Liraglutide 3.0 mg once daily for the treatment of overweight and obesity in patients hospitalised at a forensic psychiatric department: A 26-week open-label feasibility study.

INTRODUCTION: Overweight and obesity constitute a major concern among patients treated at forensic psychiatric departments. The present clinical feasibility study aimed at investigating the extent to which glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment with once-daily liraglutide 3.0 mg could be a feasible pharmacological treatment of these conditions in patients with schizophrenia spectrum disorders hospitalised in forensic psychiatry. METHODS: The 26-week, open-label feasibility study included participants aged 18-65 years diagnosed with a severe mental illness and hospitalised at a forensic psychiatric department. At the time of inclusion, all participants fulfilled the indication for using liraglutide as a treatment for overweight and obesity. Participants' baseline examinations were followed by a 26-week treatment period with liraglutide injection once daily according to a fixed uptitration schedule of liraglutide, with a target dose of 3.0 mg. Each participant attended seven visits to evaluate the efficacy and adverse events. The primary endpoint was the number of "completers", with adherence defined as >80% injections obtained in the period, weeks 12-26. Determining whether liraglutide is a feasible treatment was pre-defined to a minimum of 75% completers. RESULTS: Twenty-four participants were included in the study. Sex, male = 19 (79.2%). Mean age: 42.3 [25th and 75th percentiles: 39.1; 48.4] years; body mass index (BMI): 35.7 [31.7; 37.5] kg/m2; glycated haemoglobin (HbA1c): 37 [35; 39] mmol/mol. Eleven out of 24 participants (46%) completed the study. For the completers, the median net body weight loss after 26 weeks of participation was -11.4 kg [-15.4; -5.9]. The net difference in HbA1C and BMI was -2.0 mmol/mol [-4; -1] and -3.6 kg/m2 [-4.7; -1.8], respectively. The weight change and reduction in HbA1c and BMI were all statistically significant from baseline. CONCLUSION: The study did not confirm our hypothesis that liraglutide is a feasible treatment for a minimum of 75% of the patients initiating treatment with liraglutide while hospitalised in a forensic psychiatric department. The high dropout rate may be due to the non-naturalistic setting of the clinical trial. For the proportion of patients compliant with the medication, liraglutide 3.0 mg was an efficient treatment for overweight.

Preoperative Psychopharmacological Treatment is Not a Risk factor for Poorer Patient-Reported Improvements 12 months After Hip or Knee Arthroplasty: A Multicenter Registry-Based Cohort study of 7,247 Procedures.

BACKGROUND: Preoperative psychopharmacological treatment (PPT) has been associated with increased hospital length of stay and readmission rate after hip and knee arthroplasty. However, little is known regarding the association between PPT and improvements in patient-reported outcomes postoperatively in a multicenter fast-track setting. Thus, the primary objective was to investigate whether PPT is a risk factor for poorer patient-reported improvements 12 months after surgery. Secondary objectives included assessment of additional time points and subgroups of PPT. METHODS: This multicenter registry-based cohort study included 4,021 primary hip and 3,226 primary knee arthroplasties performed from 2016 to 2020 at three fast-tack departments in Denmark due to primary osteoarthritis. The Oxford Hip/Knee Score (OHS/OKS), EQ-5D-3/5L, and EQ visual analog scale (VAS) were collected at baseline and three, six, 12, and 24 months after surgery. Exposure status was assigned using the Danish National Prescription Registry. Marginal mean differences (MD) with 95% confidence intervals (CI) were estimated using multilevel Tobit regression and adjusted for age, sex, and the Charlson Comorbidity Index obtained from the Danish National Patient Register. RESULTS: No associations were found between PPT and improvements in OHS (MD -0.5, CI -1.4 to 0.4) or OKS (MD -0.3, CI -1.2 to 0.5) after 12 months. However, PPT was associated with lower baseline OHS (MD -1.4, CI -2.2 to -0.6) and OKS (MD -2.1, CI -2.9 to -1.3), and 12 month follow-up OHS (MD -1.9, CI -2.8 to -1.1) and OKS (MD -2.4, CI -3.2 to -1.6). Similar findings were observed at other time points, using EQ-5D-3/5L or EQ VAS, and when evaluating PPT subgroups. CONCLUSION: In hip and knee arthroplasty, PPT was not a risk factor for poorer patient-reported improvements 12 months after surgery. However, PPT was associated with marginally poorer baseline and follow-up scores. Thus, arthroplasties remain effective treatments despite PPT from a patient-centered perspective.

