Depression and cardiovascular disease: mind the gap in the guidelines

Graphical Abstract

Graphical Abstract.

CAD, Coronary artery disease; CVD, Cardiovascular disease; CPG, Clinical practice guideline; DDI, Drug–drug, drug–disease or disease–disease interactions; HF, Heart failure; PAD, Peripheral artery disease.

Abstract

Patients with cardiovascular disease (CVD) experience higher rates of depression compared to the general population, complicating disease management, medication adherence, and lifestyle changes. Co-occurring CVD and depression are associated with reduced quality of life, poorer outcomes, and increased mortality. This study aimed to evaluate how CVD clinical practice guidelines (CPGs) address depression, including practical management guidance. A systematic search (2013–2024) identified 65 CPGs published in English, covering general CVD, heart failure, coronary artery disease, peripheral artery disease, stroke, and aortic disease. Seventy-one percent acknowledged depression as a risk factor and 12% referred to a dedicated CPG for comprehensive guidance. Yet only 23% of CPGs provided both screening and treatment recommendations for its management. Twelve percent involved mental health professionals in their development, while 24% focussed on cardiac or stroke rehabilitation, and 9% on women. Stroke CPGs delivered the majority of recommendations (68%), likely due to neurologists’ involvement. Cardiac and stroke rehabilitation CPGs delivered 24% of recommendations, whereas women-specific CPGs offered no treatment recommendations. While cognitive-behavioural therapy was the most recommended psychotherapeutic intervention (29% of CPGs), and selective serotonin reuptake inhibitors were the pharmacotherapy most recommended (20% of CPGs), only 3% of CPGs addressed drug-disease interactions associated with treating depression. Depression negatively impacts patients’ lives, irrespective of CVD outcomes. CVD CPGs should systematically address depression, consistently involving mental health specialists, to deliver screening and treatment guidance tailored to distinct patient populations for holistic patient care.

Introduction

Cardiovascular disease (CVD) remains the primary cause of morbidity and death worldwide.¹ Disease-specific management of patients with CVD has improved and substantially reduced mortality in recent decades,^2,3 and the resulting increased life expectancy has contributed to higher rates of comorbidities among these patients.⁴ Depression is the leading cause of disability worldwide⁵ and is a well-recognized risk factor for CVD.^6–8 The global prevalence of depression in patients with CVD is substantially higher than in the general population, ranging between 18% and 30%.^9,10 Moreover, inadequate treatment of depression is associated with an increased 10-year CVD risk.^11,12 This is particularly true for women, whose risk is two-fold higher (29% in women vs. 14% in men).¹¹ In specific cardiovascular conditions, such as heart failure (HF), the prevalence of depression can reach 40%.^13,14 Depression is also a recognized and serious complication of stroke, with incidence rates reaching up to 50% at 5 years’ follow-up and associated with increased disability and mortality, often exacerbated by functional deficits, such as aphasia.¹⁵ The prevalence of depression remains consistently higher in patients with CVD compared to the general population.^16,17 A similar observation was made for clinically relevant depressive symptoms in patients with CVD, especially those of somatic origin.¹⁸ Furthermore, recent studies reconfirm that depression is a strong independent predictor of CVD risk, even after adjusting for traditional risk factors, including age, smoking, hypertension, or diabetes.¹⁹ The question of whether depression definitively causes cardiovascular events is complex (Figure 1). Recent evidence from Mendelian randomization trials supports depression as a causal contributor to CVD, particularly coronary artery disease (CAD), myocardial infarction (MI), and small-vessel stroke.^20,21 The bidirectional relationship likely involves an intricate interplay of biological and behavioural mechanisms,²² but also genetic vulnerability and socioeconomic factors, creating a vicious cycle that can exacerbate both conditions. This was demonstrated in a large-scale meta-analysis showing that severe mental disorders, including depression, can significantly increase the risk of CVD and CVD-related mortality.⁶

Figure 1.

Cardiovascular disease and depression: possible overlapping mechanisms and pathways through which psychosocial stressors (e.g. socioeconomic constraints, depression, psychological distress), health risk behaviours, and lifestyle factors lead to biological dysregulation (e.g. hypothalamic-pituiary-adrenal axis dysregulation, neurobiological dysregulation, inflammation, sympathetic overdrive, sex hormones, genetics). These interconnected mechanisms likely collectively contribute to an exacerbated burden of depression in cardiovascular disease. HPA, hypothalamic-pituitary-adrenal. Created in BioRender. Miteva, K. (2025) https:// BioRender.com/cuvcug3

In patients with CVD, depression strongly correlates with worse outcomes,^23–25decreased quality of life,⁸ and increased healthcare utilization and expenses.^26–28 Reasons for worse outcomes include decreased adherence to medical treatment or to healthy lifestyles.^29–31 While a few studies suggest that early recognition and effective management of depressive disorders can improve overall health and CVD outcomes,^28,32–38 evidence remains limited, contributing to the ongoing controversy surrounding treatment.^28,39–41 As a result, depression in this population remains largely underdiagnosed and undertreated.^42–44

The aim of this study was to systematically review CVD clinical practice guidelines (CPGs) for guidance on depression. More specifically, we aimed to establish whether CPGs deliver clear and concise recommendations for addressing depression in patients with CVD. We also sought to identify gaps, inconsistencies, and areas for improvement within and across the guidelines, for CPG-issuing bodies to act upon. A comprehensive description of the study’s background, aims, and objectives was previously provided in the study’s protocol (PROSPERO registration number CRD42022384152).⁴⁵

Methods

Systematic literature searches of CVD CPGs were performed, as defined in the study protocol.⁴⁵ Cardiovascular conditions searched were CAD, stroke, peripheral artery disease (PAD), aortic disease, and HF, all of which are becoming increasingly prevalent with an aging population.^46–48

Clinical practice guideline identification and selection

Systematic literature searches were developed, conducted, and documented by an information specialist (C.A.-H.), adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.⁴⁹ Relevant vocabulary for cardiovascular conditions was initially defined using controlled vocabulary terms and their synonyms in the Medical Subject Headings⁵⁰ and Emtree thesauri (Supplementary data online, Appendix S1). Given the unavailability of precise search filters for CPGs, and the fact that many are not included in standard databases such as Medline,^51,52 we abstained from searching PubMed and Embase, as originally planned.⁴⁵ Instead, we developed sensitive search strategies for the specialized CPG databases Trip (via www.tripdatabase.com) and Epistemonikos (via www.epistemonikos.org) as well as for Google Scholar (via Harzing's Publish or Perish 8)⁵³ (last search 10 October 2023; Supplementary data online, Appendix S2). Records published before 2013 were excluded, considering the substantial advances in the field over the past decade. Retrieved references were exported to EndNote 20 and deduplicated using Deduklick.⁵⁴ Upon import into Covidence, further suggested duplicates were manually reviewed and removed. The titles and abstracts of the search results were independently screened by two reviewers (D.B.-A. and A.B.). Selected references were obtained in full text and independently assessed for eligibility by the two reviewers. Disagreements over eligibility were resolved by consensus or by third-author arbitration (E.B.).

To identify additional eligible CPGs, grey literature searches (last search 5 October 2024; Supplementary data online, Appendix S2) and backward citation searches were performed.⁵⁵ The websites of CPG-issuing organizations were searched, including the National Institute for Health and Care Excellence (NICE; nice.org.uk/guidance) and the Scottish Intercollegiate Guidelines Network (SIGN; SIGN.ac.uk), as well as international collections, including Guidelines International Network (GIN; https://guidelines.ebmportal.com/), Emergency Care Research Institute Guidelines Trust (https://guidelines.ecri.org/), the WHO guidelines section (https://www.who.int/publications/who-guidelines), and UpToDate (uptodate.com, published by Walter Kluwers). A systematic review of PAD CPGs was also searched.⁵⁶ Finally, all selected CPGs and online guideline repositories were checked for updates, and outdated versions were replaced.

Inclusion and exclusion criteria

Inclusion criteria were established as previously described.⁴⁵ Briefly, CPGs were considered if they addressed adult CVD management (HF, CAD, stroke, PAD, and aortic disease), were included if issued by recognized scientific or governmental bodies, developed using evidence or consensus-based methods, published in English within the last 10 years (from 1 January 2013), and available in peer-reviewed journals or official academic platforms. Only the latest versions were considered. CPGs were excluded if they were not relevant to the topic of interest, outdated or superseded by more recent versions, not in English, or focused solely on specific tests, treatments, or acute inpatient care.

Data extraction and analysis

We developed a standardized data extraction form based on predefined key elements categorized into the following domains:

• Guideline characteristics;

• General mental health information and recommendations;

• Recommendations for screening and management of depression, including strength and level of evidence; and

• Guidance on drug–disease, drug–drug, or disease–disease interactions (DDIs).

The form was generated in a spreadsheet (Microsoft Excel, Version 16.78.3). A pilot test of the usability and usefulness of the data extraction form was conducted on a subset of included CPGs. Feedback from the pilot test was used to refine the data extraction form and clarify any ambiguous data items.

We conducted a targeted full-text search of each CPG, using the search terms ‘depress’, ‘mental’, ‘psych’, and ‘mood’. These terms were selected to encompass a broad range of mental health-related language, with a focus on depression. Any information on mental health aspects of patient management, including DDIs, was documented in the data extraction form. Any mention or guidance on depression was extracted. For recommendations, strength and level of evidence were documented. Extracted data were tabulated and analysed using descriptive statistics.

Grading harmonization

To accurately compare the grading of recommendations, we developed a standardized system adapted from Uyagu et al.⁵⁶ Briefly, the strength of a recommendation (SoR) was graded as strong ‘for’ (A), moderate ‘for’ (B), weak ‘for’ (C) or strong ‘against’/harm (N). Level of evidence (LoE) was graded as high- (1), medium- (2), or low-quality (3). Supplementary data online, Tables S1 and S2 describe the grading methodology used by each organization and CPG, as well as the harmonized grading system applied in this study. Two independent reviewers (D.B.-A and A.B) attributed standardized gradings to the recommendations, and a third reviewer (F.M.) checked for consistency.

