Neuropsychiatric symptoms including depression, apathy and psychosis are experienced by the majority of patients with Parkinson's disease. A subgroup of patients develop cognitive impairment, which may increase the risk of falls due to reduced attention. Acetylcholine deficit is thought to contribute to neuropsychiatric symptoms in Parkinson's disease. The acetylcholinesterase inhibitor rivastigmine is beneficial in Parkinson's disease dementia (PDD), but the consensus for the use of rivastigmine earlier in the disease course is unclear. This systematic review aims to assess the evidence for rivastigmine in the treatment of neuropsychiatric symptoms in Parkinson's disease without dementia.

EMBASE, MEDLINE, PsychINFO, Cochrane CENTRAL, NGLC, NICE Evidence and medRxiv.org were searched for studies with terms relating to Population (Parkinson's disease) and intervention (rivastigmine).

1922 references were identified, of which 358 were duplications.

Inclusion criteria were: diagnosis of Parkinson's disease, rivastigmine intervention and the presence of neuropsychiatric symptoms or falls. Articles were excluded if they only related to patients with dementia.

Following title and abstract review, 1331 articles were excluded.

After full text review, 9 articles remained, which underwent a risk of bias analysis.

Outcomes were heterogenous, so were not suitable for meta-analysis. Therefore, the results are presented in narrative form. The articles included 6 Randomised Controlled Trials (RCTs), 2 open-label trials and 1 case-series.

Three of the studies focused on psychosis. Two of these studies indicated a benefit of rivastigmine on psychotic symptoms in Parkinson's disease. However, these studies were an open label trial and a case series, and the results were not reproduced during RCT.

One RCT indicated benefit of rivastigmine in rapid eye movement behaviour disorder (RBD).

One RCT showed improvements in apathy after treatment with rivastigmine.

Two RCTs demonstrated a reduction in falls with rivastigmine treatment compared to placebo.

One RCT showed a significant improvement on a performance-based measure of cognitive ability.

One study identified brain areas that were hypoactive in hallucinating Parkinson's patients, and the reduced activity could be restored with rivastigmine. This restoration of activity was associated with improved attention compared to baseline.

There is evidence that rivastigmine is beneficial for RBD and apathy in Parkinson's disease, independently from the presence of dementia. There is high level evidence that rivastigmine reduces falls, which may be due to improved attention. The impact of rivastigmine on psychotic symptoms is less clear, but is supported by current theoretical models which involve acetylcholine dysfunction in the generation of visual hallucinations in Parkinson's disease.

Previous findings have indicated that self-harm and suicide are associated with different rates, and different risk and protective factors in South Asian people compared with White people in the UK. Substantial qualitative research has explored experiences of self-harm and suicide in South Asian people.

The study aims to review the existing qualitative evidence on self-harm and suicidal behaviours in South Asian communities in the UK.

Systematic searches were conducted on Medline, EMBASE, PsycINFO, CINAHL, Open Dissertations and the British Library Ethos databases. We selected qualitative studies from both journals and grey literature that included South Asian participants who were resident in the UK and presented perceptions or experiences of self-harm and/or suicidal behaviour. Analysis was undertaken based on the meta-ethnographic approach.

Fifteen studies were included in the analysis. Experience of self-harm was discussed based on three aspects: behind self-harm, functions of self-harm and recovery from self-harm. ‘Behind self-harm’ refers to factors associated with self-harm and suicide. ‘Functions of self-harm’ captures the meaning attributed to self-harm and suicide. ‘Recovery from self-harm’ encapsulates personal and professional help, and practical suggestions for the improvement of mental health services.

Although some similarities with the majority White population were present, there were also crucial differences that need consideration when shaping health policies, improving access to health services and developing culturally sensitive psychosocial interventions for self-harm and suicide specific to South Asian communities in the UK.

There has been increased interest in repurposing anti-inflammatories for the treatment of bipolar depression. Evidence from high-income countries suggests that these agents may work best for specific depressive symptoms in a subset of patients with biochemical evidence of inflammation but data from lower-middle income countries (LMICs) is scarce. This secondary analysis explored the relationship between pretreatment inflammatory markers and specific depressive symptoms, clinical measures, and demographic variables in participants with bipolar depression in Pakistan.

The current study is a cross-sectional secondary analysis of a randomized controlled trial of two anti-inflammatory medications (minocycline and celecoxib) for bipolar depression (n = 266). A series of logistic and linear regression models were completed to assess the relationship between C-reactive protein (CRP) (CRP > or < 3 mg/L and log10CRP) and clinical and demographic features of interest and symptoms of depression. Baseline clinical trial data was used to extract clinical and demographic features and symptoms of depression were assessed using the 24-item Hamilton Depression Rating Scale.