I Didn't Want the Psychotic Thing to Get Out to Anyone at All: Adolescents with Early Onset Psychosis Managing Stigma.

The impact of stigmatisation on adults with mental illnesses has been thoroughly demonstrated. However, little is known about experiences of stigmatisation among adolescents with mental illness. Through semi-structured interviews with 34 Danish adolescents (14-19 years) diagnosed with psychosis, this study explores adolescents' experiences of psychosis stigma. On the basis of phenomenological analysis, we find that stigmatisation is widely experienced, and psychosis is generally regarded as more stigmatising than co-morbid mental illnesses. The participants engage in different strategies to manage possible stigma, especially strategies of (non-)disclosure. Disclosure is experienced as both therapeutic and normative, but also bears the risk of stigmatisation, and is therefore associated with numerous considerations. Being understood when disclosing is central to the participants, and lack of understanding from others is a continuous challenge. Nevertheless, participants experience benefits when feeling understood by people they confide in and can to a degree create the grounds for this through centralising aspects of their experiences of psychosis and mental illness. We argue that disclosure is both a stigma management strategy and a normative imperative, and that being understood or not is a challenge transcending stigma definitions.Clinical trial registration: Danish Health and Medicines Authority: 2612-4168. The Ethics Committee of Capital Region: H-3-2009-123. ClinicalTrials.gov: NCT01119014. Danish Data Protection Agency: 2009-41-3991.

The use of classic psychedelics among adults: a Danish online survey study.

BACKGROUND: Clinical studies report preliminary therapeutic effects of classic psychedelic drugs in several psychiatric conditions and international drug trends show increased use of these compounds. However, the epidemiology of classic psychedelic drug use in Scandinavian countries remains sparsely investigated. To this end, we investigated the patterns of use and the subjectively perceived acute and persisting effects of lysergic acid diethylamide (LSD), psilocybin, N,N-dimethyltryptamine (DMT), and mescaline, among Danish adults. METHODS: An anonymous online survey with 152 items was conducted using the secure survey web application REDCap. Results were presented descriptively and as comparisons between psychedelic drugs. RESULTS: Five-hundred participants (30.0% female, mean age 34.5 years) were included. Classic psychedelics were mostly used with therapeutic (28.0%) or spiritual (27.2%) intentions. Sixty-seven per cent used classic psychedelics once a year or less. Most participants (56.4%) preferred using psilocybin. Classic psychedelic use was for some individuals, associated with hazardous use of alcohol (39.4%). Among participants with a psychiatric treatment history, 80.9% reported subjective improvements in symptoms following classic psychedelic use. Participants' most memorable experiences were moderate-to-strong mystical-type experiences (MEQ30 mean ± SD 3.4 ± 1.0; range 1-5) and had positive persisting effects on well-being (mean ± SD 2.1 ± 1.0), social relationships (mean ± SD 1.7 ± 1.2), meaning of life (mean ± SD 1.9 ± 1.1), and mood (mean ± SD 1.8 ± 1.1); range -3 to 3. DMT users experienced significantly greater subjective positive effects. CONCLUSIONS: Classic psychedelics were mostly used therapeutically or spiritually and had self-reported positive persisting effects, but were also associated with hazardous use of alcohol, among Danish adults. DMT was associated with significantly greater positive effects compared to LSD and psilocybin.

Disruption of the PDZ domain-binding motif of the dopamine transporter uniquely alters nanoscale distribution, dopamine homeostasis, and reward motivation.

