Atypical semantic cognition in schizotypal personality disorder and borderline personality disorder.

Increased schizotypal traits have previously been associated with atypical semantic cognition in community samples. However, no study has yet examined whether adults diagnosed with schizotypal personality disorder (SPD) display atypical semantic fluency and memory. We hypothesized that 24 adults diagnosed with SPD would name more idiosyncratic words on the semantic fluency task and show decreased semantic recall for animal and fruit category words compared with 29 participants with borderline personality disorder (BPD) and a community sample of 96 age-matched controls. We examined whether atypical semantic cognition was specifically associated with disorganized and eccentric speech and thinking, or more broadly with pathological personality traits and personality functioning. Our main hypothesis was confirmed, as the SPD participants named more idiosyncratic words and recalled fewer semantically related words compared with controls. Surprisingly, participants with BPD likewise named more atypical words compared with controls. More idiosyncratic semantic fluency was associated with more eccentric speech and thinking. Increased idiosyncratic semantic fluency and reduced semantic recall were both coupled to increased detachment and lowered personality functioning, while reduced semantic recall further was related to increased interpersonal problems. Our findings suggest that persons with SPD, and to a lesser degree BPD, show atypical semantic cognition, which is associated with eccentric speech and thinking, and more broadly with impaired personality function, social withdrawal, and emotional flatness. The idiosyncratic semantic cognition may worsen difficulties with social reciprocity seen in SPD and BPD.

Psychometric validation of the Danish version of the Major Depression Inventory using data from the Lolland-Falster health study (LOFUS).

PURPOSE: The Major Depression Inventory (MDI) is a widely used self-rating depression scale commonly in primary care in Denmark. It has not been subject to robust psychometric validation in a general population setting. The aim of this study was to evaluate the psychometric measurement properties of the MDI when applied in the general population. METHODS: We evaluated statistical psychometric validity using modern test theory (confirmatory factor analysis, item response theory models and Rasch measurement theory) testing local independence and differential item function across groups defined by gender, age, education, and chronic disease status. Separate analyses across different strata and across different statistical models were employed. RESULTS: Regarding structural validity we consistently identified local dependence for the item two pairs (MDI2,MDI3) and (MDI4,MDI5) across strata. This result was confirmed by bifactor CFA models and item screening. We further identified substantial differential item functioning with respect to age group and with respect to chronic disease. We identified quantified the magnitude of this lack of measurement invariance. CONCLUSION: The MDI is psychometrically valid in homogenous sub populations, but the disclosed evidence of local dependence means that published estimates of its reliability cannot be trusted. The lack of measurement invariance means that the instrument cannot be used to compare individuals or groups unless they are similar in terms of age group and chronic disease status.

The course of borderline personality disorder from adolescence to early adulthood: A 5-year follow-up study.

BACKGROUND: Studies of the medium- to long-term clinical and functional course for treatment-seeking adolescents with borderline personality disorder (BPD) are lacking. This study aims to outline the psychopathological and functional status of participants, five years after being diagnosed with BPD during adolescence. METHODS: Participants were originally enrolled in a randomized clinical trial that compared mentalization-based group treatment with treatment as usual for adolescents with BPD. Semi-structured interview assessments at five-year follow-up included the Schedules for Clinical Assessment in Neuropsychiatry and the Structured Clinical Interview for DSM-5 Personality Disorders. Attention deficit hyperactivity disorder (ADHD), alcohol, substance and tobacco use, posttraumatic stress disorder (PTSD), complex PTSD, and general functioning were assessed using self-report instruments. RESULTS: 97 of the original sample of 111 participants (87%) participated. They were aged 19-23 years. The most prevalent disorders were ADHD (59%), any personality disorder (47%) of which half continued to meet criteria for BPD (24%), anxiety disorders (37%), depressive disorders (32%), PTSD or complex PTSD (20%), schizophrenia (16%), and eating disorders (13%). Only 16% did not meet criteria for any mental disorder. Approximately half of the sample were in psychological and/or psychopharmacological treatment at the time of follow-up. Their general functioning remained impaired, with 36% not engaged in education, employment or training (NEET), which is nearly four times the rate of NEET in the same age group in the general population. CONCLUSIONS: Although stability of the categorical BPD diagnosis is modest, adolescents meeting diagnostic criteria for BPD show a broad range of poor outcomes at five-year follow-up. BPD appears to be a marker of general maladjustment during adolescence and a harbinger of severe problems during the transition to young adulthood. Early intervention programs for adolescents diagnosed with BPD should focus upon a broad range of functional and psychopathological outcomes, especially social and vocational support, rather than the narrow BPD diagnosis.

