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1.
Psychol Med ; : 1-19, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35510505

RESUMO

BACKGROUND: Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy. METHODS: A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events. RESULTS: Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13, n = 4375), amisulpride [1.99 (1.55-2.55)], sulpiride [1.50 (1.03-2.17)], and quetiapine [1.48 (1.23-1.78)] were significantly superior to placebo regarding treatment response. However, intolerability-related discontinuations were significantly higher compared to placebo with amisulpride and quetiapine. In adjunctive therapy (studies = 32, n = 8349), ziprasidone [1.80 (1.07-3.04)], risperidone [1.59 (1.19-2.14)], aripiprazole [1.54 (1.35-1.76)], brexpiprazole [1.41 (1.21-1.66)], cariprazine [1.27 (1.07-1.52)], and quetiapine [1.23 (1.08-1.41)] were significantly superior to placebo regarding treatment response. However, of these antipsychotics that were superior to placebo, only risperidone was equivalent to placebo regarding discontinuation due to intolerability, while the other antipsychotics were inferior. CONCLUSION: Results suggest that there are significant differences regarding the risk/benefit ratio among antipsychotics for MDD, which should inform clinical care.

2.
World Psychiatry ; 21(2): 248-271, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35524619

RESUMO

People with schizophrenia die 15-20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a systematic review and random-effects meta-analysis of prospective and retrospective, nationwide and targeted cohort studies assessing mortality risk in people with schizophrenia versus the general population or groups matched for physical comorbidities or groups with different psychiatric disorders, also assessing moderators. Primary outcome was all-cause mortality risk ratio (RR); key secondary outcomes were mortality due to suicide and natural causes. Other secondary outcomes included any other specific-cause mortality. Publication bias, subgroup and meta-regression analyses, and quality assessment (Newcastle-Ottawa Scale) were conducted. Across 135 studies spanning from 1957 to 2021 (schizophrenia: N=4,536,447; general population controls: N=1,115,600,059; other psychiatric illness controls: N=3,827,955), all-cause mortality was increased in people with schizophrenia versus any non-schizophrenia control group (RR=2.52, 95% CI: 2.38-2.68, n=79), with the largest risk in first-episode (RR=7.43, 95% CI: 4.02-13.75, n=2) and incident (i.e., earlier-phase) schizophrenia (RR=3.52, 95% CI: 3.09-4.00, n=7) versus the general population. Specific-cause mortality was highest for suicide or injury-poisoning or undetermined non-natural cause (RR=9.76-8.42), followed by pneumonia among natural causes (RR=7.00, 95% CI: 6.79-7.23), decreasing through infectious or endocrine or respiratory or urogenital or diabetes causes (RR=3 to 4), to alcohol or gastrointestinal or renal or nervous system or cardio-cerebrovascular or all natural causes (RR=2 to 3), and liver or cerebrovascular, or breast or colon or pancreas or any cancer causes (RR=1.33 to 1.96). All-cause mortality increased slightly but significantly with median study year (beta=0.0009, 95% CI: 0.001-0.02, p=0.02). Individuals with schizophrenia <40 years of age had increased all-cause and suicide-related mortality compared to those ≥40 years old, and a higher percentage of females increased suicide-related mortality risk in incident schizophrenia samples. All-cause mortality was higher in incident than prevalent schizophrenia (RR=3.52 vs. 2.86, p=0.009). Comorbid substance use disorder increased all-cause mortality (RR=1.62, 95% CI: 1.47-1.80, n=3). Antipsychotics were protective against all-cause mortality versus no antipsychotic use (RR=0.71, 95% CI: 0.59-0.84, n=11), with largest effects for second-generation long-acting injectable anti-psychotics (SGA-LAIs) (RR=0.39, 95% CI: 0.27-0.56, n=3), clozapine (RR=0.43, 95% CI: 0.34-0.55, n=3), any LAI (RR=0.47, 95% CI: 0.39-0.58, n=2), and any SGA (RR=0.53, 95% CI: 0.44-0.63, n=4). Antipsychotics were also protective against natural cause-related mortality, yet first-generation antipsychotics (FGAs) were associated with increased mortality due to suicide and natural cause in incident schizophrenia. Higher study quality and number of variables used to adjust the analyses moderated larger natural-cause mortality risk, and more recent study year moderated larger protective effects of antipsychotics. These results indicate that the excess mortality in schizophrenia is associated with several modifiable factors. Targeting comorbid substance abuse, long-term maintenance antipsychotic treatment and appropriate/earlier use of SGA-LAIs and clozapine could reduce this mortality gap.

