Developing a machine learning-based short form of the positive and negative syndrome scale.

BACKGROUND AND HYPOTHESIS: The Positive and Negative Syndrome Scale (PANSS) consists of 30 items and takes up to 50 minutes to administer and score. Therefore, this study aimed to develop and validate a machine learning-based short form of the PANSS (PANSS-MLSF) that reproduces the PANSS scores. Moreover, the PANSS-MLSF estimated the removed-item scores. STUDY DESIGN: The PANSS-MLSF was developed using an artificial neural network, and the removed-item scores were estimated using the eXtreme Gradient Boosting classifier algorithm. The reliability of the PANSS-MLSF was examined using Cronbach's alpha. The concurrent validity was examined by the association (Pearson's r) between the PANSS-MLSF and the PANSS. The convergent validity was examined by the association (Pearson's r) between the PANSS-MLSF and the Clinical Global Impression-Severity, Mini-Mental State Examination, and Lawton Instrumental Activities of Daily Living Scale. The agreement of the estimated removed-item scores with their original scores was examined using Cohen's kappa. STUDY RESULTS: Our analysis included data from 573 patients with moderate severity. The two versions of the PANSS-MLSF comprised 15 items and 9 items were proposed. The PANSS-MLSF scores were similar to the PANSS scores (mean squared error=2.6-24.4 points). The reliability, concurrent validity, and convergent validity of the PANSS-MLSF were good. Moderate to good agreement between the estimated removed-item scores and the original item scores was found in 60% of the removed items. CONCLUSION: The PANSS-MLSF offers a viable way to reduce PANSS administration time, maintain score comparability, uphold reliability and validity, and even estimate scores for the removed items.

A systematic review and meta-analysis of the relationship between heavy smoking and probability discounting.

BACKGROUND AND OBJECTIVES: Probability discounting (PD), which refers to the process of adjusting the value of future probabilities when making decisions, is a method of measuring impulsive decision-making; however, the relationship between PD and nicotine remains unclear. The current study aimed at investigating the significance of PD in individuals who smoke. METHODS: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched the PubMed, Embase, PsycINFO, and Web of Science databases for articles comparing individuals who smoke and their tobacco-naïve controls using PD task as outcome measure from inception to May 2023. The main outcome was an overall difference in PD function, while subgroup analysis and meta-regression were conducted to examine the analysis methods and the moderators of PD. RESULTS: Fourteen studies in total involving 384 individuals who smoke and 493 controls (mean age = 24.32 years, range = 15.1-38.05 years) were analyzed. The effect of smoking on PD was significant (g = 0.51, p = .02). The discounting parameter from the equation, compared to the area under the curve, was more sensitive to estimating PD function (p = .01). Regression analysis showed positive correlations of PD with female percentage, age, and the number of probability options (all p < .04), but not with the number of choices at each probability and maximum reward magnitude (all p > .07). There was no significant publication bias across the eligible studies (p = .09). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Our findings, which are the first to demonstrate a smaller PD (i.e., prone to risk-taking) in individuals who smoke, shed light on the appropriate analysis method, gender effect, age, and probability options on the PD function.

Therapeutic efficacy of probiotics for symptoms of attention-deficit hyperactivity disorder in children and adolescents: meta-analysis.

