Comorbid Personality Disorders Research Articles

A prediction model for electroconvulsive therapy effectiveness in patients with major depressive disorder from the Dutch ECT Consortium (DEC).

Reliable predictors for electroconvulsive therapy (ECT) effectiveness would allow a more precise and personalized approach for the treatment of major depressive disorder (MDD). Prediction models were created using a priori selected clinical variables based on previous meta-analyses. Multivariable linear regression analysis was used, applying backwards selection to determine predictor variables while allowing non-linear relations, to develop a prediction model for depression outcome post-ECT (and logistic regression for remission and response as secondary outcome measures). Internal validation and internal-external cross-validation were used to examine overfitting and generalizability of the model's predictive performance. In total, 1892 adult patients with MDD were included from 22 clinical and research cohorts of the twelve sites within the Dutch ECT Consortium. The final primary prediction model showed several factors that significantly predicted a lower depression score post-ECT: higher age, shorter duration of the current depressive episode, severe MDD with psychotic features, lower level of previous antidepressant resistance in the current episode, higher pre-ECT global cognitive functioning, absence of a comorbid personality disorder, and a lower level of failed psychotherapy in the current episode. The optimism-adjusted R² of the final model was 19%. This prediction model based on readily available clinical information can reduce uncertainty of ECT outcomes and hereby inform clinical decision-making, as prompt referral for ECT may be particularly beneficial for individuals with the above-mentioned characteristics. However, despite including a large number of pretreatment factors, a large proportion of the variance in depression outcome post-ECT remained unpredictable.

Comorbidity, Treatment, and Service Utilization Patterns in Difficult-to-Treat Depression Patients: A Retrospective Study in a Portuguese Community Mental Health Team

Background and Objectives: Observational studies with data from real-world clinical practice with patients with difficult-to-treat depression (DTD) are rare. This study aims to collect observational data from the real-world clinical practice of a Portuguese community mental health team (CMHT) on the prevalence of DTD and to explore differences between DTD and non-DTD groups. Materials and Methods: We conducted a retrospective chart review study using data from Electronic Health Records (EHRs) of adult patients with psychiatric disorders followed by a CMHT from the Department of Psychiatry of the Coimbra Local Health Unit (between 1 December 2020–31 December 2022). The Dutch Measure for quantification of Treatment Resistance in Depression (DM-TRD) was used to assess the degree of treatment resistance and the Charlson Comorbidity Index (CCI) to measure medical comorbidity. Results: A quantity of 473 patients were referred to Cantanhede CMHT for a first assessment. Of these, 219 patients met the criteria for a primary diagnosis of any depressive disorder. Assistant psychiatrists identified 57 patients with DTD during follow-up (approximately 26%). The DTD group had higher rates of depressive episodes, greater depression severity, increased service use, higher DM-TRD scores, and a higher prevalence of comorbid anxiety symptoms, personality disorders, and severe medical comorbidities. The DTD group also had a higher prescription rate of antidepressants. Differences were observed in the use of antidepressant augmentation strategies and in the prescription of anticoagulant/antiplatelet drugs and analgesics, with higher prescription rates in the DTD group. We found correlations between DM-TRD and CCI scores, and between DM-TRD scores and all service use variables. Conclusions: Our results are consistent with a similar study in the United Kingdom, highlighting the need for a different approach to the management of DTD patients, who continue to live with a significant burden despite usual pharmacological and non-pharmacological treatments.

Commentary on 'Comorbidity of bipolar disorder and borderline personality disorder: Phenomenology, course and treatment considerations' by Temes etal.

Commentary on 'Comorbidity of bipolar disorder and borderline personality disorder: Phenomenology, course and treatment considerations' by Temes etal.

Impact of Comorbid Personality Disorder on the Risk of Involuntary Hospitalization in Patients Referred for Urgent Forensic Assessment: A Cross-Sectional Study.