3.
World Psychiatry ; 21(2): 295-307, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35524620

RESUMO

According to current evidence and guidelines, continued antipsychotic treatment is key for preventing relapse in people with schizophrenia-spectrum disorders, but evidence-based recommendations for the choice of the individual antipsychotic for maintenance treatment are lacking. Although oral antipsychotics are often prescribed first line for practical reasons, long-acting injectable antipsychotics (LAIs) are a valuable resource to tackle adherence issues since the earliest phase of disease. Medline, EMBASE, PsycINFO, CENTRAL and CINAHL databases and online registers were searched to identify randomized controlled trials comparing LAIs or oral antipsychotics head-to-head or against placebo, published until June 2021. Relative risks and standardized mean differences were pooled using random-effects pairwise and network meta-analysis. The primary outcomes were relapse and dropout due to adverse events. We used the Cochrane Risk of Bias tool to assess study quality, and the CINeMA approach to assess the confidence of pooled estimates. Of 100 eligible trials, 92 (N=22,645) provided usable data for meta-analyses. Regarding relapse prevention, the vast majority of the 31 included treatments outperformed placebo. Compared to placebo, "high" confidence in the results was found for (in descending order of effect magnitude) amisulpride-oral (OS), olanzapine-OS, aripiprazole-LAI, olanzapine-LAI, aripiprazole-OS, paliperidone-OS, and ziprasidone-OS. "Moderate" confidence in the results was found for paliperidone-LAI 1-monthly, iloperidone-OS, fluphenazine-OS, brexpiprazole-OS, paliperidone-LAI 1-monthly, asenapine-OS, haloperidol-OS, quetiapine-OS, cariprazine-OS, and lurasidone-OS. Regarding tolerability, none of the antipsychotics was significantly worse than placebo, but confidence was poor, with only aripiprazole (both LAI and OS) showing "moderate" confidence levels. Based on these findings, olanzapine, aripiprazole and paliperidone are the best choices for the maintenance treatment of schizophrenia-spectrum disorders, considering that both LAI and oral formulations of these antipsychotics are among the best-performing treatments and have the highest confidence of evidence for relapse prevention. This finding is of particular relevance for low- and middle-income countries and constrained-resource settings, where few medications may be selected. Results from this network meta-analysis can inform clinical guidelines and national and international drug regulation policies.

4.
Schizophr Bull ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524479

RESUMO

BACKGROUND AND HYPOTHESIS: Optimal doses of most antipsychotics in the maintenance treatment of schizophrenia are unknown. We aimed to study the risk of severe relapse indicated by rehospitalization for different dose categories of 15 most frequently used antipsychotics in monotherapy in Finland. STUDY METHODS: We studied the risk of rehospitalization (Adjusted Hazard Ratio, aHR) associated with six antipsychotic monotherapy dose categories (as time-varying dose, measured in defined daily dose, DDDs/day) in a nationwide cohort of persons diagnosed with schizophrenia (n = 61 889), using within-individual analyses to eliminate selection bias. STUDY RESULTS: Among the 15 most widely used antipsychotics, 13 had a U- or J-shaped dose-response curve, showing the lowest risks of relapse for doses of 0.6-<1.1 DDDs/day vs nonuse of antipsychotics. The exceptions were oral perphenazine (aHR = 0.72, 95% CI = 0.68-0.76, <0.6 DDDs/day), and olanzapine-long-acting injectable (LAI), which had the lowest aHR of any antipsychotic (aHR = 0.17, 95% CI = 0.11-0.25, 1.4-<1.6 DDDs/day). Certain risperidone and perphenazine doses <0.9 DDD/day were associated with 21%-45% lower risk of rehospitalization (P < .001) than the standard dose of 0.9-1.1 DDD/day (ie, 5 mg for risperidone and 30 mg for perphenazine). CONCLUSIONS: For most antipsychotics, the risk of severe relapse was the lowest during use of standard dose. Our results suggest that olanzapine LAI is highly effective in dose ranges >0.9 DDD/day, and especially at 1.4-<1.6 DDDs/day (405 mg/4 weeks) associated with substantially lower risk of rehospitalization than any dose of any other antipsychotic. The current WHO standard dose definitions appear to be clearly too high for perphenazine and somewhat too high for risperidone.

