Effectiveness of interventions to improve antidepressant medication adherence: a systematic review W. W. Chong, P. Aslani, T. F. Chen Introduction Depression is one of the most prevalent forms of mental disorder, with a high public health impact. It is expected that depression will become the sec- ond leading cause of disability worldwide by the year 2020 (1). Depression is frequently treated in primary care practice with antidepressant medica- tions (2). Although antidepressants may be effective in the treatment of depression (3), patients’ failure to take them as prescribed remains a significant obstacle to treatment success in clinical practice. The World Health Organization (WHO) has recog- nised depression as one of the nine chronic conditions to be focused on for improving medica- tion adherence (4). Adherence has been defined as ‘the extent to which a person’s behaviour coincides with the medical advice given’ (5). Previous studies have highlighted two main aspects of adherence problems with antidepressants – the premature discontinuation of antidepressant therapy (also known as medication non-persistence) and the lack of consistency with the prescribed regi- men in the context of ongoing use (medication non- compliance). Although treatment guidelines advocate the continuous use of antidepressants for at least Faculty of Pharmacy, The University of Sydney, NSW, Australia Correspondence to: Wei Wen Chong, PhD Student, Faculty of Pharmacy, The University of Sydney, NSW 2006, Australia Tel.: + 612 9036 9490 Fax: + 612 9351 4391 Email: weiwen.chong@sydney. edu.au Disclosures The authors have no sources of funding or conflicts of interest to declare. SUMMARY Non-adherence to antidepressant medications is a significant barrier to the suc- cessful treatment of depression in clinical practice. This review aims to systemati- cally assess the effectiveness of interventions for improving antidepressant medication adherence among patients with unipolar depression, and to evaluate the effect of these interventions on depression clinical outcomes. MEDLINE, Psy- cINFO and EMBASE databases were searched for English-language randomised controlled trials published between January 1990 and December 2010 on interven- tions to improve antidepressant adherence. The impact of interventions on antide- pressant medication adherence (compliance and persistence) and depression clinical outcomes was evaluated. Data concerning the quality of the included stu- dies were also extracted. Twenty-six studies met the inclusion criteria. Interventions were classified as educational, behavioural and multifaceted interventions. A total of 28 interventions were tested, as two studies investigated two interventions each. Sixteen (57%) of the 28 interventions showed significant effects on antide- pressant adherence outcomes, whereas 12 (43%) interventions demonstrated sig- nificant effects on both antidepressant adherence and depression outcomes. The interventions which showed significant improvement in outcomes were primarily multifaceted and complex, with proactive care management and involvement of mental health specialists. The most commonly used elements of multifaceted inter- ventions included patient educational strategies, telephone follow-up to monitor patients’ progress, as well as providing medication support and feedback to pri- mary care providers. Overall, educational interventions alone were ineffective in improving antidepressant medication adherence. In conclusion, improving adher- ence to antidepressants requires a complex behavioural change and there is some evidence to support behavioural and multifaceted interventions as the most effec- tive in improving antidepressant medication adherence and depression outcomes. More carefully designed and well-conducted studies are needed to clarify the effect of interventions in different patient populations and treatment settings. Review criteria A literature search was conducted using the MEDLINE, PsycINFO and EMBASE databases to identify randomised controlled trials of interventions to improve antidepressant adherence. A manual search was also performed on the reference lists of included studies, relevant reviews as well as the authors’ personal files. Data concerning the type of intervention, adherence measures, adherence outcomes and depression clinical outcomes were extracted from included studies to enable comparison. Message for the clinic A systematic review of 26 studies indicated that the interventions that were successful in improving both antidepressant adherence and depression clinical outcomes were primarily multifaceted interventions that employed combinations of educational, behavioural, affective and provider- targeted strategies. Given the nature of depression as a chronic and recurrent illness, ongoing supportive services may be necessary especially at critical points of treatment. More rigorous and well- conducted studies are necessary to improve antidepressant compliance and persistence in a variety of patient populations and settings. SYSTEMATIC REVIEW ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975 954 doi: 10.1111/j.1742-1241.2011.02746.x
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Effectiveness of interventions to improveantidepressant medication adherence:a systematic review
W. W. Chong, P. Aslani, T. F. Chen
Introduction
Depression is one of the most prevalent forms of
mental disorder, with a high public health impact.
It is expected that depression will become the sec-
ond leading cause of disability worldwide by the
year 2020 (1). Depression is frequently treated in
primary care practice with antidepressant medica-
tions (2). Although antidepressants may be effective
in the treatment of depression (3), patients’ failure
to take them as prescribed remains a significant
obstacle to treatment success in clinical practice.
The World Health Organization (WHO) has recog-
nised depression as one of the nine chronic
conditions to be focused on for improving medica-
tion adherence (4).
Adherence has been defined as ‘the extent to which
a person’s behaviour coincides with the medical advice
given’ (5). Previous studies have highlighted two main
aspects of adherence problems with antidepressants –
the premature discontinuation of antidepressant
therapy (also known as medication non-persistence)
and the lack of consistency with the prescribed regi-
men in the context of ongoing use (medication non-
compliance). Although treatment guidelines advocate
the continuous use of antidepressants for at least
Faculty of Pharmacy, The
University of Sydney, NSW,
Australia
Correspondence to:
Wei Wen Chong, PhD Student,
Faculty of Pharmacy, The
University of Sydney, NSW
2006, Australia
Tel.: + 612 9036 9490
Fax: + 612 9351 4391
Email: weiwen.chong@sydney.
edu.au
Disclosures
The authors have no sources of
funding or conflicts of interest
to declare.
SUMMARY
Non-adherence to antidepressant medications is a significant barrier to the suc-
cessful treatment of depression in clinical practice. This review aims to systemati-
cally assess the effectiveness of interventions for improving antidepressant
medication adherence among patients with unipolar depression, and to evaluate
the effect of these interventions on depression clinical outcomes. MEDLINE, Psy-
cINFO and EMBASE databases were searched for English-language randomised
controlled trials published between January 1990 and December 2010 on interven-
tions to improve antidepressant adherence. The impact of interventions on antide-
pressant medication adherence (compliance and persistence) and depression
clinical outcomes was evaluated. Data concerning the quality of the included stu-
dies were also extracted. Twenty-six studies met the inclusion criteria. Interventions
were classified as educational, behavioural and multifaceted interventions. A total
of 28 interventions were tested, as two studies investigated two interventions
each. Sixteen (57%) of the 28 interventions showed significant effects on antide-
48,50,51) reported at least 80% patient follow-up.
Sample size calculation was reported in 17 studies
(28,31,33,37,39–42,44–52).
