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Biological Psychiatry Apr 2024Understanding the interactions between the gut microbiome and psychotropic medications (psycho-pharmacomicrobiomics) could improve treatment stratification strategies in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Understanding the interactions between the gut microbiome and psychotropic medications (psycho-pharmacomicrobiomics) could improve treatment stratification strategies in psychiatry. In this systematic review and meta-analysis, we first explored whether psychotropics modify the gut microbiome; second, we investigated whether the gut microbiome affects the efficacy and tolerability of psychotropics.
METHODS
Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched (November 2022) for longitudinal and cross-sectional studies that investigated the effect of psychotropics on the gut microbiome. The primary outcome was the difference in diversity metrics (alpha and beta) before and after treatment with psychotropics (longitudinal studies) and in medicated compared with unmedicated individuals (cross-sectional studies). Secondary outcomes included the association between gut microbiome and efficacy and tolerability outcomes. Random effect meta-analyses were conducted on alpha diversity metrics, while beta diversity metrics were pooled using distance data extracted from graphs. Summary statistics included standardized mean difference and Higgins I for alpha diversity metrics and F and R values for beta diversity metrics.
RESULTS
Nineteen studies were included in our synthesis; 12 investigated antipsychotics and 7 investigated antidepressants. Results showed significant changes in alpha (4 studies; standard mean difference: 0.12; 95% CI: 0.01-0.23; p = .04; I: 14%) and beta (F = 15.59; R = 0.05; p < .001) diversity metrics following treatment with antipsychotics and antidepressants, respectively. Altered gut microbiome composition at baseline was associated with tolerability and efficacy outcomes across studies, including response to antidepressants (2 studies; alpha diversity; standard mean difference: 2.45; 95% CI: 0.50-4.40; p < .001, I: 0%).
CONCLUSIONS
Treatment with psychotropic medications is associated with altered gut microbiome composition, and the gut microbiome may in turn influence the efficacy and tolerability of these medications.
Topics: Humans; Cross-Sectional Studies; Psychotropic Drugs; Antidepressive Agents; Antipsychotic Agents; Gastrointestinal Microbiome
PubMed: 37567335
DOI: 10.1016/j.biopsych.2023.07.019 -
Therapeutic Advances in... 2023More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage... (Review)
Review
BACKGROUND
More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage suicidal crisis are currently limited.
OBJECTIVES
The aim of this study was to overview the findings on the use of ketamine and esketamine for the treatment of suicidal ideas and acts.
DESIGN
Systematic review.
DATA SOURCES AND METHODS
PubMed, article references, and Clinicaltrials.gov up to June 30, 2022. Meta-analyses published within the last 2 years were also reviewed.
RESULTS
We identified 12 randomized controlled trials with reduction of suicidal ideation as the primary objective and 14 trials as secondary objectives. Intravenous racemic ketamine was superior to control drugs (placebo or midazolam) within the first 72 h, in spite of large placebo effects. Adverse events were minor and transient. In contrast, intranasal esketamine did not differ from placebo in large-scale studies. Limitations, clinical considerations, and opportunities for future research include the following points: large placebo effects when studying suicidal ideation reduction; small concerns about blinding quality due to dissociative effects; no studies on the risk/prevention of suicidal acts and mortality; lack of studies beyond affective disorders; no studies in adolescents and older people; lack of knowledge of long-term side effects, notably liability for abuse; no robust predictive markers; limited understanding of the mechanisms of ketamine on suicidal ideas; need for improved assessment of suicidal ideation in clinical trials; need for studies in outpatient settings, emergency room, and liaison consultation; need for research on ketamine administration; limited knowledge on the positive and negative effects of concomitant treatments.
CONCLUSION
Overall, there is compelling evidence for a favorable short-term benefit-risk balance with intravenous racemic ketamine but not intranasal esketamine. The place of ketamine will have to be defined within a multimodal care strategy for suicidal patients. Caution remains necessary for clinical use, and pharmacovigilance will be essential.
PubMed: 36776623
DOI: 10.1177/20451253231151327 -
Clinical Neurophysiology : Official... Nov 2022Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent...
OBJECTIVE
Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES.
METHODS
We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided.
RESULTS
The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity.
CONCLUSIONS
Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases.
SIGNIFICANCE
We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.
Topics: Consensus; Electric Stimulation; Humans; Telemedicine; Transcranial Direct Current Stimulation
PubMed: 36115809
DOI: 10.1016/j.clinph.2022.08.018 -
Molecular Psychiatry Jan 2023To conduct the first systematic review and meta-analysis assessing whether attention-deficit/hyperactivity disorder (ADHD) is associated with disorders of the eye,... (Meta-Analysis)
Meta-Analysis
AIM
To conduct the first systematic review and meta-analysis assessing whether attention-deficit/hyperactivity disorder (ADHD) is associated with disorders of the eye, and/or altered measures of visual function.
