Internet-guided Cognitive Behavioural Therapy to Improve Depression in Patients With Cardiovascular Disease
Phase: NA
Conditions: Cardiovascular Disease, Depression
Sponsor: University Hospital, Linkoeping

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Study Protocol and results 
 
Internet based cognitive behavioural therapy for 
depression in patients with Cardiovascular disease - The 
DOHART Study 
 
NCT 02778074 
 
 
Date: January 28 2019  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Purpose and aims  
Tailored internet-based cognitive behavioural therapy (I-CBT) is a new innovative and 
person-centred method that is promising that may be used to decrease depression in CVD 
patients. In patients with cardiovascular disease (CVD), depressive symptoms is a common 
co-morbidity leading to decreased wellbeing, and increased morbidity and mortality. 
Depressive symptoms are both underdiagnosed and undertreated in CVD patients. Earlier 
studies have demonstrated the efficiency of cognitive behavioural therapy (CBT) for many 
psychiatric conditions, but few studies have evaluated CBT in patients with CVD.  
 
The purpose of this study is to evaluate the effects of the tailored I-CBT program on 
reducing depressive symptoms and other patient reported outcomes in patients with 
cardiovascular disease (CVD) and to explore factors related to implementation of the I-CBT 
program in clinical cardiac care.  
Aims of the study  
• To evaluate the effects of the tailored I-CBT depression program on depressive 
symptoms and quality of life. 
 
Survey of the field 
Background: The World Health Organisation (WHO) has estimated that CVD and depressive 
symptoms will in the near future become the two most common causes of disability.1 
Depressive symptoms, according to the WHO, produces greater decrements in health than 
other chronic physical diseases and a comorbid depression significantly worsens the health of 
patients with such diseases.2  
          In Europe, CVD is the major cause of hospital discharges and accounts for 43% of all 
deaths at all ages (i.e., > 4 million deaths annually).3 Depressive symptoms is highly prevalent 
in patients with CVD (20%–40%)4 and it significantly worsens the health of CVD patients. 
Depressed CVD patients experience poorer quality of life,5 more frequent rehospitalisation,6 
higher healthcare costs and a shorter life expectancy than CVD patients without depression.6 
Both biological and behavioural mechanisms can explain the negative effects of depressive 
symptoms in CVD. With regard to the biological mechanisms, our own and other studies have 
shown that depressive symptoms increases plasma levels of stress hormones and 
inflammatory activity, which may speed up the progression of atherosclerosis and impairment 
of cardiac function.4,7 Regarding behaviour, depressive symptoms can influence non-
adherence to medication, development of a sedentary lifestyle and poorer self-care 
performance.4,8  
          The WHO states that our ‘traditional care approaches’ such as primary care centres or 
outpatient clinics do not offer enough support or treatment to patients with a chronic disease 
and depressive symptoms, such as those with CVD.2 The WHO emphasises that the 
implementation of interventions targeting depression in healthcare should thus be prioritised.2 
In line with this recommendation, our proposed study will contribute to the development, 
feasibility testing, and evaluation of the effectiveness of an internet-based cognitive 
behavioural therapy treatment program (I-CBT) aimed at treating depressive symptoms in 
CVD patients.  
Rationale for the intervention: Why should CBT be chosen for this purpose? Antidepressant 
medication seem to have limited effect on depressive symptoms in CVD patients.4 
Furthermore, adding anti-depressant to the existing complex medical treatment for CVD may 
be perceived as burdensome and also increase the risk of developing side effects. CVD 

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patients with depression prefer ‘talking’ therapies.9 There are other psychotherapies, but 
rarely, if ever, do they result in better outcomes than CBT.10 However, earlier studies of CBT 
in CVD patients’ only reports small effects on depressive symptoms. One probable reason is 
that most studies only used a single CBT component, such as psychoeducation alone, 
problem-solving therapy alone, relaxation alone or behavioural activation alone.11 A program 
that combines different CBT components has been suggested to improve treatment efficacy.12 
Moreover, generic CBT programs may not be optimal for targeting depression in patients with 
chronic diseases since these programs are not adapted to the context of the disease,13 for 
example, by acknowledging the association between CVD and depression. We therefore 
believe that a CBT program that (I) includes different CBT components and (II) tailored to fit 
the context of CVD has the potential to improve the effect of CBT on depressive symptoms. 
This might also prevent the progression of CVD as well as improve quality of life and 
survival. 
 
