Nutraceuticals and phytoceuticals in the treatment of schizophrenia: a systematic review and network meta-analysis "Nutra NMA SCZ".
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
18 Jul 2024
18 Jul 2024
Historique:
received:
21
12
2023
accepted:
21
06
2024
revised:
18
06
2024
medline:
19
7
2024
pubmed:
19
7
2024
entrez:
18
7
2024
Statut:
aheadofprint
Résumé
Sub-optimal response in schizophrenia is frequent, warranting augmentation strategies over treatment-as-usual (TAU). We assessed nutraceuticals/phytoceutical augmentation strategies via network meta-analysis. Randomized controlled trials in schizophrenia/schizoaffective disorder were identified via the following databases: PubMed, MEDLINE, EMBASE, Scopus, PsycINFO, CENTRAL, and ClinicalTrials.gov. Change (Standardized Mean Difference = SMD) in total symptomatology and acceptability (Risk Ratio = RR) were co-primary outcomes. Secondary outcomes were positive, negative, cognitive, and depressive symptom changes, general psychopathology, tolerability, and response rates. We conducted subset analyses by disease phase and sensitivity analyses by risk of bias and assessed global/local inconsistency, publication bias, risk of bias, and confidence in the evidence. The systematic review included 49 records documenting 50 studies (n = 2384) documenting 22 interventions. Citicoline (SMD =-1.05,95%CI = -1.85; -0.24), L-lysine (SMD = -1.04,95%CI = -1.84; -0.25), N-acetylcysteine (SMD = -0.87, 95%CI = -1.27; -0.47) and sarcosine (SMD = -0.5,95%CI = -0.87-0.13) outperformed placebo for total symptomatology. High heterogeneity (tau
Identifiants
pubmed: 39026098
doi: 10.1038/s41380-024-02645-y
pii: 10.1038/s41380-024-02645-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1156072
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 2017131
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 2008971
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
Références
GBD 2019 MDC. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry. 2022;9:137–50.
doi: 10.1016/S2215-0366(21)00395-3
Solmi M SG, Mavridis D, Correll CU, Dragioti E, Guimond S, et al. Incidence, prevalence, and global burden of schizophrenia—data, with critical appraisal, from the Global Burden of Disease (GBD) 2019. Mol Psychiatry. 2023.
Keepers GA, Fochtmann LJ, Anzia JM, Benjamin S, Lyness JM, Mojtabai R, et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020;177:868–72.
pubmed: 32867516
doi: 10.1176/appi.ajp.2020.177901
Correll CU, Howes OD. Treatment-resistant schizophrenia: definition, predictors, and therapy options. J Clin Psychiatry. 2021; 82:MY20096AH1C.
Diniz E, Fonseca L, Rocha D, Trevizol A, Cerqueira R, Ortiz B, et al. Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates. Braz J Psychiatry. 2023;45:448–58.
pubmed: 37718484
pmcid: 10894625
Correll CU, Solmi M, Cortese S, Fava M, Højlund M, Kraemer HC, et al. The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de‐risk trial programmes of novel agents. World Psychiatry. 2023;22:48–74.
pubmed: 36640403
pmcid: 9840514
doi: 10.1002/wps.21056
Berk M, Marx W, Nierenberg AA. The aggregation of marginal gains: a pragmatic philosophy of clinical care in psychiatry. World Psychiatry. 2024;23:291–292.
Correll CU, Rubio JM, Inczedy-Farkas G, Birnbaum ML, Kane JM, Leucht S. Efficacy of 42 pharmacologic cotreatment strategies added to antipsychotic monotherapy in schizophrenia: systematic overview and quality appraisal of the meta-analytic evidence. JAMA Psychiatry. 2017;74:675–84.
pubmed: 28514486
pmcid: 6584320
doi: 10.1001/jamapsychiatry.2017.0624
Seetharaman M, Krishnan G, Schneider RH. The future of medicine: frontiers in integrative health and medicine. Medicina. 2021;57:1303.
