The aim is to examine whether music listening is effective in improving sleep quality,
reducing symptoms of depression and improving quality of life in patients with depression
related insomnia.
The following hypothesis is tested:
The controlled use of a sound pillow (figure 1) in combination with the Music Star
app (figure 2) can serve as a sleep aid in reducing depression related sleep disturbances,
reducing symptoms of depression and improving quality of life.
Music listening, music intervention and music medicine refer to the use of music as
an intervention without an active music therapist. In this protocol, music listening
implies listening to pre-recorded music.
Insomnia, sleep disturbances and sleeping problems refer to a broad understanding
of the disorder. Symptoms include difficulties initiating and maintaining sleep.
The study is named MUsic STAr For Insomnia (MUSTAFI).
A single center randomized controlled trial in a two arm parallel group design is
conducted from May 2018 to December 2019 following the revised Consolidated Standards
of Reporting Trials (CONSORT) guidelines [15]. The RCT includes two groups of participants,
an experimental group and a waitlist control group. Both groups receive standard treatment
for depression following national guidelines.
The duration of the intervention is 4 weeks. The participants are followed for 8 weeks.
Participation takes place in the home of the patient. In addition, three scheduled
visits to the hospital in relation to the research project are required. Baseline
assessment is performed on the starting day. Follow up measurements are performed
after 4 and 8 weeks (figure 3).
The black element in the left bottom of figure 3 illustrates the intervention given
as an option to the waitlist control group. The participants may take home the sound
equipment for four weeks. There is no data collection involved. This has been added
to the study for ethical reasons and to limit drop out from the control group [16].
The schedule for the trial is described in the SPIRIT flow chart (figure 4) and the
dimensions of the study protocol has been described adhering to the SPIRIT Checklist
(Additional File 1).
Based on a previous study, we assume that the mean decrease in Pittsburgh Sleep Quality
Index (PSQI) scale is 3.04 (SD 2) points for the music intervention group and 2.04
(SD 1.67) points for the waitlist control group [17]. When estimating the sample size,
we assume that 25% of the eligible patients will be willing to participate in the
project. Based on the patient flow in the outpatient clinic and the available resources
from the staff recruiting the patients, we assume that a total of 120 participants
can be recruited over a period of 18 months. A dropout rate of 20% is expected. Hence,
a total of 100 randomized patients are expected to complete the study. With 100 patients
(n=50 per group) the power of our study is 76% (at a confidence level of 5%).
The study will be conducted at a single study site: the Unit for Depression in Psychiatry
at Aalborg University Hospital, Denmark. The participants are adult outpatients aged
18-65 years in treatment for unipolar depression in the Northern part of Denmark.
Patients are referred to the unit for depression with different backgrounds. Some
patients have not previously been associated with psychiatry and are referred directly
from private practice with moderate or severe symptoms of depression. Another group
of patients are referred from an inpatient unit. These patients are in recovery and
have a stabilized condition in need of follow up treatment after discharge. A third
group of patients has been diagnosed in previous contact or hospitalization and in
need for treatment after a recurrent depression.
All patients are required to have a diagnosis of unipolar depression (ICD-10 Depressive
singular episode F32 or Periodic depression F33) and sleeping problems identified
by the Hamilton Depression Rating Scale (HAM-D) by a score of at least 2 of a single
item or at least 3 in total for the three items (sleep items 4-6). In addition, the
patients should receive treatment according to national guidelines for depression.
This may include pharmacological treatment, psychotherapy, psycho education and electro
convulsive therapy. Participants are eligible if within age 18-65, in stabilized pharmacological
treatment and having at least four weeks of treatment.
Exclusion criteria are unipolar depression with psychotic episodes, substance or alcohol
abuse or sentence to treatment by law. Patients will be excluded if they have restless
legs syndrome, obstructive sleep apnea or other organic sleep disorders as well as
hearing loss. In addition, patients with a dislike of music will be excluded.
