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Strategies to Improve Medication Adherence inPatients with Schizophrenia: The Role of SupportServicesPeggy El-MallakhUniversity of Kentucky, peggy.el-mallakh@uky.edu

Jan FindlayUniversity of Kentucky, jan.findlay@uky.edu

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Repository CitationEl-Mallakh, Peggy and Findlay, Jan, "Strategies to Improve Medication Adherence in Patients with Schizophrenia: The Role of SupportServices" (2015). Nursing Faculty Publications. 21.https://uknowledge.uky.edu/nursing_facpub/21

Strategies to Improve Medication Adherence in Patients with Schizophrenia: The Role of Support Services

Notes/Citation InformationPublished in Neuropsychiatric Disease and Treatment, v. 11, p. 1077-1090.

© 2015 El-Mallakh and Findlay.

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Digital Object Identifier (DOI)http://dx.doi.org/10.2147/NDT.S56107

This review is available at UKnowledge: https://uknowledge.uky.edu/nursing_facpub/21

© 2015 El-Mallakh and Findlay. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further

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Open Access Full Text Article

http://dx.doi.org/10.2147/NDT.S56107

Strategies to improve medication adherence in patients with schizophrenia: the role of support services

Peggy el-MallakhJan FindlayCollege of Nursing, University of Kentucky, Lexington, KY, USA

Abstract: The purpose of this review is to describe research over the past 10 years on the role

of support services in promoting medication adherence in mental health consumers diagnosed

with schizophrenia. A literature search was conducted using the terms “medication adherence,”

“schizophrenia,” and “support services,” using Medline, PubMed, and CINAHL. Reference lists

from published studies were also reviewed to identify additional research studies. Twenty-two

articles focused on support-service intervention studies, and these were selected for review.

Available support-service interventions include adherence therapy, electronic reminders via

text messages and telephones, cognitive–behavioral and motivational strategies, and financial

incentives. Support-service intervention strategies need to be tailored to the specific needs of

mental health consumers with schizophrenia. More research is needed to investigate effective

support services to enhance long-term adherence and adherence to medications for medical

illnesses in this population.

Keywords: schizophrenia, medication adherence, support services, therapy, interventions

IntroductionAdherence to pharmacological treatment is essential for alleviation of psychotic

symptoms in schizophrenia. First-line antipsychotic medications are effective in

approximately 70%–80% of persons diagnosed with schizophrenia (PWS); however,

an estimated 50% of those who respond well to medications are nonadherent to their

treatment regimen.1 Wide variations have been observed in patterns of medication

adherence among PWS. Nonadherence can range from patients who refuse to take

medications due to lack of acceptance of the need for medication, to patients who

recognize the need for medication and are committed to treatment but are nonadher-

ent due to forgetfulness or financial constraints.2 The consensus definition for adher-

ence maintains that PWS can be considered adherent if they take more than 80% of

prescribed medications; partial adherence is defined as taking 50% of prescribed

medications.3 Velligan and colleagues also report a consensus among experts that

nonadherence can be defined as being off of medications for 1 week.3

Factors associated with medication nonadherenceAs the definitions of adherence suggest, the decision to take medications in PWS is

a complex phenomenon that involves multiple patient, environmental, provider, and

medication-related factors. Patient-related factors include some demographic char-

acteristics, such as newly starting treatment, younger age at onset of illness, alcohol

dependence and other illicit substance use, homelessness, low levels of involvement

Correspondence: Peggy el-Mallakh315 College of Nursing Building, Number 547, College of Nursing, University of Kentucky, Lexington, KY 40536, USAemail peggy.el-mallakh@uky.edu

Journal name: Neuropsychiatric Disease and TreatmentArticle Designation: ReviewYear: 2015Volume: 11Running head verso: El-Mallakh and FindlayRunning head recto: Support services to improve medication adherence in schizophreniaDOI: http://dx.doi.org/10.2147/NDT.S56107

Neuropsychiatric Disease and Treatment 2015:11submit your manuscript | www.dovepress.com

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1078

el-Mallakh and Findlay

in social activities, independent housing, and financial con-

straints with consequent inability to afford copayments for

prescriptions.4–9 Membership in a minority ethnic group also

contributes to poor medication adherence; in a large study

of 34,128 US veterans with schizophrenia, Valenstein et al10

reported that the relative risk ratio for consistently poor

adherence was 3.81 for African Americans compared to

whites and 3.54 for Hispanics compared to whites. Lack of

family support for adherence, or having no family, further

contributes to nonadherence. Glick et al11 and Moritz et al12

observed that a positive attitude toward positive symptoms,

particularly the perception of importance and power resulting

from psychotic symptoms, also contributes to nonadherence.

In addition, a study by Jόnsdόttir et al6 found that nonadher-

ent PWS had significantly higher IQs, executive function-

ing, memory, and verbal learning/fluency compared to fully

adherent PWS.

Perceptions about illness and medications are very impor-

tant factors that influence adherence. For example, adherence

is higher among PWS who have insight and an awareness

of the need to take medications to alleviate symptoms and

avoid hospitalization.7,13–15 In addition, favorable attitudes

toward mediations and the expectation that medications are

effective in reducing symptoms contribute to adherence.15,16

Intolerable side effects are a major reason for discontinuing

medications.12,15 For example, side effects associated with

typical antipsychotics, such as extrapyramidal symptoms,

sedation, and elevated prolactin levels, are particularly

problematic. Metabolic side effects of atypical antipsychot-

ics, including weight gain, further contribute to lack of

adherence.17 However, some research suggests that recogni-

tion of the benefits of medications in alleviating troublesome

psychotic symptoms improves willingness to tolerate the

side-effect burden for the sake of mental wellness.18 Simi-

larly, Liu-Seifert et al19 compared adherence among 1,103

people treated with olanzapine and 1,090 people treated with

other atypical antipsychotic medications (risperidone, quetia-

pine, ziprasidone, or aripiprazole). Findings suggested that

an improvement in the positive symptom rating subscale of

the Positive and Negative Syndrome Scale was the strongest

predictor of treatment adherence, regardless of the medica-

tion that was prescribed.

Much research supports the critical need for a strong

and positive therapeutic relationship in the promotion of

medication adherence.20,21 Misdrahi et al7 found that thera-

peutic alliance was significantly associated with medication

adherence (r=0.663) among 38 PWS. Similarly, Dassa et al16

found that nonadherence to medications increased with

a low level of therapeutic alliance (odds ratio =0.45, 95%

confidence interval =0.32–0.64) among 291 PWS. Research

also suggests that patients value support from prescribers

regarding medication, particularly when prescribers provided

accurate information about potential side effects of medica-

tion, expressed understanding of the patient perspective,

and listened to patients’ concerns about the medications. In

addition, Day et al20 reported that the experience of admis-

sion to the hospital is an important factor that influences

willingness to take medications; the perception of coercion,

lack of a voice in treatment decisions, and negative pressure

to enter the hospital are all associated with nonadherence to

psychiatric medications.

Adherence to medications for medical illnessesHigh rates of cardiometabolic problems among PWS have

prompted clinicians to focus on adherence to treatment for med-

ical illnesses in this population. Research investigating adher-

ence to medical care has yielded varying results. Pratt et al22

in a study of 72 participants with serious mental illnesses,

reported adherence rates of 57% for psychiatric medications

and 64% for medications for medical illnesses. Hansen et al 23

in a study of 87,015 PWS with comorbid medical illnesses,

found that adherence to medications for hypertension, hyper-

lipidemia, and diabetes was significantly greater among those

who were adherent to antipsychotic medications, with an

adjusted odds ratio of 6.9. In a study of 11,454 US veterans,

Kreyenbuhl et al24 found poor adherence to medications for

Type 2 diabetes mellitus (T2DM) in 43% of veterans with

schizophrenia and T2DM, compared to poor adherence rates

among 52% of veterans with T2DM and no mental illness.

