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Molecular Psychiatry Jan 2023People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical...
The impact of pharmacological and non-pharmacological interventions on physical health outcomes in people with mood disorders across the lifespan: An umbrella review of the evidence from randomised controlled trials.
OBJECTIVE
People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical health in this population.
METHODS
Umbrella review of meta-analyses of randomised controlled trials (RCTs) on pharmacological/non-pharmacological interventions for physical health outcomes/intolerability-related discontinuation in mood disorders (any age).
RESULTS
Ninety-seven meta-analyses were included. Among youths, against placebo, in depression, antidepressants/antipsychotics had higher discontinuation rates; in bipolar depression, olanzapine+fluoxetine worsened total cholesterol (TC)/triglycerides/weight gain (WG) (large ES). In adults with bipolar disorder, olanzapine worsened HbA1c/TC/WG (moderate/large ES); asenapine increased fasting glucose (small ES); quetiapine/cariprazine/risperidone induced WG (small/moderate ES). In bipolar depression, lurasidone was metabolically neutral. In depression, psychological interventions improved physical health-related quality of life (PHQoL) (small ES), fasting glucose/HbA1c (medium/large ES); SSRIs improved fasting glucose/HbA1c, readmission for coronary disease, pain (small ES); quetiapine/aripiprazole/olanzapine induced WG (small to large ES). Exercise improved cardiorespiratory fitness (moderate ES). In the elderly, fluoxetine yielded more detrimental cardiovascular effects than sertraline/escitalopram (large ES); antidepressants were neutral on exercise tolerance and PHQoL. In mixed age groups, in bipolar disorder aripiprazole was metabolically neutral; in depression, SSRIs lowered blood pressure versus placebo and serotonin-noradrenaline reuptake inhibitors (small ES); brexpiprazole augmentation caused WG and was less tolerated (small ES); exercise improved PHQoL (moderate ES).
CONCLUSIONS
Some interventions (psychological therapies, exercise and SSRIs) improve certain physical health outcomes in mood disorders, few are neutral, but various pharmacological interventions are associated with negative effects. Evidence from this umbrella review has limitations, should consider evidence from other disorders and should be integrated with recent evidence from individual RCTs, and observational evidence. Effective treatments with either beneficial or physically neutral profiles should be prioritized.
Topics: Adult; Humans; Aged; Adolescent; Fluoxetine; Olanzapine; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Aripiprazole; Longevity; Glycated Hemoglobin; Antipsychotic Agents; Antidepressive Agents; Bipolar Disorder; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic
PubMed: 36138129
DOI: 10.1038/s41380-022-01770-w -
Neuroscience and Biobehavioral Reviews Nov 2022MONTELEONE, A.M., F. Pellegrino, G. Croatto, M. Carfagno, A. Hilbert, J. Treasure, T. Wade, C. Bulik, S. Zipfel, P. Hay, U. Schmidt, G. Castellini, A. Favaro, F.... (Review)
Review
MONTELEONE, A.M., F. Pellegrino, G. Croatto, M. Carfagno, A. Hilbert, J. Treasure, T. Wade, C. Bulik, S. Zipfel, P. Hay, U. Schmidt, G. Castellini, A. Favaro, F. Fernandez-Aranda, J. Il Shin, U. Voderholzer, V. Ricca, D. Moretti, D. Busatta, G. Abbate-Daga, F. Ciullini, G. Cascino, F. Monaco, C.U. Correll and M. Solmi. Treatment of Eating Disorders: a systematic meta-review of meta-analyses and network meta-analyses. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2022.- Treatment efficacy for eating disorders (EDs) is modest and guidelines differ. We summarized findings/quality of (network) meta-analyses (N)MA of randomized controlled trials (RCTs) in EDs. Systematic meta-review ((N)MA of RCTs, ED, active/inactive control), using (anorexia or bulimia or eating disorder) AND (meta-analy*) in PubMed/PsycINFO/Cochrane database up to December 15th, 2020. Standardized mean difference, odds/risk ratio vs control were summarized at end of treatment and follow-up. Interventions involving family (family-based therapy, FBT) outperformed active control in adults/adolescents with anorexia nervosa (AN), and in adolescents with bulimia nervosa (BN). In adults with BN, individual cognitive behavioural therapy (CBT)-ED had the broadest efficacy versus active control; also, antidepressants outperformed active. In mixed age groups with binge-eating disorder (BED), psychotherapy, and lisdexamfetamine outperformed active control. Antidepressants, stimulants outperformed placebo, despite lower acceptability, as did CBT-ED versus waitlist/no treatment. Family-based therapy is effective in AN and BN (adolescents). CBT-ED has the largest efficacy in BN (adults), followed by antidepressants, as well as psychotherapy in BED (mixed). Medications have short-term efficacy in BED (adults).
Topics: Adolescent; Adult; Humans; Antidepressive Agents; Binge-Eating Disorder; Bulimia; Bulimia Nervosa; Feeding and Eating Disorders; Network Meta-Analysis; Meta-Analysis as Topic
PubMed: 36084848
DOI: 10.1016/j.neubiorev.2022.104857 -
Psychological Medicine Jul 2023Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use... (Meta-Analysis)
Meta-Analysis
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, = 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, = 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.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Risperidone; Depressive Disorder, Major; Amisulpride; Olanzapine; Benzodiazepines; Dibenzothiazepines
PubMed: 35510505
DOI: 10.1017/S0033291722000745 -
Molecular Psychiatry Aug 2022Numerous 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...
