Search

Treatment with antipsychotics (APs) for schizophrenia spectrum disorders (SSDs) is generally effective, however, a significant proportion does not respond favorably. Childhood trauma (CT) subtypes (physical, sexual, and emotional abuse, physical and emotional neglect) could influence treatment effectiveness; however, research is scarce. Heterogeneity in AP response could be explained by differentiating by CT subtype. The present study was based on the Bergen-Stavanger-Trondheim-Innsbruck (BeSt InTro) study. CTQ-SF assessed CT subtypes in SSDs (n = 98). CT subtypes were examined in relation to psychosis symptoms measured by PANSS during one year of treatment with APs, by means of linear mixed effects (LME) models. Results were significant for CT subtypes, where increased levels of sexual abuse and physical neglect were associated with increased mean levels of psychosis symptoms throughout the course of treatment from baseline to 52 weeks. AP effectiveness may thus be influenced by CT subtype in SSDs. The results support clinical guidelines recommending a focus on assessment and treatment of trauma in SSDs., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Schizophrenia is a serious mental disorder, and monitoring remission is a widely used measure of effectiveness of the treatment provided. It is very important to identify possible factors correlating with remission. In our substudy of BeSt InTro, a randomized controlled trial of three antipsychotic drugs, 126 patients with ICD-10 diagnoses F20-29 (F23 excluded) were randomized to one of the second-generation antipsychotic drugs amisulpride, aripiprazole or olanzapine. Remission rate was calculated at seven assessment points, with and without using the time criterion of six months included in the consensus remission criteria. Because of drop-out (n = 77), we had data for 49 patients at one-year follow-up. These data were used to calculate the one-year remission rate to 55 % (27/49), without taking into consideration the 6-month time criterion. When we applied the consensus remission criteria with the 6-month time criterion included, the one-year remission rate was calculated for 59 patients: 29 % (17/59). Antipsychotic drug naivety and low negative symptom load at baseline correlated highly with belonging to the remission group. Use of amisulpride was more probable to lead to remission than that of aripiprazole, but it was not more probable than the use of olanzapine (in per-protocol analyses). Negative symptoms showed the largest resistance to treatment. The lack of remission for the majority of the participants in this closely monitored antipsychotic drug trial is alarming and could act as a reminder that novel treatment principles are needed, especially targeted towards the negative symptoms in schizophrenia., Competing Interests: Declaration of competing interest The authors have declared that there are no conflicts of interest in relation to this study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Drug use is prevalent in patients with schizophrenia spectrum disorders (SSD) but there is limited knowledge about the influence of drug use on the effectiveness of antipsychotic medication. This secondary explorative study compared the effectiveness of three antipsychotics in patients with SSD, with and without drug use., Methods: The BeSt InTro multi-centre, head to head, rater-blinded randomised study compared amisulpride, aripiprazole and olanzapine over a 1-year follow-up period. All patients (n = 144) were aged ≥18 years and met the ICD-10 criteria for SSD (F20-29). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The primary outcome was reduction of a PANSS positive subscale score., Results: At baseline, 38% of all patients reported drug use in the last 6 months before inclusion, with cannabis as the main drug (85%), followed by amphetamine-type stimulants (45%), sedatives (26%), hallucinogens (19%), cocaine (13%), opiates (4%), GHB (4%), solvents (4%), analgesics (4%) and anabolic steroids (2%). The predominant pattern was the use of several drugs. There were no significant overall differences in the PANSS positive subscale score reduction for the three studied antipsychotics among patients either with or without drug use. In the drug use group, older patients treated with amisulpride showed a greater PANSS positive subscale score reduction during the treatment period compared to younger patients., Conclusion: The current study showed that drug use does not appear to affect the overall effectiveness of amisulpride, aripiprazole and olanzapine in patients with SSD. However, amisulpride may be a particularly suitable choice for older patients with drug use., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Antipsychotic treatment may improve clinical insight. However, previous studies have reported inconclusive findings on whether antipsychotics improve insight over and above the reduction in symptoms of psychosis. These studies assessed homogeneous samples in terms of stage of illness. Randomised studies investigating a mixed population of first- and multiepisode schizophrenia spectrum disorders might clarify this disagreement., Methods: Our data were derived from a pragmatic, rater-blinded, semi-randomised trial that compared the effectiveness of amisulpride, aripiprazole and olanzapine. A sample of 144 patients with first- or multiepisode schizophrenia spectrum disorders underwent eight assessments during a 1-year follow-up. Clinical insight was assessed by item General 12 from the Positive and Negative Syndrome Scale (PANSS). We analysed latent growth curve models to test if the medications had a direct effect on insight that was over and above the reduction in total psychosis symptoms. Furthermore, we investigated whether there were differences between the study drugs in terms of insight., Results: Based on allocation analysis, all three drugs were associated with a reduction in total psychosis symptoms in the initial phase (weeks 0-6). Amisulpride and olanzapine were associated with improved insight over and above what was related to the reduction in total psychosis symptoms in the long-term phase (weeks 6-52). However, these differential effects were lost when only including the participants that chose the first drug in the randomisation sequence. We found no differential effect on insight among those who were antipsychotic-naïve and those who were previously medicated with antipsychotics., Conclusions: Our results suggest that antipsychotic treatment improves insight, but whether the effect on insight surpasses the effect of reduced total psychosis symptoms is more uncertain., Trial Registration: ClinicalTrials.gov Identifier: NCT01446328, 05.10.2011., (© 2023. The Author(s).)