Results

A total of 3718 unique records were identified in the bibliographic searches and screened by title and abstract, and 3530 records that did not meet the inclusion criteria were excluded. The remaining 188 records were further assessed for eligibility in full text, and 51 CPGs met the inclusion criteria. Twelve additional CPGs were identified through grey literature searches, guideline repositories, and CPG-issuing organizations. Five CPGs issued by SIGN/NICE (CVD13⁵⁷; HF3⁵⁸; CAD4⁵⁹ ; CAD6⁶⁰; Stroke3⁶¹) additionally or fully cross-referenced to the NICE Guideline dedicated to the treatment and management of depression in adults with a physical chronic disease.⁶² Since this guideline is not specific to cardiovascular conditions, it was not included in this study. The search for updates and the backward citation search identified eight previously included CPGs, as well as three new CPGs. Two CPGs^63,64 were parts I and II of the same guideline; only the one specifically addressing depression was considered for analysis. Therefore, of the 66 CPGs^{57–61,63–123} included, 65^{57–61,63–123} were analysed for content on depression (see Supplementary data online, Table S3). Figure 2 shows the PRISMA flow diagram, and Supplementary data online, Appendix S1 shows details on selection procedure and results.

Figure 2.

PRISMA Flow Diagram: Identification and selection of cardiovascular disease clinical practice guidelines for systematic review. After identifying 3,920 records, removing 152 duplicates, and excluding 3,550 studies, 188 full texts were assessed for eligibility, excluding 136 (for reasons such as not being clinical practice guidelines, duplicates, or outdated versions), and resulting in 66 studies eligible for inclusion in the systematic review

Clinical practice guideline characteristics

The selected guidelines came from five continents: 25 (37%)^{66,74,75,77,79,80,85,89,91,96,98,100,102,103,107–109,112,114,116–120,123} were issued in North America; 20 (30%)^{57–61,65,67,68,73,81,88,92,95,99,101,104,105,115,121,122} in Europe; 14 (21%)^{70,71,76,78,83,84,86,87,93,94,97,106,110,111} in Asia; four (6%)^63,64,69,72 in South America; and three (5%)^82,90,113 in Australia and New Zealand.

We categorized guidelines by disease focus: 15 were for general CVD,^57,65–78 11 for HF,^58,79–88 11 for CAD,^{59,60,89–97} five for PAD,^98–102 20 for stroke,^{61,63,64,103–120} and 3 for aortic disease.^121–123

Cardiac or stroke rehabilitation was the focus of 22% (15/65)^{61,63–65,68,70,72,74,79,97,107,110,114,116,118} CPGs. Additionally, women were the focus of 9% (6/65)^{73–76,103,105} CPGs. Mental health specialists’ involvement in guideline development was mentioned in 12% (8/65)^{57,63,67,68,70,115–117} CPGs. Table 1 shows a general overview of CPG characteristics, and Table 2 details on CPG categories and cardiovascular condition.

Table 1.

Clinical practice guidelines for cardiovascular diseases, main characteristics

CPG characteristics	CPGs by cardiovascular disease condition
	CVD (n)	HF (n)	CAD (n)	PAD (n)	Stroke (n)	Aortic disease (n)	Total (n)
CPGs (n)	15 57,65–78	11 58,79–88	11 59,60,89–97	5 98–102	20 61,63,103–120	3 121–123	65
Cardiac rehabilitation CPG (n)	5 65,68,70,72,74	1 79	1 97	0	7 61,63,107,110,114,116,118	0	14
Women-focused CPG (n)	4 73–76	0	0	0	2 103,105	0	6
Mental health specialists involved in CPG development (n)	4 57,67,68,70	0	0	0	4 63,115–117	0	8
Mention psychological health/depression as a risk factor for CVD (n)	12 57,65–70,72–74,76,78	9 58,81–86,88	10 59,60,89,91–97	1 98	13 11,61,63,107,112–118,120	1 123	46
Dedicated section on depression (n)	10 57,65–70,72,76,78	6 58,81,82,84,86,88	4 59,60,95,96	1 98	7 63,113–117,120	0	28
Cross-reference to another dedicated CPG for depression management (n)	1 57	1 58	2 59,60	0	4 61,107,118,120	0	8
In-guideline recommendations for managing depression (n)	8 57,65,67,68,70,72,74,78	5 80,83,85,87,88	5 60,89,94,96,97	1 98	12 61,63,107,112–120	0	31
Screening recommendations (n)	5 57,68,70,72,74	3 80,83,85	5 60,89,94,96,97	1 98	10 61,63,107,112,115–120	0	24
Treatment recommendations (n)	7 57,65,67,68,70,72,78	3 83,87,88	3 89,96,97	0	9 61,63,113–119	0	22
Treatment and screening recommendations (n)	4 57,68,70,72	1 83	3 89,96,97	0	7 61,63,115–119	0	15
DDIs associated with CVD and depression (n)	2 57,67	0	0	0	0	0	2

CAD, coronary artery disease; CVD, cardiovascular disease; CPG, clinical practice guideline; DDIs, drug–drug, drug–disease or disease–disease interactions; HF, heart failure; n, number; PAD, peripheral artery disease.

Table 2.

Addressing depression in cardiovascular disease clinical practice guidelines: general overview

CPG No.	CPG codea	Mental health specialist involvement in guideline development	CPGs with specific topic of focus		Level of acknowledgement of depression in CPG (excluding recommendations)
			Cardiac/stroke rehabilitation	Women	Recognized risk factor	Dedicated section
1	CVD165		X		X	X
2	CVD266				X	X
3	CVD367	X			X	X
4	CVD468	X	X		X	X
5	CVD569				X	X
6	CVD670	X	X		X	X
7	CVD771
8	CVD872	X	X		X	X
9	CVD973			X	X
10	CVD1074		X	X	X
11	CVD1175			X
12	CVD1276			X	X	X
13	CVD1357b	X			X	X
14	CVD1477
15	CVD1578				X	X
16	HF179		X
17	HF280				X
18	HF358b				X	X
19	HF481				X	X
20	HF582				X	X
21	HF683				X
22	HF784				X	X
23	HF885				X
24	HF986				X	X
25	HF1087
26	HF1188				X	X
27	CAD189				X
28	CAD290
29	CAD391				X
30	CAD459b				X	X
31	CAD592				X
32	CAD660b				X	X
33	CAD793				X
34	CAD894				X
35	CAD995				X	X
36	CAD1096				X	X
37	CAD1197		X		X
38	PAD198				X	X
39	PAD299
40	PAD3100
41	PAD4101
42	PAD5102
43	Stroke1103			X	X
44	Stroke2104
45	Stroke361b		X		X
46	Stroke4105			X
47	Stroke5106
48	Stroke6107d		X		X
49	Stroke763/864c	X	X		X	X
50	Stroke9108
51	Stroke10109				X
52	Stroke11110		X
53	Stroke12111
54	Stroke13112				X
55	Stroke14113				X	X
56	Stroke15114		X		X	X
57	Stroke16115	X			X	X
58	Stroke17116	X	X		X	X
59	Stroke18117	X			X	X
60	Stroke19118d		X		X
61	Stroke20119
62	Stroke21120d				X	X
63	Aortic1121
64	Aortic2122
65	Aortic3123				X

CAD, coronary heart disease; CPG, clinical practice guideline; CVD, cardiovascular disease; DDI, drug–drug, drug–disease, or disease–disease interactions; HF, heart failure; PAD, peripheral arterial disease; Rec., Recommendation.

^aRefer to Supplementary data online, Appendix S2, Supplementary data online, Table S3, for a detailed list of clinical practice guidelines by country, guideline-issuing body, and title.

^bFor guidance and recommendations on the management of depression, guidelines CVD13, HF3, CAD4, CAD6 and Stroke3 refer to NICE guideline 91 ‘Depression in Adults with a Chronic Physical Health Problem: Treatment and Management’.⁶²

^cThis CPG was published in two parts (Part I: Stroke7; and Part II: Stroke8), in two separate journals. Stroke8 cross-references to Stroke7 for guidance on depression, therefore only Stroke7 was considered for analysis.

^dStroke6, Stroke19, and Stroke21 refer also to Stroke18, specifically dedicated to mood and cognition management following stroke, for further guidance. Additionally, Stroke21 refers to Stroke19 for further recommendations on the management of depression.

Grading of recommendations

The CPGs were issued by 28 organizations. Ten used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.¹²⁴ NICE, SIGN, and the Heart and Stroke Foundation of Canada before October 2019 based their grading system on GRADE, as did indirectly the Korean Ministry of Health and Welfare and the German-Austrian-Swiss collaborative group, both using the SIGN grading methodology. All other organizations developed their own grading methodology. Details of guideline-issuing organizations and their respective grading methodologies, as well as the harmonised grading system we developed to enable the comparison of grading systems across the CPGs, are presented in Supplementary data online, Tables S2 and S3. All results are presented as harmonized gradings.

General mental health statements and clinical recommendations for depression

Overall, 71% (46/65)^{57–61,63,65–70,72–74,76,78,80–86,88,89,91–98,103,107,109,112–118,120,123} of CPGs mentioned depression as a potential risk factor in patients with CVD, and 43% (28/65)^{57–60,63,65–70,72,76,78,81,82,84,86,88,95,96,98,113–117,120} dedicated a section to the topic. None of the PAD CPGs and only one aortic disease¹²³ CPG mentioned depression as a risk factor.

In total, 51% (33/65)^{57–61,65,67,68,70,72,74,78–80,83,85,87–89,94,96,97,107,112–120} CPGs provided recommendations for the management of depression, the majority in-guideline (49%; 31/65)^{57–61  ,65,67,68,70,72,74,78–80,83,85,87–89,94,96,97,107,112–120}; also cross-referenced to a dedicated CPG for additional guidance, while two CPGs^58,59 only cross-referenced to a dedicated CPG for guidance (see Supplementary data online, Tables S2 and S3). Screening recommendations for depression were available in 37% (24/65)^{57,60,61,63,68,70,72,74,80,83,85,89,94,96–98,107,112,115–120} CPGs, and recommendations for its treatment in 34% (22/65)^{57,61  ,63,65,67,68,70,72,78,83,87–89,96,97,113–119}; 23% (15/65)^{57,61,63,65,67,68,70,72,78,83,88,89,96,113–119} CPGs gave both for screening and treatment recommendations. Two (2/65)^67,77 CPGs issued DDI recommendations. Table 3 summarizes those CPGs that delivered recommendations for depression, while Figure 3 provides a visual overview of these results. Table 4 informs on screening recommendations by CPG, Table 5 on treatment recommendations by CPG, and Table 6 on DDI recommendations by CPG. Five CPGs^{57,65,88,96,113} also gave ungraded practical advice for the management of depression, mentioned but not analysed in this review (Tables 3–7). Finally, all CPGs that mentioned mental health specialist involvement in their development provided recommendations.

Table 3.

