Enhanced post-awakening cortisol may serve as a biological marker for individuals with major depressive disorder. However, studies comparing post-awakening cortisol between patients with major depressive disorder (MDD) and healthy controls have produced conflicting findings. The aim of this study was to investigate whether this inconsistency could be due to the effects of childhood trauma.

A total of N = 112 patients with MDD and healthy controls were divided into four groups according to the presence of childhood trauma. Saliva samples were collected at awakening and 15, 30, 45, and 60 min later. The total cortisol output and the cortisol awakening response (CAR) were calculated.

The total post-awakening cortisol output was significantly higher in patients with MDD as compared to healthy controls, but only in those individuals reporting childhood trauma. The four groups did not differ regarding the CAR.

Elevated post-awakening cortisol in MDD may be confined to those with a history of early life stress. Tailoring and/or augmenting of currently available treatments may be required to meet the specific needs of this population.

Evidence from high- and middle-income countries indicates that psychological interventions (PSIs) can improve the well-being of people with bipolar disorder. However, there is no evidence from low-income countries. Cultural and contextual adaptation is recommended to ensure that PSIs are feasible and acceptable when transferred to new settings, and to maximise effectiveness.

To develop a manualised PSI for people with bipolar disorder in rural Ethiopia.

We used the Medical Research Council framework for the development and evaluation of complex interventions and integrated a participatory theory-of-change (ToC) approach. We conducted a mental health expert workshop (n = 12), four independent ToC workshops and a final workshop with all participants. The four independent ToC workshops comprised people with bipolar disorder and caregivers (n = 19), male community leaders (n = 8), female community leaders (n = 11) and primary care workers (n = 21).

During the workshops, participants collaborated on the development of a ToC roadmap to achieve the shared goal of improved quality of life and reduced family burden for people with bipolar disorder. The developed PSI had five sessions: needs assessment and goal-setting; psychoeducation about bipolar disorder and its causes; treatment; promotion of well-being, including sleep hygiene and problem-solving techniques; and behavioural techniques to reduce anxiety and prevent relapse. Participants suggested that the intervention sessions be linked with patients’ monthly scheduled healthcare follow-ups, to reduce economic barriers to access.

We developed a contextually appropriate PSI for people with bipolar disorder in rural Ethiopia. This intervention will now be piloted for feasibility and acceptability before its wider implementation.

There is a global drive to improve access to mental healthcare by scaling up integrated mental health into primary healthcare (PHC) systems in low- and middle-income countries (LMICs).

To investigate systems-level implications of efforts to scale-up integrated mental healthcare into PHC in districts in six LMICs.

Semi-structured interviews were conducted with 121 managers and service providers. Transcribed interviews were analysed using framework analysis guided by the Consolidated Framework for Implementation Research and World Health Organization basic building blocks.

Ensuring that interventions are synergistic with existing health system features and strengthening of the healthcare system building blocks to support integrated chronic care and task-sharing were identified as aiding integration efforts. The latter includes (a) strengthening governance to include technical support for integration efforts as well as multisectoral collaborations; (b) ring-fencing mental health budgets at district level; (c) a critical mass of mental health specialists to support task-sharing; (d) including key mental health indicators in the health information system; (e) psychotropic medication included on free essential drug lists and (f) enabling collaborative and community- oriented PHC-service delivery platforms and continuous quality improvement to aid service delivery challenges in implementation.

Scaling up integrated mental healthcare in PHC in LMICs is more complex than training general healthcare providers. Leveraging existing health system processes that are synergistic with chronic care services and strengthening healthcare system building blocks to provide a more enabling context for integration are important.

None.

Despite being a global problem, little is known about the relationship between severe mental illness (SMI) and homelessness in low- and middle-income countries (LMICs). Homeless people with SMI are an especially vulnerable population and face myriad health and social problems. In LMICs, low rates of treatment for mental illness, as well as differing family support systems and cultural responses to mental illness, may affect the causes and consequences of homelessness in people with SMI.

To conduct a systematic, scoping review addressing the question: what is known about the co-occurrence of homelessness and SMI among adults living in LMICs?

We conducted an electronic search, a manual search and we consulted with experts. Two reviewers screened titles and abstracts, assessed publications for eligibility and appraised study quality.

Of the 49 included publications, quality was generally low: they were characterised by poor or unclear methodology and reporting of results. A total of 7 publications presented the prevalence of SMI among homeless people; 12 presented the prevalence of homelessness among those with SMI. Only five publications described interventions for this population; only one included an evaluation component.

