Background: Mental health issues are common among patients with chronic physical conditions, affecting approximately one in five patients. Poor mental health is associated with worse disease outcomes and increased mortality. Problem-solving therapy (PST) may be a suitable treatment for targeting poor mental health in these patients. This study protocol describes a randomised controlled trial of the Healthy Mind intervention, a general practice-based intervention offering PST to patients with type 2 diabetes and/or ischaemic heart disease and poor mental well-being. Methods: A stepped-wedge cluster-randomised controlled trial with 1-year follow-up will be conducted in Danish general practice. At the annual chronic care consultation, patients with type 2 diabetes and/or chronic ischaemic heart disease will be screened for poor mental well-being. Patients in the control group will be offered usual care while patients in the intervention group will be offered treatment with PST provided by general practitioners (GPs) or general practice staff, such as nurses, who will undergo a 2-day PST course before transitioning from the control to the intervention group. The primary outcome is change in depressive symptoms after 6 and 12 months. Secondary outcomes include change in mental well-being, anxiety, and diabetes distress (patients with type 2 diabetes) after 6 and 12 months as well as change in total cholesterol levels, low-density lipoprotein (LDL) levels, and blood glucose levels (patients with diabetes) after 12 months. Process outcomes include measures of implementation and mechanisms of impact. We aim to include a total of 188 patients, corresponding to approximately 14 average-sized general practices. Discussion: The Healthy Mind trial investigates the impact of PST treatment for patients with chronic disease and poor mental well-being in general practice. This will be the first randomised controlled trial determining the effect of PST treatment for patients with chronic diseases in general practice. The results of this study will provide relevant insights to aid GPs, and general practice staff manage patients with poor mental well-being. Trial registration: ClinicalTrials.gov NCT05611112. Registered on October 28, 2022.
Keywords: Diabetes mellitus; Type 2; Heart diseases; Chronic disease; Mental health; Psychosocial intervention; Problem-solving therapy; Randomised controlled trial (publication type); General practice; Primary healthcare; General practitioners; Nurses
Title {1} Improving mental health in chronic care in general practice: study protocol for a cluster-randomised controlled trial of the Healthy Mind intervention Trial registration {2a and 2b} Clinical trial registry: NCT05611112 registered on October 28th 2022. Ethical approval: Central Denmark Region Committee on Health Research Ethics, study ID: 1–10-72–68-22 Protocol version {3} 15.12.2023 Version 1.0 Funding {4} The Danish Heart Foundation, the Committee for Quality Improvement and Continuing Medical Education (KEU) of general practice in the Central Denmark Region, Aarhus University, the Riisfort Foundation, the Danish Research Foundation for General Practice, the Foundation for Primary Healthcare Research of the Central Denmark Region, the Committee of Multipractice Studies in General Practice, and the Foundation for Research on Mental Disorders Author details {5a} Anne Søjbjerg, MD1, 2; Anna Mygind, MScPH, PhD1, Stinne Eika Rasmussen, MD1, 2; Bo Christensen, MD, PhD1,2; Anette Fischer Pedersen, MScPsych, PhD1,3; Helle Terkildsen Maindal, MPH, PhD2, Viola Burau, PhD2; Kaj Sparle Christensen, MD, PhD1,2 1Research Unit for General Practice, Bartholins Allé 2, 8000 Aarhus C, Denmark, 2Department of Public Health, Aarhus University, Bartholins Allé 2, 8000 Aarhus C, Denmark, 3Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark Name and contact information for the trial sponsor {5b} Department of Public Health, Aarhus University, Bartholins Allé 2, 8000 Aarhus C, Tel: + 45 87 16 79 36 Research Unit for General Practice, Aarhus, Bartholins Allé 2, 8000 Aarhus C, Tel: + 45 87 16 78 97 Role of sponsor {5c} The trial sponsor and funders do not play a role in the design, collection, management, analysis, and interpretation of the data; drafting of the report; or decision to submit the report for publication, including authority over these activities
Type 2 diabetes (T2D) and chronic ischaemic heart disease (CHD) are two of the most prevalent chronic diseases affecting approximately 8% of the global population [[
An example of such an intervention is problem-solving therapy (PST), which is an evidence-based and effective treatment for mental health issues like depression and anxiety [[
Building on the PST approach, we developed the Healthy Mind intervention offering PST to patients with T2D and/or CHD and concurrent poor mental well-being in general practice. In a small-scale feasibility study, the Healthy Mind intervention was found to be well-suited for the general practice setting and was positively received by both patients and healthcare providers [[
The overall aim of the trial is to evaluate the impact of the Healthy Mind intervention using the PST approach in general practice in patients with T2D and/or CHD and poor mental well-being.
