109 Comparative Efficacy and Tolerability of Lurasidone Versus Other Oral Atypical Antipsychotics for Pediatric Schizophrenia: A Network Meta Analysis

AbstractStudy ObjectiveThis analysis assessed the relative efficacy and tolerability of lurasidone versus other atypical antipsychotics in the treatment of pediatricschizophrenia.MethodsA systematic literature review identified 13 randomized-controlled trials for the treatment of pediatric schizophrenia. A Bayesian network meta-analysis compared the efficacy and tolerability of the following atypical antipsychotics: aripiprazole, asenapine, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, andziprasidone. Patients were 7-17 years old and trial duration ranged from 6-12 weeks. Outcomes included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), weight gain, all-cause treatment discontinuation, and extrapyramidal symptoms. Results from the fixed effect models were reported as mean differences for continuous outcomes and odds ratios for binary outcomes; each with a 95% credible interval.ResultsLurasidone had significantly greater improvement compared with placebo for PANSS (-7.95 [-11.76, -4.16]) and CGI-S (-0.44 [-0.67, -0.22]), but did not differ from comparators. The differences in weight gain for lurasidone relative to comparators were as follows: clozapine (-3.81kg [-8.03, 0.42]), olanzapine (-3.62kg [-4.84, -2.41]), quetiapine (-2.13kg [-3.20, -1.08]), risperidone (-1.16kg [-2.14, -0.17]), asenapine (-0.98kg [-1.71, -0.24]), paliperidone (-0.85kg [-1.57, -0.14]), aripiprazole (-0.15kg [-0.88, 0.58]), and ziprasidone (0.38kg [-0.49, 1.24]); all were statistically significant except for clozapine, aripiprazole, and ziprasidone. Rates of all-cause discontinuation andextrapyramidal symptoms were similar for lurasidone and comparators, except aripiprazole and paliperidone, which had higher rates of all-cause discontinuation.ConclusionsIn this network meta-analysis of atypical antipsychotics for the treatment of adolescent schizophrenia, lurasidone was associated with similar efficacy, but less weight gain than active comparators.Funding AcknowledgementsThis study was funded by Sunovion Pharmaceuticals Inc.

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Lurasidone compared to other atypical antipsychotic monotherapies for adolescent schizophrenia: a systematic literature review and network meta-analysis

European Child & Adolescent Psychiatry ◽

10.1007/s00787-019-01425-2 ◽

2019 ◽

Vol 29 (9) ◽

pp. 1195-1205

Author(s):

Celso Arango ◽

Daisy Ng-Mak ◽

Elaine Finn ◽

Aidan Byrne ◽

Antony Loebel

Keyword(s):

Weight Gain ◽

Literature Review ◽

Atypical Antipsychotic ◽

Systematic Literature Review ◽

Atypical Antipsychotics ◽

Meta Analysis ◽

Similar Efficacy ◽

Binary Outcomes ◽

Schizophrenia Spectrum Disorders ◽

Credible Intervals

AbstractThis network meta-analysis assessed the efficacy and tolerability of lurasidone versus other oral atypical antipsychotic monotherapies in adolescent schizophrenia. A systematic literature review identified 13 randomized controlled trials of antipsychotics in adolescents with schizophrenia-spectrum disorders. A Bayesian network meta-analysis compared lurasidone to aripiprazole, asenapine, clozapine, olanzapine, paliperidone extended-release (ER), quetiapine, risperidone, and ziprasidone. Outcomes included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), weight gain, all-cause discontinuation, extrapyramidal symptoms (EPS), and akathisia. Results were reported as median differences for continuous outcomes and odds ratios (ORs) for binary outcomes, along with 95% credible intervals (95% CrI). Lurasidone was significantly more efficacious than placebo on the PANSS (− 7.95, 95% CrI − 11.76 to − 4.16) and CGI-S (− 0.44, 95% CrI − 0.67 to − 0.22) scores. Lurasidone was associated with similar weight gain to placebo and statistically significantly less weight gain versus olanzapine (− 3.62 kg, 95% CrI − 4.84 kg to − 2.41 kg), quetiapine (− 2.13 kg, 95% CrI − 3.20 kg to − 1.08 kg), risperidone (− 1.16 kg, 95% CrI − 2.14 kg to − 0.17 kg), asenapine (− 0.98 kg, 95% CrI − 1.71 kg to − 0.24 kg), and paliperidone ER (− 0.85 kg, 95% CrI − 1.57 kg to − 0.14 kg). The odds of all-cause discontinuation were significantly lower for lurasidone than aripiprazole (OR = 0.28, 95% CrI 0.10–0.76) and paliperidone ER (OR = 0.25, 95% CrI 0.08–0.81) and comparable to other antipsychotics. Rates of EPS and akathisia were similar for lurasidone and other atypical antipsychotics. In this network meta-analysis of atypical antipsychotics in adolescent schizophrenia, lurasidone was associated with similar efficacy, less weight gain, and lower risk of all-cause discontinuation compared to other oral atypical antipsychotics.

