Udvalg For Kliniske Research Articles

Long-Term Effectiveness of Off-Label Risperidone Treatment in Children and Adolescents: A Randomized, Placebo-Controlled Discontinuation Study.

Objectives: Risperidone is commonly prescribed off-label in children and adolescents to manage disruptive behavior. This study aimed to investigate continued benefits of risperidone after at least 1 year of treatment and effects of discontinuation on physical health. Methods: Thirty-five youths (aged 6-18 years, intelligence quotient [IQ] >70) who were treated with risperidone for at least 1 year in regular clinical practice receiving outpatient care were randomly assigned to double-blind continuation of risperidone during 16 weeks or continuation for 2 weeks, gradual dose lowering over 6 weeks, and placebo for 8 weeks. Primary outcome was the total Disruptive Behavior (D-total) score of the parent-reported Nisonger Child Behavior Rating Form-Typical IQ (NCBRF-TIQ). Secondary outcome measures were the clinician-rated Clinical Global Impressions-Improvement scale (CGI-I), the parent, child, and teacher-rated Strengths and Difficulties Questionnaire (SDQ), the parent-rated Retrospective Modified Overt Aggression Scale (R-MOAS), and several health parameters (Udvalg for Kliniske Undersøgelser Side Effect Rating Scale [UKU-SERS], dyskinesia, akathisia, parkinsonism, body mass index (BMI), waist circumference, and laboratory outcomes). Mixed models for repeated measures were conducted for continuous outcomes and a chi-square test for the CGI-I. Results: Discontinuation of risperidone, as compared with continuation, was not associated with significant changes in parent-reported disruptive behaviors. However, discontinuation was related to significant deterioration in parent-rated verbal aggression, teacher-rated behavioral functioning, clinician-rated general functioning, and significant improvements in weight, BMI, waist circumference, and glucose, insulin, and prolactin levels. Although 56% of participants in the discontinuation group experienced relapse, causing premature withdrawal from the study, 44% was able to successfully discontinue risperidone. Conclusion: Discontinuation of risperidone was associated with deterioration on some, but not all behavioral measures according to this explorative study. Discontinuation was associated with important health gains. Despite long-term benefits of risperidone, attempts to withdraw risperidone should be undertaken in individual children. This is a crucial step in preventing harm and fostering health.

Sex differences in autonomic adverse effects related to antipsychotic treatment and associated hormone profiles

Autonomic adverse effects of antipsychotic drugs (APs) cause clinical challenges, but few studies have investigated sex differences and their underlying biological pathways. Sex-specific regulation of relevant hormones could be involved. We investigated sex differences in autonomic adverse effects related to olanzapine, quetiapine, risperidone, and aripiprazole, and the role of hormones related to APs. Patients with severe mental disorders (N = 1318) were included and grouped based on AP monotherapy: olanzapine (N = 364), quetiapine (N = 211), risperidone (N = 102), aripiprazole (N = 138), and no AP (N = 503). Autonomic symptoms from the Udvalg for Kliniske Undersøgelser (UKU) side effect scale was analyzed with logistic regression, adjusting for age, diagnosis, and polypharmacy. Further, we analyzed associations between autonomic symptoms and hormones related to APs. We found associations between autonomic adverse effects and APs, with sex-specific risk for palpitations/tachycardia associated with hormonal changes related to APs. Results showed increased salivation associated with aripiprazole, reduced salivation with quetiapine, and nausea/vomiting and palpitations/tachycardia with olanzapine, and higher risk of nausea/vomiting, diarrhea, constipation, polyuria/polydipsia, and palpitations/tachycardia in females. Significant sex x AP interaction was found for palpitations/tachycardia, with higher risk in risperidone-treated males, which was associated with different hormone profiles of prolactin, cortisol, and insulin. Our findings implicate a role of several hormones in the sex-specific autonomic adverse effects related to APs.

Pharmacogenetics May Prevent Psychotropic Adverse Events in Autism Spectrum Disorder: An Observational Pilot Study.

