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.

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.

Effectiveness of a group psychological intervention to reduce psychosocial distress in adolescents in Pakistan: a single-blind, cluster randomised controlled trial.

BACKGROUND: Emotional problems in adolescents living in low-income and middle-income countries (LMICs) remain largely unaddressed; key reasons include a scarcity of trained mental health professionals and unavailability of evidence-based, scalable psychological interventions. We aimed to evaluate the effectiveness of a non-specialist-delivered, group psychological intervention to reduce psychosocial distress in school-going adolescents in Pakistan. METHODS: In a two-arm, single-blind, cluster randomised controlled trial, eligible public school clusters from a rural subdistrict of Gujar Khan, Rawalpindi, Pakistan, were randomised (1:1, stratified by sex) using permuted block randomisation into intervention (n=20) and wait-list control (n=20) groups. Adolescents aged 13-15 years who provided informed assent and caregivers' consent were screened for psychosocial distress using the youth-reported Pediatric Symptoms Checklist (PSC; total psychosocial distress scores from 0 to 70), and those scoring 28 or more and their caregivers were enrolled into the trial. Adolescents in the intervention group received seven weekly group sessions and their caregivers received three biweekly group sessions in school settings from trained non-specialists. The primary outcome was change from baseline in the total PSC scores at 3 months post-intervention. The trial was registered prospectively with the International Standard Randomised Controlled Trial Number registry, ISRCTN17755448. FINDINGS: From the 40 school clusters that were included, 282 adolescents in the intervention group and 284 adolescents in the wait-list control group were enrolled between Nov 2 and Nov 30, 2021. At 3 months, adolescents in the intervention group had significantly lower mean total score on the PSC compared with adolescents in the control group (mean difference in change from baseline 3·48 [95% CI 1·66-5·29], p=0·0002, effect size 0·38 [95% CI 0·18-0·57]; adjusted mean difference 3·26 (95% CI 1·46-5·06], p=0·0004, effect size 0·35 (0·16-0·55). No adverse events were reported in either group. INTERPRETATION: The group psychological intervention most likely represents a feasible and effective option for adolescents with psychosocial distress in school settings. FUNDING: UK Medical Research Council, Foreign Commonwealth and Development Office, Department of Health and Social Care. TRANSLATION: For the Urdu translation of the abstract see Supplementary Materials section.