| Literature DB >> 24876768 |
Hiroharu Kamioka1, Kiichiro Tsutani2, Minoru Yamada3, Hyuntae Park4, Hiroyasu Okuizumi5, Koki Tsuruoka6, Takuya Honda7, Shinpei Okada8, Sang-Jun Park8, Jun Kitayuguchi9, Takafumi Abe9, Shuichi Handa5, Takuya Oshio10, Yoshiteru Mutoh11.
Abstract
OBJECTIVE: The objective of this review was to summarize evidence for the effectiveness of music therapy (MT) and to assess the quality of systematic reviews (SRs) based on randomized controlled trials (RCTs). STUDYEntities:
Keywords: ICD-10; Parkinson’s disease; depression; mental disorders; schizophrenia; sleep
Year: 2014 PMID: 24876768 PMCID: PMC4036702 DOI: 10.2147/PPA.S61340
Source DB: PubMed Journal: Patient Prefer Adherence ISSN: 1177-889X Impact factor: 2.711
Figure 1Flowchart of trial process.
Note: *Reduplication.
Abbreviations: CINAHL, Cumulative Index of Nursing and Allied Health Literature; CENTRAL, Cochrane Central Register of Controlled Trials; RCT, randomized controlled trial; SR, systematic review.
The special search strategies
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A structured abstract of 21 systematic reviews
| Study | Title | Aim/objective | Data source/search strategy | Study selection/selection criteria | Data extraction/data collection and analysis | Main results | The authors’ conclusions |
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| Sinha et al | Auditory integration training and other sound therapies for autism spectrum disorders (ASD) | To determine the effectiveness of auditory integration therapy or other methods of sound therapy in individuals with autism spectrum disorders. | For this update, we searched the following databases in September 2010: CENTRAL (2010, Issue 2), MEDLINE (1950 to September week 2, 2010), EMBASE (1980 to week 38, 2010), CINAHL (1937 to current), PsycINFO (1887 to current), ERIC (1966 to current), LILACS (September 2010) and the reference lists of published papers. One new study was found for inclusion. | Randomized controlled trials involving adults or children with autism spectrum disorders. Treatment was auditory integration therapy or other sound therapies involving listening to music modified by filtering and modulation. Control groups could involve no treatment, a waiting list, usual therapy, or a placebo equivalent. The outcomes were changes in core and associated features of autism spectrum disorders, auditory processing, QoL, and adverse events. | Two independent review authors performed data extraction. All outcome data in the included papers were continuous. We calculated point estimates and standard errors from paired | We identified six RCTs of auditory integration therapy and one of Tomatis therapy, involving a total of 182 individuals aged 3–39 years. Two were cross-over trials. Five trials had fewer than 20 participants. Allocation concealment was inadequate for all studies. Twenty different outcome measures were used, and only two outcomes were used by three or more studies. Meta-analysis was not possible due to very high heterogeneity or the presentation of data in unusable forms. Three studies did not demonstrate any benefit of auditory integration therapy over control conditions. Three studies reported improvements at 3 months for the auditory integration therapy group based on the Aberrant Behavior Checklist, but they used a total score rather than subgroup scores, which is of questionable validity, and Veale’s results did not reach statistical significance. Rimland 1995 also reported improvements at 3 months in the auditory integration therapy group for the Aberrant Behavior Checklist subgroup scores. The study addressing Tomatis therapy described an improvement in language with no difference between treatment and control conditions and did not report on the behavioral outcomes that were used in the auditory integration therapy trials. | There is no evidence that auditory integration therapy or other sound therapies are effective as treatments for autism spectrum disorders. As synthesis of existing data has been limited by the disparate outcome measures used between studies, there is not sufficient evidence to prove that this treatment is not effective. However, of the seven studies including 182 participants that have been reported to date, only two (with an author in common), involving a total of 35 participants, report statistically significant improvements in the auditory integration therapy group and for only two outcome measures (Aberrant Behavior Checklist and Fisher’s Auditory Problems Checklist). As such, there is no evidence to support the use of auditory integration therapy at this time. |
| Mossler et al | Music therapy for people with schizophrenia and schizophrenia-like disorders | To review the effects of music therapy, or music therapy added to standard care, compared with “placebo” therapy, standard care or no treatment for people with serious mental disorders such as schizophrenia. | We searched the Cochrane Schizophrenia Group Trials Register (December 2010) and supplemented this by contacting relevant study authors, handsearching of music therapy journals, and manual searches of reference lists. | All RCTs that compared music therapy with standard care, placebo therapy, or no treatment. | Studies were reliably selected, quality assessed, and data extracted. We excluded data where more than 30% of participants in any group were lost to follow-up. We synthesized non-skewed continuous endpoint data from valid scales using an SMD. If statistical heterogeneity was found, we examined treatment “dosage” and treatment approach as possible sources of heterogeneity. | We included eight studies (total 483 participants). These examined effects of music therapy over the short-to medium-term (1–4 months), with treatment “dosage” varying from seven to 78 sessions. Music therapy added to standard care was superior to standard care for global state (medium-term, one RCT, n=72, RR 0.10, 95% CI 0.03–0.31; NNT 2, 95% CI 1.2–2.2). Continuous data identified good effects on negative symptoms (four RCTs, n=240, SMD average endpoint SANS −0.74, 95% CI −1.00 to −0.47); general mental state (one RCT, n=69, SMD average endpoint PANSS −0.36, 95% CI −0.85 to 0.12; two RCTs, n=100, SMD average endpoint. BPRS −0.73, 95% CI −1.16 to −0.31); depression (two RCTs, n=90, SMD average endpoint. SDS −0.63, 95% CI −1.06 to −0.21; one RCT, n=30, SMD average endpoint Ham-D −0.52, 95% CI −1.25 to −0.12); and anxiety (one RCT, n=60, SMD average endpoint SAS −0.61, 95% CI −1.13 to −0.09). Positive effects were also found for social functioning (one RCT, n=70, SMD average endpoint. SDSI score −0.78, 95% CI −1.27 to −0.28). Furthermore, some aspects of cognitive functioning and behavior seem to develop positively through music therapy. Effects, however, were inconsistent across studies and depended on the number of music therapy sessions as well as the quality of music therapy provided. | Music therapy as an addition to standard care helps people with schizophrenia to improve their global state, mental state (including negative symptoms), and social functioning if a sufficient number of music therapy sessions are provided by qualified music therapists. Further research should especially address the long-term effects of music therapy, dose–response relationships, as well as the relevance of outcomes measures in relation to music therapy. |
