Dong-Bin Cai

Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials.

BACKGROUNDnDysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia.nnnMETHODSnStandardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed.nnnRESULTSnIncluded in the meta-analysis were eight RCTs (nxa0=xa0452) of 11.5xa0±xa02.6 weeks duration, with 229 patients on memantine (20xa0mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: -0.63 (95% CI -1.10 to -0.16), pxa0=xa00.009, I 2xa0=xa077%], but not in the total, positive and general symptoms [SMD: -0.46 to -0.08 (95% CI -0.93 to 0.22), pxa0=xa00.06-0.60, I 2xa0=xa00-74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI -0.24 to 0.32), pxa0=xa00.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: -0.41 (95% CI -0.72 to -0.11), pxa0=xa00.008, I 2xa0=xa047%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77-4.42), pxa0<xa00.00001, I 2xa0=xa022%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76-2.37), pxa0=xa00.31, I 2xa0=xa00%] and adverse drug reactions between the two groups.nnnCONCLUSIONSnThis meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.

N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials

This systematic review and meta‐analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N‐acetylcysteine (NAC), an antioxidant drug, in treating major depressive disorder (MDD), bipolar disorder, and schizophrenia.

Adjunctive raloxifene for postmenopausal women with schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials

OBJECTIVEnRaloxifene, a selective estrogen receptor modulator, has been used in treating postmenopausal women with schizophrenia with inconsistent results. This meta-analysis of randomized, double-blind, placebo-controlled trials (RCTs) examined its efficacy and safety for postmenopausal women with schizophrenia.nnnMETHODnStandardized mean differences (SMDs) and risk ratio (RR) together with their 95% confidence intervals (CIs) were calculated using the random effects model.nnnRESULTSnThe meta-analysis included 5 RCTs (nu202f=u202f240) comparing raloxifene (nu202f=u202f125, 60 or 120u202fmg/day) with placebo (nu202f=u202f115). Adjunctive raloxifene outperformed placebo with regard to the Positive and Negative Syndrome Scale (PANSS) total psychopathology [nu202f=u202f240, SMD:-0.64 (95%CI:-0.90, -0.37), Pu202f<u202f0.00001; I2u202f=u202f0%], positive symptoms [nu202f=u202f240, SMD:-0.49 (95%CI:-0.81, -0.16), Pu202f=u202f0.003; I2u202f=u202f29%], negative symptoms [nu202f=u202f240, SMD:-0.43 (95%CI:-0.68, -0.17), Pu202f=u202f0.001; I2u202f=u202f0%], and general psychopathology scores [nu202f=u202f240, SMD:-0.66 (95%CI:-0.92, -0.39), Pu202f<u202f0.00001; I2u202f=u202f0%]. Both groups had similar rates of adverse events and discontinuation (nu202f=u202f159, RR: 1.32 (95%CI: 0.65, 2.70), Pu202f=u202f0.44, I2u202f=u202f0%).nnnCONCLUSIONnAdjunctive raloxifene appears to be effective and safe in improving psychotic symptoms for postmenopausal women with schizophrenia. Review registration: CRD 42017059946.

Combination of Metformin and Lifestyle Intervention for Antipsychotic-Related Weight Gain: A Meta-Analysis of Randomized Controlled Trials

INTRODUCTIONnWeight gain is a common antipsychotic (AP)-related adverse drug reaction (ADR) that can increase the risk of cardiovascular diseases and premature mortality. This meta-analysis examined the efficacy and tolerability of combining metformin and lifestyle intervention for AP-related weight gain in schizophrenia.nnnMETHODSnRandomized controlled trials (RCTs) with meta-analyzable data were searched and retrieved by 2 independent investigators. RevMan software (version 5.3) was used to synthesize data, and to calculate the standardized or weighted mean differences and risk ratio with their 95% confidence intervals.nnnRESULTSnSix RCTs (n=732) were included and meta-analyzed. The metformin and lifestyle combination (MLC) group had significant reduction in weight and body mass index compared with the metformin group, lifestyle group, and placebo group. There was less frequent weight gain of≥7% in the MLC group over placebo. No other group differences in ADRs, total psychopathology, and all-cause discontinuation were found. In terms of study quality, 5 RCTs were open-labelled, 1 RCT had low risk allocation concealment, and 3 RCTs specifically described randomization methods.nnnCONCLUSIONnCombining metformin and lifestyle intervention shows significant effect in reducing AP-related weight gain. Higher quality and larger RCTs are needed to confirm these findings.Review registration: CRD42017059198.