Examining psychotic experiences in two generations - findings from a rural household-based cohort study; the Lolland-Falster Health Study.

BACKGROUND: Psychotic disorders are highly heritable, yet the evidence is less clear for subclinical psychosis expression, such as psychotic experiences (PEs). We examined if PEs in parents were associated with PEs in offspring. METHODS: As part of the Danish general population Lolland-Falster Health Study, families with youths aged 11-17 years were included. Both children and parents reported PEs according to the Psychotic Like Experiences Questionnaire, counting only 'definite' PEs. Parents additionally reported depressive symptoms, anxiety, and mental wellbeing. The associations between parental and child PEs were estimated using generalized estimating equations with an exchangeable correlation structure to account for the clustering of observations within families, adjusting for sociodemographic characteristics. RESULTS: Altogether, 984 youths (mean age 14.3 years [s.d. 2.0]), 700 mothers, and 496 fathers from 766 households completed PEs-questionnaires. Offspring of parents with PEs were at an increased risk of reporting PEs themselves (mothers: adjusted risk ratio (aRR) 2.42, 95% CI 1.73-3.38; fathers: aRR 2.25, 95% CI 1.42-3.59). Other maternal problems (depression, anxiety, and poor mental well-being), but not paternal problems, were also associated with offspring PEs. In multivariate models adjusting for parental problems, PEs, but not other parental problems, were robustly associated with offspring PEs (mothers: aRR 2.25, 95% CI 1.60-3.19; fathers: aRR 2.44, 95% CI 1.50-3.96). CONCLUSIONS: The current findings add novel evidence suggesting that specific psychosis vulnerability in families is expressed at the lower end of the psychosis continuum, underlining the importance of assessing youths' needs based on psychosis vulnerability broadly within the family systems.

Co-occurrence of borderline and schizotypal personality disorders: a scoping review.

BACKGROUND: The historical concept of borderline conditions refers to the pathology on the border between neurosis and psychosis. In DSM-III the conditions were divided into specific but also somewhat overlapping diagnostic criteria for Borderline Personality Disorder (BPD) and Schizotypal Personality Disorder (SPD). This phenomenological overlap, which results in co-occurrence of the two diagnoses, remains a clinical challenge to this day. METHODS: To address this issue we examined the co-occurrence of SPD and BPD according to the established DSM-IV/-5 diagnostic criteria. A literature search was conducted including studies that employed a structured interview with defined BPD and SPD criteria. RESULTS: Studies from 20 samples were included (i.e. 15 patients, 3 community and 2 forensic samples). For patients diagnosed primarily with BPD, 1-27% also met the criteria for SPD and for patients diagnosed primarily with SPD, 5 - 33% showed co-occurrence with BPD. In the forensic samples, co-occurrence for primary BPD was 10% and 67 - 82% for primary SPD. In the community samples, co-occurrence for primary BPD was 29% and 50% for primary SPD. The pattern of co-occurrence across community samples was particularly heterogeneous. CONCLUSION: The identified co-occurrences for BPD and SPD were considerably sample-dependent, and samples and measurements were generally too heterogeneous for a precise meta-analysis. Forensic and community samples generally showed higher co-occurrences, but these findings were characterized by potential methodological limitations.

Non-prescribing of clozapine for outpatients with schizophrenia in real-world settings: The clinicians' perspectives.