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Bayesian Meta-analysis of Multiple Continuous Treatments with Individual Participant-Level Data: An Application to Antipsychotic Drugs

Medical Decision Making ◽

10.1177/0272989x19856884 ◽

2019 ◽

Vol 39 (5) ◽

pp. 583-592 ◽

Cited By ~ 1

Author(s):

Jacob Spertus ◽

Marcela Horvitz-Lennon ◽

Sharon-Lise T. Normand

Keyword(s):

Clinical Trials ◽

Weight Gain ◽

Dose Response ◽

Meta Analysis ◽

Credible Interval ◽

Continuous Treatment ◽

Sample Population ◽

Response Curves ◽

Excessive Weight Gain ◽

Excessive Weight

Modeling dose-response relationships of drugs is essential to understanding their safety effects on patients under realistic circumstances. While intention-to-treat analyses of clinical trials provide the effect of assignment to a particular drug and dose, they do not capture observed exposure after factoring in nonadherence and dropout. We develop a Bayesian method to flexibly model the dose-response relationships of binary outcomes with continuous treatment, permitting multiple evidence sources, treatment effect heterogeneity, and nonlinear dose-response curves. In an application, we examine the risk of excessive weight gain for patients with schizophrenia treated with the second-generation antipsychotics paliperidone, risperidone, or olanzapine in 14 clinical trials. We define exposure as total cumulative dose (daily dose × duration) and convert to units equivalent to 100 mg of olanzapine (OLZ doses). Averaging over the sample population of 5891 subjects, the median dose ranged from 0 (placebo randomized participants) to 6.4 OLZ doses (paliperidone randomized participants). We found paliperidone to be least likely to cause excessive weight gain across a range of doses. Compared with 0 OLZ doses, at 5.0 OLZ doses, olanzapine subjects had a 15.6% (95% credible interval: 6.7, 27.1) excess risk of weight gain; corresponding estimates for paliperidone and risperidone were 3.2% (1.5, 5.2) and 14.9% (0.0, 38.7), respectively. Moreover, compared with nonblack participants, black participants had a 6.8% (1.0, 12.4) greater risk of excessive weight gain at 10.0 OLZ doses of paliperidone. Nevertheless, our findings suggest that paliperidone is safer in terms of weight gain risk than risperidone or olanzapine for all participants at low to moderate cumulative OLZ doses.

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Comparative Efficacy and Safety of Antipsychotic Drugs for Tic Disorders: A Systematic Review and Bayesian Network Meta-Analysis

Pharmacopsychiatry ◽

10.1055/s-0043-124872 ◽

2018 ◽

Vol 52 (01) ◽

pp. 07-15 ◽

Cited By ~ 6

Author(s):

Chunsong Yang ◽

Zilong Hao ◽

Ling-Li Zhang ◽

Cai-Rong Zhu ◽

Ping Zhu ◽

...