Background: Depressive symptoms are frequent in schizophrenia and associated with a poorer outcome. Currently, the optimal treatment for depressive symptoms in schizophrenia remains undetermined. Amisulpride, aripiprazole, and olanzapine all have antidepressive pharmacodynamic properties, ranging from serotonergic affinities to limbic dopaminergic selectivity. Consequently, in a 12-month pragmatic, randomized clinical trial, we aimed to investigate differences in antidepressive effectiveness among amisulpride, aripiprazole, and olanzapine as a secondary outcome, measured by change in the Calgary Depression Scale for Schizophrenia sum score in patients within the schizophrenia spectrum., Methods: Psychotic patients within the schizophrenia spectrum were included, and effectiveness was analyzed with latent growth curve modeling., Results: Of the 144 patients, 51 (35%) were women, the mean age was 31.7 (SD 12.7), and 39% were antipsychotic naive. At inclusion, 68 (47%) participants had a Calgary Depression Scale for Schizophrenia sum score >6, indicating severe depressive symptoms. Across the 12-month follow-up, there was a depressive symptom reduction in all medication groups, but no statistically significant differences between the study drugs. Separate analyses of the subcohort with elevated depressive symptoms at inclusion also failed to find differences in depressive symptom reduction between study drugs. The reduction in depressive symptoms mainly occurred within 6 weeks after randomization., Conclusions: There was a reduction in depressive symptoms under treatment with amisulpride, aripiprazole, and olanzapine in acutely psychotic patients with schizophrenia spectrum disorder, but no differences between the drugs., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Approximately one-third of patients with psychotic disorders does not respond to standard antipsychotic treatments. Consensus criteria for treatment resistance (TR) may aid the identification of non-response and subsequent tailoring of treatments. Since consensus criteria require stability of clinical status, they are challenging to apply in first-episode psychosis (FEP). This study aims to investigate (a) if an adaptation of consensus criteria can be used to identify FEP patients with early signs of TR (no early clinical recovery-no-ECR) after 1 year in treatment and (b) to what extent differences in antipsychotic treatments differentiate between outcome groups., Methods: Participants with FEP DSM-IV schizophrenia spectrum disorders were recruited during their first treatment. A total of 207 participated in the 1-year follow-up. Remission and recovery definitions were based on adaptations of the "Remission in Schizophrenia Working Group" criteria and TR on adaptations of the "Treatment Response and Resistance in Psychosis" (TRRIP) working group criteria., Results: 97 participants (47%) could be classified as no-ECR, 61 (30%) as ECR, and 49 (23%) as with partial ECR (P-ECR). Statistically significant baseline predictors of no-ECR matched previously identified predictors of long-term TR. Only 35 no-ECR participants had two adequate treatment trials and met the full TRRIP criteria. 21 no-ECR participants were using the same medication over the follow-up year despite the lack of significant effects., Conclusion: The difference in the percentage of FEP participants classified as no-ECR versus TR indicates that we may underestimate the prevalence of early TR when using consensus criteria.

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., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Akathisia is among the most unpleasant side effects related to antipsychotic drug (AP) use, and possible associations between akathisia and agitation, depression and suicidal behaviour, respectively, have been described in previous literature. New generation antipsychotics are however regarded less prone to induce this particular adverse effect compared to older drugs, but evidence is incomplete and in need of confirmation from clinically relevant samples and settings. We, therefore, aim to investigate akathisia at hospital discharge for patients consecutively admitted with acute-phase psychosis and treated with atypical antipsychotics according to guideline-concordant clinical practice., Methods: This exploratory study is part of a naturalistic randomised controlled study in patients admitted with acute phase psychosis ( N = 109). We report cross-sectional data at discharge/first follow-up after acute psychiatric hospital admission for patients with schizophrenia and related psychotic disorders., Results: There were statistically significant positive associations between akathisia and the following; suicidality in men (Beta 0.306, p = 0.048), but not in women; agitation in those previously unexposed to antipsychotics (Beta 0.288, p = 0.047) and depression in those exposed to antipsychotics before hospital admittance (Beta 0.375, p = 0.031)., Conclusion: Main findings were that akathisia is still a prevalent side effect in a clinically relevant sample of patients treated with atypical antipsychotics. Our results suggest that akathisia is significantly associated with depression, suicidality and agitation in different subgroups of patients receiving APs. Akathisia can be detrimental and the relations between akathisia and depression, suicidality and agitation should be investigated further in prospective, hypothesis-testing studies with larger samples.