The dopamine (DA) transporter (DAT) is part of a presynaptic multiprotein network involving interactions with scaffold proteins via its C-terminal PDZ domain-binding sequence. Using a mouse model expressing DAT with mutated PDZ-binding sequence (DAT-AAA), we previously demonstrated the importance of this binding sequence for striatal expression of DAT. Here, we show by application of direct stochastic reconstruction microscopy not only that the striatal level of transporter is reduced in DAT-AAA mice but also that the nanoscale distribution of this transporter is altered with a higher propensity of DAT-AAA to localize to irregular nanodomains in dopaminergic terminals. In parallel, we observe mesostriatal DA adaptations and changes in DA-related behaviors distinct from those seen in other genetic DAT mouse models. DA levels in the striatum are reduced to ∼45% of that of WT, accompanied by elevated DA turnover. Nonetheless, fast-scan cyclic voltammetry recordings on striatal slices reveal a larger amplitude and prolonged clearance rate of evoked DA release in DAT-AAA mice compared with WT mice. Autoradiography and radioligand binding show reduced DA D2 receptor levels, whereas immunohistochemistry and autoradiography show unchanged DA D1 receptor levels. In behavioral experiments, we observe enhanced self-administration of liquid food under both a fixed ratio of one and progressive ratio schedule of reinforcement but a reduction compared with WT when using cocaine as reinforcer. In summary, our data demonstrate how disruption of PDZ domain interactions causes changes in DAT expression and its nanoscopic distribution that in turn alter DA clearance dynamics and related behaviors.

Proinflammatory biomarkers are associated with prediabetes in patients with schizophrenia.

BACKGROUND: Treatment with antipsychotics is associated with an increased risk of type 2 diabetes mellitus (T2D), and increased levels of inflammatory biomarkers are present in patients with T2D. We previously demonstrated that the glucagon-like peptide-1 receptor agonist liraglutide significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. This study aims to assess the involvement of cytokines in the therapeutic effects of liraglutide. METHODS: Serum concentrations of 10 cytokines (interferon-γ [IFN-γ], tumor necrosis factor-α, interleukin 1ß [IL-1ß], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and IL-13) from fasting prediabetic and normal glucose-tolerant (NGT) patients with schizophrenia-spectrum disorders were measured using multiplexed immunoassays. Prediabetic patients were randomized to 16 weeks of treatment with liraglutide or placebo, and cytokines were measured again at the end of the treatment. RESULTS: IFN-γ (1.98 vs 1.17 pg/ml, P = .001), IL-4 (0.02 vs 0.01 pg/ml, P < .001), and IL-6 (0.73 vs 0.46 pg/ml, P < .001) were significantly higher in prediabetic (n = 77) vs NGT patients (n = 31). No significant changes in cytokine levels following treatment with liraglutide (n = 37) vs placebo (n = 40) were found. CONCLUSION: Prediabetic vs NGT patients with schizophrenia treated with clozapine or olanzapine had increased serum levels of several proinflammatory cytokines, further substantiating the link between inflammation and T2D. Treatment with liraglutide did not affect the investigated cytokines. Further testing of these findings in larger numbers of individuals is needed.

Differential effects of age at illness onset on verbal memory functions in antipsychotic-naïve schizophrenia patients aged 12-43 years.

BACKGROUND: The typical onset of schizophrenia coincides with the maturational peak in cognition; however, for a significant proportion of patients the onset is before age 18 and after age 30 years. While cognitive deficits are considered core features of schizophrenia, few studies have directly examined the impact of age of illness onset on cognition. METHODS: The aim of the study was to examine if the effects of age on cognition differ between healthy controls (HCs) and patients with schizophrenia at illness onset. We examined 156 first-episode antipsychotic-naïve patients across a wide age span (12-43 years), and 161 age- and sex-matched HCs. Diagnoses were made according to ICD-10 criteria. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS), and IQ was estimated using subtests from the Wechsler adult- or child-intelligence scales. Multivariate analysis of covariance (MANCOVA) was used to examine linear and quadratic effects of age on cognitive scores and interactions by group, including sex and parental socioeconomic status as covariates. RESULTS: There was a significant overall effect of age on BACS and IQ (p < 0.001). Significant group-by-age interactions for verbal memory (for age-squared, p = 0.009), and digit sequencing (for age, p = 0.01; age-squared, p < 0.001), indicated differential age-related trajectories between patients and HCs. CONCLUSIONS: Cognitive functions showing protracted maturation into adulthood, such as verbal memory and verbal working memory, may be particularly impaired in both early- and late-schizophrenia onset. Our findings indicate a potential interaction between the timing of neurodevelopmental maturation and a possible premature age effect in late-onset schizophrenia.

How to Estimate QT Interval in Patients With Left or Right Bundle Branch Block: A Systematic Review.

