Adjunctive Aripiprazole for Antipsychotic-related Hyperprolactinaemia in Patients with First-episode Schizophrenia: a Meta-analysis

Overview

Journal Gen Psychiatr

Specialty Psychiatry

Date 2019 Nov 2

PMID 31673677

Citations 5

Authors

Wei Zheng

Dong-Bin Cai

Xin-Hu Yang

Gabor S Ungvari

Chee H Ng

Zhan-Ming Shi

Mei-Ling Hu

Yu-Ping Ning

Yu-Tao Xiang

Affiliations

Soon will be listed here.

Abstract

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; I=99%), female patients (two RCTs, n=186; WMD: -22.58 ng/mL (95% CI: -25.67 to -19.49), p<0.00001; I=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; I=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; I=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.

Citing Articles

A systematic review and meta-analysis of the effects of combined aripiprazole on glycolipid metabolism in schizophrenia.

Wei T, Jiang L, Zhang R, Su H, Sun Z, Sun J Front Psychiatry. 2025; 15:1496986.

PMID: 39866685 PMC: 11757238. DOI: 10.3389/fpsyt.2024.1496986.

Challenges and opportunities in the diagnosis and treatment of early-onset psychosis: a case series from the youth affective disorders clinic in Stockholm, Sweden.

Lundberg M, Andersson P, Lundberg J, Desai Bostrom A Schizophrenia (Heidelb). 2024; 10(1):5.

PMID: 38172588 PMC: 10851694. DOI: 10.1038/s41537-023-00427-z.

Influence of antipsychotics on metabolic syndrome risk in patients with schizophrenia.

Koricanac A, Lucic A, Veselinovic M, Bazic Sretenovic D, Bucic G, Azanjac A Front Psychiatry. 2022; 13:925757.

PMID: 35958655 PMC: 9357900. DOI: 10.3389/fpsyt.2022.925757.

Minimal Effects of Cariprazine on Prolactin Levels in Bipolar Disorder and Schizophrenia.

Culpepper L, Vieta E, Kelly D, Patel M, Szatmari B, Hankinson A Neuropsychiatr Dis Treat. 2022; 18:995-1011.

PMID: 35591886 PMC: 9112044. DOI: 10.2147/NDT.S348143.

High dose antipsychotic polypharmacy and dopamine partial agonists - time to rethink guidelines?.

Reynolds G J Psychopharmacol. 2021; 35(9):1030-1036.

PMID: 34256637 PMC: 8436307. DOI: 10.1177/02698811211026456.

References

Shim J, Shin J, Kelly D, Jung D, Seo Y, Liu K . Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial. Am J Psychiatry. 2007; 164(9):1404-10. DOI: 10.1176/appi.ajp.2007.06071075. View

Li X, Tang Y, Wang C . Adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia: meta-analysis of randomized controlled trials. PLoS One. 2013; 8(8):e70179. PMC: 3731351. DOI: 10.1371/journal.pone.0070179. View

Marken P, Haykal R, FISHER J . Management of psychotropic-induced hyperprolactinemia. Clin Pharm. 1992; 11(10):851-6. View

Yamada K, Kanba S, Murata T, Fukuzawa M, Terashi B, Yagi G . Effectiveness of shakuyaku-kanzo-to in neuroleptic-induced hyperprolactinemia: a preliminary report. Psychiatry Clin Neurosci. 1996; 50(6):341-2. DOI: 10.1111/j.1440-1819.1996.tb00578.x. View

DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3):177-88. DOI: 10.1016/0197-2456(86)90046-2. View

Yamada K, Kanba S, Yagi G, Asai M . Effectiveness of herbal medicine (shakuyaku-kanzo-to) for neuroleptic-induced hyperprolactinemia. J Clin Psychopharmacol. 1997; 17(3):234-5. DOI: 10.1097/00004714-199706000-00025. View

Krysiak R, Okrzesik J, Okopien B . The effect of short-term metformin treatment on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance: a pilot study. Endocrine. 2014; 49(1):242-9. PMC: 4412386. DOI: 10.1007/s12020-014-0428-2. View

Man S, Li X, Wang H, Yuan H, Wang H, Zhang R . Peony-Glycyrrhiza Decoction for Antipsychotic-Related Hyperprolactinemia in Women With Schizophrenia: A Randomized Controlled Trial. J Clin Psychopharmacol. 2016; 36(6):572-579. DOI: 10.1097/JCP.0000000000000607. View

Bo Q, Wang Z, Li X, Ma X, Wang C, De Leon J . Adjunctive metformin for antipsychotic-induced hyperprolactinemia: A systematic review. Psychiatry Res. 2016; 237:257-63. DOI: 10.1016/j.psychres.2016.01.031. View

10.

Balshem H, Helfand M, Schunemann H, Oxman A, Kunz R, Brozek J . GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011; 64(4):401-6. DOI: 10.1016/j.jclinepi.2010.07.015. View

11.

Higgins J, Thompson S . Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186. View

12.

Moher D, Liberati A, Tetzlaff J, Altman D . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009; 151(4):264-9, W64. DOI: 10.7326/0003-4819-151-4-200908180-00135. View

13.

Yuan H, Wang C, Sze C, Tong Y, Tan Q, Feng X . A randomized, crossover comparison of herbal medicine and bromocriptine against risperidone-induced hyperprolactinemia in patients with schizophrenia. J Clin Psychopharmacol. 2008; 28(3):264-370. DOI: 10.1097/JCP.0b013e318172473c. View

14.

Zheng W, Yang X, Cai D, Ungvari G, Ng C, Wang N . Adjunctive metformin for antipsychotic-related hyperprolactinemia: A meta-analysis of randomized controlled trials. J Psychopharmacol. 2017; 31(5):625-631. DOI: 10.1177/0269881117699630. View

15.

Kim E, Kim S, Lee N, Jung D, Kim Y, Ahn Y . Relationship between prolactin levels and subjective endocrine-related adverse effects in patients with schizophrenia receiving long-term treatment with amisulpride. Pharmacopsychiatry. 2012; 45(2):57-63. DOI: 10.1055/s-0031-1291175. View

16.

Yokoi F, Grunder G, Biziere K, Stephane M, Dogan A, Dannals R . Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [11C]raclopride. Neuropsychopharmacology. 2002; 27(2):248-59. DOI: 10.1016/S0893-133X(02)00304-4. View

17.

Guyatt G, Oxman A, Vist G, Kunz R, Falck-Ytter Y, Alonso-Coello P . GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008; 336(7650):924-6. PMC: 2335261. DOI: 10.1136/bmj.39489.470347.AD. View

18.

Jadad A, Moore R, Carroll D, Jenkinson C, Reynolds D, Gavaghan D . Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials. 1996; 17(1):1-12. DOI: 10.1016/0197-2456(95)00134-4. View

19.

de Berardis D, Fornaro M, Serroni N, Marini S, Piersanti M, Cavuto M . Treatment of antipsychotic-induced hyperprolactinemia: an update on the role of the dopaminergic receptors D2 partial agonist aripiprazole. Recent Pat Endocr Metab Immune Drug Discov. 2013; 8(1):30-7. DOI: 10.2174/1872214807666131229125700. View

20.

Yang C, Qi A, Yu H, Guan X, Wang J, Liu N . Different levels of facial expression recognition in patients with first-episode schizophrenia: A functional MRI study. Gen Psychiatr. 2018; 31(2):e000014. PMC: 6234972. DOI: 10.1136/gpsych-2018-000014. View