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Amantadine for Antipsychotic-Related Weight Gain: Meta-Analysis of Randomized Placebo-Controlled Trials

Zheng, Wei MD*; Wang, Shibin PhD; Ungvari, Gabor S. MD, PhD‡§; Ng, Chee H. MBBS, MD; Yang, Xin-Hu MD*; Gu, Yu-Hong MD; Li, Ming MD*; Xiang, Ying-Qiang MD, PhD#; Xiang, Yu-Tao MD, PhD

Journal of Clinical Psychopharmacology: June 2017 - Volume 37 - Issue 3 - p 341–346
doi: 10.1097/JCP.0000000000000598
Original Contributions

Purpose Weight gain associated with antipsychotics in schizophrenia has been an ongoing concern. This meta-analysis examined the efficacy and safety of amantadine as an adjunctive treatment of weight gain in schizophrenia by systematically searching and analyzing randomized controlled trials (RCTs). RCTs comparing adjunctive amantadine with placebo in adult patients with schizophrenia were included in the meta-analysis.

Methods Two independent investigators searched the literature and extracted data. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio ± 95% confidence intervals were calculated.

Results Five RCTs (n = 265) with double-blinded design lasting 8.2 ± 5.9 weeks were included in the analysis. Amantadine outperformed placebo regarding weight reduction with moderate effect size (trials, 3; n = 205; WMD −2.22 kg; P = 0.001, I2 = 45%). Amantadine also outperformed placebo at endpoint in the negative symptom (the Positive and Negative Syndrome Scale [PANSS] [1 trial] and the Scale for the Assessment of Negative Symptoms [1 trial]) scores (trials, 2; n = 84; SMD, −0.56; P = 0.01, I2 = 12%), but not in the PANSS total scores (trials, 2) (SMD, −0.31; P = 0.16, I2 = 0%) and the positive symptom (PANSS [1 trial] and the Scale for the Assessment of Positive Symptoms [1 trial]) scores (SMD, 0.13; P = 0.54, I2 = 0%). Except for insomnia (P = 0.007; number needed to harm, 6; 95% confidence interval, 4–16), all-cause discontinuation (risk ratio, 1.12; P = 0.54, I2 = 0%) and other adverse events were similar between the amantadine and placebo groups.

Conclusions According to this meta-analysis of 5 RCTs, adjunctive amantadine seems to be an effective option for attenuating antipsychotic-related weight gain in patients with schizophrenia. More RCTs are needed to inform clinical recommendations.

Supplemental digital content is available in the text.

From *The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou; and †Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao SAR, China; ‡The University of Notre Dame Australia/Marian Centre; and §School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth; and ∥Department of Psychiatry, University of Melbourne, Melbourne, Australia; and ¶Department of Endocrinology, Beijing Hospital of Traditional Chinese Medicine, and #Beijing Anding Hospital, Capital Medical University, Beijing, China.

Received January 8, 2016; accepted after revision-1 June 20, 2016; final acceptance after revision-2 on September 8, 2016.

Reprints: Wei Zheng, MD, Guangzhou Huiai Hospital, Guangzhou, China (e-mail:; or Yu-Tao Xiang, MD, PhD, 3/F, Bldg E12, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China (e-mail:

The study was supported by the Start-up Research Grant (SRG2014-00019-FHS) and the Multi-Year Research Grant (MYRG2015-00230-FHS) from the University of Macau.

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