Titles and abstracts identified usingsearch terms and screened
(n = 9568)
Excluded n = 9357Duplicate publications = 1719Irrelevant or review = 7638
Full copies retrieved and assessed for eligibility(n = 211)
Studies identified fromreference lists
(n = 11) Excluded n = 155
Non-RCTs = 45Follow-up < 6 months = 22 No measure of antidepressantadherence = 66 No control group with usual care = 13 No results reported = 9
Potentially relevant RCTs (n = 67)
Excluded n = 41No intervention intended to improveadherence = 11 Adherence not an outcome measure = 8No measure of clinical outcomes = 1Unclear results on adherence = 4Duplicate reporting of data or sub-groupanalyses = 17
RCTs included in review(n = 26)
Figure 1 Flow chart of study selection process
Effectiveness of interventions to improve antidepressant adherence 957
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Tab
le1
Inte
rven
tio
ns
wit
han
edu
cati
on
alo
rb
ehav
iou
ral
focu
sai
med
atim
pro
vin
gan
tid
epre
ssan
tad
her
ence
inp
atie
nts
wit
hu
nip
ola
rd
epre
ssio
n
Stud
yC
ountr
ySe
ttin
g
Sub
ject
char
acte
rist
ics
Pat
ient
po
pula
tio
n
(new
or
conti
nuin
g
AD
use
rs)
Sam
ple
size
Des
crip
tio
no
f
exp
erim
enta
l
inte
rven
tio
n
Asp
ect
of
adher
ence
asse
ssed
(co
mp
lian
ce⁄
per
sist
ence
⁄bo
th)
Met
ho
ds
use
dto
asse
ssad
her
ence
Follo
w-u
p
tim
es
(mo
nth
s)
Ad
her
ence
(co
mp
lian
ce⁄
per
sist
ence
⁄co
mb
ined
*)
outc
om
es(i
nte
rven
tio
n
vs.
contr
ol
gro
up
)
Dep
ress
ion
outc
om
es�
(inte
rven
tio
nvs
.
contr
ol
gro
up
)
Inte
rven
tio
n
gro
up
Co
ntr
ol
gro
up
Educa
tio
nal
-fo
cuse
din
terv
enti
ons
Ake
rbla
det
al.�
(27)
Swed
enPr
imar
y
care
N=
1031
,
Age
=48
.4
Wom
en=
71.9
%
Unc
lear
366
339
Patie
nted
ucat
iona
l
com
plia
nce
enha
ncin
gpr
ogra
mm
e
RHYT
HM
Sco
nsis
ting
ofed
ucat
iona
lm
ater
ial
onde
pres
sion
trea
tmen
t,
mai
led
lett
ers
and
tele
phon
efo
llow
-up
Com
plia
nce
Que
stio
ning
,
seru
mle
vels
,
appo
intm
ents
kept
and
a
com
posi
tein
dex
incl
udin
gal
l
thre
em
etho
ds
1,3
and
6C
ompl
ianc
e:
No
sign
ifica
nt
diff
eren
cebe
twee
n
grou
ps
Trea
tmen
tre
spon
se
(MA
DRS
)at
wee
k24
:
Inte
rven
tion
>co
ntro
l
(71.
0%vs
.60
.5%
;
p=
0.01
)
Ath
erto
n-N
aji
etal
.(2
8)
UK
Prim
ary
care
N=
45
Age
=N
S
Wom
en=
88.9
%
New
AD
user
s
2421
Com
pute
r-ge
nera
ted
educ
atio
nal
inte
rven
tion
cons
istin
gof
mai
led
info
rmat
ion
tailo
red
topa
tient
Pers
iste
nce
Gen
eral
prac
tice
reco
rds
6Pe
rsis
tenc
e:
No
sign
ifica
nt
diff
eren
cebe
twee
n
grou
ps
Men
tal
heal
thst
atus
(HA
DS)
at6
mon
ths:
Inte
rven
tion
>co
ntro
l
(Med
ian
scor
e11
.0vs
.
18.0
;p
=0.
021)
Kutc
her
etal
.(2
9)
Can
ada
Prim
ary
care
N=
269
Age
=N
S
Wom
en=
NS
New
AD
user
s
131
138
RHYT
HM
Sad
here
nce
enha
ncem
ent
prog
ram
me
cons
istin
gof
mai
led
info
rmat
ion
abou
t
depr
essi
onan
dits
phar
mac
olog
ical
trea
tmen
t
Com
plia
nce
and
pers
iste
nce
Pill
coun
ts
Wee
ks
1,3,
5,7,
9,13
,
17,2
1,25
and
29
Com
plia
nce:
No
sign
ifica
nt
diff
eren
cebe
twee
n
grou
ps
Rem
issi
on(D
SM-1
V
⁄HD
RS):
No
sign
ifica
nt
diff
eren
cebe
twee
n
grou
ps
Mun
dt
etal
.(3
0)
USA
Prim
ary
care
N=
246
Age
=40
.5
Wom
en=
78.9
%
New
AD
user
s
122
124
Patie
nted
ucat
ion
prog
ram
me
(RH
YTH
MS)
cons
istin
gof
mai
led
educ
atio
nal
mat
eria
ls
ina
time-
phas
ed
man
ner
Pers
iste
nce
Pres
crip
tion
fill
data
1,3,
and
7Pe
rsis
tenc
e:
No
sign
ifica
nt
diff
eren
cebe
twee
n
grou
ps
Dep
ress
ion
seve
rity
(HD
RS):
No
sign
ifica
nt
diff
eren
cebe
twee
n
grou
ps
958 Effectiveness of interventions to improve antidepressant adherence
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Tab
le1
(Co
nti
nu
ed)
Stud
yC
ountr
ySe
ttin
g
Sub
ject
char
acte
rist
ics
Pat
ient
po
pula
tio
n
(new
or
conti
nuin
g
AD
use
rs)
Sam
ple
size
Des
crip
tio
no
f
exp
erim
enta
l
inte
rven
tio
n
Asp
ect
of
adher
ence
asse
ssed
(co
mp
lian
ce⁄
per
sist
ence
⁄bo
th)
Met
ho
ds
use
dto
asse
ssad
her
ence
Follo
w-u
p
tim
es
(mo
nth
s)
Ad
her
ence
(co
mp
lian
ce⁄
per
sist
ence
⁄co
mb
ined
*)
outc
om
es(i
nte
rven
tio
n
vs.
contr
ol
gro
up
)
Dep
ress
ion
outc
om
es�
(inte
rven
tio
nvs
.
contr
ol
gro
up
)
Inte
rven
tio
n
gro
up
Co
ntr
ol
gro
up
Broo
ket
al.