| Bradt et al | Music interventions for improving psychological and physical outcomes in cancer patients | To compare the effects of music therapy or music medicine interventions and standard care with standard care alone, or standard care and other interventions in patients with cancer. | We searched CENTRAL (The Cochrane Library 2010, Issue 10), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, Science Citation Index, CancerLit, | We included all RCTs and quasi-RCTs of music interventions for improving psychological and physical outcomes in patients with cancer. Participants undergoing biopsy and aspiration for diagnostic purposes were excluded. | Two review authors independently extracted the data and assessed the risk of bias. Where possible, results were presented in meta-analyses using MDs and SMDs. Post-test scores were used. In cases of significant baseline difference, we used change scores. | We included 30 trials with a total of 1,891 participants. We included music therapy interventions offered by trained music therapists, as well as listening to prerecorded music offered by medical staff. The results suggest that music interventions may have a beneficial effect on anxiety in people with cancer, with a reported average anxiety reduction of 11.20 units (95% CI −19.59 to −2.82, | This systematic review indicates that music interventions may have beneficial effects on anxiety, pain, mood, and QoL in people with cancer. Furthermore, music may have a small effect on heart rate, respiratory rate, and blood pressure. Most trials were at high risk of bias, and therefore, these results need to be interpreted with caution. |
| Bradt and Dileo | Music therapy for end-of-life care | To examine effects of music therapy with standard care versus standard care alone or standard care combined with other therapies on psychological, physiological, and social responses in end-of-life care. | We searched CENTRAL, MEDLINE, CINAHL, EMBASE, PsycINFO, LILACS, CancerLit, Science Citation Index, | We included all RCTs and quasi-RCTs that compared music interventions and standard care with standard care alone or combined with other therapies in any care setting with a diagnosis of advanced life-limiting illness being treated with palliative intent and with a life expectancy of less than 2 years. | Data were extracted, and methodological quality was assessed, independently by review authors. Additional information was sought from study authors when necessary. Results are presented using weighted MDs for outcomes measured by the same scale and SMDs for outcomes measured by different scales. Post-test scores were used. In cases of statistically significant baseline difference, we used change scores. | Five studies (175 participants) were included. There is insufficient evidence of high quality to support the effect of music therapy on QoL of people in end-of-life care. Given the limited number of studies and small sample sizes, more research is needed. No strong evidence was found for the effect of music therapy on pain or anxiety. These results were based on two small studies. There were insufficient data to examine the effect of music therapy on other physical, psychological, or social outcomes. | A limited number of studies suggest there may be a benefit of music therapy on the QoL of people in end-of-life care. However, the results stem from studies with a high risk of bias. More research is needed. |
| Vink et al | Music therapy for people with dementia | To assess the effects of music therapy in the treatment of behavioral, social, cognitive and emotional problems of older people with dementia, in relation to the type of music therapy intervention. | ALOIS, the specialized Register of the CDCIG was searched on April 14, 2010 using the terms: music therapy, music singing, sing, and auditory stimulation. Additional searches were also carried out on April 14, 2010 in the major health care databases MEDLINE, EMBASE, PsycINFO, CINAHL, and LILACS, trial registers and grey literature sources to ensure the search was as up-to-date and as comprehensive as possible. | Randomized controlled trials that reported clinically relevant outcomes associated with music therapy in treatment of behavioral, social, cognitive, and emotional problems of older people with dementia. | Two reviewers screened the retrieved studies independently for methodological quality. Data from accepted studies were independently extracted by the reviewers. | Ten studies were included. The methodological quality of the studies was generally poor, and the study results could not be validated or pooled for further analyses. | The methodological quality and the reporting of the included studies were too poor to draw any useful conclusions. |
| Bradt et al | Music interventions for mechanically ventilated patients | To examine the effects of music interventions with standard care versus standard care alone on anxiety and physiological responses in mechanically ventilated patients. | We searched CENTRAL (The Cochrane Library 2010, Issue 1) MEDLINE, CINAHL, AMED, EMBASE, PsycINFO, LILACS, Science Citation Index, | We included all RCTs and quasi-RCTs that compared music interventions and standard care with standard care alone for mechanically ventilated patients. | Two authors independently extracted the data and assessed the methodological quality. Additional information was sought from the trial researchers, when necessary. Results were presented using MDs for outcomes measured by the same scale and SMDs for outcomes measured by different scales. Post-test scores were used. In cases of significant baseline difference, we used change scores. | We included eight trials (213 participants). Listening to music was the main intervention used, and seven of the studies did not include a trained music therapist. Results indicated that listening to music may be beneficial for anxiety reduction in mechanically ventilated patients; however, these results need to be interpreted with caution due to the small sample size. Findings indicated that listening to music consistently reduced heart rate and respiratory rate, suggesting a relaxation response. No strong evidence was found for blood pressure reduction. Listening to music did not improve oxygen saturation level. No studies could be found that examined the effects of music interventions on QoL, patient satisfaction, post-discharge outcomes, mortality, or cost-effectiveness. | Listening to music may have a beneficial effect on heart rate, respiratory rate, and anxiety in mechanically ventilated patients. However, the quality of the evidence is not strong. Most studies examined the effects of listening to prerecorded music. More research is needed on the effects of music offered by a trained music therapist. |
| Cepeda et al | Music for pain relief | To evaluate the effects of music on acute, chronic, or cancer pain intensity, pain relief, and analgesic requirements. | We searched the Cochrane Library, MEDLINE, EMBASE, PsycINFO, LILACS, and the references in retrieved manuscripts. There was no language restriction. | We included RCTs that evaluated the effect of music on any type of pain in children or adults. We excluded trials that reported results of concurrent non-pharmacological therapies. | Data was extracted by two independent review authors. We calculated the MD in pain intensity levels, percentage of patients with at least 50% pain relief, and opioid requirements. We converted opioid consumption to morphine equivalents. To explore heterogeneity, studies that evaluated adults, children, acute, chronic, malignant, labor, procedural, or experimental pain were evaluated separately, as well as those studies in which patients chose the type of music. | Fifty-one studies involving 1,867 subjects exposed to music and 1,796 controls met inclusion criteria. In the 31 studies evaluating mean pain intensity there was a considerable variation in the effect of music, indicating statistical heterogeneity (I | Listening to music reduces pain intensity levels and opioid requirements, but the magnitude of these benefits is small and, therefore, its clinical importance unclear. |