Keyword(s):

Symptom Score ◽

Atypical Antipsychotics ◽

Antipsychotic Drugs ◽

Meta Analysis ◽

Tic Disorders ◽

Cochrane Library ◽

Efficacy And Safety ◽

Randomized Controlled ◽

Mean Differences ◽

Robust Evidence

Abstract Objective The purpose of this study was to evaluate the efficacy and safety of antipsychotic drugs for tic disorders (TDs) in a network meta-analysis. Methods PubMed, Embase, Cochrane Library, and 4 Chinese databases were searched. Randomized controlled trials (RCTs) evaluating the efficacy of antipsychotic drugs for TDs were included. Results Sixty RCTs were included. In terms of tic symptom score, compared with placebo, haloperidol, risperidone, aripiprazole, quetiapine, olanzapine, and ziprasidone can significantly improve tic symptom score (standardized mean differences [SMD] ranged from −12.32 to −3.20). Quetiapine was superior to haloperidol, pimozide, risperidone, tiapride, aripiprazole, and penfluridol for improving tic symptom score (SMD ranged from −28.24 to −7.59). Compared with tiapride, aripiprazole could significantly improve tic symptom score (SMD=−4.27). Compared with all other drugs, penfluridol was not effective. Atypical antipsychotics were generally well tolerated. Conclusions Atypical antipsychotics (risperidone and aripiprazole) appear to be the most robust evidence-based options for the treatment of TDs. Quetiapine may be a promising therapy. Ziprasidone and olanzapine are also effective, but the evidence is lacking. Further high-quality directly comparing different pharmacological treatment studies are justified.

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High molecular weight Intraarticular hyaluronic acid for the treatment of knee osteoarthritis: a network meta-analysis

BMC Musculoskeletal Disorders ◽

10.1186/s12891-020-03729-w ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Charles D. Hummer ◽

Felix Angst ◽

Wilson Ngai ◽

Craig Whittington ◽

Sophie S. Yoon ◽

...

Keyword(s):

Molecular Weight ◽

Hyaluronic Acid ◽

Knee Osteoarthritis ◽

Treated Patient ◽

Meta Analysis ◽

Credible Interval ◽

Pain Scale ◽

Womac Pain ◽

Knee Oa ◽

Mean Differences

Abstract Background The 2013 American Academy of Orthopaedic Surgeons (AAOS) guidelines made strong recommendations against intraarticular hyaluronic acid (IAHA) for patients with knee osteoarthritis (OA), as evidence supporting improvements in pain did not meet the minimal clinically important improvement (MCII) threshold. However, there may be important distinctions based on IAHA molecular weight (MW). Hence our objective was to evaluate the efficacy of IAHAs in knee OA based on molecular weight. Methods Randomized controlled trials were searched within MEDLINE, Embase, and CENTRAL and selected based on AAOS criteria. A pain measure hierarchy and longest follow-up were used to select one effect size from each trial. Mean differences between interventions were converted to standardized mean differences (SMDs) and incorporated into a random-effects Bayesian network meta-analysis. High MW (HMW) was defined as ≥6000 kDa, and low MW (LMW) as < 750 kDa. Results HMW IAHA was associated with a statistically significant and possibly clinically significant improvement in pain (SMD − 0.57 (95% credible interval [Crl]: − 1.04, − 0.11), exceeding the − 0.50 MCII threshold. LMW IAHA had a lesser, non-significant improvement (− 0.23, 95% Crl: − 0.67, 0.20). Back-transforming SMDs to the WOMAC pain scale indicated a 14.65 (95% CI: 13.93, 15.62) point improvement over IA placebo, substantially better than the 8.3 AAOS MCII threshold. Conclusions Unlike LMW IAHA, HMW IAHA exceeded the MCII threshold for pain relief, suggesting that improvements can be subjectively perceived by the treated patient. Amalgamation of LMW and HMW may have blurred the benefits of IAHA in the past, leading to negative recommendations. Differentiation according to MW offers refined insight for treatment with IAHA.