Patients are recruited in the Unit for Depression. Nurses, psychiatrists and psychologists
use the screening tool 4 weeks after beginning of treatment or after medical treatment
is stabilized. Participants are recruited through posters, information by doctors
and word of mouth in the unit. After an initial assessment for eligibility, the patient
is informed of the option to participate. The recruitment takes place during group
meetings or during individual consultation in the unit. When the patient has declared
an interest to participate, the psychiatrist of the patient fill out an inclusion
document based on information from the patient journal and his/her knowledge of the
patient. The document is forwarded to the research leader. If the patient is eligible,
the music therapist makes an appointment to give detailed information on participation
in the research project.
Patients are included according to the inclusion and exclusion criteria. The patient
may be discharged during participation in the research project and finalize as a private
person. If the increase in depression symptoms result in hospitalization, the patient
may continue participation in agreement with caretakers in the unit. If the patient
is changing medication but is interested in participation, the patient will be registered
on a waitlist for inclusion.
The patient may sign the informed consent after receiving oral and written information
about the research project. The information explains the aim and the procedures of
the research project, the use of sound equipment and accelerometer and the rights
as a participant in a scientific health study. The patient has the option to ask questions
and if the patient need time to consider the participation, the music therapist offer
to call the patient after one week and a new meeting is set up for the signing of
the informed consent. When the informed consent is obtained and the inclusion criteria
are confirmed in the inclusion document, the music therapist proceeds with the randomization.
An additional consent for collection and use of log file data from accelerometer and
the Music Star app is signed after randomization. Documents of informed consent are
kept in a securely locked place.
Randomization takes place when the inclusion document has confirmed eligibility and
the informed consent has been signed following the regulations of the The North Denmark
Region Committee on Health Research Ethics
Randomization is carried out by the use of REDCap (Research Electronic Data Capture)
hosted at Aalborg University Hospital. REDCap is a secure web-based application designed
to support data capture for research studies. The randomization will be stratified
according to age, i.e., under 30 years vs. 30 years and above. Randomization is performed
using computer-generated block randomization (random block sizes 2-8) with 1:1 allocation
between the intervention group and the waitlist control group.
The principal investigator is assigned to give information on the research project
to groups and individuals by team members and coming to the unit by appointment. When
offering a thorough information to obtain informed consent, the music therapist takes
the participant to the music therapy clinic situated in a hospital building close
by.
Experimental Intervention
The music intervention consists of listening to music with the use of a sound pillow
applying the music from The Music Star app with special designed playlists. The duration
of music listening for 30 minutes minimum at bedtime is guided by previous studies
[6]. The principal investigator HNL gives an oral guideline to music listening and
use of sound equipment at the baseline appointment. Adherence to the intervention
(30 min of bedtime music) is monitored through log file data from the Music Star.
Instructions concerning the experimental intervention:
•
It is required that you listen to music of your choice from the Music Star at least
30 min. at bedtime every night in four weeks. You may use The Music Star during the
night or in the early morning hours if you wake up and have difficulties falling asleep
again.
•
You may turn off the Music Star if you wake up when the music plays and it is disturbing.
•
The music will automatically stop when the playlist ends after 30 or 60 minutes
•
You may use The Music Star in the daytime to assist a rest. It is important only to
use The Music Star for relaxation and sleep.
•
You are advised to listen to the different available music to select your preferred
playlists. You may select a particular playlist to play every night. Some people find
that it is helpful to let a specific piece of music be a signal for sleep initiation.
•
Consider choosing music that you like and that may help you fall asleep.
•
You have to listen to music at night in the way it is described for the research purpose,
i.e. the sound pillow in combination with The Music Star app.
•
You may listen to your own music during the daytime.
Instructions on the use of the sound equipment:
•
Place the sound pillow in your bed (remove your own pillow) and place The Music Star
close to the bed on a small table or chair for easy access during the night.
•
Make sure that you have recharged The Music Star during the day.
•
If you have technical problems with the sound equipment, you may contact the research
leader by phone from 9-12 on weekdays.