Antipsychotic medications are generally effective in ameliorating psychotic symptoms in schizophrenia spectrum disorders (SSDs). Identifying predictors associated with poor treatment response is important for a personalized treatment approach. Childhood trauma (CT) may have a general and differential effect on the effectiveness of different types of antipsychotics in SSDs. The Bergen-Stavanger-Trondheim-Innsbruck (BeSt InTro) study is a pragmatic, researcher-initiated, semi-randomized trial. The present study aimed to investigate symptom change (the Positive and Negative Syndrome Scale) from baseline to 1, 3, 6, 12, 26, 39 and 52 weeks of antipsychotic treatment (amisulpride, aripiprazole and olanzapine) by group (CT/no CT). Participants (n = 98) with diagnoses within the schizophrenia spectrum (F20-29 in the International Classification of Diseases - 10th Revision) were randomized to receive amisulpride, aripiprazole or olanzapine, and for this study categorized into groups of none and low CT, and moderate to severe CT according to thresholds defined by the Childhood Trauma Questionnaire Short-Form manual. CT in SSDs predicted an overall slower treatment response and less antipsychotic effectiveness after 26 weeks of treatment, which was statistically nonsignificant at 52 weeks. Secondary analyses showed a differential effect of CT related to type of antipsychotic medication: patients with SSDs and CT who received olanzapine showed less antipsychotic effectiveness throughout 52 weeks of treatment. The intention-to-treat and per-protocol analyses were convergent. Our findings indicate that in patients with SSD and CT, delayed response to antipsychotics could be expected, and a longer evaluation period before considering change of medication may be recommended., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A potential role of inflammatory pathways in the pathology of schizophrenia has been suggested for at least a subgroup of patients. Elevated levels of the inflammatory marker C-reactive protein (CRP) have been observed, with associations to pathogenesis and symptoms. The current evidence regarding effects of antipsychotics on CRP levels is ambiguous., Objectives: To examine and compare the influence on CRP levels of three pharmacologically diverse new generation antipsychotics during a one-year follow-up in schizophrenia spectrum disorder., Methods: In a multicenter, pragmatic and rater-blinded randomized trial, the effects of amisulpride, aripiprazole and olanzapine were compared in 128 patients with schizophrenia spectrum disorder. All had positive symptoms of psychosis at study entry. Clinical and laboratory assessments including the measurement of CRP levels were conducted at baseline, and 1, 3, 6, 12, 26, 39, and 52 weeks thereafter., Results: For all antipsychotic drugs analysed together, there was an increase in CRP levels during the one-year follow-up. Aripiprazole, as opposed to amisulpride and olanzapine, was associated with a reduced CRP level after one week, after which the CRP level caught up with the other drugs. Compared to those previously exposed to antipsychotic drugs, antipsychotic-naïve patients had lower CRP levels at all follow-up time points, but with the same temporal patterns of change., Conclusion: Treatment with amisulpride, aripiprazole and olanzapine showed different effects on CRP levels in patients with schizophrenia spectrum disorders, modified by previous antipsychotics exposure status. This finding suggests that antipsychotic drugs may vary with respect to their influence on pro-inflammatory pathways., Trial Registration: ClinicalTrials.gov ID: NCT01446328; URL: http://www., Clinicaltrials: gov/., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In society at large, it is debated whether use of antipsychotic drugs is associated with increased or decreased mortality among patients with schizophrenia. Large register studies have demonstrated an increased mortality risk associated with non-use of antipsychotic drugs, but prospective studies are missing., Aims: To investigate the association between mortality and non-use of antipsychotics in patients with schizophrenia., Method: An open cohort study included and followed all patients with a discharge-diagnosis of schizophrenia consecutively admitted to a psychiatric acute unit at Haukeland University Hospital, Bergen, Norway during a 10 year period (n = 696). Cox multiple regression analyses were conducted with use of antipsychotic drugs as a time dependent variable, and periods of use and non-use were compared within individual patients. Adjustments were made for gender, age at index admission, number of acute psychiatric hospital admissions, excessive use of alcohol and illicit substances and use of benzodiazepines and antidepressants., Results: A total of 68 (9.8%) deaths were registered during follow-up. Of these, 40 (59%) had natural causes, whereas 26 (38%) had unnatural causes. Non-use of antipsychotics was associated with 2.15 (p = .01, CI: 1.24-3.72) times higher mortality risk compared to use of antipsychotics. The difference in mortality risk between use and