Evidence shows an association between homelessness and SMI in LMICs, however there is little information on the complex relationship and direction of causality between the phenomena. Existing programmes should undergo rigorous evaluation to identify key aspects required for individuals to achieve sustainable recovery. Respect for human rights should be paramount when conducting research with this population.

None.

Little is known about the household economic costs associated with mental, neurological and substance use (MNS) disorders in low- and middle-income countries.

To assess the association between MNS disorders and household education, consumption, production, assets and financial coping strategies in Ethiopia, India, Nepal, Nigeria, South Africa and Uganda.

We conducted an exploratory cross-sectional household survey in one district in each country, comparing the economic circumstances of households with an MNS disorder (alcohol-use disorder, depression, epilepsy or psychosis) (n = 2339) and control households (n = 1982).

Despite some heterogeneity between MNS disorder groups and countries, households with a member with an MNS disorder had generally lower levels of adult education; lower housing standards, total household income, effective income and non-health consumption; less asset-based wealth; higher healthcare expenditure; and greater use of deleterious financial coping strategies.

Households living with a member who has an MNS disorder constitute an economically vulnerable group who are susceptible to chronic poverty and intergenerational poverty transmission.

D.C. is a staff member of the World Health Organization. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy or views of the World Health Organization.

Adjunctive psychological interventions for bipolar disorder have demonstrated better efficacy in preventing or delaying relapse and improving outcomes compared with pharmacotherapy alone.

To evaluate the efficacy of psychological interventions for bipolar disorder in low- and middle-income countries.

A systematic review was conducted using PubMed, PsycINFO, Medline, EMBASE, Cochrane database for systematic review, Cochrane central register of controlled trials, Latin America and Caribbean Center on Health Science Literature and African Journals Online databases with no restriction of language or year of publication. Methodological heterogeneity of studies precluded meta-analysis.

A total of 18 adjunctive studies were identified: psychoeducation (n = 14), family intervention (n = 1), group cognitive–behavioural therapy (CBT) (n = 2) and group mindfulness-based cognitive therapy (MBCT) (n = 1). In total, 16 of the 18 studies were from upper-middle-income countries and none from low-income countries. All used mental health specialists or experienced therapists to deliver the intervention. Most of the studies have moderately high risk of bias. Psychoeducation improved treatment adherence, knowledge of and attitudes towards bipolar disorder and quality of life, and led to decreased relapse rates and hospital admissions. Family psychoeducation prevented relapse, decreased hospital admissions and improved medication adherence. CBT reduced both depressive and manic symptoms. MBCT reduced emotional dysregulation.

Adjunctive psychological interventions alongside pharmacotherapy appear to improve the clinical outcome and quality of life of people with bipolar disorder in middle-income countries. Further studies are required to investigate contextual adaptation and the role of non-specialists in the provision of psychological interventions to ensure scalability and the efficacy of these interventions in low-income country settings.

None.

There is little practical guidance on how contextually relevant mental healthcare plans (MHCPs) can be developed in low-resource settings.

To describe how theory of change (ToC) was used to plan the development and evaluation of MHCPs as part of the PRogramme for Improving Mental health carE (PRIME).

ToC development occurred in three stages: (a) development of a cross-country ToC by 15 PRIME consortium members; (b) development of country-specific ToCs in 13 workshops with a median of 15 (interquartile range 13–22) stakeholders per workshop; and (c) review and refinement of the cross-country ToC by 18 PRIME consortium members.

One cross-country and five district ToCs were developed that outlined the steps required to improve outcomes for people with mental disorders in PRIME districts.

ToC is a valuable participatory method that can be used to develop MHCPs and plan their evaluation.

Little is known about the service and system interventions required for successful integration of mental healthcare into primary care across diverse low- and middle-income countries (LMIC).

To examine the commonalities, variations and evidence gaps in district-level mental healthcare plans (MHCPs) developed in Ethiopia, India, Nepal, Uganda and South Africa for the PRogramme for Improving Mental health carE (PRIME).

A comparative analysis of MHCP components and human resource requirements.

A core set of MHCP goals was seen across all countries. The MHCPs components to achieve those goals varied, with most similarity in countries within the same resource bracket (low income v. middle income). Human resources for advanced psychosocial interventions were only available in the existing health service in the best-resourced PRIME country.

Application of a standardised methodological approach to MHCP across five LMIC allowed identification of core and site-specific interventions needed for implementation.

