Lifestyle InterVEntion Study in General Practice: LIVES - GP

Depression is a large problem, with a lifetime prevalence of 15-18% (WHO 2008)
and a 42% relapse rate over 20 years (Hardeveld et al. 2013). The yearly
economic burden of depression in het Netherlands is 1.6 billion euro for
healthcare costs and 1.8 billion euro for loss of work productivity (Trimbos
Instituut 2009). In the Netherlands, general practitioners (GP) treat 70-80% of
the patients with depression (Verhaak et al. 2009).
Next to a decreased quality of life (Rapaport 2015), patients with depression
also have a markedly heightened cardiovascular disease (CVD) risk and CVD
mortality. Studies showed that patients with depression have 81% excess risk of
developing CVD (Nicholson, Kuper, and Hemingway 2006), and a 1.4-1.8 times
elevated risk of heart disease, hypertension, and stroke (Nicholson, Kuper, and
Hemingway 2006; Meng et al. 2012). Furthermore, CVD is the most common cause of
death in patients with mental disorders (Druss and Walker 2011), vastly
exceeding the risk of suicide (Kisely et al. 2013). A small portion of this
elevated risk of CVD and CVD mortality can be attributed to antidepressant use
(Simoons et al. 2019) and underutilization of health care (Ten Have et al.
2013). However, the largest part of the elevated risk is attributed to an
unhealthy lifestyle (De Hert et al. 2010). Interestingly, this unhealthy
lifestyle feeds back to increased depressive symptoms and decreased quality of
life, thus creating a hazardous vicious circle. Therefore, a lifestyle change
might be twofold beneficial for patients with depression.
Multimodal lifestyle interventions (MLIs) are known to be effective in
preventing CVD, and as treatment of obesity and diabetes (Doughty et al. 2017).
There is also evidence that patients with mental health problems may benefit
from MLIs, both in terms of physical and mental health, mostly from studies
conducted in psychiatric outpatient settings. In patients with psychosis, a
lifestyle intervention had a large effect on depressive symptoms and resulted
in a moderate reduction in body weight after two to six months (Bruins et al.
2014). In patients with recurrent depression, a lifestyle intervention was
efficacious in preventing depressive relapse (Goracci et al. 2016), and
nutritional counseling was effective in reducing depressive symptoms (Jacka et
al. 2017). The conclusion of a recent systematic review and meta-analysis,
which included studies conducted in various settings, is that lifestyle
interventions can result in a clinically significant improvement in both
depressive symptoms and quality of life, albeit a modest one (Wong et al.,
2021).
To our best knowledge, only one study has been performed on a MLI for patients
with depression or anxiety in primary care (Forsyth, Deane, and Williams 2015).
This randomized controlled trial (RCT) with 119 participants showed a
significant effect on body mass index over a three-month period, but not on
depression scores. So even though lifestyle interventions appear to be
effective in psychiatric outpatient settings, the evidence for their use in
primary care patients is based on a single study only. This is unfortunate
because the majority (65% to 80%) of patients with mild and moderate depression
are treated in general practice (Verhaak et al., 2012). The most important
difference between primary care and psychiatric outpatient setting is that
patients in primary care usually have a less severe prognostic profile
concerning their psychiatric disorder and CVD risk than patients in a mental
health care setting. Therefore, results from studies performed in a psychiatric
outpatient setting are unlikely to be generalizable to the primary care setting.
Based on these considerations we decided to investigate the possibility of a
MLI specifically for patients with depression in general practice. Since
January 2019, four MLIs in the Netherlands are reimbursed by health insurance
companies. (https://puc.overheid.nl/nza/doc/PUC_236692_22/). However, these
MLIs do not meet the specific needs of patients with depression and in some
MLIs mental health problems are even an exclusion criterion for participation.
Therefore we developed our own MLI. To this end, we extended and adapted the
widely used Coaching on Lifestyle (CooL)-program (van Rinsum 2018), which is
recommended by the Dutch Healthcare Authority, to the disease-specific problems
and needs of patients with depression. Depressed patients often have
motivational and self-management problems (American Psychiatric Association
2013). Therefore, the substantial adaptations to the program include, for
example, the highly recommended (but not mandatory) involvement of a person in
the vicinity of the patient (*buddy* or *trustee*) and combining group and
individual formats. This MLI has been piloted (N=42) in a mental health care
(GGZ Drenthe) and general practice setting (N=8) with promising results. More
information on the development and content of our MLI can be found in chapter
5.1.

Before proceeding with a full-scale randomized study to evaluate the
cost-effectiveness of our MLI in general practice, it is essential to gain a
better understanding of its implementation feasibility in this setting.
Although we have previously tested our MLI among eight patients with depression
and obesity in primary care , many questions about a larger scale
implementation remain unanswered. The present real-world implementation
feasibility study aims to provide answers to these questions.

Primary Objective:
Our primary goal is to investigate the feasibility of a large pragmatic study
of the effectiveness of a tailored MLI for patients with depression in general
practice and to evaluate potential barriers and facilitators in a process
evaluation. This enables us in primary care to estimate the feasibility of
conducting such a study in real-world scenarios and identify key factors that
may influence its successful implementation.

