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The Effectiveness of Music Therapy for Terminally Ill Patients: A Meta-Analysis and Systematic Review

Open ArchivePublished:October 30, 2018DOI:https://doi.org/10.1016/j.jpainsymman.2018.10.504

      Abstract

      Context

      The quality of death has increasingly raised concern because of the physical and psychological suffering of patients with advanced disease. Music therapy has been widely used in palliative care; however, its physical and mental effectiveness remains unclear.

      Objective

      To assess the effectiveness of music therapy during palliative care in improving physiology and psychology outcomes.

      Methods

      Randomized controlled trials evaluating music therapy for terminally ill patients were searched and included from inception up to April 25, 2018. The quality of the studies was assessed using the risk of bias tool recommended by the Cochrane Handbook V.5.1.0.

      Results

      In this study, 11 randomized controlled trials (inter-rater agreement, κ = 0.86) involving 969 participants were included. The quality of the included studies ranged from moderate to high. Compared with general palliative care, music therapy can reduce pain (standardized mean difference: −0.44, 95% confidence interval: −0.60 to −0.27, P < 0.00001) and improve the quality of life (standardized mean difference: 0.61, 95% confidence interval: 0.41 to 0.82, P < 0.00001) in terminally ill patients. In addition, anxiety, depression, and emotional function are improved as well. However, no significant differences were found in the patient's physical status, fatigue, and social function.

      Conclusion

      This meta-analysis study demonstrated that music therapy served as an effective intervention to alleviate pain and psychological symptoms of terminally ill patients. However, considering the limitation of the quantity of the studies included, these results would need to be further confirmed.

      Key Words

      Introduction

      Terminally ill patients are characterized by the existence of an incurable illness, with limited possibilities of response to standard of care treatments and a poor survival prognosis.
      • Domingo J.P.
      • Matamoros N.E.
      • Danes C.F.
      • et al.
      Effectiveness of music therapy in advanced cancer patients admitted to a palliative care unit: a non-randomized controlled, clinical trial.
      Patients with advanced disease are always subjected to various physical and psychological issues caused by their disease, such as pain, anxiety, depression, sadness, and other symptoms. Palliative care represents an effective approach to reduce the suffering of these patients.
      • Bradt J.
      • Dileo C.
      Music therapy for end-of-life care.
      Palliative care initially focused on advanced cancer but in recent years has increasingly extended to the early stage of serious illness, and it has proliferated around the world.
      • Zimmermann C.
      • Riechelmann R.
      • Krzyzanowska M.
      • Rodin G.
      • Tannock I.
      Effectiveness of specialized palliative care: a systematic review.
      • Parikh R.B.
      • Kirch R.A.
      • Smith T.J.
      • Temel J.S.
      Early specialty palliative care--translating data in oncology into practice.
      • Sepúlveda C.
      • Marlin A.
      • Yoshida T.
      • Ullrich A.
      Palliative care.
      The World Health Organization delimited that palliative care is a way to improve the quality of life (QoL) of patients and their families facing a life-threatening illness, through the prevention and relief of suffering by early identification and impeccable assessment and treatment of pain and other symptoms.
      World Health Organization
      Definition of palliative care.
      Music therapy is defined as “the clinical and evidence-based use of music interventions, a trained music therapist provides the indicated treatment after assessing the needs of patients, including creating, singing, moving to, and/or listening to music.”
      American Music Therapy Association
      Definition and Quotes about Music Therapy.
      Music therapy is one of the most frequently used complementary therapies in palliative care.
      • Warth M.
      • Kessler J.
      • Koenig J.
      • et al.
      Music therapy to promote psychological and physiological relaxation in palliative care patients: protocol of a randomized controlled trial.
      It is a method of treating patients with physiological or psychosocial diseases by tones and rhythms and is considered one of the most effective methods of spiritual healing.
      • Young W.C.
      • Nadarajah S.R.
      • Skeath P.R.
      • Berger A.M.
      Spirituality in the context of life-threatening illness and life-transforming change.
      Music therapy can promote health in critically ill patients, and it can serve as an aid to eliminate psychosomatic disorders.
      • Shuming Z.
      • Jintao W.
      • Wei D.
      The clinical application and Challenges of music therapy.
      Markedly, psychotherapists believe that music can improve the mental state of patients, as a medium, music can help patients to better express their feelings and promote the exchange of inner moods and emotions.
      • Bieligmeyer S.
      • Helmert E.
      • Hautzinger M.
      • Vagedes J.
      Feeling the sound - short-term effect of a vibroacoustic music intervention on well-being and subjectively assessed warmth distribution in cancer patients-A randomized controlled trial.
      At present, music therapy as a complementary approach to standard of care or palliative care programs is widely used in the clinical management of disease, especially in advanced cancer and other terminal illnesses.
      • Stanczyk M.M.
      Music therapy as part of psychosocial support for cancer patients.
      Numerous studies have suggested that music therapy plays a beneficial role in patients with serious diseases. For example, in certain cases, it has been demonstrated that music therapy has the power to promote emotional functions in terminally ill patients.
      • Clements-Cortes A.
      The use of music in facilitating emotional expression in the terminally ill.
      In addition, a pilot study demonstrated that music therapy was able to reduce stress, anxiety, and depression in patients enrolled in palliative care.
      • Nakayama H.
      • Kikuta F.
      • Takeda H.
      A pilot study on effectiveness of music therapy in hospice in Japan.
      A controlled trial of 14 participants also showed that palliative care that included music therapy significantly reduced the pain level of patients.
      • Krishnaswamy P.
      • Nair S.
      Effect of music therapy on pain and anxiety levels of cancer patients: a pilot study.
      Before this meta-analysis, two related systematic reviews
      • Bradt J.
      • Dileo C.
      Music therapy for end-of-life care.
      • McConnell T.
      • Scott D.
      • Porter S.
      Music therapy for end-of-life care: an updated systematic review.
      on music therapy were published in 2010 and 2016, respectively. Dr. Joke Bradt and her team analyzed indexes that included pain, anxiety, depression, QoL, functional, psychophysiological, and social/spiritual well-being
      • Bradt J.
      • Dileo C.
      Music therapy for end-of-life care.
      . However, these results were based on a small sample size, for example, the outcomes of pain, anxiety, and depression were based on only 45 patients, the outcome of QoL was based on 125 patients, and the remaining outcomes were based on 100 patients. In addition, a review performed by McConnell et al., the effectiveness of music therapy on pain was evaluated in 243 patients with advanced disease, which was found to be an effective nonpharmacological approach to managing distressing symptoms
      • McConnell T.
      • Scott D.
      • Porter S.
      Music therapy for end-of-life care: an updated systematic review.
      . Nonetheless, the effectiveness of music therapy on patients with advanced disease or terminal illnesses has not yet fully been elucidated. Based on the findings of the above two systematic reviews,
      • Bradt J.
      • Dileo C.
      Music therapy for end-of-life care.
      • McConnell T.
      • Scott D.
      • Porter S.
      Music therapy for end-of-life care: an updated systematic review.
      this meta-analysis was conducted to comprehensively evaluate the effectiveness of music therapy in improving physiology and psychology outcomes.

