Use of the RBANS to Evaluate Cognition in Patients with Schizophrenia and Metabolic Syndrome: a Meta-Analysis of Case-Control Studies.

Schizophrenia is associated with an increased risk of metabolic syndrome (MetS), which is an important risk factor for developing cognitive impairment in the general population. A few case-control studies have explored the relationship between MetS and cognitive deficits in individuals with schizophrenia but with inconsistent findings. This meta-analysis of case-control studies was carried out to explore the association between MetS and cognitive performance in patients with schizophrenia. Only case-control studies assessing the association of cognitive function and MetS in patients with schizophrenia were identified. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale. Six case-control studies (n = 992) comparing cognition between patients with schizophrenia with MetS (n = 426) and those without MetS (n = 566) using the RBANS were identified. Compared to patients with schizophrenia without MetS, patients with schizophrenia and MetS had significantly more impairments in RBANS total scores [standardized mean difference (SMD) = -0.26, 95% confidence interval (CI): -0.51 to -0.02; I2 = 72%; p = 0.03], immediate memory (SMD = -0.32, 95% CI: -0.54 to -0.10; I2 = 66%; p = 0.005), attention (SMD = -0.29, 95% CI: -0.56 to -0.02; I2 = 77%; p = 0.03), and delayed memory (SMD = -0.24, 95% CI: -0.46 to -0.03; I2 = 64%; p = 0.03). No group difference was found regarding visuospatial skills and language (p > 0.05). This meta-analysis found that schizophrenia patients with MetS had worse performance on certain cognitive tasks than non-MetS patients.

Adjunctive Fluvoxamine for Schizophrenia: A Meta-analysis of Randomized Double-Blind, Placebo-Controlled Trials.

BACKGROUND: This was a meta-analysis of double-blind, randomized controlled trials that examined the therapeutic effects and tolerability of adjunctive fluvoxamine versus placebo for schizophrenia. METHODS: The Review Manager, Version 5.3, was used to analyze data. RESULTS: Five double-blind randomized controlled trials (N = 284) covering 145 patients on adjunctive fluvoxamine and 139 patients on placebo were included in the analyses. Meta-analyses of total psychopathology, and negative, positive, and depressive symptoms did not show significant differences between the fluvoxamine and placebo groups. Two studies examined the effects of adjunctive fluvoxamine on cognitive functioning with mixed findings. Fluvoxamine was superior over placebo in lessening weight gain and metabolic abnormalities. Although fluvoxamine led to more discontinuation, no significant group differences were found regarding adverse drug reactions. CONCLUSIONS: There was inconsistent evidence for the therapeutic effect of adjunctive fluvoxamine on cognitive functions and preliminary evidence for alleviating metabolic syndrome caused by clozapine. More studies are needed to explore further the effectiveness of adjunctive fluvoxamine for schizophrenia.

Amantadine for Antipsychotic-Related Weight Gain: Meta-Analysis of Randomized Placebo-Controlled Trials.

PURPOSE: Weight gain associated with antipsychotics in schizophrenia has been an ongoing concern. This meta-analysis examined the efficacy and safety of amantadine as an adjunctive treatment of weight gain in schizophrenia by systematically searching and analyzing randomized controlled trials (RCTs). RCTs comparing adjunctive amantadine with placebo in adult patients with schizophrenia were included in the meta-analysis. METHODS: Two independent investigators searched the literature and extracted data. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio ± 95% confidence intervals were calculated. RESULTS: Five RCTs (n = 265) with double-blinded design lasting 8.2 ± 5.9 weeks were included in the analysis. Amantadine outperformed placebo regarding weight reduction with moderate effect size (trials, 3; n = 205; WMD -2.22 kg; P = 0.001, I = 45%). Amantadine also outperformed placebo at endpoint in the negative symptom (the Positive and Negative Syndrome Scale [PANSS] [1 trial] and the Scale for the Assessment of Negative Symptoms [1 trial]) scores (trials, 2; n = 84; SMD, -0.56; P = 0.01, I = 12%), but not in the PANSS total scores (trials, 2) (SMD, -0.31; P = 0.16, I = 0%) and the positive symptom (PANSS [1 trial] and the Scale for the Assessment of Positive Symptoms [1 trial]) scores (SMD, 0.13; P = 0.54, I = 0%). Except for insomnia (P = 0.007; number needed to harm, 6; 95% confidence interval, 4-16), all-cause discontinuation (risk ratio, 1.12; P = 0.54, I = 0%) and other adverse events were similar between the amantadine and placebo groups. CONCLUSIONS: According to this meta-analysis of 5 RCTs, adjunctive amantadine seems to be an effective option for attenuating antipsychotic-related weight gain in patients with schizophrenia. More RCTs are needed to inform clinical recommendations.