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.
Topics: Child; Female; Humans; Pregnancy; Incidence; Mental Disorders; Prospective Studies; Psychotic Disorders; Risk Factors; Meta-Analysis as Topic
PubMed: 35484237
DOI: 10.1038/s41380-022-01586-8 -
PLoS Medicine Apr 2022Severe mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and... (Meta-Analysis)
Meta-Analysis
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.
Topics: Cardiovascular Diseases; Heart Failure; Humans; Mental Disorders; Psychotic Disorders; Schizophrenia
PubMed: 35439243
DOI: 10.1371/journal.pmed.1003960 -
JAMA Psychiatry May 2022A substantial increase in the number of trials examining metacognitive training (MCT) for psychosis necessitates an updated examination of the outcomes associated with... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
A substantial increase in the number of trials examining metacognitive training (MCT) for psychosis necessitates an updated examination of the outcomes associated with MCT.
OBJECTIVES
To review the immediate and sustained associations of MCT with proximal (directly targeted) and distal (indirectly influenced) outcomes and assess treatment- and participant-related moderators to identify the potential factors associated with the expected heterogeneity of effect sizes.
DATA SOURCES
Eleven electronic databases were searched from 2007 to June 3, 2021 (alert until September 10, 2021). Reference lists of earlier meta-analyses and included reports were screened.
STUDY SELECTION
Reports examined MCT and included participants with schizophrenia spectrum and related psychotic disorders (1045 reports identified; 281 assessed). There were no age, sex, gender, race and ethnicity, language, or study design restrictions. Two reviewers performed the selection of studies to be analyzed.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Data were extracted by 3 reviewers and pooled using random effects models. Hedges g effect sizes were computed. The Mixed-Methods Appraisal tool was used to assess study quality.
MAIN OUTCOMES AND MEASURES
Proximal outcomes were global positive symptoms, delusions, hallucinations, and cognitive biases. Distal outcomes were self-esteem, negative symptoms, quality of life, well-being, and functioning. Immediate and sustained outcomes were examined. Meta-regressions, subgroup, and sensitivity analyses assessed moderators.
RESULTS
This systematic review and meta-analysis included 43 studies (46 reports). Forty reports were synthesized in meta-analysis (N=1816 participants) and 6 reports were included in narrative review. In the studies examined, MCT was associated with positive symptoms (g = 0.50; 95% CI, 0.34-0.67), delusions (g = 0.69; 95% CI, 0.45-0.93), hallucinations (g = 0.26; 95% CI, 0.11-0.40), cognitive biases (g = 0.16; 95% CI, 0.03-0.29), self-esteem (g = 0.17; 95% CI, 0.03-0.31), negative symptoms (g = 0.23; 95% CI, 0.10-0.37), and functioning (g = 0.41; 95% CI, 0.12-0.69). These associations were maintained up to 1 year. The quality of life effect size was nonsignificant (g = 0.20; 95% CI, -0.07 to 0.47); only 1 study assessed well-being. Publication year was associated with moderated hallucinations (β = 0.04; 95% CI, 0.00-0.07). Overall, narrative review results corroborated meta-analytic findings.
CONCLUSIONS AND RELEVANCE
In this meta-analysis, MCT for psychosis was associated with benefits up to 1 year postintervention in several treatment contexts. These findings suggest that MCT may merit integration in treatment guidelines for schizophrenia.
Topics: Hallucinations; Humans; Metacognition; Psychotic Disorders; Quality of Life; Schizophrenia
PubMed: 35320347
DOI: 10.1001/jamapsychiatry.2022.0277 -
Schizophrenia (Heidelberg, Germany) Feb 2022Clinical practice guidelines (CPGs) translate evidence into recommendations to improve patient care and outcomes. To provide an overview of schizophrenia CPGs, we...
Clinical practice guidelines (CPGs) translate evidence into recommendations to improve patient care and outcomes. To provide an overview of schizophrenia CPGs, we conducted a systematic literature review of English-language CPGs and synthesized current recommendations for the acute and maintenance management with antipsychotics. Searches for schizophrenia CPGs were conducted in MEDLINE/Embase from 1/1/2004-12/19/2019 and in guideline websites until 06/01/2020. Of 19 CPGs, 17 (89.5%) commented on first-episode schizophrenia (FES), with all recommending antipsychotic monotherapy, but without agreement on preferred antipsychotic. Of 18 CPGs commenting on maintenance therapy, 10 (55.6%) made no recommendations on the appropriate maximum duration of maintenance therapy, noting instead individualization of care. Eighteen (94.7%) CPGs commented on long-acting injectable antipsychotics (LAIs), mainly in cases of nonadherence (77.8%), maintenance care (72.2%), or patient preference (66.7%), with 5 (27.8%) CPGs recommending LAIs for FES. For treatment-resistant schizophrenia, 15/15 CPGs recommended clozapine. Only 7/19 (38.8%) CPGs included a treatment algorithm.
PubMed: 35210430
DOI: 10.1038/s41537-021-00192-x -
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