Tsiaka T, Kritsi E, Tsiantas K, Christodoulou P, Sinanoglou VJ, Zoumpoulakis P. Design and development of novel nutraceuticals: current trends and methodologies. Nutraceuticals. 2022;2:71–90.
doi: 10.3390/nutraceuticals2020006
Sarris J, Ravindran A, Yatham LN, Marx W, Rucklidge JJ, McIntyre RS et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce. World J Biol Psychiatry. 2022:1–32.
DeFelice SL. The nutraceutical revolution: its impact on food industry R&D. Trends Food Sci Technol. 1995;6:59–61.
doi: 10.1016/S0924-2244(00)88944-X
Lee SY, Shin YW, Hahm KB. Phytoceuticals: mighty but ignored weapons against Helicobacter pylori infection. J Dig Dis. 2008;9:129–39.
pubmed: 18956590
doi: 10.1111/j.1751-2980.2008.00334.x
Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, et al. The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials. World Psychiatry. 2019;18:308–24.
pubmed: 31496103
pmcid: 6732706
doi: 10.1002/wps.20672
Sarris J, Marx W, Ashton MM, Ng CH, Galvao-Coelho N, Ayati Z, et al. Plant-based medicines (Phytoceuticals) in the treatment of psychiatric disorders: a meta-review of meta-analyses of randomized controlled trials: Les médicaments à base de plantes (phytoceutiques) dans le traitement des troubles psychiatriques: une méta-revue des méta-analyses d’essais randomisés contrôlés. Can J Psychiatry. 2021;66:849–62.
pubmed: 33596697
pmcid: 8573706
doi: 10.1177/0706743720979917
Xu X, Shao G, Zhang X, Hu Y, Huang J, Su Y, et al. The efficacy of nutritional supplements for the adjunctive treatment of schizophrenia in adults: A systematic review and network meta-analysis. Psychiatry Res. 2022;311:114500.
pubmed: 35287043
doi: 10.1016/j.psychres.2022.114500
Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162:777–84.
pubmed: 26030634
doi: 10.7326/M14-2385
Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.
pubmed: 31462531
doi: 10.1136/bmj.l4898
Nikolakopoulou A, Higgins JP, Papakonstantinou T, Chaimani A, Del Giovane C, Egger M, et al. CINeMA: an approach for assessing confidence in the results of a network meta-analysis. PLoS Med. 2020;17:e1003082.
pubmed: 32243458
pmcid: 7122720
doi: 10.1371/journal.pmed.1003082
Higgins JPT TJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane handbook for systematic reviews of interventions version 6.3 (updated February 2022), 2022.
Solmi M, Wade TD, Byrne S, Del Giovane C, Fairburn CG, Ostinelli EG, et al. Comparative efficacy and acceptability of psychological interventions for the treatment of adult outpatients with anorexia nervosa: a systematic review and network meta-analysis. Lancet Psychiatry. 2021;8:215–24.
pubmed: 33600749
doi: 10.1016/S2215-0366(20)30566-6
Levine J, Stahl Z, Sela BA, Ruderman V, Shumaico O, Babushkin I, et al. Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry. 2006;60:265–9.
pubmed: 16412989
doi: 10.1016/j.biopsych.2005.10.009
Hosseininasab M, Zarghami M, Mazhari S, Salehifar E, Moosazadeh M, Fariborzifar A, et al. Nanocurcumin as an add-on to antipsychotic drugs for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol. 2021;41:25–30.
pubmed: 33347019
doi: 10.1097/JCP.0000000000001324
Miodownik C, Lerner V, Kudkaeva N, Lerner PP, Pashinian A, Bersudsky Y, et al. Curcumin as add-on to antipsychotic treatment in patients with chronic schizophrenia: A randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 2019;42:117–22.
pubmed: 31045590
doi: 10.1097/WNF.0000000000000344
Roffman JL, Lamberti JS, Achtyes E, Macklin EA, Galendez GC, Raeke LH, et al. Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia. JAMA Psychiatry. 2013;70:481–9.