Clozapine is the gold standard for treating treatment-resistant schizophrenia although continuously underutilized. Previous surveys of clinicians have found that some of the most frequently cited barriers to clozapine prescribing are related to the blood-monitoring requirements. However, these surveys tend to explore general perspectives and may not reflect the true impact of different barriers in real-world outpatient settings. This study aimed to explore this issue. First, by surveying the clinicians responsible for the treatment of 39 clozapine-eligible, yet clozapine-naive, outpatients with schizophrenia. Then, based on the survey results, explanatory interviews with the participating psychiatrists were conducted and analyzed thematically. The most frequently cited reason for non-prescribing of clozapine was the expected non-compliance with blood-monitoring requirements; however, overall stability and/or severe mental illness was chosen as the most important reason in most patient-cases. The qualitative analysis highlighted the combined impact of standard clinical practice, personal experiences, and organizational constraints on clozapine utility.

Facilitating In-House Mobile App Development Within Psychiatric Outpatient Services for Patients Diagnosed With Borderline Personality Disorder: Rapid Application Development Approach.

BACKGROUND: Mobile app development within mental health is often time- and resource-consuming, challenging the development of mobile apps for psychiatry. There is a continuum of software development methods ranging from linear (waterfall model) to continuous adaption (Scrum). Rapid application development (RAD) is a model that so far has not been applied to psychiatric settings and may have some advantages over other models. OBJECTIVE: This study aims to explore the utility of the RAD model in developing a mobile app for patients with borderline personality disorder (BPD) in a psychiatric outpatient setting. METHODS: The 4 phases of the RAD model: (1) requirements planning, (2) user design, (3) construction, and (4) cutover, were applied to develop a mobile app within psychiatric outpatient services for patients diagnosed with BPD. RESULTS: For the requirements planning phase, a short time frame was selected to minimize the time between product conceptualization and access within a clinical setting. Evidenced-based interactive content already developed was provided by current staff to enhance usability and trustworthiness. For the user design phase, activity with video themes and a discrete number of functions were used to improve the app functionality and graphical user interface. For the construction phase, close collaboration between clinicians, researchers, and software developers yielded a fully functional, in-house-developed app ready to be tested in clinical practice. For the cutover phase, the mobile app was tested successfully with a small number (n=5) of patients with a BPD. CONCLUSIONS: The RAD model could be meaningfully applied in a psychiatric setting to develop an app for BPD within a relatively short time period from conceptualization to implementation in the clinic. Short time frames and identifying a limited number of stakeholders with relevant skills in-house facilitated the use of this model. Despite some limitations, RAD could be a useful model in the development of apps for clinical populations to enable development and access to evidence-based technology.

How first-episode psychosis patients' subjective beliefs about their childhood trauma's causal effect provide support for potential schizophrenia subtypes.

BACKGROUND: Childhood and adolescent trauma is a risk factor for developing psychosis-spectrum disorders. The current study aimed to assess how childhood trauma might predict psychosis symptomatology, and how patients' beliefs of whether trauma is the cause of psychosis might affect this association. METHODS: Ninety-six first-episode psychosis patients were assessed for childhood traumatic experiences with the Brief Betrayal Trauma Survey, and for psychosis symptoms with the Positive and Negative Syndrome Scale. RESULTS: Non-interpersonal trauma predicted higher positive symptoms, whereas more trauma domains experienced predicted lower negative symptoms. Almost half of the participants believed trauma to be related to psychosis, were 12 times more likely to reexperience trauma through psychosis, and had higher excitative and emotional symptoms. Non-interpersonal trauma also predicted higher positive symptoms in this group. Those who did not believe trauma to be the cause of psychosis had higher negative symptoms, and a negative dose-response was found for negative and disorganised symptoms, in which more trauma domains experienced predicted lower scores. CONCLUSIONS: Results imply two traumagenic pathways to psychosis, one characterised by positive, excitative, and emotional symptoms, and one negative subtype, characterised by negative and disorganised symptoms. Clinical implications for how findings might contribute to better treatments are discussed.

ICD-11 personality disorder features in the danish general population: Cut-offs and prevalence rates for severity levels.