Up to 73% of individuals with autism spectrum disorder (ASD) and intellectual disability (ID) currently have prescriptions for psychotropic drugs. This is explained by a higher prevalence of medical and psychiatric chronic comorbidities, which favors polypharmacy, increasing the probability of the appearance of adverse events (AEs). These could be a preventable cause of harm to patients with ASD and an unnecessary waste of healthcare resources. To study the impact of pharmacogenetic markers on the prevention of AE appearance in a population with ASD and ID. This is a cross-sectional, observational study (n = 118, 72 participants completed all information) in the ASD population. Sociodemographic and pharmacological data were gathered. The Udvalg for Kliniske Undersøgelser Scale (UKU Scale) was used to identify AEs related to the use of psychotropic medication. Polymorphisms of DOP2, ABCB1, and COMT were genotyped and correlated with the AE to find candidate genes. Furthermore, a review of all medications assessed in a clinical trial for adults with autism was performed to enrich the search for potential pharmacogenetic markers, keeping in mind the usual medications. The majority of the study population were men (75%) with multiple comorbidities and polypharmacy, the most frequently prescribed drugs were antipsychotics (69%); 21% of the participants had four or more AEs related to psychotropic drugs. The most common were "Neurological" and" Psychiatric" (both 41%). Statistical analysis results suggested a significant correlation between the neurological symptoms and the DOP2 genotype, given that they are not equally distributed among its allelic variants. The final review considered 19 manuscripts of medications for adults with ASD, and the confirmed genetic markers for those medications were consulted in databases. A possible correlation between neurologic AEs and polymorphisms of DOP2 was observed; therefore, studying this gene could contribute to the safety of this population's prescriptions. The following studies are underway to maximize statistical power and have a better representation of the population.

Usefulness of mirtazapine and SSRIs in late-life depression: post hoc analysis of the GUNDAM study.

Mirtazapine and SSRIs are widely prescribed as first-line agents for late-life depression. However, evidence for these drugs is mostly based on non-elderly patients. Therefore, we reanalyzed a randomized controlled trial of mirtazapine versus SSRIs for depression in a sub-population of late-life patients. A randomized controlled trial was conducted with 141 patients, of whom 41 were elderly, and 100 were non-elderly. This study compared SSRIs and mirtazapine in late-life depression, examined late-onset and early adult-onset separately and compared elderly and non-elderly patients for each drug. Treatment effects and adverse events were assessed using the Hamilton Depression Rating Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, respectively. In late-life depression, mirtazapine showed faster HAM-D total score improvement (3.3 points difference, p = 0.021) and higher improvement in insomnia (1.7 points difference, p = 0.001) and appetite (1.2 points difference, p = 0.020). Similar findings were observed for late-onset depression with the HAM-D total score (4.3 points difference, p = 0.007) and appetite (0.9 points difference, p = 0.004), favoring mirtazapine. Depressive symptoms were generally less improved in late-life depression than in non-late-life depression. Regarding the effect of mirtazapine on appetite, late-life depression showed greater improvement (0.7 points difference, p = 0.008). Nausea and micturition disturbances were more common with SSRIs in late-life depression than in non-late-life depression. In contrast, somnolence was less common in late-life depression with mirtazapine. The potential usefulness of mirtazapine in elderly patients was demonstrated. The results also showed differences in the treatment response to SSRIs and mirtazapine between elderly and non-elderly patients.

Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients.

