A randomised double-blind placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at risk Mental States: The NAYAB study.

At-risk mental state Early intervention Inflammation Minocycline Omega-3 Psychosis

Journal

Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478

Informations de publication

Date de publication:
Jan 2024
Historique:
received: 05 03 2023
revised: 03 10 2023
accepted: 28 10 2023
pubmed: 5 11 2023
medline: 5 11 2023
entrez: 4 11 2023
Statut: ppublish

Résumé

Inflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan. 10,173 help-seeking individuals aged 16-35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months. Forty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores. In keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation. The study was funded by the Stanley Research Medical Institute.

Sections du résumé

BACKGROUND BACKGROUND
Inflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan.
METHODS METHODS
10,173 help-seeking individuals aged 16-35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months.
FINDINGS RESULTS
Forty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores.
INTERPRETATION CONCLUSIONS
In keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation.
FUNDING BACKGROUND
The study was funded by the Stanley Research Medical Institute.

Identifiants

DOI: 10.1016/j.bbi.2023.10.025 PMID: 37924960
pubmed: 37924960
pii: S0889-1591(23)00325-2
doi: 10.1016/j.bbi.2023.10.025
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

609-616

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: IBCreports giving lectures or advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, AstraZeneca, and Janssen pharmaceuticals for which he or his employing institution have been reimbursed, outside the submitted work; IBC was previously trustee of the Pakistan Institute of Living and Learning (PILL). NH has been a past Trustee of the PILL, Abaseen Foundation UK, Lancashire Mind UK and Manchester Global Foundation (MGF). He is an executive member of the Academic Faculty at the Royal College of Psychiatrists, London. He is a NIHR Senior Investigator. He is director of research and innovation at Mersey Care NHS Foundation Trust. NH/IBC/AB & TK has attended educational events organized by various pharmaceutical industries.IQ is associate director of research and innovation at Mersey Care NHS Foundation Trust.

Auteurs

Inti Qurashi (I)

Institute of Population Health, University of Liverpool, Liverpool, UK; Mersey Care NHS Foundation Trust, Prescott, UK.

Imran B Chaudhry (IB)

Division of Psychology and Mental Health, University of Manchester, Manchester, UK; Department of Psychiatry, Ziauddin University, Karachi, Pakistan; Pakistan Institute of Living and Learning, Karachi, Pakistan.

Ameer B Khoso (AB)

Pakistan Institute of Living and Learning, Karachi, Pakistan.

Muhammad Omair Husain (M)

Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.

Danish Hafeez (D)

Homerton University Hospital, London, UK.

Tayyeba Kiran (T)

Pakistan Institute of Living and Learning, Karachi, Pakistan.

Steven Lane (S)

Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

Haider A Naqvi (HA)

Department of Psychiatry, Dow University of Health Sciences, Karachi, Pakistan.

Fareed A Minhas (FA)

Institute of Psychiatry, Rawalpindi Medical University, Rawalpindi, Pakistan.

Asad Tamizuddin Nizami (A)

Institute of Psychiatry, Rawalpindi Medical University, Rawalpindi, Pakistan.

Bushra Razzaque (B)

Institute of Psychiatry, Rawalpindi Medical University, Rawalpindi, Pakistan.

Sumira Qambar Bokhari (S)

Department of Psychiatry & Behavioural Sciences, Services Institute of Medical Sciences, Lahore, Pakistan.

Alison R Yung (AR)

Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia; Orygen, Parkville, Victoria, Australia.

Bill Deakin (B)

Division of Neuroscience and Experimental Psychology, School of Biological Sciences, University of Manchester, Manchester, UK. Electronic address: bill.deakin@manchester.ac.uk.

Nusrat Husain (N)

Division of Psychology and Mental Health, University of Manchester, Manchester, UK; Mersey Care NHS Foundation Trust, Prescott, UK.

Classifications MeSH