      Methods

      Literature Search

      Online databases, including PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine (CBM), were searched from inception to April 25, 2018. In addition, references of related literature were retrieved. To build the search strategy, the following search terms were used: (music* OR melod* OR improvis* OR sing* OR song OR rhy* OR lyric OR sound* OR acoustic OR vibroacoustic OR voice OR vocalise) AND (palliative OR hospice OR terminal* OR dying OR “end of life” OR “end stage”) AND (random* OR “controlled clinical trial*” OR “single blind” OR “double blind” OR placebo OR RCT).

      Inclusion and Exclusion Criteria

      The inclusion criteria for our analysis were 1) randomized controlled trials (RCTs); 2) enrolled participants who were diagnosed with incurable terminal illness or who were receiving palliative care; 3) patients who were 18 years or older; 4) the control group received palliative care, which included the following forms: general nursing, breathing relaxation, muscle relaxation, and conversation, and so forth, whereas the experimental group received music therapy based on palliative care; and 5) full study text was written in English or Chinese. The exclusion criteria were 1) conference proceedings or abstracts; 2) psychotherapy and art therapy; 3) duplicate reports of a study; and 4) data that were incomplete or could not be obtained.

      Data Extraction and Quality Assessments

      Two evaluators independently screened the medical literature and extracted the data. If one of the evaluators presented an opinion different from the other, a third evaluator resolved disagreement by consulting. A Risk of Bias (RoB) tool recommended by the Cochrane Handbook V.5.1.0 (Cochrane Collaboration, London, UK) was used to assess the quality of the trials. The quality factor was classified as yes (low risk of bias), no (high risk of bias), or unclear (moderate risk of bias). Assessment principles included the following aspects: generation of random sequence, allocation concealment, blinding of participants and assessment, integrity of the data, selective reporting, and other bias.

      Statistical Analysis

      Meta-analysis was performed to integrate the outcomes of the RCTs. The primary outcomes included pain, QoL, and physical status. Secondary outcomes included anxiety, depression, fatigue, emotional function, and social function. Outcomes were presented as continuous variables. In cases where studies used different instruments to measure the same parameter (e.g., pain), we reported the standardized mean difference (SMD) with a 95% confidence interval (CI). The Higgins I2 test was used to evaluate the heterogeneity between studies. A fixed-effects model was used when absence of marked heterogeneity (I2 < 50%). Otherwise, a random-effects model was implemented (I2 ≥ 50%), and subgroup analysis was used to measure heterogeneity. Sensitivity analysis was conducted to test the robustness of the results by omitting any single study. Data were pooled and analyzed using Excel (Microsoft, Redmond, WA) and Review Manager (RevMan) Software (Cochrane, London, UK), respectively. In addition, Kappa coefficient for inter-rater agreement was calculated manually.

