Distribution and Conduct of Clinical Trials Involving Music Therapy: Registered Clinical Trials in the Lost 15 Years

*Corresponding author: Keiko Yukawa, Hitoshi Fuji and Hajime Sato*

Author Affiliations

Department of Health Policy and Technology Assessment, National Institute of Public Health,
Wako, Saitama 351-0197, Japan

Citation

Yukawa K, Fuji H, Sato H. Distribution
and conduct of clinical trials involving
music therapy: Registered clinical
trials in the last 15 years. Clin Trail
Pract Open J. 2017; 1(1): 1-9. doi:
10.17140/CTPOJ-1-101

Copyright

©2017 Sato H. This is an open
access article distributed under the
Creative Commons Attribution 4.0
International License (CC BY 4.0),
which permits unrestricted use,
distribution, and reproduction in
any medium, provided the original
work is properly cited.

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original research

Abstract

Objective: This study aimed to conduct an evaluation of music therapy clinical trials
worldwide, to understand what trials have been conducted and to show the chronological
changes. Additionally, we sought to clarify issues related to providing clinical trial registration
information.
Methods: We searched the International Clinical Trials Registry Platform (ICTRP) database for
“music therapy,” and identified the disease target for each article found.
Results: A total of 150 clinical trial studies were found in the ICTRP using the term “music
therapy.” In these trials, music therapy was used for improvement of social functioning in
schizophrenia and/or serious mental disorders, anxiety and depressive symptoms, and cancer
symptoms. Twenty-five clinical trials were actively recruiting. Sixteen of the 25 trials were
registered in the United States at ClinicalTrials.gov, of which 9 trials were conducted in the US.
Seven trials were conducted in other countries such as Spain, Taiwan, and China.
Conclusion: A search for music therapy clinical trials retrieved 150 trials from the ICTRP, and
the number of clinical trial registrations has increased yearly. Music therapy is widely used in
patients with various diseases, including Alzheimer’s disease, anxiety, and arthritic pain and
has the potential to improve certain disease outcomes, but there is not enough evidence to
substantiate its efficacy. It is important to enlighten researchers and pharmaceutical companies
on the proper management of the quality of such clinical trial information, as this is an important
issue.

Abbreviations

ICTRP: International Clinical Trials Registry Platform; AMTA: American
Music Therapy Association; JMTA: Japanese Music Therapy Association; IFPMA: International
Federation of Pharmaceutical Manufacturers and Associations.

Introduction

Music therapy originated in the early 20th century in the United States and is practiced
worldwide. The American Music Therapy Association (AMTA) was founded in 1998 in the
US1 and in Japan, the Japanese Music Therapy Association (JMTA) was established in 2001.2
By combining the physiological, and social effects of hearing or playing music, music therapy
can enable the recovery or improvement of mental and physical health. Music therapy can be
divided into two types, namely, passive music therapy such as listening to music, and active
music therapy such as performing to music, singing, or playing music.
In Japan, music therapy was administered by pioneering experts for a few decades
following World War II. Music psychology was introduced into the curriculum of music
colleges around 1955, and music therapy originated as a form of local volunteerism by music
experts. In the 1990’s, there was an increase in the number of experts who were self-educated,
had studied abroad, and had implemented music therapy at a local level.