Similarly, Nelson et al25 found that gaps in filled prescriptions

for antihyperlipidemic medications were 44 days for veter-

ans diagnosed with schizophrenia and T2DM, compared to

62 days for veterans with T2DM and no mental illness.

Piette et al26 noted that in a study of 1,686 veterans diag-

nosed with schizophrenia and comorbid diabetes and hyper-

tension, differential rates of adherence depended on the type

of medication prescribed to participants; findings suggest

that treatment with antihypertensive and diabetes medica-

tions was associated with an increased risk for low adher-

ence compared to antipsychotic medications. Dolder et al27

found that rates of adherence to antihypertensive agents in

89 veterans with psychotic disorders were similar to rates

in 89 randomly selected, age-matched veterans without

psychotic disorders; however, blood pressure control was

significantly poorer over a 1-year period in the participants

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Support services to improve medication adherence in schizophrenia

with psychotic disorders. In contrast, Dolder et al28 found

that among 76 middle-aged and older veterans with schizo-

phrenia, 12-month adherence rates ranged from 52%–64%

for antipsychotic medications and medications to treat

hypertension, diabetes, and hyperlipidemia. Beebe et al29 in a

study that compared the effectiveness of a telephone interven-

tion to improve medication adherence (n=15) to usual care

(n=14), found that average adherence rates to medications

for medical illnesses was 33% for the intervention group and

22% for the treatment-as-usual (TAU) group throughout the

duration of the study.

Consequences of nonadherencePartial or complete lack of adherence to medications is asso-

ciated with several negative outcomes in PWS.8,30 Medication

nonadherence is associated with an increased risk for relapse

of psychosis, persistent symptoms, and suicide attempts.8,31

Among PWS experiencing a first episode of psychosis,

symptom recurrence rates are an average of 77% within

1 year of stopping medications, and over 90% within 2 years

of stopping medications.30 Bodén et al32 found that nonadher-

ence to medications during the first week after discharge from

an inpatient hospitalization was associated with a high risk

for rehospitalization within 1 month of discharge. Length of

hospital stay is also extended due to nonadherence.30 Finally,

Gilmer et al5 found that average hospital costs in nonadherent

inpatients were three times higher than costs for adherent

inpatients, although pharmacy costs were higher among

adherent compared to nonadherent inpatients.

Current strategies to improve adherenceSeveral support services are available to address specific

problems with adherence.33 For example, therapeutic support

services provide counseling, with the goal of identifying and

modifying cognitive and motivational barriers to adherence.

Cognitive-behavioral therapy (CBT) addresses inaccurate

beliefs and negative perceptions about medications and the

need for treatment.3 CBT is often used in conjunction with

motivational interviewing (MI), which seeks to resolve

ambivalence about taking medications and addresses per-

ceptions about the importance of taking medications and

confidence in the ability to adhere to a medication regimen.34

Cognitive adaption training provides tailored environmental

cues and supports to compensate for cognitive impairments

that cause memory problems; these include alarms, pillboxes,

activity checklists, and organization of personal belongings.33

Adherence/compliance therapy is a multifaceted approach

that includes CBT, psychoeducation, and MI.3 Support

services can also address logistic barriers to adherence, such

as arranging transportation to pharmacies and obtaining

insurance benefits.3

This review summarizes research from the past 10 years

on interventions that examined the role of support services in

promoting adherence to psychiatric medications and medica-

tions for medical illnesses among PWS. A literature search

was conducted using the terms “medication adherence,”

“schizophrenia,” and “support services” and “interventions”

using Medline, PubMed, and CINAHL. Reference lists from

published studies were also reviewed to identify additional

research studies. A total of 22 articles were located using

these search terms and are included in this review.

ResultsFindings from this literature review are displayed in

Tables 1–4. Of the 22 studies reviewed, eleven significantly

improved adherence to medications in the study samples, and

five did not result in significant improvements.

Support service interventionsFamily and/or clinician support/educationSeven intervention studies examined the effectiveness of

family and/or clinician support and education (Table 1).35–41

Two family studies showed promising findings. Farooq et al37

implemented an intervention to train family members to be

key care supervisors of medication adherence (coupled with

free medications). Findings indicated that medication adher-

ence was significantly increased in the intervention group.37

Kopelowicz et al39 found that culturally adapted multifamily

groups tailored to Spanish-speaking Mexican Americans,

who had three individual and family psychotherapy sessions,

a 1-day family workshop, and 24 family group sessions that

focused on attitudes, beliefs, planned behaviors, and subjec-

tive norms, had increased adherence compared to multifamily

groups only or TAU.

Interventions involving clinician support and education

yielded varying results. Sajatovic et al41 examined the effec-

tiveness of a psychosocial/psychoeducational customized

adherence enhancement program for homeless people taking

long-acting antipsychotic injections (LAIs), which focused

on medication routines, communicating with clinicians, and

managing adherence in the presence of substance abuse. The

customized adherence enhancement program was associated

with good adherence to LAIs in 76% of participants. Oral

medication adherence improved to only 10% missed medica-

tion doses postintervention compared to 46% missed doses

prestudy. However, only four out of 30 continued taking

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1080

el-Mallakh and Findlay

Tab

le 1

Fam

ily a

nd/o

r cl

inic

ian

educ

atio

nal s

uppo

rt

Cit

atio

nA

nder

son

et a

l35B

yerl

y et

al36

Faro

oq e

t al

37G

ray

et a

l38K

opel

owic

z et

al39

Mit

tal e

t al

40Sa

jato

vic

et a

l41

Des

ign

type

RC

TQ

uasi

- ex

peri

men

tal

RC

TR

CT

3-ar

med

RC

TR

CT

Pros

pect

ive,

no

ncon

trol

led

tria

lin

terv

entio

n de

scri

ptio

nA

T –

wee

kly

se

ssio

ns fo

r

8 w

eeks

, 20

–60

min

utes

Focu

s: p

robl

em

solv

ing,

m

edic

atio

n

timel

ine,

am

biva

lenc

e,

med

icat

ion

be

liefs

/con

cern

s,

usin

g m

edic

atio

ns

in t

he fu

ture

Com

plia

nce

th

erap

y

4–6

sess

ions

, 30

–60

min

utes

ea

chFo

cus:

illn

ess

hi

stor

y,

med

icat

ion

be

liefs

/ un

ders

tand

ing,

tr

eatm

ent

am

biva

lenc

e,

stig

ma

STO

PS –

fam

ily

mem

ber

as k

ey

care

sup

ervi

sor

One

ses

sion

to

tra

in k

ey

care

sup

ervi

sor

Free

m

edic

atio

ns fo

r al

l par

ticip

ants

in

ST

OPS

gr

oup

and

for

th

ose

in t

he

TA

U g

roup

w

ho c

ould

no

t af

ford

m

edic

atio

ns

AT

– w

eekl

y se

ssio

ns

for

8 w

eeks

Focu

s:

prob

lem

so

lvin

g,

med

icat

ion

tim

elin

e,

ambi

vale

nce,

m

edic

atio

n

belie

fs/

conc

erns

, us

ing

m

edic

atio

ns

in t

he fu

ture

Hea

lth

educ

atio

n –

wee

kly

se

ssio

ns fo

r

8 w

eeks

Cul

tura

lly a

dapt

ed

mul

tifam

ily g

roup

Tai

lore

d to

Spa

nish

-sp

eaki

ng M

exic

an-

Am

eric

ans

(MFG

-A

d) c

ompa

red

to

MFG

-S a

nd T

AU

3 in

divi

dual

and

fa

mily

ses

sion

sO

ne-d

ay fa

mily

w

orks

hop

MFG

-Ad:

24

fam

ily

grou

p

sess

ions

, foc

us:

attit

udes

, be

liefs

, pla

nned

be

havi

ors

MFG

-S: n

o fo

cus

on

attit

udes

, bel

iefs

, pl

anne

d be

havi

ors

AA

i – 9

ses

sion

s:Fa

ce t

o fa

ce

daily

×3

Face

to

face

w

eekl

y ×3

Tel

epho

ne

mon

thly

×3

educ

atio

n, s

kills

tr

aini

ng, a

llian

ce

build

ing

Focu

s on

m

edic

atio

n

man

agem

ent,

co

mm

unic

atio

n,

build

ing

re

latio

nshi

ps

with

hea

lth c

are

pr

ovid

ers

CA

e, a

ps

ycho

soci

al/

psyc

hoed

ucat

iona

l pr

ogra

m a

bout

m

edic

atio

n

use

plus

hal

oper

idol

de

cano

ate-

LAi =

C

Ae-

L

adm

inis

tere

d ov

er

6 m

onth

s

Dat

a co

llect

ion

time

poin

tsBa

selin

ePo

stin

terv

entio

nM

onth

ly –

3

mon

ths

pr

eint

erve

ntio

n to

6 m

onth

s

post

inte

rven

tion

Base

line,

3

mon

ths,

6

mon

ths,

12

mon

ths

Base

line

and

52 w

eeks

Base

line,

4 m

onth

s,

8 m

onth

s, 12

mon

ths,

18 m

onth

s,

24 m

onth

s

Base

line,

4 w

eeks

, an

d 4

mon

ths

Tre

atm

ent

= ba

selin

e, 1

3, a

nd 2

5 w

eeks

follo

w-u

p;Po

sttr

eatm

ent

fo

llow

-up

=9

and

12 m

onth

sSa

mpl

eA

T =

12T

AU

=14

n=30

No

cont

rol

grou

p

STO

PS =

55T

AU

=55

AT

=20

4H

e =2

05M

FG-A

d =6

4M

FG =

53T

AU

=57

AA

i =22

TA

U =

18n=

30

Mea

sure

sA

TSA

TLU

NSe

RS

PAN

SSPe

TiT

MeM

SPA

NSS

DA

i

PAN

SSG

AF

Adh

eren

ce

to M

edic

atio

n

Scal

e

MO

S SF

-36

SAi-e

MA

QBP

RS-

e

Tre

atm

ent

Com

plia

nce

in

terv

iew

Self/

care

give

r

adhe

renc

e re

port

Phar

mac

y re

fill

reco

rds

PAN

SSQ

wBS

CD

SBA

SA

iMS

DA

iiT

AS

14-Q

Prim

ary

= m

edic

atio

n

adhe

renc

e an

d ho

usin

g st

atus

vi

a se

lf-re

port

s:T

RQ

MR

SA

TM

SQD

Ai

Psyc

hiat

ric

sy

mpt

oms:

BP

RS,

PA

NSS

, CG

iFu

nctio

ning

: SO

FAS

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1081

Support services to improve medication adherence in schizophrenia

Find

ings

No

sign

ifica

nt

impr

ovem

ents

in

med

icat

ion

adhe

renc

e

or p

sych

iatr

ic

sym

ptom

s

Adh

eren

ce

sign

ifica

ntly

in

crea

sed

1

mon

th a

fter

in

terv

entio

n,

decl

ined

by

1.4%

pe

r m

onth

for

rem

aini

ng

mon

ths

No

chan

ge in

sy

mpt

oms,

in

sigh

t,

attit

udes

to

tak

ing

m

edic

atio

ns

STO

PS:

sign

ifica

nt

redu

ctio

n

in P

AN

SS

scor

es,

posi

tive/

gene

ral

sym

ptom

s,

sign

ifica

nt

impr

ovem

ent

in

GA

FSi

gnifi

cant

ly

high

er

adhe

renc

e

in t

he S

TO

PS

grou

p

com

pare

d

to T

AU

at

3

mon

ths,

6

mon

ths,

an

d 12

mon

ths

(67%

vs

45%

at

1 y

ear

fo

llow

-up,

P

0.02

)

No

si

gnifi

cant

di

ffere

nce

in

med

icat

ion

ad

here

nce

an

d qu

ality

of

life

be

twee

n A

T

and

He

gr

oups

MFG

-Ad

had

in

crea

sed

adhe

renc

e co

mpa

red

to M

FG-S

an

d T

AU

Long

er t

ime

to fi

rst

hosp

italiz

atio

nLe

ss li

kely

to

be

hosp

italiz

ed

65%

of A

Ai g

roup

ad

here

nt a

fter

4

mon

ths

55.6

% T

AU

gro

up

adhe

rent

No

sign

ifica

nt

diffe

renc

e

CA

e-L

asso

ciat

ed

with

goo

d ad

here

nce

to L

Ai

at 6

mon

ths

=76%

,O

vera

ll or

al

med

icat

ion

ad

here

nce:

46

% m

isse

d

prio

r to

stu

dy

vers

us 1

0%

at 6

mon

ths

(P

=0.0

3)O

nly

4 co

ntin

ued

to

tak

e LA

i 6

mon

ths

po

stst

udy

Sign

ifica

nt

impr

ovem

ents

in

psy

chia

tric

sy

mpt

oms

(P

0.

001)

an

d fu

nctio

ning

(P

0.

001)

Abb

revi

atio

ns: 1

4-Q

, 14-

Poin

t Q

uest

ionn

aire

; AA

i, an

tipsy

chot

ic a

dher

ence

inte

rven

tion;

AiM

S, A

bnor

mal

invo

lunt

ary

Mov

emen

t Sc

ale;

AT

, adh

eren

ce t

hera

py; A

TM

SQ, A

ttitu

de T

owar

ds M

ood

Stab

ilize

r Q

uest

ionn

aire

; AT

SAT

, A

dher

ence

The

rapy

Pat

ient

Sat

isfa

ctio

n Q

uest

ionn

aire

; BA

S, B

arne

s A

kath

isia

Sca

le; B

PRS-

e, B

rief

Psy

chia

tric

Rat

ing

Scal

e-ex

pand

ed; C

Ae,

cus

tom

ized

adh

eren

ce e

nhan

cem

ent

prog

ram

; CA

e-L,

cus

tom

ized

adh

eren

ce e

nhan

cem

ent

plus

long

-act

ing

inje

ctab

le a

ntip

sych

otic

; CD

S, C

alga

ry D

epre

ssio

n Sc

ale;

CG

i, C

linic

al G

loba

l im

pres

sion

s Sc

ale;

DA

i, D

rug

Att

itude

inve

ntor

y; G

AF,

Glo

bal A

sses

smen

t of

Fun

ctio

ning

; He,

hea

lth e

duca

tion;

iTA

S, in

sigh

t an

d T

reat

men

t A

ttitu

de S

cale

; L o

r LA

i, lo

ng-a

ctin

g in

ject

ion;

LU

NSe

RS,

Liv

erpo

ol U

nive

rsity

Neu

role

ptic

Sid

e ef

fect

Rat

ing

Scal

e; M

AQ

, Med

icat

ion

Adh

eren

ce Q

uest

ionn

aire

; MeM

S, M

edic

atio

n ev

ent M

onito

ring

Sca

le; M

FG, m

ultif

amily

gro

up; M

FG-A

d,

Mul

tifam

ily G

roup

-Adh

eren

ce; M

FG-S

, Mul

tifam

ily G

roup

– S

tand

ard;