non-use of antipsychotic drugs was age dependent, with the largest risk difference in young patients., Conclusions: Non-use of antipsychotic drugs was associated with twofold increased mortality risk in patients with schizophrenia., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Amisulpride, aripiprazole, and olanzapine are first-line atypical antipsychotics that have not previously been compared head-to-head in a pragmatic trial. We aimed to compare the efficacy and safety of these agents in a controlled trial., Methods: This pragmatic, rater-blind, randomised controlled trial was done in three academic centres of psychiatry in Norway, and one in Austria. Eligible patients were aged 18 years or older, met ICD-10 criteria for schizophrenia-spectrum disorders (F20-29), and had symptoms of active psychosis. Eligible patients were randomly assigned to receive oral amisulpride, aripiprazole, or olanzapine. Treatment allocation was open to patients and staff, and starting dose, treatment changes, and adjustments were left to the discretion of the treating physician. Computer-generated randomisation lists for each study centre were prepared by independent statisticians. Patients were followed up for 52 weeks after random assignment, during which assessments were done 8 times by researchers masked to treatment. The primary outcome was reduction of the Positive And Negative Syndrome Scale (PANSS) total score at 52 weeks, and primary analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01446328., Findings: Between Oct 20, 2011, and Dec 30, 2016, we assessed 359 patients for eligibility. 215 patients were excluded (107 did not meet inclusion criteria, 82 declined to participate, 26 other reasons). 144 patients (mean baseline PANSS total estimated score 78·4 [SD 1·4]) were randomly assigned 1:1:1 to receive amisulpride (44 patients), aripiprazole (48 patients) or olanzapine (52 patients). After 52 weeks, the patients allocated to amisulpride had a PANSS total score reduction of 32·7 points (SD 3·1) compared with 21·9 points reduction with aripiprazole (SD 3·9, p=0·027) and 23·3 points with olanzapine (2·9, p=0·025). We observed weight gain and increases of serum lipids and prolactin in all groups. 26 serious adverse events (SAEs) among 20 patients were registered (four [9%] of 44 patients allocated to amisulpride, ten [21%] of 48 patients allocated to aripiprazole, and six [12%] of 52 patients allocated to olanzapine), with no statistically significant differences between the study drugs. 17 (65%) of the 26 SAEs occurred during the use of the study drug, with readmission or protracted hospital admission accounting for 13 SAEs. One death by suicide, one unspecified death, and one life-threatening accident occurred during follow-up, after cessation of treatment., Interpretation: Amisulpride was more efficacious than aripiprazole or olanzapine for reducing the PANSS total scores in adults with schizophrenia-spectrum disorders. Side-effect differences among the groups were generally small. This study supports the notion that clinically relevant efficacy differences exist between antipsychotic drugs. Future research should aim to compare first-line antipsychotics directly in pragmatic clinical trials that reflect everyday clinical practice., Funding: The Research Council of Norway, the Western Norway Regional Health Trust, and participating hospitals and universities., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Remission in schizophrenia is difficult to achieve. Antipsychotic drugs are critical in the treatment of schizophrenia. International guidelines for the pharmacological treatment of schizophrenia recommend a 3-step algorithm with clozapine being the third-line antipsychotic agent. This study investigated the 1-year outcome and the application of the guidelines for the pharmacological treatment of nonremitted first-episode schizophrenia (FES) patients during the first year of follow-up., Methods: A sample of 78 FES patients from the Norwegian TIPS (Early Treatment and Intervention in Psychosis) 2 study was assessed at the end of the first year of follow-up. The symptom remission criteria were those defined by the Remission in Schizophrenia Working Group. The adherence to the pharmacological guidelines was assessed by reading the medical files and by a digital search of the words "clozapine," "klozapin," and "Leponex" in the hospital electronic data system., Results: The majority (n = 53, 67.9%) of the patients included were nonremitted at the 1-year follow-up. The majority of the nonremitted patients received either none (7.5%), one (56.6%), or 2 types (15.1%) of antipsychotic drugs during the first year of follow-up. Only 2 (3.8%) received treatment with clozapine, and 3 (5.7%) in total were offered it., Conclusions: For our FES sample, there was a low 1-year remission rate and a poor adherence to the pharmacological guidelines. Higher adherence to treatment guidelines with a more intensified antipsychotic treatment, which in some cases will include clozapine, will enhance the quality of treatment and may enhance the rates of remission for schizophrenia.

