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JAMA Psychiatry May 2021Schizophrenia is associated with cognitive dysfunction and cardiovascular risk factors, including metabolic syndrome (MetS) and its constituent criteria. Cognitive... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Schizophrenia is associated with cognitive dysfunction and cardiovascular risk factors, including metabolic syndrome (MetS) and its constituent criteria. Cognitive dysfunction and cardiovascular risk factors can worsen cognition in the general population and may contribute to cognitive impairment in schizophrenia.
OBJECTIVE
To study the association between cognitive dysfunction and cardiovascular risk factors and cognitive impairment in individuals with schizophrenia.
DATA SOURCES
A search was conducted of Embase, Scopus, MEDLINE, PubMed, and Cochrane databases from inception to February 25, 2020, using terms that included synonyms of schizophrenia AND metabolic adversities AND cognitive function. Conference proceedings, clinical trial registries, and reference lists of relevant publications were also searched.
STUDY SELECTION
Studies were included that (1) examined cognitive functioning in patients with schizophrenia or schizoaffective disorder; (2) investigated the association of cardiovascular disease risk factors, including MetS, diabetes, obesity, overweight, obesity or overweight, hypertension, dyslipidemia, and insulin resistance with outcomes; and (3) compared cognitive performance of patients with schizophrenia/schizoaffective disorder between those with vs without cardiovascular disease risk factors.
DATA EXTRACTION AND SYNTHESIS
Extraction of data was conducted by 2 to 3 independent reviewers per article. Data were meta-analyzed using a random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was global cognition, defined as a test score using clinically validated measures of overall cognitive functioning.
RESULTS
Twenty-seven studies involving 10 174 individuals with schizophrenia were included. Significantly greater global cognitive deficits were present in patients with schizophrenia who had MetS (13 studies; n = 2800; effect size [ES] = 0.31; 95% CI, 0.13-0.50; P = .001), diabetes (8 studies; n = 2976; ES = 0.32; 95% CI, 0.23-0.42; P < .001), or hypertension (5 studies; n = 1899; ES = 0.21; 95% CI, 0.11-0.31; P < .001); nonsignificantly greater deficits were present in patients with obesity (8 studies; n = 2779; P = .20), overweight (8 studies; n = 2825; P = .41), and insulin resistance (1 study; n = 193; P = .18). Worse performance in specific cognitive domains was associated with cognitive dysfunction and cardiovascular risk factors regarding 5 domains in patients with diabetes (ES range, 0.23 [95% CI, 0.12-0.33] to 0.40 [95% CI, 0.20-0.61]) and 4 domains with MetS (ES range, 0.15 [95% CI, 0.03-0.28] to 0.40 [95% CI, 0.20-0.61]) and hypertension (ES range, 0.15 [95% CI, 0.04-0.26] to 0.27 [95% CI, 0.15-0.39]).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, MetS, diabetes, and hypertension were significantly associated with global cognitive impairment in people with schizophrenia.
Topics: Cognitive Dysfunction; Comorbidity; Diabetes Mellitus; Heart Disease Risk Factors; Humans; Hypertension; Metabolic Syndrome; Schizophrenia
PubMed: 33656533
DOI: 10.1001/jamapsychiatry.2021.0015 -
European Psychiatry : the Journal of... Feb 2021During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life...
BACKGROUND
During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent.
METHODS
In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice.
RESULTS
Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.Several recommendations are provided for the identification of secondary negative symptoms in clinical settings.
CONCLUSIONS
The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.
Topics: Humans; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Symptom Assessment
PubMed: 33597064
DOI: 10.1192/j.eurpsy.2021.11 -
Revista Brasileira de Psiquiatria (Sao... 2021Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of...
Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials.
Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.
Topics: Adult; Brain; Depression; Depressive Disorder, Major; Humans; Magnetic Phenomena; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Transcranial Direct Current Stimulation
PubMed: 33111776
DOI: 10.1590/1516-4446-2020-1169 -
Journal of Affective Disorders Apr 2020Currently, no specific, systematic assessment tool for the monitoring and reporting of ketamine-related side effects exists. Our aim was to develop a comprehensive...