BACKGROUND: The efficacy of probiotics as a therapeutic alternative for attention-deficit hyperactivity disorder (ADHD) remain unclear. AIMS: To investigate the effectiveness of probiotics for symptoms of ADHD and identify possible factors affecting their efficacy. METHOD: Randomised placebo-controlled trials were identified through searching major databases from inception to April 2023, using the main keywords 'probiotics' and 'ADHD' without limitation on languages or geographic locations. The outcome of interest included improvement in total symptoms of ADHD, symptoms of inattention and hyperactivity/impulsivity, and drop-out rate. Continuous and categorical data were expressed as effect sizes based on standardised mean differences (SMDs) and odds ratios, respectively, with 95% confidence intervals. RESULTS: Meta-analysis of seven trials involving 379 participants (mean age 10.37 years, range 4-18 years) showed no significant improvement in total symptoms of ADHD (SMD = 0.25; P = 0.12), symptoms of inattention (SMD = 0.14; P = 0.3) or hyperactivity/impulsivity (SMD = 0.08; P = 0.54) between the probiotic and placebo groups. Despite non-significance on subgroup analyses, there was a large difference in effect size between studies using probiotics as an adjunct to methylphenidate and those using probiotics as supplementation (SMD = 0.84 v. 0.07; P = 0.16), and a moderate difference in effect size between studies using multiple strains of probiotics and those using single-strain regimens (SMD = 0.45 v. 0.03; P = 0.19). CONCLUSIONS: Current evidence shows no significant difference in therapeutic efficacy between probiotics and placebos for treatment of ADHD symptoms. However, albeit statistically non-significant, higher therapeutic efficacies associated with multiple-strain probiotics or combining probiotics with methylphenidate may provide direction for further research.

Effects of probiotics on neurocognitive outcomes in infants and young children: a meta-analysis.

Background: Therapeutic efficacies of probiotics in improving neurocognitive functions in infants and young children remained unclear. This meta-analysis focused on different cognitive outcomes in this population. Methods: Major databases were searched electronically from inception to October 2023 to identify randomized controlled trials (RCTs) that investigated the therapeutic efficacy of probiotics in enhancing cognitive functions assessed by standardized tasks. The overall effect size was calculated as standardized mean difference (SMD) based on a random effects model. Results: Nine RCTs with 3,026 participants were identified. Both our primary and secondary results demonstrated no significant difference in neurocognitive outcomes between infants/children treated with probiotics and those receiving placebos. However, our subgroup analysis of studies that offered a probiotics treatment course of over six months demonstrated a significantly better neurocognitive outcome than placebos (SMD = 0.21, p = 0.03, two studies with 451 participants), but this finding was based on only two RCTs. Conclusion: Despite lack of significant therapeutic effects of probiotics on neurocognitive outcomes, our finding of a positive impact of probiotics on neurocognitive development in those undergoing treatment for over six months may provide an important direction for further investigations into the enhancement of therapeutic effects of probiotics on neurocognitive development in infants and young children. Systematic review registration: PROSPERO CRD42023463412.

A meta-analysis on the therapeutic efficacy of repetitive transcranial magnetic stimulation for cognitive functions in attention-deficit/hyperactivity disorders.

BACKGROUND: Therapeutic efficacies of repetitive transcranial magnetic stimulation (rTMS) for improving cognitive functions in patients with deficit/hyperactivity disorder (ADHD) remained unclear. The aim of this meta-analysis was to investigate the therapeutic efficacy of rTMS focusing on different cognitive performances. METHODS: Major databases were searched electronically from inception to February 2023 by using keywords mainly "rTMS" and "ADHD" to identify randomized controlled trials (RCTs) that investigated the therapeutic efficacy of rTMS for improving cognitive functions assessed by standardized tasks in patients with ADHD. The overall effect size (ES) was calculated as standardized mean difference (SMD) based on a random effects model. RESULTS: Meta-analysis of five RCTs with 189 participants (mean age of 32.78 and 8.53 years in adult and child/adolescent populations, respectively) demonstrated that rTMS was more effective for improving sustained attention in patients with ADHD compared with the control groups (SMD = 0.54, p = 0.001).Our secondary analysis also showed that rTMS was more effective for improving processing speed than the control groups (SMD = 0.59, p = 0.002) but not for enhancing memory or executive function. CONCLUSIONS: Our results supported the therapeutic efficacy of rTMS for improving sustained attention and processing speed. However, the limitation of available data warrants further studies to verify these findings.

