Effects of Couple-based Interventions on Psychological Outcomes among Cancer Patients: A Systematic Review and Meta-analysis

doi:10.21203/rs.3.rs-3746336/v1

Objective: Cancer and its treatment can generate substantial psychological distress (depression and anxiety). The objective of this systematic review and meta-analysis is to explore the effectiveness of couples-based interventions on psychological outcomes among people with cancer, and to test subgroup analyses to explore sources of heterogeneity affecting effect sizes.

Design: Systematic searching across eight databases identified studies related to couples-based interventions for psychological outcomes of cancer patients published between 2007–2022. Rigorous inclusion and exclusion criteria were utilized. Random-effects models were used to compute effect sizes with Hedge’s g, forest plot, and Q and I2 statistics to measure heterogeneity. Moderator analyses were examined.

Results: Twelve primary studies were identified (938 participants, 56.14±7.29 years old). Overall, couples-based interventions significantly improved depression (g=.36 95% confidence interval .03 to .68, I²=76%) and anxiety (g=.29, 95% confidence interval 0.14 to .45, I²=0%) compared to controls. With subgroup analyses, fidelity of couple-based intervention, number of weeks across intervention, and timing of outcome assessment (number of days post- intervention) were moderators affecting effect sizes.

Discussion: Couples-based interventions appear to be effective among adults with cancer. Additional research is needed to explore the efficacy of couple-based interventions among more diverse samples, and to examine routes for integrating couple-based interventions into practice.

PROSPERO registration id: CRD42023389697

Couple-based intervention. Anxiety. Depression

Systematic review

Cancer

Cancer is a major public health issue and is one of the leading causes of death worldwide [1]. According to updated global cancer statistics, it is estimated that nearly 20 million new cancer cases are reported in 2020 [2] and the total number of people diagnosed with cancer will rise to 28.5 million by 2040 [2]. Cancer diagnosis and its treatment can be impacted by changes in mental and physical health of patients. The struggles of facing cancer and its treatment can generate substantial negative emotion and psychological distress (depression and anxiety) across the cancer treatment trajectory [3–4].

According to previous studies, approximately 20–30% of cancer patients undergoing treatment have been reported experiencing significant levels of anxiety and depression [5–6]. High levels of anxiety and depression are common among cancer patients, with higher intensity of these symptoms being associated with worse quality of life and lower cancer treatment adherence [7–8]. Cancer patients experiencing the greatest psychological distress in their treatment trajectory tend to show chronically elevated distress from months to years later [9]. During the cancer treatment trajectory, collaborative strategies are required among patients, family caregivers, and the patient’s care team to support coping to managing adverse symptoms from cancer and its treatment.

Couple-based interventions may be one route to support patients’ psychosocial needs during the cancer trajectory [8]. Previous systematic reviews and meta-analyses have been focused on couple interventions between cancer patients and their intimate partners, such as breast cancer and prostate cancer [10–12]. However, the mode of intervention delivery to cancer patients sometimes relied on friends or family members to assist with cancer treatment and patient’s needs. Thus, the term “couple-based intervention” in this review refers to the action which focuses on cancer patients and family caregivers as a unit/group -based delivery mode. In the last decade, several couple-based interventions have been developed for targeting psychological distress among cancer patients and their caregivers [13–15].

Therefore, this review is conducted to gain a better understanding of the existing couple-based interventions for reducing psychological distress among cancer patients. The purpose of this study is to provide a systematic review and meta-analysis to explore the effectiveness of couple-based interventions on psychological outcomes among people with cancer and to determine areas where future research and practice change are needed.

The present systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [16]. The protocol of this review was registered in the International Prospective Register of Systematic Reviews (PROSPERO registration id: CRD42023389697).

Search strategy

In compiling publications for this study, literature searches were performed across twelve databases including: CINAHL (1937+), Clinical Trials (2000+), Cochrane (1995+), Ovid APA (1967+), Ovid MEDLINE (1946+), ProQuest & Theses (1996+), PubMed (1809+) and Scopus (1788+) for studies published from first available date to January 5, 2022, with the ancestry search performed prior to data analysis. Initial searches combined the following search terms: Population (cancer OR neoplasm) AND Intervention (couple-based intervention) AND Outcome (depress* OR major depressive disorder or anxiety or stress). The full strategies were then revised by an experienced nursing librarian and team. Additional studies were identified by reviewing the reference lists of the included publications.

