music-based intevention and palliative care

8/20/2019 Music-based Intevention and Palliative Care

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REVIEW ARTICLE

Music-based interventions in palliative cancer care: a review

of quantitative studies and neurobiological literature

Patrick Archie & Eduardo Bruera & Lorenzo Cohen

Received: 19 April 2012 /Accepted: 21 April 2013 /Published online: 30 May 2013# The Author(s) 2013. This article is published with open access at Springerlink.com

Abstract

Purpose This study aimed to review quantitative literature pertaining to studies of music-based interventions in pallia-

tive cancer care and to review the neurobiological literaturethat may bare relevance to the findings from these studies.

Methods A narrative review was performed, with particular emphasis on RCTs, meta-analyses, and systematic reviews.The Cochrane Library, Ovid, PubMed, CINAHL Plus,PsycINFO, and ProQuest were searched for the subject headings music, music therapy, cancer , oncology, palliativecare, pain, anxiety, depression, mood , quality of life, prev-alence, neuroscience, functional imaging , endogenous opi-oids, GABA, 5HT , dopamine, and permutations of thesesame search terms. Data for the review were comprised of articles published between 1970 and 2012. References of all

the cited articles were also reviewed. Results Available evidence suggests that music-based inter-ventions may have a positive impact on pain, anxiety, mooddisturbance, and quality of life in cancer patients. Advancesin neurobiology may provide insight into the potentialmechanisms by which music impacts these outcomes.Conclusions More research is needed to determine what subpopulation of cancer patients is most likely to respondto music-based interventions, what interventions are most

effective for individual outcomes, and what measurement parameters best gauge their effectiveness.

Keywords Music . Cancer . Oncology . Palliative . Neurobiology

Introduction

By alleviating the physical and psychological symptomsassociated with malignancy, palliative care serves a vitalrole in the multidisciplinary care of cancer patients. Com-mon symptoms such as pain, anxiety, and mood disturbancecan be difficult to manage with standard pharmaceuticaloptions and may significantly interfere with quality of life

(QOL) [1, 2]. The search for complimentary interventionsthat are both cost effective and associated with few sideeffects has led to an increased interest in the therapeuticuse of music for cancer patients within the field of palliativecare [3 – 6]. This review summarizes findings from quantita-tive research literature. Furthermore, it discusses challengesand opportunities associated with this emerging area of research and provides practical suggestions for futureinvestigation.

Different music-based interventions defined

The interventions in this review are generally classified aseither music medicine or music therapy. In “music medicine”interventions, patients listen to prerecorded music that is ad-ministered by healthcare staff and preselected by study in-vestigators, who may or may not have any formal training inmusic therapy [7, 8]. In “music therapy” interventions, pa-tients are offered prerecorded, live, and/or interactive musicthat is individualized by a trained music therapist [9, 10].Hence, the crucial distinction between music medicine

P. Archie (*)

Celilo Cancer Center, Mid-Columbia Medical Center,1800 East 19th Street, The Dalles, OR 97058, USAe-mail: [email protected]

E. BrueraDepartment of Palliative Care and Rehabilitation Medicine,Division of Cancer Medicine, The University of Texas MDAnderson Cancer Center, Houston, TX, USA

L. CohenIntegrative Medicine Program, Department of General Oncology,Division of Cancer Medicine, The University of Texas MDAnderson Cancer Center, Houston, TX, USA

Support Care Cancer (2013) 21:2609 – 2624

DOI 10.1007/s00520-013-1841-4


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(MM) and music therapy (MT) is that the former involvesonly a stimulus and response, and the latter involves a thera-

peutic relationship based on individualized assessment, treat-ment, and evaluation [7].

Specific clinical endpoints studied

Pain

Pain represents one of the most common symptoms affect-ing patients with advanced malignancy. One recent meta-analysis [11] pooled data from 52 studies (total N =19,985)and estimated pain to occur in 33 % of patients who hadcompleted treatment with curative intent, 59 % of patientsundergoing anticancer therapy, and 64 % of patientswith advanced/metastatic/terminal disease. A subsequent meta-analysis [12] pooled data from 64 studies (total

N =95,159), 34 of which reported pain prevalence in patients

with all stages of cancer (including early disease), and 30 of which reported pain prevalence in patients with ad-vanced cancer. The combined weighted mean prevalenceof pain in the 14,961 patients with advanced cancer wasestimated to be 75 %.

Multiple studies have demonstrated that music-based in-terventions may have a mild to moderate analgesic effect (Table 1). Five such randomized controlled trials (RCTs)(total N =391) were analyzed in a 2011 Cochrane Review[13]. Prerecorded music was provided perioperatively for 15out of 30 breast cancer patients undergoing mastectomy[14], during bone marrow biopsy for 29 out of 59 hemato-

logic malignancy patients [15], as a single 30-min session in62 out of 126 adult patients with various malignancies [16],during lumbar puncture in 20 out of 40 pediatric leukemia

patients [17], and as a single session with guided imagery in65 out of 136 adult patients with various malignancies [18].Based on the combined results of these five studies, theauthors classified music's analgesic effect as moderate, witha standardized mean difference (SMD) of −0.59, (95 % CIfrom −0.92 to −0.27, P =0.0003). All five of the abovestudies reported pain by self-reported measurement scales.An earlier Cochrane Review examined the effect of musicon analgesic requirements during a painful procedure (five

