Efficacy of Acceptance and Commitment Therapy in Improving Depression and Anxiety in Adults with Traumatic Brain Injury: A Systematic Review and Meta-analysis

Abstract

Purpose of the Review:

Acceptance and commitment therapy (ACT) is a third-wave psychological therapy that has shown effectiveness in managing psychological distress across various conditions, including chronic illnesses. Traumatic brain injury (TBI) often leads to cognitive impairments, mood disturbances, and psychological distress. While pharmacological treatments have limitations, non-pharmacological approaches, such as ACT, offer a promising alternative. This study systematically examined the efficacy of ACT on depression and anxiety in adults with TBI.

Collection and Analysis of Data:

A systematic search identified randomized controlled trials (RCTs) comparing ACT with treatment as usual or other psychological therapies in adults with TBI. Primary outcomes included depression and anxiety, while secondary outcomes assessed psychological flexibility, functional disability, rehabilitation participation, and quality of life (QOL). A random effects model meta-analysis was conducted using the R language. Four eligible RCTs (pooled N = 227) were included. ACT significantly reduced depression and anxiety with a moderate effect size [Cohen’s d = 0.54; 95% CI = 0.18–0.90; p = .003; I² = 61.1%]. It also improved psychological flexibility [Cohen’s d = 0.36; 95% CI = 0.19–0.53; p < .001; I² = 0%], mental health-related QOL [Cohen’s d = 0.24; 95% CI = 0.02–0.49; p = .015; I² = 90.8%], and decreased functional disability [Cohen’s d = 0.47; 95% CI = 0.18–0.76; p = .001; I² = 0%]. Regarding risk of bias, two studies had some concerns, and the rest were of low risk.

Conclusions:

The evidence for the efficacy of ACT in TBI is positive but preliminary. More methodologically sound trials using standardized measures are required to confirm the findings.

Keywords

Acceptance and commitment therapy traumatic brain injury depression anxiety third wave psychotherapy

Acceptance and commitment therapy (ACT) is categorized as a third-wave therapy. These differ from second-wave therapies by focusing on the acceptance of thoughts and feelings, as well as being present in the moment.^1,2 It has six core processes, which are: acceptance, cognitive defusion, mindfulness, commitment to values, contact with the present moment, and defining self as context.³ A key underlying concept is psychological flexibility, which suggests that individuals suffer unnecessarily due to their psychological rigidity. Therefore, they develop narrow cognitive processes, which lead to cognitive entanglement and experiential avoidance.⁴ This psychological flexibility is often impaired in individuals with brain injury, due to damage in areas involved in managing executive processing.⁵

Traumatic brain injury (TBI) results from an external force, including a forceful bump, jolt to the head or body, or a penetrating injury. It can lead to temporary issues or severe long-term consequences.⁶ Various psychological issues include cognitive deficits; personality changes; alterations in memory; difficulties in language; aggression; mood disorders; psychosis; and neurosis.⁷ Among the psychological issues, depression and anxiety are common.^8,9 Pharmacological options to manage these psychological problems include antidepressants, antipsychotics, benzodiazepines, stimulants, and a few experimental drugs.^10,11 Non-pharmacological modalities that have been tried include interpersonal, cognitive behavioral, systemic, holistic, and psychodynamic approaches. Others include yoga, meditation, music therapy, neurological music therapy, and third-wave therapies.¹²

A meta-analysis explored the efficacy of ACT and found it to be effective in anxiety disorders, depression, addiction, and somatic health problems.¹³ In the context of long-term illnesses, ACT is opined to be better than traditional second-wave therapies, as it focuses on accepting the disease-related thoughts and feelings, rather than altering them.¹⁴ The primary source of psychopathology is psychological inflexibility, in which individuals struggle with internal experiences, such as thoughts, emotions, and bodily sensations.¹⁵ This leads to avoidant and rigid behaviors, which hinder their ability to cope effectively with emotional stress and improve their overall quality of life (QOL). ACT helps patients with brain injuries gain a new perspective on their thoughts about illness and re-engage in living a meaningful life.¹⁶