Inclusion and Exclusion Criteria

The inclusion criteria used to select the articles were as follows: 1) patients 18 years or older with a diagnosis of any type of cancer and undergoing treatment; 2) any type of couples-based interventional programs consisting of education and/or psychotherapeutic strategies for cancer patients; 3) studies with control groups such as usual care, waitlist, and active control; 4) assessing anxiety and/or depression as the outcomes; and 5) published in an English peer-reviewed journal.

Exclusion criteria were as follows: 1) studies centered on major psychological disorders with physician diagnostic and/or medical treatment; and 2) studies that were brief reports, conference abstracts, study protocols, and articles without full texts. If the first and last investigators (KT and CR) had doubts concerning the eligibility of a study to be included, then the second and third reviewers (MM and RC) were involved in the decision-making process.

Data extraction

During data extraction, data were independently extracted from the included trials using a standard data extract form by two investigators. Data extracted included author, year of publication, country of research origin, demographic and clinical characteristics of participants (tumor type(s), specified tumor site(s), comorbidities), methods, interventions, and outcomes. If the outcome data of relevant studies are unclear or missing, further information was sought from the authors. Differing opinions between the two investigators were settled through discussion or consultation with the third author until consensus was reached.

Risk of bias assessment

In this review, a funnel plot, Begg and Mazumdar rank correlation test, and Egger’s regression test were used to estimate the publication bias [17]. A funnel plot is a basic scatter plot of individual study effect estimates against standard error. A visibly asymmetrical funnel diagram indicates likely publishing bias. A significant (p.05) result of the Begg and Mazumdar rank correlation test or the Egger regression test also indicates publication bias [17].

Data synthesis

SPSS software was used to assess descriptive characteristics of studies. Comprehensive Meta-Analysis (CMA) version 3.0 was then used to compute primary study effect size. Since depression was measured multiple ways across the primary studies, we used the standardized mean differences of depression scores between the post-intervention and control groups using Hedge’s g with 95% confidence intervals (CIs). A standardized mean difference allows comparison of ESs across studies with measures of different metrics [17]. We used Hedges’ g because Cohen’s d has a slight bias, which tends to overestimate the ES with a small number of primary studies. We assumed that the ESs were normally distributed with variability due to differences in participants, methods, interventions, and outcomes. To estimate mean of the effects, we utilized the random-effects model, in which CMA weights each study by the inverse of the within- and between-studies variance. Studies with higher precision were weighted more heavily than studies with lower precision [17].

Analysis of subgroups or subsets

When heterogeneity was present, we used moderator analysis to investigate the source of the heterogeneity. An ANOVA analog was used for categorical moderators and meta-regression for continuous moderators [17].

Ethical approval

This meta-analysis did not require ethical approval or patient consent because the data used in the meta-analysis were extracted for primary studies that had declared ethical approval, and no original raw data was utilized.

Demographics of included studies.

Initial database searching results yielded 1,521 results in January 2023. After 544 duplicates were removed, 980 remained. We found 3 studies through hand searches. During review of titles and abstracts, an additional 925 were excluded because they did not include couple-based interventions (primary reason for exclusion) and/or they failed to meet all other inclusion criteria. Of the remaining 28, 16 primary studies were excluded due to 1) narrative review/systematic review (n=12), 2) a case study (n=1), 3) research without results (n=2) and 4) letter (n=1). Finally, 12 primary studies (n=12) met inclusion criteria and were in this systematic review and meta-analysis. See Figure 1.