| Bradt et al | Music therapy for acquired brain injury | To examine the effects of music therapy with standard care versus standard care alone or standard care combined with other therapies on gait, upper extremity function, communication, mood and emotions, social skills, pain, behavioral outcomes, activities of daily living, and adverse events. | We searched the Cochrane Stroke Group Trials Register (February 2010), the Cochrane Central Register of Controlled Trials (the Cochrane Library Issue 2, 2009), MEDLINE (July 2009), EMBASE (August 2009), CINAHL (July 2010) PsycINFO (July 2009), LILACS (August 2009), AMED (August 2009), and Science Citation Index (August 2009). We handsearched music therapy journals and conference proceedings, searched dissertation and specialist music databases, trials and research reference lists, and contacted experts and music therapy associations. There was no language restriction. | RCTs and quasi-RCTs that compared music therapy interventions and standard care with standard care alone or combined with other therapies for people older than 16 years of age who had acquired brain damage of a non-degenerative nature and were participating in treatment programs offered in hospital, outpatient, or community settings. | Two review authors independently assessed methodological quality and extracted data. We present results using MDs (using post-test scores), as all outcomes were measured with the same scale. | We included seven studies (184 participants). The results suggest that RAS may be beneficial for improving gait parameters in stroke patients, including gait velocity, cadence, stride length, and gait symmetry. These results were based on two studies that received a low risk of bias score. There were insufficient data to examine the effect of music therapy on other outcomes. | RAS may be beneficial for gait improvement in people with stroke. These results are encouraging, but more RCTs are needed before recommendations can be made for clinical practice. More research is needed to examine the effects of music therapy on other outcomes in people with acquired brain injury. |
| Gold et al | Music therapy for autistic spectrum disorder | To review the effects of music therapy for individuals with autistic spectrum disorders. | The following databases were searched: CENTRAL, 2005 (issue 3); MEDLINE (1966 to July 2004); EMBASE (1980 to July 2004); LILACS (1982 to July 2004); PsycINFO (1872 to July 2004); CINAHL, (1872 to July 2004); ERIC (1966 to July 2004); ASSIA (1987 to July 2004); Sociofle (1963 to July 2004); Dissertation Abstracts International (late 1960s to July 2004). These searches were supplemented by searching specific sources for music therapy literature and manual searches of reference lists. Personal contacts to some investigators were made. | All RCTs or controlled clinical trials comparing music therapy added to standard care to “placebo” therapy, no treatment, or standard care. | Studies were independently selected, quality assessed, and data extracted by two authors. Continuous outcomes were synthesized using an SMD to enable a meta-analysis combining different scales, and to facilitate the interpretation of effect sizes. Heterogeneity was assessed using the I | Three small studies were included (total n=24). These examined the short-term effect of brief music therapy interventions (daily sessions over 1 week) for autistic children. Music therapy was superior to “placebo” therapy with respect to verbal and gestural communicative skills (verbal, two RCTs, n=20, SMD 0.36, 95% CI 0.15–0.57; gestyrak, 2 RCTs, n=20, SMD 0.50, 95% CI 0.22–0.79). Effects on behavioral problems were not significant. | The included studies were of limited applicability to clinical practice. However, the findings indicate that music therapy may help children with autistic spectrum disorder to improve their communicative skills. More research is needed to examine whether the effects of music therapy are enduring, and to investigate the effects of music therapy in typical clinical practice. |
| Laopaiboon et al | Music during caesarean section under regional anesthesia for improving maternal and infant outcomes | To evaluate the effectiveness of music during cesarean section under regional anesthesia for improving clinical and psychological outcomes for mothers and infants. | We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 September 2008). | We included randomized controlled trials comparing music added to standard care during cesarean section under regional anesthesia to standard care alone. | Two review authors, Malinee Laopaiboon and Ruth Martis, independently assessed eligibility, risk of bias in included trials and extracted data. We analyzed continuous outcomes using an MD with a 95% CI. | One trial involving 76 women who planned to have their babies delivered by cesarean section met the inclusion criteria, but data were available for only 64 women. This trial was of low quality with unclear allocation concealment, and only a few main clinical outcomes reported for the women. The trial did not report any infant outcomes. It appears that music added to standard care during cesarean section under regional anesthesia had some impact on pulse rate at the end of maternal contact with the neonate in the intra-operative period (MD −7.50 fewer beats per minute, 95% CI 14.08 to −0.92) and after completion of skin suture for the cesarean section (MD −7.37 fewer beats per minute, 95% CI 13.37–1.37). There was also an improvement in the birth satisfaction score (maximum possible score of 35) (MD of 3.38, 95% CI 1.59–5.17). Effects on other outcomes were either not significant or not reported in the one included trial. | The findings indicate that music during planned cesarean section under regional anesthesia may improve pulse rate and birth satisfaction score. However, the magnitude of these benefits is small and the methodological quality of the one included trial is questionable. Therefore, the clinical significance of music is unclear. More research is needed to investigate the effects of music during cesarean section under regional anesthesia on both maternal and infant outcomes, in various ethnic pregnant women, and with adequate sample sizes. |
| Bradt and Dileo | Music for stress and anxiety reduction in coronary heart disease patients | To examine the effects of music interventions with standard care versus standard care alone on psychological and physiological responses in persons with CHD. | We searched CENTRAL, MEDLINE, CINAHL, EMBASE, PsycINFO, LILACS, Science Citation Index, | We included all RCTs that compared music interventions and standard care with standard care alone for persons with CHD. | Data were extracted and methodological quality was assessed, independently by the two reviewers. Additional information was sought from the trial researchers when necessary. Results are presented using weighted MDs for outcomes measured by the same scale and SMDs for outcomes measured by different scales. Post-test scores were used. In cases of significant baseline difference, we used change scores. | Twenty-three trials (1,461 participants) were included. Listening to music was the main intervention used, and 21 of the studies did not include a trained music therapist. Results indicated that listening to music has a moderate effect on anxiety in patients with CHD; however, results were inconsistent across studies. This review did not find strong evidence for reduction of psychological distress. Findings indicated that listening to music reduces heart rate, respiratory rate, and blood pressure. Studies that included two or more music sessions led to a small and consistent pain-reducing effect. No strong evidence was found for peripheral skin temperature. None of the studies considered hormone levels, and only one study considered QoL as an outcome variable. | Listening to music may have a beneficial effect on blood pressure, heart rate, respiratory rate, anxiety, and pain in persons with CHD. However, the quality of the evidence is not strong and the clinical significance unclear. Most studies examined the effects of listening to prerecorded music. More research is needed on the effect of music offered by a trained music therapist. |