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A Systematic Review and Meta-Analysis of the Efficacy of Evening Primrose Oil for Mastalgia Treatment

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18126295 ◽

2021 ◽

Vol 18 (12) ◽

pp. 6295

Author(s):

Lina Liana Ahmad Adni ◽

Mohd Noor Norhayati ◽

Ritzzaleena Rosli Mohd Rosli ◽

Juliawati Muhammad

Keyword(s):

Vitamin E ◽

Meta Analysis ◽

Similar Efficacy ◽

Breast Pain ◽

Evening Primrose Oil ◽

Evening Primrose ◽

Number Of Patients ◽

Significant Impairment ◽

Mean Differences ◽

Topical Nsaids

Mastalgia, or breast pain, is common among women which can lead to significant impairment in daily living. Hence, finding an effective treatment that can alleviate the symptom is very important. Thus, we carry out this study to determine the efficacy of evening primrose oil (EPO) for mastalgia treatment in women. The review included published randomised clinical trials that evaluated EPO used for treating mastalgia against a placebo or other treatments, irrespective of the blinding procedure, publication status, or sample size. Two independent authors screened the titles and abstracts of the identified trials; full texts of relevant trials were evaluated for eligibility. Two reviewers independently extracted data on the methods, interventions, outcomes, and risk of bias. The random-effects model was used for estimating the risk ratios and mean differences with 95% confidence intervals. Thirteen trials with 1752 randomised patients were included. The results showed that EPO has no difference to reduce breast pain compared to topical NSAIDS, danazol, or vitamin E. The number of patients who achieved pain relief was no different compared to the placebo or other treatments. The EPO does not increase adverse events, such as nausea, abdominal bloating, headache or giddiness, increase weight gain, and altered taste compared to a placebo or other treatments. EPO is a safe medication with similar efficacy for pain control in women with mastalgia compared to a placebo, topical NSAIDS, danazol, or vitamin E.

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Efficacy and tolerability of atypical antipsychotics for acute bipolar depression: a network meta-analysis

BMC Psychiatry ◽

10.1186/s12888-021-03220-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Aditi Kadakia ◽

Carole Dembek ◽

Vincent Heller ◽

Rajpal Singh ◽

Jennifer Uyei ◽

...

Keyword(s):

Weight Gain ◽

Atypical Antipsychotics ◽

Rating Scale ◽

Bipolar Depression ◽

Meta Analysis ◽

Number Needed To Treat ◽

Continuous Variables ◽

Short Term ◽

Global Improvement ◽

Similar Weight

Abstract Background While clinical trial evidence has firmly established the efficacy of several atypical antipsychotics (AAPs) for treating bipolar depression, no randomized controlled trials (RCT’s) comparing AAPs have been conducted. This Bayesian network meta-analysis (NMA) compared the relative efficacy and tolerability of AAP monotherapy in adults with bipolar depression. Methods Efficacy measures included change in Montgomery Åsberg Depression Rating Scale (MADRS), Clinical Global Improvement – Bipolar Disorder (CGI-BP), response, and remission. Multiple tolerability outcomes were examined. Results from random effects models were reported as difference in change from baseline for continuous variables or odds ratios for dichotomous variables. Treatments were ranked using the surface under the curve cumulative ranking probabilities. Number needed to treat (NNT) and harm (NNH) were calculated. Results Eighteen RCT’s met inclusion criteria of the systematic literature review. On change in MADRS, lurasidone (− 4.71 [95% Crl − 6.98, − 2.41]), quetiapine (− 4.80 [− 5.93, − 3.72]), olanzapine (− 4.57 [− 5.92, − 3.20]), and cariprazine (− 2.29 [− 3.47, − 1.09]) were more efficacious than placebo. Lurasidone was associated with a significantly greater odds of response (≥50% improvement in MADRS) compared to cariprazine (1.78 [95% Crl 1.08, 2.77]), aripiprazole (2.38 [1.38, 3.85]), and ziprasidone (2.47 [1.41, 3.98]), but was similar to olanzapine (1.68 [0.99,2.65]) and quetiapine (1.25 [0.78, 1.90]). For change in CGI-BP-S-overall score, lurasidone was significantly better than cariprazine (− 0.38 [95% Crl − 0.66,-0.10]) and ziprasidone (− 0.58 [− 0.91,-0.26]), but similar to quetiapine (− 0.08 [− 0.36, 0.19])and olanzapine (− 0.04 [− 1.41, 1.46]). Lurasidone (0.34 kg [95% Crl − 0.22, 0.89]) and aripiprazole (0.20 kg [− 0.59, 1.00]) had a similar weight change compared to placebo, but olanzapine (2.88 kg [2.40, 3.36]), quetiapine (1.17 kg [0.84, 1.49]), and cariprazine (0.65 kg [0.34, 0.96]) were associated with greater weight gain. The NNT for response was the lowest for lurasidone (NNT = 5) followed by quetiapine (NNT = 6), olanzapine (NNT = 10) and cariprazine (NNT = 12). Conclusions In this NMA in adults with bipolar depression, which evaluated change in depressive symptoms (assessed by MADRS) across short-term trials, the largest improvement versus placebo was observed for lurasidone, olanzapine and quetiapine with cariprazine, showing a smaller treatment effect. Aripiprazole and ziprasidone were ineffective for the treatment of bipolar depression. Improvement in CGI-BP-S score for lurasidone was larger than cariprazine and ziprasidone but similar to quetiapine and olanzapine. Based on short term studies lurasidone and aripiprazole had similar weight gain compared to placebo.