Another meta-analysis¹⁷ explored the efficacy of ACT in chronic health conditions and found that it improves QOL and symptoms in various conditions. An umbrella meta-analysis¹⁸ explored the effectiveness of ACT in improving depression and anxiety and found small to moderate effect sizes, but the sample included a variety of conditions and not TBI. A review¹⁹ explored the effectiveness of ACT in reducing the psychological distress in TBI and qualitatively concluded that it is effective in reducing anxiety more than depression and stress. The existing literature has explored the usefulness of ACT for various health conditions, including, but not limited to, TBI. However, there are lacunae in understanding the therapeutic changes that ACT can bring about in patients with TBI. This review aims to systematically explore how ACT may improve both therapeutic processes and disease-related outcomes in this population.

Aims and Objectives

The primary outcome was to review and synthesize the data from studies on the efficacy of ACT in improving depression and anxiety as compared to the control group (placebo, treatment as usual, or other psychological treatments) among adult patients (above 18 years) with TBI.

Methods

This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines,²⁰ for methodological rigor and transparency. The protocol is registered on the PROSPERO (Ref: CRD420250651290).

Search Strategy

A comprehensive search was conducted across four electronic bibliographic databases: PubMed/MEDLINE, Web of Science, Embase, and Scopus. The search string (Supplementary Table S1) in PubMed retrieved 80 articles, which were applied to Embase (retrieving 451 articles using the ‘query translator’ feature), Web of Science (84 articles), and Scopus (141 articles). Additionally, reference lists of eligible studies and key review articles were manually screened to identify any additional relevant studies. The search was conducted on February 14, 2025, with no language restrictions.

Study Selection

Studies included were randomized controlled trials (RCTs) on adults (≥18 years) with TBI evaluating ACT as the primary intervention (individual/group format) against treatment-as-usual, placebo, waitlist or other psychological intervention (e.g., psychoeducation, cognitive behavioral therapy (CBT), befriending therapy). Additionally, studies were included if psychiatric diagnoses were made using a standardized manual (e.g., the International Classification of Diseases or the Diagnostic and Statistical Manual of Mental Disorders [DSM]) or if participants exhibited clinically significant scores on standardized rating scales.

Studies were excluded if they focused on children or adolescents (<18 years), non-TBI or mixed populations without a TBI subgroup analysis, or non-clinical populations (e.g., the general public, caregivers, healthcare professionals). Additionally, animal studies, observational studies, case reports and series, reviews, editorials, unpublished theses, and conference abstracts were excluded. Non-English studies were included if translations were available.

Data Extraction

Two independent reviewers (the second and third authors) screened all retrieved records in a two-stage process: title and abstract screening, followed by full-text review of potentially relevant studies. Data extraction was performed independently by two reviewers (first and third authors) using a standardized form. Extracted data included study characteristics (e.g., author, year, country, and study design), participant details (e.g., sample size, TBI severity, and demographics), intervention details (e.g., ACT protocol, duration, and mode of delivery), comparison group details, outcome measures, and key results. Discrepancies at each stage were resolved by a third reviewer (sixth author). Missing or unreported data were sought by contacting the corresponding authors by email. The systematic review management tool, Rayyan,²¹ was used for screening, and the extracted data were securely stored and reviewed for accuracy before synthesis.

Outcomes

Primary outcome: the change in depression and anxiety from baseline to post-intervention, measured using standardized scales and compared between ACT and TAU in patients with TBI.

Secondary outcomes: changes in psychological flexibility, rehabilitation participation, functional disability, and QOL in both physical and mental health following ACT intervention in patients with TBI.

