Music Therapy in Infancy and Neurodevelopmental Outcomes in Preterm Children: A Secondary Analysis of the LongSTEP Randomized Clinical Trial.

Importance: Preterm children are at risk for neurodevelopment impairments. Objective: To evaluate the effect of a music therapy (MT) intervention (parent-led, infant-directed singing) for premature children during the neonatal intensive care unit (NICU) stay and/or after hospital discharge on language development at 24 months' corrected age (CA). Design, Setting, and Participants: This predefined secondary analysis followed participants in the LongSTEP (Longitudinal Study of Music Therapy's Effectiveness for Premature Infants and Their Caregivers) randomized clinical trial, which was conducted from August 2018 to April 2022 in 8 NICUs across 5 countries (Argentina, Colombia, Israel, Norway, and Poland) and included clinic follow-up visits and extended interventions after hospital discharge. Intervention: Participants were children born preterm (<35 weeks' gestation) and their parents. Participants were randomized at enrollment to MT with standard care (SC) or SC alone; they were randomized to MT or SC again at discharge. The MT was parent-led, infant-directed singing tailored to infant responses and supported by a music therapist and was provided 3 times weekly in the NICU and/or in 7 sessions across 6 months after discharge. The SC consisted of early intervention methods of medical, nursing, and social services, without MT. Main Outcome and Measures: Primary outcome was language development, as measured by the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) language composite score, with the remaining BSID-III composite and subscale scores as the secondary outcomes. Group differences in treatment effects were assessed using linear mixed-effects models using all available data. Results: Of 206 participants (103 female infants [50%]; mean [SD] GA, 30.5 [2.7] weeks), 51 were randomized to MT and 53 to SC at enrollment; at discharge, 52 were randomized to MT and 50 to SC. A total of 112 (54%) were retained at the 24 months' CA follow-up. Most participants (79 [70%] to 93 [83%]) had BSID-III scores in the normal range (≥85). Mean differences for the language composite score were -2.36 (95% CI, -12.60 to 7.88; P = .65) for the MT at NICU with postdischarge SC group, 2.65 (95% CI, -7.94 to 13.23; P = .62) for the SC at NICU and postdischarge MT group, and -3.77 (95% CI, -13.97 to 6.43; P = .47) for the MT group at both NICU and postdischarge. There were no significant effects for cognitive or motor development. Conclusions and Relevance: This secondary analysis did not confirm an effect of parent-led, infant-directed singing on neurodevelopment in preterm children at 24 months' CA; wide CIs suggest, however, that potential effects cannot be excluded. Future research should determine the MT approaches, implementation time, and duration that are effective in targeting children at risk for neurodevelopmental impairments and introducing broader measurements for changes in brain development. Trial Registration: ClinicalTrials.gov Identifier: NCT03564184.

Music therapy and weight gain in preterm infants: Secondary analysis of the randomized controlled LongSTEP trial.

OBJECTIVES: This study assessed the association between MT and weight gain among preterm infants hospitalized in Neonatal Intensive Care Units. METHODS: Data collected during the international, randomized, Longitudinal Study of Music Therapy's Effectiveness for Premature Infants and their Caregivers (LongSTEP) study were compared between the MT group and the standard care (SC) group. Weights were recorded at birth, enrollment, and discharge. Weight percentiles, Z-scores, weight gain velocity, and extrauterine growth restriction (EUGR) were calculated. RESULTS: Among 201 preterm infants included, no significant differences in weight parameters (weight, weight percentiles, weight Z-scores; all p ≥ 0.23) were found between the MT group (n = 104) and the SC (n = 97) group at birth, enrollment, or discharge. No statistical differences in EUGR represented by change in Z-scores from birth to discharge were recorded between MT and SC (0.8 vs. 0.7). Among perinatal parameters, younger gestational age (p = 0.005) and male sex (p = 0.012) were associated with increased risk of EUGR at discharge. Antenatal steroid treatment, systemic infection, bronchopulmonary dysplasia, neurological morbidities, retinopathy of prematurity, necrotizing enterocolitis, parental factors (amount of skin-to-skin care, bonding, anxiety, and depression questionnaire scores), and type of enteral nutrition did not significantly influence weight gain parameters (all p > 0.05). CONCLUSIONS: In the LongSTEP study, MT for preterm infants and families was not associated with better weight parameters compared to the SC group. The degree of prematurity remains the main risk factor for unfavorable weight parameters.

Music for autism: a protocol for an international randomized crossover trial on music therapy for children with autism.