Pharmacological interventions and hormonal therapies for depressive symptoms in peri- and post-menopausal women: a network meta-analysis of randomized controlled trials.

Although significant portion of women experience depressive symptoms during or after menopausal transition, there has been considerable controversy over the benefits of hormone replacement therapy (HRT) and antidepressants due to insufficient evidence supporting the superiority of either treatment. This frequentist model based network meta-analysis (NMA) included randomized controlled trials (RCTs) of menopausal depression symptoms management in menopausal women. Seventy RCTs involving a total of 18,530 women (mean age 62.5) were analyzed. The results demonstrated that fluoxetine plus oral HRT [standardized mean difference (SMD)=-1.59, 95% confidence interval (95%CIs)=-2.69 to -0.50] were associated with the largest improvement in depressive symptoms than placebos in overall menopausal women. Similar findings were also noted in the subgroup of participants with a definite diagnosis of depression, while no pharmacological or hormone replacement therapy was better than placebo in the subgroup of post-menopausal women (amenorrhea > 1 year) or in patients without diagnosis of depression. This NMA presented evidence that fluoxetine plus HRT may be beneficial to menopausal women with a definite diagnosis of depression but not to those without depression or post-menopausal women. Trial registration: PROSPERO (CRD42020167459).

Efficacy of electrical cranial stimulation for treatment of psychiatric symptoms in patients with anxiety: A systematic review and meta-analysis.

Background: Therapeutic effects of electrical cranial stimulation (CES) in patients suffering from anxiety remained unclear. This meta-analysis aimed at investigating acceptability and therapeutic efficacy of CES against anxiety, depression, and insomnia for patients who experienced symptoms of anxiety. Methods: Major electronic databases were searched from inception until December 10, 2022 for randomized controlled trials (RCT) focusing on therapeutic effectiveness of CES in patients whose primary complaints included anxiety. Effect sizes (ES) for different treatment outcomes were estimated by using generic inverse variance method. Results: Eight RCTs were identified including a total of 337 participants. The therapeutic effectiveness of CES was significantly better than that in the control groups for anxiety (ES=-0.96, p <0.00001, eight trials, 337 patients), depression (ES=-0.69, p=0.003, five trials), and insomnia (ES=-1.02, p = 0.0006, three trials) in those who presented with symptoms of anxiety. Subgroup analyses found that CES was equally effective regardless of comorbid presentation of depressive symptoms (ES=-0.94 in patients with anxiety only vs. ES=-1.06 in those with depression and anxiety) and whether CES was used as monotherapy or add-on therapy to medications (ES = -0.88 vs. ES = -1.12, respectively). Moreover, subgroup analysis of RCTs using the same device "Alpha-Stim" for CES was more effective in alleviating anxiety than sham controls (ES = -0.88, p < 0.00001, four trials, 230 patients). Regarding acceptability, the use of CES did not increase the risk of treatment-related dropout compared to the control group (RR = 1.26, p = 0.57, I2 = 0%, four trials, 324 patients). Conclusion: Our study supported the use of CES for symptoms of anxiety, depression, and insomnia in those suffering from anxiety with fair acceptability and demonstrated the efficacy of "Alpha-Stim", the most commonly used device for CES, in this patient population. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022382619.

Efficacy and tolerability of psychostimulants for symptoms of attention-deficit hyperactivity disorder in preschool children: A systematic review and meta-analysis.