Introduction: Preventing side effects is important to ensure optimal psychopharmacotherapy and therapeutic adherence among psychiatric patients. Obtaining the pharmacogenetic profile of CYP2C19 and CYP2D6 can play an important role in this. When the genotype-predicted phenotype shifts because of the use of co-medication, this is called phenoconversion. The aim was to study the influence of the pharmacogenetic (PGx) profile and phenoconversion on side effects experienced by psychiatric patients. Methods: A retrospective cohort study was performed using data from 117 patients from a psychiatric outpatient clinic. Patients were genotyped with a psychiatric PGx panel and side effects were evaluated using the Udvalg for Kliniske Undersølgelser side effects rating scale (UKU). Results: Of all patients, 10.3% and 9.4% underwent phenoconversion (any shift in predicted phenotype) for CYP2C19 and CYP2D6 respectively. No significant associations were found between the phenotype and UKU-score. 75% of the patients with an Intermediate metabolizer (IM) or Poor metabolizer (PM) phenoconverted phenotype of CYP2C19 experienced nausea and vomiting compared to 9.1% of the Normal metabolizer (NM) and Ultrarapid metabolizer (UM) patients (p = 0.033). 64% of the patients with an IM or PM phenoconverted phenotype of CYP2D6 experienced the side effect depression compared to 30.4% NMs and UMs (p = 0.020). CYP2D6 IM and PM patients had a higher concentration-dose ratio than NM patients (p < 0.05). Discussion: This study underlines the importance to consider phenoconversion when looking at a patient's genotype. This is important for a better prediction of the phenotype and preventing possible side effects under a specific psychopharmacotherapy.

Lurasidone Augmentation of Clozapine in Refractory Schizophrenia: A Case Series.

Clozapine represents the criterion standard therapy for patients with treatment-resistant schizophrenia. Unfortunately, a significant percentage of such patients are also partial responders to clozapine. Consequently, several augmentation strategies have been proposed with various and sometimes controversial efficacy. Among these add-on treatments, lurasidone has been recently introduced and could represent a potential option, especially for the additional positive effect on cognitive symptoms. This case series aims to determine possible advantages of lurasidone augmentation in four patients treated with clozapine, who were diagnosed with treatment-resistant schizophrenia. Positive and Negative Syndrome Scales were used to evaluate psychopathology, the Udvalg for Kliniske Undersøgelser scale for tolerability and safety. All patients achieved a significant reduction of both positive and negative symptoms, with no significant adverse effects to be reported. Our observation suggests that lurasidone can lead to clinically significant improvements in psychopathology with a good tolerability profile when added to clozapine.

Evaluation of factors associated with medication adherence in patients with bipolar disorder using a medication event monitoring system: a 6‐month follow‐up prospective study

BackgroundNon-adherence in patients with bipolar disorder (BD) results in symptoms, such as aggravation, BD recurrence, emergency room visits, re-hospitalization, and poor psychosocial outcomes. Though non-adherence rates have been reported to range between 30–50% in patients with BD, the problem of adherence is often either overlooked by the physician or denied by the patient. An essential first step to enhancing medication adherence is to objectively estimate adherence. The Medication Event Monitoring System (MEMS), which is a pill bottle cap with a microprocessor, is an accurate device for assessing medication adherence. Using the MEMS, we aimed to measure medication adherence in patients with BD and evaluate the factors associated with and 6-month changes in medication adherence.MethodsParticipants with BD were recruited from the psychiatric outpatient clinic of the Korea University Guro Hospital. The medication adherence of each participant was assessed using the MEMS, a self-report, pill count, and clinician rating. MEMS-measured adherence was reassessed after 6 months. Patient demographics were recorded and clinical assessments were conducted. Data were analyzed using Kappa statistics and Pearson’s correlation analysis.ResultsOf the 59 participants, 50 records were included in the analysis. Patient adherence and adherence rate assessed by the MEMS were lower than those assessed by the other measures. MEMS-measured adherence was correlated more closely with pill counts than with self-reports or clinician ratings. MEMS-measured adherence was negatively associated with prescription duration and the Brief Psychiatric Rating Scale—Affect Subscale Score. Six-month changes in MEMS-measured adherence were positively associated with attitude toward drugs and negatively associated with weight gain assessed by the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale.ConclusionsClinicians may have to consider the limited accuracy of self-reporting and clinician rating methods and exercise caution when assessing the medication adherence of patients with BD using these methods. Our findings may assist clinicians in the assessment and improvement of medication adherence in patients with BD and, consequently, may be useful for the treatment and prevention of BD recurrence.