Cardiovascular disease clinical practice guidelines containing recommendations for managing depression

CPG No.	CPG codea	Location of recommendations		Type of recommendations for managing depression
		Cross-reference to dedicated CPG	In-guideline	Screening	Screening good practiceb	Treatment	Treatment good practiceb	DDIs	DDIs good practiceb
1	CVD165		X		X	X	X
2	CVD266
3	CVD367		X			X		X
4	CVD468		X	X		X
5	CVD569
6	CVD670		X	X		X
7	CVD771
8	CVD872		X	X		X
9	CVD973
10	CVD1074		X	X
11	CVD1175
12	CVD1276
13	CVD1357	Xc	X	X		X	X	X
14	CVD1477
15	CVD1578		X			X
16	HF179
17	HF280		X	X	X
18	HF358	Xc
19	HF481
20	HF582				X		X		X
21	HF683		X	X		X
22	HF784						X
23	HF885		X	X
24	HF986
25	HF1087		X			X
26	HF1188		X		X	X			X
27	CAD189		X	X		X
28	CAD290
29	CAD391
30	CAD459	Xc
31	CAD592
32	CAD660	Xc	X	X
33	CAD793
34	CAD894		X	X
35	CAD995						X
36	CAD1096		X	X	X	X
37	CAD1197		X	X		X
38	PAD198		X	X
39	PAD299
40	PAD3100
41	PAD4101
42	PAD5102
43	Stroke1103
44	Stroke2104
45	Stroke361	Xc	X	X		X
46	Stroke4105
47	Stroke5106
48	Stroke6107	Xd	X	X
49	Stroke763/864e		X	X		X
50	Stroke9108
51	Stroke10109
52	Stroke11110
53	Stroke12111
54	Stroke13112		X	X
55	Stroke14113		X		X	X
56	Stroke15114		X			X
57	Stroke16115		X	X		X
58	Stroke17116		X	X		X
59	Stroke18117		X	X		X
60	Stroke19118	Xd	X	X		X
61	Stroke20119		X	X		X
62	Stroke21120	Xd	X	X
63	Aortic1121
64	Aortic2122
65	Aortic3123

CAD, coronary heart disease; CPG, clinical practice guideline; CVD, cardiovascular disease; DDI, drug–drug, drug–disease, or disease–disease interactions; HF, heart failure; PAD, peripheral arterial disease; Rec., Recommendation.

^aRefer to Supplementary data online, Appendix S2, Supplementary data online, Table S3, for a detailed list of clinical practice guidelines by country, guideline-issuing body and title.

^bGood practice points: ungraded practical advice deemed helpful to the clinician but for which there is no direct evidence to support the recommendation.

^cFor guidance and recommendations on the management of depression, guidelines CVD13, HF3, CAD4, CAD6, and Stroke3 refer to NICE guideline 91 ‘Depression in Adults with a Chronic Physical Health Problem: Treatment and Management.’⁶²

^dStroke6, Stroke19, and Stroke21 refer to Stroke18 for additional recommendations on the management of depression. Additionally, Stroke21 refers to Stroke19 for further guidance on the management of depression.

^eThis CPG was published in two parts (Part I: Stroke7; and Part II: Stroke8), in two separate journals. Stroke8 cross-references to Stroke7 for guidance on depression, therefore only Stroke7 was considered for analysis.

Figure 3.

Number of cardiovascular clinical practice guidelines providing recommendations on screening, treatment, and/or drug and disease interactions, by cardiovascular condition and category

Table 4.

Screening recommendations for depression in cardiovascular disease clinical practice guidelines

Rec. No.	CPG code*,a	Recommendations	Cardiac/stroke rehabilitation CPG	Screening tools	Source grading (SoE/LoE)	Harmonized grading (SoR/LoE)
1	CVD4 68	Psychosocial factors (e.g. depressive symptoms, anxiety, stress, motivation, self-efficacy) are recommended to be detected at the beginning of cardiac rehabilitation and to be evaluated whether they need to be treated.	X		↑↑/4	A/3
2	CVD468	Screening (of psychological factors) is suggested to be supported by specific and validated tools such as questionnaires.	X		↑/4	B/3
3	CVD6 70	In patients with CAD, screening for depression is recommended. It is recommended to use the PHQ-9 and other scales to assess depressive symptoms.	X	PHQ-9	I/A	A/1
4	CVD8 72	We recommend the identification of patients with stress and depression to allow early intervention, through psychotherapy and lifestyle changes, not only aimed specifically at the individual but also at the family members.	X		I/B	A/2
5	CVD10 74	We do recommend such (depression) screening if program patients can access providers trained in mental health care. The psychosocial needs of women should be assessed and addressed in an evidence-based manner (e.g., social support, relationship health, depression, anxiety, stress, socioeconomic issues, informal caregiving activities). When issues are identified and the program lacks expertise on the team, referral to a specialist might be warranted. Reassessment should be undertaken, and communication be made to the woman’s primary care provider with consent to ensure ongoing monitoring and follow-up.	X		Strong/⨁⨁⨁◯	A/2
6	CVD13 57 b	Depression, anxiety and social isolation or lack of quality social support are risk factors for the development and prognosis of cardiovascular disease and should be taken into account when assessing individual risk.			Strong/2++	A/2
7	HF2 80	We recommend that patients with known or suspected HF should be assessed for multimorbidity, frailty, cognitive impairment, dementia, and depression.			Strong/High	A/1
8	HF6 83	Monitoring and specialists’ treatment for psychiatric symptoms are recommended.			1/B	A/2
9	HF8 85	In adults with HF, screening for depression, social isolation, frailty, and low health literacy as risk factors for poor self-care is reasonable to improve management.		HAM-D BDI-II PHQ-9	IIa/B-NR	B/2
10	CAD1 89	In patients with CAD, targeted discussions and screening for mental health is reasonable for clinicians to assess and to refer for additional mental health evaluation and management. It is reasonable to refer patients with positive screening for in-depth assessment by qualified mental health professionals or to accessible resources to promote mental health care.		PHQ-2	IIa/B-R	B/2
11	CAD6 60 b	Be alert to possible depression (particularly in patients with a past history of depression or a chronic physical health problem with associated functional impairment) and consider asking patients who may have depression 2 questions, specifically: ‘During the last month, have you often been bothered by feeling down, depressed or hopeless?’ ‘During the last month, have you often been bothered by having little interest or pleasure in doing things?’		Two-item (Whooly) depression screen SF-36 HADS Dartmouth COOP functional health assessment charts Seattle angina questionnaire—UK version Cardiovascular limitations and symptoms profile (CAD specific) PHQ-9	Strong/2++	A/2
12	CAD8 94	Psychosocial assessment to direct psychological interventions is recommended.			Strong/High	A/1
13	CAD10 96	The AAFP recommends that clinicians screen for depression, using a standardized depression screening tool, in patients who have recently experienced an ACS event.		BDI-II PHQ HADS GDS	Weak/Low-quality evidence	C/3
14	CAD11 97	Patients referred to CR should be assessed for psychological problems, such as anxiety, depression, and stress, and should be provided with psychological interventions if abnormal findings are observed.	X		Strong/1++	A/1
15	PAD1 98	In the evaluation of patients with PAD, clinicians should assess for and incorporate the presence of PAD-related risk amplifiers when developing patient-focused treatment recommendations. Depression is a risk amplifier for PAD.		GDS PHQ-9	1/C-EO	A/3
16	Stroke3 61 b	Carry out a comprehensive assessment of a person after stroke that both identifies and takes into account changes to, or impairment of, psychological and neuropsychological functioning relating to cognitive, emotional or behavioural functioning, such as new signs of emotionalism, mental health (for example, the onset of depression), including signs indicating an increased risk of suicide.			Strong/NA	A/NA
17	Stroke6 107 c	People with stroke, their families, and caregivers should be screened for their level of coping, risk for depression, and other physical and psychological issues. Ideally, screening should take place at each transition and additionally when indicated.	X	EQ-5D SA-SIP-30 SF-36 SIS SS-QOL	Should/B	B/2
18	Stroke6107c	People with stroke should be screened and treated for new and/or ongoing cognitive concerns, mental health issues (i.e. depression, anxiety), and psychosocial issues as required.	X		Should/B	B/2
19	Stroke6107c	Validated screening tools or approaches can be used whenever possible to ensure a consistent approach to identifying potential issues during transitions. For additional guidance, this CPG refers to Table 1 in Stroke18117 (www.strokebestpractices.ca).	X	EQ-5D SF-36 SS-QOL	Can/C	A/3
20	Stroke7 63	If erectile dysfunction is present in men after stroke, antihypertensive drug use, anxiety, and depression should be investigated.	X		I/B	A/2
21	Stroke13 112	Patients with stroke should be assessed for neurological impairments and functional limitations (e.g. screening for depression).			Should/B	B/2
22	Stroke16 115	People with stroke should be routinely screened for anxiety and depression using standardized tools. People with stroke with one mood disorder should be assessed for others.		SADQ (for patients with severe aphasia)	Should/Group consensus	B/3
23	Stroke17 116	Administration of a structured depression inventory is recommended to routinely screen for poststroke depression.		PHQ-2	l/B	A/2
24	Stroke17116	Periodic reassessment of depression, anxiety, and other psychiatric symptoms may be useful in the care of stroke survivors.	X		lla/B	B/2
25	Stroke18 117	All people who have experienced a stroke should be screened for post-stroke depression if deemed medically appropriate, given the high prevalence of post-stroke depression and the evidence for treating symptomatic depression post stroke. Note: ‘Medically appropriate’ excludes people who have experienced a stroke who are unresponsive or who have deficits that interfere with screening for mood disorders. Any pre-stroke mental health or cognitive diagnoses should be taken into consideration during the screening process.		GDS HADS PHQ-9 BDI-II CES-D	Should/B	B/2
26	Stroke18117	Screening should be undertaken by trained professionals using a validated screening tool to maximize detection of depression.			Should/B	B/2
27	Stroke18117	Stroke assessments should include evaluation of risk factors for depression, particularly a history of depression.			Should/C	B/3
28	Stroke18117	For people who experience some degree of communication challenge or deficits following stroke, appropriate strategies that do not rely on verbal communication should be implemented for screening of possible post-stroke depression to ensure adequate detection and assessment, and access to appropriate treatment.			Should/C	B/3
29	Stroke18117	People who have experienced a stroke whose screening indicates a high risk for depression should be assessed in a timely manner by a healthcare professional with expertise in diagnosis, management, and follow-up of depression.			Should/C	B/3
30	Stroke19 118 c	Additional screening of impairments, including onset of depression, cognitive ability, functional activity limitations, role participation restrictions, environmental factors, and the presence of modifiable stroke risk factors (such as lifestyle behaviours) should be considered within two weeks of stroke onset.	X		Should/C	B/3
31	Stroke20 119	Administration of a structured depression inventory such as the Patient Health Questionnaire-2 is recommended to routinely screen for poststroke depression.		PHQ-2	I/B	A/2
32	Stoke21 120 c	Functional assessment: Patients with stroke should be assessed for neurological impairments and functional limitations (e.g. cognitive evaluation, screening for depression, screening for dysphagia, screening for aphasia, screening for fitness to drive, need for rehabilitation therapy, assistance with activities of daily living, functional mobility).		DOC	Strong/Moderate	A/2
33	Stoke21120c	Patients should undergo an initial screening for depression, including screening for a history of depression.			Strong/Moderate	A/2
34	Stoke21120c	Administration of a structured depression inventory such as the Patient Health Questionnaire-2 is recommended to routinely screen for post-stroke depression.		PHQ-2	I/B	A/2
35	Stoke21120c	Stroke assessments should include evaluation of risk factors for depression, particularly a history of depression.			Strong/Low	A/3
Good practice pointsd
1	CVD165	Assessment tools for depression should be repeated over the course of rehabilitation as part of a clinical pathway to ensure ongoing monitoring of symptoms and provide outcome measures of care.		PHQ-9 BDI-II
2	HF280	Depression in older patients with HF should be suspected when chronic physical complaints persist despite optimal HF therapy. Symptoms and psychosocial burden (e.g. depression, fear, anxiety, social isolation, home supports, and need for respite care) should be regularly evaluated, and a palliative care referral considered.
3	HF582	Regularly screen for depression using a validated questionnaire.		PHQ-2/9
4	HF1188	Patients with heart failure should be screened for depression using a validated measure and within the context of a collaborative, stepped-care model which includes a locally defined clinical care pathway.		PHQ-9 HADS BDI-II
5	CAD1096	Individuals should undergo further assessment to confirm the diagnosis of depression.
6	Stroke14113	Stroke survivors with suspected altered mood (e.g. depression, anxiety, and emotionalism) should be assessed by trained personnel using a standardised and validated scale for use in people with stroke. Diagnosis should only be made following a clinical interview.		SADQ

