-
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 -
Psychoneuroendocrinology Feb 2022Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of major depressive disorder (MDD) in adulthood. Less work has... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of major depressive disorder (MDD) in adulthood. Less work has focused on the role of the HPA axis in depression in adolescence and young adulthood globally. The aim of this study was to conduct a systematic review and meta-analysis of worldwide research investigating the relationship between cortisol, a measure of HPA axis activity, and MDD in adolescence and young adulthood.
METHOD
We searched MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, Web of Science, Lilacs, African Journals Online, and Global Health for studies which examined the relationship between cortisol and MDD in global youth (10-24 years old).
RESULTS
Twenty-six studies were included in the systematic review and 14 were eligible for the meta-analysis, but only one study included young adults in their sample. Results from the meta-analysis demonstrated that elevated morning, but not evening, cortisol levels was prospectively associated with later MDD development in adolescence and young adulthood. However, morning cortisol levels did not significantly differ between healthy controls and individuals with MDD in cross-sectional studies. Afternoon cortisol and cortisol stress response also did not differ between adolescents with MDD and healthy controls. Qualitative synthesis of the three studies examining nocturnal cortisol showed higher nocturnal cortisol was both longitudinally and cross-sectionally associated with MDD in adolescence.
CONCLUSION
Our findings suggest elevated morning cortisol precedes depression in adolescence. Despite this, we did not find any differences in other cortisol measures in association with MDD in cross-sectional studies. Taken together, these findings suggest that elevated morning and nocturnal cortisol are risk factors for depression in adolescence rather than a biomarker of existing MDD. This supports a role for the hyperactivity of the HPA axis in the development of MDD in adolescence. Most of the studies were from high-income-countries (HICs) and thus further work would need to be conducted in low- and middle-income countries (LMICs) to understand if our findings are generalisable also to these populations.
Topics: Adolescent; Adult; Child; Cross-Sectional Studies; Depression; Depressive Disorder, Major; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Young Adult
PubMed: 34920399
DOI: 10.1016/j.psyneuen.2021.105625 -
Molecular Autism Mar 2022There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD.
METHODS
We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses.
RESULTS
We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles.
LIMITATIONS
Most of the studies were inadequately powered (sample sizes of 20-80 participants), with short duration (8-13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms.
CONCLUSIONS
Some medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Humans; Network Meta-Analysis; Oxytocin; Risperidone
PubMed: 35246237
DOI: 10.1186/s13229-022-00488-4 -
BMC Psychiatry Jan 2020Medicinal cannabis has received increased research attention over recent years due to loosening global regulatory changes. Medicinal cannabis has been reported to have...
BACKGROUND
Medicinal cannabis has received increased research attention over recent years due to loosening global regulatory changes. Medicinal cannabis has been reported to have potential efficacy in reducing pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and intractable childhood epilepsy. Yet its potential application in the field of psychiatry is lesser known.
METHODS
The first clinically-focused systematic review on the emerging medical application of cannabis across all major psychiatric disorders was conducted. Current evidence regarding whole plant formulations and plant-derived cannabinoid isolates in mood, anxiety, sleep, psychotic disorders and attention deficit/hyperactivity disorder (ADHD) is discussed; while also detailing clinical prescription considerations (including pharmacogenomics), occupational and public health elements, and future research recommendations. The systematic review of the literature was conducted during 2019, assessing the data from all case studies and clinical trials involving medicinal cannabis or plant-derived isolates for all major psychiatric disorders (neurological conditions and pain were omitted).
RESULTS
The present evidence in the emerging field of cannabinoid therapeutics in psychiatry is nascent, and thereby it is currently premature to recommend cannabinoid-based interventions. Isolated positive studies have, however, revealed tentative support for cannabinoids (namely cannabidiol; CBD) for reducing social anxiety; with mixed (mainly positive) evidence for adjunctive use in schizophrenia. Case studies suggest that medicinal cannabis may be beneficial for improving sleep and post-traumatic stress disorder, however evidence is currently weak. Preliminary research findings indicate no benefit for depression from high delta-9 tetrahydrocannabinol (THC) therapeutics, or for CBD in mania. One isolated study indicates some potential efficacy for an oral cannabinoid/terpene combination in ADHD. Clinical prescriptive consideration involves caution in the use of high-THC formulations (avoidance in youth, and in people with anxiety or psychotic disorders), gradual titration, regular assessment, and caution in cardiovascular and respiratory disorders, pregnancy and breast-feeding.