studies), during a 2-h postoperative period (three studies), or during a 24-h postoperative period (five studies) [19]. Al-though none of the included studies were limited to onco-logic or palliative care settings, the 13 included studies ( N =1016) did show that exposure to music was associated witha decrease in opioid requirement, with a SMD of −1.29(95 % CI from −0.92 to −0.27, P =0.0062). These resultswere consistent with those from a separate meta-analysis[20] which studied the use of music vs. standard care inadult patients undergoing colonoscopy. This meta-analysis

included three trials [21 – 23] in which music was providedto a total of 130 out of 261 patients. The patients whoreceived music required 29.7 % less analgesia with meper-idine, alfentanil, or pethidine ( P =0.001) and 15 % lesssedation with midazolam or propofol ( P =0.055). Finally, asingle-arm study from 2006 [5] found that in 126 palliativecare patients with pain (90 % of whom had cancer), mean

self-reported pain scores decreased from 2.7 to 2.1 on a five- point VAS after a single MT session ( P


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T a b l e 1

I n d i v i d u a l s t u d i e s i n v e s t i g

a t i n g t h e a n a l g e s i c e f f e c t o f m u s i c - b a s e d i n t e r v e n t i o n s i n e i t h e r o n c o l o g i c o r p a l l i a t i v e c a r e s e t t i n g s

A u t h o r ,

y e a r ,

t y p e o f s t u d y

S t u d y p o p u l a t i o n

M u s i c i n t e r v e n t i o n

C

o n t r o l

N ,

m u s i c

g r o u p

N ,

c o n t r o l

g r o u p

R e s u l t s

B i n n s - T u r n e r , 2 0 0 8 ,

R C T a

[ 1 4 ]

B r e a s t c a n c e r p a t i e n t s

u n d e r g o i n g m a s t e c t o m y

M M : s i n g l e s e s

s i o n o f p r e r e c o r d e d

m u s i c t h r o u g h h e a d p h o n e s ( c o n t i n u o u s l y

f r o m p r e o p e r a t i v e t h r o u g h p o s t o p e r a t i v e

p e r i o d ) . P a t i e n t s c o u l d s e l e c t f r o m c l a s s i c a l ,

e a s y l i s t e n i n g ,

i n s p i r a t i o n a l , o r n e w a g e

i P o d a n d

h e a d p h o n e s b u t

n o m u s i c o r s o u n d s

1 5

1 5

S i g n i f i c a n t r e d u c t i o n i n

s e l f - r e p o r t e d p o s t o p

p a i n l e v e l b y V A S

( P = 0 . 0

0 7 )

D a n h a u e r e t a l . ,

2 0 1 0 ,

R C T a

[ 1 5 ] H e m a t o l o g i c m a l i g n a n c y

p a t i e n t s u n d e r g o i n g

l u m b a r p u n c t u r e

M M : p r e r e c o r d e d m u s i c t h r o u g h h e a d p h o n e s

f o r d u r a t i o n o

f p r o c e d u r e . P a t i e n t s c o u l d

s e l e c t f r o m c l a s s i c a l , h a r p ,

g e n e r a l i n s t r u m e n t a l ,

n a t u r e s o u n d s

, c o u n t r y , g o s p e l ,

a n d j a z z

S

t a n d a r d c a r e

2 9

3 0

N o s i g n i f i c a n t r e d u c t i o n

i n s e l f - r e p o r t e d

i n t r a - p r o c e d u r a l p a i n

l e v e l b y V A S ( P = 0 . 7 7 1 )

H u a n g ,

2 0 0 6 ,

R C T a

[ 1 6 ]

A d u l t i n p a t i e n t s w i t h

v a r i o u s m a l i g n a n c i e s

M M : s i n g l e 3 0 - m

i n s e s s i o n o f p r e r e c o r d e d m u s i c

t h r o u g h h e a d p h o n e s .

P a t i e n t s c o u l d s e l e c t f r o m

T a i w a n e s e f o l k ,

B u d d h i s t , h a r p ,

a n d p i a n o r e c o r d i n g s

B

e d r e s t

6 2

6 4


s e l f - r e p o r t e d p a i n l e v e l

b y V A S ( P < 0 . 0 0 1 )

N g u y e n e t a l . ,

2 0 1 0 ,

R C T a

[ 1 7 ]

P e d i a t r i c l e u k e m i a p a t i e n t s

u n d e r g o i n g l u m b a r

p u n c t u r e

M M : p r e r e c o r d e d m u s i c t h r o u g h h e a d p h o n e s f o r

d u r a t i o n o f p r o c e d u r e .


e i t h e r t r a d i t i o n a l V i e t n a m e s e s o n g s o r c h i l d r e n ’ s s o n g s i

P o d a n d

h e a d p h o n e s b u t

n o m u s i c o r s o u n d s

2 0

2 0


s e l f - r e p o r t e d

i n t r a - p r o c e d u r a l p a i n

l e v e l b y V A S ( P < 0 . 0 0 1 )