MO

S SF

-36,

Med

ical

Out

com

es S

urve

y 36

-item

sho

rt fo

rm q

uest

ionn

aire

; MR

S, M

oris

ky R

atin

g Sc

ale;

PA

NSS

, Pos

itive

and

Neg

ativ

e Sy

ndro

me

Scal

e; P

eTiT

, Per

sona

l ev

alua

tion

of T

rans

ition

s in

Tre

atm

ent;

Qw

BS, Q

ualit

y of

wel

l-Bei

ng S

cale

; RC

T, r

ando

miz

ed c

ontr

olle

d tr

ial;

SAi-e

, Sch

edul

e fo

r th

e A

sses

smen

t of i

nsig

ht –

exp

ande

d v

ersi

on; S

OFA

S, S

ocia

l and

Occ

upat

iona

l Fun

ctio

ning

Ass

essm

ent

Scal

e; S

TO

PS, s

uper

vise

d tr

eatm

ent

in o

utpa

tient

s fo

r sc

hizo

phre

nia;

TA

U, t

reat

men

t as

usu

al; T

RQ

, Tab

let

Rou

tine

Que

stio

nnai

re.

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1082

el-Mallakh and Findlay

LAI 6 months poststudy. In contrast, Byerly et al36 found

that adherence did not increase after four to six sessions

of compliance therapy that focused on illness history, and

medication beliefs, understanding, ambivalence, and stigma

of treatment. Anderson et al35 found no significant improve-

ments in medication adherence following eight weekly

sessions of adherence therapy that included problem solv-

ing, exploration of ambivalence toward medication beliefs,

concerns, and using medications in the future. Similarly,

Gray et al38 found that there was no significant difference

in adherence between adherence therapy that included eight

weekly sessions about problem solving, medication timeline,

ambivalence, beliefs, and concerns about using them in the

future versus eight weekly health education sessions. Mittal

et al40 found that there was no significant difference between

antipsychotic adherence therapy versus TAU following nine

weekly sessions of daily, then weekly, face-to-face and

telephone education, alliance building, and skills training in

veterans aged 40 years and older.

Technology-based servicesA variety of electronics-based strategies were studied, includ-

ing text messages, phone reminders, pill counters, electronic

pill dispensers, and a computerized program symptom alert

system (Table 2).29,42–46 Pijnenborg et al44 used text messages

in an intervention to examine the effectiveness of six weekly

group sessions focusing on coping with cognitive impair-

ment associated with schizophrenia. The study also involved

instructions on how to send/receive text messages, including

a total of 7 weeks of receiving text messages as a reminder

to adhere to medications and other self-chosen treatment

goals. Adherence to medications in the intervention group

was 57% at baseline and 65% during the intervention, but

fell to 48% at follow-up when text prompts were no longer

being received. Granholm et al42 found that sending three

sets of four text messages about medication adherence,

socialization, and auditory hallucinations to people with

schizophrenia significantly improved medication adherence

for those living independently. Similarly, Montes et al43 found

that after sending daily short-message-service reminders or

texts for 3 months as a prompt to take medications, there was

a significantly reduced score on the Medication Adherence

Questionnaire (a four-item self-report of reasons for medi-

cation adherence failure, with a low score indicating better

adherence) in the intervention group at 3 months, and at

6 months adherence was maintained.

Beebe et al29 found that study participants who received

weekly telephone call reminders to take their medications Tab

le 2

ele

ctro

nic

devi

ces

Cit

atio

nB

eebe

et

al29

Gra

nhol

m e

t al

42M

onte

s et

al43

Pijn

enbo

rg e

t al

44Šp

anie

l et

al45

Stip

et

al46

Des

ign

type

RC

TQ

uasi

-exp

erim

enta

l;

pilo

t st

udy

RC

T o

pen-

labe

l,

mul

ticen

ter

tria

lQ

uasi

-exp

erim

enta

l w

aitin

g lis

t co

ntro

lled

tria

l; ra

ndom

ass

ignm

ent

RC

T 1

-yea

r pr

ospe

ctiv

e,

para

llel-g

roup

, dou

ble-

blin

d st

udy

RC

T

inte

rven

tion

de

scri

ptio

nT

iPS

wee

kly

tele

phon

e

calls

for

3 m

onth

sFo

cus:

pro

blem

so

lvin

g, c

opin

g

stra

tegi

es, r

emin

ders

to

tak

e m

edic

atio

ns

3 se

ts o

f 4 t

ext

mes

sage

s

sent

via

mob

ile p

hone

, 6

days

per

wee

k fo

r

12 w

eeks

– C

BT fo

rmat

Focu

s: m

edic

atio

n

adhe

renc

e, s

ocia

lizat

ion,

A

H

inte

rven

tion

grou

p =

daily

re

min

ders

for

3 m

onth

s

via

text

mes

sage

(SM

S)

to t

ake

thei

r m

edic

atio

nC

ontr

ol g

roup

= n

o

text

rem

inde

rs t

o ta

ke

med

icat

ions

6 w

eekl

y ps

ycho

educ

atio

n

grou

p se

ssio

ns w

ith

5–7

patie

nts

wee

ks 1

–2 =

bas

elin

e

goal

s se

t (A

1)3

wee

ks =

rem

inde

r te

xts

ab

out

adhe

renc

e +

usua

l ca

re =

(B)

Last

3 w

eeks

dur

ing

in

terv

entio

n =

daily

goa

ls

achi

eved

3 w

eeks

pos

tinte

rven

tion

= nu

mbe

r

of d

aily

goa

ls

rem

easu

red

=(A

2)

Tex

t m

essa

ge s

ent

via

co

mpu

ter

prog

ram

: iT

AR

ePS

1 tim

e/w

eek

A

ctiv

e gr

oup

prod

rom

al

psyc

hotic

sym

ptom

s vi

a

wee

kly

ALe

RT

em

ails

PiR

e =

trig

gere

d cl

inic

ian

to

incr

ease

ant

ipsy

chot

ic

med

icat

ion

dose

Act

ive

grou

p =

used

iT

AR

ePS

and

ewSQ

-10P

/ew

SQ-1

0FM

+ u

sual

tr

eatm

ent

Con

trol

gro

up =

usu

al

trea

tmen

t

3 vi

sits

: bas

elin

e, 6

wee

ks,

and

8 w

eeks

to

mea

sure

im

pact

of D

oPill

’s®

(ele

ctro

nic

pill

disp

ense

r)

impa

ct o

n m

edic

atio

n

adhe

renc

e an

d ps

ychi

atri

c

sym

ptom

s

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1083

Support services to improve medication adherence in schizophrenia

Dat

a co

llect

ion

time

poin

tsBa

selin

e an

d m

onth

ly

for

3 m

onth

sBa

selin

e an

d 12

wee

ksBa

selin

e, 3

mon

ths,

an

d 6-

mon

ths

inte

rven

tion

grou

p:

A1

+ B

+ A

2:

A1

= ba

selin

e ph

ase,

B

= in

terv

entio

n ph

ase,

A

2 =

follo

w-u

p ph

ase

Con

trol

s: A

1 +

A0

+ B

+

A2

(A0

= ex

tra

base

line

co

nditi

on t

o co

ntro

l for

pa

ssin

g tim

e)

Base

line,

6 m

onth

s, a

nd

12 m

onth

s (e

nd o

f stu

dy)

