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Background and Hypothesis: Oxidative stress pathways may play a role in schizophrenia through direct neuropathic actions, microglial activation, inflammation, and by interfering with NMDA neurotransmission. N-acetylcysteine (NAC) has been shown to improve negative symptoms of schizophrenia, however, results from trials of other compounds targeting NMDA neurotransmission have been mixed. This may reflect poor target engagement but also that risk mechanisms act in parallel. Sodium Benzoate (NaB) could have an additive with NAC to act on several pathophysiological mechanisms implicated in schizophrenia. Study Design: A multicenter, 12 weeks, 2â ×â 2 factorial design, randomized double-blind placebo-controlled feasibility trial of NaB and NAC added to standard treatment in 68 adults with early schizophrenia. Primary feasibility outcomes included recruitment, retention, and completion of assessments as well as acceptability of the study interventions. Psychosis symptoms, functioning, and cognitive assessments were also assessed. Study Results: We recruited our desired sample (nâ =â 68) and retained 78% (nâ =â 53) at 12 weeks, supporting the feasibility of recruitment and retention. There were no difficulties in completing clinical outcome schedules. Medications were well tolerated with no dropouts due to side effects. This study was not powered to detect clinical effect and as expected no main effects were found on the majority of clinical outcomes. Conclusions: We demonstrated feasibility of conducting a clinical trial of NaB and NAC. Given the preliminary nature of this study, we cannot draw firm conclusions about the clinical efficacy of either agent, and a large-scale trial is needed to examine if significant differences between treatment groups emerge. Trial Registration: ClinicalTrials.gov: NCT03510741.
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Individuals with clinical high risk (CHR) for psychosis experience significant distress, impaired general functioning and a high lifetime risk of self-harm and attempted suicide. The CHR period is an important phase in an individual's mental health where appropriate interventions may reduce the risk of progression to several negative outcomes, including the development of schizophrenia. Given that up to 80% of individuals with CHR have another diagnosable mental illness and almost half experience poor psychosocial functioning, developing interventions that address psychosocial functioning in young people with CHR is of great importance. This mixed-methods study aims to employ qualitative and quantitative methods to adapt an evidence-based comprehensive psychosocial and mental health self-efficacy program, the Optimal Health Program (OHP), and evaluate the feasibility, acceptability and preliminary clinical efficacy in young people with CHR. We aim to recruit 30 CHR participants (age 16-29 years) in a single-arm 12-week exploratory clinical trial. Feasibility metrics will include recruitment, retention, and data completion rates. Acceptability will be informed by the Client Satisfaction Questionnaire. Clinical assessments (psychosis spectrum symptoms, depression, and anxiety), functional measures, and cognitive outcomes will be completed at study entry and repeated post-intervention at 12-weeks. We will run pre-post test data analysis to examine changes following engagement in the OHP intervention. Qualitative interviews will be conducted post-intervention to further evaluate the acceptability of the intervention and the trial design, and will be analyzed using thematic analysis. OHP may enhance the long-term mental health, well-being and functioning of CHR youth. However, the intervention must first be adapted to a CHR population; then, the feasibility and preliminary efficacy of delivering an intervention tailored around the varied needs of the CHR group must be established before a larger-scale appropriately powered study is pursued. Trial registration: The trial is registered with ClinicalTrials.gov NCT05757128.
