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 (NAYAB): study protocol

Qurashi, Inti; Chaudhry, Imran B; Khoso, Ameer B; Farooque, Sana; Lane, Stephen; Husain, Muhammad; Chu, Simon; Sarginson, Jane; Hamarani, Munir; Naqvi, Haider; Razzaque, Bushra; Minhas, Fareed Aslam; Yung, Alison R.; Deakin, Bill; Husain, Nusrat

doi:10.1186/s13063-017-2275-y

Cited by 13 publications

(6 citation statements)

References 32 publications

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“…In this sense, MIN improved the negative symptoms in early-phase ( Liu et al, 2014 ) or persistent schizophrenia ( Khodaie-Ardakani et al, 2014 ; Kelly et al, 2015 ), and it also improved working memory, anxiety, and depression ( Kelly et al, 2015 ), but its preventive potential has only recently been explored in humans. In this respect, only 1 study addresses a 6-month intervention with MIN added to regular treatment in individuals at risk of developing schizophrenia or psychosis ( Qurashi et al, 2017 ), although no results have been reported yet.…”

Section: Discussionmentioning

confidence: 99%

A Characterization of the Effects of Minocycline Treatment During Adolescence on Structural, Metabolic, and Oxidative Stress Parameters in a Maternal Immune Stimulation Model of Neurodevelopmental Brain Disorders

Romero-Miguel

Casquero-Veiga

MacDowell

et al. 2021

International Journal of Neuropsychopharmacology

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Background Minocycline (MIN) is a tetracycline with antioxidant, anti-inflammatory and neuroprotective properties. Given the likely involvement of inflammation and oxidative stress (IOS) in schizophrenia, MIN has been proposed as a potential adjuvant treatment in this pathology. We tested an early therapeutic window, during adolescence, as prevention of the schizophrenia related deficits in the maternal immune stimulation (MIS) animal model. Methods On gestational day 15, Poly I:C or vehicle were injected to pregnant Wistar rats. 93 male offspring received MIN (30 mg/Kg) or saline from postnatal day (PND) 35-49. At PND70, rats were submitted to the prepulse inhibition test (PPI). FDG-PET and T2-weighted MRI brain studies were performed at adulthood. IOS markers were evaluated in frozen brain tissue. Results MIN treatment did not prevent PPI behavioral deficits in MIS-offspring. However, MIN prevented morphometric abnormalities in the third ventricle but not in the hippocampus. Additionally, MIN reduced brain metabolism in cerebellum and increased it in nucleus accumbens. Finally, MIN reduced the expression of iNOS (prefrontal cortex, caudate-putamen) and increased the levels of KEAP1 (prefrontal cortex), HO1 and NQO1 (amygdala, hippocampus), and HO1 (caudate-putamen). Conclusions MIN-treatment during adolescence partially counteracts volumetric abnormalities and IOS deficits in the MIS model, likely via iNOS and Nrf2–ARE pathways, also increasing the expression of cytoprotective enzymes. However, MIN treatment during this peripubertal stage does not prevent sensorimotor gating deficits. Therefore, even though it does not prevent all the MIS-derived abnormalities evaluated, our results suggest the potential utility of early treatment with MIN in other schizophrenia domains.

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Section: Discussionmentioning

confidence: 99%

A Characterization of the Effects of Minocycline Treatment During Adolescence on Structural, Metabolic, and Oxidative Stress Parameters in a Maternal Immune Stimulation Model of Neurodevelopmental Brain Disorders

Romero-Miguel

Casquero-Veiga

MacDowell

et al. 2021

International Journal of Neuropsychopharmacology

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“…Psychosis is one of the 20 leading causes of disability worldwide, affecting 29 million people [ 71 ] contributing to major burden in LMIC. Global health research has now started to receive due attention from funders in high income countries and there are ongoing studies in ARMS in LMIC [ 72 ]. Research covering a wider range of settings and across LMIC is needed to ensure decision makers have evidence relevant to their locality.…”