CONCLUSIONS
There is currently encouraging, albeit embryonic, evidence for medicinal cannabis in the treatment of a range of psychiatric disorders. Supportive findings are emerging for some key isolates, however, clinicians need to be mindful of a range of prescriptive and occupational safety considerations, especially if initiating higher dose THC formulas.
Topics: Adolescent; Anxiety; Cannabidiol; Cannabinoids; Cannabis; Child; Humans; Medical Marijuana
PubMed: 31948424
DOI: 10.1186/s12888-019-2409-8 -
World Psychiatry : Official Journal of... Jun 2022People with schizophrenia die 15-20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a...
People with schizophrenia die 15-20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a systematic review and random-effects meta-analysis of prospective and retrospective, nationwide and targeted cohort studies assessing mortality risk in people with schizophrenia versus the general population or groups matched for physical comorbidities or groups with different psychiatric disorders, also assessing moderators. Primary outcome was all-cause mortality risk ratio (RR); key secondary outcomes were mortality due to suicide and natural causes. Other secondary outcomes included any other specific-cause mortality. Publication bias, subgroup and meta-regression analyses, and quality assessment (Newcastle-Ottawa Scale) were conducted. Across 135 studies spanning from 1957 to 2021 (schizophrenia: N=4,536,447; general population controls: N=1,115,600,059; other psychiatric illness controls: N=3,827,955), all-cause mortality was increased in people with schizophrenia versus any non-schizophrenia control group (RR=2.52, 95% CI: 2.38-2.68, n=79), with the largest risk in first-episode (RR=7.43, 95% CI: 4.02-13.75, n=2) and incident (i.e., earlier-phase) schizophrenia (RR=3.52, 95% CI: 3.09-4.00, n=7) versus the general population. Specific-cause mortality was highest for suicide or injury-poisoning or undetermined non-natural cause (RR=9.76-8.42), followed by pneumonia among natural causes (RR=7.00, 95% CI: 6.79-7.23), decreasing through infectious or endocrine or respiratory or urogenital or diabetes causes (RR=3 to 4), to alcohol or gastrointestinal or renal or nervous system or cardio-cerebrovascular or all natural causes (RR=2 to 3), and liver or cerebrovascular, or breast or colon or pancreas or any cancer causes (RR=1.33 to 1.96). All-cause mortality increased slightly but significantly with median study year (beta=0.0009, 95% CI: 0.001-0.02, p=0.02). Individuals with schizophrenia <40 years of age had increased all-cause and suicide-related mortality compared to those ≥40 years old, and a higher percentage of females increased suicide-related mortality risk in incident schizophrenia samples. All-cause mortality was higher in incident than prevalent schizophrenia (RR=3.52 vs. 2.86, p=0.009). Comorbid substance use disorder increased all-cause mortality (RR=1.62, 95% CI: 1.47-1.80, n=3). Antipsychotics were protective against all-cause mortality versus no antipsychotic use (RR=0.71, 95% CI: 0.59-0.84, n=11), with largest effects for second-generation long-acting injectable anti-psychotics (SGA-LAIs) (RR=0.39, 95% CI: 0.27-0.56, n=3), clozapine (RR=0.43, 95% CI: 0.34-0.55, n=3), any LAI (RR=0.47, 95% CI: 0.39-0.58, n=2), and any SGA (RR=0.53, 95% CI: 0.44-0.63, n=4). Antipsychotics were also protective against natural cause-related mortality, yet first-generation antipsychotics (FGAs) were associated with increased mortality due to suicide and natural cause in incident schizophrenia. Higher study quality and number of variables used to adjust the analyses moderated larger natural-cause mortality risk, and more recent study year moderated larger protective effects of antipsychotics. These results indicate that the excess mortality in schizophrenia is associated with several modifiable factors. Targeting comorbid substance abuse, long-term maintenance antipsychotic treatment and appropriate/earlier use of SGA-LAIs and clozapine could reduce this mortality gap.