(31)
The
Net
herla
nds
Prim
ary
care
N=
135
Age
=43
Wom
en=
70%
New
AD
user
s
6471
Com
mun
ityph
arm
acy-
base
dco
achi
ng
prog
ram
me
cons
istin
g
of3
coac
hing
cont
acts
,
take
-hom
evi
deot
ape
and
writ
ten
mat
eria
l
emph
asis
ing
impo
rtan
ce
ofad
here
nce
Com
plia
nce
Elec
tron
icpi
ll
cont
aine
r,ph
arm
acy
med
icat
ion
reco
rds
6C
ompl
ianc
e:
No
sign
ifica
nt
diff
eren
cebe
twee
n
grou
ps
Dep
ress
ive
sym
ptom
s
(SC
L-13
):
No
sign
ifica
nt
diff
eren
cebe
twee
n
grou
ps
Beh
avio
ura
l-fo
cuse
din
terv
enti
on
Ann
eSi
rey
etal
.(3
2)
USA
Prim
ary
care
N=
70
Age
=76
Wom
en=
77%
New
AD
user
s
3337
Trea
tmen
tIn
itiat
ion
and
Part
icip
atio
n(T
IP)
prog
ram
me
invo
lvin
g
indi
vidu
alm
eetin
gsan
d
follo
w-u
pte
leph
one
calls
toid
entif
yan
dta
rget
psyc
holo
gica
lba
rrie
rsto
depr
essi
ontr
eatm
ent
Com
plia
nce
Patie
ntse
lf-re
port
6w
eeks
3,6
mon
ths
Com
plia
nce:
Inte
rven
tion
>co
ntro
l
(p<
0.00
1)
Dep
ress
ion
sym
ptom
s
(HD
RS):
Inte
rven
tion
>co
ntro
l
(p<
0.01
)
*Com
bine
dm
easu
reof
adhe
renc
ein
tegr
ates
both
com
plia
nce
and
pers
iste
nce
aspe
cts
into
one
sing
lem
easu
re.�D
epre
ssio
nou
tcom
esin
stud
ies
wer
eev
alua
ted
usin
gva
rious
mea
sure
sas
stat
edin
brac
kets
.
�Stu
dyev
alua
ted
two
diff
eren
tin
terv
entio
ns;
only
patie
nt-f
ocus
edin
terv
entio
nar
mis
repo
rted
here
in.
N,
num
ber
ofsu
bjec
ts;
Age
,m
ean
year
s;A
D,
antid
epre
ssan
t;N
S,N
otst
ated
;M
AD
RS,
Mon
tgom
ery-
Asb
erg
Dep
ress
ion
Ratin
gSc
ale;
HA
DS,
Hos
pita
lA
nxie
tyan
dD
epre
ssio
nSc
ale;
DSM
-IV,
Dia
gnos
tican
dSt
atis
tical
Man
ual
ofM
enta
lD
isor
ders
-Fo
urth
Editi
on;
HD
RS,
Ham
ilton
Dep
ress
ion
Ratin
gSc
ale;
SCL,
Hop
kins
Sym
p-
tom
Che
cklis
tD
epre
ssio
nSc
ale.
Effectiveness of interventions to improve antidepressant adherence 959
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Tab
le2
Mu
ltif
acet
edin
terv
enti
on
sai
med
atim
pro
vin
gan
tid
epre
ssan
tad
her
ence
inp
atie
nts
wit
hu
nip
ola
rd
epre
ssio
n
Stud
yC
ountr
ySe
ttin
g
Sub
ject
char
acte
rist
ics
Pat
ient
po
pula
tio
n
(new
or
conti
nuin
g
AD
use
rs)
Sam
ple
size
Des
crip
tio
no
f
exp
erim
enta
l
inte
rven
tio
n
Asp
ect
of
adher
ence
asse
ssed
(co
mp
lian
ce⁄
per
sist
ence
⁄bo
th)
Met
ho
ds
use
dto
asse
ssad
her
ence
Follo
w-u
p
tim
es(m
onth
s)
Ad
her
ence
(co
mp
lian
ce⁄
per
sist
ence
⁄co
mb
ined
*)
outc
om
es(i
nte
rven
tio
nvs
.
contr
ol
gro
up
)
Dep
ress
ion
outc
om
es�
(inte
rven
tio
nvs
.
contr
ol
gro
up
)
Inte
rven
tio
n
gro
up
Co
ntr
ol
gro
up
Kato
n
etal
.(3
3)
USA
Prim
ary
care
N=
217
Age
=47
Wom
en
=76
%
Not
clea
r
108
109
Mul
tifac
eted
inte
rven
tion
cons
istin
gof
incr
ease
d
inte
nsity
and
freq
uenc
y
ofvi
sits
with
aPC
P
and
psyc
hiat
rist,
patie
nt
educ
atio
n,co
ntin
ued
surv
eilla
nce
ofad
here
nce
tom
edic
atio
nre
gim
ens
and
PCP
trai
ning
inth
e
trea
tmen
tof
depr
essi
on
Com
plia
nce
and
pers
iste
nce
Com
pute
rised
pres
crip
tion
refil
l
reco
rds
1,4
and
7C
ombi
ned:
Maj
orde
pres
sion
:In
terv
entio
n
grou
p>
cont
rol
grou
p
(75.
5%vs
.50
.0%
;p
<0.
01)
Min
orde
pres
sion
:In
terv
entio
n
grou
p>
cont
rol
grou
p
(79.
7vs
.40
.3%
;p
<0.
001)
50%
Impr
ovem
ent
in
depr
essi
on
sym
ptom
s(S
CL-
90)
Maj
orde
pres
sion
:
Inte
rven
tion
grou
p
>co
ntro
lgr
oup
(74.
4
vs.
43.8
%;
p<
0.01
)
Min
orde
pres
sion
:N
o
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Kato
n
etal
.(3
4)
USA
Prim
ary
care
N=
153
Age
=47
Wom
en
=74
%
Not
clea
r
7776
Stru
ctur
edde
pres
sion
trea
tmen
tpr
ogra
mm
e
cons
istin
gof
patie
ntan
d
PCP
educ
atio
n,di
rect
and
tele
phon
eco
ntac
ts
with
psyc
holo
gist
s,
beha
viou
ral
trea
tmen
t
toin
crea
seus
eof
adap
tive
copi
ngst
rate
gies
and
coun
selli
ngto
impr
ove
med
icat
ion
adhe
renc
e
Com
plia
nce
and
pers
iste
nce
Patie
ntse
lf-re
port
by
tele
phon
ein
terv
iew
,
com
pute
rised
pres
crip
tion
refil
l
reco
rds
1,4
and
7M
ajor
depr
essi
on:
Com
plia
nce
(pat
ient
self-
repo
rt):
4-m
onth
:
Inte
rven
tion
grou
p>
cont
rol
grou
p(8
9%vs
.62
%;
p=
0.02
)
7-m
onth
:N
osi
gnifi
cant
diff
eren
cebe
twee
ngr
oups
Com
bine
d(A
utom
ated
pres
crip
tion
data
):N
o
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Min
orde
pres
sion
:C
ompl
ianc
e:
4-m
onth
:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(74%
vs.