      Results

      Literature Search

      The detailed retrieval and screening process are presented in Fig. 1. A total of 3423 relevant records were identified, of which 1135 records were excluded as duplicates. After browsing the titles and abstracts of the related references, 2236 records were excluded. The full text of the remaining 52 articles was browsed, and 43 studies were excluded. In addition, two studies were included by hand-searching references of related literature. Finally, a total of 11 studies
      • Nguyen J.T.
      The Effect Of Music Therapy On End-Of-Life Patients' Quality Of Life, Emotional State, And Family Satisfaction As Measured By Self-Report.
      • Hilliard R.E.
      The effects of music therapy on the quality and Length of life of People diagnosed with terminal cancer.
      • Horne-Thompson A.
      • Grocke D.
      The effect of music therapy on anxiety in patients who are terminally ill.
      • Gutgsell K.J.
      • Schluchter M.
      • Margevicius S.
      • et al.
      Music therapy reduces pain in palliative care patients: a randomized controlled trial.
      • Juan L.
      • Yufang H.
      • Yufei Y.
      • Chunyan X.
      • Hao W.
      Chinese medicine five elements music improves the quality of life of elderly and non elderly cancer patients: a randomized controlled study.
      • Haiyan L.
      • Yuhua W.
      Observation of the impact of music therapy on the life quality of dying patients.
      • Juan L.
      The Effects of Traditional Chinese Medicine Five Elements Music on the Quality of Life for Advanced Cancer Patients: A Randomized controlled Trial.
      • Juan L.
      • Yuanchen Z.
      • Jing L.
      • Hao W.
      • Nan Z.
      A randomized controlled trial of Traditional Chinese medicine non-pharmacological Techniques to improve anxiety and depression of cancer patients.
      • Huirong Z.
      • Hongning J.
      • Bo Y.
      • et al.
      Effect of music therapy on end-stage quality of life in elderly patients with malignant tumors.
      • Warth M.
      • Kessler J.
      • Hillecke T.K.
      • Bardenheuer H.J.
      Music therapy in palliative care: a randomized controlled trial to evaluate effects on relaxation.
      • Zhai W.
      • Liu N.
      Effect of TCM music therapy for hospice care of patients with gastrointestinal cancer.
      were included in our meta-analysis. Inter-rater agreement was κ = 0.84.
      Figure thumbnail gr1
      Fig. 1Literature screening process and results.

      Study Characteristics

      The clinical trials included in this meta-analysis spanned between the years 2003 and 2017. The average sample size was 88, ranging from 20 to 198 patients. Six studies were performed in China, three in America, one in Australia, and one in Germany. The average patient age was more than 55 years, and most of the patients were diagnosed with advanced cancer. Of all included studies, the average number of sessions was 2, ranging from 1 session up to 13 sessions. Single intervention of music therapy generally took between 15 or 40 minutes. In addition, three music therapy interventions were most commonly used—instrument playing, live music playing, and recorded music playing. More detailed characteristics of the 11 studies were shown in Table 1.
      Table 1Characteristics of the Included Studies
      StudyPopulationNo. of Patients (E/C)Mean Age, YearsInterventionOutcomes
      Experimental GroupControl Group
      Nguyen 2003, AmericanCongestive heart failure, chronic renal failure, different types of cancer, and other terminal illness.10/1064.5Two sessions

      The first session involved singing music chosen by the patient, finding out the patient's favorite songs. The second session conducted an end-of-life celebration.
      Did not receive any music and consented only to participating in the studyPain (VAS), anxiety (VAS), depression (VAS), QOL (HRQOL), social function (HRQOL)
      Hilliard 2003, AmericanAdvanced cancer40/4065.5Least two sessions up to 13 sessions

      Music therapy with palliative care: song choice, music-prompted reminiscence, singing, live music listening, lyric analysis, instrument playing, song parody, etc. Music therapists used subject-preferred, live music
      Routine palliative careQOL (HRQOL), physical status (PPS), emotional function (HRQOL), social function (HRQOL)
      Thompson 2008, AustraliaTerminal cancer and other diseases13/1273.9 ± 13.32Single session

      A music therapist provided a range of techniques that included singing, playing familiar live or recorded music, music and relaxation, music and imagery, improvisation, and music-assisted counseling.
      A single volunteer session consisting of conversationPain (ESAS), anxiety (ESAS), depression (ESAS)
      Gutgsell 2013, AmericanAdvanced cancer (87%)99/9956.09 ± 15.08Single session

      Music therapy with standard care: The music therapist used an ocean drum, followed by a harp. The music played at a low volume in a slow tempo.
      Standard carePain (NRS)
      Liao 2013, ChinaAdvanced cancer29/1463.5 ± 13.3Three sessions music therapy with standard care: patients receive music therapy by CD playersStandard careQOL (HRQOL), physical status (KPS)
      Leng 2014, ChinaPatients receiving palliative care50/5073.4 ± 10.2Single session

      Music therapy with palliative care: patients receive music therapy by MP3 headphones
      Palliative carePain (SF-MPQ), physical status (KPS)
      Liao 2014, ChinaAdvanced cancer57/3162.9 ± 12.9Three sessions

      Music therapy with standard care: patients receive music therapy by CD player
      Standard carePhysical status (KPS)
      Zhang 2015, ChinaAdvanced cancer58/9775.5Single session