In Belgium, involuntary psychiatric hospitalization is authorized in the presence of certain criteria governed by the law relating to the protection of the mentally ill. The number of involuntary hospitalizations has been increasing continuously in recent years. Since personality disorders are frequent comorbidities in involuntarily hospitalized patients, the aim of this study was to investigate the potential role played by comorbid personality disorders in the decisions about involuntary hospitalization made during urgent forensic assessment. A total of 565 individuals were retrospectively recruited from the database of urgent forensic assessment carried out in the Psychiatric Emergency Department. Logistic regression analyses were performed to investigate the risk of involuntary hospitalization associated with comorbid personality disorders in patients referred for urgent forensic assessment. 66.7% of urgent forensic assessments resulted in involuntary hospitalization. In addition, comorbid personality disorders (especially borderline personality disorder) were associated with a lower risk of involuntary hospitalization in patients referred for urgent forensic assessment. In this study, we demonstrated that urgent forensic assessments frequently result in involuntary hospitalizations. Furthermore, this study highlighted that comorbid personality disorders (especially borderline personality disorder) appeared to have a major impact on the decision not to involuntarily hospitalize patients referred for urgent forensic assessment. These elements therefore justify the establishment of adequate clinical reflection to avoid the stigmatization related to these frequent comorbidities in patients at risk of involuntary hospitalization.

The interplay of personality pathology and treatment outcome in psychosomatic psychotherapy: A longitudinal analysis using latent change score modelling

IntroductionWhile ample data demonstrate the effectiveness of inpatient psychosomatic treatment, clinical observation and empirical evidence demonstrate that not all patients benefit equally from established therapeutic methods. Especially patients with a comorbid personality disorder often show reduced therapeutic success compared to other patient groups. Due to the heterogeneous and categorical personality assessment, previous studies indicated no uniform direction of this influence. This complicates the derivation of therapeutic recommendations for mental disorders with comorbid personality pathology. MethodsAnalyzing n = 2094 patients from German university hospitals enrolled in the prospective “MEPP” study, we tested the dynamic interaction between dimensionally assessed personality functioning and psychopathology of anxiety and depression. ResultsLongitudinal structural equation modelling replicated the finding that the severity of symptoms at admission predicts symptom improvement within the same symptom domain. In addition, we here report a significant coupling parameter between the baseline level of personality function and the change in general psychopathology - and vice versa. Discussion and conclusionThese results imply that personality pathology at admission hinders the therapeutic improvement in anxiety and depression, and that improvement of personality pathology is hindered by general psychopathology. Furthermore, the covariance between both domains supports the assumption that personality functioning and general psychopathology cannot be clearly distinguished and adversely influence each other. A dimensional assessment of the personality pathology is therefore recommendable for psychotherapy research and targeted therapeutic treatment.

Exploring real-world prescribing patterns for maintenance treatment in bipolar disorders: a focus on antidepressants and benzodiazepines

Objective Bipolar disorders (BD) are characterized by highly recurrent nature, necessitating adequate maintenance treatment for long-term disorder control. This study aimed to investigate real-world prescribing patterns among outpatients with BD, focusing on the utilisation of antidepressants (AD) and benzodiazepines (BDZ). Methods We analysed prescription patterns of the five main groups of psychotropic medications (antipsychotics, mood stabilizers, AD, BDZ, and anticholinergic medications) and their relationships with basic socio-demographic and clinical data in a sample of 107 clinically stable BD outpatients (75.7% female, age 44.8 ± 11.7). Results Maintenance therapy predominantly involved polypharmacy (92.5%), with mood stabilizers (87.9%) and antipsychotics (80.4%, predominantly second-generation) being the most commonly prescribed. Our findings highlight a high percentage of patients prescribed AD (50.5%) and BDZ (54.2%). BDZ patients, compared to the non-BDZ group in maintenance treatment, were significantly older with longer psychiatric history and a decreased likelihood of comorbid personality disorder diagnoses. Conclusions This study offers insights into prescribing practices within a university psychiatric clinic in the Western Balkans. The prevalent use of polypharmacy in real-world clinical settings, along with high percentage of patients prescribed AD and BDZ, suggests a gap between guideline recommendations and clinical practice, indicating a lack of consensus or standardized approaches in clinical practice.

Provider decisions to use evidence-based psychotherapy for PTSD among veterans: Assessments of overidentification with the sick role and comorbid personality disorders.

Provider decisions to use evidence-based psychotherapy for PTSD among veterans: Assessments of overidentification with the sick role and comorbid personality disorders.