44%
;p
=0.
01)
7-m
onth
:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(65%
vs.
41%
;p
=0.
04)
Com
bine
d:N
osi
gnifi
cant
diff
eren
cebe
twee
ngr
oups
50%
Impr
ovem
ent
in
depr
essi
onsy
mpt
oms
(SC
L-20
)
Maj
orde
pres
sion
:
Inte
rven
tion
grou
p
>co
ntro
lgr
oup
(70.
4%vs
.42
.3%
;
p=
0.04
)
Min
orde
pres
sion
:N
o
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
960 Effectiveness of interventions to improve antidepressant adherence
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Tab
le2
(Co
nti
nu
ed)
Stud
yC
ountr
ySe
ttin
g
Sub
ject
char
acte
rist
ics
Pat
ient
po
pula
tio
n
(new
or
conti
nuin
g
AD
use
rs)
Sam
ple
size
Des
crip
tio
no
f
exp
erim
enta
l
inte
rven
tio
n
Asp
ect
of
adher
ence
asse
ssed
(co
mp
lian
ce⁄
per
sist
ence
⁄bo
th)
Met
ho
ds
use
dto
asse
ssad
her
ence
Follo
w-u
p
tim
es
(mo
nth
s)
Ad
her
ence
(co
mp
lian
ce⁄
per
sist
ence
⁄co
mb
ined
*)
outc
om
es(i
nte
rven
tio
nvs
.
contr
ol
gro
up
)
Dep
ress
ion
outc
om
es�
(inte
rven
tio
nvs
.
contr
ol
gro
up
)
Inte
rven
tio
n
gro
up
Co
ntr
ol
gro
up
Kato
n
etal
.(3
5)
USA
Prim
ary
care
N=
228
Age
=47
Wom
en
=75
%
Con
tinui
ng
AD
user
s
114
114
Step
ped
colla
bora
tive
care
inte
rven
tion
targ
etin
gpa
tient
s
with
pers
iste
nt
depr
essi
vesy
mpt
oms;
inte
rven
tion
cons
iste
d
ofen
hanc
eded
ucat
ion,
incr
ease
dfr
eque
ncy
of
visi
tsby
aps
ychi
atris
t
wor
king
with
the
PCP
and
antid
epre
ssan
t
phar
mac
yre
fill
mon
itorin
g.
Com
plia
nce
and
pers
iste
nce
Patie
ntse
lf-re
port
,
com
pute
rised
phar
mac
yre
cord
s
1,3,
and
6C
ompl
ianc
e(p
atie
ntse
lf-re
port
):
3-m
onth
:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(78.
6%vs
.
62.1
%;
p=
0.02
)
6-m
onth
:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(73.
2%vs
.
50.5
%;
p=
0.00
2)
Com
bine
d(A
utom
ated
pres
crip
tion
data
):
Inte
rven
tion
grou
p>
cont
rol
grou
p(6
8.8%
vs.
43.8
%;
p<
0.00
01)
Rem
issi
on(S
CID
):
3-m
onth
:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(40%
vs.
23%
;p
=0.
01)
6-m
onth
:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(44%
vs.
31%
;p
=0.
05)
Kato
n
etal
.(3
6)
USA
Prim
ary
care
N=
386
Age
=46
Wom
en
=73
.7%
Con
tinui
ng
AD
user
s
194
192
Rela
pse
prev
entio
n
prog
ram
me
that
incl
uded
enha
nced
patie
nted
ucat
ion,
2vi
sits
with
a
depr
essi
onsp
ecia
list,
phar
mac
yre
fill
mon
itorin
g,an
d
tele
phon
em
onito
ring
and
follo
w-u
p
Com
plia
nce
and
pers
iste
nce
Com
pute
rised
auto
mat
edda
ta
from
pres
crip
tion
refil
ls
3,6,
9an
d12
Com
bine
d:
Inte
rven
tion
grou
p>
cont
rol
grou
p(O
dds
ratio
2.08
;
95%
CI,
1.41
-3.0
6;
p<
0.00
1)
Dep
ress
ive
sym
ptom
s(S
CL-
20):
Inte
rven
tion
grou
p>
cont
rol
grou
p(M
ean
diff
eren
ce=
0.08
,
p=
0.04
)
Rela
pse
⁄recu
rren
ce(S
CID
):N
o
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Effectiveness of interventions to improve antidepressant adherence 961
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Tab
le2
(Co
nti
nu
ed)
Stud
yC
ountr
ySe
ttin
g
Sub
ject
char
acte
rist
ics
Pat
ient
po
pula
tio
n
(new
or
conti
nuin
g
AD
use
rs)
Sam
ple
size
Des
crip
tio
no
f
exp
erim
enta
l
inte
rven
tio
n
Asp
ect
of
adher
ence
asse
ssed
(co
mp
lian
ce⁄
per
sist
ence
⁄bo
th)
Met
ho
ds
use
dto
asse
ssad
her
ence
Follo
w-u
p
tim
es
(mo
nth
s)
Ad
her
ence
(co
mp
lian
ce⁄
per
sist
ence
⁄co
mb
ined
*)
outc
om
es(i
nte
rven
tio
nvs
.
contr
ol
gro
up
)
Dep
ress
ion
outc
om
es�
(inte
rven
tio
nvs
.
contr
ol
gro
up
)
Inte
rven
tio
n
gro
up
Co
ntr
ol
gro
up
Unu
tzer
etal
.(3
7)
USA
Prim
ary
care
N=
1801
Age
=71
.2
Wom
en=
65%
All
curr
ent
user
s
906
895
IMPA
CT
prog
ram
(Impr
ovin
gM
ood-
Prom
otin
gA
cces
s
toC
olla
bora
tive
Trea
tmen
t)in
volv
ing
acce
ssto
a
depr
essi
onca
re
man
ager
who
prov
ided
educ
atio
n,
care
man
agem
ent,
med
icat
ion
supp
ort
for
PCP
and
abr
ief
psyc
hoth
erap
yfo
r
depr
essi
on,
Prob
lem
Solv
ing
Trea
tmen
tin
Prim
ary
Car
e
Pers
iste
nce
(any
AD
use)
Patie
ntse
lf-re
port
3,6
and
12Pe
rsis
tenc
e:
6m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(68.
9%vs
.