Statistical Analysis

Meta-analysis was conducted using random-effects model, heterogeneity was assessed using Cochran’s Q and the I² statistic in R language²² with R Studio²³ as integrated development environment with packages ‘metaviz’²⁴ (forest plots), ‘meta’²⁵ (heterogeneity), ‘ggplot2’,²⁶ and ‘metasens’²⁷ for obtaining distance of influence (DOI) plot with Luis Furuya-Kanamori (LFK) index. Summary effect measures were reported as standardized mean differences (SMD) with 95% confidence intervals for continuous outcomes. As the number of available studies was only four and had heterogeneous participants, a random effect was chosen over fixed effect,²⁸ and publication bias was assessed using the DOI plot with LFK index (interpretation is within ± 1: no asymmetry; ± 1 to ±2: minor asymmetry; and > ± 2: major asymmetry).^29,30 Missing data were imputed using the open-source Campbell Calculator (https://www.campbellcollaboration.org/calculator/) to calculate Cohen’s d from the regression coefficient and standard error for one of the included studies.³¹ Risk of bias was evaluated independently by two reviewers using the Cochrane Risk of Bias³² tool, with disagreements resolved by a third reviewer. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE),³³ approach, with the help of GRADEpro software,³⁴ categorizing evidence as high, moderate, low, or very low.

Results

Baseline Characteristics of the Included Studies

A total of 756 articles were retrieved from four databases. After de-duplication and initial screening, 35 conflicts were resolved, leading to 38 articles being included for full-text screening. Finally, four of them,^5,31,35,36 were included in this review (Figure 1). The characteristics of the included individual studies are summarized in Table 1.

Figure 1.

PRISMA Flow Chart Depicting the Steps of the Synthesis of Evidence from the Literature.

Table 1.

Baseline Characteristics of the Included Studies.

Study Name, Country, Design and Population	Number of Participants in Intervention and Comparison	Age of the Participants (Years)	Male: Female Ratio (Intervention vs. Comparator)	Inclusion Criteria	Exclusion Criteria	ACT Details	Comparator Details	Primary Outcome	Conclusions
Sander 2021,³⁶ USA, Parallel RCT, patients with TBI.	44 in intervention vs. 49 in comparison group	37.73 ± 11.64 vs. 38.27 ± 12.71	25:19 vs. 31:18	Adults > 18 years with mild, moderate and severe TBI and BSI-18 T score > 63 on GSI of two or more in BSI subscales	Score of 2 or more standard deviations normative mean on RAVLT	ACT for 12 hours in eight sessions.	Devised Usual care group: the typical psychological care	Improvement in psychological distress among persons with TBI.	ACT reduces the psychological distress in TBI patients who are in chronic phase of recovery.
Whiting 2020,⁵ Australia, Phase two RCT, patients with severe TBI (post traumatic amnesia ≥7 days) after 18 years of age.	10 in Intervention vs. nine in comparison group	36.4 vs. 37.2	8:2 vs. 7:2	Severe TBI less than five years post-injury and the age of TBI patients between 18-65 years.	History of primary psychotic disorder, schizophrenia, substance dependence, suicidal/homicidal ideation	ACT -adjusted involved seven weekly, 1.5 hours group section	Befriending Therapy	Improvement in Psychological flexibility, rehabilitation participation, and decrease in psychological distress.	ACT is a promising transdiagnostic approach for reducing psychological distress in TBI patients.
Dindo 2020, USA,³⁵ Pilot RCT, patients with TBI.	20 in intervention vs. 12 in comparison group	37.7 ± 6.3 vs. 34.7 ± 5.8	No females in both groups	TBI accordance with defense clinical guidelines or Boston assessment with depressive disorder, anxiety or PTSD scale assessment by SCID-1	History of primary psychotic disorder, schizophrenia, substance dependence, suicidal/homicidal ideation	ACT portion of work shop four hours	Treatment as usual	Improvement in symptoms of stress-based psychopathology, psychosocial functioning and pain interference.	A 1-day ACT workshop can have positive a positive impact on veterans with poly trauma.
Bomyea 2017,³¹ USA, Secondary analysis from a two group RCT, mild to moderate TBI	41 in intervention group vs. 42 in comparison group	35.27 vs. 34.21	36:5 vs. 36:6	Participants in the trial were 160 veterans, who met current criteria for at least one anxiety or depressive disorder (including PTSD) based in the Diagnostic and Statistical Manual of Mental Disorders-IV.	History of primary psychotic disorder, schizophrenia, substance dependence, suicidal/homicidal ideation	ACT covered six core process	Present Centered therapy	Improvement in psychological symptoms, disability and functioning.	Veterans who experienced TBI (mild to moderate) do not require a differential treatment for most of the after deployment mental health issues.