Efficacy and Safety of Adjunctive Aripiprazole in Schizophrenia: Meta-Analysis of Randomized Controlled Trials.

This meta-analysis of randomized controlled trials (RCTs) evaluated the efficacy and safety of adding aripiprazole to other antipsychotics in schizophrenia. A systematic computer search identified 55 RCTs including 4457 patients who were randomized to aripiprazole (14.0 ± 7.0 mg/d) versus placebo (18 RCTs) or open antipsychotic treatment (37 RCTs). Aripiprazole significantly outperformed the comparison interventions based on psychiatric scales: (1) total score in 43 RCTs (N = 3351) with a standardized mean difference (SMD) of -0.48 (95% confidence interval [CI], -0.68 to -0.28; P < 0.00001; I = 88%), (2) negative symptom score in 30 RCTs (N = 2294) with an SMD of -0.61(95% CI, -0.91 to -0.31; P < 0.00001; I = 91%), and (3) general psychopathology score in 13 RCTs (N = 1138) with a weighted mean difference (WMD) of -4.02 (95% CI, -7.23 to -0.81; P = 0.01; I = 99%), but not in positive symptoms in 29 RCTs (N = 2223) with a SMD of -0.01 (95% CI, 0.26 to 0.25; P = 0.95; I = 88%). Differences in total score based on psychiatric scales may be explained by the use of an antipsychotic for comparison rather than placebo in 31 RCTs with a nonblind design. Aripiprazole outperformed the comparison interventions for body weight in 9 RCTs (N = 505) with a WMD of -5.08 kg (95% CI, -7.14 to -3.02; P < 0.00001; I = 35%) and for body mass index (BMI) in 14 RCTs (N = 809) with a WMD of -1.78 (CI: -2.25 to -1.31; P < 0.00001; I = 54%). The BMI meta-regression analysis indicated aripiprazole's association with lower BMI was stronger in females. Adjunctive aripiprazole appears safe but better RCTs are needed to demonstrate efficacy. Chinese journals and scientific societies should encourage the publication of high-quality RCTs and require registration in a centralized Chinese database.

Adjunctive huperzine A for cognitive deficits in schizophrenia: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to examine the efficacy of huperzine A (HupA), an isolate of Huperzine serrata, in the treatment of cognitive deficits in schizophrenia spectrum disorders. METHODS: PubMed, PsycINFO, Embase, Cochrane Library, Cochrane Controlled Trials Register, WanFang, Chinese Biomedical, and China Journal Net databases were searched from inception to 15 July 2015 for randomized controlled trials (RCTs) in English or Chinese of HupA augmentation of antipsychotic drug therapy versus placebo or ongoing antipsychotic treatment. RESULTS: Twelve RCTs (n = 1117) lasting 11.7 ± 6.0 weeks met inclusion criteria. All had been conducted in China. HupA outperformed comparators on the following outcome measures: the Wechsler Memory Scale-Revised including memory quotient (weighted mean difference (WMD: 10.59; 95% confidence interval (CI): 5.65, 15.53; p < 0.0001); Wechsler Adult Intelligence Scale-Revised including verbal intelligence quotient (IQ), performance IQ, and full IQ (WMD: 3.97 to 5.66; 95%CI: 0.20, 8.58; p = 0.01 to 0.00001); Wisconsin Card Sorting Test including response administer and non-perseverative errors (WMD: -12.79 to -12.29; 95%CI: -23.70, -0.88; p = 0.03 to 0.003). In studies using the Positive and Negative Syndrome Scale (n = 7)/Brief Psychiatric Rating Scale (n = 1), the differences in total score were significant (standard mean difference: -0.77; 95%CI: -1.27, -0.27; p = 0.002). All-cause discontinuation (risk ratio: 0.67; 95%CI: 0.36, 1.24; p = 0.20) and adverse events were similar between groups. CONCLUSIONS: This review suggests that adjunctive HupA is an effective choice for improving cognitive function for patients with schizophrenia spectrum disorders. More well-designed RCTs are needed to further confirm HupA's efficacy. Copyright © 2016 John Wiley & Sons, Ltd.