The study aims to:
- Evaluate the effect of PST on mental health outcomes defined as depressive symptoms, symptoms of anxiety and diabetes distress (for patients with T2D) and general mental well-being
- Evaluate the effect of PST on somatic disease outcomes, defined as cholesterol levels and blood glucose levels (for patients with diabetes)
- Evaluate the process outcomes, including measures of implementation and mechanisms of impact
The study is conducted from November 1, 2022, to January 16, 2024, with follow-up after 6 and 12 months. The design is a stepped-wedge cluster-randomised controlled trial with 1-year follow-up (Fig. 1). General practices are randomised into two clusters. Initially, all participating general practices act as the control group. After 4 months, healthcare professionals in cluster 1 undergo a 2-day PST course, following which they transition to the intervention group and begin offering the intervention to eligible patients. Healthcare providers from cluster 2 attend the PST course after 8 months and will subsequently be part of the intervention group.
Graph: Fig. 1 The stepped-wedge cluster-randomised trial design
The study setting is Danish general practice. The Danish healthcare system is primarily tax-financed, and residents have free and equal access to general practice services. General practitioners (GPs) are self-employed, working on contracts for the public funder and offer services in their practices within the frames of a national agreement with Danish regional authorities that details which services are offered in general practice and how these are reimbursed. Nurses and other healthcare professionals (e.g. midwives, healthcare assistants) are frequently employed and trained to conduct independent consultations, including chronic care consultations in general practice [[
Patients with T2D and CHD are typically offered annual chronic care consultations provided by either the GP or trained general practice staff. National and international guidelines on disease management encourage healthcare professionals to pay attention to psychological symptoms, but they do not offer specific recommendations on how to identify and manage mental health issues [[
A list of participating general practices can be provided upon request by the corresponding author.
The following are the inclusion criteria:
- Above 18 years of age
- Diagnosed with T2D and/or CHD
- Attend annual chronic care consultations
- Poor mental well-being, defined as a WHO-5 Well-Being Index score < 50 points [[
19 ]]
The following are the exclusion criteria:
- Severe mental illness (active psychosis, suicidal mental state, or dementia)
- Unable to understand, read, and write Danish
All general practices in the Central Denmark Region are eligible (n = 349). Participating healthcare professionals are GPs and general practice staff with experience in conducting independent consultations.
The healthcare professional delivering the annual chronic care consultation will deliver both oral and written information about the study and obtain informed consent from eligible participants.
No additional consent provisions are necessary and there are no ancillary studies.
This study aims to test the effectiveness of the Healthy Mind intervention, which is provided in addition to the existing annual chronic care consultation. Therefore, usual care is the most appropriate comparator and acts as the control group.
The intervention was developed using the UK Medical Research Council framework for developing complex interventions [[
PST is a well-established psychological treatment aiming at improving the patient's problem-solving and coping skills [[
All patients with T2D and/or CHD attending annual chronic care consultations in general practice are screened for poor mental well-being using the WHO-5 Well-Being Index (WHO-5) [[
Table 1 Participant timeline
Time point Baseline During or immediately after the intervention 6 months 12 months X X X X Primary outcome X X X Secondary outcomes X X X X X X X X X X X X X X X Process outcomes Implementation X X X Mechanisms of impact X X
Before transitioning to the intervention protocol, healthcare professionals attend a 2-day PST course. The course is designed on the basis of knowledge from a previous small-scale study and further refined by insights from our feasibility study [[
The training course comprises both a theoretical component and a component focusing on implementation. Two psychologists with expertise in PST facilitate the theoretical component, which includes lectures on PST in combination with hands-on exercises, including role play, to familiarise participants with PST and ensure that they develop sufficient skills to deliver the intervention after the course. Two members of the research team facilitate the implementation component where participants will formulate specific implementation strategies tailored to their particular general practices to ensure that the intervention is properly integrated into each participating general practice.
Patients may discontinue participation at any time. The exclusion criteria ensure that patients with severe psychopathology (psychosis, suicidal mental state, or dementia) are not invited to participate in the study. If a patient develops severe psychopathological symptoms during the study, the intervention is terminated immediately, and relevant standard treatment is initiated. If a patient withdraws from the study, data collected until the withdrawal will be part of the study.
During the PST course, healthcare providers are trained to deliver the intervention with high fidelity. The booklet used during PST sessions is designed to support adherence to the methodology of PST and facilitate patient involvement.
All usual care is allowed in both the control and the intervention group, including medical treatment of mental illness and referral to mental health specialists, e.g., a psychologist or psychiatrist.
