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Frontiers in Psychiatry 2021Co-occurring substance use disorders (SUDs) among individuals with schizophrenia are a prevalent and complex psychiatric comorbidity, which is associated with increased...
Co-occurring substance use disorders (SUDs) among individuals with schizophrenia are a prevalent and complex psychiatric comorbidity, which is associated with increased symptom severity, worsened illness trajectory and high rates of treatment non-adherence. Recent evidence suggests that the use of long-acting injectable (LAI) antipsychotics may provide an effective treatment option for individuals with this dual-diagnosis. A systematic review of the literature was conducted using the databases PubMed, PsychInfo and Google Scholar for English-language studies, investigating the use of LAIs in co-occurring schizophrenia and substance use disorders (SCZ-SUDs). Eight reports [one case study ( = 1), one case series ( = 8), three open-label retrospective studies ( = 75), and three randomized controlled trials ( = 273)] investigated the use of LAI antipsychotics in 357 participants with SCZ-SUDs [alcohol use disorder: 5 studies, = 282; cocaine use disorder: 5 studies, = 85; amphetamine use disorder: 1 study, = 1; cannabis use disorder: 3 studies, = 160; opioid use disorder: 3 studies, = 19; methylenedioxymethamphetamine (MDMA) use disorder: 2 studies, = 9; ketamine use disorder: 1 study, = 4] and were included in this systematic review. Findings indicate significant improvements in substance use related outcomes across 7 of 8 studies, while in 6 of 8 studies, significant improvements in psychopathology-related outcomes were reported. LAI antipsychotics may be an efficacious intervention option for the treatment of SCZ-SUDs. However, varying methodological rigor, generally small sample sizes and heterogeneity of samples, settings, substances of abuse, tested LAIs and comparators, as well as psychosocial cotreatments and level of reported detail across studies requires that these findings be considered preliminary and interpreted with caution. Further research is required to better understand the effects of LAIs among individuals with SCZ-SUDs.
PubMed: 34975600
DOI: 10.3389/fpsyt.2021.808002 -
Journal of Medical Virology May 2022The COVID-19 pandemic and related restrictions can impact mental health. To quantify the mental health burden of COVID-19 pandemic, we conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
The COVID-19 pandemic and related restrictions can impact mental health. To quantify the mental health burden of COVID-19 pandemic, we conducted a systematic review and meta-analysis, searching World Health Organization COVID-19/PsycInfo/PubMed databases (09/29/2020), including observational studies reporting on mental health outcomes in any population affected by COVID-19. Primary outcomes were the prevalence of anxiety, depression, stress, sleep problems, posttraumatic symptoms. Sensitivity analyses were conducted on severe mental health problems, in high-quality studies, and in representative samples. Subgroup analyses were conducted stratified by age, sex, country income level, and COVID-19 infection status. One-hundred-seventy-three studies from February to July 2020 were included (n = 502,261, median sample = 948, age = 34.4 years, females = 63%). Ninety-one percent were cross-sectional studies, and 18.5%/57.2% were of high/moderate quality. The highest prevalence emerged for posttraumatic symptoms in COVID-19 infected people (94%), followed by behavioral problems in those with prior mental disorders (77%), fear in healthcare workers (71%), anxiety in caregivers/family members of people with COVID-19 (42%), general health/social contact/passive coping style in the general population (38%), depression in those with prior somatic disorders (37%), and fear in other-than-healthcare workers (29%). Females and people with COVID-19 infection had higher rates of almost all outcomes; college students/young adults of anxiety, depression, sleep problems, suicidal ideation; adults of fear and posttraumatic symptoms. Anxiety, depression, and posttraumatic symptoms were more prevalent in low-/middle-income countries, sleep problems in high-income countries. The COVID-19 pandemic adversely impacts mental health in a unique manner across population subgroups. Our results inform tailored preventive strategies and interventions to mitigate current, future, and transgenerational adverse mental health of the COVID-19 pandemic.
Topics: Adult; COVID-19; Depression; Female; Humans; Mental Health; Pandemics; Prevalence; SARS-CoV-2; Young Adult
PubMed: 34958144
DOI: 10.1002/jmv.27549 -
European Neuropsychopharmacology : the... Jan 2022Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and...
Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and outcome. This may be due to a high prevalence of somatic comorbidities and an increased risk of delays in and poorer treatment of somatic disease in patients with severe mental illness in general. Vaccination is the most important public health intervention to tackle the ongoing pandemic. We undertook a systematic review regarding the data on vaccinations in individuals with BD. Proportion of prevalence rates, efficacy and specific side effects of vaccinations and in individuals with BD were searched. Results show that only five studies have investigated vaccinations in individuals with BD, which substantially limits the interpretation of overall findings. Studies on antibody production after vaccinations in BD are very limited and results are inconsistent. Also, the evidence-based science on side effects of vaccinations in individuals with BD so far is poor.
Topics: Bipolar Disorder; COVID-19; Communicable Disease Control; Communicable Diseases; Humans; Pandemics; SARS-CoV-2; Vaccines
PubMed: 34607722
DOI: 10.1016/j.euroneuro.2021.09.001 -
The Lancet. Psychiatry Jun 2021Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is... (Comparative Study)
Comparative Study Meta-Analysis
Standard versus reduced dose of antipsychotics for relapse prevention in multi-episode schizophrenia: a systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is unclear. We aimed to compare risks and benefits of reduced versus standard doses of antipsychotics.
METHODS
We searched Embase, Medline, PsycINFO, and the Cochrane Library from database inception until June 17, 2020, for randomised trials in adults with schizophrenia or schizoaffective disorder lasting at least 24 weeks, including individuals clinically stable at baseline, and comparing at least two doses of the same antipsychotic, excluding trials in first-episode psychosis or treatment-resistant schizophrenia. We compared low-dose (within 50-99% of the lower limit of the standard dose) and very-low dose (less than 50% of the lower limit) with standard dose, defined as doses higher than the lower limit of the treatment dose recommended by the International Consensus Study. Data from published reports on number of participants, treatment, sex, age, number of events, and changes in psychopathology scores were extracted independently by at least two authors. Investigators or sponsors were contacted by email to obtain missing information regarding outcomes. Co-primary outcomes were relapse and all-cause discontinuation. Study-level data were meta-analysed using random-effects models, calculating risk ratios (RRs) for dichotomous data, and Hedges' g for continuous data. The protocol was registered with OSF registries.
FINDINGS
7853 references were identified in the database search and one additional reference from a manual review of relevant studies. 5744 abstracts were assessed for eligibility, and 101 references were assessed for full-text review. Of these, 79 were excluded for a variety of reasons, resulting in 22 studies being included in the meta-analysis, reporting on 24 trials and 3282 individuals. Study participants had a median age of 38 years (IQR 36-40) with 2166 (65·9%) males and 1116 (34·0%) females. Compared with standard dose, low dose increased the risk of relapse by 44% (16 trials, 1920 participants; RR 1·44, 95% CI 1·10-1·87; p=0·0076; I=46%) and the risk of all-cause discontinuation by 12% (16 trials, 1932 participants; RR 1·12, 1·03-1·22; p=0·0085; I=0%). Very low dose increased the risk of relapse by 72% (13 trials, 2058 participants; RR 1·72, 95% CI 1·29-2·29; p=0·0002; I=70%) and all-cause discontinuation by 31% (11 trials, 1866 participants; RR 1·31, 1·11-1·54; p=0·0011; I=63%). Compared with low dose, very low dose did not significantly increase the risk of relapse (five trials, 686 participants; RR 1·31, 95% CI 0·96-1·79; p=0·092; I=51%) or all-cause discontinuation (five trials 686 participants; RR 1·11, 95% CI 0·95-1·30; p=0·18; I=43%). Subgroup analyses comparing double-blind versus open-label studies, first-generation versus second-generation antipsychotics, and oral versus long-acting injectable antipsychotics were consistent with the overall results. Most studies were classified as having some concerns in the risk of bias assessment, which was mainly caused by absence of publicly available study registrations.
INTERPRETATION
During maintenance treatment in multi-episode schizophrenia, antipsychotic doses should probably not be reduced below the standard dose range recommended for acute stabilisation, because reducing the dose further is associated with an increased risk of both relapse and all-cause discontinuation.
FUNDING
None.