INTRODUCTION: Prevalence rates and correlates of personality disorders (PD) are relevant to health care policy and planning. OBJECTIVES: To present normative data for self-reported ICD-11 personality disorder (PD) features including tentative cut-off scores and prevalence rates for severity levels along with psychosocial correlates. METHODS: The Personality Disorder Severity ICD-11 (PDS-ICD-11) scale and criterion measures of impairment were administered to a social-demographically stratified sample of Danish citizens (N = 8,941) of which 3,044 delivered complete data. Item-Response Theory (IRT) was employed to indicate cut-offs based on standard deviations from the latent mean. RESULTS: The unidimensionality of the PDS-ICD-11 score was supported and IRT analysis suggested norm-based thresholds at latent severity levels. Expected associations with criterion measures were found. CONCLUSION: The normative data portray ICD-11 PD features in the general population and allow for interpretation of PDS-ICD-11 scores (e.g., scores of 12, 16, and 19 may indicate mild, moderate, and severe dysfunction), which may inform health care policy and planning. A total weighted prevalence of 6.9 % of the Danish general population is estimated to have clinically significant personality dysfunction, proportionally composed of Mild (4.8 %), Moderate (1.2 %), and Severe (0.9 %) levels. Future research should corroborate these findings using relevant clinical samples and methods.

Correction: Psychiatric Treatment Conducted via Telemedicine Versus In-Person Modality in Posttraumatic Stress Disorder, Mood Disorders, and Anxiety Disorders: Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.2196/44790.].

Prevalence and incidence of personality disorders among children and adolescents in Danish mental health services: a nationwide register study.

A few epidemiological studies have examined personality disorders (PDs) among children and adolescents in secondary mental health services. This study aims to describe the prevalence and incidence of PDs among children and adolescents who have attended Danish child and adolescent psychiatric services (CAPS). Using register-based data, we studied all patients under the age of 18 years who were admitted to in- and outpatient CAPS (N = 115,121) in Denmark from 2007 to 2017. A total of 4952 patients were diagnosed with a PD during the study period. The mean prevalence was 859 patients per year, and the mean incidence was 274 patients per year, including an increased incidence and prevalence of borderline, anxious, and unspecified PDs over the decade. The number of patients diagnosed with PDs increased from 700 to 851 per year, but the proportion of patients with PDs compared to all psychiatric diagnoses decreased from 4.2% to 2.8% over the study period. The PD population had an older age (14.8 years vs. 11.3 years; p < 0.001), a higher likelihood of being female (74% vs. 44%; p < 0.001), and four times more contacts with the psychiatric emergency departments than other patients with a psychiatric diagnosis. Future studies should focus on (a) implementing further epidemiological studies in different countries; (b) tracking diagnostic practices to facilitate comparisons and provide feedback for training clinicians and raising awareness; and (c) estimating trajectories of PDs, including costs within the CAPS, to facilitate informed decision-making regarding the future organization and provision of services to these children, adolescents, and their families.

Psychiatric Treatment Conducted via Telemedicine Versus In-Person Modality in Posttraumatic Stress Disorder, Mood Disorders, and Anxiety Disorders: Systematic Review and Meta-Analysis.