Y o n g h u i e t a l . ,

2 0 0 9 ,

R C T a

[ 1 8 ]

A d u l t i n p a t i e n t s w i t h

v a r i o u s m a l i g n a n c i e s

M M : s i n g l e 3 0 - m

i n s e s s i o n o f u n s p e c i f i e d m u s i c

w i t h u n s p e c i f i e d g u i d e d i m a g e r y

S

t a n d a r d c a r e

6 5

7 1

N o s i g n i f i c a n t r e d u c t i o n

i n s e l f - r e p o r t e d p a i n

d e t e c t e d b y n u m e r i c

r a t i n g s c a l e ( P > 0 . 0 5 )

G a l l a g h e r ,

2 0 0 6 ,

s i n g l e - a r m s t u d y A d u l t s w i t h a t e r m i n a l

i l l n e s s b i n a n i n p a t i e n t

p a l l i a t i v e c a r e s e t t i n g

M T : s i n g l e s e s s

i o n o f v a r y i n g l e n g t h i n c l u d i n g

l i v e p e r f o r m a n c e ,

l i s t e n i n g t o p r e r e c o r d e d m u s i c ,

a n d i n t e r a c t i v e t e c h n i q u e s

N

o n e

1 2 6

0


s e l f - r e p o r t e d p a i n b y

V A S ,

f r o m m e a n s c o r e

o f 2 . 7 b e f o r e t h e s e s s i o n

t o m e a n s c o r e o f 2 . 1

a f t e r t h e s e s s i o n

( P < 0 . 0 0 1 )

M M m u s i c m e d i c i n e ,

M T m u s i c t h e

r a p y

a

I n c l u d e d i n 2 0 1 1 C o c h r a n e R e v i e w

b

F o r 9 0 %

o f t h e p a t i e n t s i n t h i s s t u

d y , t h e t e r m i n a l i l l n e s s w a s c a n c e r

Support Care Cancer (2013) 21:2609 – 2624 2611


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5/16

T a b l e 2

( c o n t i n u e d )

A u t h o r ,

y e a r ,

s t u d y t y p e

S t u d y p o p u l a t i o

n


C o n t r o l

N ,

m u s i c

g r o u p

N ,

c o n t r o l

g r o u p

R e s u l t s

Y o n g h u i e t a l . ,

2 0 0 9 , R

C T a ,

c

[ 1 8 ]

H o s p i t a l i z e d a d u l t

c a n c e r p a t i e n t s w i t h p a i n

M M : S i n g l e 3 0 - m i n s e s s i o n o f

p r e r e c o r d e d m u s i c w i t h i m a g e r y

d u r i n g h o s p i t a l i z a t i o n

S t a n d a r d c a r e

6 5

7 1

S i g n i f i c a n t r e d u c t i o n

i n a n x i e t y d e t e c t e d

( P < 0 . 0

5 ) .

M e a n S T A I i n m u s i c g r o u p

f e l l f r o m 5 7 . 9 t o 3 3 . 8 , b u t m e a n S T A I i n

c o n t r o l g r o u p o n l y

f e l l f r o m 5 8 . 6 t o 5 5 . 9

H o r n e - T h o m p s o n

a n d G r o c k e , 2 0 0 8 ,

R C T [ 4 2 ]

A d u l t s w i t h a t e

r m i n a l

i l l n e s s i n a n i n p a t i e n t

p a l l i a t i v e c a r e

s e t t i n g

( 2 4 o u t o f 2 5

o f w h i c h

h a d a d i a g n o s i s o f c a n c e r )

M T : s i n g l e 2 0 - t o 4 0 - m i n s e s s i o n

c o n d u c t e d b y a r e g i s t e r e d m u s i c

t h e r a p i s t . T e c h n i q u e s i n c l u d e d

“ p l a y i n g l i v e f a m i l i a r m u s i c ,

s i n g i n g , m u s i c a n d r e l a x a t i o n ,

m u s i c a n d i m a g e r y , i m p r o v i s a t i o n ,

m u s i c - a s s i s t e d c o u n s e l i n g ,

r e m i n i s c e n c e ,

a n d l i s t e n i n g t o

r e c o r d e d m u s i c ”

V i s i t f r o m v o l u n t e e r

t h a t e i t h e r r e a d t o ,

c o n v e r s e d w i t h , o r

p r o v i d e d e m o t i o n a

l

s u p p o r t t o t h e p a t i e n t

1 3

1 2

S i g n i f i c a n t r e d u c t i o n

o f a n x i e t y i n m u s i c

g r o u p c o m p a r e d t o

t h e c o n t r o l g r o u p b y

M a n n – W h i t n e y t e s

t i n g ( P = 0 . 0 0 5 ) .