5.
Front Psychiatry ; 13: 795866, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35546936

RESUMO

Introduction: Schizophrenia is a severe psychiatric disorder with a large symptomatic heterogeneity. Moreover, many patients with schizophrenia present with comorbid psychiatric symptoms or disorders. The relation between depressive symptoms and negative symptoms, such as blunted affect, alogia, anhedonia, asociality and avolition, is particularly intriguing. The negative symptoms can be primary or secondary of depression or overlapping with depressive symptoms. The aim of the present network analysis was to better understand the interactions between depressive symptoms and the different symptoms of schizophrenia and to investigate whether negative symptoms and depressive symptoms can be better delineated. Methods: A network analysis on the baseline item scores of the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) from the cariprazine-risperidone study in patients with predominant negative symptoms (PNS) was performed. The connections between all these symptoms (PANSS and CDSS) were investiged: node strength and network centrality were estimated and the Mohr 5-factor model of the PANSS was applied to test the validity of its different symptoms clusters. Results: Across 460 patients with schizophrenia and PNS, the most central symptom (largest node strength) was depression (PANSS) followed by depression (CDSS), anxiety, lack of judgment and insight and tension. The PANSS negative symptom cluster together and was only poorly connected with CDSS depresson symptoms. The Mohr 5 factor model was clearly recognized in the overall clustering of symptoms. Conclusion: This network analysis suggests that depression and anxiety symptoms are the most central in this PNS patient population, despite the baseline low depression scores, and that negative symptoms are a clearly independent symptom cluster that can be delineated from depressive symptoms.

6.
Eur Neuropsychopharmacol ; 59: 45-55, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35550205

RESUMO

Schizophrenia is a severely debilitating neurodevelopmental disorder that requires continuous multidisciplinary treatment. Early onset schizophrenia (EOS, onset before 18) is associated with poorer outcomes than the adult-onset type. The transition from adolescent to adult mental healthcare services (AMHS) poses various challenges for maintaining continuity of care. The heterogeneous availability of specialized mental health services and resources for people with schizophrenia across Europe and the inadequacy of training programs in creating a shared culture and knowledge base between child and adult mental health professionals are major challenges at the policy level. More flexible and individualized transition timing is also needed. While changes in the relationship between patients, caregivers and mental health professionals at a time when young people should acquire full responsibility for their own care are challenges common to all mental health disorders, these are particularly relevant to the care of schizophrenia because of the severe associated disability. This Expert Opinion Paper examines the main aspects of transitioning of care in schizophrenia with the aim of identifying the challenges and the potential approaches that could enhance continuity of care.

7.
J Clin Med ; 11(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35566710

RESUMO

Evidence accumulates that, with close medical monitoring and phosphate supplementation, higher-caloric re-alimentation protocols beginning at 2000 kcal/day (HCR) are not associated with an increased incidence of electrolyte abnormalities in patients with anorexia nervosa (AN) but rather result in faster weight gain. These studies are still scant and have largely been performed in adults or moderately malnourished adolescents. METHODS: A retrospective chart review of patients with AN aged 12-20 years and with a body mass index (BMI) < 15 kg/m2 alimented according to a standardized treatment protocol in a German clinic specialized in AN was conducted. All patients received 2000 kcal/day from day one. The effect of HCR was examined with respect to laboratory changes and weight development over 4 weeks. RESULTS: In 120 youth (119 (99.2%) females and 1 (0.8%) male, the mean BMI was 13.1 ± 1.1 (range = 10.2-15.0), %mBMI was 62.1 ± 6.0% and weight gain was 0.76 ± 0.22 kg per week, with the highest rate of weight gain during week 1 (1.25 ± 1.28 kg/week). Over 4 weeks, the total weight gain was 3.00 ± 1.92 kg. Nine patients (7.5%) developed mild hypophosphatemia, and none developed refeeding syndrome. CONCLUSIONS: Starting re-alimentation with 2000 kcal/d under close medical surveillance, severely malnourished youth with AN met the recommended weight gain targets between 0.5 and 1 kg/week according to current treatment guidelines, without anyone developing refeeding syndrome.

