Overactive, aggressive, disruptive and agitated behavior associated with the use of psychotropic medications in schizophrenia

Background Evidence is limited for the associations between use of psychotropic medications and overactive, aggressive, disruptive or agitated behavior (OADA)1 in clinical practice. Aims To investigate the associations between risk of readmission with OADA and use of antipsychotics, antidepressants, mood stabilizers and benzodiazepines in patients with schizophrenia. Method A consecutive total cohort diagnosed with schizophrenia (N = 663) after admission to the Haukeland University Hospital psychiatric acute unit in Bergen, Norway, was followed from discharge over a 10-year period. At every following readmission, the level of OADA was assessed using the first item of the Health of the Nation Outcome Scale (HoNOS). Periods of use versus non-use of antipsychotics, antidepressants, mood stabilizers and benzodiazepines were recorded as time-dependent variables in each patient and compared using Cox multiple regression analyses. Results A total of 161 (24.3 %) patients were readmitted with OADA, and the mean (SD) and median times in years to readmission with OADA were 2.8 (2.6) and 2.1, respectively. We found that the risk of readmission with OADA was negatively associated with use of antipsychotics (adjusted hazard ratio (AHR) = 0.33, p < 0.01, CI: 0.24–0.46) and antidepressants (AHR = 0.57, p = 0.03, CI: 0.34–0.95), positively associated with use of benzodiazepines (AHR = 1.95, p < 0.01, CI: 1.31–2.90) and not significantly associated with use of mood stabilizers. Conclusions Use of antipsychotics and antidepressants is associated with reduced risk of readmission with OADA whereas benzodiazepines are associated with an increased risk of readmission with OADA in patients with schizophrenia.publishedVersio

Illicit substances detected through high-resolution MS analysis in urine samples are associated with greater symptom burden in patients with psychosis

Background The prevalence of new psychoactive substances (NPS) in acute psychotic patients has not been investigated systematically. We applied a highly sensitive and specific mass spectrometry method for detection of NPS as well as traditional drugs of abuse (including illicit or prescription substances) in order to assess their prevalence and associations with symptom severity. Identification of these substances is useful in both the diagnostic process and evaluation of treatment effects. Methods Demographic data, results from the Positive and Negative Syndrome Score (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) and urine samples from admission were collected from 53 patients recruited into a clinical study of psychosis during 2014-2017. Urine samples were analysed with liquid chromatography high resolution mass spectrometry (LC-QTOF-MS), through both highly specific detection of 191 substances using internal standards and untargeted screening by means of pre-defined libraries. PANSS and CDSS scores in patients with or without drugs of abuse were compared. Results Potential drugs of abuse, i.e. drugs that could be used in a controlled therapeutic or a non-prescribed manner, were detected in samples from 20 of the 53 patients. Seven samples contained illicit drugs, but no NPS were detected. In this small patient subgroup, PANSS total score and CDSS score were significantly higher than in patients with negative urine sample results. Conclusion Drug screening could play an important role in the differential diagnostic evaluation of patients admitted with psychotic symptoms. Although no NPS were detected in the study population, we found other substances that were associated with psychotic and depressive symptoms.publishedVersio

Use of Benzodiazepines and Antipsychotic Drugs Are Inversely Associated with Acute Readmission Risk in Schizophrenia

Purpose: Little is known about the impact of different psychotropic drugs on acute readmission risk, when used concomitantly in a real-life setting. We aimed to investigate the association between acute readmission risk and use of antipsychotic drugs, antidepressants, mood stabilizers, and benzodiazepines in patients with schizophrenia. Methods: A cohort study included all patients diagnosed with schizophrenia admitted to a psychiatric acute unit at Haukeland University Hospital in Bergen, Norway, during a 10-year period (N = 663). Patients were followed from discharge until first readmission or censoring. Cox multiple regression analyses were conducted using antipsychotic drugs, antidepressants, mood stabilizers, and benzodiazepines as time-dependent variables, and periods of use and nonuse were compared within individual patients. Adjustments were made for sex, age at index admission, and excessive use of alcohol and illicit substances. Results: A total of 410 patients (61.8%) were readmitted during follow-up, and the mean and median times in days to readmission were 709 and 575, respectively. Compared with nonuse, the use of antipsychotic drugs was associated with reduced risk of readmission (adjusted hazards ratio, 0.20; P < 0.01; confidence interval, 0.16–0.24), and the use of benzodiazepines was associated with increased risk of readmission (adjusted hazards ratio, 1.51; P < 0.01; confidence interval, 1.13–2.02). However, no relation to readmission risk was found for the use of antidepressants and mood stabilizers. Conclusions: We found that use of benzodiazepines and antipsychotic drugs are inversely associated with acute readmission risk in schizophrenia.publishedVersio

