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Revista Social psychiatry and psychiatric epidemiology
Año 2020
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PURPOSE: The objectives of this review were to understand the prevalence of cannabis use and how cannabis is associated with transition to psychosis, symptoms, cognition, trauma and family history in clinical high risk (CHR) for psychosis individuals. METHOD: A systematic literature review was conducted to find studies that examined cannabis use in CHR individuals, with no limitations on the geographical area, and included publications up to November 2018. Studies were screened for inclusion based on detailed criteria, and data were extracted on cannabis use and associated outcomes. A quantitative synthesis by meta-analysis was performed where appropriate, otherwise, a qualitative synthesis was conducted. RESULTS: Overall, 36 studies met inclusion criteria with an average age of 20.1 years and 58.4% males. Prevalence of lifetime cannabis use was 48.7%, whereas current cannabis use was 25.8% and the prevalence of cannabis use disorder/abuse or dependence was 14.9% across the studies. All cannabis use results had statistically significant heterogeneity ranging from 75.7 to 92.8%. The most commonly reported association with cannabis use was transition to psychosis, although the pooled relative risk (RR) was not statistically significant (RR = 1.11, 95% confidence interval = 0.89-1.37). For all other outcomes including symptoms, cognition, trauma, and family history, the evidence was limited, and therefore, the results were synthesized qualitatively. CONCLUSION: Almost half of CHR individuals have ever used cannabis. However, cannabis use has not been thoroughly researched regarding frequency and dose of use, and how other factors, such as symptoms, are associated with cannabis in CHR individuals.

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Revista Early intervention in psychiatry
Año 2019
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AIM: Youth at clinical high risk (CHR) for psychosis often exhibit difficulties in social functioning and poorer social functioning may be predictive of transition to a psychotic disorder. Therefore, the primary objective of this systematic review was to summarize the impact of all interventions on social functioning in CHR samples. METHOD: Electronic databases PsycINFO, CINAHL, Embase, EBM, and MEDLINE were searched from 1951 to June 2017. Studies were selected if they included any intervention that reported changes in social functioning in youth at CHR. Data were evaluated using random effects pairwise meta-analyses, stratified by time, and reported as the standardized mean difference (SMD). RESULTS: Nineteen studies met our inclusion criteria, including a total of 1513 CHR participants. The mean age was 20.5 years and 47% were male. Cognitive behavioural therapy (4 studies) did not significantly improve social functioning at 6 months (SMD = 0.06; 95% confidence interval [CI] = -0.35, 0.46), 12 months (SMD = -0.15; 95% CI = -0.38, 0.08) and 18 months (SMD = 0.20; 95% CI = -0.10, 0.50). Omega-3 (2 studies) did not significantly improve social functioning at 6 months (SMD = 0.01; 95% CI = -0.21, 0.24) and 12 months (SMD = -0.08; 95% CI = -0.33, 0.17). Lastly, cognitive remediation (3 studies) did not significantly improve social functioning at 2- to 3-month follow-up (SMD = 0.13, 95% CI = -0.18, 0.43). CONCLUSIONS: This systematic review and meta-analysis demonstrated that no treatment significantly improved social functioning in youth at CHR. Future randomized control trials are required that are designed to target and improve social functioning in youth at CHR for psychosis.

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Revista Early intervention in psychiatry
Año 2019
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AIM: Attenuated psychotic symptoms (APSs) have been the primary emphasis in youth at clinical high risk (CHR) for psychosis for assessing symptomology and determining subsequent transition to a psychotic disorder. Previous reviews primarily focused on the efficacy of cognitive behavioural therapy (CBT) on APS; however, a comprehensive assessment of other interventions to date is lacking. Therefore, we conducted a systematic review and meta-analysis of all intervention studies examining APS in CHR youth. METHOD: The authors searched Embase, CINAHL, PsycINFO, Medline and EBM from inception to May 2017. Studies were selected if they included any intervention that reported follow-up APS in youth at CHR. Interventions were evaluated and stratified by time using both pairwise and network meta-analyses (NMAs). Due to the differences in APS scales, effect sizes were calculated as Hedges g and reported as the standardized mean difference (SMD). RESULTS: Forty-one studies met our inclusion criteria. In pairwise meta-analyses, CBT was associated with a significant reduction in APS compared to controls at 18- to 24-month follow-up (SMD, -0.22; 95% CI, -0.43 to -0.01; I2 =0%; P = .04, 3 studies, N = 356). In the NMA, integrated psychological therapy, CBT, supportive therapy, family therapy, needs-based interventions, omega-3, risperidone plus CBT and olanzapine were not significantly more effective at reducing APS at 6 and 12 months relative to any other intervention. CONCLUSIONS: CBT was more effective at reducing APS at long-term follow-up compared to controls. No interventions were significantly more effective at reducing APS compared to all other interventions in the NMA.