The notion of a connection between autism and music is as old as the first reported cases of autism, and music has been used as a therapeutic tool for many decades. Music therapy holds promise as an intervention for individuals with autism, harnessing their strengths in music processing to enhance communication and expression. While previous randomized controlled trials have demonstrated positive outcomes in terms of global improvement and quality of life, their reliance on psychological outcomes restricts our understanding of underlying mechanisms. This paper introduces the protocol for the Music for Autism study, a randomized crossover trial designed to investigate the effects of a 12-week music therapy intervention on a range of psychometric, neuroimaging, and biological outcomes in school-aged children with autism. The protocol builds upon previous research and aims to both replicate and expand upon findings that demonstrated improvements in social communication and functional brain connectivity following a music intervention. The primary objective of this trial is to determine whether music therapy leads to improvements in social communication and functional brain connectivity as compared to play-based therapy. In addition, secondary aims include exploring various relevant psychometric, neuroimaging, and biological outcomes. To achieve these objectives, we will enroll 80 participants aged 6-12 years in this international, assessor-blinded, crossover randomized controlled trial. Each participant will be randomly assigned to receive either music therapy or play-based therapy for a period of 12 weeks, followed by a 12-week washout period, after which they will receive the alternate intervention. Assessments will be conducted four times, before and after each intervention period. The protocol of the Music for Autism trial provides a comprehensive framework for studying the effects of music therapy on a range of multidimensional outcomes in children with autism. The findings from this trial have the potential to contribute to the development of evidence-based interventions that leverage strengths in music processing to address the complex challenges faced by individuals with autism. Clinical Trial Registration: Clinicaltrials.gov identifier NCT04936048.

Effect of Music Therapy on Parent-Infant Bonding Among Infants Born Preterm: A Randomized Clinical Trial.

Importance: Parent-infant bonding contributes to long-term infant health but may be disrupted by preterm birth. Objective: To determine if parent-led, infant-directed singing, supported by a music therapist and initiated in the neonatal intensive care unit (NICU), improves parent-infant bonding at 6 and 12 months. Design, Setting, and Participants: This randomized clinical trial was conducted in level III and IV NICUs in 5 countries between 2018 and 2022. Eligible participants were preterm infants (under 35 weeks' gestation) and their parents. Follow-up was conducted across 12 months (as part of the LongSTEP study) at home or in clinics. Final follow-up was conducted at 12 months' infant-corrected age. Data were analyzed from August 2022 to November 2022. Intervention: Participants randomized to music therapy (MT) plus standard care or standard care alone during NICU admission, or to MT plus standard care or standard care alone postdischarge, using computer-generated randomization (ratio 1:1, block sizes of 2 or 4 varying randomly), stratified by site (51 allocated to MT NICU, 53 to MT postdischarge, 52 to both, and 50 to neither). MT consisted of parent-led, infant-directed singing tailored to infant responses and supported by a music therapist 3 times per week throughout hospitalization or 7 sessions across 6 months' postdischarge. Main Outcome and Measure: Primary outcome was mother-infant bonding at 6 months' corrected age, measured by the Postpartum Bonding Questionnaire (PBQ), with follow-up at 12 months' corrected age, and analyzed intention-to-treat as group differences. Results: Of 206 enrolled infants with 206 mothers (mean [SD] age, 33 [6] years) and 194 fathers (mean [SD] age, 36 [6] years) randomized at discharge, 196 (95.1%) completed assessments at 6 months and were analyzed. Estimated group effects for PBQ at 6 months' corrected age were 0.55 (95% CI, -2.20 to 3.30; P = .70) for MT in the NICU, 1.02 (95% CI, -1.72 to 3.76; P = .47) for MT postdischarge, and -0.20 (95% CI, -4.03 to 3.63; P = .92) for the interaction (12 months: MT in NICU, 0.17; 95% CI, -2.71 to 3.05; P = .91; MT postdischarge, 1.78; 95% CI, -1.13 to 4.70; P = .24; interaction, -1.68; 95% CI, -5.77 to 2.41; P = .42). There were no clinically important between-group differences for secondary variables. Conclusions and Relevance: In this randomized clinical trial, parent-led, infant-directed singing did not have clinically important effects on mother-infant bonding, but was safe and well-accepted. Trial Registration: ClinicalTrials.gov Identifier: NCT03564184.

Process-outcome relations in music therapy versus music listening for people with schizophrenia viewed through a mediational model: the role of the therapeutic alliance.

Objectives: Examine whether change in clinical outcomes for patients with schizophrenia and negative symptoms randomized to either Music Therapy (MT) or Music Listening (ML) is associated to moderators and mediators, with focus on alliance, attendance and dropout. Method: An exploratory post-hoc analysis of data from an original randomized controlled trial (RCT) investigating the effect of MT vs. ML for people with schizophrenia and negative symptoms. Inclusion to the study was implemented through screening of referred patients for symptoms of schizophrenia and negative symptoms. A total of 57 patients were randomly assigned, 28 to MT and 29 to ML. Session logs and notes were included in this study. Statistical analysis investigated moderator and mediator relation to outcome variables: Negative symptoms, functioning, quality of life, and retention to treatment. Results: On average, participants in MT attended 18.86 sessions (SD = 7.17), whereas those in ML attended 12.26 (SD = 9.52), a statistically significant difference (p = 0.0078). Dropout at 25 weeks was predicted by intervention, with dropout being 2.65 (SE = 1.01) times more likely in ML than in music therapy (p = 0.009). Helping alliance score at weeks was explained by intervention, with mean score being 0.68 (SE = 0.32) points lower in ML than in MT (p = 0.042). The number of sessions attended was also explained by intervention, with participants in ML attending on average 6.17 (SE = 2.24) fewer sessions than those randomized to MT (p = 0.008). Though both groups improved significantly, improvements in negative symptoms, depression, and functioning tended to be higher in ML, whereas improvements in alliance and quality of life tended to be higher in MT. Conclusion: The analysis could not detect a direct link between helping alliance score and outcome variables. However, the analysis documented a stronger alliance developed in the MT group, a lower dropout rate, as well as higher attendance in treatment.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02942459.