The prevalence of low-grade inflammation (CRP > 3 mg/L) in the sample was 70.9%. After adjusting for baseline body mass index, socioeconomic status, age, gender, symptoms related to anhedonia, fatigue, and motor retardation were most associated with low-grade inflammation.

Bipolar disorder (BD) patients from LMICs may experience higher rates of peripheral inflammation than have been reported in Western populations with BD. Future trials of repurposed anti-inflammatory agents that enrich for participants with these symptom profiles may inform the development of personalized treatment for bipolar depression in LMICs.

Bipolar disorder is a source of marked disability, morbidity and premature death. There is a paucity of research on personalised psychosocial interventions for bipolar disorder, especially in low-resource settings. A pilot randomised controlled trial (RCT) of a culturally adapted psychoeducation intervention for bipolar disorder (CaPE) in Pakistan reported higher patient satisfaction, enhanced medication adherence, knowledge and attitudes regarding bipolar disorder, and improvement in mood symptom scores and health-related quality of life measures compared with treatment as usual (TAU).

The current protocol describes a larger multicentre RCT to confirm the clinical and cost-effectiveness of CaPE in Pakistan. Trial registration: NCT05223959.

A multicentre individual, parallel-arm RCT of CaPE in 300 Pakistani adults with bipolar disorder. Participants over the age of 18, with a diagnosis of bipolar I or II disorder who are currently euthymic, will be recruited from seven sites: Karachi, Lahore, Multan, Rawalpindi, Peshawar, Hyderabad and Quetta. Time to recurrence will be the primary outcome assessed using the Longitudinal Interval Follow-up Evaluation (LIFE). Secondary measures will include mood symptoms, quality of life and functioning, adherence to psychotropic medications, and knowledge and attitudes regarding bipolar disorder.

This trial will assess the effectiveness of the CaPE intervention compared with TAU in reducing the time to recurrence for people with bipolar disorder currently in remission in Pakistan and determine the effect on clinical outcomes, quality of life and functioning.

A successful trial might lead to rapid implementation of CaPE in clinical practice, not only in Pakistan, but also in other low-resource settings, including those in high-income countries, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority group patients with bipolar disorder.

Research in the area of mHealth, has shown much promise in the development of mobile phone interventions which look at the assessment and treatment in real-time of psychiatric disorders. Within the context of Severe Mental Illnesses (SMI), such as psychosis, communication and understanding between health professionals and service users in the reporting of distress and reoccurrence of symptoms is essential in reducing the chances of relapse. An alternative pathway which uses mobile technology to engage with services, may hold the key to gaining a deeper understanding of the lived experiences of those with mental health difficulties, in particular experiences of recovery from SMI's. AIM: The aim of the study was to explore the perspectives and opinions of health professionals on the development and refinement of the TechCare App for psychosis. A qualitative approach was adopted for data collection, which provided an understanding of factors in relation to the development of the intervention.

A total of two focus groups were held with health professionals to elicit their views on optimising the utility of the TechCare App. The total sample size for the focus groups was n = 16 with a total of 6 males and 10 females. This qualitative study was part of a feasibility study, investigating a novel intervention (TechCare) (Husain et al., 2016; Gire et al., 2021) which monitored participants symptoms and provided a tailored psychosocial response in real-time. Data obtained from the focus groups was transcribed. Framework analysis were used to analyse the data for emerging themes, focusing on feasibility, acceptability and further development.

The key themes that emerged from the data were; access and usage of digital technologies, implications for clinical practice, challenges & barriers to delivery and development and refinement considerations for the TechCare App.

Results of the focus group with health professionals provided a unique perspective of conducting mHealth research within an EIS context, and the differing challenges professionals anticipated facing in delivering the TechCare App intervention. The main finding of the focus group was that professionals saw the potential for the TechCare App to increase access to digital technologies, providing service users with an alternative medium to communicate with EIS health professionals. However, the participants felt that despite mHealth Apps being a useful platform to deliver interventions, face-to-face contact should remain an important aspect of routine care.

Prevalence of post-traumatic stress disorder (PTSD) is high in Pakistan both due to natural disasters and ongoing conflicts. Offspring of trauma survivors are at increased risk for mental and physical illnesses. Parental PTSD has been linked to troubled parent–child relationships, behaviour problems, trauma symptoms, and depression in children. This study aims to explore the acceptability, feasibility and indications of the effectiveness of group learning through play plus trauma-focused cognitive behaviour therapy (LTP Plus TF-CBT) for parents experiencing PTSD.