Erythropoietin for Cognitive Deficits Associated with Schizophrenia, Bipolar Disorder, and Major Depression: A Systematic Review

INTRODUCTIONnThe purpose of this study is to systematically review the efficacy and safety of adjunctive erythropoietin (EPO) in treating cognitive deficits associated with schizophrenia, bipolar disorder, and major depression based on randomized controlled trials (RCTs).nnnMETHODSnTwo evaluators independently and systematically searched and selected studies, extracted data, and conducted quality assessment.nnnRESULTSnFour RCTs with 144 patients (71 in the EPO group and 73 in the placebo group) met the study entry criteria. Adjunctive EPO could improve schizophrenia-related cognitive performance. In patients with bipolar disorder, EPO could also enhance sustained attention, recognition of happy faces, and speed of complex information processing across learning, attention, and executive function when compared with placebo. In addition, EPO could enhance verbal recall, recognition, and memory in patients with major depression.nnnDISCUSSIONnThis preliminary study found that adjunctive EPO appears to be effective in treating cognitive deficits associated with schizophrenia, bipolar disorder, and major depression without major adverse effects observed. Further higher quality RCTs with larger samples are needed to confirm the findings.nnnREVIEW REGISTRATIONnCRD42017058094.

Adjunctive melatonin for tardive dyskinesia in patients with schizophrenia: A meta-analysis

Background Tardive dyskinesia (TD) is characterized by abnormal and involuntary movements. Importantly, TD could cause considerable personal suffering and social and physical disabilities. Aims This meta-analysis based on randomized controlled trials (RCTs) systematically assessed the therapeutic effect and tolerability of melatonin for TD in schizophrenia. Methods A computerized and systematical search of both Chinese (Wanfang Data, Chinese National Knowledge Infrastructure (CNKI), SINOMED) and English (PubMed, PsycINFO, Embase, Cochrane Library databases) databases, from their inception until June 8, 2017, was conducted by two independent authors. The severity of TD symptoms were the primary outcome measure and analyzed using a random effects model by the Review Manager (RevMan) Version 5.3. Quality evaluation of included RCTs was conducted using the Cochrane risk of bias and Jadad scale. The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system recommendation grading method was used to assess the overall quality level of meta-analytic outcomes. Results Four RCTs (n=130) were identified and analyzed. Three RCTs used double blind and 1 RCT used masked assessors using the Cochrane risk of bias, and 3 RCTs were rated as high quality based on Jadad scale. Compared with the control group, adjunctive melatonin was superior in reducing the severity of TD as measured by the Abnormal Involuntary Movement Scale (AIMS) (4 RCTs, n=130, weighted mean difference (WMD): -1.52 (95% confidence intervals (CI): -3.24, 0.20), p=0.08; I2=0%) although the improvement did not reach a significant level. The overall evidence quality of the improvement of TD symptoms, according to GRADE approach, was rated as “Low”. The data on the ADRs and cognitive effect were limited. Conclusions This meta-analysis shows that melatonin has potential for improving TD symptoms in schizophrenia. Future higher quality and larger RCTs are warranted to confirm the findings.

ECT augmentation of clozapine for clozapine-resistant schizophrenia: A meta-analysis of randomized controlled trials