52.3
%;
p<
0.00
1)
12m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(73%
vs.
57.2
%;
p<
0.00
1)
Trea
tmen
tre
spon
se(S
CL-
20):
6m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(49.
3%vs
.
30.9
%,
p<
0.00
1)
12m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(44.
7%vs
.
19.2
%;
p<
0.00
1)
Katz
elni
ck
etal
.(3
8)
USA
Prim
ary
care
N=
407
Age
=45
.4
Wom
en=
77.5
%
New
AD
user
s
218
189
Dep
ress
ion
man
agem
ent
prog
ram
me
(DM
P)
cons
istin
gof
patie
nt
educ
atio
nm
ater
ials
,
phys
icia
ned
ucat
ion
prog
ram
mes
,te
leph
one-
base
dtr
eatm
ent
coor
dina
tion,
and
AD
phar
mac
othe
rapy
initi
ated
and
man
aged
bypr
imar
yca
re
prov
ider
s
Com
plia
nce
(>3
fills
at
6m
onth
s)
Phar
mac
yre
fill
data
6w
eeks
,3,
6,
12m
onth
s
Com
plia
nce:
6m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(69.
3%vs
.
18.5
%;
p<
0.00
1)
Trea
tmen
tre
spon
se(H
DRS
):
12m
onth
s:In
terv
entio
n>
cont
rol
(53.
2%vs
.32
.8%
;
p<
0.00
1)
962 Effectiveness of interventions to improve antidepressant adherence
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Tab
le2
(Co
nti
nu
ed)
Stud
yC
ountr
ySe
ttin
g
Sub
ject
char
acte
rist
ics
Pat
ient
po
pula
tio
n
(new
or
conti
nuin
g
AD
use
rs)
Sam
ple
size
Des
crip
tio
no
f
exp
erim
enta
l
inte
rven
tio
n
Asp
ect
of
adher
ence
asse
ssed
(co
mp
lian
ce⁄
per
sist
ence
⁄bo
th)
Met
ho
ds
use
dto
asse
ssad
her
ence
Follo
w-u
p
tim
es
(mo
nth
s)
Ad
her
ence
(co
mp
lian
ce⁄
per
sist
ence
⁄co
mb
ined
*)
outc
om
es(i
nte
rven
tio
nvs
.
contr
ol
gro
up
)
Dep
ress
ion
outc
om
es�
(inte
rven
tio
nvs
.
contr
ol
gro
up
)
Inte
rven
tio
n
gro
up
Co
ntr
ol
gro
up
Wel
ls
etal
.(3
9)
USA
Prim
ary
care
N=
1356
Age
=44
Wom
en=
71%
All
curr
ent
user
s
913
443
Qua
lity
impr
ovem
ent
prog
ram
me
(QI-m
eds
&Q
I-the
rapy
)in
volv
ing
inst
itutio
nal
com
mitm
ent,
trai
ning
loca
lle
ader
sto
prov
ide
clin
icia
nan
d
patie
nted
ucat
ion,
iden
tifica
tion
ofa
pool
ofpo
tent
ially
depr
esse
d
patie
nts,
and
eith
ernu
rses
for
med
icat
ion
follo
w-u
p
orac
cess
totr
aine
d
psyc
hoth
erap
ists
.
Com
plia
nce
and
pers
iste
nce
Patie
ntse
lf-re
port
6an
d12
Com
bine
d:
6m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(34.
7%vs
.
25.1
%;
p=
0.00
1)
12m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(31%
vs.
24%
;
p=
0.01
)
Prob
able
diso
rder
(CES
-D)�
6m
onth
s:In
terv
entio
ngr
oup
<co
ntro
lgr
oup
(39.
9%vs
.
49.9
%;
p=
0.00
1)
12m
onth
s:In
terv
entio
ngr
oup
<co
ntro
lgr
oup
(41.
6%vs
.
51.2
%;
p=
0.00
5)
Dob
scha
etal
.(4
0)
USA
Prim
ary
care
N=
375
Age
=57
Wom
en=
7%
All
curr
ent
user
s
189
186
The
depr
essi
onde
cisi
on
supp
ort
team
prov
ided
a
sing
lepa
tient
educ
atio
nal
cont
act
asw
ell
as
sym
ptom
and
adhe
renc
e
mon
itorin
gw
ithfe
edba
ck
tocl
inic
ians
over
12
mon
ths
Com
plia
nce
and
pers
iste
nce
Com
pute
rised
data
base
6an
d12
Pers
iste
nce:
AD
sfo
r90
days
orm
ore:
Inte
rven
tion
grou
p>
cont
rol
grou
p
(76.
2%vs
.61
.6%
;p
=0.
008)
AD
sfo
r18
0da
ysor
mor
e:
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Com
bine
d:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(72.
1%vs
.
58.4
%;
p=
0.01
9)
Dep
ress
ion
seve
rity
(SC
L-20
)
at6
and
12m
onth
s:N
o
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Die
tric
h
etal
.(4
1)
USA
Prim
ary
care
N=
405
Age
=42
Wom
en=
80%
New
AD
user
s
224
181
Tele
phon
esu
ppor
t
byca
rem
anag
ers
with
feed
back
to
clin
icia
nsan
d
supe
rvis
ion
from
psyc
hiat
rists
Pers
iste
nce
(any
AD
use)
Patie
ntse
lf-re
port
3an
d6
Pers
iste
nce:
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Trea
tmen
tre
spon
se(S
CL-
20)
at6
mon
ths:
Inte
rven
tion
grou
p
>co
ntro
lgr
oup
(59.
9%vs
.46
.6%
;
p=
0.02
1)
Rem
issi
on(S
CL-
20)
at6
mon
ths:
Inte
rven
tion
grou
p>
cont
rol
grou
p
(37.
3%vs
.26
.7%
;p
=0.