E i g h t

p a t i e n t s i n m u s i c g

r o u p r e p o r t e d a

d e c r e a s e i n a n x i e t y

o f b e t w e e n 1 a n d

5 p o i n t s o n E S A S s c a l e , w h i l e o n l y 1

p a t i e n t i n c o n t r o l g

r o u p r e p o r t e d a

d e c r e a s e i n a n x i e t y

o f 1 p o i n t . T h r e e

p a t i e n t s i n c o n t r o l g r o u p r e p o r t e d

i n c r e a s e d a n x i e t y a

f t e r t h e s t u d y i n t e r v a l


M T m u s i c t h e

r a p y

a


[ 1 3 ]

b

I n s u f f i c e n t i n f o r m a t i o n r e g a r d i n g

p r e s e n c e / a b s e n c e / m e t h o d o f r a n d o m i z a t i o n

l e d t o t h e c l a s s i f i c a t i o n o f t h e B u f a l i n i 2 0 0 9 s t u d y [ 3 4 ] a s a c o n t r o l l e d c l i n i c a l t r i a l b y t h e a u t h o r s o f t h e 2 0 1 1

C o c h r a n e r e v i e w [ 1 3 ] . N o t e t h a t t h e

B u f a l i n i 2 0 0 9 s t u d y [ 3 4 ] u s e d m Y P A S s c o r e

s t o m e a s u r e a n x i e t y i n t h e p a t i e n t s , b u t o n l y

u s e d S T A I - S s c o r e s t o m e a s u r e a n x i e t y i n t h

e p a r e n t s . S i n c e t h e S T A I - S

s c o r e s i n t h e p a r e n t s ( u n l i k e t h e m Y

P A S s c o r e s i n t h e p a t i e n t s ) s h o w e d n o s i g n i f i c a n t d i f f e r e n c e , i t s i n c l u s i o n i n t h e p o o l e d a n a l y s i s w i t h t h e o t h e r s i x t r i a l s w o u l d h a v e t e n d e d t o u n d e r e s t i m a t e t h e

e f f e c t o f m u s i c o n a n x i e t y . F u r t h e r m

o r e , a s e n s i t i v i t y a n a l y s i s , e x c l u d i n g t h e r e s u

l t s o f b o t h t h e B u f a l i n i 2 0 0 9 [ 3 4 ] a n d Y o n g h

u i 2 0 0 9 [ 1 8 ] s t u d i e s ( b a s e d o n u n c l e a r r a n d o m i z a t i o n m e t h o d s ) , r e s u l t e d

i n a m e a n d i f f e r e n c e o f − 9 . 4 6 ( 9 5 %

C I − 1 9 . 0 1 t o 0 . 0 9 ,

P = 0 . 0 5 )

c

P a t i e n t s i n t h e Y o n g h u i 2 0 0 9 s t u d y

[ 1 8 ] w e r e c l e a r l y r a n d o m i z e d , h e n c e i t s c l a s

s i f i c a t i o n a s a n R C T b y t h e a u t h o r s o f t h e 2 0 1 1 C o c h r a n e R e v i e w [ 1 3 ] . H o w e v e r , s i n c e i

t s m e t h o d o f r a n d o m i z a t i o n

w a s n o t e n t i r e l y c l e a r , i t w a s e x c l u d

e d i n t h e s e n s i t i v i t y a n a l y s i s



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with those from four other RCTs involving patients without cancer, in whom perioperative anxiety was significantly re-duced by music-based interventions [38 – 41]. One small but well-designed RCT specifically examined the effectiveness of a single 20 – 40-min MT session in reducing anxiety for termi-nally ill patients [42]. Although cancer was not an inclusioncriterion, 24 out of 25 patients in the study had cancer, and all

study participants were inpatients receiving palliative careservices. Based on the Edmonton Symptom Assessment Scaleanxiety scores before and after the intervention, the Mann – Whitney test showed that anxiety was significantly reduced inthe music group compared to the control group ( P =0.005).

Overall, these data (derived from six studies using MM andtwo studies using MT) support the use of music to reduceanxiety in situations such as before/during invasive proce-dures, chemotherapy, and radiation therapy. Relatively less isknown about music’s capacity to decrease the need for phar-macologic anxiolytics/sedatives/hypnotics. Although one stud-y in 327 patients undergoing elective surgery showed a greater

decrease in preoperative STAI-S scores with relaxing musicthan 0.05 – 0.1mg/kg of midazolam ( P


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T a b l e 3


a t i n g t h e e f f e c t o f m u s i c - b a s e d i n t e r v e n t i o n s o n m o o d d i s t u r b a n c e i n e i t h e r o n c o l o g i c o

r p a l l i a t i v e c a r e s e t t i n g s

A u t h o r ,

y e a r ,

t y p e o f s t u d y

S t u d y

p o p u l a t i o n


C o n t r o l

N ,

m u s i c g r o u p

N ,

c o n t r o l

g r o u p

R e s u l t s

B e c k , 1 9 8 9 ,

R C T a

[ 5 8 ]

A d u l t s w i t h d o c u m e n t e d

c a n c e r - r e l a t e d p a i n

( s e t t i n g : p a t i e n t s ’ h o m e s )

M M : t h r e e 4 5 - m

i n s e s s i o n s

o f p r e r e c o r d e d

m u s i c

t h r o u g h h e a d p h

o n e s .


c l a s s i c a l , j a z z , f o l k ,

r o c k ,

c o u n t r y a n d w e

s t e r n , e a s y

l i s t e n i n g , a n d n

e w a g e

L i s t e n i n g t o 6 0 - c y c l e h u m

t h r o u g h h e a d p h o n e s

8

7

N o s i g n i f i c a n t d i f f e r e n c e

d e t e c t e d i n m e a n p e r c e n t

c h a n g e o f f i v e - p o i n t V A S

b e t w e e n g r o u p s ( P = 0 . 5 9 9 ) .

