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

BACKGROUND: Suicide 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. METHOD: Participants 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. RESULTS: The 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). CONCLUSION: These 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.

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.

Promising use of minocycline augmentation with clozapine in treatment-resistant schizophrenia.

Treatment-resistant schizophrenia is a major health problem in the UK with the majority of patients treated with clozapine. In up to 70% of cases there is only a partial response to clozapine with continuing refractory symptoms. We describe two cases in a UK mental health service where minocycline was found to be useful and well tolerated as an augmentation agent with clozapine in the improvement of previously resistant positive and negative symptoms.

Management of physical health in patients with schizophrenia: international insights.

This international meeting discussed the management of physical health in patients with schizophrenia in several countries including France, Spain, Germany, the UK and Italy. Physical health parameters, including weight, blood pressure, blood glucose, lipids and standard biochemical assessments are measured in many patients at the first hospital consultation. These reveal physical disorders such as obesity, hypertension, dyslipidaemia, the metabolic syndrome, substance abuse, cardiovascular disease, extrapyramidal symptoms, sexual dysfunction and diabetes in substantial proportions of patients. Psychiatrists consider switching antipsychotic therapy if excessive sedation, extrapyramidal symptoms, unacceptable weight gain, hyperglycaemia or dyslipidaemia occur. In general, switching is more likely to be considered for symptomatic adverse events than for laboratory abnormalities. Switching is discouraged by limited knowledge of protocols, the absence of guidelines and fears of relapse or reduced treatment adherence. The physical health of patients with schizophrenia receives much less attention in the community setting than in the hospital setting. Improved guidelines, protocols, resources and support are needed to improve the physical health of patients in the community.

Psychiatrists' use, knowledge and attitudes to first- and second-generation antipsychotic long-acting injections: comparisons over 5 years.

Psychiatrists' attitudes and knowledge about antipsychotic long-acting injections (LAIs) are important given the increasing emphasis on patient choice in treatment and the availability of second-generation antipsychotic (SGA) LAIs. A cross-sectional study of consultant psychiatrists' attitudes and knowledge in North West England was carried out. A pre-existing questionnaire on clinicians' attitudes and knowledge regarding LAIs was updated. Of 102 participants, 50% reported a decrease in their use of LAIs. LAI prescribing was evenly split between first-generation antipsychotic (FGA) and SGA-LAIs. Most regarded LAIs as associated with better adherence (89%) than tablets. A substantial proportion believed that LAIs could not be used in first-episode psychosis (38%) and that patients always preferred tablets (33%). Compared with a previous sample, the current participants scored more favourably on a patient-centred attitude subscale (60.4% vs 63.5%, P = 0.034) and significantly fewer regarded LAIs as being stigmatising and old-fashioned. Reported LAI prescribing rates have decreased in the last 5 years despite an SGA-LAI becoming available and most clinicians regarding LAIs as effective. Most attitudes and knowledge have remained stable although concerns about stigma with LAI use have decreased. Concerns about patient acceptance continue as do negative views about some aspects of LAI use; these may compromise medication choices offered to patients.

A population-based study of irritable bowel syndrome in a non-Western population.

Previous studies have found no female predominance in irritable bowel syndrome (IBS) in non-Western countries. The aim of the study was to assess the prevalence and correlates of Rome II (IBS) in both sexes in Pakistan. A Population-based survey in a low-income inner city area using questionnaires to diagnose Rome II IBS and assess distress, disability and stressful life events. Data were collected from 880/938 (93%) randomly selected residents. 13.4% of women and 13.1% men met criteria for Rome II IBS; 34 (3.9%) had diarrhoea-predominant, 59 (6.7%) had constipation-predominant IBS and 24 (2.7%) had 'mixed IBS'. In logistic regression analysis, IBS was associated in men with high income (OR = 1.56; 95% CI: 1.05-2.3) and few years of education (OR = 2.17; 95% CI: 1.2-3.9) and in women with being married (OR = 3.6; 95% CI: 1.1-11.9) and stressful life events score (OR = 1.14; 95% CI: 1.01-1.3). Disability was associated with constipation-predominant IBS (OR = 1.99; 95% CI: 1.1-3.6), distress (OR = 1.19; 95% CI: 1.14-1.23) and stressful life events (OR = 1.19; 95% CI: 1.1-1.3). Investigations were more likely in men (54%) than in women (27%) (P = 0.003). These findings suggest that the equal sex ratio of IBS in urban Pakistan could result from a close association between marked distress and IBS in men similar to that found in women in western studies.

Life stress and depression in a tribal area of Pakistan.

BACKGROUND: Depression is common in Pakistan but no research on this subject has been reported from the North West Frontier Province (NWFP), host to numerous Afghan refugees. AIMS: To measure depressive symptoms and associated features in a population-based sample. METHOD: A Pushto translation of the Self Reporting Questionnaire (SRQ) was administered to 471 adults living in a village in one of the federally administered tribal areas. Respondents were also assessed with a life events checklist for social problems, a social support questionnaire and the Brief Disability Questionnaire. RESULTS: Sixty per cent (95/158) of women and 45% (140/313) of men scored 9 or more on the SRQ. High SRQ score was associated with few years of education, higher social problem score, less social support and greater disability. High social problem score was the strongest correlate. CONCLUSIONS: This population reports more depressive symptoms than other communities in Pakistan and this probably reflects the very high degree of social stress experienced in the NWFP, which has been affected by years of turmoilin neighbouring Afghanistan.

Prevalence and social correlates of postnatal depression in a low income country.

BACKGROUND: Postnatal depression is an important public health problem worldwide. Recent evidence suggests that rates may be relatively higher in developing countries. We aimed to explore the prevalence of postnatal depression and its association with social support and other risk factors in a sample of Pakistani women. METHODS: Population-based survey of 149 women at 12 weeks postnatal using the Edinburgh Postnatal Depression Scale (EPDS), Multidimensional Scale of Perceived Social Support (MSPSS) and Personal Information Questionnaire (PIQ). RESULTS: Thirty six percent women scored > or =12 on EPDS. High depression score was associated with lower social support, increased stressful life events in the preceding year and higher levels of psychological distress in the antenatal period. CONCLUSIONS: There is a high prevalence of postnatal depression in Pakistani women. Early interventions should be developed that target the antenatal period and strengthen social support networks in women at risk.

Effects of the 5HT antagonist cyproheptadine on neuropsychological function in chronic schizophrenia.

This study tests the hypothesis that the ability of atypical neuroleptics to improve negative symptoms is due to 5HT-receptor antagonism and enhanced frontal lobe function. We investigated the effects of cyproheptadine (a 5HT2 antagonist) on neuropsychological tests of frontal lobe functions in chronic schizophrenic patients. Eighteen stable schizophrenic patients on depot neuroleptic medication participated in a 4-week double blind crossover study. Outcome measures were clinical symptoms rating scales, neuropsychological tests (verbal fluency, Stroop colour word task, trail making) and antisaccade eye movements. During the cyproheptadine phase statistically significant improvement was seen on Stroop colour word task, verbal fluency and Trail B tests. The ability to suppress reflexive eye movement to a target light in an anti saccade task was also significantly enhanced. The patients had low clinical ratings of negative symptoms and they were unaffected by cyproheptadine. The results indicate that 5HT2C receptors selectively modulate speed and motor control mechanisms related to frontal lobe functions but this was not associated with changes in symptoms.