BACKGROUND
Currently, no specific, systematic assessment tool for the monitoring and reporting of ketamine-related side effects exists. Our aim was to develop a comprehensive Ketamine Side Effect Tool (KSET) to capture acute and longer-term side effects associated with repeated ketamine treatments.
METHODS
Informed by systematic review data and clinical research, we drafted a list of the most commonly reported side effects. Face and content validation were obtained via feedback from collaborators with expertise in psychiatry and anaesthetics, clinical trial piloting and a modified Delphi Technique involving ten international experts.
RESULTS
The final version consisted of four forms that collect information at time points: screening, baseline, immediately after a single treatment, and longer-term follow-up. Instructions were developed to guide users and promote consistent utilisation.
LIMITATIONS
Further evaluation of feasibility, construct validity and reliability is required, and is planned across multiple international sites.
CONCLUSIONS
The structured Ketamine Side Effect Tool (KSET) was developed, with confirmation of content and face validity via a Delphi consensus process. This tool is timely, given the paucity of data regarding ketamine's safety, tolerability and abuse potential over the longer term, and its recent adoption internationally as a clinical treatment for depression. Although based on data from depression studies, the KSET has potential applicability for ketamine (or derivatives) used in other medical disorders, including chronic pain. We recommend its utilisation for both research and clinical scenarios, including data registries.
Topics: Chronic Pain; Drug-Related Side Effects and Adverse Reactions; Humans; Ketamine; Reproducibility of Results
PubMed: 32056935
DOI: 10.1016/j.jad.2020.01.120 -
JAMA Psychiatry Dec 2019Antidepressant use is increasing worldwide. Yet, contrasting evidence on the safety of antidepressants is available from meta-analyses, and the credibility of these...
IMPORTANCE
Antidepressant use is increasing worldwide. Yet, contrasting evidence on the safety of antidepressants is available from meta-analyses, and the credibility of these findings has not been quantified.
OBJECTIVE
To grade the evidence from published meta-analyses of observational studies that assessed the association between antidepressant use or exposure and adverse health outcomes.
DATA SOURCES
PubMed, Scopus, and PsycINFO were searched from database inception to April 5, 2019.
EVIDENCE REVIEW
Only meta-analyses of observational studies with a cohort or case-control study design were eligible. Two independent reviewers recorded the data and assessed the methodological quality of the included meta-analyses. Evidence of association was ranked according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant.
RESULTS
Forty-five meta-analyses (17.9%) from 4471 studies identified and 252 full-text articles scrutinized were selected that described 120 associations, including data from 1012 individual effect size estimates. Seventy-four (61.7%) of the 120 associations were nominally statistically significant at P ≤ .05 using random-effects models. Fifty-two associations (43.4%) had large heterogeneity (I2 > 50%), whereas small-study effects were found for 17 associations (14.2%) and excess significance bias was found for 9 associations (7.5%). Convincing evidence emerged from both main and sensitivity analyses for the association between antidepressant use and risk of suicide attempt or completion among children and adolescents, autism spectrum disorders with antidepressant exposure before and during pregnancy, preterm birth, and low Apgar scores. None of these associations remained supported by convincing evidence after sensitivity analysis, which adjusted for confounding by indication.
CONCLUSIONS AND RELEVANCE
This study's findings suggest that most putative adverse health outcomes associated with antidepressant use may not be supported by convincing evidence, and confounding by indication may alter the few associations with convincing evidence. Antidepressant use appears to be safe for the treatment of psychiatric disorders, but more studies matching for underlying disease are needed to clarify the degree of confounding by indication and other biases. No absolute contraindication to antidepressants emerged from this umbrella review.