Project description 
 
The study has the following research questions: 
• What are the short- (nine weeks) effects of a nine-week I-CBT program on depressive 
symptoms and quality of life in patients with CVD and depressive symptoms.  
 
Methods 
Design of the study 
The effects of the I-CBT program will be evaluated in a randomised controlled study (RCT).  
 
Enrolment of study participants in the RCT  
For the RCT study, 144 patients were recruited (Figure 1).  
 
Power calculation: A recent published meta-analysis14 of studies evaluating the effect of 
internet based CBT on depression, that will be the primary outcome in the study, reported the 
effect size in studies including patients with depression to vary between 0.56-1.26 (mean 
0.89), the mean number of patients in these studies was 107. Own power calculation: Effect 
size=0.5, alpha=0.05 (Z=1.96), Power 0.80 (Z -0.84) = 122 participants. Due to drop-outs or 
deaths the size of the study population for the RCT study was decided to n=140.  
 
Step 1. Screening for participants. All CVD patients who received care at the department of 
cardiology the last 12 months in four hospitals in southeast of Sweden was contacted by a 
letter with information (n=11,992) about the study.  
 
Step 2. Patients interested (n=272) in participating registered as interested on our website 
(www.dohart.se) for more information, registration and the provision of informed consent. 
After registration, the participants will respond to questions on the website (see figure 1). 
Inclusion or exclusion will be assessed by a board consisting of a cardiologist, a psychologist, 
a cardiology nurse specialists and a psychiatric nurse specialist. 
  
 
 
 

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Inclusion 
• age > 18 years  
• treatment for CVD according to European Society of Cardiology guidelines 
• stable CVD (NYHA class I–III) and not having been hospitalised for CVD in in the 
last four weeks. 
• depressive symptoms (Patient Health Questionnaire-9 15 (PHQ-9) > 5 points)  
Exclusion  
• severe CVD (NYHA IV) or another severe chronic life-threatening disease  
• severe depression assessed as requiring acute treatment  
• not being able to dedicate 3-4 hours to participate in the program  
•  
Figure 1. Description of the enrolment and randomisation of study participants 
 
Step 3. Before final inclusion and randomisation, eligible participants was contacted for a 
telephone interview held by the psychiatric nurse specialist. Mini International 
Neuropsychiatric Interview (MINI) will be used to assess depression at this stage.  

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Step 4  The included (n=144) patients completed the baseline study questionnaires on our 
website and was then be randomised to nine weeks of internet-based CBT (n=72) or nine 
weeks in an web based discussion forum  (n=72). As suggested by the ethical committee, 
those in the web-based discussion forum  was offered I-CBT treatment after the termination 
of the study. 
 