Cognitive–behavioural therapy for complex post-traumatic stress disorder

SUMMARY Complex post-traumatic stress disorder (CPTSD) was adopted as a new diagnosis in ICD-11. Trauma-focused cognitive–behavioural therapy (CBT) is effective in treating PTSD but with CPTSD being a recently defined diagnosis, the evidence for its effectiveness in that disorder is not as clear, but it is still promising. This article reviews the diagnosis, psychopathology and some key differential diagnoses, and looks at the two CBT approaches that are currently used in clinical practice: the phase-oriented approach and the unimodal approach. The key aims of this article are to clarify the concept of CPTSD, its differentiation from borderline personality disorder and prominent comorbidities, how it develops and how CBT is used to treat it.

Evaluation of health services and treatment alliance among extensively hospitalized patients due to severe self-harm – results from the Extreme Challenges project

Background Extensive psychiatric hospitalization due to repeated severe self-harm (SH), is a poorly researched area, but a challenge within health services (HS). Recent studies have demonstrated high levels of involuntary treatment among patients with severe personality disorder (PD) and complex comorbidity. Keeping focus on extensively hospitalized SH patients, this study aimed to investigate patients’ and clinicians’ evaluation of HS and treatment alliance. Method A cross-sectional study with an inpatient sample (age >18 years) with frequent (>5) or long (>4 weeks) psychiatric hospital admissions last year due to SH or SA recruited from 12 hospitals across health regions (N = 42). Evaluation included patient and clinician report. Results A minority of the patients (14%) were satisfied with HS before the current admission, 45% (patients) and 20% (clinicians) found the current admission helpful, and 46% (patients) and 14% (clinicians) worried about discharge. Treatment complaints were received in 38% of the cases. Outpatient mental HS were available after discharge for 68% and a majority of clinicians indicated satisfactory contact across HS. More intensive or specialized formats were unusual (structured outpatient treatment 35%, day treatment 21%, ambulatory services 32%, planned inpatient services 31%). Mutual problem understanding, aims, and confidence in therapists during the hospital stay were limited (patient-rated satisfactory mutual problem understanding: 39%, aims of stay: 50%, confidence: 50%). Patient and therapist alliance-ratings were in concordance for the majority. Conclusion The study highlights poor HS satisfaction, poor patient–therapist coherence, limited treatment alliance and limited follow-up in structured treatments addressing SH or intermediary supportive ambulatory/day/inpatient services.

Dosage effects of psychodynamic and schema therapy in people with comorbid depression and personality disorder: four-arm pragmatic randomised controlled trial: commentary, Mulder.

Dosage effects of psychodynamic and schema therapy in people with comorbid depression and personality disorder: four-arm pragmatic randomised controlled trial: commentary, Mulder.

Comorbidity of bipolar disorder and borderline personality disorder: Phenomenology, course, and treatment considerations.

Bipolar disorder (BD) and borderline personality disorder (BPD) are both serious psychiatric conditions that elevate the risk for harmful outcomes. Although these conditions represent distinct diagnostic entities, existing research suggests that approximately 20% of individuals with BD meet the criteria for comorbid BPD. Individuals with comorbid BD/BPD appear to have a markedly more severe and phenomenologically distinct clinical course when compared with those with BD alone. However, treatments have generally not been tested in this specific population, and currently, no formal treatment guidelines exist for this subgroup of patients. In the current paper, we review the epidemiological and descriptive research characterizing those with comorbid BD/BPD and discuss the impact of this comorbidity on psychosocial treatment. We also review current findings on evidence-based treatments for BD and BPD that show promise in treating those with comorbid BD/BPD. In our review of the literature, we highlight the importance of recognizing this comorbidity and discuss avenues for developing and integrating evidence-based treatment approaches for this understudied clinical population. Although formal trials of interventions targeted to comorbid BD/BPD are limited, there is promising evidence regarding the possibility of using or integrating existing evidence-based approaches for this population. There are also several areas of clinical practice improvement and future research directions that stem from this literature.

