All-cause Treatment Discontinuation Research Articles

Real-world effectiveness of long-acting injectable vs. oral antipsychotics in patients with bipolar I disorder: a 1-year retrospective observational study

Objective Long-acting injectable (LAI) antipsychotics are recommended in the treatment non-adherence. Despite the widespread use of LAI antipsychotics, there is limited data on clinical outcomes in bipolar I disorder (BD-I) patients with real-world data. We aimed to compare BD-I patients treated with LAI and oral antipsychotics (OAP) in terms of treatment effectiveness in a 1-year follow-up period. Methods The study was conducted retrospectively with electronic health records of 116 BDI patients. The primary outcomes were whether patients in the LAI group and the OAP group differed in relapse, rehospitalization, emergency room (ER) visits, and all-cause treatment discontinuation at 1-year follow-up after a mania episode. Cox regression modeling was used to predict the recurrence of any mood episode and all-cause treatment discontinuation during follow-up. The secondary outcomes evaluated were the effects of sociodemographic and clinical parameters and concomitant psychotropic medications on the course of the illness and treatment adherence. Results Of all 116 patients, 33 (28.4%) were under LAI, and 83 (71.6%) were under OAP treatment. LAI users had a history of more hospitalizations and total mood episodes. Patients in the LAI group had more treatment non-adherence before the index hospitalization. At 1-year follow-up, there was no difference between the groups in terms of any mood relapse, rehospitalization, ER visits, and all-cause treatment discontinuation. As a secondary outcome, lithium users were found to have fewer new episodes and discontinuations of treatments. Conclusions In real-world data, there is no evidence that LAI antipsychotics (compared to OAP) are superior in the maintenance treatment of BD. These results are important in terms of reflecting clinical practices for the treatment of BD-I. These results do not devalue the use of LAI therapy in BD; however, more studies are needed to identify positive predictors for LAI treatments in BD.

Considering multiple outcomes with different weights informed the hierarchy of interventions in network meta-analysis

ObjectivesRanking metrics in network meta-analysis (NMA) are computed separately for each outcome. Our aim is to 1) present graphical ways to group competing interventions considering multiple outcomes and 2) use conjoint analysis for placing weights on the various outcomes based on the stakeholders’ preferences. Study Design and SettingWe used multidimensional scaling (MDS) and hierarchical tree clustering to visualize the extent of similarity of interventions in terms of the relative effects they produce through a random effect NMA. We reanalyzed a published network of 212 psychosis trials taking three outcomes into account as follows: reduction in symptoms of schizophrenia, all-cause treatment discontinuation, and weight gain. ResultsConjoint analysis provides a mathematical method to transform judgements into weights that can be subsequently used to visually represent interventions on a two-dimensional plane or through a dendrogram. These plots provide insightful information about the clustering of interventions. ConclusionGrouping interventions can help decision makers not only to identify the optimal ones in terms of benefit-risk balance but also choose one from the best cluster based on other grounds, such as cost, implementation etc. Placing weights on outcomes allows considering patient profile or preferences.

Treatment persistence with aripiprazole once monthly: a 4-year follow-up

ObjectivesTreatment persistence refers to the act of continuing a treatment as prescribed and reflects the patient's or doctor's judgment about efficacy, tolerability, and acceptability. In patients with schizophrenia, antipsychotic persistence is often poor, because of issues such as lack or loss of efficacy, side effects, and poor adherence, which is often related to the degree to which patients find the medication and overall intervention to be helpful, tolerable, fair, reasonable, appropriate, and consistent with expectations of treatment. Despite the poor antipsychotic persistence that has been reported to date in patients with schizophrenia, we previously observed a relatively high (86%) 6 months persistence with aripiprazole once-monthly (AOM) in a group of patients with schizophrenia, treated in the real world Italian clinical practice. The present study explores the longer term persistence with AOM, over a mean follow-up period of 48 months.MethodsThis was a multicenter, retrospective, non-interventional follow-up study, aimed at evaluating the longer term persistence with AOM in a group of patients with schizophrenia who had already shown persistence over a period of at least 6 months. The study included 161 individuals who had participated in our previous study, where 86% of participating individuals had shown persistence with AOM for at least 6 months. Non-persistence was defined as discontinuing the medication for any reason. Baseline demographic and clinical characteristics of patients who continued AOM were then compared to those of patients who discontinued the medication.ResultsStudy subjects were predominantly male (64.4%) and their mean age was 39.7 (SD: 12.24). Treatment persistence with AOM was 69.6% and 112 out of 161 patients were still receiving AOM treatment at the last follow-up visit.The mean duration of AOM treatment until the last recorded observation was 55.87 months (median 56.17, SD6.23) for the 112 persistent patients and 32.23 (median 28.68.SD 15.09) months for the 49 non-persistent individuals. The mean observation period for all patients (persistent and non-persistent) was 48.78 months (median 52.54, SD 14.64). For non-persistent subjects, the observation period ended with the discontinuation of AOM.Subjects treated with AOM at 400 mg presented a 69.6% lower risk of all-cause treatment discontinuation when compared with patients treated with 300 mg (HR: 0.314; 95% confidence interval [CI] 0.162–0.608; P = 0.001). The main reasons for discontinuation were lack of efficacy (30.6%), patient/caregiver choice (18.4%), physician’s choice (16.3%), non-adherence (12.2%) and inconvenience (6.1%). Only 3 patients (6.1%) discontinued AOM for tolerability issues.ConclusionsIn subjects with schizophrenia, who had already shown a 6 months persistence with AOM, a high number of patients (69.6%) continued to be persistent over a 4-year follow-up period. This may reflect a favourable profile of efficacy, tolerability, and acceptability. Larger and prospective studies are warranted to confirm our observations.