BACKGROUND: There was no previous meta-analysis investigating the efficacy/tolerability of psychostimulants for symptoms of attention-deficit hyperactivity disorder (ADHD) in preschool children. METHODS: Databases including PubMed, the Cochrane Library, EMBASE, ScienceDirect, and ClinicalTrials.gov were searched from inception to March 2022 for randomized controlled trials (RCTs) on therapeutic efficacy of psychostimulants against ADHD symptoms in preschool children (age ≤6 years) compared with placebos. Primary outcomes were (a) changes in ADHD symptoms evaluated by validated rating scales from parents'/teacher's observation, or (b) post-intervention improvements in neuropsychological performance. Secondary outcomes were risks of adverse events. RESULTS: Meta-analysis of nine eligible trials including 544 preschool children (mean age=4.86 years, female=11.98%, median treatment duration=4.33 weeks) supported the efficacy of psychostimulants against global symptoms from observations of parents (Hedges' g=0.6152, p<0.0001) and teachers (Hedges' g=0.6563, p=0.0039). Efficacy of psychostimulants was also noted against symptoms of inattention and hyperactivity/impulsivity, especially the latter (i.e., main symptoms in preschool children). Moreover, male gender, older age, and longer treatment duration were associated with better efficacy. Regarding adverse events, only the risk of poor appetite was higher in the psychostimulant group (odds ratio [OR]=2.39). However, the qualities of evidence were low to very low, indicating potential discrepancy between the true and estimated effect. CONCLUSIONS: Our results showed that psychostimulants might be beneficial for preschool children with ADHD, especially hyperactivity/impulsivity from teachers' observation, with tolerable side effects. Nevertheless, the true magnitude of the effect needs to be confirmed with more research due to low to very low certainty of the evidence.

Surface electroencephalographic neurofeedback improves sustained attention in ADHD: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of surface electroencephalographic neurofeedback (EEG-NF) for improving attentional performance assessed by laboratory measures in patients with attention-deficit/hyperactivity disorder (ADHD) remains unclear. METHODS: Following the PRISMA guidelines, the PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials on the efficacy of surface EEG-NF against ADHD focusing on attentional performance evaluated by laboratory measures from inception to January 2022. RESULTS: Fourteen eligible studies were analyzed. Of the 718 participants involved, 429 diagnosed with ADHD received EEG-NF treatment. Significant improvement in attentional performance in ADHD subjects receiving EEG-NF was noted compared to their comparators (p < 0.01). Besides, there was a significant EEG-NF-associated beneficial effect on sustained attention (Hedges' g = 0.32, p < 0.01), whereas the impact on selective attention (p = 0.57) and working memory (p = 0.59) was limited. Moreover, protocol including beta wave enhancement was superior to that only focusing on reducing theta/beta ratio or modulation of slow cortical potential. Subgroup analyses showed that three sessions per week of EEG-NF produced the best effect, while the efficacy of surface EEG-NF was much poorer (Hedges' g = 0.05) when only studies that blinded their participants from knowledge of treatment allocation were included. No significant difference was noted in the improvement of attentional performance 6-12 months after EEG-NF intervention (n = 3, p = 0.42). CONCLUSIONS: Our results demonstrated the satisfactory effectiveness of surface EEG-NF for improving sustained attention, especially when beta wave enhancement was included, despite its failure to sustain a long-term effect. Further large-scale trials are warranted to support our findings.

Additive effects of EEG neurofeedback on medications for ADHD: a systematic review and meta-analysis.

To elucidate possible additive effects of electroencephalogram-based neurofeedback (EEG-NF) on medications against the core symptoms of attention-deficit/hyperactivity disorder (ADHD), randomized controlled trials (RCTs) were retrieved from electronic databases including PubMed, EMBASE, ClinicalKey, Cochrane CENTRAL, ScienceDirect, and ClinicalTrials.gov from inception to March 2022. The primary outcomes were changes in ADHD symptoms (i.e., global, inattention, hyperactivity/impulsivity) assessed with validated rating scales, while secondary outcome was all-cause discontinuation rate. Meta-analysis of five RCTs involving 305 participants [Median age = 9.285 years (range 8.6-11.05)] with a median follow-up of 12 weeks showed additive effects of EEG-NF on medications from parents' observations against ADHD global symptoms (Hedges' g = 0.2898, 95%CI [0.0238; 0.5557]) and inattention symptoms (Hedges' g = 0.3274, 95%CI [0.0493; 0.6055]). However, additive effects failed to sustain six months after EEG-NF intervention. Besides, there was no difference in improvement of hyperactivity/impulsivity from parents' observation, attentional performance, and all-cause discontinuation rate between the two groups. Our results supported additional benefits of combining EEG-NF with medications compared to medication alone in treating global symptoms and symptoms of inattention in ADHD patients. Nevertheless, given a lack of evidence showing a correlation between underlying physiological changes and small effect sizes in our preliminary results, further studies are warranted to support our findings.