A comprehensive investigation of comorbidities of prolonged grief disorder in a bereaved inpatient psychiatric sample

Prolonged Grief Disorder (PGD) was recently added to ICD-11 and DSM-5-TR. Depression and Posttraumatic Stress Disorder (PTSD) are frequent comorbidities, but findings regarding comorbid somatoform disorder and personality disorders remain mixed and studies with severely impaired patients are scarce. It was therefore the objective of the present study to examine comorbidities of PGD in a bereaved inpatient psychiatric sample. We assessed N = 101 bereaved inpatients in a psychiatric hospital with clinical interviews and self-report questionnaires. We calculated differences between patients with and without a PGD-diagnosis in number and type of comorbid disorders as well as associations between the severity of PGD and comorbid disorders. On average, patients had 2.53 comorbid psychiatric diagnoses. Patients with and without a PGD-diagnosis did not differ in their number of comorbid diagnoses, and there was no association between number of comorbid diagnoses and PGD-severity. However, patients with PGD, had significantly more comorbid diagnoses belonging to neurotic-, stress-related and somatoform disorders of the ICD-10. Patients with PGDICD-11 also had significantly higher scores in self-reported depressive, PTSD-, and somatoform symptoms, as well as the negative affectivity personality domain than those without a PGD diagnosis. To the best of our knowledge, this is the first study to provide insights into comorbidities of PGD in a bereaved inpatient psychiatric sample. It highlights the importance of considering PGD symptoms as part of the complaints of bereaved patients to achieve a tailored treatment approach. Future longitudinal studies are needed to unveil relationships between pre-existing mental disorders and PGD.

Predictors of treatment attendance in patients with posttraumatic stress disorder and comorbid personality disorders

IntroductionHigh dropout and low treatment attendance rates among patients with posttraumatic stress disorder (PTSD) and personality disorders (PDs) continue to pose a significant challenge. Despite numerous studies focusing on enhancing treatment attendance, the identification of consistent and reliable predictors in patients with PTSD and comorbid PDs remains limited. ObjectivesThis study aims to investigate a wide range of potential predictors of treatment attendance, encompassing demographic, patient-severity, treatment, and therapist-related variables in patients with PTSD and comorbid borderline and/or cluster C PDs. MethodsUtilizing data from 255 patients participating in two randomized controlled trials comparing trauma-focused treatment with or without concurrent PD treatment, candidate predictors were individually analyzed in univariate regression models. Significant predictors were then combined in a multiple ordinal regression model. ResultsIn total, 40% of patients attended fewer trauma-focused treatment sessions than the minimum recommended in treatment guidelines. Out of the 38 candidate predictors examined, five significant, independent predictors of treatment attendance emerged in a multiple ordinal regression model. Higher baseline PTSD severity (OR = 1.04, p = .036), higher education level (OR = 1.22, p = .009) and a stronger patient-rated working alliance (OR = 1.72, p = .047) with the therapist predicted higher treatment attendance. Conversely, inadequate social support from friends (OR = 0.90, p = .042) and concurrent PD treatment and trauma-focused treatment (OR = 0.52, p = .022) were associated with lower treatment attendance. ConclusionsIn conclusion, this constitutes the first study investigating predictors of treatment attendance in patients with PTSD and comorbid PDs. The results highlight the complexity of pinpointing reliable predictors. Nevertheless, the identification of five predictors provides valuable insights, aiding clinicians in customizing treatment strategies for individual patients and enhancing overall treatment attendance.

Personality disorders among a sample of Egyptian patients with major depressive disorder and their association with suicide

BackgroundDepression is a prevalent psychiatric disorder that can arise at any age and is often present as a co-occurring illness in different illnesses. There is a high comorbidity rate between major depressive disorder and personality disorders (PDs). The current study aimed to investigate the significant impact of personality disorders on depression severity, functional impairment, and suicidal tendencies in individuals with depression.MethodsThe researchers conducted a cross-sectional observational study involving 120 patients, with an age range from 18 to 56 years of both genders, recruited from Okasha’s Institute of Psychiatry in Cairo, Egypt. Their major depressive disorder diagnosis was verified through the use of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Participants underwent evaluations using the SCID-II to evaluate personality disorders, the Hamilton Depression-Rating Scale (HAM-D) to assess the severity of depression, the Columbia Suicide Severity Rating Scale (C-SSRS) to investigate suicidal ideation, and the Global Assessment of Functioning Scale (GAF) to determine functional level.ResultsBorderline personality disorder and narcissistic personality disorder were the predominant personality disorders in the sample, with prevalence rates of 55.8% and 40.8%, respectively. Sixty-six percent of the participants reported experiencing suicidal thoughts at some point in their lifetime, whereas only 17.5% had actually attempted suicide. Borderline personality disorder showed a strong correlation with more severe depression (P value 0.043), a decline in functioning (P value 0.001), the existence of suicidal thoughts (P value 0.001), and a past of suicide attempts (P value 0.038).ConclusionsPersonality disorders are highly prevalent in patients with depression, borderline PD, and narcissistic PD were the most common PDs. Borderline PD showed a significant effect on depression severity. PDs, mainly borderline, avoidant, depressive, and narcissistic PDs contribute to more impairment of functioning of the MDD patients. There is a significant effect of the presence of co-morbid personality disorder on suicidal thoughts and suicidal attempts, mainly depressive and borderline PDs.

