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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 -
The Lancet. Psychiatry Nov 2023Side-effects of psychiatric medication impair quality of life and functioning. Furthermore, they contribute to morbidity, mortality, stigma, and poor treatment...
BACKGROUND
Side-effects of psychiatric medication impair quality of life and functioning. Furthermore, they contribute to morbidity, mortality, stigma, and poor treatment concordance resulting in relapse of psychiatric illness. Guidelines recommend discussing side-effects with patients when making treatment decisions, but a synthesis of antidepressant and antipsychotic side-effects to guide this process is missing, and considering all side-effects is a complex, multidimensional process. We aimed to create comprehensive databases of antipsychotic and antidepressant side-effects, and a digital tool to support database navigation.
METHODS
To create the databases, we did an umbrella review of Embase, PsycINFO, and MEDLINE from database inception to June 26, 2023. We included meta-analyses of randomised controlled trials examining antipsychotic monotherapy in the treatment of schizophrenia or antidepressant monotherapy in the treatment of major depressive disorder. We included meta-analyses in adults (aged ≥18 years) that assessed drugs with a common comparator. The search was complemented by a review of national and international guidelines and consensus statements for the treatment of major depressive disorder and schizophrenia in adults. Effect sizes for antipsychotic and antidepressant side-effects were extracted from meta-analyses examining the largest number of drugs. In cases of incomplete meta-analytic coverage, data were imputed on the basis of guideline-derived ordinal rankings or, if imputation was not possible, ordinal scores were extracted. Both meta-analytic and ordinal outcomes were normalised to provide values between 0 and 1. We then constructed a digital tool, the Psymatik Treatment Optimizer, to combine the side-effect databases with side-effect concerns of an individual user, to enable users to select side-effects of concern and the relative degree of concern for each side-effect. Concern weightings and the side-effect databases are synthesised via a multicriteria decision analysis method (technique for order of preference by similarity to ideal situation, or TOPSIS).
FINDINGS
Of 3724 citations, 14 articles containing 68 meta-analyses of individual side-effects met inclusion criteria. After review of 19 guidelines, seven provided ordinal data. Antipsychotic data were extracted from five studies (11 meta-analyses, n=65 594 patients) and four guidelines, and antidepressant data were extracted from three guidelines. The resultant databases included data on 32 antipsychotics (14 side-effects) and 37 antidepressants (nine side-effects). The databases highlighted the clinical dilemma associated with balancing side-effects, with avoidance of one side-effect (eg, weight gain for antipsychotics) increasing the risk of others (eg, akathisia). To aid with this dilemma, the Psymatik Treatment Optimizer synthesises the side-effect databases with individual user-defined concern weights. After computing up to 5851 pairwise comparisons for antidepressants and 5142 pairwise comparisons for antipsychotics, Psymatik ranks treatments in order of preference for the individual user, with the output presented in a heatmap.
INTERPRETATION
By facilitating collaborative, personalised, and evidence-based prescribing decisions, the side-effect databases and digital application supports care delivery that is consistent with international regulatory guidance for the treatment of schizophrenia and depression, and it therefore has promise for informing psychiatric practice and improving outcomes.
FUNDING
National Institute for Health and Care Research, Maudsley Charity, Wellcome Trust, Medical Research Council.
Topics: Adult; Humans; Adolescent; Antipsychotic Agents; Depressive Disorder, Major; Quality of Life; Antidepressive Agents; Schizophrenia
PubMed: 37774723
DOI: 10.1016/S2215-0366(23)00262-6 -
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 -
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 -
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 -
Revista Brasileira de Psiquiatria (Sao... 2023To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis.
RESULTS
The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%.
CONCLUSION
Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention.
Topics: Humans; Antipsychotic Agents; Clozapine; Prevalence; Schizophrenia; Drug Resistance
PubMed: 37718484
DOI: 10.47626/1516-4446-2023-3126 -
Neuroscience and Biobehavioral Reviews Jun 2023We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and... (Review)
Review
The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications.
We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010-08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.
Topics: Humans; Child; Adolescent; Psychopharmacology; Randomized Controlled Trials as Topic; Attention Deficit Disorder with Hyperactivity; Prader-Willi Syndrome; Clinical Trials, Phase II as Topic
PubMed: 37001575
DOI: 10.1016/j.neubiorev.2023.105149 -
EClinicalMedicine Nov 2023Mental disorders are associated with premature mortality. There is increasing research examining life expectancy and years-of-potential-life-lost (YPLL) to quantify the...