RCT: Randomized controlled trial, TBI: Traumatic brain injury, ACT: Acceptance and commitment therapy, vs.: Versus, BSI 18: Brief symptom Inventory 18, GSI: Global severity index, RAVLT: Ray auditory visual learning test, SCID: Structured clinical interview for DSM, PTSD: Post-traumatic stress disorder.

The total number of participants included in the ACT group was 115 and 112 in the control group, with a male preponderance in both groups. In two of the studies, the efficacy of ACT was compared with treatment as usual (n = 61),^35,36 while in the other two studies, it was compared with other psychological therapies, such as befriending (n = 9),⁵ and present-centered therapy (n = 42).³¹ The duration of post-treatment follow-up ranged from 1 to 3 months.^35,36 The effect size was calculated for all outcomes based on the available data, and further analysis was carried out using these effect sizes. Among the outcomes, ACT-related outcomes include psychological flexibility, while rehabilitation participation, functional disability, and QOL are disease-related.

Studies have included patients from mild to severe TBI, age ranging from 35³¹ to 51 years,³⁶ recruited from a specialist hospitals^5,36 or those dealing with veterans,^31,35 with post traumatic amnesia <7 days³¹ or >7 days,⁵ duration of TBI ranging from at least six months,³⁶ and significant scores in psychological distress as measured by standardized measuring scales.

Primary Outcome

It was defined as an improvement in the composite score post-intervention, indicating a reduction in depression and anxiety. The group receiving ACT showed a significant improvement in depression and anxiety compared to the control group, with a Cohen’s d of 0.54 (95% CI = 0.18–0.90; p = .003) (Figure 2), with low certainty of evidence (Supplementary Table S2). However, there was high heterogeneity among the four included studies (I² = 61.1%), along with a high risk of publication bias, as depicted in the DOI plot with an LFK index of 6.88 (Supplementary Figure S4).

Figure 2.

Forest Plot Showing the Effect of ACT on Depression and Anxiety in Adults with TBI.

Figure 3.

Forest Plot Showing the Effect of ACT on Psychological Flexibility in Adults with TBI.

Secondary Outcomes

Three studies provided data on both psychological flexibility and participation in rehabilitation.^5,35,36 Meanwhile, two studies each reported on functional disability,^31,35 physical health QOL,^5,31 and mental health QOL.^5,31 Due to the limited number of studies for each of the secondary outcomes, publication bias was not assessed.

Psychological Flexibility

ACT group experienced a significant enhancement in psychological flexibility compared to the control group [Cohen’s d = 0.36, 95% CI = 0.19–0.53) (p < .001] (Figure 3). The findings were highly consistent across studies, with no observed heterogeneity (I² = 0%) and no publication bias (LFK index 0.28; Supplementary Figure S5). In adults with TBI, ACT significantly improves psychological flexibility, with a high certainty of evidence, as assessed by GRADE (Supplementary Table S2). This, in turn, can improve the psychological well-being in this population.

Rehabilitation Participation

Among adults with TBI, the ACT group did not demonstrate a significant improvement in rehabilitation participation compared to the control group [Cohen’s d = 0.24, 95% CI = −0.02–0.49, p = .065] (Figure 4), with no observed heterogeneity (I² = 0%). However, high publication bias was observed for this outcome (LFK index 2.6; Supplementary Figure S6), with very low certainty of evidence (Supplementary Table S2).