Treatment fidelity in a pragmatic clinical trial of music therapy for premature infants and their parents: the LongSTEP study.

BACKGROUND: Treatment fidelity (TF) refers to methodological strategies used to monitor and enhance the reliability and validity of interventions. We evaluated TF in a pragmatic RCT of music therapy (MT) for premature infants and their parents. METHODS: Two hundred thirteen families from seven neonatal intensive care units (NICUs) were randomized to receive standard care, or standard care plus MT during hospitalization, and/or during a 6-month period post-discharge. Eleven music therapists delivered the intervention. Audio and video recordings from sessions representing approximately 10% of each therapists' participants were evaluated by two external raters and the corresponding therapist using TF questionnaires designed for the study (treatment delivery (TD)). Parents evaluated their experience with MT at the 6-month assessment with a corresponding questionnaire (treatment receipt (TR)). All items as well as composite scores (mean scores across items) were Likert scales from 0 (completely disagree) to 6 (completely agree). A threshold for satisfactory TF scores (≥4) was used in the additional analysis of dichotomized items. RESULTS: Internal consistency evaluated with Cronbach's alpha was good for all TF questionnaires (α ≥ 0.70), except the external rater NICU questionnaire where it was slightly lower (α 0.66). Interrater reliability measured by intraclass correlation coefficient (ICC) was moderate (NICU 0.43 (CI 0.27, 0.58), post-discharge 0.57 (CI 0.39, 0.73)). Gwet's AC for the dichotomized items varied between 0.32 (CI 0.10, 0.54) and 0.72 (CI 0.55, 0.89). Seventy-two NICU and 40 follow-up sessions with 39 participants were evaluated. Therapists' mean (SD) TD composite score was 4.88 (0.92) in the NICU phase and 4.95 (1.05) in the post-discharge phase. TR was evaluated by 138 parents. The mean (SD) score across intervention conditions was 5.66 (0.50). CONCLUSIONS: TF questionnaires developed to assess MT in neonatal care showed good internal consistency and moderate interrater reliability. TF scores indicated that therapists across countries successfully implemented MT in accordance with the protocol. The high treatment receipt scores indicate that parents received the intervention as intended. Future research in this area should aim to improve the interrater reliability of TF measures by additional training of raters and improved operational definitions of items. TRIAL REGISTRATION: Longitudinal Study of music Therapy's Effectiveness for Premature infants and their caregivers - "LongSTEP". CLINICALTRIALS: gov Identifier: NCT03564184. Registered on June 20, 2018.

Clinical effectiveness of music interventions for dementia and depression in elderly care (MIDDEL): Australian cohort of an international pragmatic cluster-randomised controlled trial.

BACKGROUND: Dementia and depression are highly prevalent and comorbid conditions among older adults living in care homes and are associated with individual distress and rising societal costs. Effective, scalable, and feasible interventions are needed. Music interventions have shown promising effects, but the current evidence base is inconclusive. The present study aimed to determine the effectiveness of two different music interventions on the depressive symptoms of people with dementia living in residential aged care. METHODS: We implemented a 2 × 2 factorial cluster-randomised controlled trial to determine whether group music therapy (GMT) is more effective than no GMT with standard care, or recreational choir singing (RCS) is more effective than no RCS with standard care, for reducing depressive symptoms and other secondary outcomes in people with dementia with mild to severe depressive symptoms living in residential aged care. Care home units with at least ten residents were allocated to GMT, RCS, GMT plus RCS, or standard care, using a computer-generated list with block randomisation (block size four). The protocolised interventions were delivered by music therapists (GMT) and community musicians (RCS). The primary outcome was Montgomery-Åsberg Depression Rating Scale score at 6 months, assessed by a masked assessor and analysed on an intention-to-treat basis using linear mixed-effects models, which examined the effects of GMT versus no-GMT and RCS versus no-RCS, as well as interaction effects of GMT and RCS. We report on the Australian cohort of an international trial. This trial is registered with ClinicalTrials.gov, NCT03496675, and anzctr.org.au, ACTRN12618000156280. FINDINGS: Between June 15, 2018, and Feb 18, 2020, we approached 12 RAC facilities with 26 eligible care home units and, excluding six units who could not be enrolled due to COVID-19 lockdowns, we screened 818 residents. Between July 18, 2018, and Nov 26, 2019, 20 care home units were randomised (318 residents). Recruitment ceased on March 17, 2020, due to COVID-19. The primary endpoint, available from 20 care home units (214 residents), suggested beneficial effects of RCS (mean difference -4·25, 95% CI -7·89 to -0·62; p=0·0221) but not GMT (mean difference -0·44, -4·32 to 3·43; p=0·8224). No related serious adverse events occurred. INTERPRETATION: Our study supports implementing recreational choir singing as a clinically relevant therapeutic intervention in reducing depressive symptoms for people with dementia in the Australian care home context. FUNDING: National Health and Medical Research Council, Australia.