Sex differences in antipsychotic efficacy and side effects in schizophrenia spectrum disorder:results from the BeSt InTro study

Current guidelines for patients with schizophrenia spectrum disease do not take sex differences into account, which may result in inappropriate sex-specific treatment. In the BeSt InTro study, a total of 144 patients (93 men and 51 women) with a schizophrenia spectrum diagnosis and ongoing psychosis were included and randomized to amisulpride, aripiprazole, or olanzapine in flexible dose. This trial is registered with ClinicalTrials.gov (NCT01446328). Primary outcomes were sex differences in dose, dose-corrected serum levels, efficacy, and tolerability. Dosing was higher for men than for women in the aripiprazole group (p = 0.025) and, at trend level, in the olanzapine group (p = 0.056). Dose-corrected serum levels were 71.9% higher in women than in men for amisulpride (p = 0.019) and 55.8% higher in women than in men for aripiprazole (p = 0.049). In the amisulpride group, men had a faster decrease in psychotic symptoms than women (p = 0.003). Moreover, amisulpride was more effective than the other medications in men but not in women. Prolactin levels were higher in women than in men, especially for amisulpride (p < 0.001). Also, women had higher BMI increase on amisulpride compared to the two other antipsychotics (p < 0.001). We conclude that clinicians should be aware of the risks of overdosing in women, especially for amisulpride and aripiprazole. Amisulpride is highly effective in men, but in women, amisulpride showed more severe side effects and may thus not be the drug of first choice. Our study shows that sex differences should be taken into account in future studies on antipsychotics. Future research is warranted to evaluate these preliminary results

Homogeneity in prediction of survival probabilities for subcategories of hipprosthesis data: the Nordic Arthroplasty Register Association, 2000-2013

Introduction: The four countries in the Nordic Arthroplasty Register Association (NARA) share geographic proximity, culture, and ethnicity. Pooling data from different sources in order to obtain higher precision and accuracy of survival-probability estimates is appealing. Nevertheless, survival probabilities of hip replacements vary between the countries. As such, risk prediction for individual patients within countries may be problematic if data are merged. In this study, our primary question was to address when data merging for estimating prosthesis survival in subcategories of patients is advantageous for survival prediction of individual patients, and at what sample sizes this may be advised.Methods: Patients undergoing total hip replacements for osteoarthritis between January 1, 2000 and December 31, 2013 in the four Nordic countries were studied. A total of 184,507 patients were stratified into 360 patient subcategories based on country, age-group, sex, fixation, head size, and articulation. For each patient category, we determined the sample size needed from a single country to obtain a more accurate and precise estimate of prosthesis-survival probability at 5 and 10 years compared to an estimate using data from all countries. The comparison was done using mean-square error.Results: We found large variations in the sample size needed, ranging from 40 to 2,060 hips, before an estimate from a single Nordic country was more accurate and precise than estimates based on the NARA data.Conclusion: Using pooled survival-probability estimates for individual risk prediction may be imprecise if there is heterogeneity in the pooled data sources. By applying mean-square error, we demonstrate that for small sample sizes, applying the larger NARA database may provide a more accurate and precise estimate; however, this effect is not consistent and varies with the characteristics of the subcategory.</p