| Maratos et al | Music therapy for depression | To examine the efficacy of music therapy with standard care compared with standard care alone among people with depression and to compare the effects of music therapy for people with depression against other psychological or pharmacological therapies. | CCDANCTR studies and CCDANCTR references were searched on November 7, 2007, and MEDLINE, PsycINFO, EMBASE, PsycLIT, PSYindex, and other relevant sites were searched in November 2006. Reference lists of retrieved articles were handsearched, as well as specialist music and arts therapies journals. | All RCTs comparing music therapy with standard care or other interventions for depression. | Data on participants, interventions, and outcomes were extracted and entered into a database independently by two review authors. The methodological quality of each study was also assessed independently by two review authors. The primary outcome was reduction in symptoms of depression, based on a continuous scale. | Five studies met the inclusion criteria of the review. Marked variations in the interventions offered and the populations studied meant that meta-analysis was not appropriate. Four of the five studies individually reported greater reduction in symptoms of depression among those randomized to music therapy than to those in standard care conditions. The fifth study, in which music therapy was used as an active control treatment, reported no significant change in mental state for music therapy compared with standard care. Dropout rates from music therapy conditions appeared to be low in all studies. | Findings from individual randomized trials suggest that music therapy is accepted by people with depression and is associated with improvements in mood. However, the small number and low methodological quality of studies mean that it is not possible to be confdent about its effectiveness. High quality trials evaluating the effects of music therapy on depression are required. |
| de Dreu et al | Rehabilitation, exercise therapy and music in patients with Parkinson’s disease: a meta-analysis of the effects of music-based movement therapy on walking ability, balance and quality of life | To study that people with PD benefit from MbM therapy when compared with conventional therapy or no therapy in terms of standing balance, transfers, gait performance, severity of freezing, and QoL. | We searched PubMed, EMBASE, Cochrane, CINAHL, and SPORTDiscus for articles published until 1st August, 2011. | The following selection criteria were applied: 1) people with PD were targeted, 2) the study was an RCT of high quality (PEDro score of >4), 3) the intervention contained MbM, and 4) the rhythmic cues were embedded in music. | Two reviewers extracted relevant data from the included studies. A meta-analysis of RCTs on the efficacy of MbM therapy, including individual rhythmic music training and partnered dance classes, was performed. Identified studies (N=6) were evaluated on methodological quality, and SESs were calculated. | Studies were generally small (total N=168). significant homogeneous SESs were found for the Berg Balance Scale, Timed Up and Go test, and stride length (SESs, 4.1, 2.2, and 0.11; | MbM therapy appears promising for the improvement of gait and gait-related activities in PD. Future studies should incorporate larger groups and focus on long-term compliance and follow-up. |
| Cogo-Moreira et al | Music education for improving reading skills in children and adolescents with dyslexia | To study the effectiveness of music education on reading skills (ie, oral reading skills, reading comprehension, reading fluency, phonological awareness, and spelling) in children and adolescents with dyslexia. | We searched the following electronic databases in June 2012: CENTRAL (2012, Issue 5), MEDLINE (1948 to May week 4 2012), EMBASE (1980 to 2012 week 22), CINAHL (searched June 7, 2012), LILACS (searched June 7, 2012), PsycINFO (1887 to May week 5 2012), ERIC (searched June 7, 2012), Arts and Humanities Citation Index (1970 to 6 June 2012), Conference Proceedings Citation Index – Social Sciences and Humanities (1990 to June 2012), and WorldCat (searched June 7, 2012). We also searched the WHO ICTRP and reference lists of studies. We did not apply any date or language limits. | We planned to include RCTs. We looked for studies that included at least one of our primary outcomes. The primary outcomes were related to the main domain of reading: oral reading skills, reading comprehension, reading fuency, phonological awareness, and spelling measured through validated instruments. The secondary outcomes were self-esteem and academic achievement. | Two authors (HCM and RBA) independently screened all titles and abstracts identified through the search strategy to determine their eligibility. For our analysis we had planned to use MD for continuous data, with 95% CIs, and to use the random-effects statistical model when the effect estimates of two or more studies could be combined in a meta-analysis. | We retrieved 851 references via the search strategy. No RCTs testing music education for the improvement of reading skills in children with dyslexia could be included in this review. | There is no evidence available from RCTs on which to base a judgment about the effectiveness of music education for the improvement of reading skills in children and adolescents with dyslexia. This uncertainty warrants further research via RCTs, involving an interdisciplinary team: musicians, hearing and speech therapists, psychologists, and physicians. |
| Drahota et al | Sensory environment on health-related outcomes of hospital patients | To assess the effect of hospital environments on adult patient health-related outcomes. | We searched: CENTRAL (last searched January 2006); MEDLINE (1902 to December 2006); EMBASE (January 1980 to February 2006); 14 other databases covering health, psychology, and the built environment; reference lists; and organization websites. This review is currently ongoing (MEDLINE last search October 2010), see Studies awaiting classification. | RCTs and non-randomized controlled trials, before-and-after studies, and interrupted times series of environmental interventions in adult hospital patients reporting health-related outcomes. | Two review authors independently undertook data extraction and “risk of bias” assessment. We contacted authors to obtain missing information. For continuous variables, we calculated an MD or SMD, and 95% CIs for each study. For dichotomous variables, we calculated RR with 95% CI. When appropriate, we used a random-effects model of meta-analysis. Heterogeneity was explored qualitatively and quantitatively based on risk of bias, case mix, hospital visit characteristics, and country of study. | Overall, 102 studies were included in this review. Interventions explored were: “positive distracters”, to include aromas (two studies), audiovisual distractions (five studies), decoration (one study), and music (85 studies); interventions to reduce environmental stressors through physical changes, to include air quality (three studies), bedroom type (one study), flooring (two studies), furniture and furnishings (one study), lighting (one study), and temperature (one study); and multifaceted interventions (two studies). We did not find any studies meeting the inclusion criteria to evaluate: art, access to nature for example through hospital gardens, atriums, flowers, and plants, ceilings, interventions to reduce hospital noise, patient controls, technologies, way-finding aids, or the provision of windows. Overall, it appears that music may improve patient-reported outcomes such as anxiety; however, the benefit for physiological outcomes, and medication consumption has less support. There are few studies to support or refute the implementation of physical changes, and except for air quality, the included studies demonstrated that physical changes in the hospital environment at least did no harm. | Music may improve patient-reported outcomes in certain circumstances, so support for this relatively inexpensive intervention may be justified. For some environmental interventions, well designed research studies have yet to take place. |
