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JAMA Psychiatry May 2024Placebo is the only substance systematically evaluated across common psychiatric diagnoses, but comprehensive cross-diagnostic comparisons are lacking.
IMPORTANCE
Placebo is the only substance systematically evaluated across common psychiatric diagnoses, but comprehensive cross-diagnostic comparisons are lacking.
OBJECTIVE
To compare changes in placebo groups in recent high-quality randomized clinical trials (RCTs) across a broad spectrum of psychiatric disorders in adult patients.
DATA SOURCES
MEDLINE and the Cochrane Database of Systematic Reviews were systematically searched in March 2022 for the latest systematic reviews meeting predetermined high-quality criteria for 9 major psychiatric diagnoses.
STUDY SELECTION
Using these reviews, the top 10 highest-quality (ie, lowest risk of bias, according to the Cochrane Risk of Bias tool) and most recent placebo-controlled RCTs per diagnosis (totaling 90 RCTs) were selected, adhering to predetermined inclusion and exclusion criteria.
DATA EXTRACTION AND SYNTHESIS
Following the Cochrane Handbook, 2 authors independently carried out the study search, selection, and data extraction. Cross-diagnosis comparisons were based on standardized pre-post effect sizes (mean change divided by its SD) for each placebo group. This study is reported following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline.
MAIN OUTCOME AND MEASURE
The primary outcome, pooled pre-post placebo effect sizes (dav) with 95% CIs per diagnosis, was determined using random-effects meta-analyses. A Q test assessed statistical significance of differences across diagnoses. Heterogeneity and small-study effects were evaluated as appropriate.
RESULTS
A total of 90 RCTs with 9985 placebo-treated participants were included. Symptom severity improved with placebo in all diagnoses. Pooled pre-post placebo effect sizes differed across diagnoses (Q = 88.5; df = 8; P < .001), with major depressive disorder (dav = 1.40; 95% CI, 1.24-1.56) and generalized anxiety disorder (dav = 1.23; 95% CI, 1.06-1.41) exhibiting the largest dav. Panic disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, social phobia, and mania showed dav between 0.68 and 0.92, followed by OCD (dav = 0.65; 95% CI, 0.51-0.78) and schizophrenia (dav = 0.59; 95% CI, 0.41-0.76).
CONCLUSION AND RELEVANCE
This systematic review and meta-analysis found that symptom improvement with placebo treatment was substantial in all conditions but varied across the 9 included diagnoses. These findings may help in assessing the necessity and ethical justification of placebo controls, in evaluating treatment effects in uncontrolled studies, and in guiding patients in treatment decisions. These findings likely encompass the true placebo effect, natural disease course, and nonspecific effects.
PubMed: 38809560
DOI: 10.1001/jamapsychiatry.2024.0994 -
Psychiatry and Clinical... Sep 2023Gray matter alterations play a role in the panic disorder's pathophysiology origin. However, the current literature seemed inadequate to reach a consistent conclusion....
BACKGROUND
Gray matter alterations play a role in the panic disorder's pathophysiology origin. However, the current literature seemed inadequate to reach a consistent conclusion. Therefore, we conducted this gray matter meta-analysis on panic disorder.
METHODS
A systematic review and a voxel-wise meta-analysis based on voxel-based morphometry were conducted for the gray matter studies in patients with panic disorder. The Seed-based d Mapping toolbox was applied for the voxel-wise meta-analysis. Fourteen gray matter studies (954 subjects) were enrolled in the current meta-analysis. The subgroup analysis of typical-onset versus late-onset patients was also performed. At last, the clinical severity was meta-regressed with gray matter alterations.
RESULTS
Significant gray matter alterations were found in the left para-cingulate gyrus and the right amygdala of panic disorder patients. The subgroup analysis of typical-onset panic disorder patients showed a similar pattern. However, gray matter alterations were demonstrated in the bilateral opercular cortex of late-onset panic disorder patients. A significant association between the clinical severity and the gray matter alterations was found in the fronto-cingulate regions of panic disorder patients.
CONCLUSION
Gray matter alterations might represent a significant pillar of panic disorder's neurobiology, especially for the amygdala, cingulate, and frontal regions. Future gray matter studies in panic disorder should be needed to reconfirm this pattern of gray matter alterations.