Impact of parental rheumatoid arthritis on risk of autism spectrum disorders in offspring: A systematic review and meta-analysis.

Background: To investigate the association of risk of offspring autism spectrum disorder (ASD) with both maternal and paternal rheumatoid arthritis (RA). Methods: The Embase, Medline, Cochrane Library databases were searched for studies that investigated the association of parental RA with risk of offspring ASD. The primary outcome was the associations of maternal/paternal RA with the risk of offspring ASD. Subgroup analyses were conducted based on the timing of maternal RA diagnosis (i.e., before/after childbirth) and geographical location (i.e., Western vs. Asian countries) of studies. Results: Ten studies published between 2005 and 2022 involving 6,177,650 participants were analyzed. Pooled results revealed a significant association between maternal RA and the risk of ASD (OR = 1.246, p < 0.001, 10 studies), while there was no association of paternal RA with the risk of offspring ASD (OR = 1.104, p = 0.253, four studies). Subgroup analysis demonstrated no correlation between diagnosis of maternal RA before childbirth and the risk of offspring ASD (OR = 1.449, p = 0.192, four studies), while there was a significant association of maternal RA regardless of the timing of diagnosis with the risk of offspring ASD (OR = 1.227, p = 0.001, six studies). Subgroup analysis on geographical location showed a significant association of maternal RA with the risk of offspring ASD regardless of the study location (all p < 0.05). Conclusion: Our findings supported an association between maternal RA and an elevated risk of ASD in offspring. However, given the limited numbers of studies investigating the risk of offspring ASD in mothers diagnosed with RA before childbirth, further studies are warranted to elucidate this issue. Systematic review registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42022358470].

Therapeutic effects of antidepressants for global improvement and subdomain symptoms of autism spectrum disorder: a systematic review and meta-analysis.

BACKGROUND: No established pharmacological treatment is available for the core symptoms of autism spectrum disorder (ASD). This study aimed at investigating the efficacy of antidepressants for the core and associated symptoms of ASD. METHODS: We searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science and ClinicalTrials.gov using the keywords "ASD" and "antidepressants." We searched from database inception to June 2021 for randomized controlled trials of antidepressant use in patients with ASD. We calculated pooled effect sizes based on a random-effects model. RESULTS: Analysis of 16 studies with 899 participants showed improvements in restricted and repetitive behaviours (effect size = 0.27) and global symptoms (effect size = 1.0) in patients with ASD taking antidepressants versus those taking placebos (p ≤ 0.01). We found no differences between the 2 groups (p ≥ 0.36) in terms of dropout rate (odds ratio [OR] = 1.17) or rate of study discontinuation because of adverse events (OR = 1.05). We also noted improvements in irritability and hyperactivity in the antidepressant group (Hedges g = 0.33 and 0.22, respectively, both p < 0.03). Subgroup analyses showed significant effects of medication type (i.e., clomipramine was better than SSRIs) and age (antidepressants were more effective in adults than in children or adolescents) on both restricted and repetitive behaviours and global improvement (p < 0.05). Meta-regression demonstrated that better therapeutic effects were associated with lower symptom severity and older age. LIMITATIONS: The small effect sizes and variations in treatment response that we found warrant further study. CONCLUSION: Our results supported the effectiveness of antidepressants for global symptoms and symptom subdomains of ASD, with tolerable adverse effects. Low symptom severity and adulthood were associated with better outcomes.