pubmed: 23467813
pmcid: 4394629
doi: 10.1001/jamapsychiatry.2013.900
Roffman JL, Petruzzi LJ, Tanner AS, Brown HE, Eryilmaz H, Ho NF, et al. Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial. Mol Psychiatry. 2018;23:316–22.
pubmed: 28289280
doi: 10.1038/mp.2017.41
Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, et al. N-acetyl cysteine as a glutathione precursor for schizophrenia-a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008;64:361–8.
pubmed: 18436195
doi: 10.1016/j.biopsych.2008.03.004
Krivoy A, Onn R, Vilner Y, Hochman E, Weizman S, Paz A, et al. Vitamin D supplementation in chronic schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled clinical trial. EBioMedicine. 2017;26:138–45.
pubmed: 29226809
pmcid: 5832639
doi: 10.1016/j.ebiom.2017.11.027
Sepehrmanesh Z, Heidary M, Akasheh N, Akbari H, Heidary M. Therapeutic effect of adjunctive N-acetyl cysteine (NAC) on symptoms of chronic schizophrenia: a double-blind, randomized clinical trial. Prog Neuro-Psychopharmacol Biol Psychiatry. 2018;82:289–96.
doi: 10.1016/j.pnpbp.2017.11.001
Sheikhmoonesi F, Zarghami M, Mamashli S, Charati JY, Hamzehpour R, Fattahi S, et al. Effectiveness of vitamin D supplement therapy in chronic stable schizophrenic male patients: a randomized controlled trial. Iran J Pharm Res. 2016;15:941–50.
pubmed: 28243293
pmcid: 5316275
Farokhnia M, Azarkolah A, Adinehfar F, Khodaie-Ardakani MR, Hosseini SM, Yekehtaz H, et al. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 2013;36:185–192.
pubmed: 24201233
doi: 10.1097/WNF.0000000000000001
Breier A, Liffick E, Hummer TA, Vohs JL, Yang Z, Mehdiyoun NF, et al. Effects of 12-month, double-blind N-acetyl cysteine on symptoms, cognition and brain morphology in early phase schizophrenia spectrum disorders. Schizophr Res. 2018;199:395–402.
pubmed: 29588126
doi: 10.1016/j.schres.2018.03.012
Qiao Y, Liu CP, Han HQ, Liu FJ, Shao Y, Xie B. No impact of omega-3 fatty acid supplementation on symptoms or hostility among patients with schizophrenia. Front Psychiatry. 2020;11:312.
Peet M, Brind J, Ramchand CN, Shah S, Vankar GK. Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Research. 2001;49:243–51.
Peet M, Horrobin DF. A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. J Psychiatr Res. 2002;36:7–18.
pubmed: 11755456
doi: 10.1016/S0022-3956(01)00048-6
Pawełczyk T, Grancow-Grabka M, Kotlicka-Antczak M, Trafalska E, Pawełczyk A. A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia. J Psychiatr Res. 2016;73:34–44.
pubmed: 26679763
doi: 10.1016/j.jpsychires.2015.11.013
Jamilian H, Ghaderi A. The effects of probiotic and selenium co-supplementation on clinical and metabolic scales in chronic schizophrenia: a randomized, double-blind, placebo-controlled trial. Biol Trace Elem Res. 2021;199:4430–8.
pubmed: 33409919
doi: 10.1007/s12011-020-02572-3
Jamilian H, Solhi H, Jamilian M. Randomized, placebo-controlled clinical trial of omega-3 as supplemental treatment in schizophrenia. Glob J Health Sci. 2014;6:103–8.
pubmed: 25363186
pmcid: 4796520
doi: 10.5539/gjhs.v6n7p103
Emsley R, Chiliza B, Asmal L, du Plessis S, Phahladira L, van Niekerk E, et al. A randomized, controlled trial of omega-3 fatty acids plus an antioxidant for relapse prevention after antipsychotic discontinuation in first-episode schizophrenia. Schizophr Res. 2014;158:230–5.