Theoretical underpinning for the CBT intervention 
According to CBT theory16, depression arises from negative thoughts, emotions and 
behaviours that can be activated as a response to stressful life events, such as the development 
of CVD. Figure 2 shows a CBT model, inspired by Moorey17 of how CVD can cause 
depression. The inner circle of the model describes perceived losses, threats and stressful 
symptoms caused be CVD. This activate negative thoughts, emotions and behaviours, thus a 
process leading to development of depression (the outer circle). In the model, a vicious circle 
can be seen since the negative thoughts, emotions and behaviours in turn can worsen patients’ 
perceived stress of CVD and thus both worsen depressive symptoms and CVD.  
Intervention: With CBT the patients become active participants and perform exercises that 
enable them to become aware of, modify, as well as learn skills to cope with negative 
thoughts and unhelpful behaviours, which contributes to decrease negative emotions.16 CBT 
can help CVD patients to break the vicious circle. The nine-week tailored I-CBT program 
consists of the components of psychoeducation, relaxation, problem-solving and behavioural 
activation. Table 1 describes the I-CBT program and Figure 2 describes how the four 
components in the I-CBT will work to decrease depression. CBT usually includes some form 
of homework. Specifically, just seeing a therapist is insufficient, and change must be 
implemented in real life, which is achieved by collaborating with the patient and prescribing 
homework. The present I-CBT program thus also has homework assignments (Table 1) and 
the patients are provided with weekly feedback on them by a nurse specialising in mental 
health care who is supported by a psychologist and can consult with a cardiologist as well as a 
specialist cardiac nurse. Feedback is delivered in writing and focuses on positive aspects of 
the patient’s progress; support is also provided to help the patients proceed with the program. 
 
Figure 2. A CBT model describing how CVD can cause depression. The figure also describes how the 
4 components in the I-CBT program (1) psychoeducation, (2) problem solving, (3) behavioural 
activation and (4) relaxation can help to decrease depression by modification of negative thoughts, 
behaviours and emotions. 
 
 
 
 
 
 
 
 
 
 
CVD 
-loss of health and functions 
-life threatening disease 
-confusing/unpredictable 
symptoms 
Negative thoughts 
3. BEHAVIOURAL-
ACTIVATION 
2. PROBLEM-
SOLVING 
1. PSYCHOEDUCATION 
4. RELAXATION 

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Table 1. A brief overview of the I-CBT program 
 
The control group participated in a web-based moderated discussion forum (i.e. ODF group) 
where new discussion topics were presented each week over a nine-week period. During 
participation in the ODF, no individual feedback was provided. However, participants could 
contact the moderator for support regarding how to use the ODF and for technical support. 
The topic was introduced without any extended background in a presentation consisting of 
statements and questions such as: What are the symptoms of CVD? Do you have any tips you 
would like to share on how you can handle the symptoms of CVD? How do you think that 
depressive symptoms and CVD affect the relationship between you and your significant 
others? Do you have any suggestions about how to handle problems related to feeling 
depressed or downhearted? The discussion took place in writing. 
Measurements to evaluate the RCT  
The PHQ-915 will be used to measure the primary outcome (i.e. depressive symptoms). The 
PHQ-9 is a valid and frequently used depression questionnaire. To detect depression a 
sensitivity of 88% and a specificity of 88% has been reported in primary care patients18 
whereas a sensitivity and specificity of 70 %r respectively 92% has been reported in patients 
with CVD.19 Table 2 gives an overview of the primary and secondary outcomes and the 
timing for measurements in the RCT. 
Statistical analysis plan 
Primary and secondary outcome data were checked for normal distribution by visual 
inspection or Q-Q plots. The primary analysis for comparison between groups (i.e. iCBT vs. 
ODF) was made on an intention-to-treat basis. Analysis of covariance (ANCOVA), which 
allows adjusting for baseline scores and regression to the mean was used for the comparison 
between groups. Missing data in the ANCOVA was imputed using last observation carried 
forward.  
 
