exposure sessions. Measurements will take place at baseline, first administration of medication, every session, mid-treatment, last administration of medication, post-treatment and at 3 and 6 months' follow-up. The primary outcome measure is the score on the Fear Questionnaire (FQ). In addition, determinants of the expected treatment enhancing effect of CBD will be explored. DISCUSSION: This is the first trial to investigate whether the addition of CBD to exposure therapy is effective in reducing phobic symptoms in treatment refractory patients with social phobia or panic disorder with agoraphobia. TRIAL REGISTRATION: Netherlands Trial Register NTR5100 . Registered 13 March 2015. Protocol version: issue date 17 Jan 2018, protocol amendment number 7.