pubmed: 24996507
doi: 10.1016/j.schres.2014.06.004
Emsley R, Myburgh C, Oosthuizen P, Van Rensburg SJ. Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Am J Psychiatry. 2002;159:1596–8.
pubmed: 12202284
doi: 10.1176/appi.ajp.159.9.1596
Tang W, Wang Y, Xu F, Fan W, Zhang Y, Fan K, et al. Omega-3 fatty acids ameliorate cognitive dysfunction in schizophrenia patients with metabolic syndrome. Brain Behav Immun. 2020;88:529–34.
pubmed: 32304881
doi: 10.1016/j.bbi.2020.04.034
Ritsner MS, Miodownik C, Ratner Y, Shleifer T, Mar I, Pintov L, et al. L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: An 8-week, randomized, double-blind, placebo-controlled, 2-center study. J Clin Psychiatry. 2011;72:34–42.
pubmed: 21208586
doi: 10.4088/JCP.09m05324gre
Ghaderi A, Banafshe HR, Mirhosseini N, Moradi M, Karimi MA, Mehrzad F, et al. Clinical and metabolic response to vitamin D plus probiotic in schizophrenia patients. BMC Psychiatry. 2019;19:77.
Chengappa KNR, Brar JS, Gannon JM, Schlicht PJ. Adjunctive use of a standardized extract of withania somnifera (ashwagandha) to treat symptom exacerbation in schizophrenia: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2018;79:17m11826.
Chen EY, Hui CL. HT1001, a proprietary North American ginseng extract, improves working memory in schizophrenia: a double-blind, placebo-controlled study. Phytother Resem. 2012;26:1166–1172.
doi: 10.1002/ptr.3700
Atmaca M, Tezcan E, Kuloglu M, Ustundag B, Kirtas O. The effect of extract of ginkgo biloba addition to olanzapine on therapeutic effect and antioxidant enzyme levels in patients with schizophrenia. Psychiatry Clin Neurosci. 2005;59:652–6.
pubmed: 16401239
doi: 10.1111/j.1440-1819.2005.01432.x
Zhang XY, Zhou DF, Su JM, Zhang PY. The effect of extract of ginkgo biloba added to haloperidol on superoxide dismutase in inpatients with chronic schizophrenia. J Clin Psychopharmacol. 2001;21:85–88.
pubmed: 11199954
doi: 10.1097/00004714-200102000-00015
Doruk A, Uzun Ö, Özşahin A. A placebo-controlled study of extract of ginkgo biloba added to clozapine in patients with treatment-resistant schizophrenia. Int Clin Psychopharmacol. 2008;23:223–7.
pubmed: 18545061
doi: 10.1097/YIC.0b013e3282fcff2f
Miyaoka T, Furuya M, Horiguchi J, Wake R, Hashioka S, Tohyama M, et al. Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled trial (a Positive and Negative Syndrome Scale, five-factor analysis). Psychopharmacology. 2015;232:155–164.
pubmed: 24923986
doi: 10.1007/s00213-014-3645-8
Dickerson F, Origoni A, Katsafanas E, Squire A, Newman T, Fahey J, et al. Randomized controlled trial of an adjunctive sulforaphane nutraceutical in schizophrenia. Schizophr Res. 2021;231:142–144.
pubmed: 33839372
doi: 10.1016/j.schres.2021.03.018
Xiao SF, Xue HB, Li X, Chen C, Li GJ, Yuan CM, et al. A double-blind, placebo-controlled study of traditional Chinese medicine sarsasapogenin added to risperidone in patients with negative symptoms dominated schizophrenia. Neurosci Bull. 2011;27:258–68.
pubmed: 21788997
pmcid: 5560307
doi: 10.1007/s12264-011-1417-6
Lane HY, Chang YC, Liu YC, Chiu CC, Tsai GE. Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study. Arch Gen Psychiatry. 2005;62:1196–204.