Putting music to trial: Consensus on key methodological challenges investigating music-based rehabilitation.

Major advances in music neuroscience have fueled a growing interest in music-based neurological rehabilitation among researchers and clinicians. Musical activities are excellently suited to be adapted for clinical practice because of their multisensory nature, their demands on cognitive, language, and motor functions, and music's ability to induce emotions and regulate mood. However, the overall quality of music-based rehabilitation research remains low to moderate for most populations and outcomes. In this consensus article, expert panelists who participated in the Neuroscience and Music VII conference in June 2021 address methodological challenges relevant to music-based rehabilitation research. The article aims to provide guidance on challenges related to treatment, outcomes, research designs, and implementation in music-based rehabilitation research. The article addresses how to define music-based rehabilitation, select appropriate control interventions and outcomes, incorporate technology, and consider individual differences, among other challenges. The article highlights the value of the framework for the development and evaluation of complex interventions for music-based rehabilitation research and the need for stronger methodological rigor to allow the widespread implementation of music-based rehabilitation into regular clinical practice.

Demographic and clinical profile of residents living with dementia and depressive symptoms in Australian private residential aged care: Data from the Music Interventions for Dementia and Depression in ELderly care (MIDDEL) cluster-randomised controlled trial.

OBJECTIVES: 1) To describe the demographic and clinical characteristics of residents with dementia and depressive symptoms in the Australian private residential aged care (RAC) context; and 2) to investigate the association between neuropsychiatric symptoms, depression and quality of life and their interactions with dementia severity. METHODS: This study examined the baseline demographic and clinical data from the Australian arm of the Music Interventions for Dementia and Depression in ELderly care (MIDDEL) study, a multinational, cluster-randomised controlled trial. Demographic characteristics, neuropsychiatric symptoms, depression, quality of life and dementia severity were collected in 330 residents of 12 private RAC facilities across Melbourne, Australia. Descriptive statistics, the Kruskal-Wallis test and the Pearson Χ2 test were used to describe and compare the demographic and clinical characteristics according to dementia severity. The association between clinical characteristics and dementia severity was examined using linear regression analyses. RESULTS: Residents' mean age was 86.5 years, 69% were female, and 44.2% had severe dementia. There were no significant differences between the dementia severity groups on age, sex and education. Residents with severe dementia were more likely to have a diagnosis of Alzheimer's disease (40.3%) and be born overseas (46.8%). Higher levels of neuropsychiatric symptoms, distress and depressive symptoms, and lower quality of life were associated with more severe dementia. CONCLUSIONS: The findings from our study highlight the diverse and complex care needs of people living with dementia in the Australian private RAC setting, which can be used to inform targeted, person-centred dementia care planning, staff training and allocation of resources.

Study protocol for the Alzheimer and music therapy study: An RCT to compare the efficacy of music therapy and physical activity on brain plasticity, depressive symptoms, and cognitive decline, in a population with and at risk for Alzheimer's disease.

BACKGROUND: There is anecdotal evidence for beneficial effects of music therapy in patients with Alzheimer's Disease (AD). However, there is a lack of rigorous research investigating this issue. The aim of this study is to evaluate the effects of music therapy and physical activity on brain plasticity, mood, and cognition in a population with AD and at risk for AD. METHODS: One-hundred and thirty-five participants with memory complaints will be recruited for a parallel, three-arm Randomized Controlled Trial (RCT). Inclusion criteria are a diagnosis of mild (early) AD or mild cognitive impairment (MCI), or memory complaints without other neuropsychiatric pathology. Participants are randomised into either a music therapy intervention (singing lessons), an active control group (physical activity) or a passive control group (no intervention) for 12 months. The primary outcomes are the brain age gap, measured via magnetic resonance imaging (MRI), and depressive symptoms. Secondary outcomes include cognitive performance, activities of daily living, brain structure (voxel-based morphometry and diffusion tensor imaging), and brain function (resting-state functional MRI). TRIAL STATUS: Screening of participants began in April 2018. A total of 84 participants have been recruited and started intervention, out of which 48 participants have completed 12 months of intervention and post-intervention assessment. DISCUSSION: Addressing the need for rigorous longitudinal data for the effectiveness of music therapy in people with and at risk for developing AD, this trial aims to enhance knowledge regarding cost-effective interventions with potentially high clinical applicability. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03444181, registered on February 23, 2018.

