-
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 -
Schizophrenia Bulletin Jul 2023Psychotic experiences (PEs) are associated with increased risk for mental disorders, in particular persistent PEs. PEs therefore might be useful within intervention... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND HYPOTHESIS
Psychotic experiences (PEs) are associated with increased risk for mental disorders, in particular persistent PEs. PEs therefore might be useful within intervention research. We sought to systematically determine the incidence and persistence of PEs in the general population.
STUDY DESIGN
A double-blind search of databases (Embase, Pubmed PMC, Psychinfo, Medline, and Web of Science) from inception to January 2023 and data extraction, were conducted. Study quality was assessed using the NIH assessment tool. Random effects models were conducted to calculate pooled incidence rate per person-year and proportion of persistent PEs per year. Age and study design were all examined using subgroup analyses. Demographic, risk factors, and outcomes for incidence and persistence of PEs were reported in a narrative synthesis.
STUDY RESULTS
Using a double-blind screening method for abstract (k = 5763) and full text (k = 250) were screened. In total 91 samples from 71 studies were included, of which 39 were included in a meta-analysis (incidence: k = 17, n = 56 089; persistence: k = 22, n = 81 847). Incidence rate was 0.023 per person-year (95% CI [0.0129;0.0322]). That is, for every 100 people, 2 reported first onset PEs in a year. This was highest in adolescence at 5 per 100(13-17 years). The pooled persistence rate for PEs was 31.0% (95% CI [26.65,35.35]) This was highest in adolescence at 35.8%. Cannabis was particularly associated with incidence of PEs, and persistence of PEs were associated with multiple mental disorders.
CONCLUSIONS
Each year incidence of PEs is 2 of every 100 people, and persists each year in 31% of cases, this risk is highest in adolescents.
Topics: Adolescent; Humans; Psychotic Disorders; Incidence; Mental Disorders; Risk Factors; Randomized Controlled Trials as Topic
PubMed: 37402250
DOI: 10.1093/schbul/sbad056 -
Psychopharmacology Oct 2023Clozapine is a unique medication with a potential role in the treatment of severe borderline personality disorder (BPD). (Review)
Review
RATIONALE
Clozapine is a unique medication with a potential role in the treatment of severe borderline personality disorder (BPD).
OBJECTIVES
The review examines the effectiveness of clozapine as a medication for management for severe BPD with high risk of suicide, violence or imprisonment, and aims to help guide clinical practice in managing severe BPD.
METHODS
A database search of the terms "Clozapine" AND "BPD"; "Antipsychotics" AND "BPD"; "Clozapine" AND "Borderline Personality Disorder"; and "Antipsychotics" AND "Borderline Personality Disorder" were performed in CINAHL, Cochrane Library, Embase, Medline, PsychINFO, PubMed, and Web of Science. Full-text articles of clinical clozapine use for BPD were included for review.
RESULTS
A total of 24 articles consisting of 1 randomised control trial, 10 non-controlled trials, and 13 case reports were identified. Most of the studies reported benefits from clozapine when used for severe BPD. Many of the studies focused on clozapine use in BPD patients at high risk of suicide. Results from these non-controlled and case reports support the use of clozapine in patients with severe BPD at high risk of suicide.
CONCLUSION
There may be a role for clozapine in treating severe treatment refractory BPD, especially for those patients at high risk of suicide and frequent hospitalisations.
Topics: Humans; Clozapine; Antipsychotic Agents; Suicide; Borderline Personality Disorder; Randomized Controlled Trials as Topic
PubMed: 37572113
DOI: 10.1007/s00213-023-06431-6 -
Frontiers in Neurology 2023Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective...
BACKGROUND
Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective properties of female sex hormones (especially estrogen). The potential pathomechanisms of any such effect on alpha-synucleinopathies, however, are far from understood. With that aim, we undertook to systematically review, and to critically assess, contemporary evidence on sex and gender differences in alpha-synucleinopathies using a bench-to-bedside approach.
METHODS
In this systematic review, studies investigating sex and gender differences in alpha-synucleinopathies (Rapid Eye Movement (REM) Behavior Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) from 2012 to 2022 were identified using electronic database searches of PubMed, Embase and Ovid.
RESULTS
One hundred sixty-two studies were included; 5 RBD, 6 MSA, 20 DLB and 131 PD studies. Overall, there is conclusive evidence to suggest sex-and gender-specific manifestation in demographics, biomarkers, genetics, clinical features, interventions, and quality of life in alpha-synucleinopathies. Only limited data exists on the effects of distinct sex hormones, with majority of studies concentrating on estrogen and its speculated neuroprotective effects.
CONCLUSION
Future studies disentangling the underlying sex-specific mechanisms of alpha-synucleinopathies are urgently needed in order to enable novel sex-specific therapeutics.