Introduction: Psychosis is a multifaceted clinical phenomenon in which the various symptoms may show a differential response to treatment. Important information may be lost when heterogeneous symptoms are grouped together in global sum scores when studying treatment effects. Aims: The aim of this study was to compare the level and rate of change in the two separate symptoms hallucinations and delusions during the acute psychotic phase, and to explore whether potential temporal differences depend on diagnosis or patients being previously medicated with antipsychotics or not. Method: Patients admitted with active symptoms of schizophrenia or related psychotic disorders were included in the Bergen Psychosis Project (BPP) ( N   =   226), a prospective, pragmatic, study of four second-generation antipsychotics. The Positive and Negative Syndrome Scale were assessed at baseline, one, three and six months. Results: Over the total follow-up period, latent growth curve models showed greater reductions in delusions than in hallucinations. However, the percentage of the total reduction was found to be larger in hallucinations than that of delusions in the first interval (91% vs. 64%). The levels and changes in these variables were dependent on diagnosis and whether or not patients had a life-time history of antipsychotic use. Conclusion: Focusing on separate symptoms rather than general symptom clusters could offer clinicians a useful approach when evaluating the early response of antipsychotics. ClinicalTrials.gov ID: NCT00932529; URL: http://www.clinicaltrials.gov/.

Background: Treatment satisfaction predicts treatment adherence and long-term outcome for patients with psychosis. It is therefore important to understand the underpinnings of patient satisfaction in psychosis treatment for optimal treatment delivery. Aims: To examine the associations between satisfaction and level and change in positive symptoms, insight, depression and side effects of antipsychotics in previously medicated and antipsychotic-naïve patients. Method: Data derive from a randomised trial, with 226 respondents at baseline and 104 at follow-up. The measures were the positive subscale and insight item from the Positive and Negative Syndrome Scale, Calgary Depression Scale, the UKU Consumer Satisfaction Rating Scale, and the UKU side effects scale. Structural equation modelling was used to test the model. The full information maximum likelihood estimator used all available data. Results: In the sample of 226 patients, 67.3% were male and 44.2% were antipsychotic-naïve. The mean age was 34.1 years. For previously medicated patients, satisfaction was predicted by level of insight ( b  = -2.21, β = -0.42) and reduction in positive symptoms ( b  = -0.56, β = -0.39). For antipsychotic-naïve patients, satisfaction was predicted by level and change of insight ( b  = -2.21, β = -0.46), change in depression ( b  = -0.37, β = -0.26) and side effects ( b  = -0.15, β = -0.30). All predictors were significant at the 0.05 level. Conclusion: Reducing positive symptoms and side effects are important to enhance patient satisfaction. However, improving insight and reducing depression are more important in antipsychotic-naïve patients.

Aims: The aim of this study was to investigate time trends in dosing and prevalence of antipsychotic prescriptions in Scandinavia., Methods: We retrieved data on antipsychotic use between 2006 and 2016 from Danish, Norwegian and Swedish national prescription registers. For each antipsychotic, we calculated prevalence of use and mean doses, overall and for specific age groups (young, adults and elderly)., Results: Antipsychotic use in Scandinavia increased from 16.5 to 17.2 users/1000 inhabitants between 2006 and 2016 (+2.4%, annual change: 0.07 users/1000 inhabitants/year, 95% CI: 0.02-0.20, P = 0.02). In 2006, chlorprothixene and levomepromazine were the most commonly used antipsychotics. By 2016, quetiapine was the most used antipsychotic in all three countries and across all age groups, with an overall 1-year prevalence of 4.05-9.97 users/1000 inhabitants (annual change: 0.57 users/1000 inhabitants/year, 95% CI: 0.54-0.60, P < 0.001). Quetiapine showed a marked decrease in mean doses during the 11-year study period (0.46-0.28 defined daily doses (DDD)/user/day: 39.1%, -0.02 DDD/user/day/year, 95% CI: -0.020 to -0.015, P < 0.001). In 2016, the highest mean doses were seen for clozapine (0.90-1.07 DDD/user/day) and olanzapine (0.66-0.88 DDD/user/day)., Conclusions: There is an increased prevalence of antipsychotic prescriptions that coincides with low and/or decreasing mean doses of the majority of commonly used antipsychotics in Scandinavia. Of all antipsychotics, this development was most pronounced for quetiapine. Reasons for and consequences of increased antipsychotic use that lasts shorter periods of time requires further study., (© 2019 The British Pharmacological Society.)

Background: Psychosis is associated with a high prevalence of substance use, leading to worsened prognosis. Less is known about how comorbid substance abuse may influence the effectiveness of antipsychotic medications. The aim of this study was to compare the effectiveness of second generation antipsychotics in patients with psychosis with and without substance use. Methods: All patients ( n  = 226) were aged >18 years old had symptom level scores of ≥4 on selected psychosis items on the Positive and Negative Syndrome Scale and met ICD-10 diagnostic criteria for psychosis. Information on substance use was collected based on the Clinician Drug Use Scale. Patients were grouped at baseline according to the presence of substance use, medication history and diagnosis group. Clinical symptoms at baseline and changes at follow-up were assessed with the PANSS. Results: At baseline about 30% of the patients used substances, most frequently cannabis followed by methamphetamine. About half (47%) of the patients had no prior exposure to antipsychotic medication at inclusion. Patients who had consumed substances showed no substantial differences in the PANSS score reduction as a result of antipsychotic medication compared to patients without substance. There were, however, some group differences in relation to pattern of change that were influenced by medication history. Substance use was found to be related to stronger reduction of positive symptoms from week 4 to week 27. Conclusion: Substance use alone did not influence antipsychotic effectiveness in this sample of patients with psychosis.