H o w e v e r ,

“ 6 0 % o f t h e

s u b j e c t s [ i n t h e m u s i c

g r o u p ] d e m o n s t r a t e d a t

l e a s t s o m e i m p r o v e m e n t

i n m o o d ”

C a s s i l e t h e t a l . ,

2 0 0 3 ,

R C T a

[ 5 5 ]

A d u l t s w i t h h e m a t o l o g i c

m a l i g n a n c y a d m i t t e d

f o r

S C T

M T : m e d i a n o f f i v e 2 0 –

3 0 -

m i n s e s s i o n s ( o

v e r m e d i a n

o f 1 0 d a y s ) . L i

v e b e d s i d e

m u s i c t h e r a p y w a s

p r o v i d e d b y t r a

i n e d m u s i c

t h e r a p i s t


3 6

3 3

S i g n i f i c a n t i m p r o v e m e n t i n

m o o d d e t e c t e d : P a t i e n t s i n

t h e m u s i c t h e r a p y g r o u p

s c o r e d 3 7 % l o w e r o n t o t a l

P O M S o f m o o d d i s t u r b a n c e

( P = 0 . 0 1 ) a n d 2 8 % l o w e r

i n t h e c o m b i n e d a n x i e t y /

d e p r e s s i o n d o m a i n s

( P = 0 . 0 6 5 )

D u o c a s t e l l a ,

1 9 9 9 ,

R C T a

[ 5 9 ]

P e d i a

t r i c c a n c e r p a t i e n t s

r e c e i v i n g i n p a t i e n t

c h e m o t h e r a p y

M T : s i n g l e 4 5 - m

i n

i n d i v i d u a l i z e d M T s e s s i o n .

S e s s i o n s i n c l u d

e d s i n g i n g ,

i n s t r u m e n t p l a y

i n g ,

m o v e m e n t t o m

u s i c ,

a n d

m u s i c a l g a m e s

S i n g l e s e s s i o n o f n o n -

m u s i c a l a c t i v i t i e s l e d b y

m u s i c t h e r a p i s t

1 5

1 5

N o s i g n i f i c a n t i m p r o v e m e n t

i n m o o d d e t e c t e d u s i n g

f i v e - p o i n t L i k e r t s c a l e

G a l l a g h e r e t a l . ,

2 0 0 6 ,

s i n g l e - a r m s t u d y b [ 5 ]

A d u l t s w i t h a t e r m i n a l i l l n e s s

i n a

n i n p a t i e n t p a l l i a t i v e

c a r e s e t t i n g b

M T : s i n g l e s e s s i o

n o f v a r y i n g

l e n g t h i n c l u d i n g l i v e

p e r f o r m a n c e , l i

s t e n i n g t o

p r e r e c o r d e d m u

s i c , a n d

i n t e r a c t i v e t e c h

n i q u e s

N o n e

1 2 3

0

S i g n i f i c a n t i m p r o v e m e n t i n

m o o d d e t e c t e d : m e a n s e l f -

r e p o r t e d m o o d d i s t u r b a n c e

s c o r e s i m p r o v e d f r o m 1 . 8

t o 0 . 7 o n a f i v e - p o i n t V A S

a f t e r a s i n g l e m u s i c t h e r a p y

s e s s i o n ( P < 0 . 0 0 1 )


M T m u s i c t h e

r a p y

a


b

P e r c e n t a g e o f p a t i e n t s w i t h c a n c e r

n o t s p e c i f i e d



8/16

T a b l e 4


a t i n g t h e e f f e c t o f m u s i c - b a s e d i n t e r v e n t i o n s o n Q O L i n e i t h e r o n c o l o g i c o r p a l l i a t i v e c

a r e s e t t i n g s

A u t h o r ,

y e a r , t y p e o f s t u d y S t u d y p

o p u l a t i o n


C o n t r o l

N m u s i c

g r o u p

N c o n t r o l

g r o u p

R e s u l t s

H a n s e r , 2 0 0 6 ,

R C T a

[ 5 7 ]

M e t a s t a t i c b r e a s t c a n c e r

p a t i e n

t s ( o u t p a t i e n t s e t t i n g )

M T : t h r e e 4 5 - m

i n s e s s i o n s

c o n s i s t i n g o f l i v e m u s i c ,

i m p r o v i s a t i o n , a n d s o n g w r i t i n g


2 0

2 2

N o s i g n i f i c a n t i m p r o v e m e n t i n Q O L

d e t e c t e d u s i n g t h e 1 3 6 - p o i n t F A C T - G

s c a l e . A l t h o u g h t h e

m u s i c g r o u p ’ s m e a n

s c o r e r o s e f r o m 7 5 . 4

t o 7 8 . 9 ,

a n d t h e c o n t r o l

g r o u p ’ s m e a n s c o r e

o n l y r o s e f r o m

8 2 . 2

t o 8 3 . 1 ,

P > 0 . 0

5

B u r n s , 2 0 0 1 ,

R C T a

[ 7 5 ]

A d u l t o

u t p a t i e n t s w i t h c a n c e r M T : 1 0 w e e k l y 9 0 –

1 2 0 - m i n

s e s s i o n s o f t h e B o

n n y M e t h o d

o f G u i d e d I m a g e r y a n d “ s p e c i a l l y

s e q u e n c e d W e s t e r n A r t ”

m u s i c

W a i t - l i s t g r o u p

4

4

N o s i g n i f i c a n t i m p r o v e m e n t i n Q O L d e t e c t e d

u s i n g 1 0 0 - p o i n t Q O

L - C a n c e r S c a l e .