Switching from originator infliximab to biosimilar versus continuing on originator in inflammatory bowel disease: results from the observational Project NORTH study

Objective Project NORTH compared real-world clinical and economic outcomes in Swedish patients with inflammatory bowel disease (IBD) who switched from originator infliximab to its biosimilar. Materials and methods Data from electronic medical records and Swedish national registries were linked. Switchers (patients switching from originator infliximab to its biosimilar between 1 April 2014, and 31 December 2017) and non-switchers (patients who received originator infliximab and did not switch to a biosimilar by 31 December 2017) were followed up until 31 October 2019. Results Baseline concomitant medication use, disease duration, and inflammatory markers were lower among switchers than non-switchers. At 6 months, the proportion of patients with stable disease was higher among switchers than non-switchers (71/109 [65%] vs 54/107 [50%]; p = .0385); differences were not significant in subsequent follow-ups. At 6 and 24 months, 98% and 93% of switchers, respectively, used concomitant medications versus 96% and 79% of non-switchers. Throughout the study, all-cause treatment discontinuation occurred in 74 (67%) switchers and 105 (95%) non-switchers. At 36-months, mean (SD) number of IBD-related in-patient care days was higher among non-switchers (2.95 [4.71]) than switchers (1.40 [4.20]), as were total medical costs (€16,740 vs €3,872). Conclusions No substantial differences in clinical outcomes or healthcare resource utilization were observed between switchers and non-switchers. Several analyses indicate that non-switchers might have more poorly controlled/severe disease than switchers at baseline. Overall, numerous difficulties might arise when executing a high-quality, real-world study, including possible selection bias for patients with better disease control for NMS, limiting the generalizability of the results.

Effectiveness and Safety of Atazanavir Use for the Treatment of Children and Adolescents Living With HIV: A Systematic Review.

BackgroundAtazanavir/ritonavir is recommended as a preferred second-line antiretroviral regimen in children older than 3 months, alternatively to lopinavir/ritonavir. We performed a systematic review to assess safety and effectiveness of atazanavir use in children and adolescents.MethodsWe searched observational studies and clinical trials on Web of Science, Embase and Cochrane CENTRAL database between 2009/01/01 and 2020/10/01; as well as grey literature. We extracted safety (adverse events, grade 3 or 4 adverse events, treatment discontinuation) and effectiveness (CD4 cell counts and HIV viral load) outcomes. We estimated weighted summary pooled incidence with corresponding 95% confidence intervals.ResultsOut of the 1,085 records screened, we included five studies (one comparative cohort, three single phase 2-3 trial arms, one retrospective cohort) reporting 975 children and adolescents, of whom 56% (544) received atazanavir. Three studies reported all-cause treatment discontinuation rates, yielding a pooled incidence of 19% [15–22] at 12 months. The comparative cohort compared atazanavir to darunavir, with few grade 3–4 adverse events, except transient hyperbilirubinemia, occurring in half (92/188) of the atazanavir patients. No death occurred (two studies reporting). Four studies described increased CD4 cell counts and decreased HIV viral load at 6 or 12 months.ConclusionFew safety and effectiveness data were available for children and adolescents exposed to atazanavir. Transient grade 3–4 hyperbilirubinemia was the main adverse outcome reported. Immune and viral responses were descriptive. The use of atazanavir/ritonavir in children and adolescents needs further investigation, but remains a suitable option for a preferred second-line antiretroviral regimen.PROSPERO numberCRD42022309230

A Multicenter, Prospective, Observational Study to Assess the Clinical Activity and Impact on Symptom Burden and Patients' Quality of Life in Patients with Advanced Soft Tissue Sarcomas Treated with Trabectedin in a Real-World Setting in Greece.

