Hsu, Tien-Wei ORCID: https://orcid.org/0000-0003-4136-1251, Thompson, Trevor ORCID: https://orcid.org/0000-0001-9880-782X, Solmi, Marco, Vieta, Eduard, Yang, Fu-Chi, Tseng, Ping-Tao, Hsu, Chih-Wei ORCID: https://orcid.org/0000-0002-8650-4060, Tu, Yu-Kang, Yu, Chia-Ling, Tsai, Chia-Kuang ORCID: https://orcid.org/0000-0001-7693-1408, Liang, Chih-Sung ORCID: https://orcid.org/0000-0003-1138-5586 and Carvalho, Andre F. (2022) Variability and efficacy in treatment effects on manic symptoms with lithium, anticonvulsants, and antipsychotics in acute bipolar mania: A systematic review and meta-analysis. eClinicalMedicine, 54:101690. pp. 1-10. ISSN 2589-5370 (Online) (doi:10.1016/j.eclinm.2022.101690)

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Abstract

Background: Acute mania is a psychiatric emergency requiring rapid management. However, randomised controlled trials (RCTs) have shown considerable individual differences in treatment effects on manic symptoms with antimanic drugs.
Methods: We searched the MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov to identify RCTs without language restrictions from inception to April 19, 2022. We included double-blind RCTs of oral antimanic monotherapy versus placebo in adult patients. The primary outcome was variability in improvement of manic symptoms (assessed using the coefficient of variation ratio [CVR]). The secondary outcomes were overall improvement of manic symptoms and acceptability (i.e., discontinuation for any reason). The pooled effects of outcomes were calculated by random-effects meta-analyses using restricted maximum likelihood methods. The quality of the included studies was assessed using the Cochrane Risk of Bias (ROB) Assessment Tool. This study was registered with OSF (DOI:10.17605/OSF.IO/G4JNY).
Findings: We included 39 RCTs (N=12150; mean age=39·9 years, interquartile range [IQR]=38·7-41·1; mean proportion of female=48·6%, IQR=42·3%-52·3%) and investigated 14 antimanic drugs. We found that eight antimanic drugs compared to placebo were associated with lower CVRs (95% confidence interval [CI]; I2), including risperidone (0·51; 0·37-0·70; 0%), haloperidol (0·54; 0·44-0·67; 4%), olanzapine (0·59; 0·44-0·79; 47%), ziprasidone (0·61; 0·53-0·71; 0%), lithium (0·63; 0·52-0·76; 0%), quetiapine (0·65; 0·48-0·87; 2%), aripiprazole (0·68; 0·56-0·84; 25%), and cariprazine (0·70; 0·49-0·99; 28%). There were nine antimanic drugs associated with greater efficacy than placebo, including risperidone (reported as standardised mean difference; 95% CI; I2: 0·64; 0·31-0·97; 15%), haloperidol (0·57; 0·29-0·85; 64%), cariprazine (0·51; 0·24-0·78; 0%), olanzapine (0·44; 0·30-0·58; 0%), lithium (0·42; 0·29-0·55; 0%), ziprasidone (0·42; 0·26-0·58; 0%), quetiapine (0·40; 0·13-0·67; 0%), asenapine (0·40; 0·13-0·67; 0%), and aripiprazole (0·32; 0·14-0·49; 53%). Ziprasidone (reported as risk ratio; 95% CI; I2: 0·83; 0·79-0·89; 0%) and olanzapine (0·63; 0·49-0·80; 35%) were associated with better acceptability relative to placebo. Among the 39 RCTs, none had a high ROB.
Interpretation: We demonstrated that eight antimanic drugs were associated with lower variability and better efficacy than placebo, suggesting that these antimanic drugs were associated with more homogenous and predictable improvements of manic symptoms in patients with acute mania.

Item Type:	Article
Uncontrolled Keywords:	anticonvulsants; antipsychotics; bipolar mania; meta-analysis; mood stabilisers; variability in improvement of manic symptoms
Subjects:	B Philosophy. Psychology. Religion > BF Psychology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry R Medicine > RS Pharmacy and materia medica
Faculty / School / Research Centre / Research Group:	Faculty of Education, Health & Human Sciences Faculty of Education, Health & Human Sciences > Institute for Lifecourse Development Faculty of Education, Health & Human Sciences > Institute for Lifecourse Development > Centre for Chronic Illness and Ageing Faculty of Education, Health & Human Sciences > School of Human Sciences (HUM)
Last Modified:	28 Nov 2022 12:53
URI:	http://gala.gre.ac.uk/id/eprint/38093

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