PubMed: 35524619
DOI: 10.1002/wps.20994 -
Neuroscience and Biobehavioral Reviews Nov 2020Sleep problems and depression are both common and have a high impact on quality of life. They are also strongly associated and commonly occur together. During the... (Review)
Review
Sleep problems and depression are both common and have a high impact on quality of life. They are also strongly associated and commonly occur together. During the reproductive age, both sleep problems and depression are almost twice as common in women than men. Epidemiological studies show that women experience more sleep problems and depressive symptoms around times when sex hormones change, such as puberty and menopause, but it is unclear what effect sex hormones have on sleep problems and depression. This systematic review aims to summarize and evaluate studies that investigated the relationship between sex hormones, sleep and depression. Systematic search resulted in 2895 articles, of which 13 met inclusion criteria. Depressed patients showed worse sleep than controls, but no significant difference in endogenous hormone levels was found. Additionally, higher endogenous estrogen was associated with better sleep in controls, but associations between endogenous sex hormones and depressive symptoms were inconclusive. More research on the effect of sex hormones on sleep and depression is necessary.
Topics: Depression; Female; Gonadal Steroid Hormones; Humans; Male; Menopause; Quality of Life; Sleep Wake Disorders
PubMed: 32882313
DOI: 10.1016/j.neubiorev.2020.08.006 -
Frontiers in Psychiatry 2019Determining the clinical effects of coercion is a difficult challenge, raising ethical, legal, and methodological questions. Despite limited scientific evidence on...
Determining the clinical effects of coercion is a difficult challenge, raising ethical, legal, and methodological questions. Despite limited scientific evidence on effectiveness, coercive measures are frequently used, especially in psychiatry. This systematic review aims to search for effects of seclusion and restraint on psychiatric inpatients with wider inclusion of outcomes and study designs than former reviews. A systematic search was conducted following PRISMA guidelines, primarily through Pubmed, Embase, and CENTRAL. Interventional and prospective observational studies on effects of seclusion and restraint on psychiatric inpatients were included. Main search keywords were , , , , , , , , and . Thirty-five articles were included, out of 6,854 records. Studies on the effects of seclusion and restraint in adult psychiatry comprise a wide range of outcomes and designs. The identified literature provides some evidence that seclusion and restraint have deleterious physical or psychological consequences. Estimation of post-traumatic stress disorder incidence after intervention varies from 25% to 47% and, thus, is not negligible, especially for patients with past traumatic experiences. Subjective perception has high interindividual variability, mostly associated with negative emotions. Effectiveness and adverse effects of seclusion and restraint seem to be similar. Compared to other coercive measures (notably forced medication), seclusion seems to be better accepted, while restraint seems to be less tolerated, possibly because of the perception of seclusion as "non-invasive." Therapeutic interaction appears to have a positive influence on coercion perception. Heterogeneity of the included studies limited drawing clear conclusions, but the main results identified show negative effects of seclusion and restraint. These interventions should be used with caution and as a last resort. Patients' preferences should be taken into account when deciding to apply these measures. The therapeutic relationship could be a focus for improvement of effects and subjective perception of coercion. In terms of methodology, studying coercive measures remains difficult but, in the context of current research on coercion reduction, is needed to provide workable baseline data and potential targets for interventions. Well-conducted prospective cohort studies could be more feasible than randomized controlled trials for interventional studies.
PubMed: 31404294
DOI: 10.3389/fpsyt.2019.00491 -
Journal of the American Academy of... Jul 2021Alopecia areata (AA) is an immune-mediated disease resulting in nonscarring hair loss. Systematic reviews on the psychosocial and psychiatric comorbidities,...
BACKGROUND
Alopecia areata (AA) is an immune-mediated disease resulting in nonscarring hair loss. Systematic reviews on the psychosocial and psychiatric comorbidities, health-related quality of life, and interventions targeting psychosocial well-being are limited.
OBJECTIVE
To conduct a systematic review of the psychosocial comorbidities, health-related quality of life, and treatment options targeting psychosocial well-being in adult and pediatric AA patients.
METHODS
A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines within the PubMed database. Specific search terms included, but were not limited to, alopecia areata, psychosocial, psychiatry, and quality of life. Studies were then evaluated for their design and categorized into corresponding levels of evidence according to the guidelines adapted from the Oxford Center for Evidence Based Medicine.
