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Adjunctive aripiprazole for antipsychotic-related hyperprolactinaemia in patients with first-episode schizophrenia: a meta-analysis
  1. Wei Zheng1,
  2. Dong-Bin Cai2,
  3. Xin-Hu Yang1,
  4. Wei Zheng3,
  5. Gabor S Ungvari4,5,
  6. Chee H Ng6,
  7. Zhan-Ming Shi7,
  8. Mei-Ling Hu8,
  9. Yu-Ping Ning1 and
  10. Yu-Tao Xiang9,10
  1. 1The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou Huiai Hospital, Guangzhou, China
  2. 2Shenzhen Traditional Chinese Medicine, Shenzhen, China
  3. 3School of Medicine, Xiamen University, Xiamen, China
  4. 4University of Notre Dame Australia, Fremantle, Western Australia, Australia
  5. 5Division of Psychiatry, School of Medicine, University of Western Australia, Perth, Western Australia, Australia
  6. 6Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia
  7. 7Chongqing Jiangbei Mental Health Center, Chongqing, China
  8. 8Shangrao Fifth People's Hospital, Shangrao, China
  9. 9Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao SAR, China
  10. 10Center for Cognition and Brain Sciences, University of Macau, Macao SAR, China
  1. Correspondence to Dr Wei Zheng; zhengwei0702{at}; Professor Yu-Tao Xiang; ytxiang{at}


Background Hyperprolactinaemia is a common antipsychotic (AP)-induced adverse effect, particularly in female patients.

Aims This meta-analysis examined the efficacy and safety of adjunctive aripiprazole in preventing AP-related hyperprolactinaemia in patients with first-episode schizophrenia.

Methods PubMed, PsycINFO, EMBASE, Cochrane Library, WanFang and China Journal Net databases were searched to identify eligible randomised controlled trials (RCTs). Primary outcomes were the reductions of serum prolactin level and prolactin-related symptoms. Data were independently extracted by two reviewers and analysed using RevMan (V.5.3). Weighted/standardised mean differences (WMDs/SMDs)±95% CIs were reported.

Results In the five RCTs (n=400), the adjunctive aripiprazole (n=197) and the control groups (n=203) with a mean of 11.2 weeks of treatment duration were compared. The aripiprazole group had a significantly lower endpoint serum prolactin level in all patients (five RCTs, n=385; WMD: −50.43 ng/mL (95% CI: −75.05 to −25.81), p<0.00001; I2=99%), female patients (two RCTs, n=186; WMD: −22.58 ng/mL (95% CI: −25.67 to −19.49), p<0.00001; I2=0%) and male patients (two RCTs, n=127; WMD: −68.80 ng/mL (95% CI: −100.11 to −37.49), p<0.0001). In the sensitivity analysis for the endpoint serum prolactin level in all patients, the findings remained significant (p<0.00001; I2=96%). The aripiprazole group was superior to the control group in improving negative symptoms as assessed by the Positive and Negative Syndrome Scale (three RCTs, n=213; SMD: −0.51 (95% CI: −0.79 to −0.24), p=0.0002; I2=0%). Adverse effects and discontinuation rates were similar between the two groups.

Conclusions Adjunctive aripiprazole appears to be associated with reduced AP-induced hyperprolactinaemia and improved prolactin-related symptoms in first-episode schizophrenia. Further studies with large sample sizes are needed to confirm these findings.

  • prolactin
  • aripiprazole
  • schizophrenia
  • first episode
  • meta-analysis

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  • WZ and D-BC contributed equally.

  • Correction notice This article has been corrected since it was first published online. The author list has been updated and amended. Affiliations have been corrected.

  • Contributors WZ and D-BC selected studies and conducted statistical analysis. X-HY and D-BC extracted the data. WZ reviewed all the data and helped mediate disagreements. WZ and D-BC wrote the first draft. All the authors contributed to the interpretation of data and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No additional data are available.