Aripiprazole for Tourette's syndrome: a systematic review and meta-analysis.

OBJECTIVE: To review the efficacy and safety of aripiprazole (ARI) for Tourette's syndrome (TS). METHODS: This review included randomized controlled trials (RCTs) of children and adolescents (6-18 years) with TS comparing ARI monotherapy with another monotherapies in relation to clinical improvement and adverse events. RESULTS: Six RCTs with a total of 528 subjects (ARI treatment group: n = 253; control group: n = 275) met the inclusion criteria. These included two RCTs (n = 255) that compared ARI monotherapy with tiapride (TIA). Tic symptoms control assessed by Yale Global Tic Severity Scale (Standard Mean Difference (SMD) = -0.38 (Confidence Interval (CI) = -1.32 to 0.56); I(2) = 90%, P = 0.42) revealed no significant differences between the two groups. Extrapyramidal symptoms were significantly different when ARI (1.5%) was compared with haloperidol (HAL) (43.5%). No significant group differences were found in the rates of nausea/vomiting, dizziness, and dry mouth between ARI and TIA (RR = 0.57 to 1.00 (95%CI = 0.14-4.20); I(2) = 0% to 69%, P = 0.35 to 1.00). CONCLUSION: This review found that ARI has similar efficacy to TIA and HAL for TS, while extrapyramidal symptoms were significantly less with ARI than with HAL. ARI can be considered as an alternative treatment option for TS.

Adjunctive Electroconvulsive Therapy for Schizophrenia: A Meta-analysis of Randomized Rater-Masked Controlled Trials [RETRACTED].

OBJECTIVE: The aim of the study was to examine published randomized controlled trials (RCTs) for the efficacy and safety of adjunctive electroconvulsive therapy (ECT) when combined with antipsychotics (APs) versus AP therapy for schizophrenia and related disorders during the acute phase. METHODS: Two evaluators independently selected studies, extracted data, and conducted quality assessment and data synthesis. Standardized and weighted mean differences (SMD/WMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. RESULTS: Twenty-two RCTs (n = 1365, age = 36.9 years, male = 53%), including double-blind (8 RCTs) and rater-masked (14 RCTs) designs, were identified and analyzed. Adjunctive ECT was superior to AP therapy regarding (1) symptomatic improvement at last-observation endpoint (standardized mean difference, -0.67; P < 0.00001; I = 79%); (2) study-defined response (RR = 1.81, I = 0%, P < 0.00001, NNT = 4) and remission (RR = 2.05, I = 0%, P = 0.0004, NNT = 13); and (3) positive, negative, and general psychopathology subscores (weighted mean difference, -4.01 to -1.79; P = 0.005-0.0001). Results were similar in all preplanned subgroup analyses including Chinese (11 RCTs) versus non-Chinese (7 RCTs) origin, those with a Jadad score 3 or higher (12 RCTs) versus lower than 3 (6 RCTs), and those with clozapine (5 RCTs) versus those with non-clozapine treatments (13 RCTs). Compared with AP therapy, adjunctive ECT AP was significantly associated with more headache (RR = 2.72, P = 0.04, NNH = 5) and memory impairment (RR = 14.24, P = 0.01, NNH = 7). CONCLUSIONS: Adjunctive ECT seems to be an effective and safe option for schizophrenia and related disorders during acute phases but was associated with transient memory impairment and headaches.