Music therapy for autistic people.

BACKGROUND: Social interaction and social communication are among the central areas of difficulty for autistic people. Music therapy uses music experiences and the relationships that develop through them to enable communication and expression, thus attempting to address some of the core problems of autistic people. Music therapy has been applied in autism since the early 1950s, but its availability to autistic individuals varies across countries and settings. The application of music therapy requires specialised academic and clinical training which enables therapists to tailor the intervention to the specific needs of the individual. The present version of this review on music therapy for autistic people is an update of the previous Cochrane review update published in 2014 (following the original Cochrane review published in 2006). OBJECTIVES: To review the effects of music therapy, or music therapy added to standard care, for autistic people. SEARCH METHODS: In  August 2021, we searched  CENTRAL, MEDLINE, Embase, eleven other databases and two trials registers. We also ran citation searches, checked reference lists, and contacted study authors to identify additional studies. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-randomised trials and controlled clinical trials comparing music therapy (or music therapy alongside standard care) to 'placebo' therapy, no treatment, or standard care for people with a diagnosis of autism spectrum disorder were considered for inclusion. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Four authors independently selected studies and extracted data from all included studies. We synthesised the results of included studies in meta-analyses. Four authors independently assessed risk of bias (RoB) of each included study using the original RoB tool as well as the certainty of evidence using GRADE.   MAIN RESULTS: We included 16 new studies in this update which brought the total number of included studies to 26 (1165 participants). These studies examined the short- and medium-term effect of music therapy (intervention duration: three days to eight months) for autistic people in individual or group settings. More than half of the studies were conducted in North America or Asia. Twenty-one studies included children aged from two to 12 years. Five studies included children and adolescents, and/or young adults. Severity levels, language skills, and cognition were widely variable across studies. Measured immediately post-intervention, music therapy compared with 'placebo' therapy or standard care was more likely to positively effect global improvement (risk ratio (RR) 1.22, 95% confidence interval (CI) 1.06 to 1.40; 8 studies, 583 participants; moderate-certainty evidence; number needed to treat for an additional beneficial outcome (NNTB) = 11 for low-risk population, 95% CI 6 to 39; NNTB = 6 for high-risk population, 95% CI 3 to 21) and to slightly increase quality of life (SMD 0.28, 95% CI 0.06 to 0.49; 3 RCTs, 340 participants; moderate-certainty evidence, small to medium effect size). In addition, music therapy probably results in a large reduction in total autism symptom severity (SMD -0.83, 95% CI -1.41 to -0.24; 9 studies, 575 participants; moderate-certainty evidence). No clear evidence of a difference between music therapy and comparison groups at immediately post-intervention was found for social interaction (SMD 0.26, 95% CI -0.05 to 0.57, 12 studies, 603 participants; low-certainty evidence); non-verbal communication (SMD 0.26, 95% CI -0.03 to 0.55; 7 RCTs, 192 participants; low-certainty evidence); and verbal communication (SMD 0.30, 95% CI -0.18 to 0.78; 8 studies, 276 participants; very low-certainty evidence). Two studies investigated adverse events with one (36 participants) reporting no adverse events; the other study found no differences between music therapy and standard care immediately post-intervention (RR 1.52, 95% CI 0.39 to 5.94; 1 study, 290 participants; moderate-certainty evidence).  AUTHORS' CONCLUSIONS: The findings of this updated review provide evidence that music therapy is probably associated with an increased chance of global improvement for autistic people, likely helps them to improve total autism severity and quality of life, and probably does not increase adverse events immediately after the intervention. The certainty of the evidence was rated as 'moderate' for these four outcomes, meaning that we are moderately confident in the effect estimate. No clear evidence of a difference was found for social interaction, non-verbal communication, and verbal communication measured immediately post-intervention. For these outcomes, the certainty of the evidence was rated as 'low' or 'very low', meaning that the true effect may be substantially different from these results. Compared with earlier versions of this review, the new studies included in this update helped to increase the certainty and applicability of this review's findings through larger sample sizes, extended age groups, longer periods of intervention and inclusion of follow-up assessments, and by predominantly using validated scales measuring generalised behaviour (i.e. behaviour outside of the therapy context). This new evidence is important for autistic individuals and their families as well as for policymakers, service providers and clinicians, to help in decisions around the types and amount of intervention that should be provided and in the planning of resources. The applicability of the findings is still limited to the age groups included in the studies, and no direct conclusions can be drawn about music therapy in autistic individuals above the young adult age. More research using rigorous designs, relevant outcome measures, and longer-term follow-up periods is needed to corroborate these findings and to examine whether the effects of music therapy are enduring.

Music therapy for people with substance use disorders.