BACKGROUND: Telemedicine has played a vital role in providing psychiatric treatment to patients during the rapid transition of services during the COVID-19 pandemic. Furthermore, the use of telemedicine is expected to expand within the psychiatric field. The efficacy of telemedicine is well described in scientific literature. However, there is a need for a comprehensive quantitative review that analyzes and considers the different clinical outcomes and psychiatric diagnoses. OBJECTIVE: This paper aimed to assess whether individual psychiatric outpatient treatment for posttraumatic stress disorder, mood disorders, and anxiety disorders in adults using telemedicine is equivalent to in-person treatment. METHODS: A systematic search of randomized controlled trials was conducted using recognized databases for this review. Overall, 4 outcomes were assessed: treatment efficacy, levels of patient satisfaction, working alliance, and attrition rate. The inverse-variance method was used to summarize the effect size for each outcome. RESULTS: A total of 7414 records were identified, and 20 trials were included in the systematic review and meta-analysis. The trials included posttraumatic stress disorder (9 trials), depressive disorder (6 trials), a mix of different disorders (4 trials), and general anxiety disorder (1 trial). Overall, the analyses yielded evidence that telemedicine is comparable with in-person treatment regarding treatment efficacy (standardized mean difference -0.01, 95% CI -0.12 to 0.09; P=.84; I2=19%, 17 trials, n=1814), patient satisfaction mean difference (-0.66, 95% CI -1.60 to 0.28; P=.17; I2=44%, 6 trials, n=591), and attrition rates (risk ratio 1.07, 95% CI 0.94-1.21; P=.32; I2=0%, 20 trials, n=2804). The results also indicated that the working alliance between telemedicine and in-person modalities was comparable, but the heterogeneity was substantial to considerable (mean difference 0.95, 95% CI -0.47 to 2.38; P=.19; I2=75%, 6 trials, n=539). CONCLUSIONS: This meta-analysis provided new knowledge on individual telemedicine interventions that were considered equivalent to in-person treatment regarding efficacy, patient satisfaction, working alliance, and attrition rates across diagnoses. The certainty of the evidence regarding efficacy was rated as moderate. Furthermore, high-quality randomized controlled trials are needed to strengthen the evidence base for treatment provided via telemedicine in psychiatry, particularly for personality disorders and a range of anxiety disorders where there is a lack of studies. Individual patient data meta-analysis is suggested for future studies to personalize telemedicine. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021256357; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=256357.

Association between early suicidal trajectories in first-episode psychosis and 10-year follow-up: TIPS registry-linked study.

BACKGROUND: Although the risk of suicidality is high in first-episode psychosis, patterns and individual variability in suicidal thoughts and behaviours over time are under-researched. We aimed to identify early trajectories of suicidality over a 2-year follow-up, assess their baseline predictors, and explore associations between those trajectories and later suicidality. METHODS: This longitudinal follow-up study was a part of the Early Treatment and Intervention in Psychosis (TIPS)study. Participants, linked to Norwegian and Danish death registries, were recruited from four catchment areas (665 000 inhabitants) in Norway and Denmark (both inpatient and outpatient). We included participants aged 15-65 years, with an intelligence quotient of more than 70, willing to give informed consent, and with a first episode of active psychotic symptoms. Individuals with comorbid neurological or endocrinal disorders, or those with contraindications to antipsychotics, were excluded. Growth mixture modelling was used to identify trajectories of suicidal thoughts and behaviours over the first 2 years. Multinomial logistic regression was applied to examine the baseline predictors of those trajectories and their associations with suicidality at 10-year follow-up. FINDINGS: A total of 301 participants were recruited from Jan 1, 1997, to Dec 31, 2000. Of the 299 with completed suicidality data at baseline, 271 participated in 1-year follow-up, 250 in 2-year follow-up, 201 in 5-year follow-up, and 186 at 10-year follow-up. At baseline, 176 (58%) were male, 125 (42%) were female. The mean age was 27·80 years (SD 9·64; range 15-63). 280 (93%) participants were of Scandinavian origin. Four trajectories over 2 years were identified: stable non-suicidal (217 [72%]), stable suicidal ideation (45 [15%]), decreasing suicidal thoughts and behaviours (21 [7%]), and worsening suicidal thoughts and behaviours (18 [6%]). A longer duration of untreated psychosis (odds ratio [OR] 1·24, 95% CI 1·02-1·50, p=0·033), poorer premorbid childhood social adjustment (1·33, 1·01-1·73, p=0·039), more severe depression (1·10, 1·02-1·20, p=0·016), and substance use (2·33, 1·21-4·46, p=0·011) at baseline predicted a stable suicidal ideation trajectory. Individuals in the stable suicidal ideation trajectory tended to have suicidal thoughts and behaviours at 10-year follow-up (3·12, 1·33-7·25, p=0·008). Individuals with a worsening suicidal trajectory were at a higher risk of death by suicide between 2 and 10 years (7·58, 1·53-37·62, p=0·013). INTERPRETATION: Distinct suicidal trajectories in first-episode psychosis were associated with specific predictors at baseline and distinct patterns of suicidality over time. Our findings call for early and targeted interventions for at-risk individuals with persistent suicidal ideation or deteriorating patterns of suicidal thoughts and behaviours, or both. FUNDING: Health West, Norway; the Norwegian National Research Council; the Norwegian Department of Health and Social Affairs; the National Council for Mental Health and Health and Rehabilitation; the Theodore and Vada Stanley Foundation; the Regional Health Research Foundation for Eastern Region, Denmark; Roskilde County, Helsefonden, Lundbeck Pharma; Eli Lilly; Janssen-Cilag Pharmaceuticals, Denmark; a National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award and The National Institute of Mental Health grant; a National Alliance for Research on Schizophrenia & Depression Young Investigator Award from The Brain & Behavior Research Foundation; Health South East; Health West; and the Regional Centre for Clinical Research in Psychosis.