Validation of the Glasgow Antipsychotic Side-Effect Scale (GASS) in an Italian Sample of Patients with Stable Schizophrenia and Bipolar Spectrum Disorders.

Antipsychotics are a class of psychotropic drugs that improve psychotic symptoms and reduce relapse risk. However, they may cause side effects (SE) that impact patients’ quality of life and psychosocial functioning. Therefore, there is a need for practical tools to identify them and possibly intervene. The objective of the present study was to translate into Italian the Glasgow Antipsychotic Side Effect Scale (GASS), which is suggested as the questionnaire of choice to collect SE reported by patients treated with antipsychotics. We administered the GASS and the Udvalg for Kliniske Undersøgelser (UKU) SE scale—which is considered the gold standard—to 100 stable patients with schizophrenia and bipolar spectrum disorders. We measured the structural validity, internal consistency, concurrent criterion validity, construct validity, and clinical feasibility. GASS was characterized by modest structural validity and good internal consistency. The binary correlations concerning the presence of specific symptoms investigated with the GASS and the UKU were strong or relatively strong for only half of them. The GASS total scale score was inversely related to patients’ quality of life and psychosocial functioning. The GASS is useful to briefly assess the burden of antipsychotic SE (~5 min) but is not optimal in identifying them.

Metabolizing status of CYP2C19 in response and side effects to medications for depression: Results from a naturalistic study

Major depressive disorder (MDD) is one of the leading causes of disability worldwide. Polymorphisms in cytochrome P450 genes (CYP450) were demonstrated to play a significant role in antidepressant response and side effects, but their effect in real-world clinical practice is poorly known.We determined the metabolic status of CYP2C19 based on the combination of *1, *2, *3 and *17 alleles extracted from genome-wide data in 1239 patients with MDD, pharmacologically treated in a naturalistic setting. Symptom improvement and side effects were assessed using the Montgomery and Åsberg Depression Rating Scale and the Udvalg for Kliniske Undersøgelse scale, respectively. We tested if symptom improvement, response and side effects were associated with CYP2C19 metabolic status adjusting for potential confounders. We considered patients treated with drugs for depression having CYP2C19 genotyping recommended by guidelines (T1 Drugs); secondarily, with all psychotropic drugs having CYP2C19 as relevant metabolic path (T2 Drugs).In the group treated with T1 drugs (n = 540), poor metabolizers (PMs) showed higher response and higher symptom improvement compared to normal metabolizers (p = 0.023 and p = 0.009, respectively), but also higher risk of autonomic and neurological side effects (p = 0.022 and p = 0.022 respectively). In patients treated with T2 drugs (n = 801), similar results were found. No associations between metabolizer status and other types of side effects were found (psychic and other side effects).Our study suggests potential advantages of CYP2C19 pharmacogenetic testing to guide treatment prescription, that may not be limited to the drugs currently recommended by guidelines.

Clinical evaluation of switching from immediate-release to prolonged-release lithium in bipolar patients, poorly tolerant tolithium immediate-release treatment: A randomized clinicaltrial.