| Chan et al | The effectiveness of music listening in reducing depressive symptoms in adults: a systematic review | To review trials of the effectiveness of listening to music in reducing depressive symptoms in adults, and identify areas requiring further study. | A comprehensive search strategy was employed to identify all published papers in English language between January 1989 and March 2010. We searched nine databases with initial search terms including “music”, “depression”, or “depressive symptoms”. | We searched the published literature for RCTs and quasi-experimental trials that included an intervention with music listening designed to reduce the depression level, compared with a control group. The intervention was music listening, it is defined as listening to music via any form of music device or live music, without the active involvement of a music therapist. | The data extracted included specific details about the interventions, populations, study methods, and outcomes of significance to the review question and specific objectives. Two studies were pooled together for meta-analysis due to similarity in outcome measures and intervention time points. | Listening to music over a period of time helps to reduce depressive symptoms in the adult population. Daily intervention does not seem to be superior over weekly intervention, and it is recommended that music listening sessions be conducted repeatedly over a time span of more than 3 weeks to allow an accumulative effect to occur. | All types of music can be used as listening material, depending on the preferences of the listener. It is recommended that the listeners are given choices over the kind of music they listen to. There is a need to conduct more studies, which replicate the designs used in the existing studies that met the inclusion criteria, on the level of efficacy of music listening and on the reduction of depressive symptoms for a more accurate meta-analysis of the findings and which would reflect with greater accuracy the significant effects that music has on the level of depressive symptoms. |
| Naylor et al | The effectiveness of music in pediatric healthcare: a systematic review of randomized controlled trials | To systematically review the effectiveness of music on pediatric health-related outcomes. | The following international electronic databases were searched on March 4, 2009: Ovid Medline (Medical Literature Analysis and Retrieval System Online), 1950 to February, week 3, 2009; EMBASE, 1980–2009 week 9; PsycINFO, 1967 to February, week 4, 2009; AMED (Allied and Complementary Medicine), 1985–February 2009; and CINAHL, 1983–2008. | Studies were included if they met the following six criteria: 1) examined the effectiveness of a music intervention; 2) involved a clinical population in a health care, research, or education setting; 3) involved children and adolescents between 1 and 18 years of age (or reported a mean age within this range); 4) used an RCT design (parallel or crossover); 5) reported at least one quantifiable outcome measure; and 6) was published between 1984 and 2009. | Data extraction includes information about each study (authorship, year of publication, country, recruitment setting, and experimental design), participants (sample size, sex, population, and age), intervention (treatment, delivery, participant involvement, and dosage), and quality rating. Because of heterogeneity in the study populations, interventions used, and outcome measures applied, it was neither feasible nor appropriate to conduct a meta-analysis. | Qualitative synthesis revealed significant improvements in one or more health outcomes within four of seven trials involving children with learning and developmental disorders; two of three trials involving children experiencing stressful life events; and four of five trials involving children with acute and/or chronic physical illness. No significant effects were found for two trials involving children with mood disorders and related psychopathology. | These findings offer limited qualitative evidence to support the effectiveness of music on health-related outcomes for children and adolescents with clinical diagnoses. Recommendations for establishing a consensus on research priorities and addressing methodological limitations are put forth to support the continued advancement of this popular intervention. |
| Irons et al | Singing for children and adults with cystic fibrosis | To evaluate the effects of a singing intervention in addition to usual therapy on the QoL, morbidity, respiratory muscle strength, and pulmonary function of children and adults with cystic fibrosis. | We searched the Group’s Cystic Fibrosis Trials Register, the CENTRAL, major allied complementary databases, and clinical trial registers. Handsearching for relevant conference proceedings and journals was also carried out. Date of search of trials register: September 2, 2009. Date of additional searches: September 17, 2009. | RCTs in which singing (as an adjunctive intervention) is compared with either a sham intervention or no singing in people with cystic fibrosis. | No trials were found that met the selection criteria. | No meta-analysis could be performed. | As no studies that met the criteria were found, this review is unable to support or refute the benefits of singing as a therapy for people with cystic fibrosis. Future RCTs are required to evaluate singing therapy for people with cystic fibrosis. |
| Irons et al | Singing for children and adults with bronchiectasis | To evaluate the effects of a singing intervention as a therapy on the QoL, morbidity, respiratory muscle strength, and pulmonary function of children and adults with bronchiectasis. | We searched the CAG trial register, CENTRAL, major allied complementary databases, and clinical trials registers. Professional organizations and individuals were also contacted. CAG performed searches in February 2011, and additional searches were carried out in February 2011. | RCTs in which singing (as an intervention) is compared with either a sham intervention or no singing in patients with bronchiectasis. | Two authors independently reviewed the titles, abstracts, and citations to assess potential relevance for full review. No eligible trials were identified and thus no data were available for analysis. | No meta-analysis could be performed. | In the absence of data, we cannot draw any conclusion to support or refute the adoption of singing as an intervention for people with bronchiectasis. Given the simplicity of the potentially beneficial intervention, future RCTs are required to evaluate singing therapy for people with bronchiectasis. |