CBT component/Content 
Aim 
Homework 
Week 1: Psychoeducation 
Introduction 
Inform and engage the participant. 
Goal setting.  
Identify values and set up goals for the 
participation in the program  
Week 2: Psychoeducation 
Living with CVD 
To understand what CVD is and 
its impact on life. 
Self-assessment of CVD symptoms. 
Identification of situations when symptoms 
occurs. Propose coping strategies.  
Week 3 Psychoeducation 
Depression and CVD 
To understand what depression is 
and its link to CVD. 
Identify symptoms of depression, fear and 
worries Identify situations when symptoms 
affects the participant.  
Week 3: Relaxation 
To learn relaxation 
Practice relaxation continuously during the 
CBT program. 
Week 4 and 5: 
Behavioural activation 
To identify behaviours that have 
negative and positive impacts on 
wellbeing.   
Mapping activities in a week schedule. 
Making a list of desirable activities. 
Planning and implementing new activities  
Week 6 and 7: 
Behavioural activation 
To reduce negative behaviours 
and increase positive ones.  
Eliminate or reduce negative activities. 
Increase number of positive activities. 
Week 8: Problem-solving 
To identify perceived problems. 
To solve or cope with a problem.  
Practicing problem solving in accordance to 
the problem solving tool 
Week 9: Final module 
Learn strategies to maintain the 
changes achieved.  
Set up a personal strategy that can be used if 
depressive symptoms re-occur. 

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Table 2. The different measurements and the timing for measurements in the study. 
 
Results of the I-CBT program 
Main results (Table 3) Compared to web-based discussion forum (ODF), iCBT had a 
significant and moderate treatment effect on the primary outcome depression (i.e. PHQ-9) 
(mean group difference -2.34 [95 % CI -3.58 to -1.10], P <0.001, Cohen’s d=0.62). In the 
secondary outcomes, compared to ODF, iCBT had a significant and large effect on depression 
(i.e. MADRS-S) (P<.001, Cohen’s d=0.86) and a significant and moderate effect on the 
mental component scale of the SF-12 (P<.001, Cohen’s d=0.66) and the EQ-VAS (P<.001, 
Cohen’s d=0.62). A total of 60% (n=43) of the iCBT group completed all seven modules, 
whereas 82% (n=59) completed at least half of the modules. No patients were discontinued 
from the study due to high risk of suicide or deterioration in depression. 
Table 2: Treatment effects for the primary and secondary outcomes. Data are mean (SD) 
unless otherwise stated. 
 
Abbreviations: PHQ-9 = Patient Health Questionnaire 9. MADRS-S = Montgomery Åsberg 
Depression Rating Scale (self-rating version). EQ-VAS = EuroQol Visual Analogue Scale. 
PCS12 = Physical Component Score of the Short Form 12. MCS12 = Mental Component 
Score of the Short Form 12. 
 
Internet-cognitive 
behavioural therapy (n=72) 
Online discussion forum (n=72) 
Mean between-group 
treatment difference, 
95 % CI 
P 
Effect-
size (d) 
Baseline 
9 weeks 
Baseline 
9 weeks 
PHQ-9 
10.71 (4.47) 
6.63 (4.76) 
10.22 (5.10) 
8.68 (4.60) 
-2.34 
-3.58 to -1.10 
<.001 
0.62 
MADRS-S 
18.27 (6.98) 
10.90 (7.45) 
17.67 (6.19) 
16.10 (7.93) 
-5.58 
-7.72 to -3.44 
<.001 
0.86 
EQ-VAS 
53.31 (20.03) 
65.11 (21.81) 
57.15 (18.10) 
56.99 (22.08) 
10.83 
5.02 to 16.64 
<.001 
0.62 
PCS12 
39.70 (10.07) 
41.84 (10.56) 
37.63 (10.98) 
37.80 (11.61) 
2.46 
-0.11 to 5.03 
.06 
0.32 
MCS12 
35.88 (9.22) 
43.41 (11.04) 
36.38 (10.02) 
38.03 (10.52) 
5.71 
2.83 to 8.60 
<.001 
0.66 
 
Questionnaires 
Baseline 
Post-CBT 
9 weeks, 
 
Primary outcome 
 
Depressive symptoms 
 
 
Patient Health Questionnaire-915 
 
 
X 
 
 
X 
Secondary outcomes 
 
Depressive symptoms 
 
 
Montgomery-Asberg Depression 
Scale 
 
 
X 
 
 
X 
 
 
X 
X 
Quality of life 
Short Form-1220  
Euro-QoL-5D21 
X 
X 
X 
X 

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