8.
PLoS Med ; 19(4): e1003960, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35439243

RESUMO

BACKGROUND: Severe mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and CVD-related mortality. To date, no systematic review has investigated changes in population level CVD-related mortality over calendar time. It is unclear if this relationship has changed over time in higher-income countries with changing treatments. METHODS AND FINDINGS: To address this gap, a systematic review was conducted, to assess the association between SMI and CVD including temporal change. Seven databases were searched (last: November 30, 2021) for cohort or case-control studies lasting ≥1 year, comparing frequency of CVD mortality or incidence in high-income countries between people with versus without SMI. No language restrictions were applied. Random effects meta-analyses were conducted to compute pooled hazard ratios (HRs) and rate ratios, pooled standardised mortality ratios (SMRs), pooled odds ratios (ORs), and pooled risk ratios (RRs) of CVD in those with versus without SMI. Temporal trends were explored by decade. Subgroup analyses by age, sex, setting, world region, and study quality (Newcastle-Ottawa scale (NOS) score) were conducted. The narrative synthesis included 108 studies, and the quantitative synthesis 59 mortality studies (with (≥1,841,356 cases and 29,321,409 controls) and 28 incidence studies (≥401,909 cases and 14,372,146 controls). The risk of CVD-related mortality for people with SMI was higher than controls across most comparisons, except for total CVD-related mortality for BD and cerebrovascular accident (CVA) for mixed SMI. Estimated risks were larger for schizophrenia than BD. Pooled results ranged from SMR = 1.55 (95% confidence interval (CI): 1.33 to 1.81, p < 0.001), for CVA in people with BD to HR/rate ratio = 2.40 (95% CI: 2.25 to 2.55, p < 0.001) for CVA in schizophrenia. For schizophrenia and BD, SMRs and pooled HRs/rate ratios for CHD and CVD mortality were larger in studies with outcomes occurring during the 1990s and 2000s than earlier decades (1980s: SMR = 1.14, 95% CI: 0.57 to 2.30, p = 0.71; 2000s: SMR = 2.59, 95% CI: 1.93 to 3.47, p < 0.001 for schizophrenia and CHD) and in studies including people with younger age. The incidence of CVA, CVD events, and heart failure in SMI was higher than controls. Estimated risks for schizophrenia ranged from HR/rate ratio 1.25 (95% CI: 1.04 to 1.51, p = 0.016) for total CVD events to rate ratio 3.82 (95% CI: 3.1 to 4.71, p < 0.001) for heart failure. Incidence of CHD was higher in BD versus controls. However, for schizophrenia, CHD was elevated in higher-quality studies only. The HR/rate ratios for CVA and CHD were larger in studies with outcomes occurring after the 1990s. Study limitations include the high risk of bias of some studies as they drew a comparison cohort from general population rates and the fact that it was difficult to exclude studies that had overlapping populations, although attempts were made to minimise this. CONCLUSIONS: In this study, we found that SMI was associated with an approximate doubling in the rate ratio of CVD-related mortality, particularly since the 1990s, and in younger groups. SMI was also associated with increased incidence of CVA and CHD relative to control participants since the 1990s. More research is needed to clarify the association between SMI and CHD and ways to mitigate this risk.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Transtornos Mentais , Transtornos Psicóticos , Esquizofrenia , Doenças Cardiovasculares/epidemiologia , Humanos , Transtornos Mentais/complicações , Transtornos Mentais/epidemiologia , Esquizofrenia/complicações , Esquizofrenia/epidemiologia
9.
Eur Eat Disord Rev ; 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35474627

RESUMO

OBJECTIVE: Various approaches exist to treat youth with anorexia nervosa (AN). Family-based treatment (FBT) has never been compared to long inpatient, multimodal treatment (IMT) in a randomized controlled trial (RCT). The aim of this study was to compare data on body weight trajectories, change in eating disorder psychopathology, hospital days and treatment costs in RCTs delivering FBT or IMT. METHOD: Review of RCTs published between 2010 and 2020 in youth with AN, delivering FBT or IMT. RESULTS: Four RCTs delivering FBT (United States, n = 2; Australia, n = 2), one RCT delivering Family Therapy for AN (United Kingdom) and two RCTs delivering IMT (France, n = 1; Germany, n = 1) were identified from previous meta-analyses. The comparison of studies was limited by (1) significant differences in patient baseline characteristics including pretreated versus non-pretreated patients, (2) use of different psychometric and weight measures and (3) different initial velocity of weight recovery. Minimal baseline and outcome reporting standards for body weight metrics and nature/dose of interventions allowing international comparison are needed and suggestions to developing these standards are presented. DISCUSSION: An RCT should investigate, whether FBT is a viable alternative to IMT, leading to comparable weight and psychopathology improvement with less inpatient time and costs.

10.
Nutrients ; 14(7)2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35406009

RESUMO

In the USA, family-based treatment (FBT) with inpatient medical stabilization as needed is the leading evidence-based treatment for youth with anorexia nervosa (AN). In continental Europe, typically inpatient multimodal treatment targeting weight recovery followed by outpatient care (IMT) is standard care, if prior outpatient treatment was not sufficient. Our aim was to compare weekly weight gain and hospital days over six months for adolescents receiving FBT (USA) versus IMT (Germany) using naturalistic treatment data. To yield similar subgroups of youth aged 12-18 years, inclusion criteria were a percent median BMI (%mBMI) between 70-85 and the restrictive AN subtype. Weight gain and hospital days were compared, adjusted further in a multiple linear regression analysis (MLRA) for baseline group differences. Samples differed on baseline %mBMI (FBT [n = 71], 90.5 ± 12.8; IMT [n = 29], 78.3 ± 9.1, p < 0.05). In subgroups with comparable baseline %mBMI, the weekly weight gain over 6 months was similar (FBT [n = 21]: 0.35 ± 0.18 kg/week; IMT [n = 20]: 0.30 ± 0.18, p = 0.390, p = 0.166 after MLRA), but achieved fewer hospital days in FBT (FBT [n = 7]: 4 ± 6 days, IMT [n = 20]: 121 ± 42 days, p < 0.0001 before and after MLRA). FBT may be effective for a subgroup of adolescents with AN currently receiving IMT, but head-to-head studies in the same healthcare system are needed.