Few studies have evaluated the implementation and impact of real-world mental health programmes delivered at scale in low-resource settings.

To describe the cross-country research methods used to evaluate district-level mental healthcare plans (MHCPs) in Ethiopia, India, Nepal, South Africa and Uganda.

Multidisciplinary methods conducted at community, health facility and district levels, embedded within a theory of change.

The following designs are employed to evaluate the MHCPs: (a) repeat community-based cross-sectional surveys to measure change in population-level contact coverage; (b) repeat facility-based surveys to assess change in detection of disorders; (c) disorder-specific cohorts to assess the effect on patient outcomes; and (d) multilevel case studies to evaluate the process of implementation.

To evaluate whether and how a health-system-level intervention is effective, multidisciplinary research methods are required at different population levels. Although challenging, such methods may be replicated across diverse settings.

Developing evidence for the implementation and scaling up of mental healthcare in low- and middle-income countries (LMIC) like Ethiopia is an urgent priority.

To outline a mental healthcare plan (MHCP), as a scalable template for the implementation of mental healthcare in rural Ethiopia.

A mixed methods approach was used to develop the MHCP for the three levels of the district health system (community, health facility and healthcare organisation).

The community packages were community case detection, community reintegration and community inclusion. The facility packages included capacity building, decision support and staff well-being. Organisational packages were programme management, supervision and sustainability.

The MHCP focused on improving demand and access at the community level, inclusive care at the facility level and sustainability at the organisation level. The MHCP represented an essential framework for the provision of integrated care and may be a useful template for similar LMIC.

An essential element of mental health service scale up relates to an assessment of resource requirements and cost implications.

To assess the expected resource needs of scaling up services in five districts in sub-Saharan Africa and south Asia.

The resource quantities associated with each site's specified care package were identified and subsequently costed, both at current and target levels of coverage.

The cost of the care package at target coverage ranged from US$0.21 to 0.56 per head of population in four of the districts (in the higher-income context of South Africa, it was US$1.86). In all districts, the additional amount needed each year to reach target coverage goals after 10 years was below $0.10 per head of population.

Estimation of resource needs and costs for district-level mental health services provides relevant information concerning the financial feasibility of locally developed plans for successful scale up.

Evidence on mortality in severe mental illness (SMI) comes primarily from clinical samples in high-income countries.

To describe mortality in people with SMI among a population cohort from a low-income country.

We followed-up 919 adults (from 68 378 screened) with SMI over 10 years. Standardised mortality ratios (SMR) and years of life lost (YLL) as a result of premature mortality were calculated.

In total 121 patients (13.2%) died. The overall SMR was twice that of the general population; higher for men and people with schizophrenia. Patients died about three decades prematurely, mainly from infectious causes (49.6%). Suicide, accidents and homicide were also common causes of death.

Mortality is an important adverse outcome of SMI irrespective of setting. Addressing common natural and unnatural causes of mortality are urgent priorities. Premature death and mortality related to self-harm should be considered in the estimation of the global burden of disease for SMI.

Systematic studies on the outcome of treatment-resistant depression are scarce.

To describe the longer-term outcome and predictors of outcome in treatment-resistant depression.

Out of 150 patients approached, 118 participants with confirmed treatment-resistant depression (unipolar, n= 7; bipolar, n=27; secondary, n=14) treated in a specialist in-patient centre were followed-up for between 8 and 84 months (mean=39, s.d.=22).

The majority of participants attained full remission (60.2%), most of whom (48.3% of total sample) showed sustained recovery (full remission for at least 6 months). A substantial minority had persistent subsyndromal depression (19.5%) or persistent depressive episode (20.3%). Diagnosis of bipolar treatment-resistant depression and poorer social support were associated with early relapse, whereas strong social support, higher educational status and milder level of treatment resistance measured with the Maudsley Staging Method were associated with achieving quicker remission. Exploratory analysis of treatment found positive associations between treatment with a monoamine oxidase inhibitor (MAOl) in unipolar treatment-resistant depression and attaining remission at discharge and at final follow-up, and duloxetine use predicted attainment of remission at final follow-up.

Although many patients with treatment-resistant depression experience persistent symptomatology even after intensive, specialist treatment, most can achieve remission. The choice of treatment and presence of good social support may affect remission rates, whereas those with low social support and a bipolar diathesis should be considered at higher risk of early relapse. We suggest that future work to improve the long-term outcome in this disabling form of depression might focus on social interventions to improve support, and the role of neglected pharmacological interventions such as MAOIs.