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Estudos de Viabilidade , Transtornos Psicóticos , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Saúde Mental , Transtornos Psicóticos/terapia , Transtornos Psicóticos/psicologia , Ensaios Clínicos como AssuntoRESUMO
BACKGROUND: Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We conducted a systematic review of the literature to identify neuroimaging studies specifically examining synaptic density across the psychosis spectrum. METHODS: PRISMA guidelines on reporting were followed. We systematically searched MEDLINE, Embase, APA PsycINFO, Web of Science and The Cochrane Library from inception to December 8, 2023, and included all original peer-reviewed articles or completed clinical neuroimaging studies of any modality measuring synaptic density in participants with a diagnosis of psychosis spectrum disorder as well as individuals with psychosis-risk states. The NIH quality assessment tool for observational cohort and cross-sectional studies was used for the risk of bias assessment. RESULTS: Five studies (k = 5) met inclusion criteria, comprising n = 128 adults (psychotic disorder; n = 61 and healthy volunteers; n = 67 and specifically measuring synaptic density via positron emission tomography (PET) imaging of the synaptic vesicle glycoprotein 2 A (SV2A). Three studies were included in our primary meta-analysis sharing the same outcome measure of SV2A binding, volume of distribution (VT). Regional SV2A VT was reduced in psychotic disorder participants in comparison to healthy volunteers, including the occipital lobe (Mean Difference (MD)= -2.17; 95% CI: -3.36 to -0.98; P < 0.001 ), temporal lobe (MD: -2.03; 95% CI: -3.19 to -0.88; P < 0.001 ), parietal lobe (MD:-1.61; 95% CI: -2.85 to -0.37; P = 0.01), anterior cingulate cortex (MD= -1.47; 95% CI: -2.45 to -0.49; P = 0.003), frontal cortex (MD: -1.16; 95% CI: -2.18 to -0.15; P = 0.02), amygdala (MD: -1.36; 95% CI: -2.20 to -0.52, p = 0.002), thalamus (MD:-1.46; 95% CI:-2.46 to -0.46, p = 0.004) and hippocampus (MD= -0.96; 95% CI: -1.59 to -0.33; P = 0.003). CONCLUSIONS: Preliminary studies provide in vivo evidence for reduced synaptic density in psychotic disorders. However, replication of findings in larger samples is required prior to definitive conclusions being drawn. PROSPERO: CRD42022359018.
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Neuroimagem , Tomografia por Emissão de Pósitrons , Transtornos Psicóticos , Sinapses , Humanos , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/patologia , Transtornos Psicóticos/fisiopatologia , Neuroimagem/métodos , Sinapses/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Proteínas do Tecido Nervoso , Glicoproteínas de MembranaRESUMO
BACKGROUND: Psychosis spectrum symptoms (PSSs) occur in a sizable percentage of youth and are associated with poorer cognitive performance, poorer functioning, and suicidality (i.e., suicidal thoughts and behaviors). PSSs may occur more frequently in youths already experiencing another mental illness, but the antecedents are not well known. The Toronto Adolescent and Youth (TAY) Cohort Study aims to characterize developmental trajectories in youths with mental illness and understand associations with PSSs, functioning, and suicidality. METHODS: The TAY Cohort Study is a longitudinal cohort study that aims to assess 1500 youths (age 11-24 years) presenting to tertiary care. In this article, we describe the extensive diagnostic and clinical characterization of psychopathology, substance use, functioning, suicidality, and health service utilization in these youths, with follow-up every 6 months over 5 years, including early baseline data. RESULTS: A total of 417 participants were enrolled between May 4, 2021, and February 2, 2023. Participants met diagnostic criteria for an average of 3.5 psychiatric diagnoses, most frequently anxiety and depressive disorders. Forty-nine percent of participants met a pre-established threshold for PSSs and exhibited higher rates of functional impairment, internalizing and externalizing symptoms, and suicidality than participants without PSSs. CONCLUSIONS: Initial findings from the TAY Cohort Study demonstrate the feasibility of extensive clinical phenotyping in youths who are seeking help for mental health problems. PSS prevalence is much higher than in community-based studies. Our early data support the critical need to better understand longitudinal trajectories of clinical youth cohorts in relation to psychosis risk, functioning, and suicidality.
