Objective: ECT is the most effective treatment for severe depression. Previous efficacy studies, using thrice-weekly brief-pulse ECT, reported that high-dose (63 seizure threshold) right unilateral ECT is similar to bitemporal ECT but may have fewer cognitive side effects. The authors aimed to assess the effectiveness and cognitive side effects of twice-weekly moderate-dose (1.53 seizure threshold) bitemporal ECT with high-dose unilateral ECT in real-world practice.Method: This was a pragmatic, patient-and rater-blinded, noninferiority trial of patients with major depression (N=138; 63% female; age=56.7 years [SD=14.8]) in a national ECT service with a 6-month follow-up. Participants were independently randomly assigned to bitemporal or highdose unilateral ECT. The primary outcome was change in the 24-item Hamilton Depression Rating Scale (HAM-D) score after the ECT course; the prespecified noninferiority margin was 4.0 points. Secondary outcomes included response and remission rates, relapse status after 6 months, and cognition.Results: Of the eligible patients, 69 were assigned to bitemporal ECT and 69 to unilateral ECT. High-dose unilateral ECT was noninferior to bitemporal ECT regarding the 24-item HAM-D scores after the ECT course (mean difference=1.08 points in favor of unilateral ECT [95% CI=21.67 to 3.84]). There were no significant differences for response and remission or 6-month relapse status. Recovery of orientation was quicker following unilateral ECT (median=19.1 minutes versus 26.4 minutes). Bitemporal ECT was associated with a lower percent recall of autobiographical information (odds ratio=0.66) that persisted for 6 months.Conclusions: Twice-weekly high-dose unilateral ECT is not inferior to bitemporal ECT for depression and may be preferable because of its better cognitive side-effect profile.

Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5–15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer’s disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI.

Bifrontal ECT is not more effective than BT or RUL ECT but may have modest short-term benefits for specific memory domains. BF ECT has potential advantages, but given longer experience with BT and RUL, bifrontal ECT requires better characterization.

ObjectiveTo produce a strategic roadmap for supporting the development of dementia research in Pakistan.BackgroundWhile global research strategies for dementia research already exist, none is tailored to the specific needs and challenges of low- and middle-income countries (LMIC) like Pakistan.MethodsWe undertook an iterative consensus process with lay and professional experts to develop a Theory of Change-based strategy for dementia research in Pakistan. This included Expert Reference Groups (ERGs), strategic planning techniques, a “research question” priority survey, and consultations with Key Opinion Leaders.ResultsWe agreed on ten principles to guide dementia research in Pakistan, emphasizing pragmatic, resource sparing, real-world approaches to support people with dementia, both locally and internationally. Goals included capacity/capability building. Priority research topics included raising awareness and understanding of dementia, and improving quality of life.ConclusionThis roadmap may be a model for other LMIC health ecosystems with emerging dementia research cultures.

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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.

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression.

The Mental Health Act (MHA) 2001 has major implications for treating patients with electroconvulsive therapy (ECT), especially as those referred for treatment are among the most severely ill and often lose capacity. Under the MHA 2001, a person may only be treated without consent if they are an involuntary patient. However, there is no provision in the Act for treating voluntary inpatients whose mental state has deteriorated but who do not seek to leave hospital. Such people may lack capacity to make treatment decisions but be passively compliant.The Wards of Court system is currently the only legal recourse but has been criticised by the Law Reform Commission and is unwieldy. Further legislation governing treatment of people lacking capacity to consent to ECT or withhold consent is required to protect and advance treatment of all concerned.