Simple SummarySoft tissue sarcomas (STS) constitute a group of heterogeneous tumors. For patients with advanced or metastatic disease, prognosis is poor and only a few treatments are available, including trabectedin. The aim of our prospective multicenter study was to evaluate the real-world activity of trabectedin, and its impact on symptom burden and quality of life in patients with advanced STS treated in routine clinical settings in Greece. Between 21 December 2015 and 6 June 2018, 64 eligible patients from 13 Greek centers were evaluated. Our study provides real-world evidence on the effectiveness, tolerability and safety of trabectedin in a population of patients with advanced STS of multiple histological subgroups who have either experienced a relapse or disease progression after standard-of-care front-line therapy, or were unsuited to receive front-line agents.This non-interventional, multicenter, prospective study aimed to evaluate the real-world activity of trabectedin, and its impact on symptom burden and quality of life in patients with advanced soft tissue sarcoma (aSTS) treated in routine clinical settings in Greece. Patients with histologically confirmed aSTS newly initiated on trabectedin were enrolled. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS rate at 3 months, median PFS, objective response rate (ORR), disease control rate (DCR), overall survival (OS), and an assessment of the impact of treatment on health-related quality of life (HRQoL), cancer-related symptom burden and symptom interference with function, as well as all-cause treatment discontinuation rate. A total of 64 eligible patients from 13 Greek centers were evaluated. Patients received a median of three trabectedin cycles per patient (interquartile range [IQR]: 2.0–6.0). Median PFS was 6.6 months with 67.9% and 51.2% of patients free from progression at 3 and 6 months, respectively. ORR was 7.8% and DCR 21.9%. Median OS was 13.1 months. No significant changes from enrolment were noted in HRQoL scores. In total, 30 patients (46.9%) had at least one trabectedin-related adverse drug reaction (ADR) and 9 (14.1%) at least one serious ADR. The treatment discontinuation rate due to toxicity was 9.4%. These results suggest that trabectedin is an active treatment with clinically meaningful benefits in patients with aSTS with no new safety signals.

Specialized inpatient treatment for young people with early psychosis: acute-treatment and 12-month results

The objective of the study was to investigate the development of clinical outcomes of young people with early psychosis in a specialized inpatient treatment and assess the feasibility of such an intervention in an inpatient setting. The study was a prospective cohort study of patients with early psychosis treated at the specialized inpatient treatment “Fühinterventions-und Therapiezentrum, FRITZ” (early intervention and therapy center) in Berlin, Germany. The primary outcomes were attitudes towards psychiatric medication and patient satisfaction with treatment after 6 weeks. Secondary outcomes were clinical symptoms, functioning, remission, recovery, all-cause treatment discontinuation, and rehospitalisation at 6 and 12 months after inpatient treatment. We recruited 95 inpatients with early psychosis. Attitudes towards psychiatric medication (Δ6weeks = 3.00, d6weeks = 0.55; Δ6mo = 2.15, d6mo = 0.35; Δ12mo = 3.03, d12mo = 0.52) and patient satisfaction (Δ6weeks = 0.21, d6weeks = 0.40; Δ6mo = 0.32, d6mo = 0.43; Δ12mo = 0.13, d12mo = 0.17) changed with medium effect sizes at six weeks up to a 6- and 12-month follow-up. Clinical outcomes changed significantly with medium-to-large-effect sizes over 12 months CGIΔ12mo = 1.64, d12mo = −1.12; PANSS totalΔ12mo = 20.10, d12mo = −0.76; GAFΔ12mo = 19.58, d12mo = 1.25). The all-cause treatment discontinuation rate was 13.69% (n = 13) at a 6-month and 35.79% (n = 34) at a 12-month follow-up. The rehospitalization rate was 30.53% (n = 29) at a 6-month and 43.16% (n = 41) at a 12-month follow-up. Patients with specialized inpatient treatment for early psychosis showed improvements in attitude towards psychiatric medication, patient satisfaction, symptoms, and functioning for up to 12 months.Trial registration: DRKS00024351, 2021/02/11 retrospectively registered.

A Noninterventional Cohort Study Assessing Time to All-Cause Treatment Discontinuation After Initiation of Aripiprazole Once Monthly or Daily Oral Atypical Antipsychotic Treatment in Patients With Recent-Onset Schizophrenia.