AimThe effect of switching from lithium immediate release (Li‐IR) to lithium prolonged release (Li‐PR) on lithium‐induced tremor after 1 and 12 weeks of treatment was evaluated in a randomized, multicenter, open trial, in bipolar patients from the participating sites with a tremor severity ≥2 (Udvalg for Kliniske Undersøgelser [UKU] rating scale) despite optimal lithium titration.MethodsThe primary endpoint was the evaluation of tremor by means of the UKU scale after 1 week of treatment. Secondary endpoints included manic Young Mania Rating Scale (YMRS) and depressive symptoms (Montgomery–Asberg Depression Rating Scale), a global assessment of the patient's status (Clinical Global Impression), polyuria/polydipsia (UKU item 3.8) and patient‐reported outcomes.ResultsOwing to difficulties in including suitable patients the enrollment phase was closed when 73 patients were randomized. Notwithstanding the lower number of patients, in the modified intention‐to‐treat population (n = 70) the primary endpoint was statistically significant: tremor improved after 1 week in 62.9% in Li‐PR group against 20.0% of patients in Li‐IR group (p = .0006; two‐tailed Fisher's exact test). The difference remained statistically significant after 4 (p = .0031) and 12 weeks (p = .0128). The same analysis performed in the PP population confirmed these results. Among the secondary endpoints, only the factor convenience of the treatment satisfaction questionnaire showed a statistically significant difference between groups. There were no apparent differences in the safety profile of the two formulations.ConclusionsThis study is the first comparative documentation of a potential benefit of the prolonged‐release formulation in reducing the symptom tremor, a well‐known adverse effect of lithium therapy. Indeed, the study results should be interpreted taking into account the sample size lower than planned.

Dose-dependent transcriptional effects of lithium and adverse effect burden in a psychiatric cohort

Lithium is the first-line treatment for bipolar disorder (BD), but there is a large variation in response rate and adverse effects. Although the molecular effects of lithium have been studied extensively, the specific mechanisms of action remain unclear. In particular, the molecular changes underlying lithium adverse effects are little known. Multiple linear regression analyses of lithium serum concentrations and global gene expression levels in whole blood were carried out using a large case-control sample (n = 1450). Self-reported adverse effects of lithium were assessed with the “Udvalg for Kliniske Undersøgelser” (UKU) adverse effect rating scale, and regression analysis was used to identify significant associations between lithium-related genes and six of the most common adverse effects. Serum concentrations of lithium were significantly associated with the expression levels of 52 genes (FDR < 0.01), largely replicating previous results. We found 32 up-regulated genes and 20 down-regulated genes in lithium users compared to non-users. The down-regulated gene set was enriched for several processes related to the translational machinery. Two adverse effects were significantly associated (p < 0.01) with three or more lithium-associated genes: tremor (FAM13A-AS1, FAR2, ITGAX, RWDD1, and STARD10) and xerostomia (ANKRD13A, FAR2, RPS8, and RWDD1). The adverse effect association with the largest effect was between CAMK1D expression and nausea/vomiting. These results suggest putative transcriptional mechanisms that may predict lithium adverse effects, and could thus have a large potential for informing clinical practice.

Effect of nurse-led screening linked brief psycho-education for improving adherence to antipsychotic medications among clients with mental illness: A quasi-experimental study

Background: Despite the significant improvements in pharmacotherapy, nonadherence to antipsychotic medication is consistently reported in the literature. Many studies evaluated the side effects of antipsychotic medications but there is scanty evidence regarding screening linked intervention. Aim: The study investigated the effect of nurse-led screening linked brief psycho-education in improving adherence to antipsychotic medication among treatment-seeking clients with mental illness. Materials and Methods: This study is a quasi-experimental study in which a total of 80 subjects were consecutively recruited as per the sampling criteria. The side effect of antipsychotic medication was measured using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU-SERS). A trained nurse delivered a 30-minute individual-based screening linked brief psychoeducation for the management of side effects as per the standard module. The outcome measures were changes in adherence to medication measured as per the medication adherence rating scale (MARS-5©Professor Rob Horne) during a 1-month follow-up. Results: Anxiety (40%), reduced duration of sleep (40%), reduced salivation (36%) were the most common moderate-to-severe side effects as per UKU-SERS. Overall, the study observed a significant improvement of self-reported medication adherence in the intervention group as compared to the control group during the 1-month follow-up (F = 46.49; P < 0.001). Conclusion: The nurse-led screening linked brief psychoeducation may be an effective strategy for improving adherence to antipsychotic medication in this setting. More studies should be conducted in similar settings for an evidence base to advocate the role of the nurse as a brief intervention therapist in the routine mental health care setting.