PURPOSE/BACKGROUND: Prolonged QT interval related to psychopharmacological treatment is a risk factor for potentially life-threatening arrhythmias. Electrocardiographic measurements are recommended in patients with cardiovascular risk factors before initiating treatment with potentially QT-prolonging medications, such as certain antidepressants or antipsychotics. In patients with left bundle branch block (LBBB) or right bundle branch block (RBBB), conventional QT-estimation methods will lead to overestimation of the QT interval, as the conduction defect, reflected by the QRS duration, will increase the QT interval without representing longer repolarization as in drug-induced QT prolongation. METHODS/PROCEDURES: We conducted a systematic review of methods to estimate QT interval in the presence of LBBB or RBBB. We searched electronic databases Embase and Medline (last search, August 12, 2020). FINDINGS/RESULTS: We found 8 different methods, including linear correction formulae with and without correction for heart rate, or simpler formula correcting QRS duration with empirically derived modifiers. Only 3 of 8 methods were applicable in the presence of RBBB, whereas all 8 methods could be applied in the presence of LBBB. IMPLICATIONS/CONCLUSIONS: The QT interval is overestimated in patients with LBBB or RBBB, when using conventional measurements. Several alternative correction formulae exist, which can be applied using standard measurements from ordinary electrocardiographic readings. However, it is currently unknown whether or not the QT prolongation observed in the presence of bundle branch block significantly increases the risk of arrhythmias, as these formulae have not been tested against patient-specific clinical outcomes.

CYP2D6 Genotyping and Antipsychotic-Associated Extrapyramidal Adverse Effects in a Randomized Trial of Aripiprazole Versus Quetiapine Extended Release in Children and Adolescents, Aged 12-17 Years, With First Episode Psychosis.

PURPOSE/BACKGROUND: The aim of this study was to examine the association between genetically predicted CYP2D6 phenotypes and extrapyramidal symptoms (EPSs). METHODS/PROCEDURES: Data from the Tolerability and Efficacy of Antipsychotics trial of adolescents with first-episode psychosis randomized to aripiprazole versus quetiapine extended release were studied. Extrapyramidal symptom assessments included the Simpson-Angus Scale and the Barnes Akathisia Rating Scale. Patients were CYP2D6 genotyped. Plasma concentrations of antipsychotics and antidepressants were analyzed. FINDINGS/RESULTS: One hundred thirteen youths (age, 12-17 years; males, 30%; antipsychotic naive, 51%) were enrolled. Poor metabolizers had a significantly higher dose-adjusted aripiprazole plasma concentration (±SD) compared with normal metabolizers at week 4 (24.30 ± 6.40 ng/mL per milligram vs 14.85 ± 6.15 ng/mL per milligram; P = 0.019), but not at week 12 (22.15 ± 11.04 ng/mL per milligram vs 14.32 ± 4.52 ng/mL per milligram; P = 0.067). This association was not found in the quetiapine extended release group. No association between CYP2D6 genotype groups and global Barnes Akathisia Rating Scale score or Simpson-Angus Scale score was found in any of the treatment arms. IMPLICATIONS/CONCLUSIONS: Our results do not support routine use of CYP2D6 testing as a predictor of drug-induced parkinsonism or akathisia risk in clinical settings. Further studies with larger samples of CYP2D6 poor metabolizers are needed.

Use of ketogenic diets in the treatment of central nervous system diseases: a systematic review.

BACKGROUND: Studies have consistently shown that patients with epilepsy could benefit from ketogenic diets (KDs). Recent evidence suggests that KD could be used in the treatment of central nervous system (CNS) diseases. The aim of this systematic review was to investigate the use and efficacy of KD, modified Atkins diet (MAD) and medium-chain triglyceride (MCT) diet in infants, children, adolescents, and adults with CNS diseases. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main databases, i.e. EMBASE, PubMed and PsycINFO, were searched on 4 December 2019. Only randomized clinical trials (RCTs) were included and only if they reported KD, MCT or MAD interventions on patients with CNS diseases. RESULTS: Twenty-four publications were eligible for inclusion (n = 1221). Twenty-one publications concerned epilepsy, two concerned Alzheimer's disease (AD), and one concerned Parkinson's disease (PD). All studies regarding epilepsy reported of seizure reduction compared to baseline. MCT did not significantly change regional cerebral blood flow (rCBF) in patients with AD, but MAD significantly improved memory at 6 weeks (p = .03). KD significantly improved motor and nonmotor functions in patients with PD at 8 weeks (p < .001). There was a trend towards fewer adverse effects in MAD compared to KD. CONCLUSION: In conclusion, various forms of KDs seem tolerable and effective as part of the treatment for epilepsy, AD and PD, although more investigation concerning the mechanism, efficacy and adverse events is necessary.