Patients retain their usual continuous free and equal access to general practice prior to, during, and after the intervention.
A programme theory was created to identify anticipated mental, somatic, and process outcomes of the Healthy Mind intervention.
The primary outcome is the mean change in depressive symptoms measured with the nine-item Patient Health Questionnaire (PHQ-9) from baseline to 6 and 12 months [[
Secondary outcomes include the mean change in general mental well-being measured with the WHO-5 questionnaire [[
Somatic outcomes include the mean change in total cholesterol levels (mmol/L), low-density lipoprotein (LDL) levels (mmol/L), and, for patients with diabetes, HbA1c (mmol/mol) from baseline to 12 months.
Process outcomes include measures of implementation: fidelity, dose, reach, and mechanisms of impact: mediators and unintended consequences.
The participant timeline is outlined in Table 1.
The sample size was calculated according to the following assumptions: We expect 20% of patients with T2D and/or CHD who attend annual chronic care consultations to decline participation or be excluded from the study. We expect 15% of participating patients to report reduced mental well-being (WHO-5 score < 50 points), and 20% of patients participating in the study are expected to be lost to follow-up after 12 months. The intraclass correlation coefficient (ICC) is conservatively estimated at 0.05, reflecting a realistic expectation that a mental outcome is likely to show a larger dependence on the individual general practice than somatic outcomes, where an ICC of 0.01 is often applied. To achieve a significance level of 5% and a power of 90%, the study is required to include a total of 188 patients.
In Denmark, the size of a general practice depends on its number of practice capacities. Each general practice capacity accommodates approximately 1600 patients, with an average of 2.5 practice capacities per practice. Based on these assumptions, we need to include at least 35 practice capacities (corresponding to 14 average-size general practices) to be able to include 188 patients over a 1-year study period.
An e-mail describing the study is sent by the national health authorities to all general practices in the Central Denmark Region, and interested general practices can sign up for participation. Additionally, general practices who have previously expressed an interest in participating in mental health studies and/or research projects are contacted directly by the research team.
Enrolment of patients relies on the general practices to systematically recruit patients at the annual chronic care consultations. The research team will take a number of initiatives to support the workflow of patient recruitment in each general practice. Prior to commencing the study, initial online meetings will be held between two members of the research team and one GP (practice owner) from each general practice to map the staff composition, current chronic care management, and workflow. Together with the GP, the research team tailors a plan for the management of patient recruitment in each individual general practice. Immediately before the study commencement, a visit is paid to each general practice to inform healthcare professionals and administrative staff about the study and facilitate the implementation of the tailored recruitment plan. One healthcare professional from each general practice is appointed the study contact person and study champion, responsible for patient recruitment and implementation of the intervention. Subsequently, videos demonstrating how to provide oral and written information to patients will be distributed to general practices. Throughout the study period, monthly newsletters are forwarded to the participating general practices with general information about the study and individual statistics regarding patient enrolment and number of conducted PST sessions during the intervention period. Patient recruitment is monitored weekly by the research team and champions are promptly contacted by e-mail, telephone, or a visit in case recruitment rates decline, to explore the underlying reasons and support further recruitment.
A computer-generated cluster randomisation is applied at the general practice level. Randomisation includes stratification by number of practice capacities and geographical location.
Due to the nature of the intervention design, concealment is not possible.
The allocation sequence is generated by a statistician independent of the research team. Details regarding participant and patient enrolment are outlined in the "Recruitment {15}" section.
Due to the nature and design of the intervention, blinding is not applicable. To avoid a potential impact on the healthcare providers' professional behaviour, they only receive cursory information about PST during the control period.
Blinding is not applicable in this study.
Information about patients is entered into the Healthy Mind website database by healthcare professionals upon enrolment. For patients with a WHO-5 score > 50 points, sex, age, and diagnosis (T2D and/or CHD) are registered. For patients with a WHO-5 score < 50 points, additional registration of social security number, name, contact information, and WHO-5 score is made.
Upon enrolment, an automatically generated link to a questionnaire is sent out to participating patients with a WHO-5 score < 50 points. The questionnaire assesses the primary and secondary mental health outcomes as described above. This link is sent via email/SMS at baseline, as well as after 6 and 12 months. Reminders are sent to non-responders by email/SMS after 1 and 2 weeks, followed by a reminder telephone call after 3 weeks. Patients who are unable to access the electronic questionnaire are provided with an identical paper version at baseline and receive follow-up paper questionnaires by mail after 6 and 12 months. The questionnaires are forwarded to the research team and entered manually into the Healthy Mind database by a data manager independent of the research team. Non-responders to mailed questionnaires receive a reminder telephone call after 3 weeks. The Healthy Mind database mandates that all questionnaire items must be completed before submission, and duplicate registrations cannot be entered, ensuring comprehensive and accurate registrations. More detail on questionnaire properties is provided in Table 2.