Introduction: Aripiprazole once-monthly 400 mg (extended-release injectable suspension) is effective in long-term maintenance treatment of schizophrenia based on clinical studies. As study results may not reflect clinical practice, we compared treatment persistence with aripiprazole once-monthly 400 mg versus daily oral atypical antipsychotics in a naturalistic setting.Methods: This was an observational, noninterventional study of patients (aged 18-35 years) with recent-onset schizophrenia (< 5 years post diagnosis) who initiated maintenance treatment with aripiprazole once-monthly 400 mg or any daily oral atypical antipsychotic during a schizophrenia-related hospitalization or within 3 months post hospital discharge (timeframe: July 13, 2017-July 31, 2019). Data were from patient files/obtained during routine visits. Patients were followed for ≤ 12 months or until all-cause treatment discontinuation (including lost to follow-up), whichever came first. Data were analyzed using a sample constructed with inverse probability of treatment weighting (IPTW).Results: Among 357 patients (aripiprazole once-monthly 400 mg: 215, oral atypical antipsychotics: 142), all-cause treatment discontinuation occurred in 87 (41%) of aripiprazole once-monthly 400 mg, 68 (48%) of oral atypical antipsychotic patients over 52 weeks. In the IPTW sample, time to all-cause discontinuation was significantly different between both groups in favor of aripiprazole once-monthly 400 mg (hazard ratio = 1.46; 95% CI, 1.05-2.03; P = .023). Generalizability of results to the overall population with schizophrenia was limited due to incomplete overlap of patient characteristics between cohorts. The primary reason for treatment discontinuation in both groups was voluntary discontinuation by subject (aripiprazole once-monthly 400 mg: 11%; oral atypical antipsychotics: 8%).Conclusions: In a naturalistic setting, younger patients with recent-onset schizophrenia treated with aripiprazole once-monthly 400 mg after hospitalization tended to discontinue treatment later than patients treated with daily oral atypical antipsychotics.Trial Registration: ClinicalTrials.gov identifier: NCT03130465.

Comparison of aripiprazole and risperidone effectiveness in first episode non-affective psychosis: Rationale and design of a prospective, randomized, 3-phase, investigator-initiated study (PAFIP-3)

BackgroundSelecting the most effective treatment represents a critical challenge with the potential of modifying the long-term prognosis of individuals suffering a first break of psychosis. Head-to-head clinical trials comparing effectiveness among antipsychotic drugs in individuals with a first-episode of non-affective psychosis (FEP) are scarce. MethodsThe rationale and design of a 3 phases clinical trial (PAFIP-3, NCT02305823) comparing the effectiveness of aripiprazole and risperidone, and to additionally assess the benefits of an early use of clozapine in primary treatment-resistant patients is reported. The design encompasses of 5 work packages (medication algorithm, cognitive functioning, psychoeducation/vocational functioning, imaging and biological markers) addressing critical issues and needs of first episode psychosis individuals and their cares. The primary outcome measure was treatment effectiveness assessed by all-cause treatment discontinuation rate. Results266 individuals have been included in the randomization study phase I (risperidone vs. aripiprazole). At 3 months, the retention rate was of 94% (249/266), 48(19.3%) patients have gone through phase II (olanzapine treatment), and 7(2.8%) entered the clozapine phase (phase III). DiscussionThe PAFIP 3 clinical trial may provide relevant information about clinical guidelines to optimally treat patients with a first episode of non-affective psychosis and the benefits and risks of an early use of clozapine in treatment resistant patients.Clinicaltrials.gov: NCT02305823.

Comparative Efficacy and Acceptability of Psychotherapies for Self-harm and Suicidal Behavior Among Children and Adolescents