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Transtornos Psicóticos , Suicídio , Humanos , Adolescente , Criança , Adulto Jovem , Adulto , Ideação Suicida , Estudos de Coortes , Estudos Longitudinais , Suicídio/psicologia , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologiaRESUMO
BACKGROUND: South Asian (SA) Canadians are disproportionately affected by higher rates of mood and anxiety disorders. SA Canadians with depression report significant barriers to accessing mental health care and the highest proportion of unmet mental health needs. The Mental Health Commission of Canada (MHCC) advocates for culturally and linguistically relevant services for SA Canadians. Culturally adapted cognitive behavior therapy (CaCBT) has shown to be more effective than standard cognitive behavior therapy (CBT). Adapting CBT for the growing SA population in Canada will ensure equitable access to effective, culturally-appropriate mental health interventions. METHOD: The study used a qualitative design to elicit stakeholder consultation via in-depth interviews. This study is reported using the criteria included in Consolidated Criteria for Reporting Qualitative Studies (COREQ). The analysis follows an ethnographic approach and was informed by the principles of emergent design. RESULTS: Five themes were identified from the analysis, (i) Awareness and preparation: factors that impact the individual's understanding of therapy and mental illness. (ii) Access and provision: SA Canadians' perception of barriers, facilitators, and access to treatment. (iii) Assessment and engagement: experiences of receiving helpful treatment. (iv) Adjustments to therapy: modifications and suggestions to standard CBT. (v) Ideology and ambiguity: racism, immigration, discrimination, and other socio-political factors. CONCLUSIONS: Mainstream mental health services need to be culturally appropriate to better serve SA Canadians experiencing depression and anxiety. Services must understand the family dynamics, cultural values and socio-political factors that impact SA Canadians to reduce attrition rates in therapy.
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Terapia Cognitivo-Comportamental , Serviços Comunitários de Saúde Mental , Assistência à Saúde Culturalmente Competente , Transtornos Mentais , Humanos , Canadá , Povo AsiáticoRESUMO
Personality disorders (PDs) have a global prevalence of 7.8% and are associated with increased rates of morbidity and mortality. Most research on PDs has been conducted in High Income Countries (HICs). We conducted a systematic review to investigate the effectiveness of psychosocial and pharmacological interventions for personality disorders (PDs) in individuals from Low- and Middle-Income Countries (LMICs.) We systematically searched MEDLINE, Embase, APA PsycInfo, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and The Cochrane Library from inception to January 5, 2023. Inclusion criteria were quantitative studies and grey literature where participants received a psychosocial or pharmacological intervention for PD. Exclusion criteria were qualitative studies, review articles, studies in which PD was not the primary condition, and articles not available in English. The Cochrane Risk of Bias tool version 2.0 and Joanna Briggs Institute instruments were used to measure risk of bias. Studies were pooled by type of study, PD investigated, type of intervention, assessment methods, and outcomes. Sixteen studies met inclusion criteria and were included. Fifteen were intervention studies related to borderline PD. Only one studied mixed PDs. Twelve studies were of psychotherapy, one pharmacotherapy, one combination of both, and two neurostimulation. Most of the studies showed improvement in symptoms though data was largely collected using self-report measures. There were only six RCTs. There is a dearth of literature on interventions for PDs in LMICs and funding bodies should prioritize research in LMICs. Systematic Review Registration Number: PROSPERO CRD42021233415.
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BACKGROUND: Suicide is one of the leading causes of mortality worldwide, and the majority of suicide deaths occur in low- and middle-income countries. AIMS: To evaluate the demographic and clinical characteristics of individuals who have presented to health services following self-harm in Pakistan. METHOD: This study is a cross-sectional baseline analysis of participants from a large multicentre randomised controlled trial of self-harm prevention in Pakistan. A total of 901 participants with a history of self-harm were recruited from primary care clinics, emergency departments and general hospitals in five major cities in Pakistan. The Beck Scale for Suicide Ideation (BSI), Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS) and Suicide Attempt Self Injury Interview assessment scales were completed. RESULTS: Most participants recruited were females (n = 544, 60.4%) in their 20s. Compared with males, females had lower educational attainment and higher unemployment rates and reported higher severity scores on BSI, BDI and BHS. Interpersonal conflict was the most frequently cited antecedent to self-harm, followed by financial difficulties in both community and hospital settings. Suicide was the most frequently reported motive of self-harm (N = 776, 86.1%). Suicidal intent was proportionally higher in community-presenting patients (community: N = 318, 96.9% v. hospital: N = 458, 79.9%; P < 0.001). The most frequently reported methods of self-harm were ingestion of pesticides and toxic chemicals. CONCLUSIONS: Young females are the dominant demographic group in this population and are more likely to attend community settings to seek help. Suicidal intent as the motivator of self-harm and use of potentially lethal methods may suggest that this population is at high risk of suicide.