Attachment security and disorganization in infants of mothers with severe psychiatric disorder: Exploring the role of comorbid personality disorder

The aim of this preliminary study was to explore infant-mother attachment quality in a Dutch clinical sample of mothers with severe psychiatric disorder, with or without comorbid personality disorder. Thirty-two mothers were recruited through specialized secondary and tertiary outpatient clinics and mental health institutions. Maternal psychiatric and personality diagnoses were verified with structured clinical interviews during pregnancy. Maternal concurrent level of psychiatric symptoms was assessed by self-report and infant-mother attachment quality by observation in the Strange Situation Procedure at 14 months postpartum. In the full sample, almost half of the infants were classified as disorganized. All infants of mothers with a comorbid personality disorder were classified as either insecure or disorganized. Infants of mothers with a comorbid personality disorder had a significantly higher disorganization score than infants of mothers with a psychiatric disorder only. Continuous attachment security scores did not differ significantly between groups. In the full sample, continuous infant attachment security and disorganization score were not significantly correlated with the level of maternal concurrent psychiatric symptoms. Our exploratory findings suggest a specific link between maternal psychiatric and comorbid personality disorder and attachment disorganization. Moreover, chronicity of symptoms appears more relevant for attachment behaviors than the severity of concurrent psychiatric symptoms. Maternal personality disorder may have a strong formative impact on infant attachment security and disorganization, which warrants further research to inform clinical practice, in order to reduce the risk of intergenerational transmission of maternal psychopathology.

Patient-related factors associated with patient retention and non-completion in psychosocial treatment of borderline personality disorder: A systematic review.

The potential efficacy of psychosocial interventions in the treatment of borderline personality disorder (BPD) is impacted by significant treatment non-completion (TNC), with meta-analytic studies reporting rates of attrition of between 25% and 28%. Increasing patient retention could facilitate outcomes and improve resource utilization, given limited healthcare services. A systematic search of PsycINFO, CINAHL, EMBASE, CENTRAL, and Web of Science Core Collection identified 33 articles that met the criteria for inclusion. Although substantial heterogeneity in terms of methodology and quality of analysis limited conclusions that could be drawn in the narrative review, a few consistent patterns of findings were elucidated, such as Cluster B personality disorder comorbidities and lower therapeutic alliance were associated with TNC. Interestingly, the severity of BPD symptoms was not a predictor of TNC. These findings are discussed in terms of their potential theoretical contribution to TNC. Clinically, there may be value in applying mindfulness and motivational interviewing strategies early on in treatment for individuals who present uncertainty about engaging in treatment. Further research to develop this empirical landscape includes focusing on high-powered replications, examining burgeoning lines of research, and investigating dynamic predictors of TNC.

Bipolar disorder with personality disorders: A difficult diagnosis

Bipolar disorder poses some diagnostic difficulties because it is colored by the personality of the patients. What complicates the problem are the personality disorders, which make the diagnosis difficult. Comorbid personality disorders are frequent and may complicate the course of bipolar illness. We have much information about treating patients with uncomplicated Bipolar Disorder (BD) but much less knowledge about possibilities for patients with the comorbidity of BD and personality disorder. This review tries to make a point to avoid confusion.