AAFP, American Academy of Family Physicians; ASCVD, Atherosclerotic cardiovascular disease; BDI-II, Beck Depression Inventory II; CAD, Coronary artery disease; CDS, Cardiac Depression Scale; CES-D, Center for Epidemiological Studies Depression Scale; CPG, Clinical practice guideline; CR, Cardiac rehabilitation; CVD, Cardiovascular disease; DOC, Cardiovascular disease; DOC, Depression, Obstructive Sleep Apnoea and Cognitive Impairment–DOC Screening Tool; EQ-5D, EuroQol Quality of Life Scale; GDS, Geriatric Depression Scale; HADS, Hospital Anxiety and Depression Scale; HAM-D, Hamilton Depression Rating Scale; HF, Heart failure; LoE, Level of evidence; NICE, National Institute for Health and Care Excellence; NA, not available; PAD, Peripheral artery disease; PHQ, Patient Health Questionnaire; Rec., Recommendation; SS-QOL, Stroke Specific Quality of Life Scale; SADQ, Stroke Aphasic Depression Questionnaire; SA-SIP-30, Stroke-Adapted Sickness Impact Profile; SF-36, Medical Outcomes Study Short Form Short-Form Survey; SIS, Stroke Impact Scale.

^*Bold letters indicate the first mention of each CPG.

^aRefer to Supplementary data online, Appendix S2, Supplementary data online, Table S3, for a detailed list of clinical practice guidelines by country, guideline-issuing body, and title.

^bFor guidance and recommendations on the management of depression, the guideline cross-references another guideline, NICE guideline 91 ‘Depression in Adults with a Chronic Physical Health Problem: Treatment and Management.⁶²

^cStroke6, Stroke19, and Stroke21 refer to Stroke18 for additional recommendations on the management of depression. Additionally, Stroke21 refers to Stroke19 for further recommendations on the management of depression.

^dUngraded practical advice deemed helpful to the clinician but for which there is no direct evidence to support the recommendation.

Table 5.

Treatment recommendations for depression in cardiovascular disease clinical practice guidelines