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BACKGROUND: Suicidal ideation and attempts are growing public health concerns globally. Evidence from high-income countries suggests that individuals with psychosis and bipolar disorder are at increased risk of suicidal ideation and attempts, but there is a scarcity of evidence from South Asia. AIMS: To estimate the prevalence of suicidal ideation and attempts in individuals with psychosis and bipolar disorder in South Asia. METHOD: In this systematic review and meta-analysis, four databases (PsycINFO, Web of Science, EMBASE and Medline) were searched until December 2022. Pooled prevalence was estimated with random-effects models. Heterogeneity was quantified with the I2-statistic. RESULTS: The pooled sample size across the 21 studies was 3745 participants, 1941 (51.8%) of which were male. The pooled prevalence of suicide attempts in South Asian people with either psychosis or bipolar disorder was 22% (95% CI 17-27; n = 15). The pooled prevalence of suicidal ideation with psychosis or bipolar disorder combined was 38% (95% CI 27-51; n = 10). Meta-regression, subgroup and sensitivity analysis showed that the pooled prevalence estimates for both suicide attempt and ideation remained unaffected by variations in critical appraisal ratings and study designs. Only one study reported data on suicide-related deaths. CONCLUSIONS: One in four individuals diagnosed with psychosis or bipolar disorder have reported suicide attempts, whereas up to one in three have experienced suicidal ideation. These findings underscore the urgent need for clinicians to regularly assess and monitor suicidal ideation and attempts among individuals with these disorders in South Asia.
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Schizophrenia spectrum disorders (SSDs) are associated with significant functional impairments, disability, and low rates of personal recovery, along with tremendous economic costs linked primarily to lost productivity and premature mortality. Efforts to delineate the contributors to disability in SSDs have highlighted prominent roles for a diverse range of symptoms, physical health conditions, substance use disorders, neurobiological changes, and social factors. These findings have provided valuable advances in knowledge and helped define broad patterns of illness and outcomes across SSDs. Unsurprisingly, there have also been conflicting findings for many of these determinants that reflect the heterogeneous population of individuals with SSDs and the challenges of conceptualizing and treating SSDs as a unitary categorical construct. Presently it is not possible to identify the functional course on an individual level that would enable a personalized approach to treatment to alter the individual's functional trajectory and mitigate the ensuing disability they would otherwise experience. To address this ongoing challenge, this study aims to conduct a longitudinal multimodal investigation of a large cohort of individuals with SSDs in order to establish discrete trajectories of personal recovery, disability, and community functioning, as well as the antecedents and predictors of these trajectories. This investigation will also provide the foundation for the co-design and testing of personalized interventions that alter these functional trajectories and improve outcomes for people with SSDs.