014)
Effectiveness of interventions to improve antidepressant adherence 963
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Tab
le2
(Co
nti
nu
ed)
Stud
yC
ountr
ySe
ttin
g
Sub
ject
char
acte
rist
ics
Pat
ient
po
pula
tio
n
(new
or
conti
nuin
g
AD
use
rs)
Sam
ple
size
Des
crip
tio
no
f
exp
erim
enta
l
inte
rven
tio
n
Asp
ect
of
adher
ence
asse
ssed
(co
mp
lian
ce⁄
per
sist
ence
⁄bo
th)
Met
ho
ds
use
dto
asse
ssad
her
ence
Follo
w-u
p
tim
es
(mo
nth
s)
Ad
her
ence
(co
mp
lian
ce⁄
per
sist
ence
⁄co
mb
ined
*)
outc
om
es(i
nte
rven
tio
nvs
.
contr
ol
gro
up
)
Dep
ress
ion
outc
om
es�
(inte
rven
tio
nvs
.
contr
ol
gro
up
)
Inte
rven
tio
n
gro
up
Co
ntr
ol
gro
up
Fort
ney
etal
.(4
2)
USA
Prim
ary
care
N=
395
Age
=59
.2
Wom
en=
8%
All
curr
ent
user
s
177
218
Tele
med
icin
e-ba
sed
colla
bora
tive
care
inte
rven
tion
cons
istin
g
ofsc
ripte
dte
leph
one
enco
unte
rsw
ithnu
rse
care
man
ager
s,
feed
back
toPC
Ps,
med
icat
ion
man
agem
ent
by
phar
mac
ists
and
psyc
hiat
ricco
nsul
tatio
ns
with
tele
psyc
hiat
rists
Com
plia
nce
Patie
ntse
lf-re
port
and
phar
mac
yre
cord
s
6an
d12
Com
plia
nce
6m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(74.
5%vs
.
68.3
%;
p=
0.04
)
12m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(76.
4%vs
.
66.2
%;
p=
0.01
)
Trea
tmen
tre
spon
se(S
CL-
20)
6m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(23.
8%vs
.15
.5%
;
p=
0.02
)
12m
onth
s:N
osi
gnifi
cant
diff
eren
ce
betw
een
grou
ps
Rem
issi
on(S
CL-
20)
6m
onth
s:N
osi
gnifi
cant
diff
eren
ce
betw
een
grou
ps
12m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(24.
0%vs
.12
.7%
;
p=
0.02
)
Hun
kele
r
etal
.(4
3)
USA
Prim
ary
care
N=
302
Age
=55
.4
Wom
en=
69%
New
AD
user
s
I1:
117
I2:
62
123
Inte
rven
tion
1:Te
lehe
alth
care
cons
istin
gof
emot
iona
lsu
ppor
tan
d
focu
sed
beha
viou
ral
inte
rven
tions
inte
n6-
min
calls
bypr
imar
yca
re
nurs
esIn
terv
entio
n2:
Tele
heal
thca
repl
uspe
er
supp
ort
cons
istin
gof
tele
phon
ean
din
-per
son
supp
ortiv
eco
ntac
tsby
trai
ned
heal
thpl
an
mem
bers
reco
vere
d
from
depr
essi
on
Com
plia
nce
and
pers
iste
nce
Patie
ntse
lf-re
port
,
com
pute
rised
phar
mac
y
reco
rds
6w
eeks
and
6m
onth
s
Com
plia
nce
and
pers
iste
nce:
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Both
inte
rven
tions
:D
epre
ssiv
e
sym
ptom
s(5
0%im
prov
emen
t
inH
DRS
):
6m
onth
s:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(57%
vs.
38%
;
p=
0.00
3)
964 Effectiveness of interventions to improve antidepressant adherence
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Tab
le2
(Co
nti
nu
ed)
Stud
yC
ountr
ySe
ttin
g
Sub
ject
char
acte
rist
ics
Pat
ient
po
pula
tio
n
(new
or
conti
nuin
g
AD
use
rs)
Sam
ple
size
Des
crip
tio
no
f
exp
erim
enta
l
inte
rven
tio
n
Asp
ect
of
adher
ence
asse
ssed
(co
mp
lian
ce⁄
per
sist
ence
⁄bo
th)
Met
ho
ds
use
dto
asse
ssad
her
ence
Follo
w-u
p
tim
es
(mo
nth
s)
Ad
her
ence
(co
mp
lian
ce⁄
per
sist
ence
⁄co
mb
ined
*)
outc
om
es(i
nte
rven
tio
nvs
.
contr
ol
gro
up
)
Dep
ress
ion
outc
om
es�
(inte
rven
tio
nvs
.
contr
ol
gro
up
)
Inte
rven
tio
n
gro
up
Co
ntr
ol
gro
up
Rost et
al.
(44)
USA
Prim
ary
care
N=
479
Age
=42
.6
Wom
en=
83.9
%
All
curr
ent
user
s
239
240
Qua
lity
Enha
ncem
ent
by
Stra
tegi
cTe
amin
g
(QU
EST)
inte
rven
tion
invo
lvin
gtw
opr
imar
y
care
phys
icia
ns,
one
nurs
e,an
don
e
adm
inis
trat
ive
staf
f
mem
ber
inea
ch
inte
rven
tion
prac
tice
rece
ivin
gbr
ief
trai
ning
to
impr
ove
the
dete
ctio
n
and
man
agem
ent
of
maj
orde
pres
sion
Com
plia
nce
and
pers
iste
nce
Patie
ntse
lf-re
port
6C
ombi
ned:
New
trea
tmen
tep
isod
e:
Inte
rven
tion
grou
p>
cont
rol
grou
p(3
6.1%
vs.
9.8%
;
p=
0.00
03)
Rece
nttr
eatm
ent:
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Dep
ress
ion
sym
ptom
sse
verit
y
(mC
ES-D
):
New
trea
tmen
tep
isod
e:
Inte
rven
tion
grou
p>
cont
rol
grou
p(D
ecre
ase
insc
ore
8.2,
95%
CI,
0.2-
16.1
;p
=0.
04)
Rece
nttr
eatm
ent:
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Sim
on
etal
.(4
5)
USA
Psyc
hiat
ric
prac
tice
N=
207
Age
=43
Wom
en=
65%
New
AD
user
s
103
104
Thre
ese
ssio
nte
leph
one
care
man
agem
ent
prog
ram
invo
lvin
g
asse
ssm
ent
ofde
pres
sive
sym
ptom
s,m
edic
atio
n
adhe
renc
ean
dm
edic
atio
n
side
-eff
ects
with
stru
ctur
ed
feed
back
totr
eatin
g
psyc
hiat
rists
Com
plia
nce
and
pers
iste
nce
Com
pute
rised
phar
mac
y
reco
rds
3an
d6
Com
bine
d:
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Dep
ress
ion
seve
rity
(SC
L-20
):
6m
onth
s:N
osi
gnifi
cant
diff
eren
ce
betw
een
grou
ps
Effectiveness of interventions to improve antidepressant adherence 965
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Tab
le2
(Co
nti
nu
ed)
Stud
yC
ountr
ySe
ttin
g
Sub
ject
char
acte
rist
ics
Pat
ient
po
pula
tio
n
(new
or
conti
nuin
g
AD
use
rs)
Sam
ple
size
Des
crip
tio
no
f
exp
erim
enta
l
inte
rven
tio
n
Asp
ect
of
adher
ence
asse
ssed
(co
mp
lian
ce⁄
per
sist
ence
⁄bo
th)
Met
ho
ds
use
dto
asse
ssad
her
ence
Follo
w-u
p
tim
es
(mo
nth
s)
Ad
her
ence
(co
mp
lian
ce⁄
per
sist
ence
⁄co
mb
ined
*)
outc
om
es(i
nte
rven
tio
nvs
.