Rec. No.	CPG code*,a	Recommendations	Recommendation to involve mental health professionals	Treatment recommendation characteristics						Source SoR/LoE	Harmonized grading (SoR/LoE)
				Preventive	Pharmac. (P)/Non-pharmac. (NP)/Unspecific	Psychological intervention	Cognitive-behavioural therapy	Physical activity	Antidepressants (X)/SSRIs (S)
1	CVD1 65	CBT should be the first choice of psychological intervention for patients in cardiac rehabilitation with clinical depression or anxiety. Oher evidence-based psychological therapies for depression such as interpersonal psychotherapy or problem-solving therapy can be offered if CBT is not appropriate.			NP	X	X			Strong/4	A/3
2	CVD165	Cardiac rehabilitation should incorporate a stepped-care pathway to meet the psychological needs of patients.			NP	X				Strong/4	A/3
3	CVD165	All patients should be offered a package of psychological care, based on a cognitive behavioural model (e.g. stress management, cognitive restructuring, communication skills) as an integral part of cardiac rehabilitation.			NP	X	X			Strong/4	A/3
4	CVD3 67	Patients with mental disorders need intensified attention and support to improve adherence to lifestyle changes and drug treatment.			NP/Pa				X	1/C	A/3
5	CVD367	In ASCVD patients with mental disorders, evidence-based mental healthcare, and interdisciplinary cooperation are recommended.			Unspecific					1/B	A/2
6	CVD367	Patients with CHD and moderate-to-severe major depression should be considered for antidepressive treatment with an SSRI.			P				X/S	lla/B	B/2
7	CVD367	In patients with HF and major depression, SSRIs, SNRIs, and tricyclic antidepressants are not recommended.			P				X/S	III/B	C/2
8	CVD4 68	Based on the screening procedure, it is recommended to deliver appropriate psychological interventions and support after a shared decision making.			NP	X				↑↑/4	A/3
9	CVD468	Non-specific psychological interventions for all patients in CR without individual indication are not recommended.			NP	X				↓↓/4	N/3
10	CVD468	Mental disorders, according to ICD-10, are recommended to be diagnosed and treated according to guidelines, taking into account cardiovascular comorbidities.			NP/Pa					↑↑/1-	A/1
11	CVD468	Mental disorders according to ICD-10 are not recommended to be treated only by psychological interventions to improve health behaviour, coping with the disease and distress management.			Unspecific					↓↓/1	N/1
12	CVD468	Psychological interventions are suggested to be performed by qualified physicians or psychologists.	X		NP	X				↑/4	A/3
13	CVD6 70	It is recommended to perform CR to improve depressive symptoms.			Unspecific					l/A	A/1
14	CVD670	It should be considered to administer antidepressants and to conduct psychotherapy, such as CBT, to improve depressive symptoms.			NP/Pa		X		X	lla/B	B/2
15	CVD8 72	Patients at risk of depression: Allow early intervention, through psychotherapy and lifestyle changes, not only aimed specifically at the individual but also at the family members. These measures may include group therapy, specific medication, physical activity, and social support, which are all administered by specialized professionals.	X	X	NP	X		X		I, B	A/2
16	CVD13 57 b	Individual CBT is recommended as a treatment option for patients with depression or anxiety disorders.			NP	X	X			Strong/1++	A/1
17	CVD1357b	Pharmacological treatment with SSRIs in patients with depression and coronary heart disease should be considered, although caution should be taken over patients receiving polypharmacy in whom bleeding risk may be increased.			P				X/S	Strong/1++	A/1
18	CVD15 78	Coronary patients with clinically significant depression can be safely and effectively treated with psychotherapy.			NP	X				lla/B	B/2
19	CVD1578	Coronary patients with clinically significant depression can be safely and effectively treated with Selective serotonin reuptake inhibitors.			P					lla/B	B/2
20	CVD1578	A prudent approach at present is to offer patients with clinically significant depression or anxiety treatment with psychotherapy and antidepressant/anxiolytic medication. Those not accepting treatment should be followed closely, and treatment offered again if symptoms persist for 4–6 weeks.			NP/Pa				X	lla/B	B/2
21	HF6 83	Monitoring and specialists’ treatment for psychiatric symptoms are recommended	X		Unspecific					I/B	A/2
22	HF10 87	SSRI may be considered to treat depression, unless contraindicated.			P				X/S	Strong	A/NA
23	HF11 88	CBT should be considered for patients with heart failure and clinical depression.			NP	X	X			1++/Strong	A/1
24	CAD1 89	In patients with chronic coronary disease, treatment for mental health conditions with either pharmacologic or nonpharmacologic therapies, or both, is reasonable to improve cardiovascular outcomes.			NP/Pa				X	2a/B-R	B/2
25	CAD10 96	The AAFP strongly recommends that clinicians prescribe antidepressant medication, preferably SSRIs or SNRIs, and/or CBT to improve symptoms of depression in patients who have a history of ACS and have been diagnosed with depression.			NP/P		X		X/S	Strong/moderate-quality evidence	A/2
26	CAD11 97	Patients referred to CR and diagnosed with depression should be provided with psychological interventions.			NP	X				Strong/1++	A/1
27	Stroke3 61 b	Manage depression or anxiety in people after stroke who have no cognitive impairment in line with NICE's guidelines on depression in adults with a chronic physical health problem and generalised anxiety disorder and panic disorder in adults.			Unspecific			X		Strong/NA	A/NA
28	Stroke7 63	Pharmacological treatment with antidepressants, such as SSRIs, can be recommended for the treatment of post stroke depression.			P				X/S	lla/A	B/1
29	Stroke763	Selective serotonin reuptake inhibitors SSRIs may be used prophylactically after stroke to prevent post-stroke depression.		X	P				X/S	llb/B	B/2
30	Stroke763	Family support, CBT, and lifestyle interventions can be considered in patients with post-stroke depression.			NP		X			lla/B	B/2
31	Stroke763	Exercise training may be used as a complementary treatment option in cases of post-stroke depression.			NP			X		llb/B	B/2
32	Stroke763	The combination of pharmacological and nonpharmacological treatments may be considered in patients with post-stroke depression.			NP/Pa				X	llb/B	B/2
33	Stroke763	Transcranial magnetic stimulation has unclear benefits for post-stroke depression.			NP					lll/B	C/2
34	Stroke763	Antidepressants should be taken in the morning.			P					lla/B	B/2
35	Stroke14 113	For stroke survivors, antidepressant medication may be used to prevent depression.		X	P				X	Weak/Very low	C/3
36	Stroke14113	For stroke survivors, psychological therapies (e.g. problem solving, motivational interviewing) may be used to prevent depression.		X	NP	X				Weak/Very low	C/3
37	Stroke14113	For stroke survivors with depression, antidepressants, which include SSRIs should be considered. There is no clear evidence that particular antidepressants produce greater effects than others and will vary according to the benefit and risk profile of the individual.			P				X/S	Weak/Very low	C/3
38	Stroke14113	For stroke survivors with depression or depressive symptoms, psychological therapy may be provided.			NP	X				Weak/Very low	C/3
39	Stroke14113	For stroke survivors with depression or depressive symptoms, structured exercise programmes, particularly resistance training or programmes of high intensity, may be used.			NP	X		X		Weak/Low	C/3
40	Stroke14113	For stroke survivors with depression, non-invasive brain stimulation (repetitive transcranial magnetic stimulation [rTMS]) may be used.			NP					Weak/Very low	C/3
41	Stroke14113	For stroke survivors with depression or depressive symptoms, acupuncture may be used.			NP					Weak/Low	C/3
42	Stroke15 114	We suggest the following interventions for patients and their caregivers: • Behavioural health/psychosocial interventions to improve patient and caregiver depression • Psychoeducation to improve family function, patient functional independence, and quality of life.			NP	X				Neither for nor against/NA	B/NA
43	Stroke15114	There is insufficient evidence to recommend for or against selective serotonin reuptake inhibitors to improve motor outcomes in patients with or without depression.			P				X/S	Neither for nor against/NA	B/NA
44	Stroke15114	Prevention of depression: There is insufficient evidence to recommend for or against solution-focused psychological interventions (e.g. motivational interviewing, problem-solving therapy) to prevent the development of depression.		X	NP	X				Neither for nor against/NA	B/NA
45	Stroke15114	Prevention of depression: We suggest against the use of antidepressants for the prevention of post-stroke depression.		X	P				X	Weak against/NA	C/NA
46	Stroke15114	We suggest a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor for depression symptoms.			P				X/S	Weak for/NA	C/NA
47	Stroke15114	We suggest psychotherapy (e.g. cognitive behavioural therapy) for depression following stroke.			NP	X	X			Weak for/NA	C/3
48	Stroke15114	We suggest mindfulness-based therapies for the treatment of depression following stroke.			NP					Weak for/NA	C/NA
49	Stroke15114	There is insufficient evidence to recommend for or against acupuncture, either alone or as an adjunct to pharmacotherapy, for depression following stroke.			NP					Neither for nor against/NA	B/NA
50	Stroke16 115	People with depression or anxiety after stroke, and those assessed to be at risk, should be considered by the multidisciplinary team for approaches, education, and a reasonable period of watchful waiting where appropriate.		X	Unspecific					Strong	A/3
51	Stroke16115	People with stroke should be offered one-to-one motivational interviewing or problem-solving therapy, adapted as necessary for people with aphasia or cognitive impairment, as part of a multidisciplinary rehabilitation approach to prevent depression.		X	NP	X	X			Strong	A/3
52	Stroke16115	People with stroke at significant risk of anxiety or depression should be offered psychological therapies (motivational interviewing, CBT, problem-solving therapy or acceptance and commitment therapy) provided they have sufficient cognitive and language skills to engage with the therapy.	X	X	NP	X	X			Strong	A/3
53	Stroke16115	People with stroke should not be routinely offered SSRIs for the prevention of depression.		X	P				X	Medium/NA	B/NA
54	Stroke16115	SSRIs may be considered when other preventative approaches are not appropriate (e.g. in people with severe cognitive or language impairment) or when the risk of depression is high (e.g. in people with a previous history of depression). The balance of risk and benefit from SSRIs should take account of the potential for increased adverse effects (seizures and hip fracture).		X	P				X/S	Weak	C/1
55	Stroke16115	People with depression after stroke should be offered psychological interventions (motivational interviewing, CBT or problem-solving therapy) adapted as necessary for use with people with aphasia or cognitive impairment and/or an SSRI.			NP/Pa	X	X		X/S	Strong	A/3
56	Stroke16115	People with depression after stroke may be considered for non-invasive brain stimulation in the context of a clinical trial.			NP					Weak	C/1
57	Stroke16115	People with depression after stroke who are treated with antidepressant medication should be monitored for effectiveness and adverse effects within the first 6 weeks. If there has been a benefit people should be treated for at least four months beyond initial recovery. If the person’s mood has not improved after 6 weeks, medication adherence should be checked before considering a dose increase, a change to another antidepressant or an alternative treatment.			NP/Pa				X	Strong	A/NA
58	Stroke16115	People with persistent moderate to severe emotional disturbance after stroke who have not responded to high-intensity psychological intervention or pharmacological treatment should receive collaborative care, which should include long-term follow-up and involve liaison between the GP, stroke team and secondary care mental health services with supervision from a senior mental health professional.	X		NP					Strong	A/3
59	Stroke16115	Where people with depression or anxiety after stroke are being treated within primary care health services or secondary care mental health services, advice, consultation and training should be available from the stroke service. Guidance for the management of people with significant language and cognitive impairment should be agreed between services and joint working offered where appropriate.			Unspecific					Strong	A/3
60	Stroke17 116	Patients diagnosed with poststroke depression should be treated with antidepressants in the absence of contraindications and closely monitored to verify effectiveness.			P				X	I/B	A/2
61	Stroke17116	Consultation by a qualified psychiatrist or psychologist for stroke survivors with mood disorders causing persistent distress or worsening disability can be useful.	X		NP	X				IIa/C	B/3
62	Stroke17116	The usefulness of routine use of prophylactic antidepressant medications is unclear		X	P				X	IIb/A	B/1
63	Stroke17116	Combining pharmacological and nonpharmacological treatments of poststroke depression may be considered.			NP/Pa				X	IIb/A	B/1
64	Stroke17116	The efficacy of individual psychotherapy alone in the treatment of poststroke depression is unclear.			NP	X				IIb/B	B/2
65	Stroke17116	Patient education, counselling, and social support may be considered components of treatment for poststroke depression.			NP	X				IIb/B	B/2
66	Stroke17116	An exercise program of at least 4 weeks duration may be considered as a complementary treatment for poststroke depression.			NP			X		IIb/B	B/2
67	Stroke17116	Early effective treatment of depression may have a positive effect on the rehabilitation outcome.			Unspecific					IIb/B	B/2
68	Stroke17116	No recommendation for the use of any particular class of antidepressants is made. SSRIs are commonly used and generally well tolerated in this patient population.			P				X/S	III/A	C/1
69	Stroke18 117	It is reasonable to consider either CBT or interpersonal therapy as one of the first-line treatments for depressive symptoms post stroke as a monotherapy.			NP	X	X			Weak/B	C/2
70	Stroke18117	Treatment for post-stroke depression may include psychotherapy as an adjunct in combination with antidepressants, as appropriate to the person who has experienced a stroke’s health state and other deficits (e.g. communication and other cognitive deficits).			NP/Pa	X			X	Weak/A	C/1
71	Stroke18117	People who have experienced a stroke with mild depressive symptoms or those diagnosed with minor depression may initially be managed by ‘watchful waiting’ (a period of monitoring a patient closely without additional therapeutic interventions to determine whether the mild depressive symptoms will improve. The timeframe for watchful waiting varies in the literature, typically between 2–4 weeks. It is often described as including suggestions for self-help strategies and participation in physical exercise).			NP			X		Weak/B	C/2
72	Stroke18117	Pharmacological treatment should be considered and started if the depression is persistent or worsens and interferes with clinical goals.			P				X	Strong/B	A/2
73	Stroke18117	People diagnosed with a depressive disorder following stroke should be considered for a trial of antidepressant medication.			P				X	Strong/A	A/1
74	Stroke18117	No one drug or drug class has been found to be superior for post-stroke depression treatment. Side effect profiles, however, suggest that some selective serotonin reuptake inhibitors (SSRIs) may be favoured in this patient population. Choice of an antidepressant medication will depend upon symptoms of depression, potential known side effects of the medication, particularly in the child or older adult, drug interactions with other current medications and underlying disease conditions.			P				X/S	Weak/A	C/1
75	Stroke18117	Response to treatment (with an antidepressant) should be monitored regularly by a health professional. Monitoring should include evaluation of any changes in the severity of depression, review of potential side effects, and update of ongoing management plans.			P				X	Strong/C	A/3
76	Stroke18117	If a good response to (antidepressant) treatment is achieved, treatment should be continued for a minimum of six to 12 months.			P				X	Strong/C	A/3
77	Stroke18117	If the person’s mood has not improved 2–4 weeks after initiating treatment (of antidepressant), assess patient compliance with medication regime. If compliant, then consider increasing the dosage, adding an additional medication, or changing to another antidepressant.			P				X	Weak/B	C/2
78	Stroke18117	Following the initial course of treatment (of antidepressant), maintenance therapy could be considered on an individual basis (consider previous history and risk factors for recurrence of depression).			P				X	Weak/C	C/3
79	Stroke18117	If a decision is made to discontinue an antidepressant, it should be tapered over one to two months.			P				X	Strong/C	A/3
80	Stroke18117	Prophylactic pharmacotherapy has been shown to prevent post-stroke depressive symptoms.		X	P				X	Strong/Level A	A/1
81	Stroke18117	The impact of prophylactic pharmacology on function is less clear. At this time routine use of prophylactic antidepressants for ALL people who have experienced a stroke is not recommended as the riskbenefit ratio has not been clearly established.		X	P				X	Strong/Level B	A/2
82	Stroke18117	Problem-solving therapy (i.e. CBT) has been shown to have efficacy for prophylactic treatment for post-stroke depression.		X	NP	X	X			Strong/B	A/2
83	Stroke19 118 c	Patients should receive a tricyclic antidepressant (e.g. amitriptyline) or a Serotonin-norepinephrine reuptake inhibitor (particularly duloxetine) as second-line treatment.			P				X/S	Should/C	B/3
84	Stroke20 119	Patients diagnosed with poststroke depression should be treated with antidepressants in the absence of contraindications and closely monitored to verify effectiveness.			P				X	I/B-R	A/2
Good practice pointsd
1	CVD165	To ensure clinical governance and quality, psychological therapies should be evidence based, and delivered by psychologically-trained and supervised healthcare professionals within the context of a locally-defined care pathway.			Unspecific
14	CVD1477	Patients who present with more complex psychological problems should be considered for referral to mental health services for assessment and delivery, where appropriate, of high-intensity or specialist treatments.			Unspecific
20	HF5 82	CBT, pharmacological treatment and exercise training may be considered in patients with heart failure associated with depression.			NP/Pa		X	X
20	HF582	SSRIs are the safest choice if pharmacological treatment for depression.			P				X
22	HF784	Address psychosocial problems encountered by the patient and the family.			Unspecific
35	CAD995	Psychosocial aspects: Avoid psychosocial stress; Treat depression and anxiety by psychological or pharmacological interventions.			NP/Pa

AAFP, American Academy of Family Physicians; ACS, Acute coronary syndrome; CAD, Coronary artery disease; CBT, Cognitive-behavioural therapy; CPG, clinical practice guideline; CVD, cardiovascular disease; HF, Heart failure; LoE, Level of evidence; PAD, Peripheral artery disease; Pharmac., pharmacological; Rec., Recommendation; SSRI, Selective serotonin reuptake inhibitor; SNRI, Serotonin and norepinephrine reuptake inhibitors; SoR, Strength of recommendation.