Electroconvulsive Therapy Alone for Schizophrenia: A Meta-analysis of Randomized, Single-blind, Controlled Trials [RETRACTED].

PURPOSE: Electroconvulsive therapy (ECT) is a common treatment in practice for schizophrenia in most developing countries. This is a meta-analysis of the efficacy and safety of ECT alone versus antipsychotic (AP) monotherapy for schizophrenia using randomized, single-blind, controlled trial (RCT) data. METHODS: Two assessors independently extracted data. Standardized and weighted mean difference (SMD/WMD), odds ratios (ORs) ± 95% confidence intervals (CIs), and number needed to harm (NNH) were calculated by Review Manager Version 5.3 and the Comprehensive Meta-Analysis Version 2 software. RESULTS: Five RCTs (n = 365; age, 34.1 ± 4.7 years; percentage of male, 52.8 ± 9.5; range on the Jaded scale, 2-3) were identified and analyzed. Electroconvulsive therapy alone was superior to AP monotherapy with chlorpromazine, haloperidol, paliperidone, clozapine, and risperidone, respectively, regarding symptomatic improvement at last-observation end point (SMD, -0.84; P = 0.02; I = 89%). Improvement with ECT separated from AP as early as weeks 1 to 2 (SMD, -1.26; P = 0.01; I = 89%). Meta-analysis of the end point memory quotient of the Wechsler Memory Scale-Revised, Chinese version, revealed that the ECT alone group had poorer memory performance than the AP group (WMD, -9.34; P < 0.00001; I = 0%), but the difference lost its significance within 2 weeks after ECT (WMD, 0.09 to -6.54; P = 0.11-0.97; I = 0%). Compared with AP monotherapy, ECT was associated with more memory impairment (OR, 14.11; P = 0.004; NNH, 6) but with less akathisia (OR, 0.06; P = 0.0009; NNH, 6), tremor (OR, 0.08; P = 0.02; NNH, 7), and tachycardia (OR, 0.06; P = 0.006; NNH, 5). There were no significant differences in other adverse events and all-cause discontinuation. CONCLUSIONS: Electroconvulsive therapy alone could be an effective and safe treatment option for schizophrenia, with transient memory impairment and headache being the major side effects.

Metformin for Weight Gain and Metabolic Abnormalities Associated With Antipsychotic Treatment: Meta-Analysis of Randomized Placebo-Controlled Trials.

This meta-analysis examined the effectiveness and safety of metformin to prevent or treat weight gain and metabolic abnormalities associated with antipsychotic drugs. We systematically searched in both English- and Chinese-language databases for metformin randomized controlled clinical trials (RCTs) using placebo in patients taking antipsychotics. Twenty-one RCTs (11 published in English and 10 in Chinese) involving 1547 subjects (778 on metformin, 769 on placebo) were included in this meta-analysis. Metformin was significantly superior to placebo (standard mean differences, -0.69 to -0.51; P = 0.01-0.0001) in the primary outcome measures (body weight, body mass index, fasting glucose, fasting insulin, triglycerides, and total cholesterol). Metformin was significantly superior to placebo in some secondary outcome measures but not in others. Significantly higher frequencies of nausea/vomiting and diarrhea were found in the metformin group, but no differences were found in other adverse drug reactions. In the metformin group, the frequency of nausea/vomiting was 14%, and of diarrhea, 7%. Subgroup and sensitivity analyses demonstrated that primary outcomes were influenced by ethnicity, treatment style (intervention vs prevention), metformin dose, study duration, and mean age. Body weight standard mean difference was -0.91 (confidence interval [CI], -1.40 to -0.41) in 3 prevention RCTs in naive patients, -0.66 (CI, -1.02 to -0.30) in 5 intervention RCTs during the first year, and -0.50 (CI, -0.73 to -0.27) in 9 intervention RCTs in chronic patients. This meta-analysis suggests that adjunctive metformin is an effective, safe, and reasonable choice for antipsychotic-induced weight gain and metabolic abnormalities.