Self-harm and suicidal behavior are associated with substantial morbidity and mortality among children and adolescents. The comparative performance of psychotherapies for suicidality is unclear because few head-to-head clinical trials have been conducted. To compare the efficacy of psychotherapies for the treatment of self-harm and suicidality among children and adolescents. Four major bibliographic databases (PubMed, MEDLINE, PsycINFO, and Embase) were searched for clinical trials comparing psychotherapy with control conditions from inception to September 2020. Randomized clinical trials comparing psychotherapies for suicidality and/or self-harm with control conditions among children and adolescents were included after a blinded review by 3 independent reviewers (A.B., M.P., and J.W.). The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed for data abstraction, and the Cochrane risk of bias tool was used to evaluate study-level risk of bias. Data abstraction was performed by 1 reviewer (A.B.) and confirmed by 2 independent blinded reviewers (J.W. and M.P.). Data were analyzed from October 15, 2020, to February 15, 2021. The primary outcomes were dichotomized self-harm and retention in treatment. The secondary outcomes were dichotomized all-cause treatment discontinuation and scores on instruments measuring suicidal ideation and depressive symptoms. Effect sizes were pooled using frequentist random-effects network meta-analysis models to generate summary odds ratios (ORs) and Cohen d standardized mean differences (SMDs). Negative Cohen d SMDs or ORs less than 1 indicated that the treatment reduced the parameter of interest relative to the control condition (eg, signifying a beneficial association with suicidal ideation). The systematic search generated 1272 unique records. Of those, 44 randomized clinical trials (5406 total participants; 4109 female participants [76.0%]) from 49 articles were selected (5 follow-up studies were merged with their primary clinical trials to avoid publication bias). The selected clinical trials spanned January 1, 1995, to December 31, 2020. The median duration of treatment was 3 months (range, 0.25-12.00 months), and the median follow-up period was 12 months (range, 1-36 months). None of the investigated psychotherapies were associated with increases in study withdrawals or improvements in retention in treatment compared with treatment as usual. Dialectical behavioral therapies were associated with reductions in self-harm (OR, 0.28; 95% CI, 0.12-0.64) and suicidal ideation (Cohen d SMD, -0.71; 95% CI, -1.19 to -0.23) at the end of treatment, while mentalization-based therapies were associated with decreases in self-harm (OR, 0.38; 95% CI, 0.15-0.97) and suicidal ideation (Cohen d SMD, -1.22; 95% CI, -2.18 to -0.26) at the end of follow-up. The quality of evidence was downgraded because of high risk of bias overall, heterogeneity, publication bias, inconsistency, and imprecision. Although some psychotherapeutic modalities appear to be acceptable and efficacious for reducing self-harm and suicidality among children and adolescents, methodological issues and high risk of bias prevent a consistent estimate of their comparative performance.

Aripiprazole vs Risperidone for the acute-phase treatment of first-episode psychosis: A 6-week randomized, flexible-dose, open-label clinical trial

Selecting the first antipsychotic agent for the acute phase of a first episode of psychosis (FEP) is a critical task that may impact on the long-term outcome. Despite that, there is a lack of research comparing head-to-head different second-generation antipsychotics at this stage. The aim of this study was to compare the effectiveness of aripiprazole and risperidone in the treatment of the acute phase after a FEP. For that purpose, from February 2011 to October 2018, a prospective, randomized, open-label study was undertaken. Two hundred-sixty-six first-episode, drug-naïve patients were randomly assigned to aripiprazole (n = 136), or risperidone (n = 130) and followed-up for 6-weeks. The primary effectiveness measure was all-cause treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted to assess clinical efficacy. The overall dropout rate at 6-week reached 19.5%. Effectiveness measures were similar between both treatment groups as treatment discontinuation rates (χ2 = 1.863; p = 0.172) and mean time until all-cause discontinuation (log rank = 1.421; p = 0.233) showed no statistically significant differences. In terms of clinical efficacy, risperidone proved a statistically significant better performance according to BPRS mean change between baseline and 6-week total score (t = 3.187; p = 0.002). Patients under risperidone treatment were significantly more likely to suffer sex-related adverse events. In conclusion, no differences regarding effectiveness were found between aripiprazole and risperidone for the acute-phase treatment of FEP. Despite the importance of efficacy during this phase of treatment, selecting the most effective treatment for the long-term outcome, requires addressing safety and patient´s preferences.

Comparison of aripiprazole and risperidone effectiveness in first episode non-affective psychosis: Rationale and design of a prospective, randomized, 3-phase, investigator-initiated study (PAFIP-3)

Selecting the most effective treatment represents a critical challenge with the potential of modifying the long-term prognosis of individuals suffering a first break of psychosis. Head-to-head clinical trials comparing effectiveness among antipsychotic drugs in individuals with a first-episode of non-affective psychosis (FEP) are scarce. The rationale and design of a 3 phases clinical trial (PAFIP-3, NCT02305823) comparing the effectiveness of aripiprazole and risperidone, and to additionally assess the benefits of an early use of clozapine in primary treatment-resistant patients is reported. The design encompasses of 5 work packages (medication algorithm, cognitive functioning, psychoeducation/vocational functioning, imaging and biological markers) addressing critical issues and needs of first episode psychosis individuals and their cares. The primary outcome measure was treatment effectiveness assessed by all-cause treatment discontinuation rate. 266 individuals have been included in the randomization study phase I (risperidone vs. aripiprazole). At 3 months, the retention rate was of 94% (249/266), 48(19.3%) patients have gone through phase II (olanzapine treatment), and 7(2.8%) entered the clozapine phase (phase III). The PAFIP 3 clinical trial may provide relevant information about clinical guidelines to optimally treat patients with a first episode of non-affective psychosis and the benefits and risks of an early use of clozapine in treatment resistant patients. Clinicaltrials.gov: NCT02305823.