The data are derived from four questionnaires (three are self-reported and one is
scored by the psychiatrist, researcher or project nurse) and log file data from the
accelerometer and from The Music Star app. The references concerning validation of
each instrument below are selected according to their relevance to this study.
The Pittsburgh Sleep Quality Index (PSQI) is a commonly used questionnaire measuring self-reported sleep habits in clinical
populations in research and clinical practice [18] . A Danish version of the questionnaire
will be used [19]. The items refer to sleep habits and disturbances within the last
month. The 19 items are divided in 7 domains: subjective sleep quality, sleep latency,
sleep duration, sleep efficiency, sleep disturbances, daytime dysfunctions and use
of antidepressant agents. The seven components form a global score ranging from 0
to 21, each component with a range from 0 to 3. Buysse reported a score of >5 (indicating
poor sleep) yielded a diagnostic sensitivity of 89.6 % and a specificity of 86.5%
[18]. The scale shows good homogeneity with an internal consistency, with α = 0.83.
Acceptable measures of validity were obtained through the ability to distinguish between
clinically distinct groups and comparing these with polysomnographic results [19].
A score of > 5 is indicative of severe sleep difficulties in at least two areas, and
separating participants in two categories “good” and “poor”. PSQI is validated in
psychiatric populations [20] .
The Hamilton Depression Scale (HAM-D17). The HAM-D17 consists of 17 items [21]. The items cover the depressive state, the
unspecific stress and arousal symptoms, the suicidal thoughts and lack of insight.
The respondent is asked to consider the last three days when responding.
Each item in the score is rated from 0-4 or 0-2, the higher number indication an increase
in the symptoms of depression. A guide to the Hamilton rating questioning is used
in combination with a rating sheet. The total score indicates the severity of depression symptoms graduating in four
categories from unlikely depression to severe depression, with 8-12 indication minimal
depression, 13-17 indicating light depression, 18-24 indicating moderate depression
and 25-52 indicating severe depression.
The Hamilton Depression Rating Scale in the 17-item version is validated [22].
The World Health Organization Well-Being Index. (WHO-5). The 5-item World Health Organization Well-Being Index (WHO-5) is among the most widely
used questionnaires assessing subjective psychological well-being [23]. It measures
subjective quality of life based on positive mood (good spirits, relaxation), vitality
(being active and waking up fresh and rested), and general interest (being interested
in things). WHO-5 only contains positively phrased items. The WHO-5 items are: (1) ‘I have felt
cheerful and in good spirits', (2) ‘I have felt calm and relaxed', (3) ‘I have felt
active and vigorous', (4) ‘I woke up feeling fresh and rested' and (5) ‘My daily life
has been filled with things that interest me'. The respondent is asked to rate how
well each of the five statements applies to him or her when considering the last 14
days. Each of the five items is scored from five (all of the time) to zero (none of
the time). The score therefore theoretically ranges from zero (absence of well-being) to 25 (maximal
well-being). The use of WHO-5 as a measure of severity of depression is validated [24).
The World Health Organization Quality of Life (WHOQOL-Bref). In 1991, the World Health Organization initiated a project with the aim of developing
an international, cross-culturally comparable QOL assessment instrument. “It assesses the individual's perceptions in the context of their culture and value
systems, and their personal goals, standards and concerns. The WHOQOL instruments
were developed collaboratively in a number of centres worldwide, and have been widely
field-tested.” [25]. The WHOQOL-BREF instrument is a shorter version of the original
100 item self-report questionnaire, comprising 26 items measuring four domains: physical
health, psychological health, social relationships and environment. In each question,
the respondent reports his/her QOL in the four domains on a five point Likert scale. A high score reflects the subjective experience of high
QOL. The use of WHO-QOL Bref is validated [26].
The Music Star app. An app designed for iPad in 2014. The Music Star is a self-explanatory user interface
to select music from specifically designed playlists. Music therapists have selected
the music for the playlists. The app has a built-in log function that registers each
event when using the app. The Music Star gives information from log files of music
played, time and duration [24].