Adjunctive intranasal esketamine for major depressive disorder: A systematic review of randomized double-blind controlled-placebo studies.

OBJECTIVES: This is a meta-analysis of randomized double-blind controlled-placebo trials (RCTs) examining the effectiveness, tolerability, and safety of intranasal esketamine in treating major depressive disorder (MDD). METHODS: Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were calculated using RevMan version 5.3. RESULTS: Four RCTs with 7 active arms covering 708 patients with MDD on intranasal esketamine (n = 419) and placebo (n = 289) were included. Compared with placebo, adjunctive intranasal esketamine was associated with significantly greater study-defined response (RR=1.39, 95%CI: 1.18 to 1.64, P<0.0001) and remission (RR=1.42, 95%CI: 1.17 to 1.72, P = 0.0004) at endpoint assessment. Intranasal esketamine had greater study-defined response starting at 2 h (RR= 2.77, 95%CI: 1.62 to 4.76, P = 0.0002), peaking at 24 h (RR=5.42, 95%CI: 1.38 to 21.20, P = 0.02), and at least lasting for 28 days (RR=1.36, 95%CI: 1.16 to 1.58, P = 0.0001). Similarly, intranasal esketamine had significantly greater study-defined remission starting at 2 h (RR=7.71, 95%CI: 2.16 to 27.55, P = 0.002), peaking at 24 h (RR=6.87, 95%CI: 1.55 to 30.35, P = 0.01), and lasting for 28 days (RR=1.38, 95%CI: 1.11 to 1.72, P = 0.004). Intranasal esketamine had a significantly higher rate of discontinuation due to intolerability (RR=3.50, 95%CI: 1.38 to 8.86, P = 0.008). Discontinuation due to any reasons and inefficacy were similar between the two groups. CONCLUSION: Intranasal esketamine appears to have an ultra-rapid antidepressant effect for MDD, at least lasting for 28 days. The long-term therapeutic effect and safety of intranasal esketamine need to be further examined in large-scale RCTs.

Alcohol-related disorders in Beijing, China: prevalence, socio-demographic correlates, and unmet need for treatment.

BACKGROUND: The study aimed to determine the prevalence of alcohol use, episodic heavy drinking, and alcohol dependence and their socio-demographic correlates in Beijing, China. methods: A total of 5,926 subjects were randomly selected in Beijing and interviewed using the Composite International Diagnostic Interview (CIDI 1.0). Data on basic socio-demographic and current major medical conditions were also collected. RESULTS: The 12-month prevalence of alcohol use and episodic heavy drinking were 32.5 and 13.8%, respectively. The 12-month and lifetime prevalence of alcohol dependence were 1.7 and 4.3%, respectively. Age above 24 years, male sex, being married and employed, low education level (junior high school, primary school or illiterate), rural residence, and having comorbid psychiatric disorders were all significantly associated with a higher likelihood of alcohol-related disorders. Only 2.4% of the subjects with alcohol dependence were receiving treatment, and a mere 1.4% had sought treatment from mental health professionals. CONCLUSIONS: Nationwide surveys are urgently needed to further explore the prevalence of alcohol-related disorders in China.

Lifetime prevalence of suicidal ideation, suicide plans and attempts in rural and urban regions of Beijing, China.

OBJECTIVE: There has been no large-scale survey of suicide-related behaviours including suicidal ideations, plans and attempts in China involving both rural and urban areas and using standardized assessment tools. The aim of the present study was to determine the lifetime prevalence of suicide-related behaviour and its relationship with sociodemographic factors and psychiatric disorders in the rural and urban regions of Beijing, China. METHODS: A total of 5926 subjects were randomly selected in Beijing and interviewed using the Composite International Diagnostic Interview. Basic sociodemographic and clinical data and data on suicide-related behaviour were also collected. RESULTS: The overall lifetime prevalence estimates of suicidal ideation, plans and attempts were 2.3%, 1.4%, and 1.0%, respectively; the corresponding figures were 2.8%, 1.6%, and 1.3% in the rural sample, and 1.8%, 1.3%, and 0.9% in the urban sample. Age (>25 years), female sex, unmarried status, lower education level, lower (RMB2000 month(-1)) monthly income and presence of major medical disorders were significantly associated with increased risk of suicide-related behaviour. 36.2% of subjects with suicide-related behavior consulted a medical practitioner and 20.7% consulted a psychiatrist. CONCLUSIONS: The prevalence of lifetime suicide-related behaviour in Beijing is lower than in Western countries, but the low percentage of subjects treated for suicide-related behaviour indicates a major public health problem that should be addressed. National surveys are needed to further explore the prevalence of suicide-related behaviour in China.