Early intervention services, patterns of prescription and rates of discontinuation of antipsychotic treatment in first-episode psychosis.

Non-compliance is still an important problem in psychotic patients. Although antipsychotic (AP) treatment leads to a decrease in psychotic relapses, there are no clear recommendations about how long treatment should be maintained after first-episode psychosis (FEP) and no indication of the rates and causes of treatment withdrawal in this group. We evaluated a large sample of patients with FEP for 2 years to compare the time to all-cause treatment discontinuation of AP drugs and the time to the first relapse. We collected the sociodemographic and psychopathological characteristics of the sample. The number of relapses was also recorded. A total of 310 FEP patients were assessed across seven early intervention teams (mean age=30.2 years; SD=11.2). The most prevalent diagnosis at baseline was psychotic disorder not otherwise specified (36.1%), and the most commonly used APs were risperidone (26.5%) and olanzapine (18.7%). A lack of efficacy was the most frequent reason for the withdrawal of the first AP prescribed, followed by non-compliance. There were no differences in the relapse rates between different APs. Patients treated with long-acting injectable (LAI) APs presented less disengagement from services than patients treated with oral APs. Although there were no differences between the different APs in terms of relapse rates, LAIs had higher retention rates than oral APs in early intervention services. Compliance is still an important issue in Psychiatry, so clinicians should use different strategies to encourage it, such as the use of LAI treatments.

Comparative effectiveness of second generation long-acting injectable antipsychotics based on nationwide database research in Hungary.

BackgroundSchizophrenia is a severe condition that affects approximately 1% of the population. Certain elements of antipsychotic treatment can only be examined in large population, thus the need for population-based real-world analyses has been increasing.Patients and methodsHungarian National Health Fund database includes all healthcare data of the population of Hungary. All patients diagnosed with schizophrenia between 01.01.2006 and 31.12.2015 were included in the study. We analyzed all patients with newly initiated second-generation antipsychotic during the inclusion period (01.01.2012–31.12.2013). Patients were followed for 2 years. All-cause treatment discontinuation served as the primary outcome of the study. Patients with newly initiated long-acting injectable treatments were further investigated in stratified analyses based on their previous treatment.Results106,624 patients had schizophrenia diagnosis during the study period. 12,232 patients met the inclusion criteria for newly initiating second-generation antipsychotic during the inclusion period. The proportion of patients still on treatment after 1 year for oral treatments varied between 17% (oral risperidone) and 31% (oral olanzapine) while the analogous data for long acting injectables were between 32% (risperidone long acting) and 64% (paliperidone long acting one monthly). The 2-year data were similarly in favor of long-actings. Median time to discontinuation in the oral group varied between 57 days (clozapine) and 121 days (olanzapine). The median time to discontinuation for long-actings was significantly longer: between 176 and 287 days; in case of paliperidone long acting, median was not reached during the observation period. Patients receiving long-acting treatment switched from another long-acting remained on the newly initiated treatment significantly longer than those switched from orals.ConclusionOur results indicate the superiority of second generation long-acting antipsychotics with regard to rates of treatment discontinuation and periods of persistence to the assigned medication.

Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer\u2019s disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients

BackgroundThe risk-benefit relationship of memantine treatment for Alzheimer’s disease (AD) remains unclear. In addition, variability between the results of clinical trials has been observed. The aim of this study was to investigate the risk-benefit relationship of memantine treatment in patients with AD and to determine the predictor effect of patient, intervention, and study design related covariates.MethodsA systematic review and meta-analysis of double-blind, placebo controlled clinical trials was performed. Primary outcomes were all-cause discontinuation, discontinuation due to adverse events (AE) and efficacy on cognitive function. Odds ratio (OR) and standard mean difference (SMD) with 95% confidence intervals were calculated. Meta-regression was conducted to identify related covariates. Cochrane Collaboration tool was used to evaluate the risk of bias of included trials.ResultsEighteen studies involving 5004 patients were included. No differences between memantine and placebo were found for all-cause treatment discontinuation (OR=0.97 [0.82, 1.14]) and discontinuation due to AE (OR=1.18 [0.91, 1.53]). Memantine showed small improvement on cognitive function (SMD=0.15 [0.08, 0.22]). Baseline functional ability was positively associated with all-cause treatment discontinuation and discontinuation due to AE.ConclusionsOur study suggests that memantine has a very small efficacy on AD symptomatology and its safety profile is similar to that of placebo. No evidence of treatment discontinuation improvement with memantine is found, indicating a dubious risk-benefit relationship. No intervention characteristic or subgroup of patients clearly shows a significantly better risk-benefit relationship.PROSPERO registrationCRD42014015696.