A l t h o u g h

t h e m u s i c g r o u p ’ s m

e a n s c o r e r o s e f r o m

7 5 . 4

0 t o 9 1 . 7

7 , a n d

c o n t r o l g r o u p ’ s m e a n

s c o r e o n l y r o s e f r o m 7 6 . 0

2 t o 7 7 . 8

5 , P > 0 . 0 5

H i l l i a r d , 2 0 0 3 ,

R C T a

[ 7 6 ]

A d u l t s

w i t h t e r m i n a l c a n c e r

( s e t t i n g : h o m e h o s p i c e )

M T : 2 – 1 3 w e e k l y / b

i w e e k l y M T

s e s s i o n s o f v a r y i n g l e n g t h s .

T e c h n i q u e s i n c l u d

e d s i n g i n g ,

l y r i c a n a l y s i s ,

i n s t r u m e n t p l a y i n g ,

s o n g p a r o d y ,

p l a n n i n g o f f u n e r a l s ,

s o n g g i f t s


4 0

4 0

S i g n i f i c a n t i m p r o v e m

e n t i n Q O L d e t e c t e d u s i n g

2 8 0 - p o i n t H o s p i c e Q O L I n d e x - R e v i s e d s c a l e

( P < 0 . 0 5 ) . M u s i c g r o u p ’ s m e a n s c o r e r o s e

f r o m 2 0 6 . 8 t o 2 1 4 . 6 , w h i l e c o n t r o l g r o u p ’ s

m e a n s c o r e f e l l f r o m 1 8 8 . 5 t o 1 7 7 . 9

Z h o n g a n d G a n g , 2 0 0 1 ,

R C T a

[ 7 7 ]

A d u l t c

a n c e r p a t i e n t s

r e c e i v

i n g c h e m o t h e r a p y

M M : t w i c e d a i l y 6 0

- m i n s e s s i o n s f o r 2 0 d a y s


1 2 4

1 3 6

S i g n i f i c a n t i m p r o v e m

e n t i n Q O L d e t e c t e d u s i n g

Q O L Q u e s t i o n n a i r e

f o r C h i n e s e p a t i e n t s

( P < 0 . 0 1 ) . M u s i c g r o u p ’ s m e a n s c o r e f e l l

s l i g h t l y f r o m 4 9 . 2

t o 4 7 . 2 ,

w h i l e c o n t r o l

g r o u p ’ s m e a n s c o r e

f e l l f r o m 4 9 . 9

t o 3 4 . 5


M T m u s i c t h e

r a p y

a


[ 1 3 ]

2616 Support Care Cancer (2013) 21:2609 – 2624


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the unavailability of any fast-acting pharmacologic antide- pressant, may point toward potentially important neurobio-logical differences underlying these symptoms. With this inmind, particular consideration should be given to the fre-quency and duration (as well as the type) of interventions infuture studies investigating the impact of music on mood incancer patients.

Quality of life

Although there may be less prevalence data measuringoverall QOL impairment in cancer patients (relative to pain,anxiety, and depression), the available data suggest that cancer is indeed associated with impaired QOL comparedto the normal population [60 – 62]. This association could beexpected for a number of reasons: first, because pain, anx-iety, and depression are frequently incorporated into thetools used to measure HR-QOL in cancer patients; secondly,

because all three of these symptoms have been shown to

commonly affect patients with cancer [63]; and finally, because multiple studies in patients with multiple types of cancer have demonstrated independent associations betweenHR-QOL impairment and pain [64 – 68], anxiety [69 – 71],and depression [72 – 74].

Although the impact of music-based interventions onQOL has not been as extensively studied as pain, anxiety,or mood disturbance, four RCTs analyzed in the 2011Cochrane Review [13] compared the impact of music-

based int erventi ons to standard care on QOL scores(Table 4). Clearly, QOL represents a more complex andmulti-faceted outcome than pain, anxiety, or depression,

and the comparison of results from these four studies wasmade even more complex by the fact that they all useddifferent QOL assessment tools. In one of the four studies[57], pretest differences were too large for the results to beincluded in the pooled estimate. Through the other threetrials, music was offered to 4 of 8 adults with cancer [75], 40out of 80 adults with terminal cancer [76], and 124 out of 260 cancer patients receiving chemotherapy [77]. When theresults from these three trials were subject to meta-analysis, aheterogeneous, nonsignificant effect was found (SMD= 2.01,95 % CI −0.09 to 4.11, P =0.06). Paradoxically, thisnonsignificance actually resulted from a much larger benefi-

cial effect reported in the study by Zhong [77] than that reported in the studies by Burns [75] and Hilliard [76]. Whenthe results from the Burns and Hilliard studies were subject tometa-analysis ( N =88), this resulted in a homogenous andsignificant effect of MT on QOL (SMD=1.02, 95 %CI 0.58to 1.47, P =0.00001). One interesting aspect of the Hilliardstudy was that even as the physical health of the patients in themusic group declined, QOL scores improved. This was not thecase in the control group, in whom QOL scores worsened astheir physical health declined [76].