Table 2 Overview of mental health outcomes in questionnaires at baseline and after 6 and 12 months
Questionnaire Number of items Range Cut-off values Measure 9 0–27 0–5: no depression 5–10: mild depression 10–15: moderate depression 15–20: moderately severe depression > 20: severe depression Depressive symptoms 7 0–21 0–4: minimal anxiety 5–9: mild anxiety 10–14: moderate anxiety > 15: severe anxiety Anxiety symptoms 5 0–20 > 7: elevated diabetes distress Diabetes distress 5 0–100 < 50: impaired mental well-being Mental well-being
Somatic outcomes are obtained through the local LABKA II database, which contains all results of blood samples analysed in the Central Denmark Region.
The process outcome data are part of an explanatory sequential mixed methods process evaluation, guided by the UK Medical Research Council framework for process evaluations [[
Qualitative data will be collected through semi-structured interviews with purposefully selected patients (n = 10) after their final PST session. The interview guide will focus on reach, fidelity, mediators, and unintended consequences and will be informed by quantitative process measures from each individual patient. Qualitative interview data will be transcribed verbatim and analysed thematically. The process evaluation will be supplemented by ethnographic case studies exploring the role of context.
At baseline, the Brief Health Literacy Scale for Adults (B-HLA) [[
General practices receive remuneration for providing information (written and oral), screening eligible patients and completing PST sessions. Remuneration will match the standard remuneration for equivalent services. This incentive will facilitate continuous patient recruitment and delivery of the intervention.
Moreover, healthcare providers are encouraged to monitor patient attendance and ensure that new PST sessions are scheduled upon cancellation or non-attendance.
The number of questionnaire items is kept at a minimum to prevent item attrition, and both electronic and paper questionnaires are available.
In compliance with the General Data Protection Regulations (GDPR), the study is listed in the record of processing activities at Aarhus University (journal number: 2016–051-000001) [[
Data collection, storage, and access will comply with the GDPR regulations [[
No collection of biological specimens for genetic or molecular analysis is made in this study.
The comparative analysis will estimate the mean change in PHQ-9 score from baseline to follow-up at 6 and 12 months. A linear mixed model will be used, adjusting for patients' age, gender, and socioeconomic status. The cluster effect by general practice and the correlation between repeated measurements on the same patient over time will be taken into account in the multilevel analysis [[
The mean change in WHO-5, GAD-7, and PAID-5 (for patients with diabetes) scores from baseline to follow-up at 6 and 12 months will be estimated using the same methods as for the primary outcome.
Comparative analyses will estimate the mean change in total cholesterol levels (mmol/L), LDL levels (mmol/L) and (for patients with diabetes) HbA1c levels (mmol/mol) from baseline to 12 months using a generalised linear mixed model. The model will consider patient demographics, clustering, and time effects as described above.
Descriptive analyses will estimate the extent of implementation (fidelity, dose, reach) and mechanisms of impact (mediators and unintended consequences). Process outcome data will be combined with effect outcome data to explore the associations between process and effect measures.
PST is a well-established treatment, which is considered safe and not expected to result in potentially serious adverse outcomes. Thus, no interim analyses are planned.
Exploratory subgroup analyses will be conducted to explore the potential differential effects of the intervention based on pre-specified characteristics of participating patients. These include sex, age, socioeconomic status, health literacy level, severity of mental health outcomes, and diagnosis (T2D or IHS). Furthermore, subgroup analysis will explore the impact of dosage received defined as a number of completed PST sessions, whether PST was provided by a GP or general practice staff, and the size of the general practice in which the intervention was delivered.
The intention-to-treat analysis will be supplemented with a sensitivity analysis employing multiple imputation models for handling missing values to investigate the potential impact of missing data and attrition.
This study protocol covers all aspects of the trial. Survey data and patient outcomes are not publicly available, but deidentified data are available upon reasonable request to the corresponding author. The statistical code will be published in the manuscripts describing the effect evaluation.
Throughout the development phase, a steering committee consisting of all authors met monthly to discuss and plan the trial. During the trial, this group will meet every 3 months to discuss the trial progress. During the enrolment period, day-to-day support and continuous monitoring of the trial for operational issues will be carried out by a group of six researchers, who will meet on a weekly basis.