Objective: Inverse relationships between the C-reactive protein (CRP) levels and cognitive performance in acute psychosis have been demonstrated. We aimed to investigate how the serum level and initial change of CRP in acutely admitted patients with psychosis was correlated with cognitive performance during a 6-months follow-up period., Methods: The study is part of a pragmatic, randomised trial comparing four different second-generation antipsychotic drugs, and consists of 208 acute phase patients recruited at admittance for psychosis. This study reports data for all groups collectively, and does not compare treatment groups. Measurements of CRP and cognitive performance were conducted at baseline (T1) and after 4 weeks on average after inclusion (T2). Cognition was also assessed after 3 months (T3) and 6 months (T4) of follow-up., Results: Global cognition improved during the follow-up period of 6 months, especially in the T1-T2 interval. The different cognitive subdomains showed different time-dependent profiles of improvement, with memory and attention improving significantly also in the later phases. Reduction of the CRP level during the initial follow-up interval (T1-T2) was associated with increased overall cognitive performance in the T2-T4 interval, but not in the T1-T2 interval. For the cognitive subdomains, we found an inverse association between change in CRP level and verbal abilities (T2-T4 interval), and attention (T2-T3 interval)., Conclusion: These findings indicate that initial changes in the serum level of CRP in the acute phase of psychosis may predict cognitive function in later phases of the disease.

Background: Hallucinations are prevalent in schizophrenia and related psychotic disorders and may have severe consequences for the affected patients. Antipsychotic drug trials that specifically address the anti-hallucinatory effectiveness of the respective drugs in representative samples are rare. The aims of the present study were to investigate the rate and severity of hallucinations in acutely admitted psychotic patients at hospital admission and discharge or after 6 weeks at the latest, if not discharged earlier (discharge/6 weeks); and to compare the anti-hallucinatory effectiveness of risperidone, olanzapine, quetiapine, and ziprasidone with up to 2 years' follow-up., Methods: Adult patients acutely admitted to an emergency ward for psychosis were consecutively randomized to risperidone, olanzapine, quetiapine, or ziprasidone and followed for up to 2 years in a pragmatic design. Participants were assessed repeatedly using the hallucinatory behavior item of the Positive and Negative Syndrome Scale (PANSS)., Results: A total of 226 patients, 30.5% of those assessed for eligibility, were randomized and 68% were hallucinating at baseline. This proportion was reduced to 33% at discharge/6 weeks. In the primary analyses based on intention to treat groups of patients experiencing frequent hallucinations, the quetiapine and ziprasidone groups both had faster decreases of the mean hallucination scores than the risperidone group., Conclusions: Hallucinations are fairly responsive to antipsychotic drug treatment and differential anti-hallucinatory effectiveness may be found among existing antipsychotic drugs. If replicated, this could pave the way for a more targeted pharmacotherapy based on individual symptom profiles, rather than on the diagnostic category., Trial Registration: ClinicalTrials.gov ID; NCT00932529.

Purpose: Cognitive effects of second generation antipsychotics (SGAs) are indicated in efficacy studies but the generalizability of the results may be limited by rigid designs and selected samples. The aim of this naturalistic, industry-independent study is to investigate whether differential neurocognitive effectiveness can be found among olanzapine, quetiapine, risperidone, and ziprasidone in a clinically relevant sample with psychosis., Subjects and Methods: Adult patients acutely admitted to an emergency ward for psychosis were randomized to risperidone, olanzapine, quetiapine or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale and a repeatable neurocognitive test battery., Results: A total of 226 patients were included and 171 patients underwent neurocognitive assessments. The sample had a global cognitive performance score at baseline about one standard deviation below that of the general population. The ziprasidone group had the fastest increase in global functioning which was significantly superior to that of the olanzapine group for the entire follow-up period. Before 90 days, the quetiapine group had the fastest increase which was statistically superior to the olanzapine group., Discussion: Ziprasidone and quetiapine demonstrated superiority to olanzapine in increasing global neurocognitive performance in this naturalistic sample., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Objective: Evidence based treatment of schizophrenia as well as antipsychotic drug utility patterns have changed considerably in recent years and the present study aims to investigate the current level of unplanned hospital readmissions in a cohort of patients with schizophrenia, and to determine the risk-reducing effects of current antipsychotic drug treatment., Method: An open cohort study included all consecutively discharged patients with schizophrenia in a 3-year period (n=277). The treatment-dependent variables were entered in a multivariate Cox survival analyses with time to unplanned readmission as the dependent variable., Results: 11.2% of patients were readmitted within 30 days of discharge, and 44.8% were readmitted within 12 months. Antipsychotic monotherapy reduced the risk of readmission by 74.9%. Treatment in CMHC also had a risk-reducing effect. The prescription rate of clozapine in this sample was 10.1%., Discussion: The over-all level of unplanned readmissions was in correspondence with the findings of others. Current antipsychotic drug treatment independently offers strong protection against unplanned readmissions. There may be a potential for further optimalizing antipsychotic drug treatment according to treatment guidelines., Conclusions: Unplanned readmissions are very common for patients with schizophrenia but antipsychotic drug treatment is associated with a strong risk-reducing effect in this regard., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Antipsychotic polytherapy (APT) has evolved as a common treatment strategy at odds with recommendations from schizophrenia treatment guidelines. The literature on combinations with clozapine as a means to enhance efficacy and with aripiprazole to reduce side effects was reviewed. No solid evidence supporting antipsychotic combinations with clozapine for treatment-resistant patients with schizophrenia was identified. The reason for this may be that most combinations with clozapine increase the D(2)-receptor blockade, and this strategy is probably not efficient for patients with treatment-resistant schizophrenia. Some basic and clinical evidence for the addition of aripiprazole to lower prolactin levels was identified. In conclusion, there is very limited support in the evidence for the feasibility of rational APT.