Childhood trauma, antipsychotic medication, and symptom remission in first-episode psychosis.

BACKGROUND: To what extent psychotic symptoms in first-episode psychosis (FEP) with a history of childhood interpersonal trauma (CIT) are less responsive to antipsychotic medication is not known. In this longitudinal study, we compare symptom trajectories and remission over the first 2 years of treatment in FEP with and without CIT and examine if differences are linked to the use of antipsychotics. METHODS: FEP (N = 191) were recruited from in- and outpatient services 1997-2000, and assessed at baseline, 3 months, 1 and 2 years. Inclusion criteria were 15-65 years, actively psychotic with a DSM-IV diagnosis of psychotic disorder and no previous adequate treatment for psychosis. Antipsychotic medication is reported as defined daily dosage (DDD). CIT (<18) was assessed with the Brief Betrayal Trauma Survey, and symptomatic remission based on scores from the Positive and Negative Syndrome Scale. RESULTS: CIT (n = 63, 33%) was not associated with symptomatic remission at 2 years follow-up (71% in remission, 14% in relapse), or time to first remission (CIT 12/ no-CIT 9 weeks, p = 0.51). Those with CIT had significantly more severe positive, depressive, and excited symptoms. FEP with physical (N = 39, 20%) or emotional abuse (N = 22, 14, 7%) had higher DDD at 1 year (p < 0.05). Mean DDD did not excerpt a significant between-group effect on symptom trajectories of positive symptoms. CONCLUSION: Results indicate that antipsychotic medication is equally beneficial in the achievement of symptomatic remission in FEP after 2 years independent of CIT. Still, FEP patients with CIT had more severe positive, depressive, and excited symptoms throughout.

Narrative Identity within Mentalization-Based Group Therapy for Adolescents: A Feasibility Study.

Borderline personality disorder (BPD) is characterized by severe disturbances related to understanding oneself and other people and can be reliably detected and treated in adolescence. In this feasibility study, we aimed to focus on the features of, and changes in, narrative identity throughout the course of Mentalization-Based Treatment in Groups (MBT-G) for adolescents with BPD. Six female patients (M = 15.2, SD = 0.75) joined between 16 and 31 (M = 23.83) MBT g sessions. The narrated events within each session across sessions were coded for themes of agency and communion and the narrated reactions were coded for personality functioning. The patients and their parents also completed several self-report measures before and after therapy. Themes of diminished agency and communion were identified, with communion as the dominating theme. When comparing the patients' first five sessions with their last five sessions, there was an increase in themes related to agency and decreased in communion. The narrated reactions were dominated by themes related to thwarted self-functioning and primarily identity, although intimacy was also present. Patients improved in terms of self-reported functioning and internalizing and externalizing behavior before and after end of treatment. The importance of narration in BPD (group) therapy is discussed alongside clinical implications.

Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD).

