A Group Parenting Intervention for Depressed Fathers (LTP + Dads): A Feasibility Study from Pakistan

Introduction: In this study, we feasibility tested Learning Through Play Plus Dads (LTP+ Dads), a group parenting psychoeducation program adapted for depressed Pakistani fathers of children under three years of age. Methods: A total of 18 fathers with depression were recruited in Karachi, Pakistan for a pre-post feasibility study. Ten sessions of group LTP+ Dads were offered over three months. Clinical assessments were administered at baseline, 3 and 6 months and included the Edinburgh Postnatal Depression Scale, 17-item Hamilton Depression Rating Scale, Brief Disability Questionnaire, Multidimensional Scale of Perceived Social Support, Euro-Qol-5 Dimensions, Rosenberg Self-esteem Scale, Parenting Stress Index, and Knowledge, Attitude and Practices questionnaire. Results: The intervention was feasible to implement and acceptable based on a recruitment rate of 100% of eligible participants and a 100% attendance rate for 5 of the 10 sessions. Within this preliminary sample, fathers showed, on average, a reduction in depressive symptoms, an increase in most areas of fathers’ knowledge and positive attitudes about child development. Perceived social support, self-esteem and functioning scores also increased. Limitations: The small sample size and lack of control group are limitations of this study. Conclusions: In this first study of paternal depression in Pakistan, a low cost culturally adapted group intervention was found to be feasible and acceptable. Changes in depression, parenting-related and other outcomes are promising and inform a future larger trial. Keywords: Paternal depression, Cultural Adaptation, CBT, Parenting, Low and middle income countr

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

Background The At Risk Mental State (ARMS) describes individuals at high risk of developing schizophrenia or psychosis. The use of antipsychotics in this population is not supported because most individuals with ARMS are unlikely to develop psychosis. Anti-inflammatory treatments and polyunsaturated fatty acids (PUFAs) may have some beneficial effects in the treatment of ARMS. There have been no controlled clinical trials that have investigated the use of minocycline for ARMS and no trials involving PUFAs in combination with other proposed treatments. There is a need to find effective, tolerable and inexpensive interventions for ARMS that are available both in high, low and middle-income countries. Methods A six-month intervention study of minocycline and/or Omega-3 fatty acids added to treatment as usual (TAU) in patients with ARMS will be conducted in Pakistan using a randomised, placebo-controlled, double-blind factorial design. 320 consenting patients with capacity will be recruited from community, general practitioner clinics and psychiatric units. Allowing for a 25% dropout rate, we will recruit 59 completing participants to each study arm, and 236 will complete in total. We will determine whether the addition of minocycline and/or Omega-3 fatty acids to TAU attenuates rate of transition from ARMS to first-episode psychosis and improves symptoms and/or level of functioning in ARMS. We will also investigate whether any candidate risk factors such as negative symptoms, influence treatment response in the ARMS group. The primary efficacy end-point is conversion to psychotic disorder at 12 months post study entry. Analysis will be by intention-to-treat, using analysis-of variance, chi-squared tests and adjusted odds ratios to assess between-group differences. Cox regression analyses will be used to analyse potential between-group differences in time-to-onset of psychosis. Discussion The outcomes of this trial will provide evidence of the potential benefits of minocycline and PUFAs in the treatment of ARMS. Both minocycline and PUFAs are inexpensive are readily available in low/middle-income countries such as Pakistan, and if evidenced, may prove to be safe and effective for treating ARMS

Prevalence of suicidal ideation and suicide attempts in individuals with psychosis and bipolar disorder in South Asia: systematic review and meta-analysis.

BackgroundSuicidal 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.AimsTo estimate the prevalence of suicidal ideation and attempts in individuals with psychosis and bipolar disorder in South Asia.MethodIn 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.ResultsThe 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.ConclusionsOne 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

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.

BackgroundInflammatory 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.Methods10,173 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.FindingsForty-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 InterpretationIn 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.FundingThe study was funded by the Stanley Research Medical Institute

Minocycline as an adjunct for treatment-resistant depressive symptoms:study protocol for a pilot randomised controlled trial

BACKGROUND: Depression is one of the leading causes of disability worldwide. A high proportion of patients do not respond to standard drug treatments. Recent evidence has suggested that anti-inflammatory treatment may have beneficial effects in major depression. Minocycline is a tetracycline antibiotic with good CNS penetration that exerts effects on multiple interacting symptoms implicated in the pathophysiology of mood disorders. Open-label studies have suggested that minocycline is effective as an adjunct drug in improving depressive symptoms. METHODS/DESIGN: This is a multi-centre, 3-month, double-blind, placebo-controlled, pilot trial of minocycline added to treatment as usual for patients suffering from DSM-IV major depressive disorder. This will be a double-blind, randomised, controlled, two parallel-arm study with 20 participants in each arm, giving a total of 40 participants. There will be a screening visit, a randomization visit and four follow-up visits. Clinical assessments using the Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ −9) and the Generalised Anxiety Disorder scale (GAD-7) will be carried out at every visit. Side effects checklists will also be undertaken at each visit. Biomarkers (inflammatory cytokines and CRP) will be measured at baseline and at the end of the treatment phase. Minocycline will be started at 100 mg once daily (OD) and will be increased to 200 mg at two weeks. DISCUSSION: Anti-inflammatory treatments have been shown to have some beneficial effects in the treatment of major depressive disorder. The aim of this pilot randomised controlled trial is to establish the degree of improvement in depressive symptoms with the addition of minocycline to treatment as usual. TRIAL REGISTRATION: ClinicalTrials.gov NCT02263872 registered 10 October 2014

Suicidality in patients with bipolar depression:Findings from a lower middle-income country

AIMS: Among low- and middle-income countries (LMICs), bipolar disorder is recognized as one of the leading causes of disease burden for adults and is associated with marked suicide risk. There are limited data on suicidal ideation in bipolar disorder from LMICs. This study presents cross-sectional data on the prevalence of suicidality and associated patient characteristics among patients with bipolar depression in Pakistan, a lower-middle income country and the fifth most populous country in the world. METHOD: Participants were recruited through outpatient psychiatric clinics in between 2016–2019 in Karachi, Lahore, Hyderabad and Rawalpindi between 2016–2019. Participants were aged 18 to 65 years 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 proportional odds regression models were applied to establish correlates to suicidal ideation. RESULT: 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. No patient demographic data, including age, gender, marital status, socioeconomic status, and years of education were associated with severity of suicidality. CONCLUSION: There exists a high prevalence of suicidal ideation among patients with bipolar depression in Pakistan. 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. More studies are needed to see whether such findings can be replicated in other similar LMIC settings, and to explore potential physiological pathways linking BMI, inflammatory biomarkers and suicidality in bipolar disorder