contr
ol
gro
up
)
Dep
ress
ion
outc
om
es�
(inte
rven
tio
nvs
.
contr
ol
gro
up
)
Inte
rven
tio
n
gro
up
Co
ntr
ol
gro
up
Sim
on
etal
.(4
6)
USA
Prim
ary
care
N=
600
Age
=44
.5
Wom
en=
74.3
%
New
AD
user
s
I1:
207
I2:1
98
195
Inte
rven
tion
1:Te
leph
one
care
man
agem
ent
cons
istin
gof
atle
ast
thre
eou
trea
chca
lls,
stru
ctur
edfe
edba
ckto
the
trea
ting
phys
icia
n
and
care
coor
dina
tion
Inte
rven
tion
2:Te
leph
one
care
man
agem
ent
plus
psyc
hoth
erap
yco
nsis
ting
ofca
rem
anag
emen
t
inte
grat
edw
itha
stru
ctur
ed8-
sess
ion
cogn
itive
-beh
avio
ural
psyc
hoth
erap
ypr
ogra
m
deliv
ered
byte
leph
one
Com
plia
nce
and
pers
iste
nce
Com
pute
rised
phar
mac
y
reco
rds
6w
eeks
,3
and
6m
onth
s
Com
bine
d
Inte
rven
tion
1:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(54%
vs.
41%
;
p=
0.01
)
Inte
rven
tion
2:N
osi
gnifi
cant
diff
eren
cebe
twee
ngr
oups
50%
Impr
ovem
ent
inde
pres
sion
sym
ptom
s(S
CL)
at6
mon
ths:
Inte
rven
tion
1:N
osi
gnifi
cant
diff
eren
cebe
twee
ngr
oups
Inte
rven
tion
2:In
terv
entio
n
grou
p>
cont
rol
grou
p
(58%
vs.
43%
;p
=0.
005)
Gen
sich
en
etal
.(4
7)
Ger
man
yPr
imar
y
care
N=
626
Age
=51
Wom
en=
76.4
%
Maj
ority
cont
inui
ng
AD
user
s
310
316
Tele
phon
eca
se
man
agem
ent
byhe
alth
care
assi
stan
tsin
volv
ing
stru
ctur
edte
leph
one
inte
rvie
ws
tom
onito
r
depr
essi
onsy
mpt
oms
and
supp
ort
med
icat
ion
adhe
renc
e,w
ithfe
edba
ck
toth
efa
mily
phys
icia
ns
Com
plia
nce
Mod
ified
Mor
isky
patie
ntse
lf-re
port
scal
e
6an
d12
Com
plia
nce
12-m
onth
:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(mea
nsc
ore
2.70
vs.
2.53
;p
=0.
042)
Dep
ress
ion
sym
ptom
s(P
HQ
-9):
12-m
onth
:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(mea
nsc
ore
10.7
vs.
12.1
;p
=0.
014)
Sim
on
etal
.§(4
8)
USA
Prim
ary
care
N=
613
Age
=46
.5
Wom
en=
72%
New
AD
user
s
196
196
Feed
back
plus
care
man
agem
ent
invo
lvin
g
syst
emat
icfo
llow
-up
by
tele
phon
e,so
phis
ticat
ed
trea
tmen
t
reco
mm
enda
tions
and
prac
tice
supp
ort
bya
care
man
ager
Com
plia
nce
and
pers
iste
nce
Com
pute
rised
phar
mac
y
data
3an
d6
Com
bine
d:In
terv
entio
ngr
oup
>co
ntro
lgr
oup
(mod
erat
e
adeq
uate
dose
for
‡90
days
)
(30%
vs.
18%
;p
<0.
05)
50%
Impr
ovem
ent
inde
pres
sion
sym
ptom
s:(S
CL-
20)
Inte
rven
tion
grou
p>
cont
rol
grou
p(5
6%vs
.40
%;
p<
0.05
)
966 Effectiveness of interventions to improve antidepressant adherence
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Tab
le2
(Co
nti
nu
ed)
Stud
yC
ountr
ySe
ttin
g
Sub
ject
char
acte
rist
ics
Pat
ient
po
pula
tio
n
(new
or
conti
nuin
g
AD
use
rs)
Sam
ple
size
Des
crip
tio
no
f
exp
erim
enta
l
inte
rven
tio
n
Asp
ect
of
adher
ence
asse
ssed
(co
mp
lian
ce⁄
per
sist
ence
⁄bo
th)
Met
ho
ds
use
dto
asse
ssad
her
ence
Follo
w-u
p
tim
es
(mo
nth
s)
Ad
her
ence
(co
mp
lian
ce⁄
per
sist
ence
⁄co
mb
ined
*)
outc
om
es(i
nte
rven
tio
nvs
.
contr
ol
gro
up
)
Dep
ress
ion
outc
om
es�
(inte
rven
tio
nvs
.
contr
ol
gro
up
)
Inte
rven
tio
n
gro
up
Co
ntr
ol
gro
up
Adl
er
etal
.(4
9)
USA
Prim
ary
care
N=
507
Age
=42
.3
Wom
en=
71.8
%
All
curr
ent
user
s
258
249
Phar
mac
ist
inte
rven
tion
invo
lvin
gm
edic
atio
n
revi
ewan
dm
onito
ring
byph
arm
acis
ts,
patie
nt
cont
act
and
educ
atio
n,
gene
ral
soci
alsu
ppor
t
and
prov
idin
gfe
edba
ck
toPC
Ps
Pers
iste
nce
Patie
ntse
lf-re
port
3an
d6
Pers
iste
nce
at6
mon
ths:
Inte
rven
tion
grou
p>
cont
rol
grou
p(5
7.5%
vs.