FINDINGS
Seventy-three reports met inclusion criteria, involving approximately 414,319 unique participants. AA patients were found to have psychiatric comorbidities, particularly anxiety and depression. Health-related quality of life is reduced in AA patients, but data on pediatric AA quality of life are limited. Psychotherapy is often recommended as adjuvant treatment.
CONCLUSION
AA has substantial psychosocial impact on patients and results in reduced health-related quality of life. Addressing this should be an active part of treatment.
Topics: Alopecia Areata; Anxiety; Child; Child Behavior Disorders; Comorbidity; Depression; Humans; Mental Disorders; Quality of Life; Suicide
PubMed: 32561373
DOI: 10.1016/j.jaad.2020.06.047 -
European Child & Adolescent Psychiatry Jul 2023COVID-19 was declared a pandemic in March 2020, resulting in many countries worldwide calling for lockdowns. This study aimed to review the existing literature on the... (Review)
Review
COVID-19 was declared a pandemic in March 2020, resulting in many countries worldwide calling for lockdowns. This study aimed to review the existing literature on the effects of the lockdown measures established as a response to the COVID-19 pandemic on the mental health of children and adolescents. Embase, Ovid, Global Health, PsycINFO, Web of Science, and pre-print databases were searched in this PRISMA-compliant systematic review (PROSPERO: CRD42021225604). We included individual studies reporting on a wide range of mental health outcomes, including risk and protective factors, conducted in children and adolescents (aged ≤ 19 years), exposed to COVID-19 lockdown. Data extraction and quality appraisal were conducted by independent researchers, and results were synthesised by core themes. 61 articles with 54,999 children and adolescents were included (mean age = 11.3 years, 49.7% female). Anxiety symptoms and depression symptoms were common in the included studies and ranged 1.8-49.5% and 2.2-63.8%, respectively. Irritability (range = 16.7-73.2%) and anger (range = 30.0-51.3%), were also frequently reported by children and adolescents. Special needs and the presence of mental disorders before the lockdown, alongside excessive media exposure, were significant risk factors for anxiety. Parent-child communication was protective for anxiety and depression. The COVID-19 lockdown has resulted in psychological distress and highlighted vulnerable groups such as those with previous or current mental health difficulties. Supporting the mental health needs of children and adolescents at risk is key. Clinical guidelines to alleviate the negative effects of COVID-19 lockdown and public health strategies to support this population need to be developed.
Topics: Humans; Adolescent; Female; Child; Male; COVID-19; Mental Health; Pandemics; SARS-CoV-2; Communicable Disease Control; Anxiety; Depression
PubMed: 34406494
DOI: 10.1007/s00787-021-01856-w -
The American Journal of Psychiatry Jan 2023The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials.
METHODS
A systematic review of MEDLINE, Embase, and Scopus was conducted in April 2020. Seven criteria were applied to focus on original research that includes quantifiable response biomarkers measured alongside ASD symptoms. Interventional studies or human studies that assessed the correlation between biomarkers and ASD-related behavioral measures were included.
RESULTS
A total of 5,799 independent records yielded 280 articles for review that reported on 940 biomarkers, 755 of which were unique to a single publication. Molecular biomarkers were the most frequently assayed, including cytokines, growth factors, measures of oxidative stress, neurotransmitters, and hormones, followed by neurophysiology (e.g., EEG and eye tracking), neuroimaging (e.g., functional MRI), and other physiological measures. Studies were highly heterogeneous, including in phenotypes, demographic characteristics, tissues assayed, and methods for biomarker detection. With a median total sample size of 64, almost all of the reviewed studies were only powered to identify biomarkers with large effect sizes. Reporting of individual-level values and summary statistics was inconsistent, hampering mega- and meta-analysis. Biomarkers assayed in multiple studies yielded mostly inconsistent results, revealing a "replication crisis."
CONCLUSIONS
There is currently no response biomarker with sufficient evidence to inform ASD clinical trials. This review highlights methodological imperatives for ASD biomarker research necessary to make definitive progress: consistent experimental design, correction for multiple comparisons, formal replication, sharing of sample-level data, and preregistration of study designs. Systematic "big data" analyses of multiple potential biomarkers could accelerate discovery.
Topics: Humans; Autism Spectrum Disorder; Biomarkers; Phenotype; Magnetic Resonance Imaging; Research Design
PubMed: 36475375
DOI: 10.1176/appi.ajp.21100992