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Esquizofrenia , Humanos , Esquizofrenia/terapia , Conhecimento , Mortalidade Prematura , Neurobiologia , Exame FísicoRESUMO
BACKGROUND: Self-harm is an important predictor of a suicide death. Culturally appropriate strategies for the prevention of self-harm and suicide are needed but the evidence is very limited from low- and middle-income countries (LMICs). This study aims to investigate the effectiveness of a culturally adapted manual-assisted problem-solving intervention (CMAP) for patients presenting after self-harm. METHODS: This was a rater-blind, multicenter randomised controlled trial. The study sites were all participating emergency departments, medical wards of general hospitals and primary care centres in Karachi, Lahore, Rawalpindi, Peshawar, and Quetta, Pakistan. Patients presenting after a self-harm episode (n = 901) to participating recruitment sites were assessed and randomised (1:1) to one of the two arms; CMAP with enhanced treatment as usual (E-TAU) or E-TAU. The intervention (CMAP) is a manual-assisted, cognitive behaviour therapy (CBT)-informed problem-focused therapy, comprising six one-to-one sessions delivered over three months. Repetition of self-harm at 12-month post-randomisation was the primary outcome and secondary outcomes included suicidal ideation, hopelessness, depression, health-related quality of life (QoL), coping resources, and level of satisfaction with service received, assessed at baseline, 3-, 6-, 9-, and 12-month post-randomisation. The trial is registered on ClinicalTrials.gov. NCT02742922 (April 2016). RESULTS: We screened 3786 patients for eligibility and 901 eligible, consented patients were randomly assigned to the CMAP plus E-TAU arm (n = 440) and E-TAU arm (N = 461). The number of self-harm repetitions for CMAP plus E-TAU was lower (n = 17) compared to the E-TAU arm (n = 23) at 12-month post-randomisation, but the difference was not statistically significant (p = 0.407). There was a statistically and clinically significant reduction in other outcomes including suicidal ideation (- 3.6 (- 4.9, - 2.4)), depression (- 7.1 (- 8.7, - 5.4)), hopelessness (- 2.6 (- 3.4, - 1.8), and improvement in health-related QoL and coping resources after completion of the intervention in the CMAP plus E-TAU arm compared to the E-TAU arm. The effect was sustained at 12-month follow-up for all the outcomes except for suicidal ideation and hopelessness. On suicidal ideation and hopelessness, participants in the intervention arm scored lower compared to the E-TAU arm but the difference was not statistically significant, though the participants in both arms were in low-risk category at 12-month follow-up. The improvement in both arms is explained by the established role of enhanced care in suicide prevention. CONCLUSIONS: Suicidal ideation is considered an important target for the prevention of suicide, therefore, CMAP intervention should be considered for inclusion in the self-harm and suicide prevention guidelines. Given the improvement in the E-TAU arm, the potential use of brief interventions such as regular contact requires further exploration.
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Terapia Cognitivo-Comportamental , Comportamento Autodestrutivo , Suicídio , Humanos , Adulto , Qualidade de Vida , Comportamento Autodestrutivo/prevenção & controle , Comportamento Autodestrutivo/psicologia , Ideação SuicidaRESUMO
OBJECTIVES: Chronic obstructive pulmonary disease contributes to substantial health and economic burden worldwide. Co-morbid depression and anxiety are highly prevalent in patients with chronic obstructive pulmonary disease. Depressive symptoms in chronic obstructive pulmonary disease are associated with poorer survival, longer hospitalisation and impaired quality of life. Literature on chronic obstructive pulmonary disease is largely derived from high-income countries; yet 90% of deaths related to chronic obstructive pulmonary disease occur in low- and middle-income countries. We aimed to establish the prevalence of anxiety and depression in patients with chronic obstructive pulmonary disease, as well as the association with psychosocial outcomes. METHODS: This was a cross-sectional study of chronic obstructive pulmonary disease patients attending outpatient primary care clinics in Karachi, Pakistan. The Patient Health Questionnaire-9 was used to assess depression and the Generalised Anxiety Disorder-7 scale was used for the assessment of anxiety. Health-related quality of life was assessed with EuroQol-Five Dimensions, social support with Oslo-3 and social stress with Life Events Checklist. We recruited 293 subjects. RESULTS: The prevalence of depression and anxiety in the sample was 51% (n = 149) and 20% (n = 59), respectively. Depressed chronic obstructive pulmonary disease patients reported significantly lower health-related quality of life scores as compared to non-depressed patients. Participants with depression had significantly higher levels of anxiety, less social support, higher social stress and more subjective impairment in quality of life. CONCLUSION: Given the association with reduced social support and increased perceived stress, the role of psychosocial interventions must be explored in improving outcomes of chronic obstructive pulmonary disease patients in Pakistan.