Measuring movements in adolescents with psychosis using the Microsoft Kinect sensor: a pilot study exploring a new tool for assessing aspects of antipsychotic-induced parkinsonism.

BACKGROUND: The assessment of motor disturbances in antipsychotic-treated adolescent patients is often limited to the use of observer-based rating scales with interobserver variability. The objectives of this pilot study were to measure movement patterns associated with antipsychotic-induced parkinsonism in young patients with psychosis and initiating/treated with antipsychotics, using a computer application connected with the Microsoft Kinect sensor (Motorgame). METHOD: All participants were assessed by neurological examination, clinical side effect rating scales (Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, Barnes Akathisia Rating Scale, Simpson Angus Scale (SAS), and Abnormal Involuntary Movement Scale), and the Motorgame. Furthermore, speed of information processing and motor speed with subtests from the Brief Assessment of Cognition in Schizophrenia test battery was assessed. RESULTS: We included 21 adolescents with first-episode psychosis (62% treated with antipsychotics; males 38%; mean age 16 ± 1.4 years) and 69 healthy controls (males 36%; mean age 16 ± 1.5 years). Prolonged time of motor performance (TOMP) in the Motorgame was associated with higher SAS scores for arm dropping (p = .009). A consistent practice effect was detected (p < .001). We found no significant associations between TOMP and age, height, body weight, sex, antipsychotic dosage, or information processing speed. CONCLUSIONS: We found an uncorrected significant association between prolonged TOMP and shoulder bradykinesia. The Motorgame was found useful in assessing parkinsonian symptoms in early-onset psychosis and accepted by participants. Future studies of larger cohorts, including patients with high scores in clinical motor side effect scales, are required to establish solid validity of the novel test.

Glucagon-like peptide-1 receptor agonists for antipsychotic-associated cardio-metabolic risk factors: A systematic review and individual participant data meta-analysis.

AIMS: To evaluate if glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce antipsychotic-associated body weight gain in patients with schizophrenia, when compared to controls. MATERIALS AND METHODS: We systematically searched PubMed/EMBASE/PsycINFO/Cochrane using the search terms '(antipsychotic and GLP-1RA)'. Individual participant data from studies randomizing patients to GLP-1RA or control were meta-analysed. The primary outcome was difference in body weight between GLP-1RA and control; secondary outcomes included cardio-metabolic variables and adverse drug reactions (ADRs). Multiple linear regression was conducted including sex, age, psychosis severity, metabolic variable, ADRs, and GLP-1RA agent. RESULTS: Three studies (exenatide once-weekly = 2; liraglutide once-daily = 1) provided participant-level data (n = 164, age = 40.0 ± 11.1 years, body weight = 105.8 ± 20.8 kg). After 16.2 ± 4.0 weeks of treatment, body weight loss was 3.71 kg (95% CI = 2.44-4.99 kg) greater for GLP-1RA versus control (p < 0.001), number-needed-to-treat ≥5% body weight loss = 3.8 (95% CI = 2.6-7.2). Waist circumference, body mass index, HbA1c, fasting glucose and visceral adiposity were each significantly lower with GLP-1RA. Sex, age, psychosis severity, nausea, any ADR, and GLP-1RA agent did not significantly impact outcomes. Body weight loss with GLP-1RAs was greater for clozapine/olanzapine-treated patients (n = 141) than other antipsychotics (n = 27) (4.70 kg, 95% CI = 3.13-6.27 vs. 1.5 kg, 95% CI = -1.47-4.47) (p < 0.001). Nausea was more common with GLP-1RAs than control (53.6% vs. 27.5%, p = 0.002, number-needed-to-harm = 3.8). CONCLUSION: GLP-1RAs are effective and tolerable for antipsychotic-associated body weight gain, particularly clozapine/olanzapine-treated patients. With few included patients, further studies are required before making routine use recommendations for GLP-1RAs.

High prevalence of prediabetes and metabolic abnormalities in overweight or obese schizophrenia patients treated with clozapine or olanzapine.