Along with traditional Chinese medicine and
acupuncture, music therapy is considered a complementary
and alternative medicine strategy or as a familiar nonpharmacotherapy.
A 2011 survey showed that music therapy was
used by 3% of the Japanese population.3
Music therapy has also
been recommended by the national center for complementary
and integrative health for patients with Alzheimer’s disease.
Several studies have shown that music therapy helped relieve
agitation and depression, and had a positive effect on patient’s
quality of life.4
Evidence for the benefits of music therapy is
increasing, as music therapy has been found to improve quality
of life for many patients with a range of diseases.
Numerous studies have demonstrated that music
therapy cannot only provide minor benefits but also improve
medical outcomes and the quality of life in a variety of conditions.
Kamioka et al5 conducted a review on the efficacy of music
therapy and evaluated the quality of systematic reviews (SRs)
in the current literature. Music therapy has also been shown to
improve outcomes during invasive procedures. For example, in
controlled clinical trials of people undergoing colonoscopies
and cardiac angiography, patients who listened to music in the
operating room reported less discomfort during their procedures.
Music therapy can also help restore lost speech. Music has been
shown to help patients with stroke or those with traumatic brain
injury who have damage to the areas of the brain responsible for
speech. Moreover, music has also been shown to reduce anxiety
and the side effects, such as nausea and vomiting, associated
with chemotherapy and radiotherapy during cancer treatment.
In addition to these benefits, music therapy can also aid
pain relief. Music therapy has been tested in patients with intense
acute pain and those with chronic pain from arthritis; music
therapy has been shown to relieve depression, and provides
patients with a better sense of control over their pain when used
as an adjunctive therapy. Moreover, music therapy improves
patient quality of life,6
facilitates memory recall, reduces
agitation, assists with communication, and improves physical
coordination. The primary impairments of people with autism
spectrum disorder include social interaction and communication
difficulties. With music therapy, musical experiences and the
relationships that develop through these experiences enable
communication and expression, thereby helping address some
of the core difficulties in patients with autism.7
The World Health Organization (WHO) has recognized
the need for the establishment of a registration system for
clinical trials as an important health-related policy issue.8
In July
2004, the International Committee of Medical Journal Editors
(ICMJE), which includes other major medical journals, issued
a statement that all medical journal editors should require that
clinical trials be registered in a public trials registry.9
Furthermore,
the International Federation of Pharmaceutical Manufacturers
and Associations (IFPMA) released the document, titled “Joint
Position on the Disclosure of Clinical Trial Information via
Clinical Trial Registries and Databases”.10 The WHO established
and released the International Clinical Trials Registry Platform
(ICTRP) in August 2005 to promote the registration of clinical
research information. The appendix details the inclusion of
various national clinical trial registration systems in the ICTRP.
However, reporting of supportive evidence in the
complementary and alternative medicine (CAM) field compared
to conventional medicine is often insufficient. The purpose of
the present study was to understand how music therapy clinical
trials have been conducted internationally, and to investigate if
the content of music therapy depends on the country in which it
is conducted.

Results

Characteristics of the Clinical Trials of Music Therapy
We included 150 clinical trials in our analysis; no trials were
excluded. Their characteristics are summarized in Table 1.

Country
Four international clinical trials that were conducted in two or
more countries were identified. The number of other clinical
trials per country was as follows: The United States (39 trials);
Iran (23 trials); Germany (12 trials); Australia (11 trials); China
(10 trials); Brazil (7 trials); France (3 trials); Spain (3 trials);
Taiwan (3 trials); the Netherlands (3 trials); the United Kingdom
(3 trials); India (3 trials); South Korea (3 trials); Japan (2 trials);
Sweden (2 trials); Canada (2 trials); Finland (2 trials); and
Lebanon, New Zealand, Norway, Singapore, South America,
Switzerland, Israel, and Hong Kong all had 1 trial.
Phase
Five trials were registered as being in Phase 1; 1 was in Phase
1-2; 6 were in Phase 2; 2 were in Phase 2-3; 6 were in Phase 3;

and 2 were in Phase 4. In 122 clinical trials, the phase was not
identified.
Primary Sponsor
More than 80 trials were conducted by universities; in the
remaining studies, the primary sponsor was not clear.
Study Type
There were 143 interventional trials and 7 observational trials.
The most frequent minimum age for inclusion in the trials was
over 18 years.
Condition
Music therapy has been widely used in patients with various
diseases, including Alzheimer’s disease, anxiety, arthritic pain, a
variety of symptoms associated with cancer, such as depression
or pain, chronic pain, dementia, or depression, mental and
behavioral disorders, head injuries, Parkinson’s disease,
pregnancy, schizophrenia, and stroke.