Clearly, more research is needed to investigate the impact of music on QOL. Given the crucial importance of this

Fig. 1 a Sagittal view of neuroanatomic regions affected by music(and implicated in the pathophysiology of pain, anxiety, and/or depres-sion). b Inferior view of neuroanatomic regions affected by music (andimplicated in the pathophysiology of pain, anxiety, and/or depression)



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outcome to cancer patients in palliative care settings, futurestudies investigating the effect of music-based interventionson pain, anxiety, or mood disturbance in this patient popu-lation should incorporate QOL measurements into their outcome assessment.

Relevant advances in neurobiology

Previous speculations regarding the potential mechanisms of music-based interventions may have drastically oversimplifiedan extremely complex set of possible neurobiological process-es [78]. Many investigators have proposed that music maycompete with noxious stimuli and thereby close neurologicalgates of pain signal transmission, or that it may distract patientsfrom threats that cause them to feel anxious, and/or that it may

promote a sense of well-being in patients with an otherwisedepressed mood. While these may all be valid theories,advances in neuroscience, and functionalneuroimaging studies

in particular, are providing dramatic new insights intothe findings from clinical trials involving music-basedinterventions (Table 5).

Multiple studies have explored changes in activity withinthe brains of healthy, asymptomatic adults upon exposure tomusic. Broadly speaking, functional imaging data have shownthat music modulates the activity of multiple limbic and

paralimbic brain structures, but especially the ventral striatum(including the nucleus accumbens), the dorsomedial midbrain(including the ventral tegmental area and periaqueductalgray), the amygdala, and the hippocampus (Fig. 1a, b). This

particular neuroanatomic distribution is striking for at least

two reasons. The first is that functional abnormalities in thesesame structures are implicated in the pathophysiology of pain[79 – 81], anxiety [82 – 84], and depression [85 – 87]. The sec-ond is that these same structures are known to be densely

populated by receptors of ligands associated with pain, anxi-ety, and depression — namely, endogenous opioids [88, 89],GABA [90, 91], and dopamine [92, 93].

Listening to music has long been known to evoke strongemotional responses which can sometimes be accompanied by

physical manifestations, e.g., piloerection, more commonlyknown as “goosebumps” or “chills” [94, 95]. The suppression

of this response with the mu-opioid receptor agonist nalaxolone provided early evidence that endogenous opioidactivity might underlie pleasurable responses to music [96].Positron emission tomography experiments subsequentlyshowed that piloerection in response to music may be associ-ated with increased regional cerebral blood flow to the ventralstriatum and the dorsomedial midbrain but decreased regional

cerebral blood flow (rCBF) to the hippocampus and amygdala[97]. Even in the absence of piloerective responses, fMRIevidence suggested that consonant musical excerpts may in-crease activity in the ventral striatum and the anterior insula[98, 99], while dissonant excerpts may increase activity in theamygdala and hippocampus [99]. Data collected from [11C]raclopride PET demonstrated that intensely pleasurable re-sponses to music may be associated with dopamine releasein the striatal system [100]. This dopaminergic activity in the

NAc following exposure to music (and other pleasurablestimuli, e.g., sex, food, and drugs of abuse) may itself bemodulated by endogenous opioids [101]. Furthermore, evi-

dence from animal models suggests that opioid efferent pro- jections from the NAc may directly mediate reward-related behavior [102]. Within the dorsomedial midbrain (which wasfound to receive increased rCBF during highly pleasurablemusical experiences as shown in [97]), the substructureknown as the periaqueductal gray has been shown to bedensely populated with endogenous opioid receptors andmay be involved in both opioid-mediated reward [103] andanalgesia [79, 104]. Preliminary research suggests that theaction of endogenous opioids in the PAG may be influenced

by the hormone oxytocin [105]; the blood concentrations of which was found to be increased (along with subjective re-

laxation) in perioperative patients exposed to soothing music[106]. Although multiple functional imaging studies haveshown music to modulate the activity of the amygdala [97,107], and multiple functional imaging studies have demon-strated an association between anxiety and enhancedamygdalar activity [82, 83, 108, 109], no radioligand bindingexperiments have specifically investigated the effect of musicon gamma amino-butyric acid activity in the brain. Withregard to mood disturbance, it is worth noting that music has

been shown to modulate the activity of the subcallosal cingu-late region [107, 110], an area which has been shown to have

Fig. 2 General conceptualmodel for the potentiallytherapeutic impact(s) of music-based interventions incancer patients



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decreased rCBF in patients with depression [111]. Further-more, deep brain stimulation of the subcallosal cingulateregion has been shown to be an effective treatment for severedepression [86]. Finally, platelet concentrations of serotonin,which may correlate with neuronal concentrations of seroto-nin [112, 113], were found to be increased in humans exposedto euphonic music, but decreased in humans exposed to

cacophonic music [114].Overall, these advances in neurobiology suggest that

music may affect specific neuronal pathways that are impli-cated in the pathophysiology of pain, anxiety, and depres-sion. Thus, future neurobiological studies may provideobjective insight into the mechanisms by which musicmay affect these subjective symptoms that commonly afflict

patients with cancer.