BACKGROUND: Substance use disorder (SUD) is the continued use of one or more psychoactive substances, including alcohol, despite negative effects on health, functioning, and social relations. Problematic drug use has increased by 10% globally since 2013, and harmful use of alcohol is associated with 5.3% of all deaths. Direct effects of music therapy (MT) on problematic substance use are not known, but it may be helpful in alleviating associated psychological symptoms and decreasing substance craving. OBJECTIVES: To compare the effect of music therapy (MT) in addition to standard care versus standard care alone, or to standard care plus an active control intervention, on psychological symptoms, substance craving, motivation for treatment, and motivation to stay clean/sober. SEARCH METHODS: We searched the following databases (from inception to 1 February 2021): the Cochrane Drugs and Alcohol Specialised Register; CENTRAL; MEDLINE (PubMed); eight other databases, and two trials registries. We handsearched reference lists of all retrieved studies and relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials comparing MT plus standard care to standard care alone, or MT plus standard care to active intervention plus standard care for people with SUD. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included 21 trials involving 1984 people. We found moderate-certainty evidence of a medium effect favouring MT plus standard care over standard care alone for substance craving (standardised mean difference (SMD) -0.66, 95% confidence interval (CI) -1.23 to -0.10; 3 studies, 254 participants), with significant subgroup differences indicating greater reduction in craving for MT intervention lasting one to three months; and small-to-medium effect favouring MT for motivation for treatment/change (SMD 0.41, 95% CI 0.21 to 0.61; 5 studies, 408 participants). We found no clear evidence of a beneficial effect on depression (SMD -0.33, 95% CI -0.72 to 0.07; 3 studies, 100 participants), or motivation to stay sober/clean (SMD 0.22, 95% CI -0.02 to 0.47; 3 studies, 269 participants), though effect sizes ranged from large favourable effect to no effect, and we are uncertain about the result. There was no evidence of beneficial effect on anxiety (mean difference (MD) -0.17, 95% CI -4.39 to 4.05; 1 study, 60 participants), though we are uncertain about the result. There was no meaningful effect for retention in treatment for participants receiving MT plus standard care as compared to standard care alone (risk ratio (RR) 0.99, 95% 0.93 to 1.05; 6 studies, 199 participants). There was a moderate effect on motivation for treatment/change when comparing MT plus standard care to another active intervention plus standard care (SMD 0.46, 95% CI -0.00 to 0.93; 5 studies, 411 participants), and certainty in the result was moderate. We found no clear evidence of an effect of MT on motivation to stay sober/clean when compared to active intervention, though effect sizes ranged from large favourable effect to no effect, and we are uncertain about the result (MD 0.34, 95% CI -0.11 to 0.78; 3 studies, 258 participants). There was no clear evidence of effect on substance craving (SMD -0.04, 95% CI -0.56 to 0.48; 3 studies, 232 participants), depression (MD -1.49, 95% CI -4.98 to 2.00; 1 study, 110 participants), or substance use (RR 1.05, 95% CI 0.85 to 1.29; 1 study, 140 participants) at one-month follow-up when comparing MT plus standard care to active intervention plus standard care. There were no data on adverse effects. Unclear risk of selection bias applied to most studies due to incomplete description of processes of randomisation and allocation concealment. All studies were at unclear risk of detection bias due to lack of blinding of outcome assessors for subjective outcomes (mostly self-report). We judged that bias arising from such lack of blinding would not differ between groups. Similarly, it is not possible to blind participants and providers to MT. We consider knowledge of receiving this type of therapy as part of the therapeutic effect itself, and thus all studies were at low risk of performance bias for subjective outcomes.  We downgraded all outcomes one level for imprecision due to optimal information size not being met, and two levels for outcomes with very low sample size.  AUTHORS' CONCLUSIONS: Results from this review suggest that MT as 'add on' treatment to standard care can lead to moderate reductions in substance craving and can increase motivation for treatment/change for people with SUDs receiving treatment in detoxification and short-term rehabilitation settings. Greater reduction in craving is associated with MT lasting longer than a single session. We have moderate-to-low confidence in our findings as the included studies were downgraded in certainty due to imprecision, and most included studies were conducted by the same researcher in the same detoxification unit, which considerably impacts the transferability of findings.

The Impact of Music on Stress Biomarkers: Protocol of a Substudy of the Cluster-Randomized Controlled Trial Music Interventions for Dementia and Depression in ELderly Care (MIDDEL).

Recently, a large cluster-randomized controlled trial was designed-Music Interventions for Dementia and Depression in ELderly care (MIDDEL)-to assess the effectiveness of music interventions on depression in care home residents with dementia (ClinicalTrials.gov NCT03496675). To understand the pathophysiological mechanisms, we observed the effect of repeated music interventions on stress in this population since chronic stress was associated with depression and an increased risk for dementia. An exploratory study was designed to assess: (1) changes in hair cortisol concentrations as an indicator of longer-term stress; (2) whether baseline stress is a predictor of therapy outcome; (3) pre- and post-treatment effects on salivary α-amylase and cortisol response as an indicator of immediate stress in 180-200 care home residents with dementia and depressive symptoms who partake in the MIDDEL trial. Insights into mediatory effects of stress to explain the effect of music interventions will be gained. Hair cortisol concentrations were assessed at baseline and at 3, 6, and 12 months along with the Perceived Stress Scale. Salivary α-amylase and cortisol concentrations were assessed at 1, 3, and 6 months. Saliva was collected just before a session and 15 and 60 min after a session, along with a stress Visual Analogue Scale.