BACKGROUND
Mental disorders are associated with premature mortality. There is increasing research examining life expectancy and years-of-potential-life-lost (YPLL) to quantify the disease impact on survival in people with mental disorders. We aimed to systematically synthesize studies to estimate life expectancy and YPLL in people with any and specific mental disorders across a broad spectrum of diagnoses.
METHODS
In this systematic review and meta-analysis, we searched Embase, MEDLINE, PsychINFO, WOS from inception to July 31, 2023, for published studies reporting life expectancy and/or YPLL for mental disorders. Criteria for study inclusion were: patients of all ages with any mental disorders; reported data on life expectancy and/or YPLL of a mental-disorder cohort relative to the general population or a comparison group without mental disorders; and cohort studies. We excluded non-cohort studies, publications containing non-peer-reviewed data or those restricted to population subgroups. Survival estimates, i.e., life expectancy and YPLL, were pooled (based on summary data extracted from the included studies) using random-effects models. Subgroup analyses and random-effects meta-regression analyses were performed to explore sources of heterogeneity. Risk-of-bias assessment was evaluated using the Newcastle-Ottawa Scale. This study is registered with PROSPERO (CRD42022321190).
FINDINGS
Of 35,865 studies identified in our research, 109 studies from 24 countries or regions including 12,171,909 patients with mental disorders were eligible for analysis (54 for life expectancy and 109 for YPLL). Pooled life expectancy for mental disorders was 63.85 years (95% CI 62.63-65.06; = 100.0%), and pooled YPLL was 14.66 years (95% CI 13.88-15.98; = 100.0%). Disorder-stratified analyses revealed that substance-use disorders had the shortest life expectancy (57.07 years [95% CI 54.47-59.67]), while neurotic disorders had the longest lifespan (69.51 years [95% CI 67.26-71.76]). Substance-use disorders exhibited the greatest YPLL (20.38 years [95% CI 18.65-22.11]), followed by eating disorders (16.64 years [95% CI 7.45-25.82]), schizophrenia-spectrum disorders (15.37 years [95% CI 14.18-16.55]), and personality disorders (15.35 years [95% CI 12.80-17.89]). YPLLs attributable to natural and unnatural deaths in mental disorders were 4.38 years (95% CI 3.15-5.61) and 8.11 years (95% CI 6.10-10.13; suicide: 8.31 years [95% CI 6.43-10.19]), respectively. Stratified analyses by study period suggested that the longevity gap persisted over time. Significant cross-study heterogeneity was observed.
INTERPRETATION
Mental disorders are associated with substantially reduced life expectancy, which is transdiagnostic in nature, encompassing a wide range of diagnoses. Implementation of comprehensive and multilevel intervention approaches is urgently needed to rectify lifespan inequalities for people with mental disorders.
FUNDING
None.
PubMed: 37965432
DOI: 10.1016/j.eclinm.2023.102294 -
Research Square Jan 2024Sub-optimal response in schizophrenia is frequent, warranting augmentation strategies over treatment-as-usual (TAU).
BACKGROUND
Sub-optimal response in schizophrenia is frequent, warranting augmentation strategies over treatment-as-usual (TAU).
METHODS
We assessed nutraceuticals/phytoceutical augmentation strategies via network meta-analysis. Randomized controlled trials in schizophrenia/schizoaffective disorder were identified via the following databases: PubMed, MEDLINE, EMBASE, Scopus, PsycINFO, CENTRAL, and ClinicalTrials.gov. Change (Standardized Mean Difference=SMD) in total symptomatology and acceptability (Risk Ratio=RR) were co-primary outcomes. Secondary outcomes were positive, negative, cognitive, and depressive symptom changes, general psychopathology, tolerability, and response rates. We conducted subset analyses by disease phase and sensitivity analyses by risk of bias and assessed global/local inconsistency, publication bias, risk of bias, and confidence in the evidence.