Background: No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis. The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation, duration of index admission, time until readmission, change of psychopathology scores and tolerability outcomes., Methods: Patients >or= 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively randomized to risperidone (n = 53), olanzapine (n = 52), quetiapine (n = 50), or ziprasidone (n = 58), and followed for up to 2 years., Results: A total of 213 patients were included, of which 68% were males. The sample represented a diverse population suffering from psychosis. At admittance the mean Positive and Negative Syndrome Scale (PANSS) total score was 74 points and 44% were antipsychotic drug naïve. The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug, until discharge from index admission, or until readmission. Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore. Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore; in decreasing the Clinical Global Impression - Severity of Illness scale score (CGI-S); and in increasing the Global Assessment of Functioning - Split version, Functions scale score (GAF-F). Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score, and in increasing the GAF-F score. The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone, and more galactorrhoea for risperidone compared to the other groups., Conclusions: Quetiapine appears to be a good starting drug candidate in this sample of patients admitted to hospital for symptoms of psychosis., Trial Registration: ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529.

Background: Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level., Methods: Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines., Results: In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA). The mean chlorpromazine equivalent dose was 450 (SD 347, range 25-2800). In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in the previous 12 months also predicted prescription of at least one FGA., Conclusion: Our national survey of antipsychotic treatment at discharge from emergency inpatient treatment revealed antipsychotic drug regimens that are to some degree at odds with current guidelines, with increased risk of side effects. Patients with high relapse rates, comorbid conditions, and previous inpatient treatment are especially prone to be prescribed antipsychotic drug regimens not supported by international guidelines.

Objective: To investigate the prevalence of hyperprolactinemia and common hyperprolactinemia-related symptoms and explore the association between them in patients using a modern antipsychotic drug regimen and, in addition, investigate the prevalence of the inert fraction of prolactin called macroprolactin, which, to our knowledge, has not been investigated systematically in this population before. Macroprolactin may cause misdiagnosis of hyperprolactinemia., Method: A cross-sectional design was applied, and 106 patients who were using antipsychotics for symptoms of psychosis were included., Results: Hyperprolactinemia was found in 39% of the patients. Women were overrepresented in the group with the highest prolactin levels. Macroprolactin was not detected in any cases. Several of the second-generation antipsychotics were associated with hyperprolactinemia. Pearson correlation between prolactin level and symptoms revealed no association, and some patients did not report any symptoms despite grossly elevated levels of biologically active prolactin., Conclusions: The results suggest that hyperprolactinemia is still an important and prevalent side effect. In patients using antipsychotics with prolactin-elevating potential, prolactin levels should be routinely measured to prevent potential long-term complications of "silent" hyperprolactinemia, although we are still in the early stages of knowing what to do with the information.

Background: Systematic reviews based on efficacy trials are inconclusive about which second generation antipsychotic drug (SGA) should be preferred in normal clinical practice, and studies with longer duration and more pragmatic designs are called for. Effectiveness studies, also known as naturalistic, pragmatic, practical or real life studies, adhere to these principles as they aim to mimic daily clinical practice and have longer follow-up., Objective: To review the head-to-head effectiveness of SGAs in the domains of global outcomes, symptoms of disease, and tolerability., Methods: Searches were made in Embase, PubMED, and the Cochrane central register of controlled trials for effectiveness studies published from 1980 to 2008, week 1. Different combinations of the keywords antipsychotic*, neuroleptic* AND open, pragmatic, practical, naturalistic, real life, effectiveness, side effect*, unwanted effect*, tolera* AND compar* AND random* were used., Results: Sixteen different reports of randomized head-to-head comparisons of SGA effectiveness were located. There were differences regarding sample sizes, inclusion criteria and follow-up periods, as well as sources of financial sponsorship. In acute-phase and first-episode patients no differences between the SGAs were disclosed regarding alleviating symptoms of disease. Olanzapine was associated with more weight gain and adverse effects on serum lipids. In the chronic phase patients olanzapine groups had longer time to discontinuation of treatment and better treatment adherence compared to other SGAs. The majority of studies found no differences between the SGAs in alleviating symptoms of psychosis in chronically ill patients. Olanzapine was associated with more metabolic adverse effects compared to the others SGAs. There were surprisingly few between-drug differences regarding side effects. First generation antipsychotics were associated with lower total mental health care costs in 2 of 3 studies on chronically ill patients, but were also associated with more extrapyramidal side effects compared to the SGAs in several studies., Conclusion: In chronically ill patients olanzapine may have an advantage over other SGAs regarding longer time to treatment discontinuation and better drug adherence, but the drug is also associated with more metabolic side effects. More effectiveness studies on first-episode psychosis are needed.