The prevalence of insomnia, its sociodemographic and clinical correlates, and treatment in rural and urban regions of Beijing, China: a general population-based survey.

STUDY OBJECTIVES: To determine the prevalence of insomnia, its sociodemographic and clinical correlates, and treatment patterns in Chinese people. DESIGN: A total of 5,926 subjects were randomly selected in the urban and rural areas of Beijing and interviewed using standardized assessment tools. Basic sociodemographic and clinical data were also collected. SETTING: Urban and rural regions of Beijing municipality, China. Patients or Participants Adult residents older than 15 years. Interventions N/A. MEASUREMENTS AND RESULTS: The prevalence of at least one type of insomnia was 9.2%; the rates of difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA) were 7.0%, 8.0%, and 4.9%, respectively. Increased age (age >44 and 24 years in the urban and rural samples, respectively), female sex, married, divorced, separated, or widowed marital status; having a major medical condition; and suffering from a psychiatric disorder were risk factors for all types of insomnia in both the urban and rural samples. A low level of education (primary school or illiteracy) was significantly associated with a higher likelihood of all types of insomnia in the urban sample. Current smokers and current drinkers were less likely to report any type of insomnia in the rural sample. Unemployment was associated with DMS in the urban sample, while it was associated with DIS and DMS in the rural sample. Only 5.4% of the participants with any type of insomnia reported their symptoms to medical practitioners. In contrast, nearly one-third of the subjects with insomnia reported taking benzodiazepines as sleep-enhancing drugs. CONCLUSIONS: Nationwide epidemiologic surveys are needed to further explore the prevalence of insomnia in China. The low percentage of subjects treated for insomnia indicates a major public health problem that should be addressed. Strict controls on use of benzodiazepines are warranted.

Prevalence and socio-demographic correlates of schizophrenia in Beijing, China.

OBJECTIVE: There has been no large-scale survey of schizophrenia in China involving both rural and urban areas using standardized assessment tools and diagnostic criteria. This study aimed to determine the lifetime prevalence of schizophrenia and its socio-demographic correlates in Beijing, China. METHODS: A total of 5926 subjects were randomly selected in Beijing and interviewed using the Composite International Diagnostic Interview (CIDI 1.0). Basic socio-demographic and clinical data were collected during the interviews. RESULTS: The lifetime prevalence of schizophrenia was 0.49%, and 0.44% and 0.55% for men and women, respectively. Unmarried status, lower monthly income, urban abode and positive family history were associated with an increased risk of schizophrenia; 9.7% of the subjects with lifetime schizophrenia reported a history of suicide attempts. The percentage of subjects with schizophrenia who were receiving treatment and their preference to seek treatment from mental health professionals were 58% and 29%, respectively. CONCLUSIONS: National surveys are urgently needed to further explore the prevalence of schizophrenia in China. The low percentage of subjects treated for schizophrenia is a serious public health issue that should be addressed in the near future.

Memory Impairment Following Electroconvulsive Therapy in Chinese Patients with Schizophrenia: Meta-Analysis of Randomized Controlled Trials.

PURPOSE: To evaluate memory impairment associated with electroconvulsive therapy (ECT)-antipsychotic (AP) combination in comparison to AP monotherapy in schizophrenia. DESIGN AND METHODS: A systematic literature search of randomized controlled trial (RCTs) was performed. FINDINGS: Eleven RCTs that compared ECT-AP combination (n = 508) with AP monotherapy (n = 510) were analyzed. ECT-AP combination was associated with greater impairment than AP monotherapy in (1) endpoint memory quotient (MQ) of the Wechsler Memory Scale (WMS)-Revised at the end of the ECT course; and (2) picture recall, counting, recognition, and associative learning of the WMS. However, no group difference was found in MQ at 1 and 2 weeks post-ECT. PRACTICE IMPLICATIONS: The ECT-AP combination was associated with greater transient memory impairment compared to AP monotherapy.