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OBJECTIVE: Anxiety symptoms are highly prevalent among individuals with bipolar disorder (BD) but there is little guidance on pharmacotherapy for these symptoms. The objective of this systematic review and meta-analysis was to evaluate the available evidence for pharmacotherapy of comorbid anxiety symptoms in BD. METHODS: Completed randomized clinical trials (RCTs) of medications for BD published prior to December 2020 were identified through a systematic search of MEDLINE, Embase, PsycInfo, Web of Science, clinicaltrials.gov, and the ISRCTN. Data from RCTs measuring anxiety symptoms at baseline and endpoint and all-cause discontinuation were pooled to compare the efficacy and acceptability of medications with control conditions. RESULTS: Thirty-seven RCTs met our inclusion criteria; 13 placebo-controlled RCTs with 2175 participants had sufficient data to be included in the meta-analysis assessing anxiety symptoms. Compared with placebo, the overall effect size of medications (primarily atypical antipsychotics) on anxiety symptoms was small with a standardized mean difference (SMD) = -0.22 (95% CI: -0.34 to -0.11). Study heterogeneity was low (I2 = 26%). The acceptability of these medications was comparable with placebo with odds ratio of discontinuation from all causes = 0.98 (95% CI: 0.91-1.06). CONCLUSION: There is limited evidence for a small anxiolytic effect and good acceptability of pharmacotherapy (primarily atypical antipsychotics) in the treatment of comorbid anxiety symptoms in BD. These results highlight the need for further research on medications other than atypical antipsychotics.
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Antipsicóticos , Transtorno Bipolar , Antipsicóticos/uso terapêutico , Ansiedade/tratamento farmacológico , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Comorbidade , HumanosRESUMO
Major depressive disorder (MDD) and bipolar disorder (BD) are often chronic with many patients not responding to available treatments. As these mood disorders are frequently associated with metabolic dysfunction, there has been increased interest in novel treatments that would target metabolic pathways. The objectives of this scoping review were to synthesize evidence on the impact on mood symptoms of lipid lowering agents and anti-diabetics drugs, while also reviewing current knowledge on the association between mood disorders and dyslipidemia or hyperglycemia. We propose that metabolic dysfunction is prevalent in both MDD and BD and it may contribute to the development of these disorders through a variety of pathophysiological processes including inflammation, brain structural changes, hormonal alterations, neurotransmitter disruptions, alteration on brain cholesterol, central insulin resistance, and changes in gut microbiota. Current evidence is conflicting on the use of statins, polyunsaturated fatty acids, thiazolidinediones, glucagon-like peptide agonists, metformin, or insulin for the treatment of MDD and BD. Given the paucity of high-quality randomized controlled trials, additional studies are needed before any of these medications can be repurposed in routine clinical practice. Future trials need to enrich patient recruitment, include evaluations of mechanism of action, and explore differential effects on specific symptom domains such as anhedonia, suicidality, and cognition.
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BACKGROUND: Associations between childhood trauma, personality, and Major Depressive Disorder (MDD) have been well established in studies conducted in high-income countries. However, there are limited studies on these associations in low and middle-income countries (LMICs), where MDD is highly prevalent. We assessed the relationships between childhood trauma, personality, and MDD in women in Karachi, Pakistan. METHOD: In this cross-sectional study of 455 female patients attending general medical outpatient clinics, a diagnosis of MDD was confirmed using the Structured Clinical Interview for DSM-IV (SCID); retrospective reports of childhood trauma were collected using the childhood trauma questionnaire (CTQ); and Big Five personality traits were assessed using the NEO Personality Inventory Revised (NEO PI-R). Other measures included the Life Events Questionnaire (LEQ) and the Multidimensional Scale of Perceived Social Support (MSPSS). Factors independently associated with MDD were determined using logistic regression analyses. RESULTS: Of the 455 women recruited between August 1, 2011 and July 31, 2013, 242 (53%) had a diagnosis of MDD. Women with MDD were significantly more likely to be separated, had more stressful life events and higher CTQ scores. Higher perceived social support, conscientiousness and extraversion were independently associated with significantly reduced odds of MDD. There were no significant associations between CTQ scores and any of the NEO PI-R subscales. LIMITATIONS: Ratings of childhood trauma were based on retrospective recall. CONCLUSION: MDD and a history of childhood trauma were highly prevalent in Pakistani women attending general medical clinics. Interventions to prevent childhood trauma and promote social support in women may improve public mental health in LMICs like Pakistan.