      Music therapy with palliative care: recorded music
      Palliative carePain (EORTC QLQ-C30), QOL (EORTC QLQ-C30), physical status (EORTC QLQ-C30), emotional function (EORTC QLQ-C30), social function (EORTC QLQ-C30)
      Warth 2015, GermanyMalignant tumor except two cases40/3863 ± 13.4Two sessions

      Live music based on relaxation exercise: music played live on a monochord, then vocal improvisation was begun in Ionian or Mixolydian mode
      Verbal relaxation exercisePain (VAS), QOL (EORTC QLQ-C15), fatigue (EORTC QLQ-C15), emotional function (VAS)
      Liao 2016, ChinaAdvanced cancer39/3760.8 ± 1.3Single session

      Music therapy with progressive muscle relaxation training: recorded music
      Progressive muscle relaxation trainingAnxiety (HADS), depression (HADS)
      Zhai 2017, ChinaGastrointestinal cancer53/5358.3 ± 10.2Single session

      Music therapy with standard care: recorded music
      Standard carePhysical status (KPS), depression(HAMD)
      Abbreviations: VAS = Visual Analog Scales; HRQOL = Health-Related Quality of Life scales; PPS = Palliative Performance Scale; ESAS = Edmonton Symptom Assessment System; NRS = Numeric Rating Scale; KPS = Karnofsky Performance Status; SF-MPQ = Short Form-McGill Pain Questionnaire; EORTC QLQ-C15/30 = European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15/30 palliative questionnaire; HADS = Hospital Anxiety and Depression Scale; HAMD = Hamilton Depression Scale.

      Quality Assessment

      The RoB of included studies is presented in Fig. 2. Six clinical trials described the randomization procedures in detail, whereas the remaining trials only mentioned the randomization without any introduction of the procedures. Moreover, four studies concealed the allocation sequence through sealed opaque envelopes, and others not reported. Because of the particularity of music therapy, blinding of participants cannot be implemented. Two studies reported blinding of outcome assessment. In two studies, a few participants withdrew, resulting in a dropout rate of 0.1 and 0.7, respectively, and the authors explained the reasons for withdrawal without intentionality analysis. In addition, one study has high risk of bias of selective reporting.
      Figure thumbnail gr2
      Fig. 2The risk of bias of included studies. Green plus circle = low risk of bias; red minus circle = high risk of bias; yellow ? circle = unclear risk of bias. (For interpretation of the references to color in this figure legend, the reader is Referred to the web version of this article.)

      Primary Outcomes

      In our analysis, six studies including 576 patients reported the effect of music therapy on pain intensity of terminally ill (Fig. 3). A fixed model was applied to these studies, presenting a significant difference between the music therapy group and the control group (SMD: −0.44, 95% CI: −0.60 to −0.27, P < 0.00001; heterogeneity: χ2 = 7.19, I2 = 37%, P = 0.16). In addition, we performed sensitivity analysis by omitting any single-choice study, and the result did not change, indicating that this result was robust and reliable. Accordingly, music therapy was found to significantly relieve pain of terminally ill patients.
      Figure thumbnail gr3
      Fig. 3The effectiveness of music therapy versus standard care for pain of terminally ill patients.
      Moreover, QoL was used as one of the outcomes in five of the studies. When dividing the 421 participants of the five studies into two subgroups based on different scales (European Organization for Research and Treatment of Cancer [EORTC] and the Health-Related Quality of Life [HRQOL]), homogeneous results were obtained. Pooling the outcomes of two scales resulted in statistically significant results. Our meta-analysis (Fig. 4) showed that participants who received music therapy exhibited significant improvement in QoL (SMD: 0.61, 95% CI: 0.41 to 0.82, P < 0.00001; heterogeneity: χ2 = 14.96, I2 = 73%, P < 0.05), compared with participants who received general palliative care. Subgroup analysis of EORTC scale showed that music therapy can improve QoL of terminally ill patients (SMD: 0.29, 95% CI: 0.03 to 0.55, P = 0.03; heterogeneity: χ2 = 0.56, I2 = 0%,P = 0.46), and the results of HRQOL subgroup analysis were even more remarkable (SMD: 1.07, 95% CI: 0.76 to 1.38, P < 0.0.00001; heterogeneity: χ2 = 0.51, I2 = 0%,P = 0.78). Statistical difference was observed between the two subgroups (χ2 = 13.89, I2 = 92.8%, P = 0.0002). A sensitivity analysis was conducted by omitting a single-choice study, and the result of the subgroups did not change, suggesting that the result obtained was stable.
      Figure thumbnail gr4
      Fig. 4The effectiveness of music therapy versus standard care for QOL of terminally ill patients.
      Moreover, six studies involving 572 patients assessed their physical status. Fig. 5 shows the results of our meta-analysis examining the effect of music therapy on the physical status of terminally ill patients. Overall, meta-analysis showed no statistical difference between experimental and control groups in physical status (SMD: 0.68, 95% CI: 0.01 to 1.34, P = 0.05). Notably, high heterogeneity was seen among the meta-analysis results (I2 = 93%, P < 0.05). A sensitivity analysis was also conducted, and the result changed when we omitted Zhang's study,
      • Juan L.
      • Yufang H.
      • Yufei Y.
      • Chunyan X.
      • Hao W.
      Chinese medicine five elements music improves the quality of life of elderly and non elderly cancer patients: a randomized controlled study.
      suggesting that this result was unstable.
      Figure thumbnail gr5
      Fig. 5The effectiveness of music therapy versus standard care for physical status of terminally ill patients.