METHOD
Based on a pre-registered protocol (PROSPERO: CRD42021256352), we searched PubMed, Web of Knowledge/Science, Ovid Medline, Embase and APA PsycINFO up to 16th November 2021, with no language/type of document restrictions. We included observational studies reporting at least one measure of vision in people of any age meeting DSM/ICD criteria for ADHD and in people without ADHD; or the prevalence of ADHD in people with and without vision disorders. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS). Random effects meta-analyses were used for data synthesis.
RESULTS
We included 42 studies in the narrative synthesis and 35 studies in the meta-analyses (3,250,905 participants). We found meta-analytic evidence of increased risk of astigmatism (OR = 1.79 [CI: 1.50, 2.14]), hyperopia and hypermetropia (OR = 1.79 [CI: 1.66, 1.94]), strabismus (OR = 1.93 [CI: 1.75, 2.12]), unspecified vision problems (OR = 1.94 [CI: 1.38, 2.73]) and reduced near point of convergence (OR = 5.02 [CI: 1.78, 14.11]); increased lag (Hedge's g = 0.63 [CI: 0.30, 0.96]) and variability (Hedge's g = 0.40 [CI: 0.17, 0.64]) of the accommodative response; and increased self-reported vision problems (Hedge's g = 0.63 [CI: 0.44, 0.82]) in people with ADHD compared to those without ADHD (with no significant heterogeneity). We also found meta-analytic evidence of no differences between people with and without ADHD on retinal nerve fiber layer thickness (Hedge's g = -0.19 [CI: -0.41, 0.02]) and refractive error (Hedge's g = 0.08 [CI: -0.26, 0.42]) (with no significant heterogeneity).
DISCUSSION
ADHD is associated with some self-reported and objectively ascertained functional vision problems, but not with structural alterations of the eye. Further studies should clarify the causal relationship, if any, between ADHD and problems of vision.
TRIAL REGISTRATION
PROSPERO registration: CRD42021256352.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Cross-Sectional Studies; Prevalence; Eye Diseases
PubMed: 35931758
DOI: 10.1038/s41380-022-01699-0 -
Psychiatry Research Aug 2023We developed and tested a Bayesian network(BN) model to predict ECT remission for depression, with non-response as a secondary outcome.
INTRODUCTION
We developed and tested a Bayesian network(BN) model to predict ECT remission for depression, with non-response as a secondary outcome.
METHODS
We performed a systematic literature search on clinically available predictors. We combined these predictors with variables from a dataset of clinical ECT trajectories (performed in the University Medical Center Utrecht) to create priors and train the BN. Temporal validation was performed in an independent sample.
RESULTS
The systematic literature search yielded three meta-analyses, which provided prior knowledge on outcome predictors. The clinical dataset consisted of 248 treatment trajectories in the training set and 44 trajectories in the test set at the same medical center. The AUC for the primary outcome remission estimated on an independent validation set was 0.686 (95%CI 0.513-0.859) (AUC values of 0.505 - 0.763 observed in 5-fold cross validation of the model within the train set). Accuracy 0.73 (balanced accuracy 0.67), sensitivity 0.55, specificity 0.79, after temporal validation in the independent sample. Prior literature information marginally reduced CI width.
DISCUSSION
A BN model comprised of prior knowledge and clinical data can predict remission of depression after ECT with reasonable performance. This approach can be used to make outcome predictions in psychiatry, and offers a methodological framework to weigh additional information, such as patient characteristics, symptoms and biomarkers. In time, it may be used to improve shared decision-making in clinical practice.
Topics: Humans; Electroconvulsive Therapy; Depression; Bayes Theorem; Prognosis; Biomarkers; Treatment Outcome
PubMed: 37429173
DOI: 10.1016/j.psychres.2023.115328 -
Neuroscience and Biobehavioral Reviews Apr 2022Sleep and circadian rhythms disturbances (SCRD) in young people at high risk or with early onset of bipolar disorders (BD) are poorly understood. We systematically... (Meta-Analysis)
Meta-Analysis Review
Sleep and circadian rhythms disturbances (SCRD) in young people at high risk or with early onset of bipolar disorders (BD) are poorly understood. We systematically searched for studies of self, observer or objective estimates of SCRD in asymptomatic or symptomatic offspring of parents with BD (OSBD), individuals with presentations meeting recognised BD-at-risk criteria (BAR) and youth with recent onset of full-threshold BD (FT-BD). Of 76 studies eligible for systematic review, 35 (46%) were included in random effects meta-analyses. Pooled analyses of self-ratings related to circadian rhythms demonstrated greater preference for eveningness and more dysregulation of social rhythms in BAR and FT-BD groups; analyses of actigraphy provided some support for these findings. Meta-analysis of prospective studies showed that pre-existing SCRD were associated with a 40% increased risk of onset of BD, but heterogeneity in assessments was a significant concern. Overall, we identified longer total sleep time (Hedges g: 0.34; 95% confidence intervals:.1, .57), especially in OSBD and FT-BD and meta-regression analysis indicated the effect sizes was moderated by the proportion of any sample manifesting psychopathology or receiving psychotropic medications. This evolving field of research would benefit from greater attention to circadian rhythm as well as sleep quality measures.
