The Use of Individually Tailored Environmental Supports to Improve Medication
Adherence and Outcomes in Schizophrenia
Dawn I. Velligan1,2, Pamela M. Diamond5, Jim Mintz2,
Natalie Maples2, Xueying Li2, John Zeber2,6,
Larry Ereshefsky3, Yui-Wing F. Lam4,
Desiree Castillo2, and Alexander L. Miller2
2Department of Psychiatry;3Department of Pharmacotherapy
Education and Research;4Department of Pharmacology,
University of Texas Health Science Center at San Antonio,
San Antonio, TX;5Center for Health Promotion and
Prevention Research, University of Texas School of
Public Health, Houston, TX;6VERDICT, Veterans Affairs
HSR&D, San Antonio, TX
Cognitive adaptation training (CAT) is a psychosocial
treatment that uses environmental supports such as signs,
checklists, alarms, and the organization of belongings to cue
and sequence adaptive behaviors in the home. Ninety-five
outpatients with schizophrenia (structured clinical inter-
view for diagnosis, Diagnostic and Statistical Manual of
to (1) Full-CAT (CAT focused on many aspects of commu-
nity adaptation including grooming, care of living quarters,
leisure skills, social and role performance, and medication
adherence), (2) Pharm-CAT (CAT focused only on medica-
tion and appointment adherence), or (3) treatment as usual
(TAU). Treatment lasted for 9 months, and patients were
followed for 6 months after the withdrawal of home visits.
Medication adherence (assessed during unannounced, in-
home pill counts) and functional outcomes were assessed
at 3-month intervals. Results of mixed-effects regression
models indicated that both CAT and Pharm-CAT treat-
ments were superior to TAU for improving adherence to
prescribed medication (P < .0001). Effects on medication
drawn. Full-CAT treatment improved functional outcome
relative to Pharm-CAT and TAU (P < .0001). However,
differences for functional outcome across groups decreased
following the withdrawal of home visits and were no longer
statistically significant at the 6-month follow-up. Survival
longer in both CAT and Pharm-CAT in comparison to
TAU(.004). Findingsindicate that supportstargeting med-
ication adherence can improve and maintain this behavior.
Comprehensive supports targeting multiple domains of
functioning are necessary to improve functional outcomes.
Maintenance of gains in functional outcome may require
some form of continued intervention.
Key words: medication adherence/cognitive deficits/
cognitive rehabilitation/medication compliance/cognitive
adaptation training/environmental supports
Psychosocial treatments designed to remediate or to by-
pass cognitive impairments are important to pursue in
maximizing outcomes for individuals with schizophre-
tion that utilizes compensatory strategies and supports
such as pill containers with alarms, organization of be-
longings, and activity checklists to prompt and sequence
adaptive behaviors in an individual’s home environ-
ment.2,8,9CAT strategies are tailored to the specific
cognitive impairments and behavioral approaches to
goal-directed activity exhibited by each participant.
These customized strategies have been found to decrease
levels of symptomatology and to improve social and oc-
cupational functioning for individuals with schizophre-
nia.2,9While the entire package of environmental
supports provided in CAT has been found to improve
community outcomes, it is important to demonstrate
that individualized supports targeting specific behavioral
outcomes are able to improve those specific behaviors.
Arguably, one of the most important behavioral tar-
tipsychotic medications. Medications may help to form
a foundation upon which the process of functional recov-
ery can proceed. The role of antipsychotic medications in
preventing symptom exacerbation and rehospitalization
has been firmly established.10Even small gaps in the time
during which medication is available to patients can
increase the risk of hospitalization.11More than 50%
of patients with schizophrenia do not take medications
as prescribed.12–18The adherence problem contributes
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Schizophrenia Bulletin vol. 34 no. 3 pp. 483–493, 2008
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substantially to poor outcomes and high health care costs
for individuals with this diagnosis.
Using environmental supports to cue and reinforce
taking medication have been found to be among the
most effective strategies for individuals with physical ill-
nesses.19–22CAT provides a way to customize these sup-
ports directed at adherence behavior for individuals with
In the present study, we investigated the efficacy of
environmental supports for adherence to antipsychotic
medications and functional outcome in patients with
schizophrenia. We hypothesized that both Full-CAT
(CAT focusedonmany aspectsofcommunity adaptation
including grooming, independent living skills, social
and role performance, and medication adherence) and
Pharm-CAT (a subset of CAT treatment in which par-
ticipants received environmental supports individually
tailored for cognitive impairments and overt behaviors
that were focused only on medication and appointment
adherence) would improve adherence to antipsychotic
medication as compared with a group receiving only
standard outpatient medication follow-up. Moreover,
because medication alone is not enough to substantially
improve functional outcomes for individuals with schizo-
phrenia, we hypothesized that functional outcomes
would be better for participants in Full-CAT treatment
in comparison to those in the other treatment groups.