Clozapine Augmentation With Antiepileptic Drugs for Treatment-Resistant Schizophrenia: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To meta-analyze randomized controlled trials (RCTs) for the efficacy and safety of adjunctive antiepileptic drugs (AEDs) to augment clozapine therapy for treatment-resistant schizophrenia. DATA SOURCES: The search included databases in English (PubMed, PsycINFO, Embase, and Cochrane Library databases and the Cochrane Controlled Trials Register) and in Chinese (China Journal Net [CJN], WanFang, and China Biology Medicine [CBM]) and references from retrieved articles. The databases were searched using dates inclusive from their onset until January 1, 2016, for terms reflecting (a) schizophrenia, (b) clozapine, and (c) adjunctive drugs. STUDY SELECTION: From 1,969 potentially relevant articles, 21 articles describing 22 RCTs were selected. DATA EXTRACTION: Two independent investigators extracted data for a random-effects meta-analysis and assessed the quality of the studies using risk of bias and the Jadad scale. Standard mean difference, risk ratio (RR) ± 95% confidence intervals (CIs), and the number needed to harm (NNH) were used. RESULTS: A total of 22 RCTs (N = 1,227) with 4 AEDs (topiramate [5 RCTs, n = 270], lamotrigine [8 RCTs, n = 299], sodium valproate [6 RCTs, n = 430], and magnesium valproate [3 RCTs, n = 228]) were analyzed. The means weighted by sample size were 12.1 weeks for treatment duration, 36.2 years for age, and 61% for male frequency. Significant superiority in total psychopathology was observed for topiramate (P < .0001), lamotrigine (P = .05), and sodium valproate (P = .002), compared to clozapine monotherapy. After removing outliers, the positive effect of sodium valproate remained, but the positive effect of lamotrigine disappeared (P = .40). Significantly improved efficacy in positive and general symptom severity was observed for topiramate (P = .04 and P = .02, respectively) and sodium valproate (P = .009 and P = .003, respectively). There were no significant differences regarding adverse drug reactions and all-cause discontinuations except for topiramate, which was associated with more all-cause discontinuations (RR = 1.99; 95% CI, 1.16 to 3.39; P = .01; I² = 0%; NNH = 7). CONCLUSIONS: Sodium valproate augmentation was efficacious and safe. Topiramate augmentation had a too-high discontinuation rate. High-quality RCTs are needed to inform clinical recommendations.

Adjunctive minocycline for schizophrenia: A meta-analysis of randomized controlled trials.

This study aimed to conduct a meta-analysis of the efficacy and safety of adjunctive minocycline for schizophrenia. Randomized controlled trials (RCTs) comparing adjunctive minocycline with placebo in patients with schizophrenia were included in the meta-analysis. Two independent investigators extracted and synthesized data. Standard mean differences (SMDs), risk ratio (RR) ±95% confidence intervals (CIs) and the number-needed-to-harm (NNH) were calculated. Eight RCTs with 548 schizophrenia patient including 286 (52.2%) patients on minocycline (171.9±31.2mg/day) and 262 (47.8%) on placebo completed 18.5±13.4 weeks of treatment. Meta-analyses of Positive and Negative Syndrome Scale (PANSS) (7 RCTs with 8 treatment arms)/Brief Psychiatric Rating Scale (BPRS) (1 RCT) total score [SMD: -0.64, (95%CI: -1.02, -0.27), P=0.0008; I2=74%], positive, negative and general symptom scores [SMD: -0.69 to -0.22 (95%CI: -0.98, -0.03), P=0.02-0.00001; I2=7-63%] revealed a significant superiority of adjunctive minocycline treatment over the placebo. There was no significant difference regarding neurocognitive function, discontinuation rate and adverse drug reactions between the two groups. This meta-analysis showed that adjunctive minocycline appears to be efficacious and safe for schizophrenia. Due to significant heterogeneity, future studies with a large sample size are needed to confirm these findings.