| de Niet et al | Music-assisted relaxation to improve sleep quality: meta-analysis | To evaluate the efficacy of music-assisted relaxation for sleep quality in adults and elders with sleep complaints with or without a comorbid medical condition. | We conducted searches in EMBASE (1997–July 2008), Medline (1950–July 2008), Cochrane (2000–July 2008), PsycINFO (1987–July 2008) and CINAHL (1982–July 2008) for studies published in English, German, French, or Dutch. | We included published RCTs performed in an adult (18–60 years) or elderly (60 years or older) population with primary sleep complaints or sleep complaints comorbid with a medical condition. Studies involving active use of music, such as playing instruments, were excluded. | Pre and post-test means and standard deviations, demographic data, and condition properties were extracted from each included study. Review Manager 5.0.12 (The Cochrane Collaboration, Oxford, UK) was used to calculate the effect sizes of the individual studies and for calculation of the pooled MD. | Five RCTs with six treatment conditions and a total of 170 participants in intervention groups and 138 controls met our inclusion criteria. Music-assisted relaxation had a moderate effect on the sleep quality of patients with sleep complaints (SMD −0.74; 95% CI −0.96 to −0.46). Subgroup analysis revealed no statistically significant contribution of accompanying measures. | Music-assisted relaxation can be used without intensive investment in training and materials and is therefore cheap, easily available, and can be used by nurses to promote music-assisted relaxation to improve sleep quality. |
| Gold et al | Dose–response relationship in music therapy for people with serious mental disorders: systematic review and meta-analysis | To examine the benefits of music therapy for people with serious mental disorders. | A comprehensive search strategy was applied to identify all relevant studies. The trial database PsiTri, which contains structured information on published and unpublished clinical trials in mental health, based on multiple database searches as well as handsearches by several Cochrane groups, was searched for entries containing the word “music” in any field. PubMed was searched using its “Clinical Queries” search strategy designed to identify scientifically strong studies of therapy outcome, which was expanded with the MeSH term “Evaluation Studies”, and crossed with the MeSH terms “Music Therapy” and “Mentally Ill Persons” or “Mental Disorders”. | Study participants eligible for this review were adults with serious mental disorders diagnosed by an international classification system. This included psychotic disorders as well as some non-psychotic disorders such as borderline personality disorder, depression, bipolar disorder, and suicidality connected to a mental disorder. Studies were included only if participants were offered music therapy, according to the definition above. Most importantly, this excluded interventions of the “music medicine” type, where music alone is provided as a treatment, rather than using music as a medium within a psychotherapeutic process and relationship. Secondly, it had to be possible to disentangle music therapy from other therapies. | Results for the same type of outcome were combined across studies in a meta-analysis. Results of different outcomes were not combined. If the same outcome was measured with different scales in the same study, both using equally valid methods (in terms of rater blinding and standardization and validity of instrument), the average effect size of these measures was used. | Results showed that music therapy, when added to standard care, has strong and significant effects on global state, general symptoms, negative symptoms, depression, anxiety, functioning, and musical engagement. significant dose–effect relationships were identified for general, negative, and depressive symptoms, as well as functioning, with explained variance ranging from 73% to 78%. Small effect sizes for these outcomes are achieved after 3–10, large effects after 16–51 sessions. | The findings suggest that music therapy is an effective treatment which helps people with psychotic and non-psychotic severe mental disorders to improve global state, symptoms, and functioning. Slight improvements can be seen with a few therapy sessions, but longer courses or more frequent sessions are needed to achieve more substantial benefits. |
Abbreviations: ASSIA, Applied Social Sciences Index and Abstracts; BPRS, Brief Psychiatric Rating Scale; CAG, Cochrane Airways Group; CAIRSS, Computer-Assisted Information Retrieval System; CCDANCTR, Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register; CDCIG, Cochrane Dementia and Cognitive Improvement Group; CENTRAL, Cochrane Central Register of Controlled Trials; CHD, coronary heart disease; CI, confidence interval; CINAHL, Cumulative Index of Nursing and Allied Health Literature; ERIC, Education Resource Information Centre; Ham-D, Hamilton Depression Scale; ICTRP, International Clinical Trials Registry Platform; LILACS, Latin American and Caribbean Health Sciences Literature; MbM, music-based movement; MD, mean difference; MeSH, Medical Subject Headings; NIH, National Institutes of Health; NNT, number needed to treat; PANSS, Positive and Negative Symptoms Scale; PD, Parkinson’s disease; PEDro, Physiotherapy Evidence Database; QoL, quality of life; RAS, rhythmic auditory stimulation; RCT, randomized controlled trial; RR, risk ratio; SANS, Scale for the Assessment of Negative Symptoms; SDS, Self-rating Depression Scale; SDSI, Social Disability Schedule for Inpatients; SES, summary effect size; SMD, standardized mean difference; STAI-S, State-Trait Anxiety Inventory – State; UPDRS, Unifed Parkinson’s Disease Rating Scale; WHO, World Health Organization.
International classification of target diseases in each article
| Chapter | ICD code | Classification | Study (detail ICD code) |
|---|---|---|---|
| 1 | A00–B99 | Certain infectious and parasitic diseases | |
| 2 | C00–D48 | Neoplasms | Bradt et al |
| 3 | D50–D89 | Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism | |
| 4 | E00–E90 | Endocrine, nutritional and metabolic diseases | Irons et al |
| 5 | F00–F99 | Mental and behavioral disorders | Sinha et al |
| 6 | G00–G99 | Diseases of the nervous system | Bradt et al |
| 7 | H00–H59 | Diseases of the eye and adnexa | |
| 8 | H60–H95 | Diseases of the ear and mastoid process | |
| 9 | I00–I99 | Diseases of the circulatory system | Bradt and Dileo |
| 10 | J00–J99 | Diseases of the respiratory system | Bradt et al |
| 11 | K00–K93 | Diseases of the digestive system | |
| 12 | L00–L99 | Diseases of the skin and subcutaneous tissue | |
| 13 | M00–M99 | Diseases of the musculoskeletal system and connective tissue | |
| 14 | N00–N99 | Diseases of the genitourinary system | |
| 15 | O00–O99 | Pregnancy, childbirth and the puerperium | Laopaiboon et al |
| 16 | P00–P96 | Certain conditions originating in the perinatal period | |
| 17 | Q00–Q99 | Congenital malformations, deformations and chromosomal abnormalities | |
| 18 | R00–R99 | Symptoms, signs and abnormal clinical and laboratory finding not elsewhere classified | |
| 19 | S00–T98 | Injury, positioning and certain other consequences of external causes | |
| 20 | V00–Y98 | External causes of morbidity and mortality | |
| 21 | Z00–Z99 | Factors influencing health status and contact with health services | |
| 22 | U00–U99 | Code for special purpose | |
| – | Unidentification | Because many illnesses were mixed, we could not identify it | Bradt and Dileo, |
Abbreviation: ICD, International Classification of Diseases.