Topics: Adult; Antipsychotic Agents; Dose-Response Relationship, Drug; Humans; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia; Secondary Prevention; Treatment Outcome
PubMed: 34023019
DOI: 10.1016/S2215-0366(21)00078-X -
The Lancet. Psychiatry May 2021Evidence of comparative benefits of long-acting injectable antipsychotics (LAIs) versus oral antipsychotics for schizophrenia has been inconsistent across study designs.... (Comparative Study)
Comparative Study Meta-Analysis
Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre-post studies.
BACKGROUND
Evidence of comparative benefits of long-acting injectable antipsychotics (LAIs) versus oral antipsychotics for schizophrenia has been inconsistent across study designs. The aim of this study was to evaluate the comparative benefits of LAIs versus oral antipsychotics in three study designs to inform clinical decision making.
METHODS
We did a comprehensive systematic review and meta-analysis comparing LAIs versus oral antipsychotics for schizophrenia covering three study designs: randomised controlled trials (RCTs), cohort studies, and pre-post studies. Our literature search was without language restrictions, in MEDLINE and PubMed, the Cochrane Library, Scopus, and Embase, for studies published from database inception up to a last search on March 13, 2020. We also searched for unpublished studies and ClinicalTrials.gov. We included studies lasting at least 6 months that targeted adults with schizophrenia and related disorders (>80% of participants). Studies on penfluridol (neither an LAI or daily oral antipsychotic), case reports, and case series with fewer than 20 patients were excluded. Two investigators independently extracted study-level data and resolved disagreement by consensus, or via a third investigator. Study authors were contacted to obtain additional information as needed. For our primary outcome we meta-analysed the risk ratio (RR) for hospitalisation or relapse with LAIs versus oral antipsychotics by a random-effects model, with hospitalisation used preferentially over relapse. As secondary analyses, we reversed the preferential order to relapse over hospitalisation, and assessed hospitalisation risk and relapse risk individually. Other secondary outcomes included all meta-analysable data, classed by relevance to effectiveness, efficacy, safety, quality of life, cognitive function, and other outcomes, and analysed by study design. Dichotomous outcomes were expressed as pooled RR and continuous outcomes as standardised mean difference (SMD). The protocol is registered with PROSPERO (CRD42019142094).
FINDINGS
We identified 14 687 records, of which 137 studies (397 319 patients) met the inclusion criteria (32 RCTs [23·4%; 8577 patients], 65 cohort studies [47·4%; 377 447 patients], and 40 pre-post studies [29·2%; 11 295 patients]) and were analysed. The quality of studies in terms of risk of bias varied across study designs and within each study design from low to high. LAIs were associated with a lower risk of hospitalisation or relapse than oral antipsychotics in each of the three study designs (RCTs: 29 studies, 7833 patients, RR 0·88 [95% CI 0·79-0·99], p=0·033; cohort studies: 44 studies, 106 136 patients, RR 0·92 [0·88-0·98], p=0·0044; pre-post studies: 28 studies, 17 876 patients, RR 0·44 [0·39-0·51], p<0·0001). This association was maintained across the study designs when we reversed the preferential order to risk of relapse over hospitalisation, and in individual analysis of hospitalisation risk. The association was maintained only in pre-post studies for relapse risk alone. In all other outcomes related to effectiveness, efficacy, safety, quality of life, cognitive function, and other outcomes, LAIs were more beneficial than oral antipsychotics in 60 (18·3%) of 328 comparisons, not different in 252 (76·8%) comparisons, and less beneficial in 16 (4·9%) comparisons when analysed by study design. Significant heterogeneity was observed across all three study designs. Publication biases were apparent in cohort and pre-post studies, but effect sizes were similar after trim-and-fill analyses.
INTERPRETATION
Although study designs have strengths and weaknesses, including potential low quality of observational studies, we consistently identified significant benefit with LAIs versus oral antipsychotics in preventing hospitalisation or relapse, in settings ranging from restricted research (RCTs) to real-word application (cohort and pre-post studies). Our findings suggest that increased clinical use of LAIs could improve outcomes in schizophrenia.
FUNDING
None.
TRANSLATIONS
For the Chinese, French, German, Italian, Japanese, Portugese and Spanish translations of the abstract see Supplementary Materials section.