Source-Register
The number of trials per source-register (registration destination)
was as follows: ANZCTR (Australian New Zealand Clinical
Trials Registry), 16 trials; Chi CTR (Chinese Clinical Trial
Register), 8 trials; ClinicalTrials.gov, 74 trials; CRIS (Clinical
Research Information Service, Republic of Korea), 1 trial; CTRI
(Clinical Trials Registry-India), 2 trials; German CTR (The
German Clinical Trials Register), 6 trials; IRCT (Iranian Registry
of Clinical Trials), 22 trials; ISRCTN (The International Standard
Randomized Controlled Trial Number), 14 trials; JPRN (Japan
Primary Registry Network), 2 trials; NTR (Netherlands Trial
Register), 3 trials; PACTR (Pan African Clinical Trial Registry),
1 trial; and ReBec (Registro Brasileiro de Ensaios Clinicos), 1
trial. This information is summarized in Table 1.
Recruiting Status
Of the music therapy trials identified, 125 were not recruiting
and 25 were recruiting (Table 1). Sixteen of those 25 trials were
registered with the United States website ClinicalTrials.gov. Of
those 16 registered trials, 9 were conducted in the United States,
and 7 trials were conducted in other countries such as Spain,
Taiwan, and China. In terms of target size, 7 trials were smallscale,
including 1 trial with less than 30 participants; 7 trials
were medium-sized with one of them having 100 participants;
and 11 trials were large-scale with more than 100 participants.
Patient conditions often included anxiety. Seven trials were
registered from 2008 to 2012.
Changes in the Number of Registered Trials
Figure 1 shows changes in the number of trials registered in the
ICTRP. From 2001-2007, the number of trials increased from 0
to 5. In 2010, there were more than 10 trials, and in 2011, about
20 trials were registered. In 2014, there were 27 trials. Thus,
there has been a steady increase in the number of trials registered
to date.
Clinical Trials by Country
In the United States, clinical trials have investigated the use
of music therapy as a treatment for a range of conditions such
as cancer, pain, post-traumatic stress disorder, anxiety, stress,
asthma, and burns (n=39). Danhauer and colleagues reported
that patients undergoing bone marrow biopsies found music
intervention to be beneficial and requested the use of music
during future procedures.12 Ripley and colleagues examined the efficacy of music intervention on vasodilator response, blood
pressure, anxiety, and stress.13
A unique feature of the Iranian music therapy trials was
the large number that used traditional music. Treatments, such
as traditional music therapy sessions, were administered for
pregnancy-related issues, childhood autism spectrum disorder,
insomnia disorders, cardiovascular conditions, respiratory
conditions, chronic kidney disease, pain, cancer, head trauma,
schizophrenia, conduct disorder, obsessive-compulsive disorder,
anxiety, and depression. For patients with obsessive-compulsive
disorder, the treatment was effective in reducing obsessions, as
well as comorbid anxiety and depression symptoms.14
In Germany, music therapy was used for treating lower
and upper back pain, speech impediments, tinnitus, depression,
anorexia, and obesity. For the treatment of pain, patients underwent
a method known as intensive interdisciplinary pain treatment,
combining cognitive behavioral therapy, physiotherapy, and
music therapy. Patients undergoing such therapy listened
to music 5-7 times a week for 20-30 min, underwent group
treatment, and participated in stress management, relaxation,
and diet therapy programs.15 Another form of doctor-directed
music therapy that included live harp performances was found
to reduce salivary cortisol and had beneficial effects on the
physiological parameters of stable preterm infants in a neonatal
intensive care unit (NICU).16 Music therapy was also used in
the palliative care of cancer patients; in 55% of sessions, it was
possible to deliver successful interventions.17
In Australia, music therapy was used to treat a
range of psychiatric and developmental disorders including
autism spectrum disorder, depression, mood disorders, and
schizophrenia. Infant patients underwent active music therapy
with a registered music therapist and their caregiver, during which
they participated in live music-based activities such as singing,
instrument playing, and movement to music. For psychiatric and
developmental disorders, patients were encouraged to interact
socially during group work using music.
In China, group therapy for adults was quite prominent.
For conditions such as cancer, diabetes, cerebrovascular
disorders, anxiety, depression, and schizophrenia, patients
received a combination of therapies including music therapy,
peer support, recreation, and yoga.18 Music therapy was also
shown to reduce anxiety and create a more satisfying experience
for women undergoing caesarean delivery.19