pubmed: 16275807
doi: 10.1001/archpsyc.62.11.1196
Lane HY, Huang CL, Wu PL, Liu YC, Chang YC, Lin PY, et al. Glycine transporter I Inhibitor, N-methylglycine (Sarcosine), added to clozapine for the treatment of schizophrenia. Biol Psychiatry. 2006;60:645–9.
pubmed: 16780811
doi: 10.1016/j.biopsych.2006.04.005
Lane HY, Lin CH, Huang YJ, Liao CH, Chang YC, Tsai GE. A randomized, double-blind, placebo-controlled comparison study of sarcosine (N-methylglycine) and d-serine add-on treatment for schizophrenia. Int J Neuropsychopharmacol. 2010;13:451–60.
pubmed: 19887019
doi: 10.1017/S1461145709990939
Tsai G, Lane HY, Yang P, Chong MY, Lange N. Glycine transporter I inhibitor, N-Methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 2004;55:452–6.
pubmed: 15023571
doi: 10.1016/j.biopsych.2003.09.012
Tsai GE, Yang P, Chung LC, Tsai IC, Tsai CW, Coyle JTD-. serine added to clozapine for the treatment of schizophrenia. Am J Psychiatry. 1999;156:1822–5.
pubmed: 10553752
doi: 10.1176/ajp.156.11.1822
Zeinoddini A, Ahadi M, Farokhnia M, Rezaei F, Tabrizi M, Akhondzadeh S. L-lysine as an adjunct to risperidone in patients with chronic schizophrenia: a double-blind, placebo-controlled, randomized trial. J Psychiatr Res. 2014;59:125–31.
pubmed: 25227564
doi: 10.1016/j.jpsychires.2014.08.016
Lin CY, Liang SY, Chang YC, Ting SY, Kao CL, Wu YH, et al. Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms: a randomised, double-blind, placebo-controlled trial. World J Biol Psychiatry. 2017;18:357–68.
pubmed: 26691576
doi: 10.3109/15622975.2015.1117654
Strzelecki D, Urban-Kowalczyk M, Wysokiński A. Serum levels of interleukin 6 in schizophrenic patients during treatment augmentation with sarcosine (results of the PULSAR study). Hum Psychopharmacol. 2018;33:e2652.
Ghajar A, Gholamian F, Tabatabei-Motlagh M, Afarideh M, Rezaei F, Ghazizadeh-Hashemi M et al. Citicoline (CDP-choline) add-on therapy to risperidone for treatment of negative symptoms in patients with stable schizophrenia: a double-blind, randomized placebo-controlled trial. Hum. Psychopharmacol. 2018;33:e2662.
Turner A, Baker A, Dean OM, Walker AJ, Dodd S, Cotton SM, et al. Adjunctive Garcinia mangostana Linn. (Mangosteen) Pericarp for schizophrenia: a 24-week double-blind, randomized, placebo controlled efficacy trial: Péricarpe d’appoint Garcinia mangostana Linn (mangoustan) pour la schizophrénie: un essai d’efficacité de 24 semaines, à double insu, randomisé et contrôlé par placebo. Can J Psychiatry. 2021;66:354–66.
pubmed: 33355478
doi: 10.1177/0706743720982437
Serrita J, Ralevski E, Yoon G, Petrakis I. A pilot randomized, placebo-controlled trial of glycine for treatment of schizophrenia and alcohol dependence. J Dual Diagn. 2019;15:46–55.
pubmed: 30633660
doi: 10.1080/15504263.2018.1549764
Xiao S, Xue H, Li G, Yuan C, Li X, Chen C, et al. Therapeutic effects of cerebrolysin added to risperidone in patients with schizophrenia dominated by negative symptoms. Aust NZ J psychiatry. 2012;46:153–60.
doi: 10.1177/0004867411433213
D’Souza DC, Radhakrishnan R, Perry E, Bhakta SG, Singh N, Pittman B, et al. Feasibility, safety and efficacy of the combination of D-serine and computerized cognitive retraining in schizophrenia: an international collaborative pilot study. Schizophr. Bull. 2013;39:S326.