      Secondary Outcomes

      The pooled estimates of anxiety, depression, and fatigue are represented in Fig. 6. In three trials, anxiety of 121 participants was evaluated. The results of meta-analysis indicated that music therapy relieved anxiety in these patients (SMD: −0.68, 95% CI: −1.35 to −0.02, P = 0.04, heterogeneity:χ2 = 5.25, I2 = 62%,P = 0.07). In four trials, depression among 227 patients was evaluated. In meta-analysis, depression exhibited significant relief compared to patients undergoing general palliative care (SMD: −1.08, 95% CI: −1.64 to −0.53, P = 0.0001; heterogeneity: χ2 = 9.34, I2 = 68%,P = 0.03). In two trials, fatigue of 233 participants was assessed. Meta-analysis demonstrated that there were no significant differences between experimental and control groups (SMD: −0.17, 95% CI: −0.95 to 0.61, P = 0.67). Sensitivity analysis was not carried out because of the limited number of studies in each group.
      Figure thumbnail gr6
      Fig. 6The effectiveness of music therapy versus standard care for anxiety, depression, and fatigue of terminally ill patients.
      The pooled effects of emotional function and social function are represented in Fig. 7. In three trials, emotional function of 313 participants was evaluated. Meta-analysis showed that emotional function of patients who received music therapy significantly improved (SMD: 0.58, 95% CI: 0.27 to 0.90, P = 0.0003; heterogeneity: χ2 = 3.58, I2 = 44%,P = 0.17). Finally, in three trails, social function of 255 patients was assessed. Our pooled estimate indicated a lack of strong evidence for an effect of music therapy in social function (SMD: 0.51, 95% CI: −0.17 to 1.19, P = 0.14). Sensitivity analysis was not carried out because of the limited number of studies in each group.
      Figure thumbnail gr7
      Fig. 7The effectiveness of music therapy versus standard care for emotional function and social function of terminally ill patients.