This is a two-arm pilot cluster randomised controlled trial (RCT). We aim to recruit 300 parents with a diagnosis of PTSD. The screening will be done using the Impact of Event Scale-Revised. Diagnosis of PTSD will be confirmed using the Clinician-Administered PTSD Scale-5 (CAPS-5). Union Councils from Peshawar and Karachi will be randomised into either group LTP Plus TF CBT arm or treatment as usual (TAU). The intervention includes 12 sessions of LTP Plus TF-CBT delivered weekly in the first 2 months and then fortnightly in a group setting by trained psychologists. The groups will be co-facilitated by the community health workers (CHWs). Parents will be assessed at baseline and 4th month (end of the intervention), using the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder (GAD-7) Scale, Client Service Receipt Inventory (CSRI), and Ages and Stages Questionnaire (ASQ-3)

This trial would help build an understanding of the acceptability, feasibility and indications of the effectiveness of a low-cost parenting intervention.

Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation.

161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α.

Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls.

The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).

In the UK, postnatal depression is more common in British South Asian women than White Caucasion women. Cognitive–behavioural therapy (CBT) is recommended as a first-line treatment, but there is little evidence for the adaptation of CBT for postnatal depression to ensure its applicability to different ethnic groups.

To evaluate the clinical and cost-effectiveness of a CBT-based positive health programme group intervention in British South Asian women with postnatal depression.

We have designed a multicentre, two-arm, partially nested, randomised controlled trial with 4- and 12-month follow-up, comparing a 12-session group CBT-based intervention (positive health programme) plus treatment as usual with treatment as usual alone, for British South Asian women with postnatal depression. Participants will be recruited from primary care and appropriate community venues in areas of high South Asian density across the UK. It has been estimated that randomising 720 participants (360 into each group) will be sufficient to detect a clinically important difference between a 55% recovery rate in the intervention group and a 40% recovery rate in the treatment-as-usual group. An economic analysis will estimate the cost-effectiveness of the positive health programme. A qualitative process evaluation will explore barriers and enablers to study participation and examine the acceptability and impact of the programme from the perspective of British South Asian women and other key stakeholders.

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.

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.

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.

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.

The evidence base for stigma in mental health largely originates from high-income countries.

This study from Pakistan aimed to address the gap in literature on stigma from low- and middle-income countries.

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.

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.

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.

Globally, nearly two-thirds of people with dementia reside in low- and middle-income countries (LMICs), yet research on how to support people with dementia in LMIC settings is sparse, particularly regarding the management of behavioural and psychological symptoms of dementia. Understanding how best to manage these symptoms of dementia with non-specialist approaches in LMICs is critical. One such approach is a non-pharmacological intervention based on the Montessori method.

To evaluate the feasibility and acceptability of a culturally adapted, group-based Montessori intervention for care home residents with dementia and their study partners, who were paid care workers in Pakistan.

This was a two-stage study: a cultural adaptation of the Montessori intervention and a single-arm, open-label, feasibility and acceptability study of 12 participant dyads. Feasibility and tolerability of the intervention and study procedures were determined through the recruitment rate, adherence to the protocol and acceptance of the intervention. Qualitative interviews were undertaken with the study partners. A pre–post exploratory analysis of ratings of behavioural and psychological symptoms of dementia, functional ability and quality of life were also conducted.

The recruitment and retention rates of people with dementia were acceptable, and the intervention was well tolerated by participant dyads. Findings show a reduction in agitation levels and improvement in mood and interest for the activities.

Feasibility studies of low-cost, easy-to-deliver and culturally adapted interventions are essential in laying the groundwork for subsequent definitive effectiveness and/or implementation trials for dementia in LMICs, where awareness and resources for dementia are limited.

The waiting room in psychiatric services can provide an ideal setting for offering evidence-based psychological interventions that can be delivered through electronic media. Currently, there is no intervention available that have been developed or tested in mental health.

This proof-of-concept study aimed to evaluate a pilot design of RESOLVE (Relaxation Exercise, SOLving problem and cognitiVe Errors) to test the procedure and obtain outcome data to inform future, definitive trials (trial registration at Clinicaltrials.gov NCT02536924, REB Number: PSIY-477-15).

Forty participants were enrolled and equally randomised to the intervention, RESOLVE plus treatment as usual arm (TAU), or to a control group (TAU only). Those in the intervention group watched RESOLVE in a room adjacent to the waiting area. Participants in the control received routine care. Outcome measures included the Hospital Anxiety and Depression Scale; the Clinical Outcomes in Routine Evaluations outcome measure; and the World Health Organization Disability Assessment Schedule. These measures were performed by a masked assessor at baseline and at 6-week follow-up. Additionally, we measured the number of contacts with mental health services during the prior 4 weeks. Both intention-to-treat and per protocol analyses were performed.