Brief summary of 21 systematic reviews
| Study | Published year | Intervention type | Meta-analysis | Object disease or symptom | Having effect or not | Adverse events |
|---|---|---|---|---|---|---|
| Sinha et al | 2011 | Auditory integration therapy and other sound therapies that involved listening to music modified by filtering (attenuating sounds at selected frequencies) and modulating (random alternating high and low sound) | Not performed | Autism spectrum disorders | Unclear | No study reported specific deterioration. |
| Mossler et al | 2011 | Music therapy (a systematic process of intervention wherein the therapist helps the client to promote health, using music experiences and the relationships that develop through them as dynamic forces of change) | Performed | Schizophrenia and schizophrenia-like disorders | Effective; improving their global state, mental state (including negative symptoms), and social functioning | No study reported specific deterioration. |
| Bradt et al | 2011 | All types of music therapy or music medicine | Performed | Cancer | May be effective; improving anxiety, pain, mood, and QoL | No study reported specific deterioration. |
| Bradt and Dileo | 2010 | All types of music therapy or music medicine | Performed | Advanced life-limiting illness | May be effective; improving QoL | No study reported specific deterioration. |
| Vink et al | 2003 | All types of music therapy or music medicine | Performed | Dementia | Unclear | No study reported specific deterioration. |
| Bradt et al | 2010 | All types of music therapy or music medicine | Performed | Mechanically ventilated patients | May be effective; improving heart rate, respiratory rate, and anxiety | No study reported specific deterioration. |
| Cepeda et al | 2006 | Listening to music (as defined by the investigator) | Performed | Acute, chronic, neuropathic, cancer, or experimental pain | May be effective; reducing pain intensity levels and opioid requirements | No study reported specific deterioration. |
| Bradt et al | 2010 | All types of music therapy or music medicine | Performed | Acquired brain injury | May be effective; improving gait parameters | No study reported specific deterioration. |
| Gold et al | 2006 | Music therapy delivered by a professional | Performed | Autistic spectrum disorders in children | May be effective; improving communicative skills | No study reported specific deterioration. |
| Laopaiboon et al | 2009 | All types of music therapy or music medicine | Performed | Cesarean section | May be effective; improving heart rate and birth satisfaction score | No study reported specific deterioration. |
| Bradt and Dileo | 2009 | Any form of participation in music (eg, listening to music, singing, and playing music) | Performed | Coronary heart disease | May be effective; improving blood pressure, heart rate, respiratory rate, anxiety, and pain | No study reported specific deterioration. |
| Maratos et al | 2008 | Music therapy provided by a certificated professional | Not performed | Depression | May be effective; accepted by people with depression and improving mood | No study reported specific deterioration. |
| de Dreu et al | 2012 | Music-based movement therapy (the form of individual gait training or in a group, partnered dance) | Performed | Parkinson’s disease | Effective; improving gait and gait-related activities | No study reported specific deterioration. |
| Cogo-Moreira et al | 2012 | Music education (individual or group music lessons or musical training) | No studies | Dyslexia | No evidence | Non-information due to no studies included in the review |
| Drahota et al | 2012 | Music listening | Performed | Hospital patients | May be effective; improving patient-reported outcomes such as anxiety | No study reported specific deterioration. |
| Chan et al | 2011 | Listening to music via any form of music device or live music, without the active involvement of a music therapist | Performed | Depressive symptoms | Effective; reducing depressive symptoms | No study reported specific deterioration. |
| Naylor et al | 2011 | Music as an intervention or therapy, regardless of delivery mode (ie, by a trained music therapist) | Performed | Various clinical condition | May be effective; improving health outcomes in children with learning and developmental disorder | No study reported specific deterioration. |
| Irons et al | 2010 | All types of music therapy or music medicine | No studies | Cystic fibrosis | No evidence | Non information due to no studies included in the review |
| Irons et al | 2010 | All types of singing programs | No studies | Bronchiectasis | No evidence | Non information due to no studies included in the review |
| de Niet et al | 2009 | Listening to music (CD/DVD) | Performed | Sleep complaints | Effective; improving sleep quality | No study reported specific deterioration. |
| Gold et al | 2009 | Music therapy (a systematic process of intervention wherein the therapist helps the client to promote health, using music experiences and the relationships that develop through them as dynamic forces of change) | Performed | Serious mental disorders | Effective; improve global state, symptoms, and functioning | No study reported specific deterioration. |
Abbreviation: QoL, quality of life
AMSTAR is a measurement tool created to assess the methodological quality of systematic reviews
| Total evaluation | N (%) | |
|---|---|---|
| 1. Was an “a priori” design provided? | □ Yes | 20 (95%) |
| □ No | 0 (0%) | |
| □ Can’t answer | 1 (5%) | |
| □ Not applicable | 0 (0%) | |
| 2. Was there duplicate study selection and data extraction? | □ Yes | 21 (100%) |
| □ No | 0 (0%) | |
| □ Can’t answer | 0 (0%) | |
| □ Not applicable | 0 (0%) | |
| 3. Was a comprehensive literature search performed? | □ Yes | 21 (100%) |
| □ No | 0 (0%) | |
| □ Can’t answer | 0 (0%) | |
| □ Not applicable | 0 (0%) | |
| 4. Was the status of publication (ie, grey literature) used as an inclusion criterion? | □ Yes | 14 (67%) |
| □ No | 6 (28%) | |
| □ Can’t answer | 0 (0%) | |
| □ Not applicable | 1 (5%) | |
| 5. Was a list of studies (included and excluded) provided? | □ Yes | 17 (81%) |
| □ No | 4 (19%) | |
| □ Can’t answer | 0 (0%) | |
| □ Not applicable | 0 (0%) | |
| 6. Were the characteristics of the included studies provided? | □ Yes | 18 (85%) |
| □ No | 1 (5%) | |
| □ Can’t answer | 0 (0%) | |
| □ Not applicable | 2 (10%) | |
| 7. Was the scientific quality of the included studies assessed and documented? | □ Yes | 19 (90%) |
| □ No | 0 (0%) | |
| □ Can’t answer | 0 (0%) | |
| □ Not applicable | 2 (10%) | |
| 8. Was the scientific quality of the included studies used appropriately in formulating conclusions? | □ Yes | 18 (85%) |
| □ No | 2 (10%) | |
| □ Can’t answer | 0 (0%) | |
| □ Not applicable | 1 (5%) | |
| 9. Were the methods used to combine the findings of studies appropriate? | □ Yes | 16 (76%) |
| □ No | 0 (0%) | |
| □ Can’t answer | 0 (0%) | |
| □ Not applicable | 5 (24%) | |
| 10. Was the likelihood of publication bias assessed? | □ Yes | 15 (71%) |
| □ No | 0 (0%) | |
| □ Can’t answer | 0 (0%) | |
| □ Not applicable | 6 (29%) | |
| 11. Was the conflict of interest stated? | □ Yes | 20 (95%) |
| □ No | 0 (0%) | |
| □ Can’t answer | 0 (0%) | |
| □ Not applicable | 1 (5%) |
Abbreviations: CENTRAL, Cochrane Central Register of Controlled Trials; MeSH, Medical Subject Headings; Can’t, can not.