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Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials

Pharmacopsychiatry ◽

10.1055/a-0914-3260 ◽

2019 ◽

Vol 53 (01) ◽

pp. 5-13

Author(s):

Wei Zheng ◽

Xian-Bin Li ◽

Zhan-Ming Shi ◽

Xin-Hu Yang ◽

Dong-Bin Cai ◽

...

Keyword(s):

Weight Gain ◽

Negative Symptoms ◽

Meta Analysis ◽

Antipsychotic Treatment ◽

Controlled Trials ◽

Double Blind ◽

Jadad Scale ◽

Mean Differences ◽

Double Blind Design

Abstract Background Results of previous studies on the safety and efficacy of adjunctive reboxetine for schizophrenia have been inconsistent. Aim The aim of this study was to examine the efficacy and tolerability of reboxetine as an adjunct medication to antipsychotic treatment in a meta-analysis of randomized controlled trials (RCTs). Methods Two independent investigators extracted data for a random effects meta-analysis and assessed the quality of studies using risk of bias and the Jadad scale. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio (RR)±95% confidence intervals (CIs) were calculated. Results Nine RCTs (n=630) with double-blind design were identified. Reboxetine outperformed placebo in improving negative (9 RCTs, n=602, SMD: −0.47 [95% CI: −0.87, −0.07], p=0.02; I2=82%), but not the overall, positive, and general psychopathology scores. The significant therapeutic effect on negative symptoms disappeared in the sensitivity analysis after removing an outlying study and in 50% (6/12) of the subgroup analyses. Reboxetine outperformed placebo in reducing weight (3 RCTs, n=186, WMD: −3.83 kg, p=0.04; I2=92%) and body mass index (WMD: −2.23 kg/m2, p=0.04; I2=95%). Reboxetine caused dry mouth but was associated with less weight gain overall and weight gain of ≥7% of the initial weight. All-cause discontinuation and other adverse events were similar between reboxetine and placebo. Conclusion Adjunctive reboxetine could be useful for attenuating antipsychotic-induced weight gain, but it was not effective in treating psychopathology including negative symptoms in schizophrenia.