OBJECTIVE: To assess the prevalence of prediabetes and metabolic abnormalities among overweight or obese clozapine- or olanzapine-treated schizophrenia patients, and to identify characteristics of the schizophrenia group with prediabetes. METHODS: A cross-sectional study assessing the presence of prediabetes and metabolic abnormalities in schizophrenia clozapine- or olanzapine-treated patients with a body mass index (BMI) ≥27 kg/m2. Procedures were part of the screening process for a randomized, placebo-controlled trial evaluating liraglutide vs placebo for improving glucose tolerance. For comparison, an age-, sex-, and BMI-matched healthy control group without psychiatric illness and prediabetes was included. Prediabetes was defined as elevated fasting plasma glucose and/or impaired glucose tolerance and/or elevated glycated hemoglobin A1c. RESULTS: Among 145 schizophrenia patients (age = 42.1 years; males = 59.3%) on clozapine or olanzapine (clozapine/olanzapine/both: 73.8%/24.1%/2.1%), prediabetes was present in 69.7% (101 out of 145). While schizophrenia patients with and without prediabetes did not differ regarding demographic, illness, or antipsychotic treatment variables, metabolic abnormalities (waist circumference: 116.7±13.7 vs 110.1±13.6 cm, P = 0.007; triglycerides: 2.3±1.4 vs 1.6±0.9 mmol/L, P = 0.0004) and metabolic syndrome (76.2% vs 40.9%, P<0.0001) were significantly more pronounced in schizophrenia patients with vs without prediabetes. The age-, sex-, and BMI-matched healthy controls had significantly better glucose tolerance compared to both groups of patients with schizophrenia. The healthy controls also had higher levels of high-density lipoprotein compared to patients with schizophrenia and prediabetes. CONCLUSION: Prediabetes and metabolic abnormalities were highly prevalent among the clozapine- and olanzapine-treated patients with schizophrenia, putting these patients at great risk for later type 2 diabetes and cardiovascular disease. These results stress the importance of identifying and adequately treating prediabetes and metabolic abnormalities among clozapine- and olanzapine-treated patients with schizophrenia.

Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats.

BACKGROUND: Alcohol use disorder is underdiagnosed and undertreated, and up to 50% of alcohol-abstinent patients diagnosed with alcohol dependence relapse within the first year of treatment. Current treatments for the maintenance of alcohol abstinence in patients with alcohol use disorder have limited efficacy, and there is an urgent need for novel treatment strategies. Decreased cerebral glucose metabolism and increased brain uptake of acetate were recently reported in heavy drinkers, relative to controls. Given the switch of metabolic fuel from glucose to acetate in the alcohol-dependent brain, we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. METHODS: Male Sprague Dawley rats fed either ketogenic or regular diet were administered ethanol or water orally, twice daily for 6 days while the diet conditions were maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. RESULTS: Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms' "rigidity" and "irritability." CONCLUSIONS: Our preclinical pilot study suggests that a ketogenic diet may be a novel approach for treating alcohol withdrawal symptoms in humans.

Substance use among Danish psychiatric patients: a cross-sectional study.

BACKGROUND: Patients with psychiatric disorders have a greater risk of mortality than the general population. Use or abuse of substances, including alcohol, play a crucial part in this context. Moreover, it is well known that drug use can worsen psychopathology and reduce treatment compliance. However, the magnitude of these problems among Danish psychiatric patients has not been studied previously. AIMS: The aim of this study is to investigate substance use among psychiatric patients in the Capital Region of Denmark. METHODS: Outpatients from five psychiatric units were asked to complete a questionnaire regarding their use of alcohol and other drugs of abuse. The questionnaire was based on the Alcohol Use Disorder Identification Test (AUDIT), supplemented by questions regarding use of tobacco and illicit drugs. The results were compared with those uses in the general population. RESULTS: In total, 412 psychiatric patients participated in the study, and 33% had an AUDIT-score ≥8, indicating problematic alcohol use according to the AUDIT guidelines. The mean weekly alcohol intake was 9.7 ± 28.3 standard drinks, and 47% were current smokers with a mean daily use of 19.9 ± 13.8 cigarette equivalents. Compared to the general population, the psychiatric patients had higher odds of being current smokers and having used illicit drugs within the past month. Women with psychiatric disorders were twice as likely to binge drink on a monthly basis. No significant difference was found in the patients' AUDIT scores compared to the general population. CONCLUSIONS: Our findings demonstrate a substantial and problematic use of tobacco and illicit drugs among Danish psychiatric patients, greater than in the general population.

Prospective psychometric characterization of hip and knee arthroplasty patients.