Assuntos
Anorexia Nervosa , Adolescente , Anorexia Nervosa/terapia , Terapia Combinada , Terapia Familiar , Humanos , Pacientes Internados , Resultado do Tratamento , Ganho de Peso
11.
Neurosci Biobehav Rev ; 137: 104662, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35427644

RESUMO

We mapped the evidence on the type and strength of associations between a broad range of mental and physical conditions in children and adolescents, by carrying out an umbrella review, i.e., a quantitative synthesis of previous systematic reviews and meta-analyses. We also assessed to which extent the links between mental and physical conditions vary across disorders or, by contrast, are transdiagnostic. Based on a pre-established protocol, we retained 45 systematic reviews/meta-analyses, encompassing around 12.5 million of participants. In analyses limited to the most rigorous estimates, we found evidence for the following associations: ADHD-asthma, ADHD-obesity, and depression-asthma. A transdiagnostic association was confirmed between asthma and anxiety/ASD/depression/bipolar disorder, between obesity and ADHD/ASD/depression, and between dermatitis and ASD/ADHD. We conclude that obesity and allergic conditions are likely to be associated with mental disorders in children and adolescents. Our results can help clinicians explore potential links between mental and physical conditions in children/adolescent and provide a road map for future studies aimed at shading light on the underlying factors.

12.
Mol Psychiatry ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484237

RESUMO

Numerous risk factors for mental disorders have been identified. However, we do not know how many disorders we could prevent and to what extent by modifying these risk factors. This study quantifies the Population Attributable Fraction (PAF) of potentially modifiable risk factors for mental disorders. We conducted a PRISMA 2020-compliant (Protocol: https://osf.io/hk2ag ) meta-umbrella systematic review (Web of Science/PubMed/Cochrane Central Register of Reviews/Ovid/PsycINFO, until 05/12/2021) of umbrella reviews reporting associations between potentially modifiable risk factors and ICD/DSM mental disorders, restricted to highly convincing (class I) and convincing (class II) evidence from prospective cohorts. The primary outcome was the global meta-analytical PAF, complemented by sensitivity analyses across different settings, the meta-analytical Generalised Impact Fraction (GIF), and study quality assessment (AMSTAR). Seven umbrella reviews (including 295 meta-analyses and 547 associations) identified 28 class I-II risk associations (23 risk factors; AMSTAR: 45.0% high-, 35.0% medium-, 20.0% low quality). The largest global PAFs not confounded by indication were 37.84% (95% CI = 26.77-48.40%) for childhood adversities and schizophrenia spectrum disorders, 24.76% (95% CI = 13.98-36.49%) for tobacco smoking and opioid use disorders, 17.88% (95% CI = not available) for job strain and depression, 14.60% (95% CI = 9.46-20.52%) for insufficient physical activity and Alzheimer's disease, 13.40% (95% CI = 7.75-20.15%) for childhood sexual abuse and depressive disorders, 12.37% (95% CI = 5.37-25.34%) for clinical high-risk state for psychosis and any non-organic psychotic disorders, 10.00% (95% CI = 5.62-15.95%) for three metabolic factors and depression, 9.73% (95% CI = 4.50-17.30%) for cannabis use and schizophrenia spectrum disorders, and 9.30% (95% CI = 7.36-11.38%) for maternal pre-pregnancy obesity and ADHD. The GIFs confirmed the preventive capacity for these factors. Addressing several potentially modifiable risk factors, particularly childhood adversities, can reduce the global population-level incidence of mental disorders.

14.
J Clin Psychiatry ; 83(2)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35235720

RESUMO

Objective: To evaluate the short- and long-term effects of brexpiprazole on patient functioning in schizophrenia.Methods: Data were included from three 6-week, randomized, double-blind, placebo-controlled studies (hospitalized patients); a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study (terminated early by the study sponsor based on the positive result of an interim analysis); and two 52-week, open-label extension studies-all in patients with schizophrenia (DSM-IV-TR criteria) and conducted from July 2011-February 2016. Patients allocated to oral brexpiprazole received 2-4 mg/d (short-term studies) or 1-4 mg/d (long-term studies). Functioning was measured using the Personal and Social Performance (PSP) and Global Assessment of Functioning (GAF) scales, with response defined as a PSP/GAF increase of ≥ 10 points and remission as PSP score ≥ 71 or GAF score ≥ 61.Results: Patients receiving brexpiprazole (n = 831) showed greater improvement than those receiving placebo (n = 490) from baseline to week 6 in PSP score (least squares mean difference, 3.20; 95% confidence interval, 1.82-4.58; P < .0001; Cohen d = 0.31) and in all 4 PSP domains. At week 52 of the maintenance study (which had a low completion rate primarily due to the early termination), GAF functional remission was achieved by 65.3% (62/95) of stabilized patients randomized to brexpiprazole and 47.1% (48/102) of stabilized patients randomized to placebo, with a number needed to treat of 6 (95% confidence interval, 4-22; P = .0076). At week 52 of the open-label studies (n = 177), PSP functional response and remission were achieved by 84.2% and 41.8% of patients receiving brexpiprazole, respectively.Conclusions: Although limited by the lack of an active comparator, analyses of this large dataset demonstrate that brexpiprazole treatment is associated with clinically relevant improvement in functioning among patients with schizophrenia, in the short term and long term.Trial Registration: Data used in this post hoc analysis were from studies with ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380, NCT01668797, NCT01397786, and NCT01810783.