The 16 playlists of 30-60 min duration are represented by colored triangles forming
a star. The four playlists in shades of blue are the most quiet and simple (lowest
stimuli), the four playlists in shades of green include some variation and dynamics
(moderate stimuli), the four playlists in shades of red have more intensity (highest
stimuli). The grey triangles are intended to contain playlists for specific purposes.
A grey triangle contains the only non-music playlist of ‘Summer Rain’ consisting of
sounds of rain and bird sounds. The rain sound adds a non-music track for the purpose
of variety in sound stimuli to meet individual preferences. Two other grey triangles
contain special designed playlists for sleep. The classification of music is correlated
to the degree of complexity and tension of the musical stimulus based on the taxonomy
of music by Wärje & Bonde [25]. The playlists in The Music Star are all categorized
in subdivisions of supportive music according to the taxonomy of music. The two sleep
playlists have a 30 minutes duration. Sleep 1 is a short version of a playlist with
music specially composed for relaxation and sleep including a male voice humming.
Sleep 2 is a playlist with a guitar-bass jazz duo playing slow ballads. Sleep 1 and
2 are included for meeting criteria of minimum duration and variety in the music selection.
More than 100 music pieces in different genres are available in the playlists.
Accelerometer. One tri-axial accelerometer with on board memory (Axivity Ax3, United Kingdom) placed
in a wrist bracelet will be used to measure arm movement during the night. The measurement
range was set to ±8G with a sampling frequency of 25 Hz. A sleep analysis function
using a generic algorithm will provide data on sleep duration. Assessing sleep duration
with accelerometer is validated [26].
The primary outcome measure will be changes in sleep comparing the total score of
the PSQI-DK assessed at baseline, after four and eight weeks. The sleep quality assessed
with PSQI-DK is compared with sleep estimates from accelerometer data considering
total hours of sleep per night.
Secondary outcome measures
The secondary outcomes will be 1) log file data from the accelerometer. This provides
additional data on total hours of sleep per night. The total hours of sleep per night in the experimental group is compared with waitlist
control group after 4 weeks 2) HAM-D provides data on the total depression score 3) the WHO-5 and WHO-QOL provide
data on the self-reported quality of life. Additional log file data is collected from
the Music Star app. All outcome measures are collected at baseline, after four weeks
experimental/wait-list control and again after four weeks follow up. In addition,
registration of pharmacological treatment during the period of participation is included
in the data collection.
At baseline, demographic information including age, sex, ethnicity, and partnership,
children living at home, handedness, diagnosis code for present depression, first
diagnosis of depression and first psychiatric diagnosis will be gathered. In addition,
the participant may add self-reported other disease and/or diagnosis. Work status
and education, alcohol use and present use of music for sleep will be registered.
We initially perform a descriptive analysis on age, gender, medication, illness duration
etc. The two groups are compared within groups and between groups using F-tests and
chi-squared tests. Additionally we compare the groups on outcome measures at baseline.
Data analysis for the RCT will be performed using mixed effects linear regression
with subject specific random effects. The intervention group will be initially compared
with the control group on change of all outcome measures after four and eight weeks.
Age and gender will be added as covariates in all regression analyses. Repeated-measures
analysis of variance (RM-ANOVA) will be used to compare results from baseline follow
up one and follow up two.
Finally, a descriptive analysis of the playlists is included in the study, i.e. analysis
of playlist preferences (style, duration, time of day) in the group of patients benefitting
most from treatment compared to the group of patients benefitting the least.
Blinding of the researchers performing the scorings before and after the treatment
as well as the subjects of the study will not be possible. Patients will be anonymized
when analyzing data. All main analyses will be carried out based on the intention-to-treat
principle.
Data management is carried out by the use of REDCap. Double data entry is performed
by research assistants.
The study is approved by the local ethics committee (N-20170055) and registered by
the Danish Data Protection Agency (ID 2017-236). A yearly report of adverse events
and other unintended effects of the trial is obtained by the local ethics committee.
Results of the study are published in open-access peer reviewed scientific journals
and presented at international scientific conferences. Broadcast of findings in Danish radio and TV media will be planned through the study.