Topics: Administration, Oral; Antipsychotic Agents; Cohort Studies; Delayed-Action Preparations; Humans; Injections; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome
PubMed: 33862018
DOI: 10.1016/S2215-0366(21)00039-0 -
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 -
European Neuropsychopharmacology : the... Jun 2020Iron homeostasis may be implicated in the pathophysiology of antipsychotic-related akathisia. We performed a systematic review in six databases from database inception... (Meta-Analysis)
Meta-Analysis
Iron homeostasis may be implicated in the pathophysiology of antipsychotic-related akathisia. We performed a systematic review in six databases from database inception until 03/2020, conducting a meta-analysis of studies investigating iron metabolism in antipsychotic-treated patients with versus without akathisia. Using a fixed- and a random-effects model, standardized mean difference (SMD) was estimated for levels of iron, ferritin, transferrin and total iron-binding capacity. Meta-regression analyses included sex, age, illness duration and antipsychotic treatment and dose. Subgroup analyses included chronic vs. acute akathisia and different diagnoses. Study quality was assessed using the Newcastle-Ottawa scale. In 10 studies (n = 395), compared to non-akathisia patients (n = 213), iron levels were lower in patients with akathisia (n = 182; fixed-effect model: SMD=-0.49, 95%CI=-0.28,-0.70, p<0.001; random-effects model: SMD=-0.55, 95%CI=-0.14,-0.96, p = 0.008). For secondary outcomes, differences were significant regarding lower ferritin levels in patients with akathisia in the fixed-effect model (SMD=-0.32, 95%CI=-0.08,-0.55, p = 0.007), but not in the random-effects model (SMD=-0.29, 95%CI=0.20,-0.79, p = 0.24). None of the moderators/mediators had a significant effect on the group difference of iron levels. Subgroup analyses reported lower iron levels in both patients with chronic and acute akathisia vs. patients without. Iron levels for schizophrenia patients were lower in the fixed-effect model (SMD=-0.55, 95%CI=-0.23, -0.86, p<0.001), while a trend was observed in the random-effects model (SMD=-0.52, 95%CI=-0.07, -1.12, p = 0.08). The studies' quality was overall poor, with one exception. This meta-analysis suggests lower iron levels in akathisia patients, while ferritin differences were significant only in the fixed-effect model. Further data are required to promote the understanding of related pathways.
Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Cross-Sectional Studies; Homeostasis; Humans; Iron; Observational Studies as Topic; Risk Factors; Treatment Outcome
PubMed: 32444336
DOI: 10.1016/j.euroneuro.2020.04.001 -
Clinical Psychology Review Jun 2020Cognitive biases, which are tendencies to systematically process, select and remember certain information (e.g., jumping to conclusions), are exacerbated in... (Meta-Analysis)
Meta-Analysis
Cognitive biases, which are tendencies to systematically process, select and remember certain information (e.g., jumping to conclusions), are exacerbated in schizophrenia and associated with delusions. Here we review and quantitatively assess psychological interventions targeting cognitive biases (e.g., metacognitive training, reasoning training, Maudsley review training programme) to evaluate their efficacy in improving cognitive biases, positive symptoms, and insight. Overall, thirty-two studies, including 15 distinct interventions and 2738 participants, were identified through a comprehensive keyword database search. Meta-analytic effect sizes were calculated and heterogeneity, publication bias, and subgroup analyses (study bias, active/passive intervention) were conducted. We observed significant small to moderate beneficial effects of cognitive interventions on cognitive biases (Hedges' g = 0.27; 95% CI = [0.13-0.41]; z = 3.77; p < .001), positive symptoms (Hedges' g = 0.30; 95% CI = [0.13-0.48]; z = 3.44, p < .005), and insight (Hedges' g = 0.35; 95% CI = [0.15-0.56]; z = 3.37,p < .005). Interestingly, studies with high risk of bias or passive control condition did not differ significantly from those with low risk or active control condition, respectively. Thus, cognitive biases are malleable via psychological interventions, which also exert, either directly or indirectly through reduced cognitive biases, beneficial effects on positive symptoms and insight.
Topics: Cognitive Behavioral Therapy; Humans; Outcome Assessment, Health Care; Psychosocial Intervention; Schizophrenia; Thinking
PubMed: 32361339
DOI: 10.1016/j.cpr.2020.101854