Discussion

Registration Status of Music Therapy Clinical Trials
The efficacy of music therapy has been shown for many
symptoms and diseases; it improves the quality of subjective
sleep in insomnia patients20 and psychological (e.g., anxiety) and
physical symptoms in cancer patients. It significantly reduces
anxiety during a colposcopy (endoscopy of the cervix),21 and it
is effective in children with autism, specifically improving social
interactions, verbal communication, the initiation of an action,
and socio-emotional interactions. Moreover, music therapy
improves non-verbal communication skills in therapy settings.
It has also been shown to be effective in reducing psychological
(e.g., anxiety) and physical symptoms in patients with coronary
artery disease, especially after myocardial infarction.6
Music
therapy also alleviates the general mental state of patients with
schizophrenia by effectively reducing negative symptoms,
depression, and anxiety.22
Notably, the number of registrants for music therapy
certification examinations has increased since the mandated
registration of studies to the ICTRP in 2006. Furthermore,
the annual number of registrations for the exam has exceeded
20 since Western Europe (EU), with an active music therapy
community, joined the ICTRP in 2011.
Safety of Music Therapy
Music therapy is considered to be very safe and to have no
negative effects, because it is a non-pharmaceutical therapy.
This, however, may not always be true. Indeed, most clinical
trials conducted on music therapy have found positive effects,
but when patients do not follow the appropriate methods, such as
the selected music, time, and number of sessions, among others,
there may be adverse effects. Although some patients perceive
music as positive and calming, others feel aroused when they
listen to music.17 The CAMbrella project in Europe investigated
the perspectives of CAM users and patients, in addition to their
needs and attitudes.23 The results of that investigation showed
that the context of alternative therapies for individual patients is
an important factor.24 Therefore, an analysis of semi-structured
interviews is needed to determine the effects of music therapy.
In regions where people use traditional music, or in
developing countries, music therapy is generally not considered
a valid therapy and medicines are used instead. It is possible that
there is a culture of using familiar music without attributing a
financial burden to it. For example, in Bali, Indonesia, there is
a very famous music drama called “kecak” in which performers
percussively chant “cak.” In audible high-frequency sounds
can affect brain activity and this hypersonic effect has been
studied in an europhysiological investigation.25 The relationship
between the arts, such as music and dancing, and CAM are
obvious, but this relationship also needs to be examined from
a religious perspective, especially with regard to Iranian music
and traditional music.
Issues with Registered Clinical Trials
We reviewed the details of the clinical trials in a recruitment phase
and found two problems. Seven trials were registered from 2008
to 2012; however, these studies should have been completed on
the basis of the retarget sample size and enrollment. In other
words, after the researchers registered the trial, it is likely that
no updates were made to the information in the clinical trial registration. Based on the philosophy of promoting international
knowledge in clinical trials, the information that is released to
the public and professionals around the world must be kept upto-date.
Thus, managing the quality of such clinical trial data is
an important issue.
Additionally, by registering at ClinicalTrials.gov, rather
than in the country in which the trial is conducted, unless the
country in question has no primary registry, other groups in that
particular country may not have access to the relevant information.
Music therapy is a non-pharmaceutical based treatment for the
improvement of mental disorders, and it can have sedative
effects. Music therapy is often used in complementary and
conventional medicine. However, it is also used as an important
therapy in studies of disease. If professionals and patients are
not able to find the relevant clinical trials in their own country,
the valuable knowledge pertaining to music therapy may not be
broadly communicated.
The number of future clinical trials and professionals
that will use this form of therapy depends on whether or not
the training of music therapists becomes recognized with a
national qualification. A more active approach is needed towards
conducting clinical trials to a mass more evidence in support
of music therapy and other complementary and alternative
medicines.
Areas of Future Music Therapy Application