^*Bold letters indicate the first mention of each CPG.

^aRecommendation containing both non-pharmacological and pharmacological guidance.

^bCross-references to the NICE guideline 91 ‘Depression in Adults with a Chronic Physical Health Problem: Treatment and Management.’⁶² for further guidance on depression management.

^cStroke6, Stroke19, and Stroke21 refer also to Stroke18, specifically dedicated to mood and cognition management following stroke, for further guidance. Additionally, Stroke21 refers to Stroke19 for further recommendations on the management of depression.

^dUngraded practical advice deemed helpful to the clinician but for which there is no direct evidence to support the recommendation.

Table 6.

Disease and drug interaction recommendations in cardiovascular disease clinical practice guidelines

Rec. no.	Guideline codea	Recommendations	Type of interaction	Source grading (SoR/LoE)	Harmonized grading (SoR/LoE)
1	CVD367	Antidepressants are not recommended for treating major depression in HF patients as they can be associated with harmful effects such as an increased risk of all-cause death. In patients with HF and major depression, SSRIs, SNRIs, and tricyclic antidepressants are not recommended.	Drug–Disease	III/B	N/3
2	CVD1477	Pharmacological treatment with SSRIs in patients with depression and coronary heart disease should be considered, although caution should be taken over patients receiving polypharmacy in whom bleeding risk may be increased.	Drug–Drug	Medium/1++	B/1
Good practice pointsb
1	HF582	Avoid tricyclic antidepressants for the treatment of depression in patients with HF, which can cause tachyarrhythmias, hypotension, and worsening heart failure. Citalopram and mirtazapine can prolong corrected QT and cause torsades de pointes.	Drug–Disease
2	HF1188	If antidepressant medication is prescribed, a tricyclic antidepressant should not be used in patients with HF.	Drug–Disease
Guidelines that address DDI management but not as recommendations
1	CVD266	Treatment for moderate to severe depression includes selective serotonin reuptake inhibitor antidepressants, such as sertraline or escitalopram (with occasional prolonged QTc effects).	Drug–Disease
2	CVD973	For cardiac transplant patients—Adequate psychosocial support is very helpful in managing depression, which is increased by the use of steroids and the high level of anxiety generated by the transplantation itself.	Drug–Disease Disease–Disease
3	CVD1074	In the case of post-partum hypertension, Methyldopa should be avoided because of the risk of post-partum depression.	Drug–Disease
4	HF481	Tricyclic antidepressants should be avoided for the treatment of depression in patients with HF as they may cause hypotension, worsening of HF, and arrhythmias.	Drug–Disease
5	HF986	Sertraline and escitalopram exhibited medication safety in patients with HF. Tricyclic antidepressants cause hypotension, worsening HF, and arrhythmia and should be avoided in patients with HF.	Drug–Disease
6	CAD189	Long-term use of beta-blocker therapy may also confer potential clinical risks including depression.	Drug–Disease
7	CAD290	Adverse effects of beta-blocker therapy include fatigue, reduced libido, depression.	Drug–Disease
8	CAD793	Side effects of BB include fatigue, impotence, and depression. CCBs such as verapamil and diltiazem are as efficacious as BB as anti-anginal therapy and cause less symptoms of depression.	Drug–Disease
9	CAD995	Side effects of beta-blockers include fatigue and depression Compared with atenolol in hypertension with CAD, verapamil is associated with less psychological depression.	Drug/Disease

BB, Beta-blocker; CAD, Coronary artery disease; CCB, Calcium channel blocker; CVD, Cardiovascular disease; DDI, drug–drug/drug–disease/disease–disease interaction; HF, Heart failure; INR, International normalized ratio; LoE, Level of evidence; PAD, Peripheral artery disease; Rec., Recommendation; SSRI, Selective serotonin reuptake inhibitors; SNRI, Serotonin and norepinephrine reuptake inhibitors; SoR, Strength of recommendation.

^aRefer to Supplementary data online, Appendix S2, Supplementary data online, Table S3, for a detailed list of clinical practice guidelines by country, guideline-issuing body, and title.

^bUngraded practical advice based on expert group experience deemed helpful to a clinician but for which there is no direct evidence to support the recommendation.

Table 7.

Cardiac rehabilitation and stroke rehabilitation clinical practice guideline recommendations for the management of depression

Rec. no.	CPG code*,a	Recommendation	Recommendation type (Screening/Treatment)	Source SoR/LoE	Harmonized grading (SoR/LoE)
1	CVD1 65	All patients should be offered a package of psychological care, based on a cognitive behavioural model (e.g. stress management, cognitive restructuring, communication skills) as an integral part of cardiac rehabilitation.	Treatment	Strong/4	A/3
2	CVD4 68	Screening (of psychological factors) is suggested to be supported by specific and validated tools such as questionnaires.	Screening	↑/4	B/3
3	CVD468	Mental disorders according to ICD-10 are not recommended to be treated only by psychological interventions to improve health behaviour, coping with the disease and distress management.	Treatment	↓↓/1	N/1
4	CVD468	Psychological interventions are suggested to be performed by qualified physicians or psychologists.	Treatment	↑/4	A/3
5	CVD6 70	We recommend the identification of patients with stress and depression to allow early intervention, through psychotherapy and lifestyle changes, not only aimed specifically at the individual but also at the family members. These measures may include group therapy, specific medication, physical activity, and social support, which are all administered by specialized professionals.	Screening/Treatment	I/B	A/2
6	CVD670	In patients with CAD, screening for depression is recommended. It is recommended to use the PHQ-9 and other scales to assess depressive symptoms.	Screening	I/A	A/1
7	CVD670	It is recommended to perform CR to improve depressive symptoms.	Treatment	l/A	A/1
8	CVD670	It should be considered to administer antidepressants and to conduct psychotherapy, such as CBT, to improve depressive symptoms.	Treatment	lla/B	B/2
9	CVD8 72	Patients at risk of depression: Allow early intervention, through psychotherapy and lifestyle changes, not only aimed specifically at the individual but also at the family members. These measures may include group therapy, specific medication, physical activity, and social support, which are all administered by specialized professionals.	Treatment	I, B	A/2
10	CVD10 74	We do recommend such (depression) screening if program patients can access providers trained in mental health care. The psychosocial needs of women should be assessed and addressed in an evidence-based manner (e.g. social support, relationship health, depression, anxiety, stress, socioeconomic issues, informal caregiving activities). When issues are identified and the program lacks expertise on the team, referral to a specialist might be warranted. Reassessment should be undertaken, and communication be made to the woman’s primary care provider with consent to ensure ongoing monitoring and follow-up.	Screening	Strong/⨁⨁⨁◯	A/2
11	CAD11 97	Patients referred to CR should be assessed for psychological problems, such as anxiety, depression, and stress, and should be provided with psychological interventions if abnormal findings are observed.	Screening	Strong/1++	A/1
12	CAD1197	Patients referred to CR and diagnosed with depression should be provided with psychological interventions.	Treatment	Strong/1++	A/1
13	Stroke3 61 b	Carry out a comprehensive assessment of a person after stroke that both identifies and takes into account changes to, or impairment of, psychological and neuropsychological functioning relating to cognitive, emotional or behavioural functioning, such as new signs of emotionalism, mental health (for example, the onset of depression), including signs indicating an increased risk of suicide.	Screening	Strong/NA	A/NA
14	Stroke361b	Manage depression or anxiety in people after stroke who have no cognitive impairment in line with NICE's guidelines on depression in adults with a chronic physical health problem and generalised anxiety disorder and panic disorder in adults.	Treatment	Strong/NA	A/NA
15	Stroke6 107 c	People with stroke, their families, and caregivers should be screened for their level of coping, risk for depression, and other physical and psychological issues.	Screening	Should/B	B/2
16	Stroke6107c	Validated screening tools or approaches can be used whenever possible to ensure a consistent approach to identifying potential issues during transitions.	Screening	Can/C	A/3
17	Stroke7 63	If erectile dysfunction is present in men after stroke, antihypertensive drug use, anxiety, and depression should be investigated.	Screening	I/B	A/2
18	Stroke763	Pharmacological treatment with antidepressants, such as SSRIs, can be recommended for the treatment of Post stroke depression.	Treatment	lla/A	B/1
19	Stroke763	Selective serotonin reuptake inhibitors SSRIs may be used prophylactically after stroke to prevent post-stroke depression.	Treatment	llb/B	B/2
20	Stroke763	Family support, CBT, and lifestyle interventions can be considered in patients with post-stroke depression.	Treatment	lla/B	B/2
21	Stroke763	Exercise training may be used as a complementary treatment option in cases of post-stroke depression.	Treatment	llb/B	B/2
22	Stroke763	The combination of pharmacological and nonpharmacological treatments may be considered in patients with post-stroke depression.	Treatment	llb/B	B/2
23	Stroke763	Transcranial magnetic stimulation has unclear benefits for post-stroke depression.	Treatment	lll/B	C/2
24	Stroke763	Antidepressants should be taken in the morning.	Treatment	lla/B	B/2
25	Stroke17 116	Administration of a structured depression inventory is recommended to routinely screen for poststroke depression.	Screening	l/B	A/2
26	Stroke17116	Periodic reassessment of depression, anxiety, and other psychiatric symptoms may be useful in the care of stroke survivors.	Screening	lla/B	B/2
27	Stroke17116	Early effective treatment of depression may have a positive effect on the rehabilitation outcome.	Treatment	IIb/B	B/2
28	Stroke19 118 c	Additional screening should be conducted within 2 weeks of stroke onset, including impairment, functional activity limitations, role participation restrictions, environmental factors and screening for onset of depression.	Screening	Should/C	B/3
29	Stroke19118c	Patients should receive a tricyclic antidepressant (e.g. amitriptyline) or a Serotonin-norepinephrine reuptake Inhibitor (particularly duloxetine) as second-line treatment.	Treatment	Should/C	B/3

CAD, coronary artery disease: CR, Cardiac rehabilitation; CPG, clinical practice guideline; CVD, cardiovascular disease; HF, heart failure; LoE, Level of evidence; Rec., recommendation; SoE, Strength of recommendation.