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Thrombocytopenia Is Associated with COVID-19 Severity and Outcome: An Updated Meta-Analysis of 5637 Patients with Multiple Outcomes

Laboratory Medicine ◽

10.1093/labmed/lmaa067 ◽

2020 ◽

Vol 52 (1) ◽

pp. 10-15

Author(s):

Xiaolong Zong ◽

Yajun Gu ◽

Hongjian Yu ◽

Zhenyu Li ◽

Yuliang Wang

Keyword(s):

Distress Syndrome ◽

Meta Analysis ◽

Binary Outcomes ◽

Severe Illness ◽

Multiple Outcomes ◽

Weighted Mean ◽

Data Synthesis ◽

Platelet Number ◽

Mean Differences ◽

Poor Outcomes

Abstract The COVID-19 pandemic is persistent worldwide. A prior meta-analysis suggested the association of thrombocytopenia (TCP) with more severe COVID-19 illness and high mortality. Considering newly published studies, we updated the previous meta-analysis to confirm and explain the association of TCP with COVID-19 severity and multiple outcomes. Twenty-four studies with 5637 patients with COVID-19 were included in this study. The weighted incidence of TCP in COVID-19 was 12.4% (95% confidence interval [CI], 7.9%–17.7%). Data synthesis showed that the platelet number was lower in patients with either more severe illness or poor outcomes and even lower in nonsurvivors, with weighted mean differences of −24.56 × 109/L, −22.48 × 109/L, and −49.02 × 109/L, respectively. The meta-analysis of binary outcomes (with and without TCP) indicated the association between TCP and 3-fold enhanced risk of a composite outcome of intensive care unit admission, progression to acute respiratory distress syndrome, and mortality (odds ratio [OR], 3.49; 95% CI, 1.57–7.78). Subgroup analysis by endpoint events suggested TCP to be significantly associated with mortality (OR, 7.37; 95% CI, 2.08–26.14). Overall, the present comprehensive meta-analysis indicated that approximately 12% of hospitalized patients with COVID-19 have TCP, which also represents a sign of more severe illness and poor outcomes.

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Effect of adjunctive ranitidine for antipsychotic-induced weight gain: A systematic review of randomized placebo-controlled trials

Journal of International Medical Research ◽

10.1177/0300060517716783 ◽

2017 ◽

Vol 46 (1) ◽

pp. 22-32 ◽

Cited By ~ 8

Author(s):

Xiao-Jing Gu ◽

Rui Chen ◽

Chen-Hui Sun ◽

Wei Zheng ◽

Xin-Hu Yang ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Negative Symptoms ◽

Case Reports ◽

Meta Analysis ◽

Control Group ◽

Controlled Trials ◽

Syndrome Scale ◽

Meta Analyses ◽

Negative Syndrome

This study was a meta-analysis of randomized controlled trials (RCTs) of ranitidine as an adjunct for antipsychotic-induced weight gain in patients with schizophrenia. RCTs reporting weight gain or metabolic side effects in patients with schizophrenia were included. Case reports/series, non-randomized or observational studies, reviews, and meta-analyses were excluded. The primary outcome measures were body mass index (BMI) (kg/m2) and body weight (kg). Four RCTs with five study arms were identified and analyzed. Compared with the control group, adjunctive ranitidine was associated with marginally significant reductions in BMI and body weight. After removing an outlier study for BMI, the effect of ranitidine remained significant. Adjunctive ranitidine outperformed the placebo in the negative symptom score of the Positive and Negative Syndrome Scale. Although ranitidine was associated with less frequent drowsiness, other adverse events were similar between the two groups. Adjunctive ranitidine appears to be an effective and safe option for reducing antipsychotic-induced weight gain and improving negative symptoms in patients with schizophrenia. Larger RCTs are warranted to confirm these findings. Trial registration PROSPERO: CRD42016039735

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

Pharmacopsychiatry ◽

10.1055/s-0044-101466 ◽

2018 ◽

Vol 52 (01) ◽

pp. 24-31 ◽

Cited By ~ 8

Author(s):

Wei Zheng ◽

Qing-E Zhang ◽

Dong-Bin Cai ◽

Xin-Hu Yang ◽

Gabor Ungvari ◽

...

Keyword(s):

Weight Gain ◽

Randomized Controlled Trials ◽

Lifestyle Intervention ◽

Meta Analysis ◽

Premature Mortality ◽

Allocation Concealment ◽

Controlled Trials ◽

Risk Allocation ◽

Randomized Controlled ◽

Mean Differences

Abstract Introduction Weight 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. Methods Randomized 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. Results Six 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. Conclusion Combining 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

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