Topics: Adolescent; Bipolar Disorder; Circadian Rhythm; Humans; Prospective Studies; Sleep; Sleep Wake Disorders
PubMed: 35182537
DOI: 10.1016/j.neubiorev.2022.104585 -
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 -
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 -
Real-World Implementation of Precision Psychiatry: A Systematic Review of Barriers and Facilitators.Brain Sciences Jul 2022Despite significant research progress surrounding precision medicine in psychiatry, there has been little tangible impact upon real-world clinical care. (Review)
Review
BACKGROUND
Despite significant research progress surrounding precision medicine in psychiatry, there has been little tangible impact upon real-world clinical care.
OBJECTIVE
To identify barriers and facilitators affecting the real-world implementation of precision psychiatry.
METHOD
A PRISMA-compliant systematic literature search of primary research studies, conducted in the Web of Science, Cochrane Central Register of Controlled Trials, PsycINFO and OpenGrey databases. We included a qualitative data synthesis structured according to the 'Consolidated Framework for Implementation Research' (CFIR) key constructs.
RESULTS
Of 93,886 records screened, 28 studies were suitable for inclusion. The included studies reported 38 barriers and facilitators attributed to the CFIR constructs. Commonly reported barriers included: potential psychological harm to the service user ( = 11), cost and time investments ( = 9), potential economic and occupational harm to the service user ( = 8), poor accuracy and utility of the model ( = 8), and poor perceived competence in precision medicine amongst staff ( = 7). The most highly reported facilitator was the availability of adequate competence and skills training for staff ( = 7).
CONCLUSIONS
Psychiatry faces widespread challenges in the implementation of precision medicine methods. Innovative solutions are required at the level of the individual and the wider system to fulfil the translational gap and impact real-world care.
PubMed: 35884740
DOI: 10.3390/brainsci12070934 -
Journal of Medical Internet Research Mar 2022Mental health disorders are a leading cause of medical disabilities across an individual's lifespan. This burden is particularly substantial in children and adolescents... (Review)
Review
BACKGROUND
Mental health disorders are a leading cause of medical disabilities across an individual's lifespan. This burden is particularly substantial in children and adolescents because of challenges in diagnosis and the lack of precision medicine approaches. However, the widespread adoption of wearable devices (eg, smart watches) that are conducive for artificial intelligence applications to remotely diagnose and manage psychiatric disorders in children and adolescents is promising.
OBJECTIVE
This study aims to conduct a scoping review to study, characterize, and identify areas of innovations with wearable devices that can augment current in-person physician assessments to individualize diagnosis and management of psychiatric disorders in child and adolescent psychiatry.
METHODS
This scoping review used information from the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of several databases from 2011 to June 25, 2021, limited to the English language and excluding animal studies, was conducted. The databases included Ovid MEDLINE and Epub ahead of print, in-process and other nonindexed citations, and daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; Web of Science; and Scopus.
RESULTS
The initial search yielded 344 articles, from which 19 (5.5%) articles were left on the final source list for this scoping review. Articles were divided into three main groups as follows: studies with the main focus on autism spectrum disorder, attention-deficit/hyperactivity disorder, and internalizing disorders such as anxiety disorders. Most of the studies used either cardio-fitness chest straps with electrocardiogram sensors or wrist-worn biosensors, such as watches by Fitbit. Both allowed passive data collection of the physiological signals.
CONCLUSIONS
Our scoping review found a large heterogeneity of methods and findings in artificial intelligence studies in child psychiatry. Overall, the largest gap identified in this scoping review is the lack of randomized controlled trials, as most studies available were pilot studies and feasibility trials.
Topics: Adolescent; Adolescent Psychiatry; Artificial Intelligence; Autism Spectrum Disorder; Child Psychiatry; Humans; Wearable Electronic Devices
PubMed: 35285812
DOI: 10.2196/33560