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Revista World psychiatry : official journal of the World Psychiatric Association (WPA)
Año 2018
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Preventing psychosis in patients at clinical high risk may be a promising avenue for pre-emptively ameliorating outcomes of the most severe psychiatric disorder. However, information on how each preventive intervention fares against other currently available treatment options remains unavailable. The aim of the current study was to quantify the consistency and magnitude of effects of specific preventive interventions for psychosis, comparing different treatments in a network meta-analysis. PsycINFO, Web of Science, Cochrane Central Register of Controlled Trials, and unpublished/grey literature were searched up to July 18, 2017, to identify randomized controlled trials conducted in individuals at clinical high risk for psychosis, comparing different types of intervention and reporting transition to psychosis. Two reviewers independently extracted data. Data were synthesized using network meta-analyses. The primary outcome was transition to psychosis at different time points and the secondary outcome was treatment acceptability (dropout due to any cause). Effect sizes were reported as odds ratios and 95% confidence intervals (CIs). Sixteen studies (2,035 patients, 57% male, mean age 20.1 years) reported on risk of transition. The treatments tested were needs-based interventions (NBI); omega-3 + NBI; ziprasidone + NBI; olanzapine + NBI; aripiprazole + NBI; integrated psychological interventions; family therapy + NBI; D-serine + NBI; cognitive behavioural therapy, French & Morrison protocol (CBT-F) + NBI; CBT-F + risperidone + NBI; and cognitive behavioural therapy, van der Gaag protocol (CBT-V) + CBT-F + NBI. The network meta-analysis showed no evidence of significantly superior efficacy of any one intervention over the others at 6 and 12 months (insufficient data were available after 12 months). Similarly, there was no evidence for intervention differences in acceptability at either time point. Tests for inconsistency were non-significant and sensitivity analyses controlling for different clustering of interventions and biases did not materially affect the interpretation of the results. In summary, this study indicates that, to date, there is no evidence that any specific intervention is particularly effective over the others in preventing transition to psychosis. Further experimental research is needed.

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Revista Schizophrenia bulletin
Año 2018
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OBJECTIVE: Youth at clinical high risk (CHR) for psychosis often demonstrate significant negative symptoms, which have been reported to be predictive of conversion to psychosis and a reduced quality of life but treatment options for negative symptoms remain inadequate. Therefore, we conducted a systematic review and network meta-analysis of all intervention studies examining negative symptom outcomes in youth at CHR for psychosis. METHOD: The authors searched PsycINFO, Medline, Embase, CINAHL, and EBM from inception to December 2016. Studies were selected if they included any intervention that reported follow-up negative symptoms in youth at CHR for psychosis. Treatment comparisons were evaluated using both pairwise and network meta-analyses. Due to the differences in negative symptom scales the effect sizes were reported as the standardized mean difference (SMD). RESULTS: Of 3027 citations, 32 studies met our inclusion criteria, including a total of 2463 CHR participants. N-methyl-D-aspartate-receptor (NMDAR) modulators trended toward a significant reduction in negative symptoms compared to placebo (SMD = -0.54; 95% CI = -1.09 to 0.02; I2 = 0%, P = .06). In respective order of descending effectiveness as per the treatment hierarchy, NMDAR modulators were more effective than family therapy, need-based interventions, risperidone, amisulpride, cognitive behavioral therapy, omega-3, olanzapine, supportive therapy, and integrated psychological interventions. CONCLUSIONS: Although this review demonstrated small-large effect sizes between interventions and a reduction in negative symptoms many relevant studies had small samples and the majority was not designed to target negative symptoms, thus reducing their clinical importance with respect to negative symptoms.

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Revista International journal of molecular sciences
Año 2017
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In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of ω-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far.