&nbsp;Sammenligning av ulike metoder innen ekstremverdistatistikk

Hensikten med denne oppgaven har vært å se på ulike metoder som i dag benyttes for å predikere ekstremverdier i marin sammenheng. Fem ulike metoder er sammenlignet. Metodene er valgt på grunnlag av hvor mye de benyttes og hvor gode de er ansett for å være. Det er sett på ekstremverdier for en fiktiv men realistisk responsstørrelse avhengig av bølgeparametrene HS og TP. 100, 1000 og 10 000-års verdier for responsstørrelsen er beregnet ved de ulike metodene. Utgangspunktet for alle beregningene er en ca 51 år lang tidsserie med verdier av HS og TP. De resulterende ekstremverdiene beregnet ved de ulike metodene er forholdsvis like. Men noen av metodene er allikevel å foretrekke fremfor andre. Hvor god de ulike metodene er, er vurdert ut fra; hvor gode antagelsene metodene bygger på er, hvor godt metodene benytter informasjonen i de tilgjengelige dataene, hvordan metodene tar hensyn til stor avhengighet i dataene, og hvor enkel metodene er å bruke. Den beste metoden av de det her er sett på, er etter forfatters mening, Næss-Gaidai-metoden hvor prinsippet går ut på å modellere nivåoppkrysningsfrekvensen til prosessen man studerer. Det er ved denne metoden antatt at antall ganger prosessen krysser et høyt nivå iløpet av en tidsperiode T, er Poissonfordelt, noe som er en god antagelse, med parameter lik nivåoppkrysningsfrekvensen multiplisert med T. Ved å modellere nivåoppkrysningsfrekvensen kan man derfor finne det nivået som krysses med ønskelig returperiode

Imminent and Short-Term Risk of Death by Suicide in 7,000 Acutely Admitted Psychiatric Inpatients

Objective: To prospectively investigate the predictive value of diagnosis, suicidal behavior, and subjectively experienced depressed mood for imminent risk of suicide death. Methods: This prospective study included a representative and diagnostically mixed sample of 7,000 acutely hospitalized psychiatric patients between May 2005 and July 2014 in a Norwegian catchment area of 400,000 inhabitants. Suicide deaths were registered at 1 and 2 weeks and at 1, 6, and 12 months following admission. Survival and hazard functions were estimated, and Cox regression was used to estimate the predictive values of suicidal ideation, suicide attempts, a diagnosis of depressive disorder, and severely depressed mood. Assessments were conducted at admission and included ICD-10 diagnosis, clinical interview in the form of the Health of the Nation Outcome Scales, and qualitative assessments of suicidal ideation and suicide attempts during the past week. Results: During 1-year follow-up, 101 patients (1.4%) died by suicide, of whom almost 70% were men. Only severely depressed mood, including inappropriate self-blame and guilt, predicted suicide within the first week after admission (hazard ratio [HR] = 7.3; 95% confidence interval [CI], 1.4–37.1; P = .01). Suicidal ideation predicted death by suicide at 2 weeks (HR = 3.8; 95% CI, 1.2–12.8; P = .02) and all follow-up time points after, whereas a recent suicide attempt predicted suicide from the 1-month follow-up (HR = 7.3; 95% CI, 2.2–23.7; P < .001) onward. Conclusions: We recommend thoroughly examining severity of depressed mood during assessment of imminent suicide risk.publishedVersio

Overactive, aggressive, disruptive and agitated behavior associated with the use of psychotropic medications in schizophrenia

Background Evidence is limited for the associations between use of psychotropic medications and overactive, aggressive, disruptive or agitated behavior (OADA)1 in clinical practice. Aims To investigate the associations between risk of readmission with OADA and use of antipsychotics, antidepressants, mood stabilizers and benzodiazepines in patients with schizophrenia. Method A consecutive total cohort diagnosed with schizophrenia (N = 663) after admission to the Haukeland University Hospital psychiatric acute unit in Bergen, Norway, was followed from discharge over a 10-year period. At every following readmission, the level of OADA was assessed using the first item of the Health of the Nation Outcome Scale (HoNOS). Periods of use versus non-use of antipsychotics, antidepressants, mood stabilizers and benzodiazepines were recorded as time-dependent variables in each patient and compared using Cox multiple regression analyses. Results A total of 161 (24.3 %) patients were readmitted with OADA, and the mean (SD) and median times in years to readmission with OADA were 2.8 (2.6) and 2.1, respectively. We found that the risk of readmission with OADA was negatively associated with use of antipsychotics (adjusted hazard ratio (AHR) = 0.33, p < 0.01, CI: 0.24–0.46) and antidepressants (AHR = 0.57, p = 0.03, CI: 0.34–0.95), positively associated with use of benzodiazepines (AHR = 1.95, p < 0.01, CI: 1.31–2.90) and not significantly associated with use of mood stabilizers. Conclusions Use of antipsychotics and antidepressants is associated with reduced risk of readmission with OADA whereas benzodiazepines are associated with an increased risk of readmission with OADA in patients with schizophrenia