^*Bold letters indicate the first mention of each CPG.

^aRefer to Supplementary data online, Appendix S2, Supplementary data online, Table S3, for the full list of clinical practice guideline numbers and codes.

^bFor guidance and recommendations on the management of depression, guidelines CVD13, HF3, CAD4, CAD6, and Stroke3 partly or fully refer to NICE guideline 91 ‘Depression in Adults with a Chronic Physical Health Problem: Treatment and Management.’⁶²

^cStroke6, Stroke19 and Stroke21 refer to Stroke18 for additional recommendations on the management of depression. Additionally, Stroke21 refers to Stroke19 for further recommendations on the management of depression.

In total, 121 in-guideline recommendations addressing depression were retrieved: 29% (35) were for screening (Table 4), 69% (84) for treatment (Table 5), and <1% (2) for DDIs (Table 6). Most recommendations (64%; 78/121) came from the stroke CPGs.

Eleven of the 14 cardiac and stroke rehabilitation CPGs^{61,63,65,68,70,72,79,97,107,116,118} delivered 24% (29/121) of all recommendations (Table 7), and most of these CPGs^{61,63,68,70,72,97,116,118} gave both screening and treatment recommendations. Of the six women-focussed CPGs, only one⁹⁶ issued a recommendation for managing depression.

Screening recommendations for depression

Thirty-seven per cent (24/65)^{57,60,61,63  ,68,70,72,74,80,83,85,89,94,96–98,107,112,115–120} of CPGs gave 35 in-guideline screening recommendations for depression. A further three^60,61,119 recommended to screen only in case of clinical suspicion of depression. Fifteen CPGs^{60,70,83,85,89,94,96,98,107,115–120} recommended the use of a screening tool, most often the Patient Health Questionnaire in its 2- or 9-item version (PHQ-2, PHQ-9) in ten CPGs.^{60,70,85,89,96,98,116,117,119,120} The Beck Depression Inventory (BDI-II) was the second most recommended screening tool, although only in three (3/65; 4%) CPGs.^72,84,117 Other screening tools were for special conditions or populations.^60,96,103

Recommendations were mostly evaluated as strong (57%; 20/35) or moderate 40% (14/35). Level of evidence of recommendations was mostly evaluated as medium (54%; 19/35 recommendations) or low quality (32%; 11/35 recommendations).

Treatment recommendations for depression

Thirty-four per cent (22/65)^{57,63,65,67,68,70,72,78,83,87–89,96,97,108,113–119} of CPGs delivered a total of 84 in-guideline treatment recommendations. Recommendations varied from general advice to ‘treat depression’,^83,95 to one CPG⁹⁶ fully dedicated to the topic. Overall, 19% (16/84) of treatment recommendations, including diverse aspects of treatment, were supported by high-quality evidence. Recommendations were strong in 42% (35/84) of cases, based on varying levels of evidence. Non-pharmaceutical treatments were recommended in 26% (17/65)^{57,63,65,67,68,70,72,78,88,89,96,97,113–117} of CPGs, accounting for 52% (44/84) of all treatment recommendations. In 12% (10/84) of cases, the recommendation also included pharmacological aspects of treatment. Psychotherapy was the most frequently recommended non-pharmacological treatment in 31% (26/84) of recommendations, with cognitive-behavioural therapy (CBT) as the treatment of choice in 12% (8/65)^{57,65,70,88,96,114,115,117} of CPGs, strongly recommended in 6 CPGs^{57,65,88,96,115,117} but with inconsistent LoE. Physical exercise was the second most commonly recommended intervention, in 9% (6/65)^{61,63,70,113,116,117} of CPGs, but with no clear SoR/LoE pattern. The emphasis that psychological interventions should be delivered by specialists was made in 8% (5/65)^{68,72,83,115,116} of CPGs.

Among the 20% (14/65)^{57,63,67,70,78,87,89,96,113–119} of CPGs delivering recommendations for the pharmacological management of depression, selective serotonin reuptake inhibitors (SSRIs) were the most frequently mentioned medication, in 18% (12/65)^{57,63,67,68,87,96,113–118} of CPGs, accounting for 16 recommendations, with no clear pattern in SoR/LoE (see Table 5 for a detailed analysis of the recommendations). Finally, 11% (9) recommendations for treating depression, delivered by 7 CPGs,^67,83,116 did not specify treatment type.

Stroke-specific recommendations

Nine stroke CPGs^{61,63,113–119} accounted for 69% (58/84) of all treatment recommendations, generally advocating a combination of CBT-based psychology support and SSRIs, and mostly with strong SoR.^{63,113–115,117,119} Six stroke CPGs^63,113–117 also gave recommendations for post-stroke prophylactic antidepressant use, none based on high-quality LoE. Magnetic cranial stimulation post-stroke was recommended in 5% (3/65)^63,113,115 of CPGs, with a weak SoR. One stroke CPG¹¹⁷ gave detailed stepwise pharmacological treatment recommendations, while another,¹¹⁴ more cautious, recommended alternative therapies like meditation and acupuncture (medium/low SoR and low LoE).

CVD, HF, and CAD-specific treatment recommendations

No specific pattern in treatment recommendations was detected among CPGs for CVD, HF, and CAD. Of the 15 CVD CPGs, seven^{57,65,67,68,70,72,78} delivered 24% (20/84) of all treatment recommendations. All recommended psychological therapy, and three^57,65,68 specifically endorsed CBT. For HF, three CPGs^58,83,85 each delivered one strong but inconsistent recommendation to treat depression (‘Monitoring and specialists’ treatment for psychiatric symptoms are recommended’⁵⁸; ‘SSRI may be considered to treat depression, unless contraindicated’⁸³; and ‘CBT should be considered for patients with heart failure and clinical depression’⁸⁵). Finally, all three CAD CPGs^89,96,97 with treatment recommendations gave one recommendation to treat depression, but did not specify type of intervention.

Disease–disease, drug–disease, or drug–drug interaction recommendations

Twenty per cent (13/65)^{66,67,73,74,77,80,82,86,88–90,93,95} of CPGs mentioned CVD–depression DDIs. The focus was mostly on drug–disease interactions resulting from specific pharmacological treatments against depression that increased CVD risk. However, only 3% (2)^67,77 of CPGs delivered recommendations for their management. No CPG-issued disease–disease recommendations (see Table 6 for a detailed list of DDI recommendations).

Discussion

To the best of our knowledge, this is the first systematic review to establish how CVD CPGs address depression. Most recognize depression as a risk factor for CVD, aligning with widespread evidence that co-occurring CVD and depression are associated with worse outcomes.^89,125,24 However, our findings also reveal that less than one-quarter of CPGs offer both screening and treatment recommendations, possibly reflecting the uncertainty regarding the direct impact of treating depression on cardiovascular outcomes (Structured Graphical Abstract).³⁷ In PAD and aortic disease, the absence of any guidance for managing depression was particularly striking considering the high rates of depression reported in these populations.^126–131

Recommendations for addressing depression varied also considerably in both quality and specificity. Although screening for depression was advocated in over one-third of CPGs, typically endorsing the use of standardized tools such as the PHQ-2 or PHQ-9, strong to medium strength recommendations were often underpinned by medium to low-level evidence, suggesting a gap between recommendation strength and evidentiary support. The recommendations mostly favored routine screening but lacked practical guidance on implementation. Reasons for not screening include uncertain cost-effectiveness in the absence of clear identification of which patients would most benefit from treatment, the characteristics of successful interventions, but also potential misdiagnosis by non-specialists and patient stigma.^{40,41,132,133} Despite these concerns, depression remains a CVD risk factor associated with poor prognosis,²⁴ supporting systematic routine assessment. A growing body of evidence also points towards improved patient outcomes by coupling depression screening with a structured care protocol, resulting in treatment adherence, mental health-related quality of life, and reduced cardiac events.^{39,28  ,134–137} The increasing recognition of the significant burden caused by depression on patients and society is further reflected by the U.S. Preventive Services Task Force’s decision to recommend screening all adults for depression every two years, regardless of health status.¹³⁸

Treatment recommendations for depression displayed similar inconsistencies. While a range of interventions was endorsed, including psychotherapy, pharmacological treatment, and lifestyle modifications, relatively few recommendations were supported by high-quality evidence. Non-pharmacological treatments, particularly psychotherapy, were the most commonly recommended approach, often strongly endorsed, though not consistently supported by robust evidence. Physical exercise was also frequently suggested but was rarely endorsed by clear and strong evidence. Pharmacological treatments, most often involving SSRIs, were less frequently suggested and also lacked uniformity in evidence appraisal. A subset of guidelines offered only general or unspecified recommendations, which may limit their utility in guiding clinical decision-making. These findings underscore the lack of definite outcomes on the impact of treating depression on cardiovascular outcomes, leading to inconsistencies in the development of treatment recommendations within CPGs.^40,41,133 For instance, uncertainty in recommendations for preventive treatment for post-stroke depression stems from insufficient evidence. Similarly, while psychotherapy and pharmacological treatment are widely recommended across CVD guidelines, the inconsistent strength assigned to similar recommendations likely reflects a limited evidence base.^64,118 It is worth mentioning that these inconsistencies did not deter the American Association of Family Physicians from dedicating an entire CPG to the management of depression in CVD,⁹⁶ as they recognize the importance of managing depression in improving overall patient well-being and clinical outcomes.

Overall, recommendations for treating depression aligned with those for the general population, with an emphasis on CBT and physical exercise as primary interventions.^139,140 Among pharmacological options, except in HF, SSRIs are generally preferred due to their relatively favourable safety profile, highlighting the need to balance efficacy and safety in treatment selection. For HF, in the MOOD-HF study SSRIs showed no increased cardiac risks, however, they also lacked efficacy for clinical or depression symptoms, underscoring the challenges of managing depression in HF.¹⁴¹ In contrast, a recent analysis demonstrated that mental health interventions, including pharmacotherapy, psychotherapy, or a combination of both, significantly reduced hospital readmissions and emergency visits in HF/CAD patients with anxiety or depression.²⁸ Together, these findings suggest that while SSRIs may not worsen cardiac risk, broader interventions could offer greater clinical benefit in this vulnerable population,¹⁴ highlighting the need to balance efficacy and safety in treatment selection. Stroke guidelines provide more extensive coverage of depression, including its prevention, likely because neurologists manage both neurological and mental health aspects of care.¹⁴² Notably, our review found that CPGs rarely consider DDIs, putting those patients already receiving polypharmacy for comorbid conditions at risk of increased cardiovascular side effects if antidepressants are introduced. Thus, HF often coexists with CAD, atrial fibrillation, PAD or stroke, and other conditions linked to increased prevalence of depression.⁴⁸ Additionally, as survival rates increase, patients may be subject to new comorbidities that further complicate disease management, such as in CAD patients who increasingly develop kidney disease, atrial fibrillation or cancer.²⁴ However, clinical trials largely exclude patients with comorbidities, leaving a gap in evidence for DDI management.^143–146 This emphasizes the need for clinical research that better reflects the complexity of managing patients with comorbidities, to inform evidence-based recommendations.