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Libro AHRQ Comparative Effectiveness Reviews
Año 2017
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OBJECTIVES: To review the evidence on first- and second-generation antipsychotics (FGAs and SGAs) for the treatment of various psychiatric and behavioral conditions in children, adolescents, and young adults (ages ≤ 24 years). DATA SOURCES: Eight electronic databases, gray literature, trial registries, and reference lists. METHODS: Two reviewers conducted study selection and risk of bias assessment independently, and resolved discrepancies by consensus. One reviewer extracted and a second verified the data. We conducted meta-analyses when appropriate and network meta-analysis across conditions for changes to body composition. We rated strength of evidence for prespecified outcomes. RESULTS: One hundred thirty-five studies (95 trials and 40 observational studies) were included. None of the evidence was rated as high strength of evidence; results having moderate strength (i.e., probably an accurate effect) are presented (with n studies) below.SCHIZOPHRENIA AND RELATED PSYCHOSES (N = 39): Compared with placebo, SGAs as a class probably increase response rates, decrease slightly (not clinically significant for many patients) negative and positive symptoms, and improve slightly global impressions of improvement, severity, and functioning. There is likely little or no difference between high and low doses of quetiapine for clinical severity and functioning. Many outcomes for individual drug comparisons were of low or insufficient strength of evidence. BIPOLAR DISORDER (N = 19): Compared with placebo, SGAs probably decrease mania, decrease depression symptoms slightly, and improve symptom severity and global functioning to a small extent. SGAs (and aripiprazole alone) probably increase response and remission rates versus placebo for manic/mixed phases. Quetiapine likely makes little or no difference in depression. AUTISM SPECTRUM DISORDERS (N = 23): Compared with placebo, SGAs as a class probably decrease irritability, and decrease slightly lethargy/social withdrawal, stereotypy, and inappropriate speech; they likely increase response rates and (slightly) clinical severity. It is likely that aripiprazole and risperidone decrease irritability. ATTENTION DEFICIT HYPERACVTIVITY DISORDER (ADHD) AND DISRUPTIVE, IMPULSE-CONTROL, AND CONDUCT DISORDERS (N = 13): Compared with placebo, SGAs as a class (and risperidone individually) probably decrease conduct problems and aggression. Risperidone alone likely decreases hyperactivity in children with a primary diagnosis of conduct disorders or with ADHD but not responding to stimulants. OTHER CONDITIONS: All outcomes had low or insufficient strength of evidence for tic disorders (n = 12), obsessive-compulsive disorder (n = 1), depression (n = 1), eating disorders (n = 3), and behavioral issues (n = 2). HARMS ACROSS CONDITIONS: From network meta-analysis, olanzapine was more harmful for gains in weight and body mass index (BMI) than other SGAs except for clozapine and lurasidone; results were most robust for relative harm over aripiprazole, quetiapine, and risperidone, and most applicable to the short term. Findings from pairwise meta-analysis between different SGAs were similar, except for showing longer term benefit for quetiapine and risperidone versus olanzapine, and little or no short-term differences between risperidone and quetiapine, or between different doses of aripiprazole, asenapine, or quetiapine. FGAs probably cause slightly less harm for weight and BMI compared with SGAs. There is probably little or no difference in risk for somnolence between different doses of asenapine or quetiapine. There is likely little or no difference in risk for mortality or prolonged QT interval in the short term for SGAs as a class. SGAs versus placebo/no treatment probably increase short-term risk for high triglyceride levels, extrapyramidal symptoms, sedation, and somnolence. CONCLUSION: SGAs probably improve to some extent key intermediate outcomes for which they are usually prescribed, but they have a poorer harms profile than placebo or no antipsychotic treatment, particularly for body composition and somnolence. Data for head-to-head comparisons within and between classes were generally limited and rated as insufficient or low strength of evidence. Evidence was sparse for patient-important outcomes (e.g., health-related quality of life) and outcomes for young children (<8 years). Key priorities for research are long-term comparative effectiveness and development of systems for monitoring harms.

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Revista Psychiatria Danubina
Año 2016
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Revista Psychiatria i Psychologia Kliniczna
Año 2016
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Cognitive function deficit is a constant phenomenon described in the population of patients with schizophrenia – in the premorbid period, during exacerbations and between the successive episodes. Cognitive dysfunction is an independent prognostic factor in schizophrenia. Studies indicate that this pathology dimension affects patient-functioning indicators, such as: treatment and rehabilitation outcomes, cooperation during treatment, professional, family and social functioning, the ability to live independently as well as the quality of life. Current methods for the treatment of schizophrenia fail to ensure sufficient improvement in this dimension of the disease. The usefulness of omega-3 polyunsaturated fatty acids, both as a monotherapy and an augmentation of antipsychotic treatment in schizophrenia, has been investigated during the last 25 years. The obtained results are inconclusive, however, a positive tendency in the outcomes related to symptomatic improvement have been observed. The effects of omega-3 polyunsaturated fatty acid supplementation on the cognitive functioning of patients diagnosed with schizophrenia has been relatively rarely evaluated. However, there is a theoretical rationale for the beneficial effect of omega-3 polyunsaturated fatty acid supplementation on cognitive function. The known effects of these substances that could contribute to the improvement in cognitive function include: immunomodulatory effects in the CNS, improvement of oxidative stress parameters, changes in neurotransmission as well as effects on neuroplasticity. The aim of this paper is to present a systematic review of research findings on the changes in cognitive performance in patients diagnosed with schizophrenia who receive omega-3 polyunsaturated fatty acid supplementation.

Revisión sistemática

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Revista Psychiatria Danubina
Año 2016
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INTRODUCTION: There are now many existing studies which assess the treatments available for 'at risk mental states', as patients who are believed to be in the prodromal phase of psychotic illness are referred to. However, concerns regarding side effects of possible treatments remain. We here conduct a meta-analysis of the studies available up to July 2016. The aim of this study is to decide what would be the best treatment for 'at high risk patients'. RESULTS: 18 studies were selected for inclusion; 12 showed significance, 5 did not and one tended towards significance. Both antipsychotic medication and psychological intervention show mixed results with cognitive behavioral therapy and olanzapine/amisulpride coming out on top. Omega 3 poly-unsaturated acid also shows promising and consistent results. DISCUSSION: Treatments appear promising but a balance needs to be kept between adverse events and effectiveness of preventing psychosis. CONCLUSION: It is necessary to search further for treatments in order to identify effective treatments with fewer adverse side-effects in this phase of psychotic illness.