A pilot meta-analysis on self-reported efficacy of neurofeedback for adolescents and adults with ADHD.

Self-reported effectiveness of electroencephalogram-based neurofeedback (EEG-NF) against the core symptoms of attention-deficit hyperactivity disorder (ADHD) in adolescents/adults remains unclear. We searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov from inception to August 2021 for randomized clinical trials (RCTs) of EEG-NF with self-reported ADHD symptom ratings. Comparators included participants on waitlist/treatment as usual (TAU) or receiving other interventions. Of the 279 participants (mean age = 23.48; range: 6-60) in five eligible RCTs, 183 received EEG-NF treatment. Forest plot demonstrated no difference in inattention (SMD = -0.11, 95% CI -0.39-0.18, p = 0.46), total score (SMD = -0.08, 95% CI -0.36-0.2, p = 0.56), and hyperactivity/impulsivity (SMD = 0.01, 95% CI -0.23-0.25, p = 0.91) between EEG-NF and comparison groups. Nevertheless, compared with waitlist/TAU, EEG-NF showed better improvement in inattention (SMD = -0.48, 95% CI -0.9--0.06, p = 0.03) but not hyperactivity/impulsivity (SMD = -0.03, 95% CI -0.45-0.38, p = 0.87). Follow-up 6-12 months demonstrated no difference in inattention (SMD = -0.01, 95% CI -0.41-0.38, p = 0.94), total score (SMD = 0.22, 95% CI -0.08-0.52, p = 0.15), and hyperactivity/impulsivity (SMD = -0.01, 95% CI -0.27-0.26, p = 0.96) between the two groups. Dropout rate also showed no difference (RR = 1.05, 95% CI 0.82-1.33, p = 0.72). Our results support EEG-NF for improving inattention in adolescents/young adults, although its effectiveness against hyperactivity/impulsivity remains inconclusive.

A nationwide study of the risks of major mental disorders among the offspring of parents with rheumatoid arthritis.

Rheumatoid arthritis (RA) may share genomic risks with certain mental disorders. This study aimed at investigating associations between parental RA and risks of mental disorders in offspring. Using the National Health Insurance Research Database (2001-2010), we conducted a matched cohort study involving two parent-child cohorts (i.e., RA-parent-child cohort and non-RA-parent-child cohort) between which risks of major mental disorders in offspring were compared. There were 23,981 parent-child pairs in the RA-parent-child cohort and 239,810 in the non-RA-parent-child cohort. Preliminary analysis demonstrated increased risks of autism spectrum disorders (ASDs) [Odds ratio (OR) 1.47; 95% confidence interval (CI) 1.05-2.07], attention-deficit/hyperactivity disorder (ADHD) [OR 1.34; (95% CI 1.17-1.54)], bipolar disorder [OR 1.41 (95% CI 1.17-1.70)], and major depressive disorder [OR 1.20 (95% CI 1.07-1.35)] associated with parental RA. Sub-group analysis further showed higher risks of the four disorders in children of mothers with RA but not those from fathers with RA. Higher risks of ASDs and ADHD were not noted in children of mothers with RA before childbirth. Maternal RA, but not paternal RA or mothers diagnosed with RA before childbirth, was associated with increased risks of multiple mental disorders in their offspring, suggesting potential contributions of maternal genetic factors to ASDs and ADHD development in offspring.

A systematic review and meta-analysis on the clinical implications of probability discounting among individuals with Internet gaming disorder.

