The effectiveness of adjunct mindfulness-based intervention in treatment of bipolar disorder: A systematic review and meta-analysis

BACKGROUND: Mindfulness-based interventions (MBIs) have been increasingly used as an adjunctive treatment to pharmacotherapy for a few psychiatric disorders. However, few studies have investigated the efficacy of MBIs in bipolar disorder (BD). METHODS: We performed a systematic review and meta-analysis to evaluate the efficacy of MBIs as an adjunctive treatment in BD. Major electronic databases were independently searched by two authors for controlled and uncontrolled studies which examined the effects of MBIs on psychiatric symptoms in subjects with BD. Data from original studies were synthesized by using a random effects model. RESULTS: Twelve trials were eligible for inclusion into current meta-analysis, including three controlled studies (n=132) and nine uncontrolled studies (n=142). In within-group analysis, MBIs significantly reduced depressive (7 studies, n=100, Hedges' g=0.58, p<0.001) and anxiety (4 studies, n=68, Hedges' g=0.34, p=0.043) symptoms, but not manic symptoms (6 studies, n=89, Hedges' g=0.09, p=0.488) and cognition (3 studies, n=43, Hedges' g=0.35, p=0.171), compared to baseline. In between-group analysis (intervention group versus waiting list group, all patients with BD), MBIs did not reduce depressive (3 studies, n=132, Hedges' g=0.46, p=0.315) or anxiety (3 studies, n=132, Hedges' g=0.33, p=0.578) symptoms. LIMITATIONS: Only three controlled trials compared MBIs to control conditions. CONCLUSIONS: Our meta-analysis showed significantly beneficial effects on depressive and anxiety symptoms of BD patients in within-group analysis. However, this significance was not observed in comparison with the control groups. Further clinical trials are warranted to investigate the differences in the benefits of MBIs between treatment and control subjects

Comparison of antipsychotic dose equivalents for acute bipolar mania and schizophrenia

Are antipsychotic dose equivalents between acute mania and schizophrenia the same? Study selection and analysis Six databases were systematically searched (from inception to 17 September 2022) to identify blinded randomised controlled trials (RCTs) that used a flexible-dose oral antipsychotic drug for patients with acute mania. The mean and SD of the effective dose and the pre–post changes in manic symptoms were extracted. A network meta-analysis (NMA) under a frequentist framework was performed to examine the comparative efficacy between the antipsychotics. A classic mean dose method (sample size weighted) was used to calculate each antipsychotic dose equivalent to 1 mg/day olanzapine for acute mania. The antipsychotic dose equivalents of acute mania were compared with published data for schizophrenia. Findings We included 42 RCTs which enrolled 11 396 participants with acute mania. The NMA showed that risperidone was superior to olanzapine (reported standardised mean difference: −022, 95% CI −0.41 to –0.02), while brexpiprazole was inferior to olanzapine (standardised mean difference: 0.36, 95% CI 0.08 to 0.64). The dose equivalents to olanzapine (with SD) were 0.68 (0.23) for haloperidol, 0.32 (0.07) for risperidone, 0.60 (0.11) for paliperidone, 8.00 (1.41) for ziprasidone, 41.46 (5.98) for quetiapine, 1.65 (0.32) for aripiprazole, 1.23 (0.20) for asenapine, 0.53 (0.14) for cariprazine and 0.22 (0.03) for brexpiprazole. Compared with the olanzapine dose equivalents for schizophrenia, those of acute mania were higher for quetiapine (p<0.001, 28.5%) and aripiprazole (p<0.001, 17.0%), but lower for haloperidol (p<0.001, –8.1%) and risperidone (p<0.001, –15.8%). Conclusions Antipsychotic drugs have been considered first-line treatment for acute mania, warranting specific dose equivalence for scientific and clinical purposes

Relationship between depression and frailty in older adults: A systematic review and meta-analysis

Aim Depression and frailty are prevalent and burdensome in older age. However, the relationships between these entities are unclear and no quantitative meta-analysis exists. We conducted a systematic review and meta-analysis to investigate the associations between depression and frailty. Methods Two authors searched major electronic databases from inception until November-2016 for cross- sectional/longitudinal studies investigating depression and frailty. The strength of the reciprocal associations between frailty and depression was assessed through odds ratios (ORs) adjusted for potential confounders. Results From 2306 non duplicated hits, 24 studies were included. The overall prevalence of depression in 8023 people with frailty was 38.60% (95% CI 30.07 to 47.10, I2=94%). Those with frailty were at increased odds of having depression (OR adjusted for publication bias 4.42, 95%CI 2.66-7.35, k=11), also after adjusting for potential confounders (OR=2.64; 95%CI: 1.59-4.37, I2=55%, k=4). The prevalence of frailty in 2167 people with depression was 40.40% (95%CI 27.00-55.30, I2=97%). People with depression were at increased odds of having frailty (OR=4.07, 95%CI 1.93-8.55, k=8). The pooled OR for incident frailty, adjusted for a median of 7 confounders, was 3.72 (95%CI 1.95-7.08, I2=98%, k=4), whilst in two studies frailty increased the risk of incident depression with an OR=1.90 (95%CI 1.55-2.32, I2=0%). Conclusion This meta-analysis points to a reciprocal interaction between depression and frailty in older adults. Specifically, each condition is associated with an increased prevalence and incidence of the other, and may be a risk factor for the development of the other. However, further prospective investigations are warranted