BACKGROUND: Psychiatric conditions and psychopharmacological treatments have been demonstrated to be important risk-factors for prolonged hospital length of stay, readmission and morbidity, following fast-track total hip (THA) and total knee arthroplasty (TKA). AIMS: The aim of the study was to provide a detailed description of the preoperative psychiatric characteristics of a well-defined patient population undergoing THA and TKA, using the 90-item Symptom Checklist (SCL-90-R). METHODS: A pre-surgical population of 2183 patients completed the full SCL-90-R prior to THA/TKA from 2015 to 2016. The SCL-90-R scale and total scores of the pre-surgical sample were compared to the scores of an age- and gender stratified Danish sample of healthy controls. A Mokken scalogram analysis was conducted to assess the scalability of the SCL-90-R in both samples. RESULTS: The Mokken analysis yielded acceptable scalability coefficients above 0.30 in all subscales of the SCL-90-R except psycoticism (0.28). There was no clinically significant difference (effect size = <0.50) in the SCL-90-R total score between the pre-surgical and the healthy controls samples, although pre-surgical patients had lower mean scores compared to the healthy controls in all subscales except somatization (effect size = -0.22). CONCLUSION: The Mokken analysis demonstrated that the SCL-90-R and its subscales express valid measures of psychopathology in our surgical sample. The psychiatric profile of the pre-surgical patient sample indicates that patients undergoing THA/TKA are not more burdened by psychiatric symptoms than a healthy control group with the exception of symptoms relating to somatization.

Psychopharmacologic treatment and blood transfusion in fast-track total hip and knee arthroplasty.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) and other psychotropics are receiving increasing attention due to reports on inhibition of thrombocyte function and an increased bleeding risk in surgical settings. Studies in total hip and total knee arthroplasty (THA and TKA, respectively) have shown conflicting results, questioning whether the potential increased bleeding risk is of clinical importance. STUDY DESIGN AND METHODS: Prospective consecutive collection of data on preoperative comorbidity in patients undergoing primary unilateral THA or TKA was cross-referenced with regional transfusion databases and The Danish National Database of Reimbursed Prescriptions for information regarding blood transfusions and psychopharmacologic treatment. All participating orthopedic centers followed similar perioperative guidelines. Multiple logistic regression analysis was applied to calculate odds ratios (ORs) for transfusion between preoperative users and nonusers of psychotropics. RESULTS: Of 8402 patients, 569 (6.8%) were SSRI users versus 7833 (93.2%) nonusers. A total of 109 (19,2%) patients in the SSRI group and 700 (8.9%) in the "no-SSRI" group received blood intra- or postoperatively. Preoperative SSRI treatment was a risk factor for perioperative transfusion (OR, 1.98; 95% confidence interval [CI], 1.44-2.70). Other antidepressants (OAs) were associated with an increased risk of transfusion (OR, 1.69; 95% CI, 1.17-2.44) as well as the combination of SSRIs and OAs (OR, 3.31; 95% CI, 1.79-6.13). Singular use of antipsychotics (APs) increased the transfusion risk (OR, 2.37; 95% CI, 1.04-2.41), while AP medicine in combination with antidepressants did not. CONCLUSIONS: Preoperative treatment with SSRIs, OAs, or APs are independent risk factors for blood transfusion in elective fast-track THA and TKA.

The relationship between self-reported childhood adversities, adulthood psychopathology and psychological stress markers in patients with schizophrenia.