Topics: Adolescent; Antidepressive Agents; Apgar Score; Autism Spectrum Disorder; Child; Female; Humans; Mental Disorders; Meta-Analysis as Topic; Observational Studies as Topic; Pregnancy; Premature Birth; Prenatal Exposure Delayed Effects; Suicide, Attempted; Suicide, Completed
PubMed: 31577342
DOI: 10.1001/jamapsychiatry.2019.2859 -
JAMA Psychiatry Oct 2019Recent meta-analyses of randomized clinical trials (RCTs) comparing clozapine with nonclozapine second-generation antipsychotics (NC-SGAs) in schizophrenia have... (Comparative Study)
Comparative Study Meta-Analysis
Association With Hospitalization and All-Cause Discontinuation Among Patients With Schizophrenia on Clozapine vs Other Oral Second-Generation Antipsychotics: A Systematic Review and Meta-analysis of Cohort Studies.
IMPORTANCE
Recent meta-analyses of randomized clinical trials (RCTs) comparing clozapine with nonclozapine second-generation antipsychotics (NC-SGAs) in schizophrenia have challenged clozapine's superiority in treatment-resistant patients. However, patients in RCTs are not necessarily generalizable to those in clinical practice.
OBJECTIVE
To conduct a systematic review and meta-analysis to compare various outcomes of clozapine vs oral NC-SGAs in cohort studies.
DATA SOURCES
Systematic literature search in PubMed, PsycINFO, and CINAHL without language restriction from database inception until December 17, 2018.
STUDY SELECTION
Nonrandomized cohort studies reporting effectiveness and/or safety outcomes comparing clozapine with NC-SGAs in schizophrenia or schizoaffective disorder.
DATA EXTRACTION AND SYNTHESIS
Independent investigators assessed studies and extracted data. Using a random-effects model, the study calculated risk ratio (RR) unadjusted for covariates and follow-up duration, number needed to treat/number needed to harm (NNT/NNH) for dichotomous data, and standardized mean difference (SMD) or mean difference (MD) for continuous data.
MAIN OUTCOMES AND MEASURES
Coprimary outcomes were hospitalization and all-cause discontinuation. Secondary outcomes included all effectiveness and safety outcomes reported in at least 3 analyzable studies.
RESULTS
Of 8446 hits, 68 articles from 63 individual cohort studies (n = 109 341) (60.3% male; mean [SD] age of 38.8 [6.5] years, illness duration of 11.0 [5.1] years, and study duration of 19.1 [23.3] months) were meta-analyzed. Compared with NC-SGAs, despite greater illness severity (17 studies [n = 38 766]; Hedges g, 0.222; 95% CI, 0.013-0.430; P = .04), clozapine was significantly associated with lower hospitalization risk (19 studies [n = 49 453]; RR, 0.817; 95% CI, 0.725-0.920; P = .001; NNT, 18; 95% CI, 12-40) and all-cause discontinuation (16 studies [n = 56 368]; RR, 0.732; 95% CI, 0.639-0.838; P < .001; NNT, 8; 95% CI, 6-12). Associations were statistically significant for comparisons with quetiapine fumarate and aripiprazole regarding hospitalization and all NC-SGAs, except aripiprazole, for all-cause discontinuation. Clozapine was also significantly associated with better outcomes regarding overall symptoms (SMD, -0.302; 95% CI, -0.572 to -0.032; P = .03) and Clinical Global Impressions scale severity (SMD, -1.182; 95% CI, -2.243 to -0.122; P = .03). Clozapine was significantly associated with increases in body weight (MD, 1.70; 95% CI, 0.31-3.08 kg; P = .02), body mass index (MD, 0.96; 95% CI, 0.24-1.68; P = .009), and type 2 diabetes (RR, 1.777; 95% CI, 1.229-2.570; P = .002; NNH, 27; 95% CI, 13-90).
CONCLUSIONS AND RELEVANCE
In cohort studies, despite more severely ill patients being treated with clozapine, use of clozapine was associated with better key efficacy outcomes and higher cardiometabolic-related risk outcomes vs NC-SGAs.