PubMed: 38765308
DOI: 10.5152/pcp.2023.23684 -
World Psychiatry : Official Journal of... Jun 2024Psychotherapies are first-line treatments for most mental disorders, but their absolute outcomes (i.e., response and remission rates) are not well studied, despite the...
Psychotherapies are first-line treatments for most mental disorders, but their absolute outcomes (i.e., response and remission rates) are not well studied, despite the relevance of such information for health care users, providers and policy makers. We aimed to examine absolute and relative outcomes of psychotherapies across eight mental disorders: major depressive disorder (MDD), social anxiety disorder, panic disorder, generalized anxiety disorder (GAD), specific phobia, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and borderline personality disorder (BPD). We used a series of living systematic reviews included in the Metapsy initiative (www.metapsy.org), with a common strategy for literature search, inclusion of studies and extraction of data, and a common format for the analyses. Literature search was conducted in major bibliographical databases (PubMed, PsycINFO, Embase, and the Cochrane Register of Controlled Trials) up to January 1, 2023. We included randomized controlled trials comparing psychotherapies for any of the eight mental disorders, established by a diagnostic interview, with a control group (waitlist, care-as-usual, or pill placebo). We conducted random-effects model pairwise meta-analyses. The main outcome was the absolute rate of response (at least 50% symptom reduction between baseline and post-test) in the treatment and control conditions. Secondary outcomes included the relative risk (RR) of response, and the number needed to treat (NNT). Random-effects meta-analyses of the included 441 trials (33,881 patients) indicated modest response rates for psychotherapies: 0.42 (95% CI: 0.39-0.45) for MDD; 0.38 (95% CI: 0.33-0.43) for PTSD; 0.38 (95% CI: 0.30-0.47) for OCD; 0.38 (95% CI: 0.33-0.43) for panic disorder; 0.36 (95% CI: 0.30-0.42) for GAD; 0.32 (95% CI: 0.29-0.37) for social anxiety disorder; 0.32 (95% CI: 0.23-0.42) for specific phobia; and 0.24 (95% CI: 0.15-0.36) for BPD. Most sensitivity analyses broadly supported these findings. The RRs were significant for all disorders, except BPD. Our conclusion is that most psychotherapies for the eight mental disorders are effective compared with control conditions, but absolute response rates are modest. More effective treatments and interventions for those not responding to a first-line treatment are needed.
PubMed: 38727072
DOI: 10.1002/wps.21203 -
Orthopaedic Journal of Sports Medicine Apr 2024An anterior cruciate ligament (ACL) tear is a risk factor for early osteoarthritis (OA) onset. Generally, ACL reconstruction (ACLR) is associated with better outcomes.... (Review)
Review
BACKGROUND
An anterior cruciate ligament (ACL) tear is a risk factor for early osteoarthritis (OA) onset. Generally, ACL reconstruction (ACLR) is associated with better outcomes. However, there is a lack of evidence regarding the effect of operative versus nonoperative treatment for preventing premature knee OA in isolated ACL tears while achieving good functional outcomes.
PURPOSE/HYPOTHESIS
The purpose of the study was to compare the outcomes of ACLR to primarily nonoperative management of isolated ACL tears. It was hypothesized that the outcomes between treatment types would be similar.
STUDY DESIGN
Systematic review; Level of evidence, 3.
METHODS
This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (registration No. CRD42021285901) and was conducted according to the Cochrane Handbook guidelines. We systematically searched for randomized and nonrandomized studies that compared ACLR with nonoperative treatments in isolated ACL tears in 3 databases until October 25, 2021. The risk of bias and quality of evidence of the included studies was assessed in accordance with the Cochrane guidelines. The primary outcome was radiologic signs of OA, and the secondary outcomes were functional parameters. Using the common effects model, we calculated pooled mean differences (MDs) and odds ratios (ORs) with 95% CIs.