Evins AE, Fitzgerald SM, Wine L, Rosselli R, Goff DC. Placebo-controlled trial of glycine added to clozapine in schizophrenia. Am J Psychiatry. 2000;157:826–8.
pubmed: 10784481
doi: 10.1176/appi.ajp.157.5.826
Buchanan RW, Javitt DC, Marder SR, Schooler NR, Gold JM, McMahon RP, et al. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry. 2007;164:1593–602.
pubmed: 17898352
doi: 10.1176/appi.ajp.2007.06081358
Dakhale GN, Khanzode SD, Khanzode SS, Saoji A. Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia. Psychopharmacology. 2005;182:494–8.
pubmed: 16133138
doi: 10.1007/s00213-005-0117-1
Heresco-Levy U, Javitt DC, Ebstein R, Vass A, Lichtenberg P, Bar G, et al. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry. 2005;57:577–85.
pubmed: 15780844
doi: 10.1016/j.biopsych.2004.12.037
Fenton WS, Dickerson F, Boronow J, Hibbeln JR, Knable M. A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry. 2001;158:2071–4.
pubmed: 11729030
doi: 10.1176/appi.ajp.158.12.2071
Hill M, Shannahan K, Jasinski S, Macklin EA, Raeke L, Roffman JL, et al. Folate supplementation in schizophrenia: a possible role for MTHFR genotype. Schizophr Res. 2011;127:41–45.
pubmed: 21334854
doi: 10.1016/j.schres.2010.12.006
Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261–76.
pubmed: 3616518
doi: 10.1093/schbul/13.2.261
Andreasen NC. Scale for the assessment of positive symptoms. Psychiatr Psychobiol. University of Iowa, Iowa City. 1984.
Andreasen NC. Scale for the assessment of negative symptoms (SANS). University of Iowa Iowa City. 1981.
Guy W. Clinical global impression. Assessment manual for psychopharmacology 1976: 217–22.
Nasyrova RF, Ivashchenko DV, Ivanov MV, Neznanov NG. Role of nitric oxide and related molecules in schizophrenia pathogenesis: biochemical, genetic and clinical aspects. Front Physiol. 2015;6:139.
pubmed: 26029110
pmcid: 4426711
doi: 10.3389/fphys.2015.00139
Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008;11:851–76.
pubmed: 18205981
doi: 10.1017/S1461145707008401
Matsuzawa D, Obata T, Shirayama Y, Nonaka H, Kanazawa Y, Yoshitome E, et al. Negative correlation between brain glutathione level and negative symptoms in schizophrenia: a 3T 1H-MRS study. PloS One. 2008;3:e1944.
pubmed: 18398470
pmcid: 2275307
doi: 10.1371/journal.pone.0001944
Müller N, Weidinger E, Leitner B, Schwarz MJ. The role of inflammation in schizophrenia. Front Neurosci. 2015;9:372.
pubmed: 26539073
pmcid: 4612505
doi: 10.3389/fnins.2015.00372
Marx W, McGuinness AJ, Rocks T, Ruusunen A, Cleminson J, Walker AJ, et al. The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies. Mol Psychiatry. 2021;26:4158–78.
pubmed: 33230205
doi: 10.1038/s41380-020-00951-9
McCutcheon RA, Krystal JH, Howes OD. Dopamine and glutamate in schizophrenia: biology, symptoms and treatment. World Psychiatry. 2020;19:15–33.
pubmed: 31922684
pmcid: 6953551
doi: 10.1002/wps.20693
Cole GM, Teter B, Frautschy SA. Neuroprotective effects of curcumin. Adv Exp Med Biol. 2007;595:197–212.