Serum concentrations of clozapine and norclozapine in the prediction of relapse of patients with schizophrenia.

Schizophrenic outpatients (n=102) whose condition had stabilized with clozapine (CLZ) therapy and were being maintained on CLZ were followed for 1 year. Clinical status and concentrations of serum clozapine (CLZ) and its metabolite norclozapine (NCLZ) were evaluated periodically or when relapse occurred. Relapse was defined as a significant exacerbation of psychotic symptoms or hospitalization. Thirty-three patients relapsed and 69 did not. Relapse patients displayed significantly lower serum concentrations of CLZ and a sum of CLZ and NCLZ at endpoint than non-relapses (CLZ: 162 ng/ml vs. 237 ng/ml, p<0.001; CLZ+NCLZ: 225 ng/ml vs. 301 ng/ml, p<0.001). When all subjects were pooled together, a significant inverse correlation was observed between percent increase in the total score on the Brief Psychiatric Rating Scale (BPRS) from baseline and serum levels of CLZ alone (r=0.404, p<0.001) and the sum of CLZ and NCLZ (r=0.364, p<0.001). Relapses and non-relapses were well separated by a threshold CLZ serum concentration of 200 ng/ml with a sensitivity of 73% and a specificity of 80%. The threshold value represented about a 40% lower serum CLZ level than concentration achieved in acute treatment. Survival analysis showed a similarity of the relapse risk over time defined by the CLZ serum threshold and by symptomatic criteria. These results suggest that effective relapse prevention may require maintenance of patients at CLZ serum concentrations above 200 ng/ml and above 60% of the acute-phase level during long-term maintenance treatment of schizophrenia.

Huperzine A for treatment of cognitive impairment in major depressive disorder: a systematic review of randomized controlled trials.

BACKGROUND: Acetylcholinesterase (AChE) inhibitors have been shown to be effective in treating cognitive impairment in animal models and in human subjects with major depressive disorder (MDD). Huperzine A (HupA), a Traditional Chinese Medicine derived from a genus of clubmosses known as Huperzineserrata, is a powerful AChE inhibitor that has been used as an adjunctive treatment for MDD, but no meta-analysis on HupA augmentation for MDD has yet been reported. AIM: Conduct a systematic review and meta-analysis of randomized controlled trials (RCTS) about HupA augmentation in the treatment of MDD to evaluate its efficacy and safety. METHODS: Two evaluators independently searched nine English-language and Chinese-language databases, selected relevant studies that met pre-determined inclusion criteria, extracted data about outcome and safety, and conducted quality assessments and data synthesis. RESULTS: Three low-quality RCTs (pooled n=238) from China were identified that compared monotherapy antidepressant treatment for depression versus combined treatment with antidepressants and HupA. Participants in the studies ranged from 16 to 60 years of age. The average duration of adjunctive antidepressant and HupA treatment in the studies was only 6.7 weeks. All three studies were open label and non-blinded, so their overall quality was judged as poor. Meta-analysis of the pooled sample found no significant difference in the improvement in depressive symptoms between the two groups (weighted mean difference: -1.90 (95%CI: -4.23, 0.44), p=0.11). However, the adjunctive HupA group did have significantly greater improvement than the antidepressant only group in cognitive functioning (as assessed by the Wisconsin Card Sorting Test and the Wechsler Memory Scale-Revised) and in quality of life. There was no significant difference in the incidence of adverse drug reactions between groups. CONCLUSIONS: The data available on the effectiveness and safety of adjunctive treatment using HupA in patients with MDD who are receiving antidepressants is insufficient to arrive at a definitive conclusion about its efficacy and safety. Pooling of the data from three low-quality RCTs from China found no advantage of adjunctive HupA in the treatment of depressive symptoms, but adjunctive treatment with HupA was associated with a faster resolution of the cognitive symptoms that frequently accompany MDD.