Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs.
Schizophrenia & psychotic disorders
Journal
BMJ mental health
ISSN: 2755-9734
Titre abrégé: BMJ Ment Health
Pays: England
ID NLM: 9918521385306676
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
16
05
2023
accepted:
02
09
2023
medline:
23
10
2023
pubmed:
19
10
2023
entrez:
18
10
2023
Statut:
ppublish
Résumé
This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed. Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio. The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.
Identifiants
pubmed: 37852631
pii: bmjment-2023-300771
doi: 10.1136/bmjment-2023-300771
pmc: PMC10583081
pii:
doi:
Substances chimiques
Acetylcysteine
WYQ7N0BPYC
Amino Acids
0
Anti-Inflammatory Agents
0
Antipsychotic Agents
0
Types de publication
Systematic Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
J Psychopharmacol. 2019 Oct;33(10):1215-1226
pubmed: 31294649
NPJ Schizophr. 2018 Oct 25;4(1):22
pubmed: 30361502
Lancet Psychiatry. 2022 Apr;9(4):330-336
pubmed: 35216655
Aust N Z J Psychiatry. 2020 May;54(5):453-466
pubmed: 31826654
Brain Behav Immun. 2020 Nov;90:364-380
pubmed: 32890697
Schizophr Res. 2017 Jul;185:173-181
pubmed: 28109668
N Engl J Med. 2020 Apr 16;382(16):1497-1506
pubmed: 32294346
BMJ. 2013 Jan 18;346:f185
pubmed: 23335473
CNS Drugs. 2011 Oct 1;25(10):859-85
pubmed: 21936588
Acta Psychiatr Scand. 2018 Mar;137(3):187-205
pubmed: 29431197
Arch Womens Ment Health. 2018 Feb;21(1):31-41
pubmed: 28849318
Schizophr Bull. 2021 Jul 8;47(4):1077-1087
pubmed: 33479775
Acta Psychiatr Scand. 2018 May;137(5):391-400
pubmed: 29457216
Schizophr Res. 2014 Mar;153(1-3):64-7
pubmed: 24439270
J Psychopharmacol. 2019 Apr;33(4):436-448
pubmed: 30730250
Dialogues Clin Neurosci. 2010;12(3):345-57
pubmed: 20954430
Expert Opin Drug Metab Toxicol. 2021 Apr;17(4):483-493
pubmed: 33538213
Cochrane Database Syst Rev. 2006 Jul 19;(3):CD001257
pubmed: 16855961
Schizophr Res. 2009 Apr;109(1-3):10-4
pubmed: 19186030
Am J Psychiatry. 2016 Sep 1;173(9):876-86
pubmed: 27282362
Trends Neurosci. 2019 Mar;42(3):205-220
pubmed: 30621912
Psychol Med. 2019 Oct;49(14):2307-2319
pubmed: 31439071
BMC Med Res Methodol. 2018 Sep 24;18(1):96
pubmed: 30249204
J Psychopharmacol. 2021 Mar;35(3):221-235
pubmed: 33586517
J Clin Psychiatry. 2012 Apr;73(4):414-9
pubmed: 22225599
Nat Rev Neurosci. 2016 Feb;17(2):125-34
pubmed: 26763624
Schizophrenia (Heidelb). 2022 Feb 25;8(1):7
pubmed: 35217671
Brain Behav Immun. 2020 Aug;88:867-869
pubmed: 32224057
Am J Psychiatry. 2022 Apr;179(4):288-297
pubmed: 35360921
Ann Clin Psychiatry. 2015 Nov;27(4):289-96
pubmed: 26554370
Aust N Z J Psychiatry. 2019 Aug;53(8):742-759
pubmed: 30864461
CNS Spectr. 2017 Oct;22(5):415-426
pubmed: 28181901
Lancet Psychiatry. 2021 Jun;8(6):471-486
pubmed: 34023019
JAMA Psychiatry. 2017 Jul 1;74(7):675-684
pubmed: 28514486
Schizophr Res. 2012 Nov;141(2-3):179-84
pubmed: 22998932
J Clin Psychopharmacol. 2022 Sep-Oct 01;42(5 Suppl 1):S1-S13
pubmed: 36099402
Psychother Psychosom. 2018;87(6):369
pubmed: 30227418
JAMA Psychiatry. 2021 Nov 1;78(11):1238-1248
pubmed: 34406325
Schizophr Bull. 2021 Mar 16;47(2):298-308
pubmed: 33252130
World J Biol Psychiatry. 2022 Jul;23(6):424-455
pubmed: 35311615
World J Biol Psychiatry. 2019 Jan;20(1):2-16
pubmed: 30526182
Can J Psychiatry. 2017 Nov;62(11):772-777
pubmed: 28655284
Mol Psychiatry. 2013 May;18(5):543-56
pubmed: 22641180
Neurosci Biobehav Rev. 2021 Jan;120:537-541
pubmed: 33031817
Trends Pharmacol Sci. 2022 Dec;43(12):1098-1112
pubmed: 36273943
World Psychiatry. 2019 Oct;18(3):308-324
pubmed: 31496103
Nat Rev Dis Primers. 2015 Nov 12;1:15067
pubmed: 27189524
J Psychopharmacol. 2020 May;34(5):495-505
pubmed: 32122256
Can J Psychiatry. 2017 Sep;62(9):617-623
pubmed: 28703017
Curr Pharm Des. 2010;16(5):522-37
pubmed: 19909229
Schizophr Res. 2020 Jan;215:8-16
pubmed: 31784340
Eur Neuropsychopharmacol. 2017 Jan;27(1):8-18
pubmed: 27919523
Schizophr Res. 2001 Mar 1;48(1):137-44
pubmed: 11278160
Schizophr Res. 2018 Jul;197:288-293
pubmed: 29395611
Cochrane Database Syst Rev. 2022 Nov 24;11:CD014384
pubmed: 36420692
Hum Psychopharmacol. 2014 Sep;29(5):483-91
pubmed: 25087702
J Psychopharmacol. 2021 Mar;35(3):236-252
pubmed: 33406959
Schizophr Bull. 2014 Jan;40(1):181-91
pubmed: 24106335
J Clin Psychopharmacol. 2012 Apr;32(2):179-85
pubmed: 22367656
NPJ Schizophr. 2018 Jan 10;4(1):1
pubmed: 29321530
Neuropsychopharmacology. 2020 Apr;45(5):887-901
pubmed: 31770770
J Psychiatr Res. 2017 Sep;92:139-146
pubmed: 28445800
Schizophr Res. 2012 Nov;141(2-3):153-61
pubmed: 22981812
Transl Psychiatry. 2013 Dec 17;3:e335
pubmed: 24346133
Early Interv Psychiatry. 2019 Feb;13(1):3-17
pubmed: 29749710
Schizophr Bull. 2013 Nov;39(6):1230-41
pubmed: 23720576