      Discussion

      Summary of Results

      This systematic review and meta-analysis provides a comprehensive analysis of the effects of music therapy on terminally ill patients, including their physical and psychological symptoms. Markedly, pain is one of the most unbearable symptoms of dying patients; therefore, clinicians pay more attention to pain remission in these patients.
      • Ruijs C.D.
      • Kerkhof A.J.
      • van der Wal G.
      • Onwuteaka-Philipsen B.D.
      The broad spectrum of unbearable suffering in end-of-life cancer studied in Dutch primary care.
      Moreover, according to our retrieval process, there were plenty of researches on QoL, physical status, and other symptoms of terminally ill patients.
      Our meta-analysis results suggested that music therapy can significantly relieve pain intensity in terminally ill patients. In the systematic review performed by McConnell et al.,
      • McConnell T.
      • Scott D.
      • Porter S.
      Music therapy for end-of-life care: an updated systematic review.
      similar results were presented, whereas in the systematic review by Bradt and her team,
      • Bradt J.
      • Dileo C.
      Music therapy for end-of-life care.
      the results were opposite. The difference between these three reviews may be due to the small sample size of the meta-analysis performed by Bradt et al. (n = 45). In addition, Bowers et al.
      • Bowers T.
      • Wetsel M.
      Utilization of music therapy in palliative and hospice care.
      reported that music therapy reduced pain of adult patients undergoing palliative care. Bro et al.
      • Bro M.L.
      • Jespersen K.V.
      • Hansen J.B.
      • et al.
      Kind of blue: a systematic review and meta-analysis of music interventions in cancer treatment.
      also presented a similar outcome after giving an evaluation of the application of music therapy in cancer treatment. The mitigation effect of music therapy on physical pain was in line with the expected conjecture and the general public's cognition. Notably, two theories may account for the effects of music therapy from a patient's perspective. First, listening to music can distract the concentration of patients from pain.
      • Ning X.Y.
      Effect of comfort nursing on pain control and psychological improvement of cancer patients.
      Second, modern pain theory suggests that painful experiences are affected by both physical and mental factors,
      • Witte W.
      Pain and anesthesiology : aspects of the development of modern pain therapy in the twentieth century.
      so patients experience psychological pleasure through music, which relieves pain correspondingly.
      Our findings showed that music therapy creates a favorable improvement in the QoL of terminally ill patients, when compared with patients subjected to the general palliative care. However, high heterogeneity was found in meta-analysis between the two scales analyzed (EORTC and HRQOL) for terminally ill patients. The reason may be that the specific scale indexes and specific measurement standards used in the two scales were inherently different. Nevertheless, in both subgroups, positive results on the QoL of the patients receiving music therapy were demonstrated. Similar results were obtained in the analysis of Bradt et al. based on three trials (n = 125). Several clinical reports and nonrandomized control trials have also indicated that music therapy played a positive role in improving QoL of patients.
      • Nakayama H.
      • Kikuta F.
      • Takeda H.
      A pilot study on effectiveness of music therapy in hospice in Japan.
      • Milliard R.E.
      A post-hoc analysis of music therapy services for residents in nursing homes receiving hospice care.
      • Preissler P.
      • Kordovan S.
      • Ullrich A.
      • Bokemeyer C.
      • Oechsle K.
      Favored subjects and psychosocial needs in music therapy in terminally ill cancer patients: a content analysis.
      It is well accepted that the QoL of a patient is generally affected by physical, psychological, and social factors.
      • XH L.
      • Line L.Y.
      • Xinxin L.
      • et al.
      Study on influence of music therapy on quality of life of cancer patient.
      In this study, music therapy was able to improve the mental and spiritual state, including anxiety, depression, and emotional function, thereby improving the QoL of patients as a whole.
      In our review, no statistical differences in physical status improvement were observed between experimental and control groups, and a high heterogeneity was found between groups. Sensitivity analysis demonstrated that the results were unstable when Zhang's study
      • Huirong Z.
      • Hongning J.
      • Bo Y.
      • et al.
      Effect of music therapy on end-stage quality of life in elderly patients with malignant tumors.
      was included. Therefore, we analyzed the original data reported by Zhang et al. and concluded that the lower levels of physical status at the baseline of the experimental participants may represent an alternative explanation for the outcome observed. Other related reviews did not analyze the patient's physical status, making it obvious that more high-quality RCTs are needed before conclusions can be convincingly drawn.
      In the secondary outcome results, we observed that music therapy play an active role in relieving anxiety, depression, and in improving emotional function. However, no statistical significance was observed in the effect of music in reducing fatigue and improving social functions. In several reviews and clinical reports evaluating these effects, similar results were obtained. For instance, Azoulay et al. concluded that music therapy may greatly relieve anxiety in critically ill patients.
      • Azoulay E.
      • Chaize M.
      • Kentish-Barnes N.
      Music therapy for reducing anxiety in critically ill patients.
      Another report performed by Gallagher et al. stated that music therapy improved anxiety and emotional function in patients.
      • Gallagher L.M.
      • Lagman R.
      • Walsh D.
      • Davis M.P.
      • LeGrand S.B.
      The clinical effects of music therapy in palliative medicine.
      Fatigue was not found to be appreciably affected by music therapy in another trial evaluated by Clark et al.
      • Clark M.
      • Isaacks-Downton G.
      • Wells N.
      • et al.
      Use of preferred music to reduce emotional distress and symptom activity during radiation therapy.
      Our meta-analysis evaluating the effectiveness of music therapy in terminally ill patients demonstrated sufficient evidence to support its implementation in clinical practice. Fortunately, we found no identified side effects in any of the included trials, as reported in previous reviews. Summarizing all of our results, we found that most of the improvement obtained from music therapy in terminally ill patients was mainly reflected in their psychological status. In terms of their physical status, no improvement was observed other than pain relief. This may be because the body of terminally ill patients is already in an incurable statement, and supplementary care is basically ineffective in improving their body function. Therefore, their physical symptoms can only be relieved, to some extent, through drugs or other clinical means. In addition, clinical studies of cancer have reported that a greater impact on their emotional response variables than physical symptoms,
      • Clark M.
      • Isaacks-Downton G.
      • Wells N.
      • et al.
      Use of preferred music to reduce emotional distress and symptom activity during radiation therapy.
      • Metzger L.K.
      Assessment of use of music by patients participating in cardiac rehabilitation.
      as other studies outside of cancer have previously observed.
      • Bates D.
      • Rybicki L.
      • Bates D.
      • et al.
      The effects of music therapy in Liquid and Solid Tumor oncology patients.
      The findings of this review echoed the theories mentioned previously, indicating that music therapy is more likely to play a positive role in the mental health of a terminally ill patient than the physical symptoms of the disease.

      Overall Completeness and Applicability of Evidence

      Although a comprehensive search strategy was conducted, it may still be possible that relevant published or unpublished studies were missed. Because the trails of music therapy in fatigue, anxiety, emotional function, and social function were based on small sample size, more high-quality RCTs are needed.
      In addition, the personality traits and sensitivity to music of participants can also affect the effectiveness. As a whole, the studies included in this review only involved finite information about the music, except for mentioning general music types (e.g., live or record, fast or slow, jazz or classical). However, these types of music can vary widely in their specific application process, including the particular emotions released by songs, the venue for listening, whether relatives of participants present, and other factors. These details could help music therapists make reasonable music selection after assessing preferences of patients. A review of music therapy suggested that allowing patients to select their favorite music type may enhance the sense of control of them.
      • Bradt J.
      • Dileo C.
      Music for stress and anxiety reduction in coronary heart disease patients.
      In several of the trials included, the experimenter selected music, which they felt would be beneficial to patients, but the music provided may cause the patients uncomfortable. Therefore, how to appropriately select music for patients needs to be evaluated in more all-round studies.