Topics: Adult; Antipsychotic Agents; Clozapine; Cohort Studies; Drug-Related Side Effects and Adverse Reactions; Female; Hospitalization; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Schizophrenia
PubMed: 31365048
DOI: 10.1001/jamapsychiatry.2019.1702 -
Bipolar Disorders Feb 2019The objective of this study was to evaluate the morbidity of subthreshold pediatric bipolar (BP) disorder. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to evaluate the morbidity of subthreshold pediatric bipolar (BP) disorder.
METHODS
We performed a systematic literature search in November 2017 and included studies examining the morbidity of pediatric subthreshold BP. Extracted outcomes included functional impairment, severity of mood symptoms, psychiatric comorbidities, suicidal ideation and behaviors, and mental health treatment. We used meta-analysis to compute the pooled standardized mean difference (SMD) for continuous measures and the pooled risk ratio (RR) for binary measures between two paired groups: subthreshold pediatric BP vs controls and subthreshold pediatric BP vs pediatric BP-I.
RESULTS
Eleven papers, consisting of seven datasets, were included. We compared subthreshold pediatric BP (N = 244) to non-BP controls (N = 1125) and subthreshold pediatric BP (N = 643) to pediatric BP-I (N = 942). Subthreshold pediatric BP was associated with greater functional impairment (SMD = 0.61, CI 0.25-0.97), greater severity of mood symptomatology (mania: SMD = 1.88, CI 1.38-2.38; depression: SMD = 0.66, CI 0.52-0.80), higher rates of disruptive behavior (RR = 1.75, CI 1.17-2.62), mood (RR = 1.78, CI 1.29-2.79) and substance use (RR = 2.27, CI 1.23-4.21) disorders, and higher rates of suicidal ideation and attempts (RR = 7.66, CI 1.71-34.33) compared to controls. Pediatric BP-I was associated with greater functional impairment, greater severity of manic symptoms, higher rates of suicidal ideation and attempts, and higher rates of mental health treatment compared to subthreshold pediatric BP. There were no differences between full and subthreshold cases in the severity of depressive symptoms or rates of comorbid disorders.
CONCLUSIONS
Subthreshold pediatric BP disorder is an identifiable morbid condition associated with significant functional impairment including psychiatric comorbidities and high rates of suicidality.
Topics: Adolescent; Age Factors; Bipolar Disorder; Case-Control Studies; Child; Female; Humans; Male; Morbidity; Psychotherapy; Young Adult
PubMed: 30480855
DOI: 10.1111/bdi.12734 -
JAMA Psychiatry Jun 2018The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
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.
OBJECTIVE
To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis.
DATA SOURCES
Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017.
STUDY SELECTION
Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders.
DATA EXTRACTION AND SYNTHESIS
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.
MAIN OUTCOMES AND MEASURES
The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period.
RESULTS
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).
CONCLUSIONS AND RELEVANCE
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.
Topics: Early Medical Intervention; Education; Employment; Hospitalization; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic; Regression Analysis; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index
PubMed: 29800949
DOI: 10.1001/jamapsychiatry.2018.0623 -
Neuropsychiatric Disease and Treatment 2017Antipsychotics are recommended as first-line therapy for acute mania and maintenance treatment of bipolar disorder; however, published literature suggests their... (Review)
Review
INTRODUCTION
Antipsychotics are recommended as first-line therapy for acute mania and maintenance treatment of bipolar disorder; however, published literature suggests their real-world use remains limited. Understanding attitudes toward these medications may help identify barriers and inform personalized therapy. This literature review evaluated patient and clinician attitudes toward the use of antipsychotics for treating bipolar disorder.
MATERIALS AND METHODS
A systematic search of the Cochrane Library, Ovid MEDLINE, Embase, and BIOSIS Previews identified English language articles published between January 1, 2000, and June 15, 2016, that reported attitudinal data from patients, health care professionals, or caregivers; treatment decision-making; or patient characteristics that predicted antipsychotic use for bipolar disorder. Results were analyzed descriptively.