pubmed: 17569212
pmcid: 2527619
doi: 10.1007/978-0-387-46401-5_8
Mallah K, Couch C, Borucki DM, Toutonji A, Alshareef M, Tomlinson S. Anti-inflammatory and neuroprotective agents in clinical trials for CNS disease and injury: where do we go from here? Front Immunol. 2020;11:2021.
pubmed: 33013859
pmcid: 7513624
doi: 10.3389/fimmu.2020.02021
Conant R, Schauss AG. Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature. Altern Med Rev. 2004;9:17–31.
pubmed: 15005642
Skvarc DR, Dean OM, Byrne LK, Gray L, Lane S, Lewis M, et al. The effect of N-acetylcysteine (NAC) on human cognition—a systematic review. Neurosci Biobehav Rev. 2017;78:44–56.
pubmed: 28438466
doi: 10.1016/j.neubiorev.2017.04.013
Kumar A. NMDA receptor function during senescence: implication on cognitive performance. Front Neurosci. 2015;9:473.
pubmed: 26732087
pmcid: 4679982
doi: 10.3389/fnins.2015.00473
Klauser P, Xin L, Fournier M, Griffa A, Cleusix M, Jenni R, et al. N-acetylcysteine add-on treatment leads to an improvement of fornix white matter integrity in early psychosis: a double-blind randomized placebo-controlled trial. Transl Psychiatry. 2018;8:220.
pubmed: 30315150
pmcid: 6185923
doi: 10.1038/s41398-018-0266-8
Mullier E, Roine T, Griffa A, Xin L, Baumann PS, Klauser P, et al. N-acetyl-cysteine supplementation improves functional connectivity within the cingulate cortex in early psychosis: a pilot study. Int J Neuropsychopharmacol. 2019;22:478–87.
pubmed: 31283822
pmcid: 6672595
doi: 10.1093/ijnp/pyz022
Fond G., Mallet J., Urbach M., Eriksen Benros M., Berk M., et al. Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs. BMJ Ment Health. 2023; e300771.
Tanas A, Tozlu Ö, Gezmiş T, Hacimüftüoğlu A, Abd El-Aty AM, Ceylan O, et al. In vitro and in vivo neuroprotective effects of sarcosine. Biomed Res Int. 2022;2022:5467498.
pubmed: 36281465
pmcid: 9587910
doi: 10.1155/2022/5467498
de Bartolomeis A, Vellucci L, Austin MC, De Simone G, Barone A. Rational and translational implications of D-amino acids for treatment-resistant schizophrenia: from neurobiology to the clinics. Biomolecules. 2022;12:909.
pubmed: 35883465
pmcid: 9312470
doi: 10.3390/biom12070909
Marchi M, Galli G, Magarini FM, Mattei G, Galeazzi GM. Sarcosine as an add-on treatment to antipsychotic medication for people with schizophrenia: a systematic review and meta-analysis of randomized controlled trials. Expert Opin Drug Metab Toxicol. 2021;17:483–93.
pubmed: 33538213
doi: 10.1080/17425255.2021.1885648
Mitra S, Natarajan R, Ziedonis D, Fan X. Antioxidant and anti-inflammatory nutrient status, supplementation, and mechanisms in patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2017;78:1–11.
pubmed: 28499901
doi: 10.1016/j.pnpbp.2017.05.005
van der Burg KP, Cribb L, Firth J, Karmacoska D, Sarris J. Nutrient and genetic biomarkers of nutraceutical treatment response in mood and psychotic disorders: a systematic review. Nutr Neurosci. 2021;24:279–95.
pubmed: 31397223
doi: 10.1080/1028415X.2019.1625222
Santini A, Cammarata SM, Capone G, Ianaro A, Tenore GC, Pani L, et al. Nutraceuticals: opening the debate for a regulatory framework. Br J Clin Pharmacol. 2018;84:659–72.
pubmed: 29433155
pmcid: 5867125
doi: 10.1111/bcp.13496
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
pubmed: 33782057
pmcid: 8005924
doi: 10.1136/bmj.n71