Short-term Music Therapy for Families With Preterm Infants: A Randomized Trial.

OBJECTIVES: To evaluate short-term effects of music therapy (MT) for premature infants and their caregivers on mother-infant bonding, parental anxiety, and maternal depression. METHODS: Parallel, pragmatic, randomized controlled-trial conducted in 7 level III NICUs and 1 level IV NICU in 5 countries enrolling premature infants (<35 weeks gestational age at birth) and their parents. MT included 3 sessions per week with parent-led, infant-directed singing supported by a music therapist. Primary outcome was mother-infant bonding as measured by the Postpartum Bonding Questionnaire (PBQ) at discharge from NICU. Secondary outcomes were parents' symptoms of anxiety measured by General Anxiety Disorder-7 (GAD-7) and maternal depression measured by Edinburgh Postpartum Depression Scale (EPDS). Group differences at the assessment timepoint of discharge from hospital were tested by linear mixed effect models (ANCOVA). RESULTS: From August 2018 to April 2020, 213 families were enrolled in the study, of whom 108 were randomly assigned to standard care and 105 to MT. Of the participants, 208 of 213 (98%) completed treatment and assessments. Participants in the MT group received a mean (SD) of 10 sessions (5.95), and 87 of 105 participants (83%) received the minimum of 6 sessions. The estimated group effect (95% confidence interval) for PBQ was -0.61 (-1.82 to 0.59). No significant differences between groups were found (P = .32). No significant effects for secondary outcomes or subgroups were found. CONCLUSIONS: Parent-led, infant-directed singing supported by a music therapist resulted in no significant differences between groups in mother-infant bonding, parental anxiety, or maternal depression at discharge.

Effects of Live Music Therapy on Autonomic Stability in Preterm Infants: A Cluster-Randomized Controlled Trial.

Unbuffered stress levels may negatively influence preterm-infants' autonomic nervous system (ANS) maturation, thus affecting neurobehavior and psycho-emotional development. Music therapy (MT) is an evidence-based treatment modality in neonatal care. When coupled with skin-to-skin care (SSC), it may reduce stress responses in both preterm infants and their parents and enhance family-centered care. Accordingly, we aimed to compare the effects of combined MT and SSC and SSC alone on ANS stabilization in preterm infants. In a single-center, cluster-randomized trial design, ten two-month time-clusters were randomized to either combined MT and SSC or SSC alone. Families of preterm infants were offered two sessions of the allocated condition in the NICU, and a three-month follow up session at home. The primary outcome variable was stabilization of the ANS, defined by change in the high frequency (HF) power of heart rate variability (HRV) during the second session. Secondary outcomes included other HRV measures, parent-infant attachment, and parental anxiety at each session. Sixty-eight families were included. MT combined with SSC improved infants' ANS stability, as indicated by a greater increase in HF power during MT compared to SSC alone (mean difference 5.19 m2/Hz, SE = 1.27, p < 0.001) (95% confidence interval 0.87 to 2.05). Most secondary outcomes were not significantly different between the study groups. MT contributes to preterm-infants' autonomic stability, thus laying an important foundation for neuro-behavioral and psycho-emotional development. Studies evaluating longer-term effects of MT on preterm infants' development are warranted.

Estimating Components and Costs of Standard Care for Children with Autism Spectrum Disorder in Europe from a Large International Sample.

(1) Background: European guidelines provide recommendations for services and care for people with autism spectrum disorder (ASD), but not all interventions are generally available. Knowledge of service use and costs and wider societal costs in Europe is limited; (2) Method: Using an international sample, we analysed services and costs in 357 children (4-6.99 years) with ASD based on parent reports. Costs were transformed into EU-28 average using purchasing power parity; (3) Results: 122 children (34%) received specialist autism services; 149 (42%) received sensory/motor therapy; 205 (57%) received speech/language therapy; 35 (10%) received play therapy; 55 (15%) received behavioural interventions; 31 (9%) received social skills training; 47 (13%) participated in therapeutic recreational activities; and 59 (17%) received other services. The total number of hours for these services combined over two months was M = 34 (SD = 63; range: 0 -372). Estimated total costs of health-related services were M = 1210 EUR (SD = 2160 EUR); indirect societal costs were M = 1624 EUR (SD = 1317 EUR). Regression analyses suggested that costs rise with age and presence of intellectual disabilities, but not with severity of autism; (4) Conclusions: The high extent of community-based services indicates good accessibility but also considerable variation in the receipt of services. The costs of autism services are considerable. Further research is needed to investigate whether services received match individual needs.