Figure 4.

Forest Plot Showing the Effect of ACT on Rehabilitation Participation in Adults with TBI.

Functional Disability

When evaluating secondary outcomes, adults with TBI showed a significant reduction in functional disability compared to the control group [Cohen’s d = 0.47, 95% CI = 0.18–0.76, p = .001] (Supplementary Figure S1). These results were uniform across studies, with no heterogeneity observed (I² = 0%).

Physical and Mental Health Quality of Life

Adults receiving ACT did not show a significant improvement in physical health QOL compared to the control group [Cohen’s d = 0.08, 95% CI = −0.10–0.26, p = .383] (Supplementary Figure S2). In contrast, there was a significant improvement in mental health QOL for the ACT group compared to the control group [Cohen’s d = 0.24, 95% CI = 0.02–0.49, p = .015] (Supplementary Figure S3). Despite these findings, the results were inconsistent across studies, with high heterogeneity observed for both physical health (I² = 80%) and mental health (I² = 90.8%).

Miscellaneous

As we found that only one study³¹ assessed post-traumatic stress symptoms, it was not included as a secondary outcome. Due to the smaller number of included articles, subgroup analysis was not done. Additionally, heterogeneity may be attributed to clinical differences, such as variations in TBI severity, the use of different rating scales for assessing outcomes, variations in methodologies, and the inclusion of diverse statistical reporting methods. Regarding the risk of bias assessment (Supplementary Figure S7), two studies raised some concerns, while the other two had a low risk of bias. The GRADE tables detailing the quality of evidence for outcomes analyzed in the pooled assessments are provided (Supplementary Table S2). Due to the limited number of studies for functional rehabilitation and physical and mental health-related QOL outcomes, publication bias and certainty of evidence could not be assessed.

Discussion

This review aimed to evaluate the effectiveness of ACT in treating depression and anxiety among adults with TBI, comparing its outcomes to treatment as usual (TAU) or other psychological interventions such as befriending therapy or present-centered therapy. The results showed a substantial improvement in combined depression and anxiety scores among adults treated with ACT compared to those in the control group. Moreover, the data highlighted that ACT significantly enhances psychological flexibility, improves mental health-related QOL, and reduces functional disability compared to the control group. However, it was also observed that ACT did not significantly improve rehabilitation participation or physical health-related QOL.

Studies have shown that individuals with depression tend to exhibit low psychological flexibility, which contributes to the persistence of depressive symptoms, low mood, and ACT focuses on psychological inflexibility.^37,38 A recent meta-analysis showed that ACT has significantly alleviated depressive symptoms, with an SMD of −1.05 (95% CI = −1.44–−0.66) when compared to either the control or TAU group.³⁹ These findings are in line with the current review, which also found reductions in psychological distress relative to the control group. A systematic review noted variations in outcomes based on age, gender, and severity of injury but reported reductions in psychological distress, including depression, anxiety, and stress.¹⁹ However, comparisons between ACT and CBT for depressive symptoms have found conflicting results. This comparison requires further exploration as the meta-analysis included only two studies with high heterogeneity (I² = 86%).^39,40

Regarding secondary outcomes, a meta-analysis reported that ACT significantly enhanced psychological flexibility compared to the control group, with a mean difference of 4.84 (95% CI = 2.71–6.96). Studies have shown that improvements in psychological flexibility are associated with reduced psychological distress, including depression and anxiety.⁴¹ Consistent with these findings, the current review also observed improvement in psychological flexibility and reduction in distress. Rehabilitation plays a crucial role in the management of TBI patients, aiming to help them regain their previous level of independent functioning. Although two included studies,^35,36 reported improved rehabilitation participation with ACT, the current review found divergent results. Few studies have explored the utility of ACT as a supplementary approach in various rehabilitation programs for different health conditions. However, there are limited studies assessing rehabilitation participation as an outcome.^42,43 Regarding functional disability, Faulkner et al.⁴⁴ reported a significant reduction post-treatment with ACT compared to CBT in individuals with mild TBI, with a moderate effect size of 0.58. This aligns with the current review’s finding of a significant reduction in functional disability with an effect size of 0.47. However, evidence regarding rehabilitation participation and functional disability with ACT remains limited.