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children and adolescents with ADHD find it difficult to pay attention and they are hyperactive and impulsive. Methylphenidate is the psychostimulant most often prescribed, but the evidence on benefits and harms is uncertain. This is an update of our comprehensive systematic review on benefits and harms published in 2015. OBJECTIVES: To assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases and two trials registers up to March 2022. In addition, we checked reference lists and requested published and unpublished data from manufacturers of methylphenidate. SELECTION CRITERIA: We included all randomised clinical trials (RCTs) comparing methylphenidate versus placebo or no intervention in children and adolescents aged 18 years and younger with a diagnosis of ADHD. The search was not limited by publication year or language, but trial inclusion required that 75% or more of participants had a normal intellectual quotient (IQ > 70). We assessed two primary outcomes, ADHD symptoms and serious adverse events, and three secondary outcomes, adverse events considered non-serious, general behaviour, and quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and risk of bias assessment for each trial. Six review authors including two review authors from the original publication participated in the update in 2022. We used standard Cochrane methodological procedures. Data from parallel-group trials and first-period data from cross-over trials formed the basis of our primary analyses. We undertook separate analyses using end-of-last period data from cross-over trials. We used Trial Sequential Analyses (TSA) to control for type I (5%) and type II (20%) errors, and we assessed and downgraded evidence according to the GRADE approach. MAIN RESULTS: We included 212 trials (16,302 participants randomised); 55 parallel-group trials (8104 participants randomised), and 156 cross-over trials (8033 participants randomised) as well as one trial with a parallel phase (114 participants randomised) and a cross-over phase (165 participants randomised). The mean age of participants was 9.8 years ranging from 3 to 18 years (two trials from 3 to 21 years). The male-female ratio was 3:1. Most trials were carried out in high-income countries, and 86/212 included trials (41%) were funded or partly funded by the pharmaceutical industry. Methylphenidate treatment duration ranged from 1 to 425 days, with a mean duration of 28.8 days. Trials compared methylphenidate with placebo (200 trials) and with no intervention (12 trials). Only 165/212 trials included usable data on one or more outcomes from 14,271 participants. Of the 212 trials, we assessed 191 at high risk of bias and 21 at low risk of bias. If, however, deblinding of methylphenidate due to typical adverse events is considered, then all 212 trials were at high risk of bias. PRIMARY OUTCOMES: methylphenidate versus placebo or no intervention may improve teacher-rated ADHD symptoms (standardised mean difference (SMD) -0.74, 95% confidence interval (CI) -0.88 to -0.61; I² = 38%; 21 trials; 1728 participants; very low-certainty evidence). This corresponds to a mean difference (MD) of -10.58 (95% CI -12.58 to -8.72) on the ADHD Rating Scale (ADHD-RS; range 0 to 72 points). The minimal clinically relevant difference is considered to be a change of 6.6 points on the ADHD-RS. Methylphenidate may not affect serious adverse events (risk ratio (RR) 0.80, 95% CI 0.39 to 1.67; I² = 0%; 26 trials, 3673 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 0.91 (CI 0.31 to 2.68). SECONDARY OUTCOMES: methylphenidate may cause more adverse events considered non-serious versus placebo or no intervention (RR 1.23, 95% CI 1.11 to 1.37; I² = 72%; 35 trials 5342 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 1.22 (CI 1.08 to 1.43). Methylphenidate may improve teacher-rated general behaviour versus placebo (SMD -0.62, 95% CI -0.91 to -0.33; I² = 68%; 7 trials 792 participants; very low-certainty evidence), but may not affect quality of life (SMD 0.40, 95% CI -0.03 to 0.83; I² = 81%; 4 trials, 608 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: The majority of our conclusions from the 2015 version of this review still apply. Our updated meta-analyses suggest that methylphenidate versus placebo or no-intervention may improve teacher-rated ADHD symptoms and general behaviour in children and adolescents with ADHD. There may be no effects on serious adverse events and quality of life. Methylphenidate may be associated with an increased risk of adverse events considered non-serious, such as sleep problems and decreased appetite. However, the certainty of the evidence for all outcomes is very low and therefore the true magnitude of effects remain unclear. Due to the frequency of non-serious adverse events associated with methylphenidate, the blinding of participants and outcome assessors is particularly challenging. To accommodate this challenge, an active placebo should be sought and utilised. It may be difficult to find such a drug, but identifying a substance that could mimic the easily recognised adverse effects of methylphenidate would avert the unblinding that detrimentally affects current randomised trials. Future systematic reviews should investigate the subgroups of patients with ADHD that may benefit most and least from methylphenidate. This could be done with individual participant data to investigate predictors and modifiers like age, comorbidity, and ADHD subtypes.