Assuntos
Antipsicóticos , Quinolonas , Esquizofrenia , Antipsicóticos/efeitos adversos , Método Duplo-Cego , Humanos , Quinolonas/efeitos adversos , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Tiofenos/efeitos adversos , Resultado do Tratamento
15.
Neurosci Biobehav Rev ; 136: 104608, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35303594

RESUMO

Changes over 50 years of research on antipsychotics in schizophrenia have occurred. A scientometric synthesis of such changes over time and a measure of researchers' networks and scientific productivity is currently lacking. We searched Web of Science Core Collection from inception until November 5, 2021, using the appropriate key. Our primary objective was to conduct systematic mapping with CiteSpace to show how clusters of keywords have evolved over time and obtain clusters' structure and credibility. Our secondary objective was to measure research network performance (countries, institutions, and authors) using CiteSpace, VOSviewer, and Bibliometrix. We included 32,240 studies published between 1955 and 2021. The co-cited reference network identified 25 clusters with a well-structured network (Q=0.8166) and highly credible clustering (S=0.91). The main trends of research were: 1) antipsychotic efficacy; 2) cognition in schizophrenia; 3) side effects of antipsychotics. Last five years research trends were: 'ultra-resistance schizophrenia' (S=0.925), 'efficacy/dose-response' (S=0.775), 'evidence-synthesis' (S=0.737), 'real-world effectiveness' (S=0.794), 'cannabidiol' (S=0.989), and 'gut microbiome' (S=0.842). These results can inform funding agencies and research groups' future directions.


Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Humanos , Publicações , Esquizofrenia/tratamento farmacológico
16.
J Child Adolesc Psychopharmacol ; 32(3): 178-186, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35235379

RESUMO

Editors' Note: The Editors would like to address issues related to the acceptance of this manuscript. The original manuscript referenced the study tool as the Bipolar Prodrome Symptom Interview Scale-Prospective (BPSS-P). After the manuscript's initial acceptance, the authors requested a revision of the tool name to Bipolar Prodrome Symptom Interview Scale-Full Perspective (BPSS-FP). When this request was made, the original acceptance was rescinded, and the authors were asked to formally revise and resubmit the manuscript with an explanation for the change. This revision and subsequent review led to the final acceptance of the manuscript. The authors have assured us that the tool used in the manuscript was the BPSS-FP (version 5) as opposed to abbreviated forms of this tool that are also used in research (e.g., Bipolar Prodrome Symptom Scale-Abbreviated Screen for Patients (BPSS-AS-P). Background: No scale exists to assess patients at-risk for bipolar disorder (BD) in Turkey. We aimed to assess the psychometric properties of the Turkish version of the Bipolar Prodrome Symptom Interview and Scale-Full Prospective (BPSS-FP). Method: Psychiatric service users aged 11-18 years old were interviewed using the BPSS-FP translated into Turkish and the Kiddie Schedule for Affective Disorders and Schizophrenia. Youth with major depressive disorder (MDD, n = 63), bipolar-spectrum disorder (n = 47), and healthy controls (n = 122) were included. Cronbach's alpha was calculated to assess internal consistency. The Young Mania Rating Scale (YMRS) and Children's Depression Rating Scale-Revised (CDRS-R) were administered to test convergent/discriminant validity. Discriminant validity was further tested using one-way ANOVA and "receiver operating characteristic" (ROC) curves. Inter-rater reliability was tested using correlation coefficients. Findings: Across 232 youth, Cronbach's alpha values were 0.932 for the BPSS-FP total score, 0.878 for the Mania Symptom Index, 0.887 for the Depression Symptom Index, and 0.797 for the General Symptom Index. Correlation coefficients for inter-rater reliability were high for the Mania Symptom Index (r = 0.989), Depression Symptom Index (r = 0.973), and General Symptom Index (r = 0.981). There were high correlations between the BPSS-FP Mania Symptom Index subscore and YMRS (r = 0.732), and the BPSS-FP Depression Symptom Index subscore and CDRS-R (r = 0.754), whereas cross-polarity correlations were non-significant. ROC analysis cut-off value was ≥21 for the BPSS-FP Mania Symptom Index between patients with BD and MDD (specificity = 85.7%, sensitivity = 78.7%). Conclusion: The Turkish version of the BPSS-FP has good psychometric properties and can be used in research. Longitudinal studies are needed to confirm the predictive value of the BPSS-FP.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Adolescente , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Criança , Transtorno Depressivo Maior/diagnóstico , Humanos , Mania , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Psicometria , Reprodutibilidade dos Testes , Turquia
18.
Lancet Psychiatry ; 9(4): 291-306, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35276079