Section: Discussionmentioning

confidence: 99%

A review of economic evaluations of health care for people at risk of psychosis and for first-episode psychosis

et al. 2022

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Background Preventing psychotic disorders and effective treatment in first-episode psychosis are key priorities for the National Institute for Health and Care Excellence. This review assessed the evidence base for the cost-effectiveness of health and social care interventions for people at risk of psychosis and for first-episode psychosis. Methods Electronic searches were conducted using the PsycINFO, MEDLINE and Embase databases to identify relevant published full economic evaluations published before August 2020. Full-text English-language studies reporting a full economic evaluation of a health or social care intervention aiming to reduce or prevent symptoms in people at risk of psychosis or experiencing first-episode psychosis were included. Screening, data extraction, and critical appraisal were performed using pre-specified criteria and forms based on the NHS Economic Evaluation Database (EED) handbook and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist for economic evaluations. The protocol was registered on the PROSPERO database (CRD42018108226). Results were summarised qualitatively. Results Searching identified 1,628 citations (1,326 following the removal of duplications). After two stages of screening 14 studies met the inclusion criteria and were included in the review. Interventions were varied and included multidisciplinary care, antipsychotic medication, psychological therapy, and assertive outreach. Evidence was limited in the at-risk group with only four identified studies, though all interventions were found to be cost-effective with a high probability (> 80%). A more substantial evidence base was identified for first-episode psychosis (11 studies), with a focus on early intervention (7/11 studies) which again had positive conclusions though with greater uncertainty. Conclusions Study findings generally concluded interventions were cost-effective. The evidence for the population who are at-risk of psychosis was limited, and though there were more studies for the population with first-episode psychosis, limitations of the evidence base (including generalisability and heterogeneity across the methods used) affect the certainty of conclusions.

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“…The primary outcome of the NAYAB study was transition to psychosis at 12 months. The detailed methodology of the primary study has been described in the published protocol (Qurashi et al, 2017). In this cross‐sectional secondary analysis, we sought to investigate the prevalence of depressive and suicidal ideation in people with ARMS using data collected from the Montgomery and Asberg Depression Rating Scale (MADRS) (Montgomery & Asberg, 1979).…”

Section: Methodsmentioning

confidence: 99%

Demographic and clinical correlates of suicidal ideation in individuals with at‐risk mental state (ARMS): A study from Pakistan

Husain

Chaudhry

Khoso

et al. 2023

Early Intervention Psych

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BackgroundSuicide is a major public health concern and one of the leading causes of mortality worldwide. People with an at‐risk‐mental‐state (ARMS) for psychosis are more vulnerable to psychiatric co‐morbidity and suicide, however, there are limited data from low‐middle‐income countries. The present study aimed to identify the prevalence of depressive symptoms and suicidal ideation along with sociodemographic and clinical correlates of suicidal ideation in individuals with ARMS from Pakistan.MethodParticipants between the age of 16 and 35 years who met the criteria for ARMS based on the Comprehensive Assessment of At‐Risk Mental State (CAARMS), were recruited from the community, general practitioner clinics and psychiatric units across Pakistan (n = 326). Montgomery and Asberg Depression Rating Scale (MADRS) and Social‐Occupational‐Functional‐Assessment‐Scale (SOFAS) were administered to participants.ResultsThe prevalence of depressive symptoms and suicidal thoughts in the sample at baseline were 91.1% (n = 297) and 61.0% (n = 199), respectively. There were significant mean differences between groups (mean difference [95% CI]; p‐value) without suicidal ideation and with suicidal ideation on measures of MADRS (−5.47 [−7.14, −3.81]; p < .001), CAARMS non‐bizarre ideas (−0.29 [−0.47, −0.11]; p = .002) and perceptual abnormalities (−0.23 [−0.41, −0.04]; p = .015).ConclusionThese findings indicate that suicidal ideation and depressive symptoms are highly prevalent in individuals with ARMS in Pakistan. Given the pivotal developmental stages that ARMS presents, and the poor outcomes associated with co‐morbid depression, there is an urgent need to prioritize the development of low‐cost and scalable evidence‐based interventions to address psychiatric comorbidity and suicidality in the ARMS population in Pakistan.

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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 (NAYAB): study protocol

Cited by 13 publications

References 32 publications

A Characterization of the Effects of Minocycline Treatment During Adolescence on Structural, Metabolic, and Oxidative Stress Parameters in a Maternal Immune Stimulation Model of Neurodevelopmental Brain Disorders

A Characterization of the Effects of Minocycline Treatment During Adolescence on Structural, Metabolic, and Oxidative Stress Parameters in a Maternal Immune Stimulation Model of Neurodevelopmental Brain Disorders

A review of economic evaluations of health care for people at risk of psychosis and for first-episode psychosis

Demographic and clinical correlates of suicidal ideation in individuals with at‐risk mental state (ARMS): A study from Pakistan

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