Culturally adapted psychosocial interventions (CaPSI) for early psychosis in a low-resource setting: study protocol for a large multi-center RCT.

BACKGROUND: Psychosis treatment guidelines recommend cognitive behaviour therapy (CBT) and family intervention (FI), for all patients with first episode psychosis (FEP), though guidance borrows heavily from literature in adults from high income countries. To our knowledge, there are few randomized controlled trials (RCTs) examining the comparative effect of these commonly endorsed psychosocial interventions in individuals with early psychosis from high-income countries and no such trials from low and middle-income countries (LMICs). The present study aims to confirm the clinical-efficacy and cost-effectiveness of delivering culturally adapted CBT (CaCBT) and culturally adapted FI (CulFI) to individuals with FEP in Pakistan. METHOD: A multi-centre, three-arm RCT of CaCBT, CulFI, and treatment as usual (TAU) for individuals with FEP (n = 390), recruited from major centres across Pakistan. Reducing overall symptoms of FEP will be the primary outcome. Additional aims will include improving patient and carer outcomes and estimating the economic impact of delivering culturally appropriate psychosocial interventions in low-resource settings. This trial will assess the clinical-efficacy and cost-effectiveness of CaCBT and CulFI compared with TAU in improving patient (positive and negative symptoms of psychosis, general psychopathology, depressive symptoms, quality of life, cognition, general functioning, and insight) and carer related outcomes (carer experience, wellbeing, illness attitudes and symptoms of depression and anxiety). CONCLUSIONS: A successful trial may inform the rapid scale up of these interventions not only in Pakistan but other low-resource settings, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority groups with FEP. TRIAL REGISTRATION: NCT05814913.

A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis.

NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as used in the treatment of systemic autoimmune disorders would be tolerable and effective in people with schizophrenia in a feasibility study. Ninety-two participants within 5 years of schizophrenia diagnosis were recruited from inpatient and outpatient facilities in Karachi, Pakistan. They were randomised to receive once weekly 10-mg oral methotrexate (n = 45) or matching placebo (n = 47) both with daily 5-mg folic acid, in addition to treatment as usual for 12 weeks. There were eight dropouts per group. Side effects were non-significantly more common in those on methotrexate and were not severe. One person developed leukopenia. Positive symptom scores improved more in those receiving methotrexate than placebo (ß = -2.5; [95% CI -4.7 to -0.4]), whereas negative symptoms were unaffected by treatment (ß = -0.39; [95% CI -2.01 to 1.23]). There were no immune biomarkers but methotrexate did not affect group mean leucocyte counts or C-reactive protein. We conclude that further studies are feasible but should be focussed on subgroups identified by advances in neuroimmune profiling. Methotrexate is thought to work in autoimmune disorders by resetting systemic regulatory T-cell control of immune signalling; we show that a similar action in the CNS would account for otherwise puzzling features of the immuno-pathogenesis of schizophrenia.

Self-harm in British South Asian women: psychosocial correlates and strategies for prevention.

OBJECTIVE: To review the rates of self-harm in British South Asian women, look into the factors that contribute to these high rates of self-harm and discuss possible strategies for prevention and provision of culturally sensitive service for South Asian women who harm themselves. METHOD: Review. RESULTS: South Asian women are significantly more likely to self harm between ages 16-24 years than white women. Across all age groups the rates of self harm are lower in South Asian men as compared to South Asian women. These women are generally younger, likely to be married and less likely to be unemployed or use alcohol or other drugs. They report more relationship problems within the family. South Asian women are less likely to attend the ER with repeat episode since they hold the view that mainstream services do not meet their needs. CONCLUSION: South Asian women are at an increased risk of self harm. Their demographic characteristics, precipitating factors and clinical management are different than whites. There is an urgent need for all those concerned with the mental health services for ethnic minorities to take positive action and eradicate the barriers that prevent British South Asians from seeking help. There is a need to move away from stereotypes and overgeneralisations and start from the user's frame of reference, taking into account family dynamics, belief systems and cultural constraints.

Some new 2-aryloxymethyl-3-alpha-substituted carboxymethyl-6,8-substituted-4-quinazolones as possible anticonvulsants.

In view of their expected MAO inhibitory, CNS depressant and anticonvulsant properties, thirty new 2-aryloxymethyl-3-alpha-substituted carboxymethyl-6,8-substituted-4-quinazolones were synthesized by the reaction of substituted anthranil with various amino acids in pyridine. Some of these compounds at a concentration of 1 X 10(-3) mol/l inhibited rat brain monamine oxidase (MAO) in vitro and provided protection against pentylenetetrazole induced convulsions in mice.