BACKGROUND: Childhood adversity is a well-established risk factor for the development of schizophrenia. In particular, there is evidence that childhood adversity increases the occurrence of positive symptoms, possibly through glucocorticoid influences on dopaminergic neurotransmission. AIMS: To compare levels of childhood trauma in schizophrenia patients vs. healthy control persons, and to study the association between childhood adversity and the symptomatology of adulthood schizophrenia, as well as subjective and biological markers of psychological stress. METHODS: Thirty-seven patients fulfilling ICD-10 criteria for schizophrenia and 39 healthy control persons filled out the comprehensive Childhood Abuse and Trauma Scale (CATS). Data were analyzed after a data-driven dichotomization into two groups of either high or low CATS score in patients and controls, respectively. The psychopathology of the patients was measured by the Positive and Negative Syndrome Scale (PANSS) and analyzed by a five-factor PANSS model. Measures of perceived stress (Perceived Stress Scale) and hypothalamic-pituitary-adrenal (HPA)-axis activity (9AM plasma cortisol and daytime salivary cortisol output) were recorded. RESULTS: As expected, patients had significantly higher total CATS scores than the control persons (>3-fold, P<0.001), reflecting significantly higher scores across all subscales of the CATS. In patients, the total PANSS score did not significantly differ between the high and the low CATS score group (P=0.2). However, there was a statistically significant higher level of positive symptoms in the high CATS group (P=0.014), and no difference in other psychopathological domains. Correspondingly, when using the CATS score as a continuous variable, a strong association with positive PANSS scores was found (P=0.009). The high CATS score group showed higher levels of perceived stress (P=0.02), but there was no difference between the high vs. low CATS group in HPA-axis activity. CONCLUSION: Although causal inferences cannot be made from this cross-sectional study, the study adds support to the suggestion that childhood adversity specifically increases the occurrence of positive symptoms in adulthood schizophrenia in a manner that appears to leave HPA-axis activity unaltered.

The Role of Psychiatric Diagnoses for Outcome After Hip and Knee Arthroplasty.

BACKGROUND: Surgical patients receiving psychopharmacologic treatment have been associated with adverse outcomes in total hip and knee arthroplasty (THA and TKA). The purpose of this study was to investigate whether a specific high-risk group of patients receiving psychopharmacologic treatment could be identified based upon a nationwide psychiatric diagnosis register. METHODS: From 7 different orthopedic centers, 8288 THA and TKA patients were included from January 2010 to November 2012 of which 943 (11.4%) received psychopharmacologic treatment. Patients receiving preoperative psychopharmacologic treatment were divided into 2 groups based on the presence or absence of a psychiatric diagnosis in a nationwide administrative database and analyzed with respect to length of hospital stay (LOS >4 days) and 30- and 90-day readmissions using multivariable logistic regression models. RESULTS: A total of 191 patients receiving psychopharmacologic treatment were registered with a psychiatric diagnosis while 752 patients received psychopharmacologic treatment without a registered psychiatric diagnosis. No significantly increased risk was found in patients with a preoperative registered psychiatric diagnosis compared to patients without, with regard to LOS >4 days (odds ratio [OR], 1.19; P = .51), 30-day readmission (OR, 0.56; P = .086), or 90-day readmission (OR, 0.81; P = .446), respectively. However, both groups had an increased risk of LOS >4 days and readmissions compared to a control population without psychopharmacologic treatment or any registered psychiatric diagnoses. CONCLUSION: No further risk was found for psychopharmacologically treated THA/TKA patients with an additional hospital-related psychiatric diagnosis compared to patients without, suggesting that the psychopharmacologic treatment per se is an outcome risk factor independent of severity of the psychiatric disorder.

Neurological, Metabolic, and Psychiatric Adverse Events in Children and Adolescents Treated With Aripiprazole.

Aripiprazole is a partial dopamine agonist with only minor neurological and psychiatric adverse effects, making it a potential first-line drug for the treatment of psychiatric disorders. However, the evidence of its use in children and adolescents is rather sparse. The aim of this case study is to discuss adverse drug reaction (ADR) reports concerning aripiprazole-associated neurological and psychiatric events in children and adolescents. The ADR report database at Danish Medicines Agency was searched for all ADRs involving children and adolescents (<18 years) reported by the search term [aripiprazole] AND all spontaneous reports since the introduction of aripiprazole in 2003 until December 31, 2015. Nineteen case reports were included in the study and included both patients with psychotic disorders (PS group) and nonpsychotic disorders (non-PS group). The PS group consisted of 5 patients with schizophrenia and psychoses, not otherwise specified; and the non-PS group consisted of fourteen cases including autism spectrum disorders, attention deficit and hyperactivity disorder, obsessive-compulsive disorder, and Tourette syndrome. The main reported adverse effects in the non-PS group were chronic insomnia, Parkinsonism, behavioral changes psychoses, and weight gain, whereas the adverse effects in the PS group was predominantly anxiety, convulsions, and neuroleptic malignant syndrome. Although aripiprazole is considered safe and well tolerated in children and adolescents, severe adverse events as neuroleptic malignant syndrome, extreme insomnia, and suicidal behavior has been reported to health authorities. Clinicians should pay attention to these possible hazards when prescribing aripiprazole to this vulnerable group of patients.