46.2
%;
p=
0.02
5)
Dep
ress
ion
seve
rity
(mBD
I):
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Cap
occi
a
etal
.(5
0)
USA
Prim
ary
care
N=
74
Age
=39
Wom
en=
77%
New
AD
user
s
4133
Phar
mac
ist
colla
bora
tive
care
inte
rven
tion
cons
istin
gof
addi
tiona
l
phon
efo
llow
-up
by
phar
mac
ists
;ph
one
cont
acts
focu
sed
on
supp
ort,
patie
nt
educ
atio
nan
dm
edic
atio
n
man
agem
ent
Com
plia
nce
Self-
repo
rted
tele
phon
ein
terv
iew
3,6,
9an
d12
Com
plia
nce
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Dep
ress
ion
sym
ptom
s(S
CL-
20):
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Rick
les
etal
.(5
1)
USA
Com
mun
ity
phar
mac
ies
N=
63
Age
=38
Wom
en=
84%
New
AD
user
s
3132
Phar
mac
ist-
guid
ed
educ
atio
nan
dm
onito
ring
(PG
EM)
invo
lvin
gth
ree
mon
thly
tele
phon
eca
llsto
patie
nts
toas
sess
,m
onito
r
and
mak
e
reco
mm
enda
tions
to
impr
ove
patie
nt’s
med
icat
ion
adhe
renc
e
Com
plia
nce
Phar
mac
yre
cord
s
3an
d6
Com
plia
nce
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
50%
Impr
ovem
ent
in
depr
essi
onsy
mpt
oms
(BD
I-II)
:
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
Effectiveness of interventions to improve antidepressant adherence 967
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Tab
le2
(Co
nti
nu
ed)
Stud
yC
ountr
ySe
ttin
g
Sub
ject
char
acte
rist
ics
Pat
ient
po
pula
tio
n
(new
or
conti
nuin
g
AD
use
rs)
Sam
ple
size
Des
crip
tio
no
f
exp
erim
enta
l
inte
rven
tio
n
Asp
ect
of
adher
ence
asse
ssed
(co
mp
lian
ce⁄
per
sist
ence
⁄bo
th)
Met
ho
ds
use
dto
asse
ssad
her
ence
Follo
w-u
p
tim
es
(mo
nth
s)
Ad
her
ence
(co
mp
lian
ce⁄
per
sist
ence
⁄co
mb
ined
*)
outc
om
es(i
nte
rven
tio
nvs
.
contr
ol
gro
up
)
Dep
ress
ion
outc
om
es�
(inte
rven
tio
nvs
.
contr
ol
gro
up
)
Inte
rven
tio
n
gro
up
Co
ntr
ol
gro
up
Finl
ey
etal
.(5
2)
USA
Prim
ary
care
N=
125
Age
=54
Wom
en=
85%
New
AD
user
s
7550
Phar
mac
ist
colla
bora
tive
care
inte
rven
tion
cons
istin
gof
patie
nt
educ
atio
n,fr
eque
nt
follo
w-u
pco
ntac
ts
thro
ugh
tele
phon
e
calls
and
clin
ic
appo
intm
ents
,
med
icat
ion
man
agem
ent
bycl
inic
alph
arm
acis
ts;
reco
mm
enda
tion
to
prov
ider
san
dsu
perv
isio
n
ofph
arm
acis
tsby
a
psyc
hiat
rist
Com
plia
nce
Com
pute
rised
pres
crip
tion
refil
l
reco
rds
3an
d6
Com
plia
nce
6m
onth
s:
Inte
rven
tion
grou
p>
cont
rol
grou
p(6
7%vs
.48
%;
p=
0.03
8)
Dep
ress
ion
sym
ptom
s(B
IDS)
:
No
sign
ifica
ntdi
ffer
ence
betw
een
grou
ps
*Com
bine
dm
easu
reof
adhe
renc
ein
tegr
ates
both
com
plia
nce
and
pers
iste
nce
aspe
cts
into
one
sing
lem
easu
re.�D
epre
ssio
nou
tcom
esw
ere
eval
uate
dus
ing
vario
usm
easu
res
asst
ated
inbr
acke
ts.�I
nter
vent
ion
sign
ifica
ntly
redu
ced
the
perc
enta
geof
patie
nts
with
prob
able
depr
essi
onat
6an
d12
mon
ths.
§Stu
dyev
alua
ted
two
diff
eren
tin
terv
entio
ns;
only
patie
nt-f
ocus
edin
terv
entio
nar
mis
repo
rted
here
in.
N,
num
ber
of
subj
ects
;A
ge,
mea
nye
ars;
AD
,an
tidep
ress
ant;
PCP,
prim
ary
care
phys
icia
n;SC
L,H
opki
nsSy
mpt
omC
heck
list
Dep
ress
ion
Scal
e;SC
ID,
Stru
ctur
edC
linic
alIn
terv
iew
for
Dia
gnos
tican
dSt
atis
tical
Man
ual
ofM
enta
l
Dis
orde
rs-
Four
thEd
ition
;H
DRS
,H
amilt
onD
epre
ssio
nRa
ting
Scal
e;C
ES-D
,C
ente
rfo
rEp
idem
iolo
gic
Stud
ies
Dep
ress
ion
Scal
e;PH
Q,
Patie
ntH
ealth
Que
stio
nnai
re;
BDI,
Beck
Dep
ress
ion
Inve
ntor
y;BI
DS,
Brie
fIn
ven-
tory
for
Dep
ress
ive
Sym
ptom
s.
968 Effectiveness of interventions to improve antidepressant adherence
ª 2011 Blackwell Publishing Ltd Int J Clin Pract, September 2011, 65, 9, 954–975
Effectiveness of intervention strategies
Educational focusAs shown in Table 1, five studies (27–31) utilised
interventions with an educational focus. Four (27–
30) of these used mailed educational materials
whereas one (31) used verbal counselling by pharma-
cists in addition to written materials and video.
Three (27,29,30) interventions used the RHYTHMS
programme, a patient education programme which
mails information directly to patients being treated
with antidepressant medications in a time-phased
manner. None of the educational intervention studies
reported an improvement in medication compliance
or persistence, although two studies (27,28) reported
improvement in treatment response and mental
health status at 6 months follow-up.
Behavioural focusOnly one study (32) in this review utilised an inter-
vention with a behavioural focus. The study involved
a novel psychosocial intervention aimed at identify-
ing and addressing psychological barriers, fears and
misconceptions of depression treatment. This inter-
vention resulted in improvement of both medication
compliance and depressive symptoms.
Multifaceted interventions
Components of multifaceted interventions. A
majority of interventions employed more than a sin-
gle component strategy (educational, behavioural or
affective) and targeted both the patient and the
healthcare provider. Overall, 20 studies (33–52)
reported utilising multifaceted interventions
(Table 2). Two of the studies (43,46) reported two
multifaceted interventions each, bringing the total
number of multifaceted interventions in this review
to 22.
The individual components of multifaceted inter-
ventions were grouped into educational, behavioural,
affective and provider-targeted strategies (Table 3).
Care management or patient follow-up was the cen-
tral theme in most of the multifaceted interventions
tested. In 14 studies (36,37,39–45,47,49–52), the care
managers were allied health professionals. Eleven
studies (34,36,37,39,41,43–47,49) described training
for care managers which included workshops, train-
ing manuals, didactic instruction and observed care
manager contacts.
It is clear from Table 3 that some components
were more frequently used than others. For example,