The 12 primary studies that met inclusion criteria provided 13 between-group comparison (K=13) because one study had three group comparisons [15]. We compared groups that were similar except for the couple-based intervention. All 12 primary studies had been published between 2005 and 2021. A total of 938 participants were included across the 12 primary studies; 463 participants practiced in couple-based interventions and 465 participants were served as controls. Ten of twelve primary studies were conducted in the United States of America [1-2, 15, 18-23] as well as two in Canada [24-25]. See supplementary Table 2 and 3. Participants’ mean ages ranged from 40.95 to 68.11 years. See Table 1 for intervention description including total weeks of intervention, number of session/week and duration of session in minutes/session.

Table 1 Characteristics of Primary Studies (s=12)

Characteristics	s	Min	Q1	Mdn.	Q3	Max	Mean	SD
Mean age (years)	12	40.95	51.87	54.11	61.81	68.11	56.14	7.29
Total Sample size at analysis
- MBI group	12	8	16.50	25.00	56.50	96.00	35.62	25.92
Control group	12	7	12.00	25.00	51.50	113.00	35.77	31.34
Weeks of structured CBI	12	4.00	4.50	6.00	8.00	12.00	6.30	2.25
Days across intervention (length)	12	21.00	24.50	35.00	49.00	366.00	59.38	92.69
Structured MBI session/week	10	1.00	1.00	1.00	1.00	1.00	1.00	.00
Structured MBI min./session	9	34.00	50.00	60.00	67.50	90.00	59.88	16.01
Dose (length x duration)	9	1190.0	1260.0	1540.0	2520.0	3150.0	1808.33	756.35
Days after intervention measured	11	14.00	21.35	80.50	91.50	275.00	84.09	76.93
% Attrition, CBI group	12	.00	13.11	20.00	33.97	45.00	20.92	13.90
% Attrition, Control group	12	.00	8.33	17.18	31.86	41.67	18.60	14.01

s=number of studies providing data, Min=minimum, Q1=first quartile, Mdn=median, Q3=third quartile, Max=maximum, CBI=Couple-based intervention

Effects of couples-based interventions

Depression

The summary effect size across the 11 comparisons was g=.36 (95%CI=.026, .684, p=.034, I2=76%), indicating that couples-based interventions had a moderate effect in reducing depressive symptoms among patients with cancer. Of all 11 comparisons, four comparisons had significant positive effects improvement. See Figure 2.

The couples-based intervention group’s pre-post comparisons demonstrated significant reduction in depressive symptoms with an effect size of g=.74 (p=.022) for correlated groups (r=.8) and g=.72 (p=.014) for uncorrelated groups. The control group’s pre-post effect sizes showed no improvement in depressive symptoms for uncorrelated group (g=.51, r=.0) and improvement of depressive symptoms for correlated group (g=.49, r=.8). See Table 2.

Table 2. Effect size of Couple-Based Intervention vs Control groups

Comparison	Yoga group
Comparison	k	ES	p(ES)	95% CI	SE	I²	Q	p(Q)
Depression
Couple-based intervention vs. Control groups	11	.36	.034	.026, .684	.168	76.66	42.84	<.001
Single group Couple-based intervention
pre- vs. post (r=0.0)	9	.72	.022	.105, 1.342	.316	90.56	84.76	<.001
pre- vs. post (r=0.8)	9	.74	.014	.148, 1.327	.301	98.00	401.98	<.001
Control group
pre- vs. post (r=0.0)	9	.51	.113	-.121, .499	.322	92.06	100.76	<.001
pre- vs. post (r=0.8)	9	.49	.111	-.114, 1.103	.310	98.35	484.61	<.001
Anxiety
Couple-based intervention vs Control group	8	.29	<.001	.143, .445	.077	0.00	4.66	.701
Single group
Couple-based intervention
pre- vs. post (r=0.0)	8	1.27	.003	.421, 2.114	.432	92.92	98.87	<.001
pre- vs. post (r=0.8)	8	1.31	.002	.485, 2.128	.419	98.56	496.05	<.001
Control group
pre- vs. post (r=0.0)	8	.44	.202	-.235, 1.109	.343	92.13	88.97	<.001
pre- vs. post (r=0.8)	8	.44	.195	-.233, 1.093	.336	98.39	436.97	<.001

Anxiety

The summary effect size across 8 comparisons was g=.29 (95%CI=.143, 445, p<.001, I2=0%), indicating that couples-based interventions had a small effect on improving anxiety symptoms among patients with cancer. Also, of all 8 comparisons, two comparisons had positive effects improvement. See Figure 3.