Base

line,

6 w

eeks

, an

d 8

wee

ks

Sam

ple

TiP

S =1

5T

AU

=14

n=55

SMS

=100

pat

ient

sC

ontr

ols

=154

pat

ient

sn=

62in

terv

entio

n =7

5C

ontr

ols

=71

expe

rim

enta

l gro

up =

26C

ontr

ol g

roup

=21

47 t

otal

com

plet

ed s

tudy

Mea

sure

sPi

ll co

unts

PAN

SSBD

i-ii

iLSS

MA

QD

Ai

SUM

DeQ

-5D

CG

i-SC

HC

Gi-S

i-DC

PAN

SSSF

SSC

MT

S

CG

i-S a

nd C

Gi-i

Hay

war

d M

CR

SG

AF

PiR

e de

tect

ed b

y iT

AR

ePS

BAR

SPA

NSS

DoP

ill® e

lect

roni

c/di

gita

l re

port

(fr

eque

ncy)

Ant

ipsy

chot

ic A

dher

ence

R

atio

Find

ings

TiP

S: 8

0% a

dher

ence

to

psy

chia

tric

m

edic

atio

ns;

33%

adh

eren

ce

to n

onps

ychi

atri

c

med

icat

ions

TA

U: 6

0.1%

adh

eren

ce

to p

sych

iatr

ic

med

icat

ions

; 22%

ad

here

nce

to

nonp

sych

iatr

ic

med

icat

ions

Sign

ifica

ntly

hig

her

ad

here

nce

in T

iPS

gr

oup

vs T

AU

gro

up

Sign

ifica

nt im

prov

emen

t

in m

edic

atio

n ad

here

nce

fo

r th

ose

livin

g

inde

pend

ently

; im

prov

ed

soci

al fu

nctio

ning

; red

uced

se

veri

ty o

f AH

Sign

ifica

ntly

red

uced

M

AQ

sco

re w

ith S

MS

rem

inde

rs v

s co

ntro

ls

at 3

mon

ths

(25%

ver

sus

17.5

%)

at 6

mon

ths,

m

aint

aine

d

MA

Q s

core

cha

nge

from

ba

selin

e

Ove

rall

% o

f goa

l-ac

hiev

emen

t =4

7%

acro

ss p

atie

nts,

(SD

=2

7.9%

) an

d in

crea

sed

with

tex

t pr

ompt

ing

=62%

(S

D =

20.1

%, r

etur

ned

to

base

line

leve

ls w

ithou

t pr

ompt

s =4

0% (S

D =

31.7

%);

Med

icat

ion

adhe

renc

e =

57%

at

bas

elin

e (A

1), 6

5% a

t in

terv

entio

n ph

ase

(B),

an

d 48

% a

t fo

llow

-up

(A2)

No

sign

ifica

nt d

iffer

ence

in

med

icat

ion

adhe

renc

e

betw

een

grou

ps

46%

non

-adh

eren

t;Ba

selin

e ad

here

nt p

atie

nts

had

sig

nific

antly

a

dher

ence

vs

non

-adh

eren

t pa

tient

s ov

er

6-w

eeks

via

BA

RS

mea

sure

s; ie

,M

ean

AA

R 6

7% a

fter

6-w

eeks

;Pr

opor

tion

of p

atie

nts

w

ith

70%

and

90

%

AA

R =

46%

and

54%

Abb

revi

atio

ns:

AA

R,

antip

sych

otic

adh

eren

ce r

atio

; A

H, a

udito

ry h

allu

cina

tions

; BA

RS,

Bri

ef A

dher

ence

Rat

ing

Scal

e; B

Di-i

i, Be

ck D

epre

ssio

n in

vent

ory-

Seco

nd e

ditio

n; C

BT,

cogn

itive

–beh

avio

ral

ther

apy;

CG

i-i,

Clin

ical

Glo

bal

Impr

essi

on S

cale

-Impr

ovem

ent;

CG

I-S, C

linic

al G

loba

l Im

pres

sion

Sca

le-S

ever

ity; C

GI-S

CH

, Clin

ical

Glo

bal I

mpr

essi

on S

cale

-Sch

izop

hren

ia; C

GI-S

I-DC

, Clin

ical

Glo

bal I

mpr

essi

on-S

ever

ity o

f Illn

ess

and

Deg

ree

of C

hang

e; C

L, c

onfid

ence

lim

it; D

Ai,

Dru

g A

ttitu

de i

nven

tory

; eQ

-5D

, eu

roQ

ol;

ewSQ

-10F

M,

10-it

em e

arly

war

ning

Sig

ns Q

uest

ionn

aire

(Fa

mily

Mem

ber)

; ew

SQ-1

0P,

10-it

em e

arly

war

ning

Sig

ns Q

uest

ionn

aire

(Pa

tient

); G

AF,

Glo

bal

Ass

essm

ent

of

Func

tioni

ng; i

LSS,

inde

pend

ent

Livi

ng S

kills

Sur

vey;

iTA

ReP

S, in

form

atio

n T

echn

olog

y-A

ided

Pro

gram

of R

elap

se P

reve

ntio

n in

Sch

izop

hren

ia; M

AQ

, Med

icat

ion

Adh

eren

ce Q

uest

ionn

aire

; MC

RS,

Med

icat

ion

Com

plia

nce

Rat

ing

Scal

e;

PAN

SS, P

ositi

ve a

nd N

egat

ive

Synd

rom

e Sc

ale;

PiR

e, p

harm

acol

ogic

al in

terv

entio

n re

quir

ing

even

t; R

CT

, ran

dom

ized

con

trol

led

tria

l; SC

MT

S, S

hort

Clie

nt M

otiv

atio

n fo

r T

hera

py S

cale

; SD

, sta

ndar

d de

viat

ion;

SFS

, Soc

ial F

unct

ioni

ng

Scal

e; S

MS,

sho

rt m

essa

ge s

ervi

ce; S

UM

D, S

cale

to

Ass

ess

Una

war

enes

s of

Men

tal D

isor

der;

TA

U, t

reat

men

t as

usu

al; T

iPS,

tel

epho

ne in

terv

entio

n pr

oble

m-s

olvi

ng.

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1084

el-Mallakh and Findlay

Tab

le 3

Mot

ivat

iona

l int

ervi

ewin

g

Cit

atio

nB

arkh

of e

t al

47H

udso

n et

al48

Man

eesa

korn

et

al49

Star

ing

et a

l50

Des

ign

type

RC

TR

CT

inte

rven

tion

de

scri

ptio

nM

otiv

atio

nal i

nter

view

ing

ve

rsus

hea

lth e

duca

tion

5–8

sess

ions

ove

r 26

wee

ks

vet

eran

s A

ffair

s pr

actic

e

guid

elin

e im

plem

enta

tion

RN

cou

nsel

ing/

prob

lem

sol

ving

Clin

ical

inte

rvie

w –

bas

elin

e

and

ever

y vi

sit

At

leas

t ev

ery

6 w

eeks

for

6 m

onth

s –

adhe

renc

e ba

rrie

rs a

nd s

trat

egie

s

AT

– 8

wee

kly

sess

ions

Focu

s: m

edic

atio

n pr

oble

m s

olvi

ng,

ambi

vale

nce,

bel

iefs

, con

cern

s

abou

t ta

king

med

icat

ions

, usi

ng

med

icat

ions

in t

he fu

ture

inte

rven

tion

grou

p/T

AT

= M

i,

med

icat

ion

optim

izat

ion,

beh

avio

ral t

rain

ing

Con

trol

gro

up =

TA

U

Dat

a co

llect

ion

time

poin

tsBa

selin

e, 2

6 w

eeks

, 6

mon

ths

Base

line

and

6 m

onth

sBa

selin

e an

d 9

wee

ksBa

selin

e an

d 6

mon

ths

Sam

ple

Mi =

55H

e =5

9en

hanc

ed/R

N c

ouns

elin

g =1

73St

anda

rd =

176

AT

=14

TA

U =

14T

AT

=54

TA

U =

55M

easu

res

PAN

SSM

AQ

LCS

DA

i

PAN

SSBA

RS

Schi

zoph

reni

a O

utco

mes

Mod

ule

Self-

repo

rt/m

edic

al r

ecor

d re

view

fo

r ad

here

nce

PAN

SSG

AF

DA

i-30

SwA

MLU

NSe

RS

SeS

MA

QD

Ai

CR

SPA

NSS

eQ-5

DBi

rchw

ood

insi

ght

Scal

eFi

ndin

gsN

o si

gnifi

cant

diff

eren

ces

in

med

icat

ion

adhe

renc

e

betw

een

Mi a

nd H

e;