The polymorphic variants DRD2 rs1800497 and ABCB1 3435C&gt;T are associated with antipsychotic safety parameters in adolescents with an acute psychotic episode: the results of a pilot study

Children and adolescents are more likely than adults to experience adverse side effects when taking antipsychotics. Pharmacogenetic testing allows one to more accurately choose the initial dose of a drug. The genes of pharmacokinetic factors have been shown to be of high prognostic value for the safety of antipsychotics in adults.Patients and methods. The study enrolled 36 adolescents (58.3% male) (mean age, 14.83±1.84 years). All the patients took an antipsychotic. The follow-up lasted 28 days. On 14 and 28 days of treatment, its efficiency and safety were evaluated using the Children's Global Assessment Scale (CGAS), the Positive and Negative Syndrome Scale (PANSS), the Udvalg for Kliniske Undersњgelser Side Effects Rating Scale (UKU-SERS), the Simpson-Angus Scale (SAS), and the Barnes Akathisia Rating Scale (BARS). The patients were genotyped for CYP3A4*22, CYP3A5*3, CYP2D6*4, *9, *10, ABCB1 1236C&gt;T, 2677G&gt;T/A, 3435C&gt;T, DRD2 rs1800497, DRD4 rs1800955, and HTR2A rs6313.Results and discussion. The decrease in the mean score of the PANSS subscale “Productive symptoms” was more pronounced in carriers of the DRD2 rs1800497 polymorphic variant (-6.5 [-10.25; -3.75] vs -3 [-6.5; -2 ] on 14 day (p=0.028) and (-11 [-13; -9.5] vs -5 [-9; -3.5] on 28 day (p=0.001) compared to baseline. The carriage of ABCB1 3435CT+TT was associated with worse tolerance to pharmacotherapy on 14 day (the total score of the UKU-SERS M, 8 [3; 11.75] vs M, 2 [1; 6]; p=0.034). The carriers of DRD2 rs1800497 reported a greater severity of antipsychotic-induced neurological disorders (UKU-SERS subscale score M, 1 [0; 2.25] vs M 0 [0; 1]; p=0.029).Conclusion. The polymorphic variants DRD2 rs1800497 and ABCB1 3435C&gt;T were established to be significantly associated with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode.

Risperidone versus placebo for aggression following traumatic brain injury: a feasibility randomised controlled trial

ObjectivesTo conduct a feasibility randomised controlled trial of risperidone for the treatment of aggression in adults with traumatic brain injury (TBI).DesignMulticentre, parallel design, placebo controlled (1:1 ratio) double-blind feasibility trial...

One-year Outcome of First vs. Later Episode Schizophrenia: A Real-world Naturalistic Study

ObjectiveThe aim the study was to calculate remission, recovery and relapse rates in first episode patients with schizophrenia (FES) vs. patients at a later phase (non-FES).MethodsThirty-two FES and 101 non-FES patients took part in the study. The assessment included testing at baseline and at 1 year with the Positive and Negative Syndrome Scale (PANSS), Calgary Depression scale, State-Trait Anxiety Inventory (STAI), Udvalg for Kliniske Undersøgelser (UKU) scale, Simpson Angus, and General Assessment of Functioning (GAF) subscale. The statistical analysis included chi-square test and analysis of covariance.ResultsAt baseline 15.62% FES vs. 10.89% non-FES patients were in remission; none of FES vs. 2.97% non-FES patients were in recovery. At endpoint, the respective figures were 12.50% vs. 25.00% and 3.12% vs. 3.96%. None of the differences in rates was significant between the two groups except from the percentage of patients being under medication (higher in the non-FES group). Baseline PANSS negative subscale (PANSS-N) was the only predictor of the outcome at endpoint.ConclusionThe current study reported very low rates of remission and recovery of patients with schizophrenia without any differences between FES and non-FES patients. One possibility is that the increased antipsychotic treatment compensates for the worsening of the illness with time. An accumulating beneficial effect of antipsychotic treatment suggested that early lack of remission is not prognostic of a poor outcome.