RESULTS
Of the 209 references identified, 11 met the inclusion criteria and were evaluated. These articles provided attitudinal information from 1,418 patients with bipolar disorder and 1,282 treating clinicians. Patients' attitudes toward antipsychotics were generally positive. Longer duration of clinical stability was associated with positive attitudes. Implementation of psychoeducational and adherence enhancement strategies could improve patient attitudes. Limited data suggest clinicians' perceptions of antipsychotic efficacy and tolerability may have the greatest impact on their prescribing patterns. Because the current real-world evidence base is inadequate, clinician attitudes may reflect a relative lack of experience using antipsychotics in patients with bipolar disorder.
CONCLUSION
Although data are very limited, perceived tolerability and efficacy concerns shape both patient and clinician attitudes toward use of antipsychotic drugs in bipolar disorder. Additional studies are warranted.
PubMed: 28919760
DOI: 10.2147/NDT.S139557 -
PloS One 2017The vascular risk attributable to HIV infection is rising. The heterogeneity of the samples studied is an obstacle to understanding whether HIV is a vascular risk across... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
The vascular risk attributable to HIV infection is rising. The heterogeneity of the samples studied is an obstacle to understanding whether HIV is a vascular risk across geographic regions.
OBJECTIVE
To test the hypothesis that HIV infection is a vascular risk factor, and that the risk conferred by HIV varies by geographical region.
DATA SOURCES
A systematic search of publications was carried out in seven electronic databases: PubMed, The Cochrane Library, EMBASE, Web of Science, LILACS, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform from inception to July 2015.
STUDY SELECTION
We included longitudinal studies of HIV+ individuals and their risk of vascular outcomes of ≥ 50 HIV+ cases and excluded studies on biomarkers of vascular disease as well as clinical trials.
DATA EXTRACTION AND SYNTHESIS
Data was extracted by one of the authors and independently confirmed by the other two authors. We used incidence rate (IR), incidence risk ratio (IRR) and hazard ratio (HR) with their 95% confidence intervals as measures of risk.
MAIN OUTCOME
All-death, myocardial infarction (MI), coronary heart disease (CHD), any stroke, ischemic stroke (IS) or intracranial hemorrhage (ICH).
RESULTS
We screened 11,482 references for eligibility, and selected 117 for analysis. Forty-four cohorts represented 334,417 HIV+ individuals, 49% from the United States. Compared with their European counterparts, HIV+ individuals in the United States had higher IR of death (IRR 1.78, 1.69-1.88), MI (IRR 1.61, 1.29-2.01), CHD (IRR 2.27, 1.92-2.68), any stroke (IRR 1.94, 1.59-2.38), IS (IRR 1.56, 1.23-1.98), and ICH (IRR 4.03, 2.72-6.14). Compared with HIV- controls and independent of geographical region, HIV was a risk for death (HR 4.77, 4.55-5.00), MI (HR 1.60, 1.49-1.72), any CHD (HR 1.20, 1.15-1.25), any stroke (HR 1.82, 1.53-2.16), IS (HR 1.27, 1.15-1.39) and ICH (HR 2.20, 1.61-3.02). Use of antiretroviral therapy was a consistent risk for cardiac outcomes, while immunosuppression and unsuppressed viral load were consistent risks for cerebral outcomes.
CONCLUSIONS
HIV should be considered a vascular risk, with varying magnitudes across geographical and anatomical regions. We think that strategies to reduce the HIV-related vascular burden are urgent, and should incorporate the disparities noted here.
Topics: Case-Control Studies; Cerebrovascular Disorders; Cohort Studies; Coronary Disease; Demography; Female; Geography; HIV Infections; HIV Seropositivity; Humans; Incidence; Male; Myocardial Infarction; Risk Factors; Treatment Outcome; Vascular Diseases
PubMed: 28493892
DOI: 10.1371/journal.pone.0176686