Since the introduction of chlorpromazine, an increasing number of drugs have been added to the list of antipsychotics (neuroleptics). These drugs can be further classified as either first-generation antipsychotics (FAPs) or second-generation antipsychotics (SAPs), depending on their ability to antagonize serotonine in addition to dopamine. The efficacy of various drugs is generally equal, whereas both pharmacological profiles and side-effects differ. Antipsychotic drug therapy recommendations are available both in Norway and internationally, and the purpose of this cross-sectional survey was to register the use of these drugs in representative mental hospitals (A and B), and compare our findings to the recommendations. Medical prescriptions were registered, and data further analysed. In hospital A, a total of 149 patients' prescriptions were registered. Antipsychotics were received voluntarily by 117 patients. Eighty-two of these used one antipsychotic drug, and in this group, 65% received SAPs. Antipsychotic combination therapy was received by 35 patients, and was associated with higher prescription rates of both anticholinergics and benzodiazepines. SAPs were not associated with increased use of benzodiazepines, compared to FAPs. Antipsychotics were frequently combined with mood stabilizers and antidepressants. Our findings in hospital A concerning therapy practices of antipsychotics, were confirmed in hospital B, where 64 patients' medical prescriptions were registered. We conclude that FAPs are still commonly prescribed. Antipsychotic combination therapy is used despite of lack of evidence for efficacy, and is associated with increased prescription rates of anticholinergics and benzodiazepines.

Introduction: Use of antipsychotic drugs is common in nonpsychotic disorders such as depression, anxiety, autism spectrum disorders, and insomnia. But exposure to antipsychotic drugs has been associated with a range of serious adverse events from arrythmias to diabetes. There is a need for detailed information on current practice and trends in the utilization of this drug class to guide future initiatives on the rational use of antipsychotic drugs. Objectives: To investigate trends in dosing and prevalence of antipsychotic prescriptions in Scandinavia. Methods:Weretrieved data on antipsychotic use between 2006 and 2016 from Danish, Norwegian and Swedish national prescription registers. For each antipsychotic, we calculated prevalence of use and mean doses, overall and for specific age groups. Results: Antipsychotic use in Scandinavia increased from 16.5 to 17.2 users/1,000 inhabitants between 2006 and 2016 (+2.4%, p=0.02). In 2006, chlorprothixene and levomepromazine were the most commonly used antipsychotics. By 2016, quetiapine was the most used antipsychotic in all three countries and across all age groups, with an overall one-year prevalence of 4.05 to 9.97 users/1,000 inhabitants. Mean doses of quetiapine decreased markedly during the 11-year study period (0.46 to 0.28 DDD/user/day), while mean doses for clozapine and olanzapine remained high (0.90-1.07 resp. 0.66-0.88DDD/user/day). Conclusions: We found an increasing prevalence of antipsychotic prescriptions that coincides with low and/or decreasing mean doses of the majority of commonly used antipsychotics in Scandinavia. Of all antipsychotics, this development was most pronounced for quetiapine. Reasons for and consequences of increased antipsychotic use that lasts shorter periods of time requires further study. [ABSTRACT FROM AUTHOR]

Introduction: Antipsychotic maintenance treatment for patients with schizophrenia has been demonstrated to be the single most important modifiable factor to prevent unplanned readmissions. Effectiveness studies have indicated different risk for drug discontinuation between current antipsychotics. Objectives & aims: To evaluate time until discontinuation of antipsychotic treatment, and specifically to investigate if differences between the prescribed antipsychotics could be detected. Methods: 396 patients with schizophrenia were included in an open cohort study and followed through treatment until all antipsychotics prescribed at inclusion were discontinued, predictors for time to discontinuation were analysed with univariate and multivariate Cox survival analyses with time until discontinuation as the dependent variable and antipsychotic monotherapy as the predictor variable. The analysis was controlled for common confounders. Results: 65.7% of the patients were men, mean age was 42.4 years, and 12.9% were first-episode patients. 287 were prescribed antipsychotic monotherapy. In the multivariate Cox analysis with time to all-cause discontinuation only clozapine was significant different from olanzapine, Adjusted Hazard Rate (AHR) 0.17 (0.07,0.45) (p=0.0003), this was also the case for the prediction of time to clinician-decided discontinuation, AHR (0.20 (0.06,0.70) (p=0.012). In the analysis with time to patient-decided discontinuation as the dependent variable also Second Generation Antipsychotic Long-Acting Injectables (LAI) (AHR 0.26 (0.09,0.77) (p=0.015) and First Generation Antipsychotic (LAI) (AHR 0.35 (0.16,0.80) (p=0.013) had significant lower risk for discontinuation. Conclusions: Clinicians and patients discontinued clozapine at a lower rate than olanzapine, patients also discontinued LAI formulations at a lower rate than olanzapine. [ABSTRACT FROM AUTHOR]