RESUMO

BACKGROUND: Combining antipsychotics is common in schizophrenia treatment, despite evidence-based guidelines generally not recommending such practice. Otherwise, evidence remains inconclusive, especially regarding specific combinations. The trial aimed to test whether a combination of amisulpride plus olanzapine is more effective than either intervention as a monotherapy. METHODS: A multicentre, 16-week, randomised, double-blind, controlled trial was done at 16 psychiatric in-patient centres throughout Germany. Inclusion criteria were adults aged 18-65 years with non-first episode schizophrenia or schizoaffective disorder and with a Positive and Negative Syndrome Scale (PANSS) total score of at least 70 and at least two items of the positive symptoms subscale rated at least 4. Patients were randomly assigned to receive 16 weeks of treatment with either amisulpride plus olanzapine, amisulpride plus placebo, or olanzapine plus placebo (1:1:1), and block randomisation was stratified by study site. To keep patients and investigators masked throughout the duration of the trial, amisulpride, olanzapine, and placebo were administered as identical capsules. Flexibly dosed monotherapy of oral amisulpride (amisulpride plus placebo, 200-800 mg per day) or olanzapine (olanzapine plus placebo, 5-20 mg per day) was compared with a combination of amisulpride plus olanzapine. The primary outcome was symptom reduction measured by the PANSS total score after 8 weeks, in the modified intention-to-treat population (all patients randomly assigned to an intervention and receiving at least one study drug dose). As determined a priori, group differences were examined by t tests (Bonferroni-Holm-adjustment) followed by pre-planned Bayesian analyses as well as imputation methods based on mixed models to account for missing values and post-hoc ANCOVA adjusting for PANSS baseline scores. The study was registered on ClinicalTrials.gov, NCT01609153; the German Clinical Trials Register, DRKS00003603; and the European Union Drug Regulating Authorities Clinical Trials Database, EudraCT-No. 2011-002463-20. FINDINGS: Between June 15, 2012, and Dec 15, 2018, 13 692 patients were assessed for eligibility. 13 364 patients were excluded (including for not meeting inclusion criteria, declining to participate, or inappropriate reasons for changing pharmacological treatment), and 328 were then randomly assigned to an intervention group. 112 patients were randomly assigned to receive amisulpride plus olanzapine, 109 were randomly assigned to receive amisulpride plus placebo, and 107 were randomly assigned to receive olanzapine plus placebo. 321 patients were analysed for the primary outcome in the modified intention-to-treat population after exclusion of screening failures and patients who did not receive the intervention (110 for amisulpride plus olanzapine, 109 for amisulpride plus placebo, and 102 for olanzapine plus placebo). Among the 321 patients who were randomly assigned to intervention groups and analysed for the primary outcome, 229 (71%) were male, 92 (29%) were female; the mean age was 40·2 years (SD 11·7); and 296 (92%) were White and 25 (8%) were classified as other ethnicity. PANSS total score improved significantly more at 8 weeks in the amisulpride plus olanzapine group (-29·6 [SD 14·5]) than in the olanzapine plus placebo group (-24·1 [13·4], p=0·049, Cohen's d=0·396). A significant difference was not observed in reduction of PANSS total score between the amisulpride and olanzapine group compared with the amisulpride and placebo group (-25·2 [SD 15·9], p=0·095, Cohen's d=0·29). After 8 weeks and 16 weeks, sexual dysfunction, weight, and waist circumference increase were significantly higher for patients receiving amisulpride plus olanzapine than for those receiving amisulpride plus placebo, with no differences in serious adverse events. Two patients died during study participation; one randomly assigned to the amisulpride plus olanzapine group, and one assigned to the olanzapine plus placebo group (both assessed with no relation to treatment). INTERPRETATION: The advantages of amisulpride plus olanzapine have to be weighed against a higher propensity for side-effects. The use of this specific combination therapy could be an alternative to monotherapy in certain clinical situations, but side-effects should be considered. FUNDING: German Federal Ministry of Education and Research.