The significance of probability discounting (PD) among individuals with Internet gaming disorder (IGD) remains unclear. Following the PRISMA guidelines, we systematically searched the PubMed, Embase, and ScienceDirect databases for English articles on Internet addiction that included comparison between individuals with and without IGD as well as probabilistic discounting task as the main outcome from January 1970 to July 2020 using the appropriate keyword strings. The primary outcome was the overall difference in rate of PD, while the secondary outcomes included the difference in PD with magnitude of probabilistic reward and response time of the PD task. Effect size (ES) was calculated through dividing the group means (e.g., h value or AUC) by the pooled standard deviations of the two groups. A total of five studies with 300 participants (i.e., IGD group, n = 150, mean age = 20.27 ± 2.68; healthy controls, n = 150, mean age = 20.70 ± 2.81) were analyzed. The IGD group was more willing to take risks in probabilistic gains but performances on probabilistic losses were similar between the two groups. The IGD group also exhibited a shorter response time (Hedge's g = - 0.51; 95%CI = - 0.87 to - 0.15). Meta-regression demonstrated a positive correlation between maximum reward magnitude and PD rate (p < 0.04). However, significant publication bias was noted among the included studies (Egger's test, p < 0.01). In conclusion, individuals with IGD seemed more impulsive in making risky decisions, especially when the potential gains were expected. Our findings not only supported the use of PD for assessing individuals with IGD but may also provide new insights into appropriate interventions.

Serotonergic antidepressants for sleep disturbances in perimenopausal and postmenopausal women: a systematic review and meta-analysis.

IMPORTANCE: Although previous meta-analyses mainly focused on the effects of hormonal treatment against menopausal sleep disturbances, the therapeutic role of antidepressants has not been systematically addressed. OBJECTIVE: To study the therapeutic benefit and safety of antidepressants in menopausal sleep disturbances. EVIDENCE REVIEW: Randomized controlled trials assessing the therapeutic effects of antidepressants against menopausal sleep problems were identified from the PubMed, Cochrane Library, and Science Direct databases from inception to March 1, 2020. Studies that were clinical trials with placebo controls were included. Subgroup analyses were conducted according to a random effects model. FINDINGS: Analysis of seven eligible randomized controlled trials including a total of 1,949 perimenopausal and postmenopausal women showed the effectiveness of serotonergic antidepressants against sleep disturbances despite the small effect size (Hedge  g = 0.24, 95% CI = 0.11-0.38). The efficacy remained significantly better than that of placebo for postmenopausal women (Hedge  g = 0.25, 95% CI = 0.04-0.45), participants with hot flashes (Hedge g = 0.18, 95% CI = 0.02-0.34), and those without diagnosis of major depressive disorder (Hedge g = 0.23, 95% CI = 0.06-0.40). There was no difference in therapeutic benefit between sedating and nonsedating serotonergic antidepressants. Besides, the dropout rate did not differ between antidepressant and placebo groups. CONCLUSIONS AND RELEVANCE: Our results showed that serotonergic antidepressants were effective against sleep disturbances in perimenopausal and postmenopausal women. The efficacy remained significant for women without major depressive disorder. The dropout rates were also comparable between serotonergic antidepressants and placebo groups.

The Use of Hypnotics and Mortality--A Population-Based Retrospective Cohort Study.

BACKGROUND: Sleep disorders, especially chronic insomnia, have become major health problem worldwide and, as a result, the use of hypnotics is steadily increasing. However, few studies with a large sample size and long-term observation have been conducted to investigate the relationship between specific hypnotics and mortality. METHODS: We conducted this retrospective cohort study using data from the National Health Insurance Research Database in Taiwan. Information from claims data including basic characteristics, the use of hypnotics, and survival from 2000 to 2009 for 1,320,322 individuals were included. The use of hypnotics was divided into groups using the defined daily dose and the cumulative length of use. Hazard ratios (HRs) were calculated from a Cox proportional hazards model, with two different matching techniques to examine the associations. RESULTS: Compared to the non-users, both users of benzodiazepines (HR = 1.81; 95% confidence interval [CI] = 1.78-1.85) and mixed users (HR = 1.44; 95% CI = 1.42-1.47) had a higher risk of death, whereas the users of other non-benzodiazepines users showed no differences. Zolpidem users (HR = 0.73; 95% CI = 0.71-0.75) exhibited a lower risk of mortality in the adjusted models. This pattern remained similar in both matching techniques. Secondary analysis indicated that zolpidem users had a reduced risk of major cause-specific mortality except cancer, and that this protective effect was dose-responsive, with those using for more than 1 year having the lowest risk. CONCLUSIONS: The effects of different types of hypnotics on mortality were diverse in this large cohort with long-term follow-up based on representative claims data in Taiwan. The use of zolpidem was associated with a reduced risk of mortality.

