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Randomized Controlled Trial
. 2024 Jan:115:609-616.
doi: 10.1016/j.bbi.2023.10.025. Epub 2023 Nov 2.

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

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Free article
Randomized Controlled Trial

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

Inti Qurashi et al. Brain Behav Immun. 2024 Jan.
Free article

Abstract

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: 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: 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: 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: The study was funded by the Stanley Research Medical Institute.

Keywords: At-risk mental state; Early intervention; Inflammation; Minocycline; Omega-3; Psychosis.

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Conflict of interest statement

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.

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