Music Therapy for Depression Enhanced With Listening Homework and Slow Paced Breathing: A Randomised Controlled Trial.

Introduction: There is evidence from earlier trials for the efficacy of music therapy in the treatment of depression among working-age people. Starting therapy sessions with relaxation and revisiting therapeutic themes outside therapy have been deemed promising for outcome enhancement. However, previous music therapy trials have not investigated this issue. Objective: To investigate the efficacy of two enhancers, resonance frequency breathing (RFB) and listening homework (LH), when combined with an established music therapy model (trial registration number ISRCTN11618310). Methods: In a 2 × 2 factorial randomised controlled trial, working-age individuals with depression were allocated into groups based on four conditions derived from either the presence or absence of two enhancers (RFB and LH). All received music therapy over 6 weeks. Outcomes were observed at 6 weeks and 6 months. The primary outcome was the Montgomery Åsberg Depression Rating Scale (MADRS) score. Results: There was a significant overall effect of treatment for the primary outcome favouring the breathing group (d = 0.50, 95% CI 0.07 to 0.93, p = 0.02). The effect was larger after adjustment for potential confounders (d = 0.62, 95% CI 0.16 to 1.08, p = 0.009). Treatment effects for secondary outcomes, including anxiety (anxiety scale of Hospital Anxiety and Depression Scale) and quality of life (RAND-36), were also significant, favouring the breathing group. The homework enhancer did not reach significant treatment effects. Conclusion: We found that the addition of RFB to a music therapy intervention resulted in enhanced therapeutic outcome for clients with depression.

Longitudinal Study of Music Therapy's Effectiveness for Premature Infants and Their Caregivers (LongSTEP): Feasibility Study With a Norwegian Cohort.

Premature infants and their parents experience significant stress during the perinatal period. Music therapy (MT) may support maternal-infant bonding during this critical period, but studies measuring impact across the infant's first year are lacking. This nonrandomized feasibility study used quantitative and qualitative methods within a critical realist perspective to evaluate the feasibility, acceptability, and suitability of the treatment arm of the Longitudinal Study of music Therapy's Effectiveness for Premature infants and their caregivers (LongSTEP) (NCT03564184) trial with a Norwegian cohort (N = 3). Families were offered MT emphasizing parent-led infant-directed singing during neonatal intensive care unit (NICU) hospitalization and across 3 months post-discharge. We used inductive thematic analysis of semi-structured interviews with parents at discharge from NICU and at 3 months and analyzed quantitative variables descriptively. Findings indicate that: (1) parents of premature infants are willing to participate in MT research where parental voice is a main means of musical interaction; (2) parents are generally willing to engage in MT in NICU and post-discharge phases, finding it particularly interesting to note infant responsiveness and interaction over time; (3) parents seek information about the aims and specific processes involved in MT; (4) the selected self-reports are reasonable to complete; and (5) the Postpartum Bonding Questionnaire appears to be a suitable measure of impaired maternal-infant bonding. Parents reported that they were able to transfer resources honed during MT to parent-infant interactions outside MT and recognized parental voice as a central means of building relation with their infants. Results inform the implementation of a subsequent multinational trial that will address an important gap in knowledge.

Music Therapy vs. Music Listening for Negative Symptoms in Schizophrenia: Randomized, Controlled, Assessor- and Patient-Blinded Trial.

Objective: To investigate the efficacy of music therapy for negative symptoms in patients with schizophrenia. Methods: Randomized, participant- and assessor-blinded, multicenter, controlled trial including patients diagnosed with schizophrenia according to ICD-10 with predominantly negative symptoms, between 18 and 65 years. Participants were randomized to 25 successive weekly individual sessions (excluding holidays, including cancellation by the participant) of either music therapy conducted by trained music therapists, or music listening together with a social care worker. The primary outcome was reduction in negative symptoms as measured by The Positive and negative Syndrome Scale (PANSS) negative subscale total score, assessed by a blinded rater, utilizing mixed-effects model analysis. Results: In total, 57 participants were randomized; 39 completed the study's initial 15 weeks, and 30 completed follow-up at 25 weeks. On the primary outcome of PANSS negative subscale, no significant difference was observed between groups with a coefficient of -0.24 (95% CI -1.76 to 1.27, P = 0.754) in the intention to treat analysis, and -0.98 (95% CI -5.06 to 3.09, P = 0.625) when only analyzing completers. Both interventions showed significant reduction from baseline to 25 weeks on PANSS negative subscale. On secondary outcomes, no between group differences were observed in The Brief Negative Symptom Scale, WHOQOL-Bref (Quality of Life), The Helping Alliance Questionnaire and The Global Assessment of Functioning in the intention to treat or completers populations utilizing Mixed Effects Models. Conclusion: No difference between groups randomized to music therapy vs. musical listening was observed resulting in no clear recommendation for which intervention to use as the first choice for treatment of patients diagnosed with schizophrenia and predominantly having negative symptoms. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02942459.