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Transtorno Depressivo Maior , Países em Desenvolvimento , Instituições de Assistência Ambulatorial , Estudos Transversais , Depressão , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Paquistão , Personalidade , Estudos Retrospectivos , Apoio SocialRESUMO
The prevalence and risk factors of suicidal ideation in bipolar depression in low- and middle-income countries (LMICs) are poorly understood. This study is a secondary, cross-sectional analysis of a randomized controlled trial from Pakistan, a lower middle-income country. Participants included psychiatric outpatients aged 18 to 65 with a known diagnosis of bipolar disorder and currently in a depressive episode. Suicidality was assessed using the suicide item of the 17-item Hamilton Depression Rating Scale (HAM-D) and levels of severity were categorized as absent, mild/moderate, or severe. Biometric data and biomarkers were obtained. Descriptive statistics were used to describe prevalence and logistic regression applied to establish correlates to suicidal ideation. Among the 266 participants, 67% indicated suicidality of any level and 16% endorsed severe suicidality. Lower body mass index (BMI) (OR = 0.93, 95% CI = 0.88-0.98), higher HAM-D score (OR = 1.29, 95% CI = 1.16-1.43), lower C-reactive protein (CRP) level (OR = 0.53, 95% CI = 0.40-0.70), and increased number of inpatient hospitalizations (OR = 1.16, 95% CI = 1.03-1.31) were identified as significant predictors of suicidality in the fully adjusted regression model. Our findings add to the limited literature on suicidality in bipolar disorder in the LMIC context and suggest roles of biological variables such as BMI and CRP level in predicting suicidal ideation and potentially suicidal behaviours in bipolar depression.
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Transtorno Bipolar , Suicídio , Transtorno Bipolar/epidemiologia , Estudos Transversais , Humanos , Paquistão/epidemiologia , Fatores de Risco , Ideação SuicidaRESUMO
OBJECTIVES: To establish feasibility and acceptability of a Culturally adapted Family Intervention (CulFI) that was developed using an empirically derived conceptual framework in Pakistan. METHODS: A rater-blind, randomised trial to evaluate the feasibility and acceptability of delivering CulFI compared to treatment as usual in Karachi, Pakistan. Indicators of feasibility included evaluation of recruitment rates, retention and randomisation. We also evaluated the acceptability of the intervention and trial procedures. RESULTS: Excellent recruitment and retention rates informed the feasibility of the intervention. CulFI had more than a 90% participant attendance of 8-10 sessions and retained more than 90% who commenced in the intervention. Eighty percent of those who initially provided consent were willing to be randomised and the quality of CulFI was rated as good to excellent by 85.7% of participants. CONCLUSIONS: Importantly, this study determines that pathways into a psychosocial intervention can be established in Pakistan. A combination of factors contribute to low levels of access to psychiatric care including different explanatory models of illness, small numbers of trained staff, limited resources and reliance on traditional healers. These results support the feasibility, acceptability and merit of conducting a full-scale trial of CulFI in comparison with standard care.ClinicalTrials.gov Identifier: NCT02167347KEY POINTSThe significant treatment gap in LMICs leaves families providing much of the care for people with schizophrenia.There is limited evidence from LMICs supporting the effectiveness and feasibility of psychosocial interventions more broadly, and family interventions specifically.This study adds to the scarce literature and demonstrates that pathways into delivering psychosocial interventions can be established in Pakistan.The results of this trial support the feasibility and acceptability of a Culturally adapted Family Intervention (CulFI) for schizophrenia patients and their families in PakistanA full-scale trial of CulFI in comparison with standard care is warranted to determine clinical and cost-effectiveness.