Treatment-resistant schizophrenia (TRS) is common and debilitating. A subgroup of patients even has clozapine-resistant schizophrenia (CRS). We aimed to evaluate the efficacy and safety of electroconvulsive therapy (ECT) augmentation of clozapine for CRS. Systematic literature search of randomized controlled trials (RCTs) reporting on ECT augmentation of clozapine in CRS. Co-primary outcomes included symptomatic improvement at post-ECT assessment and study endpoint. Eighteen RCTs (nu202f=u202f1769) with 20 active treatment arms were identified and meta-analyzed. Adjunctive ECT was superior to clozapine regarding symptomatic improvement at post-ECT assessment (Standardized Mean Difference (SMD)u202f=u202f-0.88, 95% Confidence Interval (CI): -1.33 to -0.44; I2u202f=u202f86%, Pu202f=u202f0.0001) and endpoint assessment (SMD: -1.44, 95%CI: -2.05 to -0.84; I2u202f=u202f95%, Pu202f<u202f0.00001), separating as early as week 1-2 (SMDu202f=u202f-0.54, 95%CI: -0.88 to -0.20; I2u202f=u202f77%, Pu202f=u202f0.002). Adjunctive ECT was also superior regarding study-defined response at post-ECT assessment (53.6% vs. 25.4%, Risk Ratio (RR)u202f=u202f1.94, 95%CI: 1.59-2.36; I2u202f=u202f0%, Pu202f<u202f0.00001, number-needed-to-treat (NNT)u202f=u202f3, 95%CI: 3-5) and endpoint assessment (67.7% vs. 41.4%, RRu202f=u202f1.66, 95%CI: 1.38-1.99; I2u202f=u202f47%, Pu202f<u202f0.00001, NNTu202f=u202f4, 95%CI: 3-8), and remission at post-ECT assessment (13.3% vs. 3.7%, RRu202f=u202f3.28, 95%CI: 1.80-5.99; I2u202f=u202f0%, Pu202f=u202f0.0001, NNTu202f=u202f13, 95%CI: 6-100) and endpoint assessment (23.6% vs. 13.3%, RRu202f=u202f1.80, 95%CI: 1.39 to 2.35; I2u202f=u202f5%, Pu202f<u202f0.0001, NNTu202f=u202f14, 95%CI: 6-50). Patient-reported memory impairment (24.2% vs. 0%; RRu202f=u202f16.10 (95%CI: 4.53-57.26); I2u202f=u202f0%, Pu202f<u202f0.0001, number-needed-to-harm (NNH)u202f=u202f4, 95%CI: 2-14) and headache (14.5% vs 1.6%; RRu202f=u202f4.03 (95%CI: 1.54-10.56); I2u202f=u202f0%, Pu202f=u202f0.005, NNHu202f=u202f8, 95%CI: 4-50) occurred more frequently with adjunctive ECT. No significant group differences were found regarding discontinuation and other adverse effects. Despite increased frequency of self-reported memory impairment and headache, ECT augmentation of clozapine is a highly effective and relatively safe treatment for CRS.nnnREGISTRATION NUMBERnCRD42018089959.

Neurocognitive dysfunction in subjects at clinical high risk for psychosis: A meta-analysis

Findings of neurocognitive dysfunction in subjects at Clinical High Risk for Psychosis (CHR-P) have been controversial. This meta-analysis systematically examined studies of neurocognitive functions using the MATRICS Consensus Cognitive Battery (MCCB) in CHR-P. An independent literature search of both English and Chinese databases was conducted by two reviewers. Standardized mean difference (SMD) was calculated using a random effects model to evaluate the effect size of the meta-analytic results. Six case-control studies (nu202f=u202f396) comparing neurocognitive functions between CHR-P subjects (nu202f=u202f197) and healthy controls (nu202f=u202f199) using the MCCB were identified; 4 (66.7%) studies were rated as high quality. Compared to healthy controls, CHR-P subjects showed impairment with large effect size in overall cognition (nu202f=u202f128, SMDu202f=u202f-1.00, 95%CI: -1.38, -0.63, Pu202f<u202f0.00001; I2u202f=u202f2%), processing speed (SMDu202f=u202f-1.21) and attention/vigilance (SMDu202f=u202f-0.83), and with medium effect size in working memory (SMDu202f=u202f-0.76), reasoning and problem solving (SMDu202f=u202f-0.71), visual (SMDu202f=u202f-0.68) and verbal learning (SMDu202f=u202f-0.67). No significant difference between CHR-P subjects and controls was found regarding social cognition (SMDu202f=u202f-0.33, 95%CI: -0.76, 0.10, Pu202f=u202f0.14; I2u202f=u202f70%) with small effect size. Apart from social cognition, CHR-P subjects performed worse than healthy control in all MCCB cognitive domains, particularly in processing speed, attention/vigilance and working memory.