Additionally, the couple-based interventions group’s pre-post comparisons demonstrated significant reduction in anxiety symptoms with effect size of g=1.31 (p=.002) for correlated group (r=.8) and g=1.27 (p=.002) for uncorrelated group. The control group’s pre-post effect sizes showed no improvement in anxiety symptoms for uncorrelated group (g=.44, r=.0) and improvement of depressive symptoms for correlated group (g=.44, r=.8). See Table 3.

Table 3 Categorical Moderator Results for Depression Comparing Couple-based intervention versus Control Groups

Moderator	k	ES	SE	Var.	95%CI	Z	p(Z)	Q_bet	p(Q_bet)
Source characteristics
Funding								.311	.577
Unfunded	2	.153	.402	.162	-.635, .941	.380	.704
Funded	9	.403	.201	.040	.009, .797	2.007	.045
Method characteristics
Intention-to-treat								.411	.522
No	8	.286	.204	.042	-.114, .687	1.402	.161
Yes	3	.541	.340	.116	-.126, 1.208	1.589	.112
Fidelity of intervention								4.048	.044
No	7	.170	.161	.026	-.145, .484	1.058	.290
Yes	4	.702	.210	.044	.290, 1.114	3.340	.001
Intervention characteristics
Group discussion								.603	.438
No	4	.455	.254	.064	-.042, .952	1.794	.073
Yes	6	.195	.219	.048	-.235, .625	.888	.375
Counseling								.022	.883
No	7	.286	.216	.047	-.138, .709	1.323	.186
Yes	3	.348	.365	.133	-.368, 1.064	.954	.340
Participants
Breast cancer								2.171	.141
No	8	.238	.186	.035	-.126, .603	1.283	.199
Yes	2	.760	.301	.091	.170, 1.350	2.525	.012

k=number of comparisons, Q=heterogeneity statistics, SE=standard error, Var.=variance, NR=not reported

Subgroup analyses

Because moderate heterogeneity was identified across studies (I2=76%) in depression outcomes, a subgroup analysis was conducted to explore the source of heterogeneity. There were four moderators that influenced the effect size. Fidelity of couple-based intervention had a greater effect (g=.702, 95%CI .290, 1.114, p=.001) than non-fidelity of intervention (g=.170, 95%CI -.145, .484, p=.290). An increase in the length of intervention in total days decreased the effect size of couple-based intervention on depressive symptoms in patients with cancer (β=-.023, Q=3.96, p=.046). The higher the number of weeks across the intervention, the lower the effect size in reducing depressive symptoms in patients with cancer (β=-.164, Q=3.96, p=.046). Finally, conducting outcome assessments at an increasing number of days post-intervention yielded lower effect size of reducing depressive symptoms in patients with cancer (β=-.003, Q=8.06, p=.004). See Table 4.

Table 4 Continuous Moderators of the Effects of Couple-based intervention on Depression

Moderator	k	Slope	SE	Tau²	Q_model	p
Study characteristic
Publication year	11	.019	.024	.124	.63	.427
Sample characteristic
Age (mean)	11	.012	.019	.139	.37	.541
Method characteristic
%Attrition	11	.009	.010	.118	.84	.360
Intervention characteristics
Intervention length (total day)	11	-.023	.011	.076	3.96	.046
Number of weeks across intervention	11	-.164	.082	.074	3.96	.046
Number of session/wks.
Duration of CBI min./session	8	-.012	.009	.083	1.62	.203
Dose (Length x Duration)	8	-.003	.001	.079	1.82	.178
Days After intervention measured	11	-.003	.001	.042	8.06	.004

k=number of comparisons, Q=heterogeneity statistics, CBI=Couple-based intervention

Publication bias

For depression outcomes, the funnel plot was visually asymmetrical suggesting that publication bias was likely; primary studies with large sample sizes with negative effects were missing. The Egger’s test was significant with an intercept of -1.64 (95%CI: -5.43, 2.15, p=.176). Begg and Mazumdar’s test was also significant (p=.500). These results indicate the no potential presence of publication bias.

