Kenji Sakuma1, Shinji Matsunaga1,2, Ikuo Nomura1, Makoto Okuya1, Taro Kishi3, Nakao Iwata1. 1. Department of Psychiatry, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. 2. Department of Department of Geriatrics and Cognitive Disorders, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. 3. Department of Psychiatry, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. tarok@fujita-hu.ac.jp.
Abstract
RATIONALE: This study aims to examine whether folate/folic acid/methylfolate/folinic acid supplemented to antipsychotics (FA + AP) is beneficial in schizophrenia treatment. OBJECTIVE: We conducted a comprehensive systematic review and meta-analysis of double-blind, placebo-controlled, randomized clinical trials (RCTs) of FA + AP for schizophrenia. METHODS: The primary outcome was an improvement in total symptoms. Other outcomes were psychopathology subscales (positive, negative, general, and depressive symptoms), discontinuation due to all-cause and adverse events, and individual adverse events. The meta-analysis evaluated the effect size based on a random-effects model. RESULTS: Although we included ten RCTs with 925 patients in total (seven folic acid RCTs (n = 789), two methylfolate RCTs (n = 96), and one folinic acid RCT (n = 40)) in the systematic review, only seven RCTs were included in the meta-analysis. Pooled FA + AP treatments were not superior to placebo + AP in the improvement of total (N = 7, n = 340; standardized mean difference (SMD) = - 0.20, 95% confidence interval (CI) = - 0.41, 0.02, p = 0.08, I2 = 0%), positive, general, or depressive symptoms. Pooled FA + AP treatments were more effective than placebo + AP for negative symptoms (N = 5, n = 281; SMD = -0.25, 95% CI = -0.49, -0.01, p = 0.04, I2 = 0%). Although pooled FA + AP treatments were associated with a lower incidence of serious adverse events than placebo treatments (N = 4, n = 241; risk ratio = 0.32, 95% CI = 0.12-0.82, p = 0.02, I2 = 0%; number needed to harm = not significant), there were no significant differences in other safety outcomes between both treatments. CONCLUSIONS: Our findings suggest that pooled FA + AP treatment improves negative symptoms in schizophrenia patients. Moreover, this treatment was well tolerated. However, because our results might exhibit a small-study effect, future studies with a larger sample should be conducted to obtain more robust results.
RATIONALE: This study aims to examine whether folate/folic acid/methylfolate/folinic acid supplemented to antipsychotics (FA + AP) is beneficial in schizophrenia treatment. OBJECTIVE: We conducted a comprehensive systematic review and meta-analysis of double-blind, placebo-controlled, randomized clinical trials (RCTs) of FA + AP for schizophrenia. METHODS: The primary outcome was an improvement in total symptoms. Other outcomes were psychopathology subscales (positive, negative, general, and depressive symptoms), discontinuation due to all-cause and adverse events, and individual adverse events. The meta-analysis evaluated the effect size based on a random-effects model. RESULTS: Although we included ten RCTs with 925 patients in total (seven folic acid RCTs (n = 789), two methylfolate RCTs (n = 96), and one folinic acid RCT (n = 40)) in the systematic review, only seven RCTs were included in the meta-analysis. Pooled FA + AP treatments were not superior to placebo + AP in the improvement of total (N = 7, n = 340; standardized mean difference (SMD) = - 0.20, 95% confidence interval (CI) = - 0.41, 0.02, p = 0.08, I2 = 0%), positive, general, or depressive symptoms. Pooled FA + AP treatments were more effective than placebo + AP for negative symptoms (N = 5, n = 281; SMD = -0.25, 95% CI = -0.49, -0.01, p = 0.04, I2 = 0%). Although pooled FA + AP treatments were associated with a lower incidence of serious adverse events than placebo treatments (N = 4, n = 241; risk ratio = 0.32, 95% CI = 0.12-0.82, p = 0.02, I2 = 0%; number needed to harm = not significant), there were no significant differences in other safety outcomes between both treatments. CONCLUSIONS: Our findings suggest that pooled FA + AP treatment improves negative symptoms in schizophreniapatients. Moreover, this treatment was well tolerated. However, because our results might exhibit a small-study effect, future studies with a larger sample should be conducted to obtain more robust results.
Authors: R E Nielsen; S Levander; G Kjaersdam Telléus; S O W Jensen; T Østergaard Christensen; S Leucht Journal: Acta Psychiatr Scand Date: 2015-01-16 Impact factor: 6.392
Authors: Michele Hill; Kelsey Shannahan; Sarah Jasinski; Eric A Macklin; Lisa Raeke; Joshua L Roffman; Donald C Goff Journal: Schizophr Res Date: 2011-02-21 Impact factor: 4.939
Authors: P S Godfrey; B K Toone; M W Carney; T G Flynn; T Bottiglieri; M Laundy; I Chanarin; E H Reynolds Journal: Lancet Date: 1990-08-18 Impact factor: 79.321
Authors: J L Roffman; L J Petruzzi; A S Tanner; H E Brown; H Eryilmaz; N F Ho; M Giegold; N J Silverstein; T Bottiglieri; D S Manoach; J W Smoller; D C Henderson; D C Goff Journal: Mol Psychiatry Date: 2017-03-14 Impact factor: 15.992
Authors: Joseph Firth; Scott B Teasdale; Kelly Allott; Dan Siskind; Wolfgang Marx; Jack Cotter; Nicola Veronese; Felipe Schuch; Lee Smith; Marco Solmi; André F Carvalho; Davy Vancampfort; Michael Berk; Brendon Stubbs; Jerome Sarris Journal: World Psychiatry Date: 2019-10 Impact factor: 49.548
Authors: André F Carvalho; Marco Solmi; Marcos Sanches; Myrela O Machado; Brendon Stubbs; Olesya Ajnakina; Chelsea Sherman; Yue Ran Sun; Celina S Liu; Andre R Brunoni; Giorgio Pigato; Brisa S Fernandes; Beatrice Bortolato; Muhammad I Husain; Elena Dragioti; Joseph Firth; Theodore D Cosco; Michael Maes; Michael Berk; Krista L Lanctôt; Eduard Vieta; Diego A Pizzagalli; Lee Smith; Paolo Fusar-Poli; Paul A Kurdyak; Michele Fornaro; Jürgen Rehm; Nathan Herrmann Journal: Transl Psychiatry Date: 2020-05-18 Impact factor: 6.222
Authors: Sabrina Mörkl; Linda Stell; Diana V Buhai; Melanie Schweinzer; Jolana Wagner-Skacel; Christian Vajda; Sonja Lackner; Susanne A Bengesser; Theresa Lahousen; Annamaria Painold; Andreas Oberascher; Josef M Tatschl; Matthäus Fellinger; Annabel Müller-Stierlin; Ana C Serban; Joseph Ben-Sheetrit; Ana-Marija Vejnovic; Mary I Butler; Vicent Balanzá-Martínez; Nikola Zaja; Polona Rus-Prelog; Robertas Strumila; Scott B Teasdale; Eva Z Reininghaus; Sandra J Holasek Journal: Nutrients Date: 2021-03-02 Impact factor: 5.717
Authors: Nathaniel W Hodgson; Mostafa I Waly; Malav S Trivedi; Verna-Ann Power-Charnitsky; Richard C Deth Journal: Transl Psychiatry Date: 2019-11-12 Impact factor: 6.222