RESULTS
Five studies-2 randomized controlled trials (RCTs) and 3 retrospective non-RCTs-were included. There was a moderate risk of bias in 2 studies and a serious risk of bias in 1 study. The quality of evidence was rated low because of the higher risk of bias and inconsistency. Nonoperatively treated knees showed a trend toward lower odds of developing radiological signs of OA (OR, 1.84 [95% CI, 0.90 to 3.75]); however, surgically reconstructed knees had significantly better stability (MD, -2.44 [95% CI, -3.21 to -1.66 ]) and a trend toward better but clinically not meaningful Lysholm scores (MD, 2.88 [95% CI, -1.09 to 6.85]). The qualitative synthesis showed that surgical reconstruction was protective against subsequent injuries but not superior when returning to previous activity levels or various functional tests.
CONCLUSION
Findings indicated that there is no certain evidence that ACLR for an isolated ACL tear is superior to nonoperative treatment. Clinicians should consider nonoperative treatments with a well-designed rehabilitative program as a primary option. However, these findings must be interpreted with caution because of low study quality and high risk of bias.
PubMed: 38601190
DOI: 10.1177/23259671241239665 -
Frontiers in Psychiatry 2024Moyamoya disease (MMD) is a life-threatening condition characterized by stenosis of intracranial arteries. Despite the frequency and the impact of psychiatric symptoms...
INTRODUCTION
Moyamoya disease (MMD) is a life-threatening condition characterized by stenosis of intracranial arteries. Despite the frequency and the impact of psychiatric symptoms on the long-term prognosis and quality of life of MMD patients, no systematic review on this topic exists.
METHODS
This systematic review and meta-analysis included 41 studies (29 being case reports), from PubMed, Scopus, Embase until 27/3/2023, on MMD patients exhibiting psychiatric symptoms.
RESULTS
Despite a fair average quality of the articles, quantitative synthesis through logistic regression was possible only for case reports, due to heterogeneity between the other studies. Psychosis, the most frequent psychiatric symptom reported in case reports, was more frequent in MMD patients with left hemisphere involvement. Neurological symptoms occurrence increased the odds of MMD diagnosis preceding psychiatric symptoms. Psychiatric symptoms are highly prevalent in MMD patients and are relatively often the only presenting symptoms.
DISCUSSION
We discuss the diagnostic, therapeutic, and prognostic implications of recognizing and characterizing specific psychiatric symptoms in MMD, outlining preliminary guidelines for targeted pharmacological and psychotherapeutic interventions. Lastly, we outline future research and clinical perspectives, striving to enhance the oft-overlooked psychiatric care for MMD patients and to ameliorate their long-term outcome.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023406303.
PubMed: 38585478
DOI: 10.3389/fpsyt.2024.1371763 -
Neuroradiology Jul 2024We reviewed 33 original research studies assessing brain perfusion, using consensus guidelines from a "white paper" issued by the International Society for Magnetic... (Review)
Review
We reviewed 33 original research studies assessing brain perfusion, using consensus guidelines from a "white paper" issued by the International Society for Magnetic Resonance in Medicine Perfusion Study Group and the European Cooperation in Science and Technology Action BM1103 ("Arterial Spin Labelling Initiative in Dementia"; https://www.cost.eu/actions/BM1103/ ). The studies were published between 2011 and 2023 and included participants with subjective cognitive decline plus; neurocognitive disorders, including mild cognitive impairment (MCI), Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB) and vascular cognitive impairment (VCI); as well as schizophrenia spectrum disorders, bipolar and major depressive disorders, autism spectrum disorder, attention-deficit/hyperactivity disorder, panic disorder and alcohol use disorder. Hypoperfusion associated with cognitive impairment was the major finding across the spectrum of cognitive decline. Regional hyperperfusion also was reported in MCI, AD, frontotemporal dementia phenocopy syndrome and VCI. Hypoperfused structures found to aid in diagnosing AD included the precunei and adjacent posterior cingulate cortices. Hypoperfused structures found to better diagnose patients with FTLD were the anterior cingulate cortices and frontal regions. Hypoperfusion in patients with DLB was found to relatively spare the temporal lobes, even after correction for partial volume effects. Hyperperfusion in the temporal cortices and hypoperfusion in the prefrontal and anterior cingulate cortices were found in patients with schizophrenia, most of whom were on medication and at the chronic stage of illness. Infratentorial structures were found to be abnormally perfused in patients with bipolar or major depressive disorders. Brain perfusion abnormalities were helpful in diagnosing most neurocognitive disorders. Abnormalities reported in VCI and the remaining mental disorders were heterogeneous and not generalisable.