For anxiety outcomes, the funnel plot was visually symmetrical suggesting that publication bias was not likely; primary studies with large sample sizes with negative effects were missing. The Egger’s test was significant with an intercept of -1.01 (95%CI: -2.92, .90, p=.121). Begg and Mazumdar’s test was also significant (p=.193). These results indicate the no potential presence of publication bias.

Given the high psychological symptom burden among people with cancer [26], novel management approaches are needed. Previous research recommends dyadic interventions to support families coping with cancer [11], and the importance of relationships and social support is well established in the context of coping with cancer and cancer-related symptoms [27-29]. This systematic review and meta-analysis offers insights into the efficacy of couples-based interventions for impacting psychological outcomes among people with cancer. Twelve studies examining unique couples-based interventions were identified and included [1-2, 15, 18-25].

Effects of couple-based intervention

Overall, this review and meta-analysis highlighted a moderate effect for couples-based interventions on depression outcomes, and small effect on anxiety outcomes among people with cancer. Components of the couples-based interventions varied across studies (didactic self-care and symptom management information, coping strategies, cognitive-behavioral strategies, communication techniques, relational strategies, sexual function support, connection with community resources, meditation, supportive-expressive programming, relaxation exercises, role-plays, etc.) All studies were RCTs, and all interventions included some aspects of psychoeducation and couples-focused support, generally delivered in a set of sessions with a trained interventionist.

Couples-based interventions were found to yield a moderate effect in reducing levels of depression among people with cancer. With high rates of depressive symptoms and the far-reaching effects of depression on cancer treatment adherence, health outcomes, and quality of life [26, 30], identifying and implementing evidence-based interventions to address depression is a high priority. Findings from this systematic review and meta-analysis can open new possibilities for research into couples-based interventions, and implementation of couples-based interventions in practice. Other evidence-based interventions are available to address depression among people with cancer, such as psychoeducation, psychotherapy, mindfulness-based cognitive therapy, yoga, and pharmacologic interventions [31], yet many patients with cancer continue to suffer and go untreated [32]. It is possible that couples-based interventions might provide an option for some people with cancer who are facing depression, with the added benefit of dyadic accountability and possible simultaneous support for lay caregivers. While findings support the efficacy of couples-based interventions, it is still unclear which specific aspects of the interventions are useful, and how these interventions could be best integrated into clinical oncology practice. Thus, additional exploration into these areas is needed.

Findings from this study also highlighted a small effect of couples-based interventions on anxiety among people with cancer. Components of the interventions varied across studies, so additional research is warranted to understand which components might contribute to anxiety relief, or how existing interventions might be modified to better address anxiety symptoms. Prior research supports the need for evidence-based interventions to address anxiety among people with cancer, with interventions focused on relaxation strategies, brief sessions (<30 minutes each), and face-to-face delivery showing greatest promise [33]. These prior findings can inform the design of future studies focused on refining and testing couples-based interventions for anxiety.

One prior systematic review of spousal couples-based interventions in the context of cancer found improvements in communication, dyadic coping, the quality of life, distress, sexual functioning, and marital satisfaction [11]. It is possible that similar changes were involved in the studies reported in this meta-analysis, and that these changes may be related to improvements in psychological outcomes. Additional research into the mechanisms underlying couples-based interventions may be useful for strengthening the evidence base and developing optimal intervention protocols.