Clinical validation of the self-reported Glasgow Antipsychotic Side-effect Scale using the clinician-rated UKU side-effect scale as gold standard reference.

Antipsychotics are key for the treatment of psychotic and several non-psychotic disorders. Unfortunately, antipsychotic medications are associated with side effects, which may reduce quality of life and treatment adherence. Therefore, regular screening of antipsychotic side effects is essential. The Glasgow Antipsychotic Side-effect Scale is a patient self-report scale developed for this purpose. However, the Glasgow Antipsychotic Side-effect Scale has only been validated against another self-report side effect measure, which is suboptimal. We aimed to validate the Glasgow Antipsychotic Side-effect Scale using the clinician-rated Udvalg for Kliniske Undersøgelser side-effect rating scale as the gold standard reference. 81 antipsychotic-treated outpatients with schizophrenia-spectrum disorders (age = 42±13 years; males = 43%, schizophrenia = 77%, illness duration: median = 11 years) completed the Glasgow Antipsychotic Side-effect Scale and were subsequently scored on the Udvalg for Kliniske Undersøgelser by trained raters. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for paired Glasgow Antipsychotic Side-effect Scale and Udvalg for Kliniske Undersøgelser items. Sensitivity of Glasgow Antipsychotic Side-effect Scale items ranged from 33-96%, with 19 (86%) having >75% sensitivity. Lowest sensitivity emerged for "nocturnal enuresis" (33%), "galactorrhea" (50%) and "hyperkinesia" 14-99%, with 14 items (64%) having >75% specificity, being lowest for "asthenia" (14%), "polyuria/polydipsia" (35%), "sedation" (41%), "akathisia" (53%), "dystonia" (65%), "hyperkinesia" (68%), "hypokinesia" (70%) and "accommodation" (70%). Positive predictive value ranged from 7-85%, with six items (27%) having a positive predictive value >75%. Negative predictive value ranged from 40-98%, with 21 items (95%) having a negative predictive value >75%. The mean time to complete the Glasgow Antipsychotic Side-effect Scale was 4±2 minutes. The Glasgow Antipsychotic Side-effect Scale demonstrated satisfactory validity as a self-rated tool for antipsychotic side effects and may aid measurement-based care and decision-making.

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.

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). 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. We included 21 adolescents with first-episode psychosis (62% treated with antipsychotics; males 38%; mean age 16±1.4years) and 69 healthy controls (males 36%; mean age 16±1.5years). 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. 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.

Differentiated approach and indications for optimization of agomelatine therapy for endogenous depression

Objective: to develop and justify differentiated indications for the use of agomelatine (valdoxan) to treat the typological variants of endogenous depressions with varying severity on the basis of an analysis of its therapeutic efficacy.Patients and methods. An open prospective study was conducted using the clinical, psychopathological, and psychometric rating scales: the Hamilton Depression Rating Scale (HAMD-21); Udvalg for Kliniske Undersњgelser Scale (UKU); the Snaith-Hamilton Pleasure Scale (SHAPS) for assessing anhedonic disorders, and statistical methods. Examinations were made in 56 patients (mean age, 34.9 years) with moderate and severe endogenous depression within affective psychosis (n=42) and shift-like schizophrenia (n=14) (ICD-10 items F31.3–4; F32.1–2, and F33.1–2). The patients received a cycle treatment with agomelatine (valdoxan) 25–50 mg once a day in the evening for 4–8 weeks. The patients' status was evaluated over time on fixed days from a reduction in the mean total score (MTS) of the respective scales as insignificant (less than 19% reduction in disorders), moderate (20–49%), good (50–69%), and excellent (70% or more) effects. The effect of agomelatine was analyzed in two patient groups. The specific features of the antidepressive effect and its dynamics in the presence of endogenous depressions of different typologies (melancholic, anxious, and adynamic depressions) were studied in Group 1 (n=26); the effect of agomelatine on anhedonic endogenous depressions and manifestations of anhedonia in different mental activity areas (interests, social activity, emotional engagement and eating/drinking) was investigated in Group 2 (n=30).Results and discussion. There was a good tolerance and a high antidepressant activity of agomelatine during its treatment cycle for moderate and severe endogenous depressions. A significant improvement (an 84.4% reduction in HAMD-21 MTS) was noted in patients at 3 and 4 weeks of the treatment cycle and consistently persisted at a subsequent follow-up. Agomelatine showed a good effect (a 50% or more reduction in HAMD-21 MTS) just at 14 days of therapy. The drug was observed to have a balanced antidepressant effect, significant thymoleptic, stimulant, anxiolytic, and antianhedonic activities (reductions in the MTS of depressive disorders by 90.83, 84.9, 82.39, and 78.9%, respectively).Conclusion. The universal spectrum of the antidepressive effect of agomelatine, its good tolerability, high efficacy, and rapid improvement makes it the drug of choice in treating a wide range of psychopathological endogenous depressions: melancholic, apatho-adynamic, anxious, and anhedonic ones.