Topics: Humans; Spin Labels; Mental Disorders; Magnetic Resonance Imaging; Cerebrovascular Circulation; Cognitive Dysfunction
PubMed: 38536448
DOI: 10.1007/s00234-024-03323-0 -
Brain and Behavior Jan 2024The existing literature on the association between brain-derived neurotrophic factor (BDNF) protein levels and panic disorder presents inconsistent findings. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The existing literature on the association between brain-derived neurotrophic factor (BDNF) protein levels and panic disorder presents inconsistent findings. This systematic review and meta-analysis aim to synthesize the available evidence and determine the overall effect of BDNF protein levels in individuals diagnosed with panic disorder.
METHODS
A comprehensive literature search was conducted using electronic databases (PubMed, Embase, Scopus, PsycINFO, and Web of Science) from inception to April 21, 2023. The search strategy included relevant keywords and medical subject headings terms related to BDNF, panic disorder, and protein levels. A random-effects model was used for the meta-analysis, and subgroup analyses were performed to explore heterogeneity. Publication bias was assessed using funnel plots and statistical tests.
RESULTS
A total of 12 studies met the inclusion criteria. The meta-analysis demonstrated a significant decrease in BDNF protein levels in individuals with panic disorder (SMD = -.53, 95% CI: -1.02 to -.04, p < .001; I : 92%). The results of subgroup and meta-regression analyses were not statistically significant. No significant publication bias was observed based on the results of Egger's regression test (p-value = .3550).
CONCLUSION
This systematic review and meta-analysis provide evidence of lower BDNF protein levels in individuals diagnosed with panic disorder compared to healthy controls. The findings suggest a potential role for BDNF dysregulation in the pathophysiology of panic disorder. Further research is warranted to elucidate the underlying mechanisms and potential therapeutic implications.
Topics: Humans; Panic Disorder; Brain-Derived Neurotrophic Factor; Regression Analysis
PubMed: 38376041
DOI: 10.1002/brb3.3349 -
Progress in Neuro-psychopharmacology &... Apr 2024As an important neurotrophic factor in the central nervous system, Brain-derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of psychiatric... (Meta-Analysis)
Meta-Analysis Review
As an important neurotrophic factor in the central nervous system, Brain-derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of psychiatric disorders in many studies. However, its value as a biomarker for the diagnosis and differential diagnosis of mental disorders is still controversial, and its change patterns among different mental disorders have not been compared. We conducted a network meta-analysis of BDNF levels in different psychiatric disorders including schizophrenia(SCZ), major depressive disorder(MDD), bipolar disorder(BD), panic disorder(PD), post-traumatic stress disorder(PTSD), obsessive-compulsive disorder(OCD), generalized anxiety disorder(GAD) and insomnia. Studies were identified by searching electronic databases through 31/05/2023. BDNF levels decreased in patients with BD, MDD, OCD, PD, SCZ compared with controls, while significantly increased in patients with PTSD. According to the network meta-analysis, BDNF levels were significantly decreased in MDD and SCZ compared with BD (-2.6, 95% CIs [-5.32 to -0.15] and - 2.68 95% CIs [-5.18 to -0.23] respectively). However, in the traditional meta-analysis, there was a trend towards lower BDNF levels in SCZ compared to BD, with no significant difference (SMD = -0.20, 95% CIs [-0.49 to 0.08]). In conclusion, abnormal BDNF levels have been found in psychiatric disorders, and the changes in peripheral BDNF levels in patients with psychiatric disorders were reconfirmed in this study, which suggests BDNF exhibits promising clinical utility and may hold diagnostic value in distinguishing between MDD and BD.