Short-term efficacy and tolerability of lurasidone in the treatment of acute schizophrenia: A meta-analysis of randomized controlled trials

BACKGROUNDnLurasidone, an azapirone derivative, is a novel second generation antipsychotic with potent binding affinity for dopamine D2, serotonin 5-HT2A, 5-HT7, 5-HT1A, and noradrenaline alpha2C receptors. This updated meta-analysis of randomized controlled trials (RCTs) examined the short-term efficacy and tolerability of lurasidone in the treatment of acute schizophrenia.nnnMETHODSnDouble-blinded RCTs reporting on the short-term effects of lurasidone were included. Standardized mean difference (SMD) with their 95% confidence interval (CI), and number needed to harm (NNH) were computed.nnnRESULTSnThe meta-analysis had 8 RCTs with 16 active arms that included 2373 patients with acute schizophrenia who were randomized to either lurasidone (20-160u202fmg/day; nu202f=u202f1570) or placebo (nu202f=u202f803) groups. Lurasidone was superior to placebo with regard to change in total psychopathology [SMD: -0.34, (95%CI: -0.48, -0.20), P<0.00001], positive symptoms [SMD: -0.47, (95%CI: -0.57, -0.36), P<0.00001], negative symptoms [SMD:-0.34, (95%CI: -0.45, -0.22), P<0.00001], and general psychopathology [SMD: -0.36, (95%CI: -0.48, -0.24), P<0.00001]. Results were consistent for total psychopathology in 11 out of the 13 subgroups. Lurasidone resulted in higher weight gain [SMD: 0.15, (95% CI: 0.06, 0.24), Pu202f=u202f0.001] and BMI [SMD: 0.17, (95%CI: 0.07, 0.28), Pu202f=u202f0.002] than placebo, but the differences were not clinically significant. Lurasidone group had less frequent inefficacy (NNHu202f=u202f14) and discontinuation due to any reason (NNHu202f=u202f17), but was associated with more frequent vomiting, akathisia, dystonia, parkinsonism, somnolence, dizziness, sedation, nausea, and weight gain of ≥7% of the initial weight (NNHu202f=u202f11-50).nnnCONCLUSIONnThis meta-analysis of 8 short-term studies supported the efficacy and safety of lurasidone in the acute phase of schizophrenia, particularly at the higher dose range of 80u202fmg/day.

Adjunctive Peony-Glycyrrhiza decoction for antipsychotic-induced hyperprolactinaemia: a meta-analysis of randomised controlled trials

Background Hyperprolactinaemia is a common adverse effect of antipsychotics (APs). The results of Peony-Glycyrrhiza decoction (PGD) as a potentially useful adjunctive treatment for hyperprolactinaemia are inconsistent. Aim This meta-analysis of randomised controlled trials (RCTs) examined the efficacy and safety of adjunctive PGD therapy for AP-induced hyperprolactinaemia. Methods English (PubMed, Embase, Cochrane Library, PsycINFO) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data) databases were systematically searched up to 10 June 2018. The inclusion criteria were based on PICOS—Participants: adult patients with schizophrenia; Intervention: PGD plus APs; Comparison: APs plus placebo or AP monotherapy; Outcomes: efficacy and safety; Study design: RCTs. The weighted mean difference (WMD) and risk ratio (RR) along with their 95% CIs were calculated using Review Manager (RevMan) V.5.3 software. Results Five RCTs (n=450) were included and analysed. Two RCTs (n=140) were double-blind and four RCTs (n=409) reported ‘random’ assignment with specific description. The PGD group showed a significantly lower serum prolactin level at endpoint than the control group (n=380, WMD: −32.69 u2009ng/mL (95% u2009CI −41.66 to 23.72), p<0.00001, I 2 =97%). Similarly, the superiority of PGD over the control groups was also found in the improvement of hyperprolactinaemia-related symptoms. No difference was found in the improvement of psychiatric symptoms assessed by the Positive and Negative Syndrome Scale (n=403, WMD: −0.62 (95% CI −2.38 to 1.15), p=0.49, I 2 =0%). There were similar rates of all-cause discontinuation (n=330, RR 0.93 (95% CI 0.63 to 1.37), p=0.71, I 2 =0%) and adverse drug reactions between the two groups. According to the Grading of Recommendations Assessment, Development and Evaluation approach, the level of evidence of primary and secondary outcomes ranged from ‘very low’ (14.3%), ‘low’ (42.8%), ‘moderate’ (14.3%), to ‘high’ (28.6%). Conclusions Current evidence supports the adjunctive use of PGD to suppress elevated prolactin and improve prolactin-induced symptoms without significant adverse events in adult patients with AP-induced hyperprolactinaemia. High-quality RCTs with longer duration are needed to confirm these findings. Trial registration number 42016037017.