RESULTS
The systematic review included 49 records documenting 50 studies (n=2,384) documenting 22 interventions. Citicoline (SMD=-1.05,95%CI=-1.85; -.24), L-lysine (SMD=-1.04,95%CI=-1.84;-.25), N-acetylcysteine (SMD=-.87,95%CI=-1.27;-.47) and sarcosine (SMD=-.5,95%CI=-.87-.13) outperformed placebo for total symptomatology. High heterogeneity (tau=.10, I=55.9%) and global inconsistency (Q=40.79, df=18, p=.002) emerged without publication bias (Egger's test, p=.42). Sarcosine improved negative symptoms (SMD=-.65, 95%CI=-1.10; -.19). N-acetylcysteine improved negative symptoms (SMD=-.90, 95%CI=-1.42; -.39)/general psychopathology (SMD=-.76, 95%CI=-1.39; -.13). No compound improved total symptomatology within acute phase studies (k=7, n=422). Sarcosine (SMD=-1.26,95%CI=-1.91; -.60), citicoline (SMD=-1.05,95%CI=-1.65;-.44), and N-acetylcysteine (SMD=-.55,95%CI=-.92,-.19) outperformed placebo augmentation in clinically stable participants. Sensitivity analyses removing high-risk-of-bias studies confirmed overall findings in all phases and clinically stable samples. In contrast, the acute phase analysis restricted to low risk-of-bias studies showed a superior effect vs. placebo for N-acetylcysteine (SMD=-1.10,95%CI=-1.75,-.45), L-lysine (SMD=-1.05,95%CI=-1.55,-.19), omega-3 fatty acids (SMD=-.83,95%CI=-1.31,-.34) and withania somnifera (SMD=-.71,95%CI=-1.21,-.22). Citicoline (SMD=-1.05,95%CI=-1.86,-.23), L-lysine (SMD=-1.04,95%CI=-1.84,-.24), N-acetylcysteine (SMD=-.89,95%CI=-1.35,-.43) and sarcosine (SMD=-.61,95%CI=-1.02,-.21) outperformed placebo augmentation of TAU ("any phase"). Drop-out due to any cause or adverse events did not differ between nutraceutical/phytoceutical vs. placebo+TAU.
CONCLUSIONS
Sarcosine, citicoline, and N-acetylcysteine are promising augmentation interventions in stable patients with schizophrenia, yet the quality of evidence is low to very low. Further high-quality trials in acute phases/specific outcomes/difficult-to-treat schizophrenia are warranted.
PubMed: 38260297
DOI: 10.21203/rs.3.rs-3787917/v1 -
The British Journal of Psychiatry : the... Jul 2023Early-onset psychosis (EOP) refers to the development of a first episode of psychosis before 18 years of age. Individuals at clinical high risk for psychosis (CHR-P)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Early-onset psychosis (EOP) refers to the development of a first episode of psychosis before 18 years of age. Individuals at clinical high risk for psychosis (CHR-P) include adolescents and young adults, although most evidence has focused on adults. Negative symptoms are important prognostic indicators in psychosis. However, research focusing on children and adolescents is limited.
AIMS
To provide meta-analytical evidence and a comprehensive review of the status and advances in the diagnosis, prognosis and treatment of negative symptoms in children and adolescents with EOP and at CHR-P.
METHOD
PRISMA/MOOSE-compliant systematic review (PROSPERO: CRD42022360925) from inception to 18 August 2022, in any language, to identify individual studies conducted in EOP/CHR-P children and adolescents (mean age <18 years) providing findings on negative symptoms. Findings were systematically appraised. Random-effects meta-analyses were performed on the prevalence of negative symptoms, carrying out sensitivity analyses, heterogeneity analyses, publication bias assessment and quality assessment using the Newcastle-Ottawa Scale.
RESULTS
Of 3289 articles, 133 were included ( = 6776 EOP, mean age 15.3 years (s.d. = 1.6), males = 56.1%; = 2138 CHR-P, mean age 16.1 years (s.d. = 1.0), males = 48.6%). There were negative symptoms in 60.8% (95% CI 46.4%-75.2%) of the children and adolescents with EOP and 79.6% (95% CI 66.3-92.9%) of those at CHR-P. Prevalence and severity of negative symptoms were associated with poor clinical, functional and intervention outcomes in both groups. Different interventions were piloted, with variable results requiring further replication.
CONCLUSIONS
Negative symptoms are common in children and adolescents at early stages of psychosis, particularly in those at CHR-P, and are associated with poor outcomes. Future intervention research is required so that evidence-based treatments will become available.
Topics: Male; Humans; Child; Psychotic Disorders; Prognosis
PubMed: 37194556
DOI: 10.1192/bjp.2022.203