Comparison of Early Intervention Services vs Treatment as Usual for Early-Phase Psychosis

The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal. To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis. Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017. Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders. This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses. The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period. Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P < .001), at least 1 psychiatric hospitalization (RR, 0.74; 95% CI, 0.61-0.90; P = .003), involvement in school or work (RR, 1.13; 95% CI, 1.03-1.24; P = .01), total symptom severity (standardized mean difference [SMD], -0.32; 95% CI, -0.47 to -0.17; P < .001), positive symptom severity (SMD, -0.22; 95% CI, -0.32 to -0.11; P < .001), and negative symptom severity (SMD, -0.28; 95% CI, -0.42 to -0.14; P < .001). Superiority of EIS regarding all outcomes was evident at 6, 9 to 12, and 18 to 24 months of treatment (except for general symptom severity and depressive symptom severity at 18-24 months). In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.

O11.5. EFFECTIVENESS OF COORDINATED SPECIALTY CARE FOR EARLY PSYCHOSIS

BackgroundThe value of early intervention in psychosis and allocation of public resources has long been debated since outcomes in people with schizophrenia-spectrum disorders have remained suboptimal. Several research programs for early psychosis yielded promising results for team-based, multi-element coordinated specialty care (CSC).MethodsSystematic literature search of PubMed/PsycInfo/Embase/clinicaltrials.gov without language restrictions until 06/06/2017. Random effects meta-analysis of randomized trials comparing CSC versus Treatment as Usual (TAU) in in first episode psychosis or early-phase schizophrenia-spectrum disorders (schizophrenia, psychotic disorder not otherwise specified, schizoaffective disorder, schizophreniform disorder, delusional disorder), calculating standardized mean differences (SMDs) and risk ratios (RRs) for continuous and categorical outcomes as well as prespecified subgroup and meta-regression analyses.Co-primary outcomes were all-cause treatment discontinuation and ≥1 psychiatric hospitalization during the treatment period. Key secondary outcomes were total symptom improvement, functioning, and work or school involvement.ResultsAcross 10 trials (n=2,176; age=27.5 ± 4.6 years; male=62.3%; trial duration=16.2 ± 7.4 (range=9–24) months), CSC outperformed TAU at the end of treatment regarding all meta-analyzable outcomes. This included all-cause discontinuation (studies=10, n=2,173, RR=0.70, 95% confidence interval (CI)=0.61–0.80, p<0.001; number-needed-to-treat (NNT)=12.4), ≥1 hospitalization (studies=10, n=2,105, RR=0.74, 95%CI=0.61–0.90, p=0.003; NNT=10.1), total symptom severity (studies=8, n=1,179, SMD=-0.32, 95%CI=-0.47, -0.17, p<0.001), positive symptoms (studies=10, n=1,532, SMD=-0.22, 95%CI=-0.32, -0.13, p<0.001), negative symptoms (studies=10, n=1,432, SMD=-0.28, 95%CI=-0.42, -0.14, p<0.001), general symptoms (studies=8, n=1,118, SMD=-0.30, 95%CI=-0.47, -0.13, p=0.001), depressive symptoms (studies=5, n=874, SMD=-0.19, 95%CI=-0.35, -0.03, p=0.017), functioning (studies=7, n=1,005, SMD=0.21, 95%CI=0.09–0.34, p=0.001), involvement in school/work (studies=6, n=1,743, RR=1.13, 95%CI=1.03–1.24, p=0.012; NNT=17.8), and quality of life (studies=4, n=505, SMD=0.23, 95%CI=0.004–0.456, p=0.046). Superiority of CSC regarding all outcomes was also evident at 6, 9–12, and 18–24 months of treatment (except general symptoms and depression at 18–24 months).DiscussionIn early psychosis, CSC is superior to TAU across all meta-analyzable, highly relevant outcomes with small-to-medium effect sizes. These results support the need for funding and utilization of CSC in patients with early-phase psychosis.