The data monitoring committee comprises the day-to-day support group (six researchers) together with the data manager, who is in charge of the Healthy Mind website database (sundtsind.au.dk). The data collection is continuously monitored throughout the trial period.
The intervention is a well-known treatment for mental health issues and is considered safe. Thus, severe adverse effects and harms are not expected. If healthcare professionals delivering the intervention suspect that the intervention has resulted in adverse events or harms, they will contact the research group immediately.
Formal trial auditing will not be carried out.
In case modifications of the protocol are found necessary, amendments will be registered on
A minimum of three published articles in international peer-reviewed journals reporting on mental health outcomes after 6 months, mental and somatic outcomes after 12 months, and a process evaluation are expected. Reportings from the study will be based on the CONSORT statement extension on stepped cluster-randomised trials [[
This study will evaluate the impact of providing PST in general practice to patients with T2D and/or CHD and concurrent poor mental well-being. The chosen stepped-wedge cluster-randomised controlled trial design offers practicality and enhances data collection. Firstly, all general practices are guaranteed inclusion in the intervention arm, easing the recruitment process. Secondly, comparison between the two groups will be affected to a minimum by contextual factors, since the general practices and the healthcare professionals are identical. Thirdly, healthcare providers' motivation to participate in the study during the control period may increase, knowing they will later transition to the intervention phase. Fourthly, cluster-level randomisation helps prevent contamination arising from treatment spillover.
Further, the embedded mixed methods process evaluation offers an in-depth understanding of how the intervention works and for whom. This comprehensive approach provides crucial insights for future implementation and valuable learning points.
There are, however, limitations in this study. Firstly, recruitment of general practices for research trials is challenging since they are self-employed often working on a tight schedule [[
The Healthy Mind intervention will be the first randomised controlled trial determining the effect of PST treatment for patients with chronic disease in general practice. Further, it will provide insights that can inform the task-shifting of psychological treatments from GPs to general practice staff. The study has broad perspectives as PST may also be applicable to other patient categories who present with mental health issues in general practice.
Protocol version 1.0 from December 2023. The recruitment period started in October 2022 and is scheduled to be completed in January 2024. This manuscript was submitted shortly before the inclusion termination date due to concurrent tasks faced by the authors, including reporting on findings from the preceding feasibility study. Nevertheless, the evaluation design was established well before the inclusion period began and remained unchanged after the trial commenced.
We thank Mette Lund Jensen for participating in the development of the PST course and Henrik Schou Pedersen for statistical assistance.
The following investigators participate in the Healthy Mind Study Group: Bo Christensen, Kaj Sparle Christensen, Helle Terkildsen Maindal, Viola Burau, Anna Mygind, Anette Fischer Pedersen, Stinne Eika Rasmussen, Anne Søjbjerg, and Amanda Nikolajew Rasmussen.
All authors have contributed to the conceptualisation and design of the study as well as the intervention development. AS wrote the initial manuscript draft. All authors have critically revised the manuscript and approved the submitted version.
The Healthy Mind Study is funded by the Danish Heart Foundation, the Committee for Quality Improvement and Continuing Medical Education (KEU) of general practice in the Central Denmark Region, the Aarhus University, the Riisfort Foundation, the Danish Research Foundation for General Practice, the Foundation for Primary Healthcare Research of the Central Denmark Region, the Committee of Multipractice Studies in General Practice, and the Foundation for Research on Mental Disorders. The funders have no role in the study design, data collection, analysis, or the publishing of results.
Survey data and patient outcome data are not publicly available, but deidentified data are available upon reasonable request to the corresponding author.
The Central Denmark Region Committee on Health Research Ethics approved the study on May 19, 2022 (study ID: 1–10-72–68-22). The Committee of Multipractice Studies in General Practice (journal number: 11–2023) evaluated the study protocol and recommended participation in the study.
Written, informed consent for participation will be obtained from all participants.
Not applicable.
The authors declare that they have no competing interests.
• B-HLA
- Brief Health Literacy Scale for Adults
• CHD
- Chronic ischemic heart disease
• GAD-7
- General Anxiety Disorder-7
• GDPR
- General Data Protection Regulation
• GP
- General practitioner
• PAID-5
- Problem Areas in Diabetes-5
• PHQ-9
- Patient Health Questionnaire-9
• PST
- Problem-solving therapy
• T2D
- Type 2 diabetes
• WHO-5
- WHO-5 Mental Well-Being Index
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By Anne Søjbjerg; Anna Mygind; Stinne Eika Rasmussen; Bo Christensen; Anette Fischer Pedersen; Helle Terkildsen Maindal; Viola Burau and Kaj Sparle Christensen
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