Future research agenda to build evidence of music therapy
| Item | |
|---|---|
| 1. | Long-term effect |
| 2. | Consensus of the intervention framework such as type, frequency, time for each disease |
| 3. | Dose–response relationship |
| 4. | Description of cost |
| 5. | Development of the original checklist for music therapy |
Notes:
Reporting guidelines for intervention on each disease;
reporting guideline for research methodology on study plan, implementation, and description.
References to studies excluded in this review
| First author. Journal (Year) | Title | Reason for exclusion |
|---|---|---|
| Standley J. | Music therapy research in the NICU: an updated meta-analysis | Not SR based on RCTs |
| Wittwer JE. | Rhythmic auditory cueing to improve walking in patients with neurological conditions other than Parkinson’s disease – what is the evidence? | Not SR based on RCTs |
| Hurkmans J. | Music in the treatment of neurological language and speech disorders: a systematic review | Not SR based on RCTs |
| Burns DS. | Theoretical rationale for music selection in oncology intervention research: an integrative review | Not SR based on RCTs |
| Fredericks S. | Anxiety, depression, and self-management: a systematic review | Not SR based on RCTs |
| Galaal K. | Interventions for reducing anxiety in women undergoing colposcopy | Not treatment or rehabilitation |
| Pittman S. | Music intervention and preoperative anxiety: an integrative review | Not SR based on RCTs |
| Cogo-Moreia H. | Music education for improving reading skills in children and adolescents with dyslexia | Updated or replacement SR |
| Schmid W. | Home-based music therapy – a systematic overview of settings and conditions for an innovative service in healthcare | Not SR based on RCTs |
| Renner RM. | Pain control in first-trimester surgical abortion: a systematic review of randomized controlled trials | Not music therapy |
| de Niet GJ. | Review of systematic reviews about the efficacy of non-pharmacological interventions to improve sleep quality in insomnia | Not music therapy |
| Engwall M. | Music as a nursing intervention for postoperative pain: a systematic review | Not treatment or rehabilitation |
| Harting L. | Music for medical indications in the neonatal period: a systematic review of randomised controlled trials | Not treatment or rehabilitation |
| Bechtold ML. | Effect of music on patients undergoing colonoscopy: a meta-analysis of randomized controlled trials | Not treatment or rehabilitation |
| Klassen JA. | Music for pain and anxiety in children undergoing medical procedures: a systematic review of randomized controlled trials | Not treatment or rehabilitation |
| Tam WW. | Effect of music on procedure time and sedation during colonoscopy: a meta-analysis | Not treatment or rehabilitation |
| Gillen E. | Effects of music listening on adult patients’ pre-procedural state anxiety in hospital | Not treatment or rehabilitation |
| Dileo C. | Music for preoperative anxiety | Protocol |
| Mays KL. | Treating addiction with tunes: a systematic review of music therapy for the treatment of patients with addictions | Not SR based on RCTs |
| Klassen JA. | Music for pain and anxiety in children undergoing medical procedures: a systematic review of randomized controlled trials | Not treatment or rehabilitation |
| Galaal K. | Interventions for reducing anxiety in women undergoing colposcopy | Not treatment or rehabilitation |
| Rudin D. | Music in the endoscopy suite: a meta-analysis of randomized controlled studies | Not treatment or rehabilitation |
| Richards T. | The effect of music therapy on patients’ perception and manifestation of pain, anxiety, and patient satisfaction | Not SR based on RCTs |
| Vanderboom T. | Does music reduce anxiety during invasive procedures with procedural sedation? An integrative research review | Not SR based on RCTs |
| Lim PH. | Music as nursing intervention for pain in five Asian countries | Not SR based on RCTs |
| Ostermann T. | Music therapy in the treatment of multiple sclerosis: a comprehensive literature review | Not SR based on RCTs |
| Dileo C. | Effects of music and music therapy on medical patients: a meta-analysis of the research and implications for the future | Not SR based on RCTs |
| Sung HC. | Use of preferred music to decrease agitated behaviors in older people with dementia: a review of the literature | Not SR based on RCTs |
| Pelletier CL. | The effect of music on decreasing arousal due to stress: a meta-analysis | Not SR based on RCTs |
| Whipple J. | Music in intervention for children and adolescents with autism: a meta-analysis | Not SR based on RCTs |
| Wilkins MK. | Music intervention in the intensive care unit: a complementary therapy to improve patient outcomes | Not SR based on RCTs |
| Gold C. | Effects of music therapy for children and adolescents with psychopathology: a meta-analysis | Not SR based on RCTs |
| Silverman MJ. | The influence of music on the symptoms of psychosis: a meta-analysis | Not treatment or rehabilitation |
| Standley JM. | A meta-analysis of the efficacy of music therapy for premature infants | Not SR based on RCTs |
| Evans D. | The effectiveness of music as an intervention for hospital patients: a systematic review | Not SR based on RCTs |
| You ZY. | Meta-analysis of assisted music therapy for chronic schizophrenia | Reduplication study/error of selection |
| You ZY. | Meta-analysis of assisted music therapy for chronic schizophrenia | Updated or replacement SR |
| Evans D. | Music as an intervention for hospital patients: a systematic review | Not SR based on RCTs |
| Koger SM. | Music therapy for dementia symptoms | Updated or replacement SR |
| Koger SM. | Music therapy for dementia symptoms | Updated or replacement SR |
| Koger SM. | Is music therapy an effective intervention for dementia? A meta-analytic review of literature | Not SR based on RCTs |
Note:
Published and reformed in the same year.
Abbreviations: NICU, neonatal intensive care unit; RCT, randomized controlled trial; SR, systematic review.