Conclusions

In 2002, the WHO approved the following definition of palliative care: “An approach that improves the quality of life of patients and their families facing the problems asso-ciated with life-threatening illness, through the preventionand relief of suffering by means of early identification andimpeccable assessment and treatment of pain and other

problems, physical, psychosocial and spiritual” [115]. Inthe future, music-based interventions may prove to becomevaluable tools in the “relief of suffering” of cancer patients.Specifically, music may help alleviate pain, anxiety, andmood disturbance, all of which commonly occur in cancer,and all of which may be associated with impaired QOL. The

potential of music to reduce the need for analgesics and/or anxiolytics, even if only by a small amount, may still havemajor clinical implications, especially given the frequencywith which advanced age and hepato-renal dysfunction co-exist in the palliative cancer care population (and hence their

predisposition to pharmacologic toxicity). Furthermore,when the only pharmacologic agents available for mooddisturbance take weeks to months to take effect, interven-tions that provide more immediate benefits, even if modest,may warrant further investigation.

It is not difficult to imagine how, for cancer patients unfa-miliar with the standard inpatient healthcare environment, the

hospital setting could be associated with unexpected pain(e.g., from repeated injections, blood draws, and other inva-sive procedures), anxiety (e.g., from loud equipment alarmsand time-constrained conversations regarding prognosis oftenclouded by medical jargon), and even depression (e.g., relatedto the existential issues of having a life-threatening illness,limited social interaction, frequently interrupted sleep, etc.).The capacity of music to restore a sense of familiarity, and thetherapeutic value of such a reassuring stimulus (regardless of where a patient may be in his or her disease trajectory), may be

underestimated. Such reassuring familiarity could be providedin the form of a playlist of favorite songs on a portable mp3

player with headphones or even through melodic arrangement by a live music therapist that actually incorporates tones fromthe surrounding environment [116]. It should not necessarily

be assumed that the benefits of music are limited to the relief of symptoms; that is to say, that music merely counteracts the

negative consequencesof disease (Fig. 2). The need for beauty(and for some, spiritual solace) may be particularly great toward the end of life for many patients. In this respect, musicmay exceed where standard pharmacologic means fall short.Many qualitative studies support both the potential symptom-alleviating and wellness-promoting effects of music [3, 10,117 – 125]. However, quantitative data in these areas still re-main limited.

In the absence of more RCTs with larger sample sizes,meta-analyses [13, 20, 126] can provide useful quantitativeassessments of impact. However, controlling for variation instudy design, study population, specific intervention(s), and

outcome assessment methods, presents enormous challenges.For example, different music therapists can introduce variabil-ity in outcomes, even when the same specific interventions areused [127]. The data presented in the individual trials and themeta-analyses discussed in this review should therefore beconsidered preliminary and interpreted with caution. The sta-tistical quality of the data in question remains diminished byhigh risk of bias, which almost invariably arises from theinherent difficulties associated with conventional blinding inmusic-based intervention studies. Furthermore, without reli-able biomarkers for pain, anxiety, and depression, defining the“gold standard” in quantitative assessment of these outcomes

remains formidable. Fortunately, the cost of music-based in-terventions remains relatively low [128], and breakthroughs inthe field of neurobiology continue to advance our understand-ing of the anatomical and biochemical basis of how musicworks in the brain, and why symptoms such as pain, anxiety,and mood disturbance might be influenced.

Further investigation is warranted to determine (1) if certain subpopulations of cancer patients are more likely torespond to music-based interventions than others, (2) what interventions are most effective for such responsive patients,and (3) what measurement parameters best gauge their ef-fectiveness. Greater collaboration between the fields of mu-

sic therapy and music neuroscience may accelerate the pursuit of these objectives. Finally, given the emergingevidence that earlier involvement of palliative care mayimprove outcomes in certain cancer patients [129], and that

psychological stress may be linked to up-regulation of in-flammatory processes that promote tumor growth and an-giogenesis [130 – 133], it follows that research into the

potential of music to specifically promote relaxation andreduce stress [134], perhaps earlier in cancer ’s trajectory,may also be warranted.



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Acknowledgments Thanks to David Aten of MDACC MedicalGraphics & Photography for illustrating all figures and to Mei Dongand Biquan Luo for the help with translation.

Conflict of Interest I have no financial relationships to disclose. Ihave full control over the content of this article. I submit the entirety of this manuscript for review by Supportive Care in Cancer.

Open Access This article is distributed under the terms of the Creative

Commons Attribution Noncommercial License which permits anynoncommercial use, distribution, and reproduction in any medium,

provided the original author(s) and the source are credited.

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