Moderator effects

Moderator effects show that higher intervention fidelity, shorter intervention duration, and shorter follow-up time for data collection yielded higher effect sizes across couples-based interventions [34]. It is well established that greater intervention fidelity can improve outcomes across various interventions, can enhance external validity, and accurate translation of findings into practice [34]. Because of the central importance of intervention fidelity, calls have been put forth to explicitly measure and report fidelity in interventions centered on patients with cancer and their lay caregivers [35]. Approaches to support fidelity in couples-based interventions, as well as best practices for measuring and reporting fidelity in research reports, are needed. While it may seem counterintuitive that shorter intervention duration would yield greater effect sizes, previous research in this area is mixed. One recent review and meta-analysis of mindfulness for cancer-related symptoms found no differences based on intervention duration [36], and another review and meta-analysis of psychological interventions in the context of cancer found that more brief interventions yielded greater effects [37]. It is possible that shorter duration interventions were more intensive in nature and were given greater investment by participants. Additional research is needed to understand whether effects of brief interventions could be maintained over time, or whether additional sessions may be needed to sustain benefits. The finding that studies with shorter follow-up times for data collection yielded greater intervention effect sizes is to be expected, as outcomes were captured more immediately after intervention administration and effects of the interventions would likely be more acutely felt. This finding also brings additional questions around optimal ways to maintain intervention effectiveness over time. This is an especially relevant area of exploration when considering how to implement couples-based interventions in practice in a way that is both effective and sustainable.

Implications and recommendations

Findings from this review and meta-analysis have implications for practice and for future research. Engaging loved ones in the care of patients’ psychological wellbeing has the potential to improve patients’ adjustment to cancer, and early evidence supports that improvements in patients’ wellbeing may help caregivers as well [7, 38], yet additional research is needed in this area. Research can begin to discern which components of couples-based interventions are most effective in reducing psychological symptoms, with the goal of designing an optimized, low-burden intervention that can be translated into routine cancer care. Research may also benefit from taking a community-based approach, including tailoring interventions to the needs and desires of a specific community (e.g., African American/Black patients, religious patients, older patients, rural patients). The need for social support among cancer patients and caregivers cannot be overstated, yet in practice, rates of social support intervention use are unclear. In addition, lay caregivers often face high burden when caring for loved ones with cancer [39], so extra care should be taken when designing and implementing couples-based interventions to avoid bringing additional strain onto caregivers. With the recognition of increasing lay caregiver burden and burnout [30, 36], future research to explore the effect of couples-based interventions on both patient and caregiver psychological outcomes is encouraged.

Limitations of this study

Given the context of this research, results are limited in their generalizability. First, the quality of the included studies was mixed, impacting on our ability to draw firm conclusions based on these results. Therefore, all findings should be interpreted with discretion. Additionally, couples in the included studies were primarily white, married, and heterosexual. It is unknown whether these couples-based interventions may need be adapted to best suit patients and caregivers from diverse ethnic/racial backgrounds, as well as non-married and/or LGBTQ+ partnerships. Despite these limitations, this systematic review and meta-analysis offers a novel understanding of the efficacy of couples-based interventions on psychological symptoms among patients with cancer to advance oncology research and practice.

This systematic review and meta-analysis suggests that couples-based interventions were beneficial in alleviating symptoms of anxiety and depression among people with cancer. Future research with large-scale, high-quality RCTs, and longer-term follow-up intervention trials are still needed. Given the centrality of addressing multidimensional psychological outcomes among cancer patients , couples-based are a promising area for additional investigation.

Funding

This study did not receive any specific funding from public, commercial, or not-for-profit agencies.

Declaration of interest

No conflict of interest has been declared by the authors.

Availability of Data and Material

The authors confirm that the data supporting the findings of this manuscript are available within the article and its supplementary material.

Code Availability

N/A

Contributions

Kanjana Thana, Megan Miller, and Chuntana Reangsing were substantially contributed to the idea for the article, literature search, identification, and data extraction. The first draft of this review was written by Kanjana Thana. Chuntana Reangsing and Megan Miller commented on the previous version of the manuscript. All authors contributed to critically revising the work for important intellectual content and provided final approval of the version to be published and agree to be accountable for all aspects of the work.

Corresponding Author

Correspondence to Chuntana Reangsing

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No competing interests reported.

Effects of Couple-based Interventions on Psychological Outcomes among Cancer Patients: A Systematic Review and Meta-analysis

Status:

Version 1

Abstract

Figures

Introduction

Material and methods

Search strategy

Inclusion and Exclusion Criteria

Data extraction

Risk of bias assessment

Data synthesis

Analysis of subgroups or subsets

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1