PubMed: 37545736
DOI: 10.3389/fneur.2023.1204104 -
Medical Education Online Dec 2023Suicide is a major cause of preventable death worldwide. Adequate training in risk assessment and intervention is key to suicide prevention. The use of simulation (role... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Suicide is a major cause of preventable death worldwide. Adequate training in risk assessment and intervention is key to suicide prevention. The use of simulation (role plays, simulated patients, virtual reality…) for practical training is a promising tool in mental health. The purpose of this study was to assess the effectiveness of simulation training in suicide risk assessment and intervention for healthcare professionals and gatekeepers.
METHODS
We conducted a systematic review in Medline and PsycINFO up to 31 July 2021 of randomized controlled trials (RCTs), non-randomized controlled trials, and pre/post-test studies. RCTs were furthermore included in a meta-analysis. We assessed the methodological quality of all studies with the Medical Education Research Study Quality Instrument, and the Cochrane Risk of Bias tool 2.0 for RCTs. Primary outcomes were changes in Kirkpatrick criteria: attitudes, skills, knowledge, behaviors, and patient outcomes.
RESULTS
We included 96 articles representing 43,656 participants. Most pre/post-test (n = 65) and non-randomized controlled (n = 14) studies showed significant improvement in attitudes, skills, knowledge, and behaviors. The meta-analysis of 11 RCTs showed positive changes in attitudes immediately after training and at 2-4 months post-training; in self-perceived skills at 6 months post-training; but not in factual knowledge. Studies assessing benefits for patients are still limited.
CONCLUSIONS
The heterogeneity of methodological designs, interventions, and trained populations combined with a limited number of RCTs and studies on patients' outcomes limit the strength of the evidence. However, preliminary findings suggest that simulation is promising for practical training in suicidal crisis intervention and should be further studied.
Topics: Humans; Simulation Training; Virtual Reality; Suicide Prevention; Suicide
PubMed: 37073473
DOI: 10.1080/10872981.2023.2199469 -
BMJ Mental Health Oct 2023This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
QUESTION
This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia.
STUDY SELECTION AND ANALYSIS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed.
FINDINGS
Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio.
CONCLUSIONS
The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.
Topics: Humans; Acetylcysteine; Amino Acids; Anti-Inflammatory Agents; Antipsychotic Agents; Schizophrenia; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 37852631
DOI: 10.1136/bmjment-2023-300771 -
Journal of Personalized Medicine Jun 2023This systematic review evaluated the animal and human evidence for pharmacomicrobiomics (PMx) interactions of antidepressant medications. Studies of gut microbiota... (Review)
Review
This systematic review evaluated the animal and human evidence for pharmacomicrobiomics (PMx) interactions of antidepressant medications. Studies of gut microbiota effects on functional and behavioral effects of antidepressants in human and animal models were identified from PubMed up to December 2022. Risk of bias was assessed, and results are presented as a systematic review following PRISMA guidelines. A total of 28 (21 animal, 7 human) studies were included in the review. The reviewed papers converged on three themes: (1) Antidepressants can alter the composition and metabolites of gut microbiota, (2) gut microbiota can alter the bioavailability of certain antidepressants, and (3) gut microbiota may modulate the clinical or modeled mood modifying effects of antidepressants. The majority (n = 22) of studies had at least moderate levels of bias present. While strong evidence is still lacking to understand the clinical role of antidepressant PMx in human health, there is evidence for interactions among antidepressants, microbiota changes, microbiota metabolite changes, and behavior. Well-controlled studies of the mediating and moderating effects of baseline and treatment-emergent changes in microbiota on therapeutic and adverse responses to antidepressants are needed to better establish a potential role of PMx in personalizing antidepressant treatment selection and response prediction.
PubMed: 37511699
DOI: 10.3390/jpm13071086 -
JAACAP Open Nov 2023There has been an increase in Child Psychiatry Access Programs (CPAP) across the United States to address the national child and adolescent psychiatry workforce shortage...
OBJECTIVE
There has been an increase in Child Psychiatry Access Programs (CPAP) across the United States to address the national child and adolescent psychiatry workforce shortage by supporting pediatric primary care providers (PCPs) in providing mental health services. The objective of this systematic review is to synthesize the expanding literature on CPAPs.
METHOD
A systematic literature search was conducted in PubMed, PsycInfo, Embase, and Web of Science databases to identify articles published from database inception to April 6, 2022, to identify CPAPs, defined as programs with mental health specialists providing rapid remote mental health consultation services to pediatric PCPs. Study outcomes included program adoption, provider experience, patient and caregiver experience, program cost, and patient mental health.
RESULTS
None of the 33 included studies were randomized controlled trials. Most of the studies (n = 30) focused on program adoption and provider experience (n = 18). Few studies examined patient and caregiver experience (n = 2), program cost(n = 4), or patient mental health (n = 4) outcomes. CPAPs showed year-over-year growth in adoption and were generally well-received by providers and caregivers. Health care provision costs were quite varied. No articles reported on changes in patient mental health according to validated measures. Heterogeneity in the methodological quality, study design, and outcomes used to evaluate CPAPs hindered comparison among programs.
CONCLUSION
Rigorous research on the impact of CPAPs is lacking. Findings show high provider satisfaction with CPAPs, yet few studies examine patient-level mental health outcomes. CPAPs and funding agencies should consider prioritizing and investing in research to build the evidence base for CPAPs.