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Assistência à Saúde Culturalmente Competente , Terapia Familiar , Esquizofrenia , Terapia Familiar/métodos , Estudos de Viabilidade , Humanos , Paquistão , Esquizofrenia/terapiaRESUMO
BACKGROUND: The evidence base for stigma in mental health largely originates from high-income countries. AIMS: This study from Pakistan aimed to address the gap in literature on stigma from low- and middle-income countries. METHOD: This cross-sectional study surveyed 1470 adults from Karachi, Pakistan. Participants from three groups (healthcare professionals, healthcare students and the general public) completed the adapted Bogardus Social Distance Scale (SDS) as a measure of stigma. RESULTS: All three groups reported higher scores of stigma toward mental disorders compared with physical disorders. SDS scores for mental illness in the general public were significantly higher than in healthcare students (mean difference (MD) 6.93, 95% CI 5.45-8.45, P < 0.001) and healthcare professionals (MD 6.93, 95% CI 5.48-8.38, P < 0.001). However, SDS scores between healthcare students and healthcare professionals were not significantly different (MD 0.003, 95% CI -1.14-1.14, P > 0.99). Being female was associated with lower stigma scores and being over the age of 30 years was associated with higher stigma scores. CONCLUSIONS: Stigma campaigns in Pakistan need to target the general population. However, evidence of negative attitudes toward mental illness in healthcare students and healthcare professionals supports the need for stronger emphasis on psychiatric education within undergraduate and postgraduate training in Pakistan.
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BACKGROUND: Several small studies suggest that the adjunctive use of anti-inflammatory agents might improve depressive symptoms in bipolar disorder. However, there are few well designed, appropriately powered clinical trials assessing the efficacy of these novel treatment strategies. We aimed to assess the efficacy of adjunctive minocycline or celecoxib in this setting. METHODS: This double-blind, 12-week, randomised, placebo-controlled trial was done in four outpatient psychiatric clinics in Pakistan. Eligible participants were adults (aged 18-65 years) with DSM-5 bipolar disorder (type I or II) and a major depressive episode. In a 2â×â2 factorial design, participants were randomly assigned (1:1:1:1) to receive either active minocycline plus active celecoxib, active minocycline plus placebo celecoxib, placebo minocycline plus active celecoxib, or placebo minocycline plus placebo celecoxib. The primary outcome was the mean change from baseline to week 12 in score on the 17-item Hamilton Depression Rating Scale (HAMD-17), assessed in all randomised participants (missing data were imputed and assumed to be missing at random). The trial was registered with ClinicalTrials.gov, NCT02703363. FINDINGS: 266 (17%) of 1542 patients assessed between May 1, 2016, and March 31, 2019, were randomly assigned to receive minocycline plus celecoxib (n=68), minocycline plus placebo (n=66), celecoxib plus placebo (n=66), or placebo plus placebo (n=66). From baseline to week 12, depressive symptoms as per HAMD-17 reduced in all four groups (from 24·5-25·2 to 11·3-12·8), but these reductions did not differ significantly between the groups. In terms of main effects, reductions in HAMD-17 did not differ for patients treated with minocycline (mean adjusted difference vs non-minocycline 1·48 [95% CI -0·41 to 3·36]; p=0·123) or for celecoxib (mean adjusted difference vs non-celecoxib -0·74 [-2·61 to 1·14]; p=0·443). Rates of serious adverse effects did not differ between groups (31 participants had a manic switch, two self-harmed, and one died in a motor vehicle accident). INTERPRETATION: We found no evidence that minocycline or celecoxib was superior to placebo for the treatment of bipolar depression. This large trial casts doubt on the potential therapeutic benefits of adjunctive anti-inflammatory drugs for the acute management of bipolar depression. FUNDING: Stanley Medical Research Institute.