Concurrent validity of the anxiety symptom-scale compared to two well-being scales: results from the Lolland-Falster health study.

OBJECTIVE: To examine the concurrent validity of the Anxiety Symptom-scale against two well-being scales, the Cantril Ladder (CL) and World Health Organization Well-Being Index (WHO-5), to test the algorithm defining anxiety against these scales, and identify cut-off points for the Anxiety Symptom-scale sum score. SUBJECTS: 14,405 adult respondents completing all psychometric questions in the Lolland Falster Health Study. METHOD: Receiver operating characteristic analyses comparing Anxiety Symptom-scale WHO-5 and CL. RESULTS: 2.5% of respondents had an anxiety disorder (3% female and 2% male) according to the Anxiety Symptom-scale algorithm. The area under the curve (AUC) was 0.87 for CL and 0.90 for WHO-5 (using inverse scores), indicating high concordance with anxiety disorder as identified by the scale. A score solely ≥2 on item 10 is a relevant cut off to low wellbeing. Anxiety disorder covers a broad range on the scale's sum score, with 3 to 4 indicating low well-being in this population sample and a sensitivity of 0.85 - 0.99 against CL and WHO-5. CONCLUSION: The Anxiety Symptom-scale is a sensitive and valid instrument for the identification of patients in low well-being with symptoms of anxiety. A score ≥2 on the functional impact (Item 10) of all symptoms is a relevant indicator of anxiety associated with low well-being in this sample. A higher Anxiety Symptom-scale sum score is coherent with lower well-being, though without specific cut-off points. Further validation of the Anxiety Symptom-scale in a clinical setting is recommended.

Clinical trials in personality disorders: Recommendations for study design and conduct.

Borderline personality disorder (BPD) is a highly studied condition. During the last 3 decades, the understanding of the disorder has substantially changed, based on thorough, accumulating research. At the same time, the interest in BPD is still not decreasing but continues to grow. This article aims to critically discuss research trends in clinical trials of personality disorders in general and BPD in particular, to highlight topics that deserve closer attention, and to give recommendations for the design and conduct of future psychotherapy or pharmacotherapy studies in the field. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Antipsychotic prescribing practices for outpatients with schizophrenia and reasons for non-clozapine treatment - Data from a Danish quality assessment audit.

BACKGROUND: Clozapine is the gold standard for treating treatment-resistant schizophrenia (TRS) although widely underutilised. Both organisational, patient- and clinician related reasons for the underutilisation have been reported, however, the clinical impact of either in real-world settings is not fully elucidated. AIM: This audit aimed to evaluate the local antipsychotic (AP) prescribing practices for outpatients with schizophrenia and to assess the spectrum and prevalence of journalised reasons for non-clozapine treatment amongst eligible outpatients. METHODS: Data on demographics, current and former AP treatments, as well as documented reasons for non-clozapine treatment, was extracted through chart audit. RESULTS: Of the 668 affiliated outpatients with schizophrenia, 43% were treated with AP polytherapy (APP) and 19.6% with clozapine. The most prevalent reason for clozapine discontinuation was related to side effects whereas the most prevalent reason for refusal or omission of clozapine treatment was related to the associated monitoring regimen. CONCLUSIONS: This audit showed that APP prescribing is a highly prevalent practice in our services when treating outpatients with schizophrenia and that clozapine is underutilised in a 'last resort' manner. The blood-monitoring regimen associated with clozapine treatment was found to be an important factor in the underutilisation. It seemed, however, that the monitoring constituted a barrier for different reasons, requiring different approaches to remedy. Future studies, directly involving both patients and clinicians in the identification and management of the most clinically relevant barriers and their corresponding facilitators, are warranted.