Translation and cross-cultural adaptation of the posttraumatic stress disorder checklist for DSM-5 for the Thai population

ObjectiveThis study aimed to perform a transcultural translation of the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) and assess its reliability within the Thai context. MethodsThe PCL-5 underwent a comprehensive translation process, including forward and backward translation, assessment by an expert panel, and comprehension testing by 10 patients with posttraumatic stress disorder (PTSD). The internal consistency of the overall scale and its subscales was examined using a sample of 100 patients with psychiatric disorders. Test-retest reliability was tested on Day 0 and Day 14. Confirmatory factor analyses were performed to assess structural validity and goodness-of-fit. ResultsExperts’ assessment of item-objective congruence indicated a satisfactory alignment of all items. The patients with PTSD demonstrated a strong understanding of the questionnaire. The translated PCL-5 exhibited excellent internal consistency (α = 0.96) with robust internal consistency of all subscales (α ranging from 0.86 to 0.91). The test-retest reliability was high (r = 0.82). Among the three structural models tested, the seven-factor Hybrid model provided the best fit to the data. Notably, patients with personality disorders scored the highest. ConclusionsThe Thai version of the PCL-5 demonstrates reliability, making it a valuable instrument for clinical application and future research among the Thai population. Patients with comorbid personality disorders may score higher on the PCL-5.

Client predictors of dropouts and outcomes in psychotherapy for generalized anxiety disorder: an exploratory study

ABSTRACT This study is a secondary analysis exploring client predictors of dropouts and outcomes in the treatment of generalized anxiety disorder (GAD). Data was taken from a feasibility randomized control trial (RCT) exploring the relative efficacy of emotion-focused therapy (EFT) compared with cognitive-behavioral therapy (CBT). Relationships between client characteristics and dropouts were explored using logistic regression analysis. Relationships between client characteristics and psychotherapy outcomes were explored using hierarchical linear regression analyses. For the full dataset (n = 58), a comorbid personality disorder predicted a higher number of dropouts. Eleven participants dropped out of therapy. Having a disability predicted less improvement in symptoms of depression and general distress. Being male-identified predicted a greater reduction in symptoms of anxiety and general distress, and comorbid agoraphobia predicted a greater reduction in symptoms of depression for the CBT condition (n = 21 completers). For the EFT condition (n = 26 completers), being older predicted greater improvements in symptoms of anxiety and comorbid panic disorder predicted a lower reduction in symptoms of depression. Caution should be taken in interpreting these findings given the small number of participants. However, they provide useful insights for the generation of hypotheses in relation to predictors of dropouts and outcomes for future studies.

Schema therapy versus treatment as usual for outpatients with difficult-to-treat depression: study protocol for a parallel group randomized clinical trial (DEPRE-ST)

BackgroundAbout one third of patients with depression are in a condition that can be termed as “difficult-to-treat”. Some evidence suggests that difficult-to-treat depression is associated with a higher frequency of childhood trauma and comorbid personality disorders or accentuated features. However, the condition is understudied, and the effects of psychotherapy for difficult-to-treat depression are currently uncertain. The aim of this trial is to investigate the beneficial and harmful effects of 30 sessions of individual schema therapy versus treatment as usual for difficult-to-treat depression in the Danish secondary, public mental health sector.MethodsIn this randomized, multi-centre, parallel-group, superiority clinical trial, 129 outpatients with difficult-to-treat depression will be randomized (1:1) to 30 sessions of individual schema therapy or treatment as usual; in this context mainly group-based, short-term cognitive behaviour or psychodynamic therapy. The primary outcome is the change from baseline in depressive symptoms 12 months after randomization, measured on the observer-rated 6-item Hamilton Rating Scale for Depression. The secondary outcomes are health-related quality of life assessed with the European Quality of Life 5 Dimensions 5 Level Version, functional impairment assessed with the Work and Social Adjustment Scale, psychological wellbeing assessed with the WHO-5 Well-being Index, and negative effects of treatment assessed with the Negative Effects Questionnaire. Exploratory outcomes are improvement on patient self-defined outcomes, personal recovery, anxiety symptoms, anger reactions, metacognitive beliefs about anger, and perseverative negative thinking. Outcomes will be assessed at 6, 12, and 24 months after randomization; the 12-month time-point being the primary time-point of interest. Outcome assessors performing the depression-rating, data managers, statisticians, the data safety and monitoring committee, and conclusion makers for the outcome article will be blinded to treatment allocation and results. To assess cost-effectiveness of the intervention, a health economic analysis will be performed.DiscussionThis trial will provide evidence on the beneficial and harmful effects, as well as the cost-effectiveness of schema therapy versus treatment as usual for outpatients with difficult-to-treat depression. The results can potentially improve treatment for a large and understudied patient group.Trial registrationClinicalTrials.gov NCT05833087. Registered on 15th April 2023 (approved without prompts for revision on 27th April 2023).