redu

ced

hosp

italiz

atio

ns

for

fem

ale

patie

nts

in t

he

Mi g

roup

vet

eran

s w

ith e

nhan

ced

guid

elin

e/R

N

coun

selin

g si

gnifi

cant

ly m

ore

likel

y

to b

e ad

here

nt a

t 6-

mon

th fo

llow

-up

Adh

eren

ce a

t 6

mon

ths

sign

ifica

ntly

as

soci

ated

with

adh

eren

ce a

t ba

selin

e,

fem

ale

sex,

and

neg

ativ

e ba

selin

e

akat

hisi

a

AT

gro

up: s

igni

fican

t im

prov

emen

t

in P

AN

SS s

core

s, p

ositi

ve

sym

ptom

s, a

ttitu

des

tow

ard

m

edic

atio

ns, s

atis

fact

ion

w

ith m

edic

atio

ns

com

pare

d to

TA

U

TA

T =

sig

nific

antly

impr

oved

ser

vice

en

gage

men

t an

d m

edic

atio

n ad

here

nce

co

mpa

red

to T

AU

TA

T e

ffect

less

at

6-m

onth

follo

w-u

p

but

rem

aine

d si

gnifi

cant

for

med

icat

ion

adhe

renc

eN

o im

prov

emen

t in

sym

ptom

s or

qua

lity

of li

fe

Abb

revi

atio

ns:

AT

, adh

eren

ce t

hera

py;

BAR

S, B

rief

Adh

eren

ce R

atin

g Sc

ale;

CR

S, C

ompl

ianc

e R

atin

g Sc

ale;

DA

i, D

rug

Att

itude

inv

ento

ry;

DA

i-30,

Hog

an D

rug

Att

itude

inv

ento

ry;

eQ-5

D, e

uroQ

ol;

GA

F, G

loba

l Ass

essm

ent

of

Func

tioni

ng; H

e, h

ealth

edu

catio

n; L

CS,

Life

Cha

rt S

ched

ule;

LU

NSe

RS,

Liv

erpo

ol U

nive

rsity

Neu

role

ptic

Sid

e ef

fect

Rat

ing

Scal

e; M

AQ

, Med

icat

ion

Adh

eren

ce Q

uest

ionn

aire

; Mi,

mot

ivat

iona

l int

ervi

ewin

g; P

AN

SS, P

ositi

ve a

nd N

egat

ive

Synd

rom

e Sc

ale;

RC

T, r

ando

miz

ed c

ontr

olle

d tr

ial;

RN

, reg

iste

red

nurs

e; S

eS, S

ervi

ce e

ngag

emen

t Sc

ale;

Sw

AM

, Sat

isfa

ctio

n w

ith A

ntip

sych

otic

Med

icat

ion

Scal

e; T

AT

, tre

atm

ent

adhe

renc

e th

erap

y; T

AU

, tre

atm

ent

as u

sual

.

Neuropsychiatric Disease and Treatment 2015:11 submit your manuscript | www.dovepress.com

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1085

Support services to improve medication adherence in schizophrenia

Tab

le 4

Mis

cella

neou

s su

ppor

t se

rvic

es

Cit

atio

nM

orke

n et

al51

Pri

ebe

et a

l52V

alen

stei

n et

al53

Vel

ligan

et

al54

Vel

ligan

et

al33

Des

ign

type

RC

TR

CT

with

clu

ster

ra

ndom

izat

ion

cont

rolle

d

tria

l of t

reat

men

t te

ams

RC

T w

ith b

lock

-ran

dom

izat

ion

of

pat

ient

s (e

xper

imen

tal

with

out

doub

le-b

lind)

3-ar

med

RC

T3-

arm

ed R

CT

inte

rven

tion

de

scri

ptio

niT

=2

year

s of

ass

ertiv

e

outr

each

com

mun

ity t

reat

men

t, fa

mily

psy

choe

duca

tion,

soc

ial

skill

s tr

aini

ng/C

BT

Patie

nts

on in

terv

entio

n

team

s w

ho a

dher

ed

75%

of

the

tim

e4

mon

ths

prio

r to

scr

eeni

ng

rece

ived

fina

ncia

l inc

entiv

e

of $

22/c

linic

vis

it to

rec

eive

pr

escr

ibed

long

-act

ing

an

tipsy

chot

ic in

ject

ion

inte

rven

tion:

Med

s-H

elp

= un

it-do

se

med

icat

ion

pack

agin

g m

edic

atio

n

educ

atio

n

Phar

m-C

AT

– t

ailo

red

en

viro

nmen

tal s

uppo

rts

an

d w

eekl

y ho

me

visi

tsM

ed e

-Mon

itor

– pr

ompt

s

from

an

elec

tron

ic d

evic

e

in t

he p

atie

nt’s

hom

e;

tele

phon

e co

ntac

tsT

AU

Full-

CA

T –

tai

lore

d en

viro

nmen

tal

supp

orts

for

inde

pend

ent

livin

g

skill

s, s

ocia

l/rol

e pe

rfor

man

ce,

med

icat

ion

adhe

renc

ePh

arm

-CA

T –

tai

lore

d

envi

ronm

enta

l sup

port

s

for

med

icat

ion

and

appo

intm

ent

ad

here

nce

only

TA

UD

ata

colle

ctio

n tim

e po

ints

Base

line,

12

mon

ths,

24

mon

ths

Base

line

to 1

2-m

onth

end

poin

t12

mon

ths

prio

r to

enr

ollm

ent

(bas

elin

e), 0

–6 m

onth

s,

and

6–12

mon

ths

afte

r en

rollm

ent

Base

line,

3 m

onth

s, 6

mon

ths,

9

mon

ths

Base

line,

3 m

onth

s, 6

mon

ths,

9

mon

ths,

12

mon

ths,

15

mon

ths

Sam

ple

iT =

30C

ontr

ol =

20in

terv

entio

n =7

8, c

ontr

ol =

63M

eds-

Hel

p =5

8T

AU

=60

Phar

m-C

AT

=46

Med

e-M

onito

r =4

6T

AU

=45

Full-

CA

T =

34Ph

arm

-CA

T =

32T

AU

=29

Mea

sure

sM

edic

atio

n A

dher

ence

(s

elf,

fam

ily a

nd c

linic

ian

repo

rts)

C

ambe

rwel

l Fam

ily in

terv

iew

BPR

S

Med

icat

ion

adhe

renc

eC

Gi

DiA

LOG

sca

leSa

tisfa

ctio

n w

ith m

edic

atio

n

Prim

ary:

MPR

Seco

ndar

y:PA

NSS

Qw

BSC

SQ

Med

icat

ion

adhe

renc

eSC

iDBP

RS

SOFA

SSe

rvic

e us

e

SCiD

Pill

coun

tsBP

RS

SOFA

SR

elap

se S

core

Find

ings

No

sign

ifica

nt d

iffer

ence

s

in m

edic

atio

n ad

here

nce

be

twee

n iT

and

ST

Men

mor

e no

n-ad

here

nt

than

wom

en

Mod

est

finan

cial

ince

ntiv

es

impr

ove

adhe

renc

e to

LA

i12

-mon

th t

rial

adh

eren

ce:

inte

rven

tion

grou

p =8

5%,

cont

rols

=71

%Se

cond

ary

outc

ome

adhe

renc

e of

95

%: i

nter

vent

ion

grou

p =2

8% c

ontr

ols

=5%

MPR

s =

Med

s-H

elp

grou

p

had

sign

ifica

ntly

M

PRs

at

6 m

onth

s (M

eds-

Hel

p M

PR 0

.91,

U

C M

PR 0

.64)

and

12

mon

ths

Med

s-H

elp

MPR

0.8

2, U

C 0

.62

(P

0.00

01)

Med

icat

ion

adhe

renc

e –

Phar

m-C

AT

=90

%M

ed e

-Mon

itor

=91%

TA

U =

73%

Both

Pha

rm-C

AT

and

Med

e-

Mon

itor

sign

ifica

ntly

hig

her

than

TA

U

Med

icat

ion

adhe

renc

e si

gnifi

cant

ly

high

er in

Ful

l-CA

T a

nd P

harm

-CA

T

grou

ps c

ompa

red

to T

AU

; rem

aine

d si

gnifi

cant

ly h

ighe

r af

ter

hom

e vi

sits

st

oppe

d

Abb

revi

atio

ns: B

PRS,

Bri

ef P

sych

iatr

ic R

atin

g Sc

ale;

CG

i, C

linic

al G

loba

l im

pres

sion

s Sc

ale;

CBT

, cog

nitiv

e–be

havi

oral

ther

apy;

CSQ

, Clie

nt S

atis

fact

ion

Que

stio

nnai

re; F

ull-C

AT

, ful

l cog

nitiv

e ad

apta

tion

trai

ning

; iT

, int

egra

ted

trea

tmen

t; LA

i, lo

ng-a

ctin

g in

ject

able

; MPR

, med

icat

ion

poss

essi

on r

atio

; PA

NSS

, Pos

itive

and

Neg

ativ

e Sy

ndro

me

Scal

e; P

harm

-CA

T, c

ogni

tive

adap

tatio

n tr

aini

ng w

ith m

edic

atio

n ed

ucat

ion;

Qw

BS, Q

ualit

y of

wel

l-Bei

ng S

cale

; RC

T, r

ando

miz

ed

cont

rolle

d tr

ial;

SCiD

, Str

uctu

red

Clin

ical

inte

rvie

w fo

r D

iagn

osis

; SO

FAS,

Soc

ial a

nd O

ccup

atio

nal F

unct

ioni

ng A

sses

smen

t Sc

ale;

ST

, sta

ndar

d tr

eatm

ent;

TA

U, t

reat

men

t as

usu

al; U

C, u

sual

car

e.

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el-Mallakh and Findlay

for psychiatric and medical conditions over 3 months had

significantly higher adherence compared to TAU controls.

Those in the intervention group were 80% adherent to psy-

chiatric medications and 33% adherent to medications for

medical conditions.

Stip et al46 found that after 8 weeks of using an electronic

pill counter to assess medication adherence, 46% were non-

adherent. The mean antipsychotic adherence ratio was 67%

after 6 weeks. Participants who were adherent at baseline

had significantly greater adherence versus those who were

nonadherent at baseline. Španiel et al45 found that after 1 year

of computer prompts to clinicians to increase antipsychotic

medication doses when participants reported psychotic symp-

toms (via an electronic message), there was no significant

difference in medication adherence in the intervention group

compared to controls.

Motivational interviewing interventionsMI was used in conjunction treatment adherence therapy

(TAT) and problem solving approaches (Table 3).47–50

Barkhof et al47 found that there were no significant differ-

ences in medication adherence after 26-week and 6-month

interventions of MI versus health education. Staring et al50

examined the effectiveness of 6 months of TAT, which

includes MI, medication optimization, and behavioral train-

ing, and found that TAT significantly improved medication

adherence. Findings also indicated that, despite a decrease

in effectiveness at the 6-month follow-up, adherence in the

intervention group remained significantly higher than in the

TAU group.

Hudson et al48 found that clinical interviews with a

registered nurse who asked people to identify barriers to

adherence and tailored strategies to overcome them via

problem solving at each clinic visit (minimum of every 6

weeks) for 6 months significantly increased adherence at

the 6-month follow-up. Adherence at 6 months was signifi-

cantly associated with baseline adherence, female sex, and

no akathisia at baseline. Maneesakorn et al49 examined the

effectiveness of eight weekly sessions of adherence therapy

which focused on medication problem-solving, beliefs/

attitudes/ambivalence toward taking medications, and tak-

ing medications in the future. Findings indicated that the

participants in the adherence-therapy group showed signifi-

cant improvements in positive symptoms, attitudes toward

medications, and satisfaction with medications. In this study,

medication adherence was not used as a primary outcome

measure; the authors noted that the outcomes of symptom

reduction and medication attitudes and satisfaction, rather

than adherence, are indicators of the potential health gain

due to the intervention.49

Other support service interventionsA variety of other support interventions were examined

(Table 4);33,51–54 these included integrated treatment,51

financial incentives,52 a pharmacy-based intervention,53 and

environmental supports.33,54 Morken et al51 found that a multi-

faceted program that implemented CBT along with assertive

outreach community treatment, family psychoeducation, and

social skills training, did not significantly improve medica-

tion adherence compared to TAU. Priebe et al52 found that

modest financial incentives, in the amount of $22 per clinic

visit, to receive an LAI during a 12-month trial increased

adherence from 75% at baseline to 85%, compared to 71%

among controls. Greater than 95% adherence was seen in

28% of the intervention group, compared to 5% in the con-

trol group. Valenstein et al found that, compared to controls,

patients using a pharmacy-based intervention that included

unit-dose prescriptions of medications for psychiatric and

medical conditions, medication education in packaging,

and refill reminders mailed 2 weeks in advance for 6 and

12 months had significantly increased medication possession

ratios (MPR, a measure that includes self-reports of adher-

ence combined with pill counts and serum labs indicating

presence of medication).53

Environmental supports involved the use of home visits

and adaptation of participants’ home environment to incor-

porate cues as reminders to adhere to treatment. Velligan

et al54 found that home visits with full cognitive adaptation

training, a tailored environmental support system aimed at

improving independent living skills, and cognitive adaptation

training with medication education, a tailored environmental

support system for medication and appointment adherence,

significantly improved medication adherence in both groups

compared to the TAU group, and this difference remained

significant after home visits stopped.

DiscussionFindings suggest that the utility of available support ser-

vices to enhance medication adherence depend on a variety

of factors, such as the PWS’s attitudes toward treatment,

perceptions of the need to take medications, and specific

environmental and cognitive characteristics. Technological

supports, such as mobile phone text message reminders, can

be beneficial to PWS who are committed to medication adher-

ence and are occasionally nonadherent due to forgetfulness.

Similarly, interventions that focus on environmental cues to

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Support services to improve medication adherence in schizophrenia

remind PWS to take their medications can be very helpful

in patients with memory problems.54 In contrast, findings

from this review suggest that therapeutic support services

are more appropriate to PWS who are ambivalent toward

taking medications and or deny the need to take medica-

tions. The most effective support service interventions are

tailored to the specific needs of PWS, use a problem-solving

approach to identify barriers to taking medications, and

address ambivalence that PWS have toward committing to

a life-long medication regimen.