Low peripheral levels of insulin growth factor-1 are associated with high incidence of delirium among elderly patients: A systematic review and meta-analysis

Introduction: Delirium, a serious condition observed in critically ill patients, clinically presents with impaired cognition and consciousness. The relationship between delirium and peripheral levels of insulin growth factor-1 (IGF-1) is unclear. Thus we conducted a meta-analysis to address this issue. Methods: Seven major electronic databases were searched from inception until October 2, 2017 to obtain relevant clinical variables to compare the difference in IGF-1 levels between delirious and non-delirious elderly in-patients. A random effects meta-analysis was conducted. Results: We studies 10 articles involving 294 delirious patients (mean age 73.0 years) and 604 non-delirious patients (mean age 76.9 years). We found that peripheral levels of IGF-1 in patients with delirium were significantly lower than in those without delirium (Hedges‘ g = −0.209, 95% confidence interval [CI] = −0.393 to −0.026, p = 0.025). Meta-regression analyses found that no variables such as percentage of cognitive impairment, mean age, and female proportion contribute to heterogeneity in terms of the entire population. Conclusions: Our data suggests that lower peripheral levels of IGF-1 could be associated with a higher incidence of delirium among elderly patients. Further prospective studies with larger sample sizes are needed to investigate the association between peripheral levels of IGF-1 and delirium

The association between diverse psychological protocols and the efficacy of psilocybin-assisted therapy for clinical depressive symptoms: a Bayesian meta-analysis

Objective: Psilocybin-assisted therapy has shown promising efficacy on clinical depressive symptoms. However, diverse psychological support or psychotherapy was performed with psilocybin treatment. This study aimed to explore the association of psychological protocols with the efficacy of psilocybin-assisted therapy for depressive symptoms. Method: Five major databases were systemic searched for clinical trials addressing psilocybin-assisted therapy for patients with clinical depressive symptoms. A Bayesian random-effects meta-analysis and meta-regression were performed. The effect size was mean difference (with 95% credible interval) measured by 17-Item Hamilton Depression Rating Scale. Results: There were 10 eligible studies including 515 adult patients with clinically diagnosed depression. The psychological protocols could be categorized into four types: (i) manualized directive psychotherapy(k=1); (ii) manualized nondirective psychological support(k=3), (iii) non-manualized nondirective psychological support(k=5); and (iv) non-manualized supportive psychotherapy(k=1). The pooled standard mean difference of psilocybin-assisted therapy was 10.08 (5.03-14.70). Conclusion: Compared with manualized nondirective psychological support, the other three psychological approaches did not differ significantly. The improvement of depressive symptoms was not associated with the psychological protocols in adult patients receiving psilocybin-assisted therapy

The CDEX-1 1 kg Point-Contact Germanium Detector for Low Mass Dark Matter Searches

The CDEX Collaboration has been established for direct detection of light dark matter particles, using ultra-low energy threshold p-type point-contact germanium detectors, in China JinPing underground Laboratory (CJPL). The first 1 kg point-contact germanium detector with a sub-keV energy threshold has been tested in a passive shielding system located in CJPL. The outputs from both the point-contact p+ electrode and the outside n+ electrode make it possible to scan the lower energy range of less than 1 keV and at the same time to detect the higher energy range up to 3 MeV. The outputs from both p+ and n+ electrode may also provide a more powerful method for signal discrimination for dark matter experiment. Some key parameters, including energy resolution, dead time, decay times of internal X-rays, and system stability, have been tested and measured. The results show that the 1 kg point-contact germanium detector, together with its shielding system and electronics, can run smoothly with good performances. This detector system will be deployed for dark matter search experiments.Comment: 6 pages, 8 figure

Trial sequential analysis and updated meta-analysis of fluvoxamine on clinical deterioration in adult patients with symptomatic COVID-19 infection