      Strengths, Limitations, and Future Research

      There were two strengths in this meta-analysis. First, our study included more trials than previous reviews, and the trials included were all RCTs. Second, our study comprehensively analyzed the role of music therapy for terminally ill patients, including multiple physiological and psychological indicators. However, there were also some limitations. First, we only included studies that were written in English or Chinese, and it was possible that we excluded relevant studies written in other languages. Second, two of the included trials
      • Nguyen J.T.
      The Effect Of Music Therapy On End-Of-Life Patients' Quality Of Life, Emotional State, And Family Satisfaction As Measured By Self-Report.
      • Horne-Thompson A.
      • Grocke D.
      The effect of music therapy on anxiety in patients who are terminally ill.
      were based on small samples. It is generally well accepted that studies with relatively small sample sizes are more likely to lack sufficient statistical power to detect a true association, and their results are more likely to be attributed to chance.
      In the future, it will be essential to assess the cost-effectiveness of music therapy for terminally ill patients. The cost of listening to music through a device is extremely low, whereas the cost of music therapy in the form of live music or sonic equipment treatment can be costlier. However, it is still unclear whether these various music perception methods have different effectiveness on patients. Cost-effectiveness research can certainly help music therapists select more suitable and cost-effective music treatment approaches. Furthermore, more high-quality RCTs are needed to precisely evaluate the effectiveness of music therapy in palliative care setting.

      Conclusion

      Based on the included studies, we confirmed the positive role of music therapy in alleviating the pain, anxiety, and depression of terminally ill patients, as well as in improving their QoL. The effectiveness of music therapy in physical status, fatigue, and social functions of terminally ill patients requires further investigation. Overall, this meta-analysis suggested that music therapy was more effective in improving psychological symptoms than physical symptoms of terminally ill patients. In the future, better designed RCTs of music therapy in palliative care should be conducted.

      Disclosures and Acknowledgments

      There are no conflicts of interest among authors.
      The authors thank Xiaohui Wang for her checking and correcting the English expression of the article and thank Lanzhou University for providing a database platform.
      Formatting of funding sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