Cardiac and stroke rehabilitation CPGs tended to more systematically address depression, likely reflecting its facilitated management in this setting, although the challenge often remains on how to ensure follow-up for depression after the completion of a cardiac or stroke rehabilitation programme.

Women were the focus of six CPGs, one of which addressed CVD and menopause.⁷⁶ Considering the increased risk of depression associated with menopause,^147,148 it was surprising that this guideline did not address the topic. It is noteworthy that only one of the women-focused CPGs provided a recommendation for the management of depression, likely an indication of the persistent under-representation of women in clinical trials, and the resulting paucity of available data.¹⁴⁹ This raises critical questions regarding the validity of extending depression management recommendations to female patients, particularly with respect to pharmacological therapies. In this regard, one stroke CPG¹⁰³ suggested the development of a women-specific stroke risk score to more adequately reflect depression and psychological stressors as prevalent risk factors in women. Of note, women’s referrals to cardiac or stroke rehabilitation programmes remain significantly lower than men’s,¹⁵⁰ possibly due to unconscious clinician bias when considering patients for a referral.⁷⁴ This observation aligns with Sweden’s higher attendance of women in such programmes attributed to greater gender equality.¹⁵⁰ Other reasons contributing to low attendance to rehabilitation programmes by women may be limited awareness, cost, distance, transportation issues, or time constraints, such as family responsibilities.¹⁵⁰ Regardless, the underrepresentation of women remains a significant barrier to their effective treatment, including for depression. Taken together, these observations reveal the critical shortcomings in delivering an integrated strategy for addressing women's mental and cardiovascular health.

In PAD and aortic disease, the absence of any guidance for managing depression was particularly striking. In PAD, depression is a prevalent comorbidity, ranging between 18% and 48%, which can manifest even before disease onset, and is associated with increased mortality and amputations, and poorer health outcomes. Similarly, patients with aortic disease are at especially high risk of depression after the age of 65 years, with more than 30% of aortic dissection survivors self-reporting new depression and anxiety. Yet, only a minority benefit from psychosocial support.¹⁵¹ Overlooking depression in these guidelines potentially increases the risk of underdiagnosis and undertreatment.¹²⁶

Clinical practice guidelines serve as invaluable tools for integrating scientific evidence into clinical decision-making. Their strength lies in their capacity to translate robust, high-quality evidence, particularly from randomized controlled trials (RCTs) and meta-analyses, into practical, graded recommendations. This is especially effective in areas where CVD comorbidities have been well studied across populations, such as diabetes, dyslipidaemias, or hypertension, and lead to a substantial body of high-level evidence for CPG-issuing organizations to substantiate strong recommendations.^152–156 However, the same methodological framework is less suited to areas where high-level evidence is sparse, difficult to generate, or inherently variable. One such area is the impact of depression on cardiovascular outcomes. Although there is increasing recognition of the association between depression and adverse cardiovascular events, including increased mortality, hospitalizations for heart failure, and poor adherence to treatment, evidence is largely observational and heterogeneous.^24,25Also, variations in how depression is diagnosed, measured, and reported across studies pose further challenges to synthesis. As such, psychosocial factors often remain underrepresented in CVD CPGs or are supported by lower-level evidence (Class II or III, Level B or C), which may give the wrong impression that they are less clinically relevant. For example, while the 2021 ESC Guidelines on cardiovascular disease prevention acknowledge psychosocial factors such as stress and depression as contributors to cardiovascular risk, they stop short of issuing detailed, intervention-focused recommendations due to the paucity of strong supporting data from RCTs.⁶⁷

The RCT methodology is ideally suited for well-defined interventions, however, it is less flexible in addressing domains where complex, multifactorial interactions and patient-specific considerations are at play, such as in multimorbid patients. To advance holistic cardiovascular care, new avenues that give greater weight to complementary approaches should be explored. For example, expert consensus statements, qualitative research, and patient-reported outcomes may prove instrumental for CPGs to better corroborate recommendations that address the complex management aspects of this growing patient population.

While further research on the impact of depression on CVD is warranted, this should not deter from its systematic management, as there is equally no evidence to suggest that it is less effective than in the general population. In fact, treating depression in patients with CVD has shown to improve quality of life, enhance treatment adherence, and increase participation in cardiac rehabilitation programmes,¹⁴ while also significantly reducing emergency department visits, hospitalizations, and even improving survival in specific subpopulations.^28,157 Integrated treatment approaches, particularly the combination of psychotherapy and medication, appear most effective in reducing acute healthcare utilization, likely by improving psychological well-being, treatment adherence, and self-management in this high-risk population.²⁸ These results advocate for the systematic integration of mental health support into cardiac rehabilitation and chronic disease management programmes to alleviate both psychological distress and clinical burden.

Our findings underline the importance of prioritizing mental health in CVD CPGs, not only to alleviate depressive symptoms but also to foster better overall patient care and health outcomes. High qualitative guidance can be achieved by systematically involving mental health specialists in guideline development to ensure the integration of structured and implementable recommendations. Ideally, a multimodal approach including cardiologists, psychiatrists, and primary care clinicians should be followed to achieve the best patient outcomes.

Future directions

While depression is expected to become an increasing concern with the aging of the CVD population, the lack of adequate guidance for its management in CVD CPGs may negatively impact patients’ quality of life and outcomes. Moreover, multimorbidity is the most common clinical presentation in patients with CVD, yet CPGs remain largely condition-specific, making it impractical for clinicians having to consult multiple sources.^66,158 Furthermore, overlapping recommendations may also interfere or contradict one another.^159–161

Based on our findings, we propose three distinct strategies for CVD CPG-issuing bodies to integrate comprehensive guidance on depression management:

1. A dedicated section on depression co-written with mental health specialists, with actionable recommendations on screening, treatment and DDI management. This approach was followed by the ESC in its 2021 CVD guidelines,¹⁶² though limited detailed recommendations for the management of depression may have resulted from space constraints.

2. Stand-alone CPG dedicated to the management of depression in CVD, for CVD CPGs to cross-reference. NICE and SIGN, as well as the Heart and Stroke Foundation, follow this approach. Additionally, they mainly publish their guidelines online, allowing for regular updates. A potential drawback is insufficient depth on disease-specific advice, like DDIs, if the depression guideline covers multiple cardiovascular conditions.

3. A comprehensive CVD comorbidity-focused CPG, developed by experts across relevant fields. Patients with CVD often present with multiple coexisting conditions and complex treatment interactions. The European AIDS Clinical Society has established a model for their CPG¹⁶³ that enables the delivery of in-depth, accessible, and comprehensive guidance for managing comorbidities, including DDIs. For such a model to be effective, ongoing multidisciplinary collaboration is essential.

Strengths and limitations

Our study has several strengths. It is the first to evaluate how CVD CPGs address depression. In particular, we identified inconsistencies across CPGs in the extent to which depression is addressed, with fewer than one in four providing comprehensive screening and treatment recommendations for its management. Furthermore, our findings show that recommendations often lack a systematic approach, and vary widely in scope and depth, even among guidelines for the same cardiovascular condition. Our study has some limitations. We may have missed some guidelines in databases we did not search. We did not include CPGs published before 2013 or in languages other than English. However, our search covered all major medical societies issuing CVD CPGs, and we therefore believe our results adequately illustrate how depression is currently addressed in the evaluated CVD conditions. This review did not cover all CVDs, which may narrow the scope of our findings. Other conditions, including congenital heart disease, atrial fibrillation, valvular heart diseases, or cardiomyopathies, undoubtedly warrant the same detailed attention in relation to their guidance on depression and should be the focus of a future dedicated systematic review. We did not analyse regional differences between CPGs; however, the widespread adoption of ESC, AHA, or NICE CPGs across different regions may complicate such an analysis. The analysis of pathology-specific disparities across cardiovascular conditions and their interactions with depression fell outside the scope of this review, as did the analysis of how mental health CPGs address CVD. All these areas warrant further investigation for improved cardiovascular condition-specific management strategies. Detailed analysis of recommendations, including variations in grading across guidelines for similar recommendations and the impact of different grading methodologies was beyond the scope of this review. These aspects, together with the clinical applicability of recommendations, consistency in recommendations across CPGs, and potential gaps in guidance for comorbid conditions warrant further investigation. We did not use the AGREE II tool¹⁶⁴ as the aim was not to assess the quality of the guidelines, compare them against established criteria, or identify strengths and weaknesses in their development processes. Instead, our aim was solely to determine whether CVD CPGs currently available to clinicians address depression and provide recommendations on its management, which falls outside the scope of the AGREE II framework.

Conclusions

To the best of our knowledge, this is the first systematic review to investigate how depression is addressed in CVD CPGs. Our analysis reveals that while depression is frequently mentioned, mental health specialists are rarely involved in guideline development, and consistent recommendations for its management are lacking. This may be due to the absence of consensus on the impact of treating depression on CVD outcomes. Until this issue is clarified, CVD CPG-issuing bodies should recognize the importance of systematically addressing this comorbidity to alleviate psychological distress, but also to reduce its clinical burden by establishing a clear and consistent approach to guide its management. In particular, there is a critical need for guidance in women with CVD and for managing DDI interactions in this highly comorbid population. By identifying the strengths and shortcomings of current CVD CPGs addressing depression, we hope to stimulate further research and improvement in this important area.

Supplementary data

Supplementary data are available in European Heart Journal online.

Declarations

Disclosure of Interest

All authors declare no disclosure of interest for this contribution.

Data Availability

No data were generated or analysed for or in support of this paper.

Funding

E.B. received a non-restricted educational and research grant from the Zurich Academy of Internal Medicine (https://www.my-zaim.ch) and from the Merian Iselin Klinik, Basel, Switzerland, to the International Center for Multimorbidity and Complexity (https://www.multimorbidity.org).