A meta-analysis evaluating the impact of ACT on QOL in individuals with chronic health conditions found that, when compared to the group on the waitlist or a few active therapies, ACT significantly improved the psychological health domain of QOL more than the physical health domains.¹⁷ The current review similarly observed significant improvements in psychological than physical QOL.

Strengths

To our knowledge, this is the first study in published literature that has systematically analyzed the effect of ACT on depression and anxiety in adults with TBI. Effect sizes were calculated based on the available data using standard formulae to ensure consistency in performing meta-analysis. The strength of our review lies in analyzing previously unexamined outcomes in this population, such as functional disability and participation in rehabilitation. These insights help enhance patient functionality and improve the rehabilitation process.

Limitations

However, there are a few limitations to the included studies. Only four studies were included in the final review, and half of them exhibited a moderate risk of bias. Furthermore, some outcomes demonstrated high heterogeneity, and the quality of evidence, as assessed using the GRADE approach, was low for specific measures. Publication bias for the primary outcome may inflate the perceived effectiveness of the intervention. These challenges underscore the need for more rigorous RCTs to strengthen the evidence base and enhance the applicability of findings across diverse clinical settings.

Conclusions

ACT shows promise as an effective approach for managing depression and anxiety after TBI. By enhancing psychological flexibility, ACT helps individuals better cope with cognitive and emotional challenges, ultimately improving their mental health and overall QOL. Its focus on acceptance, mindfulness, and committed action enables individuals to manage distressing thoughts and emotions more effectively, fostering resilience throughout the recovery process. However, further research is needed to fully understand the long-term benefits of ACT for individuals with TBI. Future studies should investigate its sustained effects over time, identify the most effective intervention strategies, and examine key factors that influence treatment outcomes. Integrating ACT with other traditional psychological therapies may enhance its effectiveness and help refine ACT as a valuable component of holistic TBI rehabilitation programs.

Supplemental Material

Supplemental material for this article available online.

Supplemental Material

Supplemental material for this article available online.

Footnotes

Acknowledgements

We sincerely thank the organizers and resource persons of SARANSH (Systematic Reviews and Networking Support in Health) workshop conducted under the DHR-SARANSH grant for Telangana and Andhra Pradesh for their valuable support. We are especially grateful to Dr. Saibal Das, Scientist-D (Medical), ICMR Centre for Ageing and Mental Health, Kolkata; Dr. Sai Krishna Tikka, Additional Professor of Psychiatry; and Dr. Madhavi Eerike, Additional Professor of Pharmacology, AIIMS Bibinagar, for their unwavering guidance, time, and efforts in making this review possible. Also, a special thanks to the corresponding author, Lilian Dindo, for the timely response and providing the required data to conduct our meta-analysis.

Data Sharing Statement

The manuscript being a systematic review and meta-analysis, following data will be made available on valid request to the corresponding author: De-identified individual study data will be made available, in addition to study protocols, the statistical analysis plan, and R language code used for generating doi plot with LFK index. The data will be made available upon publication to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal. Proposals should be submitted to drdonthu@gmail.com.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Declaration Regarding the Use of Generative AI

None used.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Prior Presentation

The work has not been presented anywhere.

Prospero ID

The systematic review and meta-analysis has been registered with PROSPERO with reference number: CRD420250651290.

Simultaneous Submission to Another Journal or Resource

The manuscript has been submitted solely to Indian Journal of Psychological Medicine and not submitted or under consideration anywhere else.

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