The study proved feasible. We were able to recruit the required number of participants. There was a statistically significant improvement in depression (P < 0.001), anxiety (P < 0.001), general psychopathology (P < 0.001) and disability (P = 0.0361) in favour of the intervention group. People in the intervention group were less likely to contact the service (P = 0.012) post-intervention.

Findings provide preliminary evidence that evidence-based psychosocial interventions can be delivered through electronic media in a waiting-room setting. The outcome data from this study will be used for future definitive trials.

None.

A third of patients diagnosed with major depressive disorder (MDD) experience treatment-resistant depression (TRD). Relatively few pharmacological agents have established efficacy for TRD. Therefore, the evaluation of novel treatments for TRD is a pressing priority. Statins are pleiotropic agents and preclinical studies as well as preliminary clinical trials have suggested that these drugs may have antidepressant properties.

To report on a protocol for a 12-week, randomised, double-blind, placebo-controlled trial of add-on treatment with simvastatin for patients meeting DSM-5 criteria for MDD who have failed to respond to at least two adequate trials with approved antidepressants. The trial has been registered with Clinicaltrials.gov in (ClinicalTrials.gov identifier: NCT03435744).

After screening and randomisation to the two parallel arms of the trial, 75 patients will receive simvastatin and 75 patients will receive placebo as adjuncts to treatment as usual. The primary outcome is change in Montgomery–Åsberg Depression Rating Scale scores from baseline to week 12 and secondary outcomes include changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. Assessments will take place at screening, baseline, and weeks 2, 4, 8 and 12. Checklists for adverse effects will be undertaken at each visit. Simvastatin (20 mg) will be given once daily. Other secondary outcomes include C-reactive protein and plasma lipids measured at baseline and week 12.

This trial will assess simvastatin's efficacy and tolerability as an add-on treatment option for patients with TRD and provide insights into its putative mechanisms of action.

As the first trial investigating the use of simvastatin as an augmentation strategy in patients with TRD, if the results indicate that adjuvant simvastatin is efficacious in reducing depressive symptoms, it will deliver immediate clinical benefit.

I.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. R.R. and M.M.H. have received educational grants and support for academic meetings from Pfizer, Roche, Novartis and Nabiqasim. A.H.Y. has been commissioned to provide lectures and advice to all major pharmaceutical companies with drugs used in affective and related disorders. A.H.Y. has undertaken investigator-initiated studies from Astra Zeneca, Eli Lilly, Lundbeck and Wyeth. None of the companies have a financial interest in this research.

The need for an age-appropriate in-patient service for 16- to 17-year-olds led to the development of a 6-bed acute admissions unit in a non-metropolitan county in the UK. We provide a descriptive evaluation of the first 2 years of its operation. All admissions from April 2010 to March 2012 were reviewed, clinical details systematically recorded and descriptively analysed.

Ninety-seven young people were admitted during this period (a third were compulsorily detained under the Mental Health Act 1983). The average length of stay was 3–4 weeks. The most common presenting complaints were self-harm and low mood, usually in the context of life events and childhood adversity. Nearly half had substance misuse and other risk-taking behaviours. A third presented with psychotic symptoms. Adjustment and anxiety disorders were most common, followed by alcohol/substance use disorders, depressive illnesses and psychotic illnesses. Comorbidity was the rule rather than the exception. Most patients improved by the time of discharge.

The unit provides an accessible and effective age-appropriate service and is likely to constitute an important component of the comprehensive child and adolescent mental health service strategy in the county.

Self-harm is a major risk factor for completed suicide.

To determine the efficacy of a brief psychological intervention – culturally adapted manual-assisted problem-solving training (C-MAP) – delivered following an episode of self-harm compared with treatment as usual (TAU).

The study was a randomised controlled assessor-masked clinical trial (trial registration: ClinicalTrials.gov NCT01308151). All patients admitted after an episode of self-harm during the previous 7 days to the participating medical units of three university hospitals in Karachi, Pakistan, were included in the study. A total of 250 patients were screened and 221 were randomly allocated to C-MAP plus treatment as usual (TAU) or to TAU alone. All patients were assessed at baseline, at 3 months (end of intervention) and at 6 months after baseline. The primary outcome measure was reduction in suicidal ideation at 3 months. The secondary outcome measures included hopelessness, depression, coping resources and healthcare utilisation.

A total of 108 patients were randomised to the C-MAP group and 113 to the TAU group. Patients in the C-MAP group showed statistically significant improvement on the Beck Scale for Suicide Ideation and Beck Hopelessness Inventory, which was sustained at 3 months after the completion of C-MAP. There was also a significant reduction in symptoms of depression compared with patients receiving TAU.

The positive outcomes of this brief psychological intervention in patients attempting self-harm are promising and suggest that C-MAP may have a role in suicide prevention.