Study protocol for a randomised pragmatic trial comparing the clinical and cost effectiveness of lithium and quetiapine augmentation in treatment resistant depression (the LQD study)

BackgroundApproximately 30–50% of patients with major depressive disorder can be classed as treatment resistant, widely defined as a failure to respond to two or more adequate trials of antidepressants in the current episode. Treatment resistant depression is associated with a poorer prognosis and higher mortality rates. One treatment option is to augment an existing antidepressant with a second agent. Lithium and the atypical antipsychotic quetiapine are two such add-on therapies and are currently recommended as first line options for treatment resistant depression. However, whilst neither treatment has been established as superior to the other in short-term studies, they have yet to be compared head-to-head in longer term studies, or with a superiority design in this patient group.MethodsThe Lithium versus Quetiapine in Depression (LQD) study is a parallel group, multi-centre, pragmatic, open-label, patient randomised clinical trial designed to address this gap in knowledge. The study will compare the clinical and cost effectiveness of the decision to prescribe lithium or quetiapine add-on therapy to antidepressant medication for patients with treatment resistant depression. Patients will be randomised 1:1 and followed up over 12 months, with the hypothesis being that quetiapine will be superior to lithium. The primary outcomes will be: (1) time to all-cause treatment discontinuation over one year, and (2) self-rated depression symptoms rated weekly for one year via the Quick Inventory of Depressive Symptomatology. Other outcomes will include between group differences in response and remission rates, quality of life, social functioning, cost-effectiveness and the frequency of serious adverse events and side effects.DiscussionThe trial aims to help shape the treatment pathway for patients with treatment resistant depression, by determining whether the decision to prescribe quetiapine is superior to lithium. Strengths of the study include its pragmatic superiority design, broad inclusion criteria (external validity) and longer follow up than previous studies.Trial registrationISRCTN registry: ISRCTN16387615, registered 28 February 2016. ClinicalTrials.gov: NCT03004521, registered 17 November 2016.

Discontinuation of pharmacological treatment of children and adolescents with attention deficit hyperactivity disorder: meta-analysis of 63 studies enrolling 11,788 patients.

The risk-benefit balance of pharmacological treatment for children and adolescents with ADHD and the factors that moderate this relationship are unclear. A systematic review and meta-analysis of randomised, placebo-controlled clinical trials (RPCCTs) investigating the efficacy of pharmacological treatment in children or adolescents with ADHD was carried out. Meta-analysis of treatment discontinuation, clinician-, parent- and teacher-rated efficacy and adverse events was performed. The effect of covariates was studied. Sixty-three studies were included. Ten drugs were investigated, with atomoxetine and methylphenidate the most frequently studied. RPCCTs had mostly a short duration (7.9weeks). All-cause treatment discontinuation was lower with pharmacological treatment than placebo (OR=0.68). Pharmacological treatment was more efficacious than placebo independently of the rater (clinician, standardised mean difference (SMD) 0.74; parent, SMD=0.63; or teacher, SMD=0.75). Evidence of publication bias was found for clinician-rated efficacy, especially in industry-sponsored RPCCT. Psychostimulants showed a higher efficacy and were associated with a better outcome on treatment discontinuation than non-stimulant drugs. Efficacy was smaller in RPCCTs for which a psychiatric comorbid disorder was an inclusion criterion, was larger in studies with a commercial sponsorship and showed a negative association with treatment length. In the short term, pharmacological treatment provides moderate-high symptom relief, is safe and shows lower treatment discontinuation than placebo, suggesting a suitable risk-benefit balance, particularly with psychostimulants. The efficacy is lower in patients with a comorbid psychiatric disorder and should be assessed periodically, as it appears to reduce over time. Publication bias of clinician-rated efficacy in studies with a commercial sponsor is suggested.

Hostility in schizophrenia: An integrated analysis of the combined Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and the European First Episode Schizophrenia Trial (EUFEST) studies

Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study enrolled a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) enrolled 498 patients. We have combined these two samples to study the effects of hostility on study discontinuation as well as to examine correlates and predictors of hostility. Individual data from 1154 patients with complete data were used for analyses. Survival analysis demonstrated that higher hostility was associated with earlier all-cause treatment discontinuation. Furthermore, regression analysis indicated that increased hostility was associated with more severe positive symptoms, lower adherence to pharmacological treatment, younger age, impaired insight, and more drug or alcohol consumption. The clinical implications of the results point to the importance of establishing therapeutic alliance while managing patient's symptoms of hostility with antipsychotics such as olanzapine combined with psychosocial interventions to improve insight and reduce substance use.