Preliminary meta-analyses suggested that fluvoxamine was effective in treating COVID-19 infection. However, the reliability of this evidence has not yet been examined. MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify any randomized controlled trials (RCTs) from the inception of the databases to 5 February 2023. We used trial sequential analysis (TSA) to examine the reliability of the current existing evidence on the benefits of fluvoxamine on COVID-19 infection. The primary outcome was clinical deterioration, as defined in the original study (reported as odds ratio (OR), with 95% confidence intervals), and the secondary outcome was hospitalization. In the TSA, we used the relative risk reduction thresholds of 10, 20, and 30%. The updated meta-analysis of the five RCTs showed that fluvoxamine was not associated with lower odds of clinical deterioration when compared with a placebo (OR: 0.81; 0.59–1.11). The effect of fluvoxamine lay within the futility boundary (i.e., lack of effect) when using a 30% relative risk reduction threshold. The effect estimates lay between the superiority and futility boundary using the 10% and 20% threshold, and the required size of information was not reached for these two thresholds. The effect of fluvoxamine on the odds of hospitalization was not statistically significant (0.76; 0.56–1.03). In conclusion, there is no reliable evidence that fluvoxamine, when compared to a placebo, reduces the relative risk of clinical deterioration among adult patients with COVID-19 infection by 30%, and a relative risk reduction of 20% or 10% is still uncertain. The role of fluvoxamine as a COVID-19 treatment cannot be justified

Do beta-adrenergic blocking agents increase asthma exacerbation? A network meta-analysis of randomized controlled trials

Beta-adrenergic blocking agents (abbreviated as beta-blockers) have been used for treating various cardiovascular diseases. However, the potential for asthma exacerbation is one of the major adverse effects of beta-blockers. This study aimed to compare the level of risk for an asthma attack in patients receiving various beta-blockers. We searched for randomized controlled trials (RCTs) of either placebo-controlled or active-controlled design. The current network meta-analysis (NMA) was conducted under a frequentist model. The primary outcome was the incidence of asthmatic attack. A total of 24 RCTs were included. Overall NMA revealed that only oral timolol [risk ratio (RR) = 3.35 (95% confidence interval (CI) 1.04–10.85)] and infusion of propranolol [RR = 10.19 (95% CI 1.29–80.41)] were associated with significantly higher incidences of asthma attack than the placebo, whereas oral celiprolol [RR = 0.39 (95% CI 0.04–4.11)], oral celiprolol and propranolol [RR = 0.46 (95% CI 0.02–11.65)], oral bisoprolol [RR = 0.46 (95% CI 0.02–11.65)], oral atenolol [RR = 0.51 (95% CI 0.20–1.28)], infusion of practolol [RR = 0.80 (95% CI 0.03–25.14)], and infusion of sotalol [RR = 0.91 (95% CI 0.08–10.65)] were associated with relatively lower incidences of asthma attack than the placebo. In participants with a baseline asthma history, in addition to oral timolol and infusion of propranolol, oral labetalol, oxprenolol, propranolol, and metoprolol exhibited significantly higher incidences of asthma attack than did the placebo. In conclusion, oral timolol and infusion of propranolol were associated with a significantly higher risk of developing an asthma attack in patients, especially in those with a baseline asthma history, and should be avoided in patients who present a risk of asthma

Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis

Objective To evaluate the comparative effectiveness and acceptability of oral monotherapy using psychedelics and escitalopram in patients with depressive symptoms, considering the potential for overestimated effectiveness due to unsuccessful blinding. Design Systematic review and Bayesian network meta-analysis. Data sources Medline, Cochrane Central Register of Controlled Trials, Embase, PsycINFO, ClinicalTrial.gov, and World Health Organization’s International Clinical Trials Registry Platform from database inception to 12 October 2023. Eligibility criteria for selecting studies Randomised controlled trials on psychedelics or escitalopram in adults with depressive symptoms. Eligible randomised controlled trials of psychedelics (3,4-methylenedioxymethamphetamine (known as MDMA), lysergic acid diethylamide (known as LSD), psilocybin, or ayahuasca) required oral monotherapy with no concomitant use of antidepressants. Data extraction and synthesis The primary outcome was change in depression, measured by the 17-item Hamilton depression rating scale. The secondary outcomes were all cause discontinuation and severe adverse events. Severe adverse events were those resulting in any of a list of negative health outcomes including, death, admission to hospital, significant or persistent incapacity, congenital birth defect or abnormality, and suicide attempt. Data were pooled using a random effects model within a Bayesian framework. To avoid estimation bias, placebo responses were distinguished between psychedelic and antidepressant trials. Results Placebo response in psychedelic trials was lower than that in antidepression trials of escitalopram (mean difference −3.90 (95% credible interval −7.10 to −0.96)). Although most psychedelics were better than placebo in psychedelic trials, only high dose psilocybin was better than placebo in antidepression trials of escitalopram (mean difference 6.45 (3.19 to 9.41)). However, the effect size (standardised mean difference) of high dose psilocybin decreased from large (0.88) to small (0.31) when the reference arm changed from placebo response in the psychedelic trials to antidepressant trials. The relative effect of high dose psilocybin was larger than escitalopram at 10 mg (4.66 (95% credible interval 1.36 to 7.74)) and 20 mg (4.69 (1.64 to 7.54)). None of the interventions was associated with higher all cause discontinuation or severe adverse events than the placebo. Conclusions Of the available psychedelic treatments for depressive symptoms, patients treated with high dose psilocybin showed better responses than those treated with placebo in the antidepressant trials, but the effect size was small. Systematic review registration PROSPERO, CRD42023469014