Results of this literature review should be regarded with

caution due to some limitations in the study designs. Adherence

to psychiatric medications may depend on the participants’

age, financial constraints/affordability of medications,9

adverse effects, severity of psychiatric symptoms, duration

of illness, side effects, and therapeutic response. Younger

age is a noteworthy predictor of nonadherence.4 However,

in the studies reviewed here, only two focused on younger

participants. One included family members as caregivers,39 in

which the mean age of participants was 24.6±8.3 years, and

one included participants with recent onset of symptoms;31

the mean age of participants in this study was 25.1±4.5 years.

In the remaining studies, the mean ages of participants ranged

from approximately 30–50 years, which limits generalizabil-

ity to other age groups. Problems with medication adherence

due to financial constraints and affordability of medications

were not addressed in these studies, which is a noteworthy

gap that warrants further research.

Medication side effects are known contributors to poor

medication adherence among PWS.17 However, only three

studies in this review included a measure of side effects as

an outcome variable. Maneesakorn et al49 found reduced

scores on the Liverpool University Neuroleptic Side Effect

Rating Scale in the TAU group at a 9-week follow-up; the

authors attribute this to the higher number of participants

who were prescribed atypical antipsychotics in the TAU

group. Hudson et al48 found greater adherence associated with

negative baseline akathisia score. Finally, Sajatovic et al41

reported that in an adherence study that included LAIs, 40%

reported akathisia, but no significant changes were seen in

body mass index or total cholesterol. Findings from this

review suggest that further research is warranted to exam-

ine the degree to which adverse or side effects of the more

frequently used atypical antipsychotics influence medication

adherence, particularly related to the emergence of obesity

and cardiovascular/metabolic problems.

Severity of psychotic symptoms and level of cognitive

functioning can also influence medication adherence. In the

studies included in this review, all but four assessed symptom

severity at the outset of the studies. Rating measures included

the Positive and Negative Syndrome Scale, the Clinical

Global Impressions Scale, and the Brief Psychiatric Rating

Scale. Across all studies that measured symptoms, baseline

symptom severity scores ranged from very mildly to mod-

erately ill. It is likely that PWS who experience very severe

symptoms are excluded from medication adherence research

because very severe symptoms prevent them from providing

informed consent for participation. Consequently, research

on medication adherence has limited generalizability toward

PWS with severe psychotic symptoms, and unfortunately

PWS who refuse or are unable to participate are most in need

of support services to improve adherence. In addition, partici-

pants’ treatment response was minimal in many of the studies,

as evidenced by nonsignificant changes in symptom severity

scores at the conclusion of the studies.33,35,36,42,43,45,53

Several authors also reported that PWS who refused to

participate in the studies had considerable deficits in cogni-

tive functioning. Limitations on eligibility based on cognitive

functioning tended to limit the sample sizes, which ranged

from 25–409; the majority of studies had less than 100 par-

ticipants. Several authors pointed out that eligibility based

on cognitive functioning and symptoms resulted in selection

bias, which increased the likelihood that participants had

higher levels of functioning.49

Very little longitudinal research has been conducted on

medication adherence over the lifetime trajectory of illness

among PWS; the maximum duration of time included in an

adherence study was 4 years.53 Patterns of adherence may be

unstable over time; Valenstein et al10 investigated patterns of

medication adherence, measured by MPR over a 4 year period

among 34,128 veterans with schizophrenia, and the findings

suggested that over 60% of veterans had adherence problems

at some point during the 4 year period. Findings also indi-

cated that over a 4 year period, about 18% had consistently

poor adherence, defined as MPRs 0.8 in all 4 years; 43%

had inconsistent adherence, defined as MPRs 0.8 in some

years in the observation period, and 39% had consistently

good adherence, defined as MPRs 0.8 in all 4 years.

Very few reviewed studies focused on the effectiveness

of support services in improving adherence to medications

in the treatment of medical illnesses. Furthermore, it is

important to note that in the study conducted by Beebe et al29

the telephone intervention problem-solving intervention

improved adherence to psychiatric medications but not to

medications for medical illnesses. Problems with adherence

to medications for medical illnesses are by no means unique

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el-Mallakh and Findlay

to PWS. Rates of medication nonadherence are about 50% in

the general population,55 which is essentially identical to rates

of nonadherence to psychiatric medications among PWS.1

Low adherence to medications in the general population

has been attributed to poor health literacy, intolerable side

effects, and unaffordable copayments.55 In addition, people

in the United States who are diagnosed with multiple chronic

medical illnesses often receive fragmented care from several

different providers, which results in complex medical regi-

mens consisting of multiple medications.55

PWS who have complex comorbid medical illnesses

likely experience barriers similar to those found in the gen-

eral population, particularly related to fragmented care.26

A supportive therapeutic alliance has been shown to promote

medication adherence in PWS, yet Piette et al26 have observed

that fragmented and poorly coordinated medical care from

multiple providers in different treatment settings is a consid-

erable barrier to the development of a trusting relationship

between patients and provider. In addition, PWS have an

even greater risk for nonadherence compared to the general

population due to problems with motivation and cognitive

impairments that interfere with memory, attention, problem-

solving, and health-related decision making.56

Adherence to medications that treat psychiatric and

medical illnesses is essential for PWS to achieve recovery

goals and optimize overall wellness, yet ongoing research

strongly suggests that physical health status and overall

wellness in this population are far from ideal. PWS suffer

from higher-than-average rates of comorbid chronic medical

illnesses and experience worse outcomes due to these ill-

nesses compared to the general population, including higher

rates of emergency hospital admissions, longer length of

hospitalization for medical problems, and shorter length of

survival.57–59 Much attention has been focused on the recent

report that the life expectancy of PWS being served in the

US state mental health system is 25 years shorter than that

of the general population.60 These appalling morbidity and

mortality statistics illustrate health disparities that are increas-

ingly untenable to patients, clinicians, policy makers, and

family members.61–63 A comprehensive initiative to reduce

health disparities, integrate physical and mental health care,

and improve mental and physical health status would need

to address multiple barriers to effective health care among

PWS, their providers, and health care delivery systems; the

development of more-effective support services to improve

adherence to medications for psychiatric and medical ill-

nesses is foundational in this effort.64

Implications for practiceAs this review illustrates, several strategies are available to

prescribers to address medication adherence issues among

PWS. The essential first step is the establishment of a trusting

therapeutic relationship with the patient.7,16,20,21 In the event that

inpatient hospitalization is needed, PWS should be included in

treatment decisions as much as possible.20 Prior to implemen-

tation of support services, it is recommended that prescribers

work with the patient to conduct a root-cause analysis of rea-

sons for nonadherence; implementation would target specific

support strategies to address them. It is recommended that

prescribers address adherence to psychiatric medications as a

priority and then address adherence to medications for medi-

cal illnesses as a secondary goal, since PWS have reported

that stable psychiatric symptoms are an essential precursor to

effective management of medical illnesses.56,65

Prescribers can also use cognitive strategies to link medi-

cation adherence to the patient’s treatment goals, such as

staying out of the hospital, living independently, maintaining

normal glycemic control, or returning to work or school, as

recommended in the Medication Treatment, Evaluation and

Management evidence-based practice.66 Finally, prescrib-

ers can promote optimal medication adherence by regularly

including PWS in decisions about medications and assessing

patient knowledge and attitudes about medications through-

out the provision of support services.66

DisclosureThis research was not funded by any extramural agency.

The authors report no conflicts of interest in this work.

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