Secondary Objective:
Get an impression of the variance in the outcome measures on mental health,
lifestyle factors, functioning, recovery, well-being, sleep quality,
self-esteem, quality of life, health care costs, anthropometry and blood
pressure for the future sample size calculation.

To meet these objectives, we will use the RE-AIM framework, which evaluates the
feasibility of implementing an intervention in practice using five dimensions:
(1) Reach, (2) Effectiveness, (3) Adoption, (4) Implementation and (5)
Maintenance (Glasgow et al., 1999). In this study, we will only assess the
Reach, Adoption and Implementation dimensions of the RE-AIM framework to
evaluate the feasibility of future large-scale (cost-)effectiveness research.
We believe that evaluating the effectiveness (2) and maintenance dimension (5)
are more appropriate for a randomized controlled trial to be performed in the
future.

The Lifestyle InterVEntion Study-GP (LIVES-GP) is an observational prospective
single-group cohort study among patients with prevalent depression in primary
care who also fulfil the criteria of at least overweight according to the
NHG-richtlijn *Obesitas*. Individual patients are included in this
implementation feasibility study and assessed for 42 weeks (including an
intervention of 18 weeks and 24 weeks of follow-up. In order to address our
research questions, we implement an MLI that was tailored specifically for
patients with comorbid depression and metabolic abnormalities in a mental
healthcare setting. The implementation will be done in patients with depression
and overweight who are treated in general practices in the Northern
Netherlands. Parameters of Reach, Adoption, and Implementation will be
documented next to measurements of outcomes to assess variance herein. These
measurements will be performed at baseline, end of treatment (18 weeks after
baseline), and six months after the completion of the intervention (week 42).
Alongside quantitative data we will collect qualitative data based on
interviews. These interviews will be conducted at baseline, at the end of the
intervention (after 18 weeks) and at follow-up (6 months post intervention).
The interviews will be conducted amongst approximately 8-12 patients, depending
on the number needed to achieve data saturation..

The starting point is the CooL intervention recommended by the Dutch Healthcare
Authority. This is complemented by innovations that can be assumed to make this
GLI suitable for patients with depression who have difficulty with initiative
and self-management. The possible adjustments are made on the basis of
literature exploration into the most theoretical augmentation strategies in
lifestyle interventions. Preliminary results show that, in addition to being
sufficiently intensive and long-term, the intervention can be made suitable for
depression by adding innovations:

a) Involvement of a buddy from the immediate living environment of the patient
(a friend, or family member) in the lifestyle intervention: augmentation with
social support. This will provide extrinsic motivation and can ensure that the
patient receives support in changing the living environment. Involving a buddy
is not mandatory but is strongly recommended.

b) Support activity level increase: augmentation of the active movement module.
With the help of an activity tracker during the entire treatment period,
patients set personal goals in the field of exercise.

c) Strengthening of motivation and belief in the successful completion of the
intervention, by supplementing the group sessions with exercises from positive
psychology and from competitive memory training;

d) Increasing health knowledge and skills by adding *hands-on* practical
lessons in buying and cooking healthy food: augmentation of the healthy food
module).

GL-LEEF is personalized based on specific lifestyle problems in a given
patient. The person sets his/her personal goals at the start of the training,
and is also followed during the training based on these personal goals.
GLI_LEEF focuses on physical activity, diet, stress, sleep, and alcohol and
tobacco use. In principle, GLI-LEEF is carried out in a multidisciplinary
manner, with practice nurses and lifestyle coaches under the direction of the
general practitioner. The prototype of GLI-LEEF has already been made by GGZ
Drenthe.

The lifestyle intervention is designed to last six months, with 14 weekly
1.5-to 2 hour group sessions and four 45 to 60 -minute individual sessions (1,
6, 12 and 18) with at least one person from the patient*s support network of
friends or family (preferably sharing the same household). All sessions will
end with individual homework exercises, and each session will start with a 10
to 15-minute positive psychology intervention (PPI) focussed at improving
self-esteem, and 5 to 15 minutes of physical activity. These sessions will be
followed by two booster sessions after about two and six months, depending on
the patient*s individual needs.

The current lifestyle intervention feasibility study is quite extensive with a
substantial number of visits, questionnaires and homework in between. On the
other hand, the study poses minimal risks on the subject. In different module
hands on experience is given to promote a healthier lifestyle, but the
intervention has an advisory and not compulsory character. Measurements are
questionnaire type or non-invasive anthropometry. Patients will be asked to
wear an activity tracker (Fitbit), but the main goal of this is to motivate the
patient, not to control him.
On the other hand the study could have positive effects, namely an improved
lifestyle, which may contribute to a better physical and mental health.
Eventually we hope to improve the life expectancy and quality of life of the
target population.
For the buddy, participation is also quite extensive and may evoke some tension
between the participant and the buddy. However, this will be closely monitored.
Moreover, the buddy may profit from the intervention in a similar way as the
participant.