Unfortunately, we could not analyze the design of clinical trials
related to music therapy, because of some missing registration
information. However, we provide examples of pioneering
clinical trials by phase.
In terms of phase 1 trials, the “Effects of Music
Therapy on Huntington’s Disease” trial is a good example.
Huntington’s disease is a progressive, neurodegenerative disease
with autosomal dominant inheritance with motor disturbances,
cognitive decline and behavioral and psychological symptoms.
Because of communication problems, most patients are not
able to express themselves sufficiently. Music therapy is a
non-pharmacological intervention, alleviating communication
problems, helping self-expression, and improving quality of life.
A pertinent example of a phase 2 trial is the “Evaluating
the Effects of Music Interventions on Hospitalized People With
Dementia” trial. As society ages, dementia is increasingly
becoming a problem. For example, in Japan, with a super
aging society, the government has estimated that the number of
dementia patients throughout the country will exceed 7 million
by 2025. Among elderly people aged 65 years or over, 1 out of
every 5 will have dementia. Distress is one of the most common
clinical manifestations associated with dementia. Although
pharmacological intervention may be appropriate for managing
distress, music therapy should be considered one of the nonpharmacological
approaches to assist in alleviating distress for
dementia patients.
An example of a phase 3 trial is the “Multimodal
Music Therapy for Children With Anxiety Disorders” trial.
Although music therapy has previously been considered an
effective intervention for children with mental health needs, its
efficacy in clinical settings is unclear. In recent years, pediatric
developmental disorders, such as dyslexia, attention-deficit
hyperactivity disorder (ADHD), and attention-deficit disorder
(ADD), have been gaining increased interest. Music therapy
may be effective for treating these conditions, by improving
children’s relationships and promoting communication.
Hopefully, such research efforts will increase so that
clear evidence of the benefits of music therapy will be obtained.
LIMITATIONS
Since music therapy is currently conducted in highly varied
ways, such as in clinical trials that combine music and rhythm
exercises, it is not possible to define a specific and concise term
for music therapy. In the future, it will be necessary to understand
the specific details of the treatment regimens that include music
therapy in combination with other treatments.
The inconsistent effects of music therapy have been
noted; this inconsistency is attributed to differences in the
number of sessions, content, and quality of the therapy. Thus,
a more detailed analysis of the different types of therapeutic
content is necessary. We also need to investigate whether
“passive listening” or “individual therapy” can provide benefits
for patients and improve their disease outcomes. In recent years,
at least 50 randomized control trials of music therapy have been
reported annually; thus, there is a need to review these trials and
their content.
Furthermore, it is necessary to show that music therapy
works for a variety of participants, including the elderly, children,
and patients with specific disease such as those with dementia,
Alzheimer’s disease, developmental disorders, autism, and
mental illness, among others. A detailed analysis of these target
groups will be needed in the future.

Conclusion

A search for music therapy clinical trials retrieved 150 trials
from the ICTRP. These were conducted in 1 or more countries,
including the United States (39 trials), Iran (23 trials), Germany
(12 trials), and Australia (11 trials). The participants of these
studies included adults from 18 to 51 years of age. Our review
finds that music therapy has been widely used in patients with
various diseases, including Alzheimer’s disease, anxiety, and
arthritic pain. The number of clinical trial registrations has
increased yearly. However, there is a need for future studies to
take into consideration different participant groups. Moreover,
the sharing of knowledge that is related to the management ofclinical trial quality between researchers and pharmaceutical
companies is an internationally important issue.

Acknowledgements

This research received the support of a 2015-2016 health
labor science research grant (Practical Research on Medical
Technology, Clinical Research Promoting Research project),
titled “A study on diffusion and enlightenment of clinical trials
and research for the nation and patients” (H27-Clinical researchgeneral-001)
from the Ministry of Health, Labor and Welfare,
Japan.

Conflicts of interest

The authors declare that there are no conflicts of interest.