Association of the PPAR-γ Gene with Altered Glucose Levels and Psychosis Profile in Schizophrenia Patients Exposed to Antipsychotics.

OBJECTIVE: Metabolic abnormalities, e.g., diabetes, are common among schizophrenia patients. Peroxisome proliferator activated receptor-γ (PPAR-γ) regulates glucose/lipid metabolisms, and schizophrenia like syndrome may be induced by actions involving retinoid X receptor-α/PPAR-γ heterodimers. We examined a possible role of the PPAR-γ gene in metabolic traits and psychosis profile in schizophrenia patients exposed to antipsychotics. METHODS: Single nucleotide polymorphisms (SNPs) of the PPAR-γ gene and a serial of metabolic traits were determined in 394 schizophrenia patients, among which 372 were rated with Positive and Negative Syndrome Scale (PANSS). RESULTS: SNP-10, -12, -18, -19, -20 and -26 were associated with glycated hemoglobin (HbA1c) whereas SNP-18, -19, -20 and -26 were associated with fasting plasma glucose (FPG). While SNP-23 was associated with triglycerides, no associations were identified between the other SNPs and lipids. Further haplotype analysis demonstrated an association between the PPAR-γ gene and psychosis profile. CONCLUSION: Our study suggests a role of the PPAR-γ gene in altered glucose levels and psychosis profile in schizophrenia patients exposed to antipsychotics. Although the Pro12Ala at exon B has been concerned an essential variant in the development of obesity, the lack of association of the variant with metabolic traits in this study should not be treated as impossibility or a proof of error because other factors, e.g., genes regulated by PPAR-γ, may have complicated the development of metabolic abnormalities. Whether the PPAR-γ gene modifies the risk of metabolic abnormalities or psychosis, or causes metabolic abnormalities that lead to psychosis, remains to be examined.

Changes in the prescription pattern of antipsychotics for schizophrenic outpatients after the implementation of a global budgeting program.

BACKGROUND: A hospital-based global budget (GB) program was implemented by the Taiwan Bureau of National Health Insurance (TBNHI) to control the rising costs of medical care. We investigated whether the introduction of the GB program affected prescriptions for second-generation antipsychotics (SGAs) for schizophrenic outpatients in public and private medical and psychiatric centers. METHODS: The prescription data of schizophrenic outpatients treated between 2001 and 2004 were retrieved from the TBNHI database, which included outpatients who were diagnosed as having schizophrenia during the period from 1996 to 2001. Because the new health insurance policy may have had a lag effect on physicians' decision regarding SGA prescription, we used January 2004 as the timepoint to divide the data, which was 6 months after GB implementation. Thus, data from the 6-month period immediately after the GB implementation were included in the pre-GB period. Second-generation antipsychotics included in the study were clozapine, risperidone, olanzapine, quetiapine, ziprasidone, zotepin, and amisulpride. RESULTS: After January 2004, the proportion of SGA use in outpatient departments did not show an upward trend, as had been observed in the pre-GB period, which appeared at a staggering pace lasting for 12 months (p = 0.0004). Compared with medical centers, SGA expenditures in the psychiatric centers were less affected in the GB period (p < 0.0001). Compared to the private sector, the SGA expenditures in the public sector were less affected in the GB period (p < 0.019). CONCLUSION: We concluded that the GB implementation reduced SGA expenditures significantly. The extent of influence varied among hospitals (i.e., public versus private, medical versus psychiatric centers), which was most likely caused by financial factors.