      References

        • Domingo J.P.
        • Matamoros N.E.
        • Danes C.F.
        • et al.
        Effectiveness of music therapy in advanced cancer patients admitted to a palliative care unit: a non-randomized controlled, clinical trial.
        Music Med. 2015; : 23-31
        • Bradt J.
        • Dileo C.
        Music therapy for end-of-life care.
        Cochrane Database Syst Rev. 2014; 3: CD007169
        • Zimmermann C.
        • Riechelmann R.
        • Krzyzanowska M.
        • Rodin G.
        • Tannock I.
        Effectiveness of specialized palliative care: a systematic review.
        JAMA. 2008; 299: 1698-1709
        • Parikh R.B.
        • Kirch R.A.
        • Smith T.J.
        • Temel J.S.
        Early specialty palliative care--translating data in oncology into practice.
        N Engl J Med. 2013; 369: 2347-2351
        • Sepúlveda C.
        • Marlin A.
        • Yoshida T.
        • Ullrich A.
        Palliative care.
        J Pain Symptom Manage. 2002; 24: 91-96
        • World Health Organization
        Definition of palliative care.
        (Available from:) (Acessed May 12, 2018)
        • American Music Therapy Association
        Definition and Quotes about Music Therapy.
        2011 (Available from:)
        • Warth M.
        • Kessler J.
        • Koenig J.
        • et al.
        Music therapy to promote psychological and physiological relaxation in palliative care patients: protocol of a randomized controlled trial.
        BMC Palliat Care. 2014; 13: 60
        • Young W.C.
        • Nadarajah S.R.
        • Skeath P.R.
        • Berger A.M.
        Spirituality in the context of life-threatening illness and life-transforming change.
        Palliat Support Care. 2015; 13: 653-660
        • Shuming Z.
        • Jintao W.
        • Wei D.
        The clinical application and Challenges of music therapy.
        Med Philos. 2017; 38: 69-74
        • Bieligmeyer S.
        • Helmert E.
        • Hautzinger M.
        • Vagedes J.
        Feeling the sound - short-term effect of a vibroacoustic music intervention on well-being and subjectively assessed warmth distribution in cancer patients-A randomized controlled trial.
        Complement Ther Med. 2018; 40: 171-178
        • Stanczyk M.M.
        Music therapy as part of psychosocial support for cancer patients.
        Psycho-Oncology. 2015; 24: 104
        • Clements-Cortes A.
        The use of music in facilitating emotional expression in the terminally ill.
        Am J Hosp Palliat Care. 2004; 21: 255-260
        • Nakayama H.
        • Kikuta F.
        • Takeda H.
        A pilot study on effectiveness of music therapy in hospice in Japan.
        J Music Ther. 2009; 46: 160-172
        • Krishnaswamy P.
        • Nair S.
        Effect of music therapy on pain and anxiety levels of cancer patients: a pilot study.
        Indian J Palliat Care. 2016; 22: 307-311
        • McConnell T.
        • Scott D.
        • Porter S.
        Music therapy for end-of-life care: an updated systematic review.
        Palliat Med. 2016; 30: 877-883
        • Nguyen J.T.
        The Effect Of Music Therapy On End-Of-Life Patients' Quality Of Life, Emotional State, And Family Satisfaction As Measured By Self-Report.
        (Master's Thesis) Florida State University, 2003
        • Hilliard R.E.
        The effects of music therapy on the quality and Length of life of People diagnosed with terminal cancer.
        J Music Ther. 2003; 40: 113-137
        • Horne-Thompson A.
        • Grocke D.
        The effect of music therapy on anxiety in patients who are terminally ill.
        Palliat Med. 2008; 4: 582-590
        • Gutgsell K.J.
        • Schluchter M.
        • Margevicius S.
        • et al.
        Music therapy reduces pain in palliative care patients: a randomized controlled trial.
        J Pain Symptom Manage. 2013; 45: 822-831
        • Juan L.
        • Yufang H.
        • Yufei Y.
        • Chunyan X.
        • Hao W.
        Chinese medicine five elements music improves the quality of life of elderly and non elderly cancer patients: a randomized controlled study.
        World Sci Technol. 2013; 15: 1379-1382
        • Haiyan L.
        • Yuhua W.
        Observation of the impact of music therapy on the life quality of dying patients.
        Shanghai Pharm. 2014; 35 (62): 59-60
        • Juan L.
        The Effects of Traditional Chinese Medicine Five Elements Music on the Quality of Life for Advanced Cancer Patients: A Randomized controlled Trial.
        (Master's Thesis) Beijing University of Chin Med, 2014
        • Juan L.
        • Yuanchen Z.
        • Jing L.
        • Hao W.
        • Nan Z.
        A randomized controlled trial of Traditional Chinese medicine non-pharmacological Techniques to improve anxiety and depression of cancer patients.
        World Sci Technol. 2016; 18: 1386-1392
        • Huirong Z.
        • Hongning J.
        • Bo Y.
        • et al.
        Effect of music therapy on end-stage quality of life in elderly patients with malignant tumors.
        Chin J Mult Organ Dis Elder. 2015; 14: 458-462
        • Warth M.
        • Kessler J.
        • Hillecke T.K.
        • Bardenheuer H.J.
        Music therapy in palliative care: a randomized controlled trial to evaluate effects on relaxation.
        Dtsch Arztebl Int. 2015; 112: 788-794
        • Zhai W.
        • Liu N.
        Effect of TCM music therapy for hospice care of patients with gastrointestinal cancer.
        World Chin J Digestology. 2017; : 388-391
        • Ruijs C.D.
        • Kerkhof A.J.
        • van der Wal G.
        • Onwuteaka-Philipsen B.D.
        The broad spectrum of unbearable suffering in end-of-life cancer studied in Dutch primary care.
        BMC Palliat Care. 2012; 11: 12
        • Bowers T.
        • Wetsel M.
        Utilization of music therapy in palliative and hospice care.
        J Hosp Palliat Nurs. 2014;
        • Bro M.L.
        • Jespersen K.V.
        • Hansen J.B.
        • et al.
        Kind of blue: a systematic review and meta-analysis of music interventions in cancer treatment.
        Psychooncology. 2018; 27: 386-400
        • Ning X.Y.
        Effect of comfort nursing on pain control and psychological improvement of cancer patients.
        Chin Gen Pract Nurs. 2018; 16: 2230-2231
        • Witte W.
        Pain and anesthesiology : aspects of the development of modern pain therapy in the twentieth century.
        Der Anaesthesist. 2011; 6: 555
        • Milliard R.E.
        A post-hoc analysis of music therapy services for residents in nursing homes receiving hospice care.
        J Music Ther. 2004; 41: 266-281
        • Preissler P.
        • Kordovan S.
        • Ullrich A.
        • Bokemeyer C.
        • Oechsle K.
        Favored subjects and psychosocial needs in music therapy in terminally ill cancer patients: a content analysis.
        BMC Palliat Care. 2016; 15: 48
        • XH L.
        • Line L.Y.
        • Xinxin L.
        • et al.
        Study on influence of music therapy on quality of life of cancer patient.
        Chin Nurs Res. 2008; : 106-108
        • Azoulay E.
        • Chaize M.
        • Kentish-Barnes N.
        Music therapy for reducing anxiety in critically ill patients.
        JAMA. 2013; 309: 2386-2387
        • Gallagher L.M.
        • Lagman R.
        • Walsh D.
        • Davis M.P.
        • LeGrand S.B.
        The clinical effects of music therapy in palliative medicine.
        Support Care Cancer. 2006; 14: 859-866
        • Clark M.
        • Isaacks-Downton G.
        • Wells N.
        • et al.
        Use of preferred music to reduce emotional distress and symptom activity during radiation therapy.
        J Music Ther. 2006; 43: 247-265
        • Metzger L.K.
        Assessment of use of music by patients participating in cardiac rehabilitation.
        J Music Ther. 2004; 1: 55-69
        • Bates D.
        • Rybicki L.
        • Bates D.
        • et al.
        The effects of music therapy in Liquid and Solid Tumor oncology patients.
        J Pain Symptom Manage. 2016; 52: e68
        • Bradt J.
        • Dileo C.
        Music for stress and anxiety reduction in coronary heart disease patients.
        Cochrane Database Syst Rev. 2009; 12: CD006577