Unmasking patient diversity: Exploring cognitive and antidepressive effects of electroconvulsive therapy

Abstract Background Electroconvulsive therapy (ECT) is an established treatment for depression, but more data on effectiveness and safety in clinical practice is needed. The aim of this register-based study was to investigate short-term effectiveness and cognitive safety after ECT, evaluated by clinicians and patients. Secondary, we investigated predictors for remission and cognitive decline. Methods The study included 392 patients from the Regional Register for Neurostimulation Treatment in Western Norway. Depressive symptoms and cognitive function were assessed with Montgomery-Åsberg Depression Rating Scale and Mini-Mental State Examination (clinician-rated) and Beck Depression Inventory and Everyday Memory Questionnaire (patient-rated). Assessments were done prior to ECT-series and a mean of 1.7 days after (range 6 days before and 12 days after) end of ECT-series. Paired samples t-tests were extended by detailed, clinically relevant subgroups. Predictors were examined using logistic regression. Results Clinician- and patient-rated remission rates were 49.5 and 41.0%, respectively. There was a large reduction in depressive symptoms and a small improvement in cognition after ECT, but we also identified subgroups with non-response of ECT in combination with cognitive decline (4.6% clinician-rated, 15.7% patient-rated). Positive predictors for patient- and clinician-rated remission were increasing age, shorter duration of depressive episode, and psychotic features. Antipsychotic medication at the commencement of treatment and previous ECT-treatment gave higher odds of clinician-rated remission, whereas higher pretreatment subjective depression level was associated with lower odds for patient-rated remission. Clinician-rated cognitive decline was predicted by higher pretreatment MMSE scores, whereas psychotic features, increasing age, and greater pretreatment subjective memory concerns were associated with lower odds for patient-rated cognitive decline. Conclusions Our study supports ECT as an effective and safe treatment, although subgroups have a less favorable outcome. ECT should be considered at an early stage for older patients suffering from depression with psychotic features. Providing comprehensive and balanced information from clinicians and patients perspectives on effects and side effects, may assist in a joint consent process

Illicit substances detected through high-resolution MS analysis in urine samples are associated with greater symptom burden in patients with psychosis

Background The prevalence of new psychoactive substances (NPS) in acute psychotic patients has not been investigated systematically. We applied a highly sensitive and specific mass spectrometry method for detection of NPS as well as traditional drugs of abuse (including illicit or prescription substances) in order to assess their prevalence and associations with symptom severity. Identification of these substances is useful in both the diagnostic process and evaluation of treatment effects. Methods Demographic data, results from the Positive and Negative Syndrome Score (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) and urine samples from admission were collected from 53 patients recruited into a clinical study of psychosis during 2014-2017. Urine samples were analysed with liquid chromatography high resolution mass spectrometry (LC-QTOF-MS), through both highly specific detection of 191 substances using internal standards and untargeted screening by means of pre-defined libraries. PANSS and CDSS scores in patients with or without drugs of abuse were compared. Results Potential drugs of abuse, i.e. drugs that could be used in a controlled therapeutic or a non-prescribed manner, were detected in samples from 20 of the 53 patients. Seven samples contained illicit drugs, but no NPS were detected. In this small patient subgroup, PANSS total score and CDSS score were significantly higher than in patients with negative urine sample results. Conclusion Drug screening could play an important role in the differential diagnostic evaluation of patients admitted with psychotic symptoms. Although no NPS were detected in the study population, we found other substances that were associated with psychotic and depressive symptoms