Topics: Humans; Depressive Disorder, Major; Brain-Derived Neurotrophic Factor; Network Meta-Analysis; Bipolar Disorder; Obsessive-Compulsive Disorder
PubMed: 38286331
DOI: 10.1016/j.pnpbp.2024.110954 -
Frontiers in Human Neuroscience 2023This systematic review examined the existing literature to determine the evidence supporting the efficacy of online group treatments for anxiety-, obsessive-compulsive-...
BACKGROUND
This systematic review examined the existing literature to determine the evidence supporting the efficacy of online group treatments for anxiety-, obsessive-compulsive- and trauma-related disorders (AOTDs).
METHODS
A systematic review using the PUBMED, PsycInfo, Web of Science, and ClinicalTrials databases with no language, date, or study design filters was performed. The inclusion criteria comprised studies that examined individuals who had received a formal diagnosis of AOTDs, were aged 18 years or older, and had baseline and endpoint assessments of symptom severity using formal tools.
RESULTS
Five studies on social anxiety disorder (SAD), four on post-traumatic stress disorder (PTSD) and one on tic disorders (TDs) were found. The studies were open-label ( = 2) and randomized controlled trials (RCTs) ( = 8), with five of the RCTs being non-inferiority trials. Most studies were conducted in the US and investigated psychological CBT based interventions via internet-based therapies (IBT: = 4), video teleconferencing (VTC: = 5) or a combination of both ( = 1). In SAD, IBT studies associated with a clinician assisted web-based forum (here termed "forum-enhanced" studies) were superior to waiting lists and not inferior to similar versions that were also "forum enhanced" but self-guided, "telephone enhanced" by a contact with a non-specialist, and "email enhanced" by a contact with a clinician individually. Studies involving VTC have shown comparable effectiveness to in-person interventions across some online group CBT based treatments for PTSD. Two open trials also demonstrated symptoms reductions of social anxiety and tics through VTC.
CONCLUSION
There is evidence supporting the effectiveness of online group treatments for SAD and PTSD. Further studies from different research groups may be needed to replicate the use of these and other forms of online treatments in individuals with SAD, PTSD, and other clinical populations, such as OCD, panic disorder, agoraphobia and specific phobias.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023408491.
PubMed: 38273884
DOI: 10.3389/fnhum.2023.1286865 -
American Journal of Health-system... Jun 2024Oral anticoagulants (OACs) and aspirin can trigger bleeding events when used alone or in combination. The purpose of this study was to compare the risk of any type of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Oral anticoagulants (OACs) and aspirin can trigger bleeding events when used alone or in combination. The purpose of this study was to compare the risk of any type of bleeding in individuals exposed to a combination of OAC and aspirin with the risk in those taking an OAC or aspirin alone.
METHODS
MEDLINE and Web of Science were queried in January 2021 for eligible articles. Studies were included if they were either randomized controlled trials (RCTs) or observational studies and evaluated the number of any bleeding events in two groups, one with exposure to both OAC and aspirin and one with exposure to OAC alone or aspirin alone. Pooled odds ratios were calculated using a random-effects model.
RESULTS
Forty-two studies were included. In an analysis of 15 RCTs and 19 observational studies evaluating OAC plus aspirin versus OAC alone, a significant difference in the risk of bleeding was observed in the combination groups, with an odds ratio [OR] of, 1.36 (95% CI, 1.15-1.59) for RCTs and an OR of 1.42 (95% CI-, 1.09-1.87) for observational studies. When OAC plus aspirin was compared to aspirin alone, a higher rate of bleeding was found in the combination group (OR, 2.36; 95%CI, 1.91-2.92) in the analysis of 15 RCTs, but no significant difference was found among 10 observational studies (OR, 1.93; 95% Cl, 0.99-3.75).
CONCLUSION
The risk of any type of bleeding was significantly increased among patients taking aspirin plus OAC compared to those taking OAC alone in both RCTs and observational studies. Evaluation of RCTs comparing OAC plus aspirin to aspirin alone suggests increased bleeding risk as well.
Topics: Aspirin; Humans; Anticoagulants; Hemorrhage; Administration, Oral; Randomized Controlled Trials as Topic; Drug Therapy, Combination; Platelet Aggregation Inhibitors; Observational Studies as Topic
PubMed: 38263263
DOI: 10.1093/ajhp/zxae010