Assuntos
Esquizofrenia , Adolescente , Adulto , Idoso , Amissulprida/efeitos adversos , Teorema de Bayes , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
19.
Child Adolesc Psychiatry Ment Health ; 16(1): 17, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35227292

RESUMO

BACKGROUND: Youths with eating disorders (EDs) engaging in nonsuicidal self-injury (NSSI) are at higher suicide risk because EDs and NSSI are associated with suicidality. However, epidemiologic data on NSSI lacks in the vulnerable group of youth ED inpatients. METHODS: This retrospective chart review included patients up to 18 years of age with an ICD-10 diagnosis of anorexia nervosa, restricting type (AN-R), anorexia nervosa, binge-purge type (AN-BP), and bulimia nervosa (BN), treated at the child and adolescent inpatient department of the University Hospital in Berlin, Germany, between 1990 and 2015. Across and within ED subgroups, lifetime NSSI prevalence, methods of self-harm, and clinical correlates were evaluated. Independent correlations of demographic and clinical factors with NSSI were identified via multivariable regression models. RESULTS: Of 382 inpatients (median = 15.6 (range = 9-18) years, females = 97.1%), 21.5% reported lifetime NSSI, consisting of cutting = 86.6%, scratching = 12.2%, and hitting = 8.5%. NSSI was more frequent in BN (47.6%) and AN-BP (39.3%) than AN-R (8.3%) (Φ = 0.43). Across ED subgroups, NSSI was associated with a higher prevalence of psychiatric comorbidities (AN-R: Φ = 0.55; AN-BP: Φ = 0.69; BN: Φ = 0.78), suicidal ideation (AN-R: Φ = 0.30; AN-BP: Φ = 0.38; BN: Φ = 0.29), and psychiatric medication use (AN-R: Φ = 0.23; AN-BP: Φ = 0.64; BN: Φ = 0.60). In multivariable regression analyses, NSSI was independently associated with a higher prevalence of psychiatric comorbidities (AN-R: OR = 2.93 [1.42, 6.04]; AN-BP: OR = 2.67 [1.13, 6.31]; BN: OR = 3.75 [1.71, 8.23]). Additionally, independent correlates with NSSI in AN-R included a higher prevalence of suicidal ideation (OR = 0.21 [0.72, 0.64]) and less weekly weight gain (OR = 0.03 [0.02, 0.43]), while in BN, NSSI was correlated with longer inpatient treatment duration (OR = 1.01 [1.00, 1.02]). CONCLUSIONS: There is a high lifetime prevalence of NSSI among youth with AN and BN requiring inpatient treatment, especially those with binge-purge behaviors. Treatment programs must be tailored to address psychiatric comorbidities and suicidality to improve patient care and suicide prevention. TRIAL REGISTRATION: This study was not considered a clinical trial but a retrospective chart review based on routinely assessed clinical parameters. The study includes data from human participants, however: (1) no intervention and no prospective assignment to interventions were performed, and (2) no evaluation of an intervention on participants was accomplished.

20.
Compr Psychiatry ; 115: 152301, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248877

RESUMO

BACKGROUND: Sertraline is a selective serotonin reuptake inhibitor with specific indications in child and adolescent psychiatry. Notwithstanding its frequent use and clinical benefits, the relationship between pharmacokinetics, pharmacodynamics, efficacy, and tolerability of sertraline across indications, particularly in non-adult patients, is not fully understood. METHOD: This naturalistic therapeutic drug monitoring (TDM) study was conducted in a transdiagnostic sample of children and adolescents treated with sertraline (n = 78; mean age, 14.22 ± 2.39; range, 7-18 years) within the prospective multicenter "TDM-VIGIL" project. Associations between dose, serum concentration, and medication-specific therapeutic and side effects based on the Clinical Global Impression scale were examined. Tolerability was measured qualitatively with the 56-item Pediatric Adverse Event Rating Scale. RESULTS: A strong linear positive dose-serum concentration relationship (with dose explaining 45% of the variance in concentration) and significant effects of weight and co-medication were found. Neither dose nor serum concentration were associated with side effects. An overall mild-to-moderate tolerability profile of sertraline was observed. In contrast with the transdiagnostic analysis that did not indicate an effect of concentration, when split into depression (MDD) and obsessive-compulsive disorder (OCD) diagnoses, the probability of clinical improvement significantly increased as both dose and concentration increased for OCD, but not for MDD. CONCLUSIONS: This TDM-flexible-dose study revealed a significant diagnosis-specific effect between sertraline serum concentration and clinical efficacy for pediatric OCD. While TDM already guides clinical decision-making regarding compliance, dose calibration, and drug-drug interactions, combining TDM with other methods, such as pharmacogenetics, may facilitate a personalized medicine approach in psychiatry.


Assuntos
Transtorno Obsessivo-Compulsivo , Sertralina , Adolescente , Criança , Monitoramento de Medicamentos/métodos , Humanos , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Estudos Prospectivos , Inibidores de Captação de Serotonina/uso terapêutico , Sertralina/uso terapêutico
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