Sexual dysfunction in patients with schizophrenia and schizoaffective disorder and its association with adherence to antipsychotic medication

Background: Antipsychotic-induced sexual dysfunction is a common complaint among patients with psychotic disorders. However, few papers have discussed its impact on treatment adherence.Aims: The aim of the study was to determine the prevalence of antipsychotic induced sexual dysfunction in patients with schizophrenia and schizoaffective disorder and assess its impact on treatment adherence.Methods: Nighty-five outpatients treated with antipsychotics for at least four weeks were recruited. Sexual dysfunction was assessed using a questionnaire inspired from the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale and the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ). An Arabic version of the Medication Adherence Rating Scale (MARS) was used to assess treatment adherence.Results: The prevalence of sexual dysfunction was 57.9%, of which 65.5% attributed it to treatment. Reduced desire was the mostly reported sexual dysfunction in males and females. Number, dose and duration of antipsychotics were not associated with sexual dysfunction. MARS score was associated with the presence of sexual dysfunction (p = 0.0001) and its attribution to antipsychotic medication (p = 0.0003), the latter being an independent associated variable (p = 0.001).Conclusion: Sexual dysfunction is prevalent in patients with schizophrenia and schizoaffective disorder treated with antipsychotic drugs. Clinicians should ask about sexual dysfunction and discuss its different causes with patients in order to improve adherence.

Side effect burden of antipsychotic drugs in real life – Impact of gender and polypharmacy

BackgroundAntipsychotic-associated side effects are well known and represent a significant treatment challenge. Still, few large studies have investigated the overall side effect burden of antipsychotics in real-life settings. ObjectiveTo describe the occurrence of side effects and perceived burden of antipsychotics in a large naturalistic sample, taking polypharmacy and patient characteristics into account. MethodPatients (n=1087) with psychotic disorders were assessed for side effects using the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale in addition to assessment of clinical and pharmacological data. Statistical analyses were performed controlling for possible confounding factors. ResultsUse of antipsychotics showed significant associations to neurologic and sexual symptoms, sedation and weight gain, and >75% of antipsychotics-users reported side effects. More side effects were observed in patients using several antipsychotics (p=0.002), with increasing total dose (p=0.021) and with antipsychotics in combinations with other psychotropic drugs. Patients and investigators evaluated the side effect burden differently, particularly related to severity, gender and antipsychotics dose. Twice as many females described side effect burden as severe (p=0.004). ConclusionPatients with psychotic disorders have a high occurrence of symptoms associated with use of antipsychotics, and polypharmacy and female gender are seemingly risk factors for reporting a severe side effect burden. Due to the cross-sectional design evaluation of causality is tentative, and these findings should be further investigated in prospective studies.