DIVERSITY & INCLUSION STATEMENT
One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science.
CLINICAL TRIAL REGISTRATION INFORMATION
Child Psychiatry Access Programs: A Systematic Review; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020146410; CRD42020146410.
PubMed: 38189028
DOI: 10.1016/j.jaacop.2023.07.003 -
EClinicalMedicine Jul 2023Currently, melatonin is used to treat children and adolescents with insomnia without knowing the full extent of the short-term and long-term consequences. Our aim was to...
BACKGROUND
Currently, melatonin is used to treat children and adolescents with insomnia without knowing the full extent of the short-term and long-term consequences. Our aim was to provide clinicians and guideline panels with a systematic assessment of serious-and non-serious adverse events seen in continuation of melatonin treatment and the impact on pubertal development and bone health following long-term administration in children and adolescents with chronic insomnia.
METHODS
We searched PubMed, Embase, Cinahl and PsycINFO via Ovid, up to March 17, 2023, for studies on melatonin treatment among children and adolescents (aged 5-20 years) with chronic insomnia. The language was restricted to English, Danish, Norwegian, and Swedish. Outcomes were non-serious adverse events and serious adverse events assessed 2-4 weeks after initiating treatment and pubertal development and bone health, with no restriction on definition or time of measurement. Observational studies were included for the assessment of long-term outcomes, and serious and non-serious adverse events were assessed via randomised studies. The certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The protocol is registered with the Danish Health Authority.
FINDINGS
We identified 22 randomised studies with 1350 patients reporting on serious-and non-serious adverse events and four observational studies with a total of 105 patients reporting on pubertal development. Melatonin was not associated with serious adverse events, yet the number of patients experiencing non-serious adverse events was increased (Relative risk 1.56, 95% CI 1.01-2.43, 17 studies, I = 47%). Three studies reported little or no influence on pubertal development following 2-4 years of treatment, whereas one study registered a potential delay following longer treatment durations (>7 years). These findings need further evaluation due to several methodological limitations.
INTERPRETATION
Children who use melatonin are likely to experience non-serious adverse events, yet the actual extent to which melatonin leads to non-serious adverse events and the long-term consequences remain uncertain. This major gap of knowledge on safety calls for caution against complacent use of melatonin in children and adolescents with chronic insomnia and for more research to inform clinicians and guideline panels on this key issue.
FUNDING
The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.
PubMed: 37483551
DOI: 10.1016/j.eclinm.2023.102083 -
Frontiers in Psychiatry 2024Unipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine and its...
BACKGROUND
Unipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine and its enantiomer, esketamine, offer promising alternative treatments that can quickly relieve suicidal thoughts. This Overview of Reviews (OoR) analyzed and synthesized systematic reviews (SRs) with meta-analysis on randomized clinical trials (RCTs) involving ketamine in various formulations (intravenous, intramuscular, intranasal, subcutaneous) for patients with unipolar or bipolar depression. We evaluated the efficacy and safety of ketamine and esketamine in treating major depressive episodes across various forms, including unipolar, bipolar, treatment-resistant, and non-resistant depression, in patient populations with and without suicidal ideation, aiming to comprehensively assess their therapeutic potential and safety profile.
METHODS
Following PRIOR guidelines, this OoR's protocol was registered on Implasy (ID:202150049). Searches in PubMed, Scopus, Cochrane Library, and Epistemonikos focused on English-language meta-analyses of RCTs of ketamine or esketamine, as monotherapy or add-on, evaluating outcomes like suicide risk, depressive symptoms, relapse, response rates, and side effects. We included studies involving both suicidal and non-suicidal patients; all routes and formulations of administration (intravenous, intramuscular, intranasal) were considered, as well as all available comparisons with control interventions. We excluded meta-analysis in which the intervention was used as anesthesia for electroconvulsive therapy or with a randomized ascending dose design. The selection, data extraction, and quality assessment of studies were carried out by pairs of reviewers in a blinded manner. Data on efficacy, acceptability, and tolerability were extracted.
RESULTS
Our analysis included 26 SRs and 44 RCTs, with 3,316 subjects. The intervention is effective and well-tolerated, although the quality of the included SRs and original studies is poor, resulting in low certainty of evidence.
LIMITATIONS
This study is limited by poor-quality SRs and original studies, resulting in low certainty of the evidence. Additionally, insufficient available data prevents differentiation between the effects of ketamine and esketamine in unipolar and bipolar depression.
CONCLUSION
While ketamine and esketamine show promising therapeutic potential, the current evidence suffers from low study quality. Enhanced methodological rigor in future research will allow for a more informed application of these interventions within the treatment guidelines for unipolar and bipolar depression.
SYSTEMATIC REVIEW REGISTRATION
[https://inplasy.com/inplasy-2021-5-0049/], identifier (INPLASY202150049).
PubMed: 38362031
DOI: 10.3389/fpsyt.2024.1325399