Secondary hypotheses included that patients in both
CAT and Pharm-CAT would demonstrate lower levels
of symptomatology and decreased rates of relapse rela-
tive to those in standard treatment.
Subjects were outpatients with a diagnosis of schizophre-
nia or schizoaffective disorder who were being seen at
a community mental health center for medication follow-
up. Participants received a baseline assessment and were
then randomized into one of 3 treatment conditions for
CATtreatment(CATtreatmentaddressingonly issues of
medication and appointment adherence), and (3) treat-
ment as usual (TAU)—no additional treatment other
than standard medication follow-up provided by the
community outpatient clinic. Randomization was strat-
ified by recruitment site (hospital vs community clinic),
gender, and age.
Treatment lasted for 9 months, and then subjects were
followed for an additional 6 months after the end of for-
mal treatment. Note that environmental supports (eg,
signs, pill containers) in CAT and Pharm-CAT were
not taken away at the end of treatment visits.
Assessments of symptomatology and functioning were
conducted at baseline and every 3 months. Medication
ization to treatment (no baseline).
Subjects were outpatients recruited in 2 streams. Ninety-
nine were recruited at the time of discharge from an in-
patient psychiatric facility and followed for 3 months
after discharge prior to baseline assessments and ran-
domization into treatment. Fifty-seven were recruited
as outpatients from one of 3 public clinics run by the
same mental health authority. As shown in figure 1, of
the 156 patients signing consent, 105 were randomized.
Of these 105, there were 95 subjects with baseline and
follow-up data for data analyses. Reasons for drops
are listed in figure 1.
Subjects were identified through chart reviews by
research staff credentialed at participating sites in
accordance with Health Insurance Portability and Ac-
countability Act requirements. All participants signed
a written consent form approved by an Institutional
Review Board, and procedures were consistent with in-
ternationally recognized standards for ethical conduct of
Diagnoses were confirmed utilizing the Structured
Clinical Interviewfor Diagnosis.23In addition to meeting
diagnostic criteria, subjects were required to (1) be be-
tween the ages of 18 and 60 years, (2) be receiving treat-
ment with an oral atypical antipsychotic with the treating
physician’s recommendation to continue the medication
and participate in follow-up at the Center for Health
Care Services, (3) have primary responsibility for taking
ropsychological testing. Individuals were excluded if they
were on clozapine or depot medication, had a docu-
mented history of significant head trauma, seizure disor-
der, or mental retardation, had a history of substance
abuse or dependence in the past month, or had a history
of violence in the past 6 months.
Fifty-four subjects were male, and 41 were female.
Thirty-five were Hispanic, 35 were Anglo, 20 were Afri-
can American, and 5 were from other or mixed ethnic
groups. Mean age of participants was 39.0 years (SD =
10.7). Seventy-five percent of patients (n = 71) were on
risperidone or olanzapine with the remaining 25% on ari-
15). Just over 70% of patients (n = 67) were on concom-
itant medications for side effects, mood, or anxiety. At
baseline, symptoms of psychosis as rated from the Brief
Psychiatric Rating Scale (BPRS) psychosis factor were in
the mild range on average (M = 2.59; SD = 1.38). There
were no significant differences in demographics for par-
ticipants not making it to randomization vs those ran-
domized to treatment (all P#s > .20). There were no
differences in baseline variables for participants in the
2 different recruitment streams (all P#s > .20) suggesting
D. I. Velligan et al.
that by the time of randomization, the outpatients re-
cruited from the inpatient site were similar to those re-
cruited from the outpatient clinics on baseline measures.
Cognitive Adaptation Training.
manual-driven compensatorystrategies and environmen-
tal supports designed to improve multiple domains of
adaptive functioning including adherence to medication,
grooming, and activities of daily living in patients with
schizophrenia.2,8,9,24,25Environmental supports in Full-
CAT treatment were based upon a comprehensive assess-
ment of neurocognitive function, behavior, adaptive
functioning, and the environment. Interventions for
each functional deficit were based on 2 dimensions, (1)
level of impairment in executive functions (as determined
byscoreson asetof neurocognitivetests) and(2) whether
the overt behavior of the individual during performance
of goal-directed activity was characterized more by apa-
thy (poverty of speech and movement and the inability to
CAT is a series of
inhibition (distractibility and behavior which is highly
cue driven), or a combination of these styles (based
upon scores from the Frontal Systems Behavior Scale).26–28
According to the CAT model, individuals with poor
executive functioning need high levels of structure and
more obviously placed environmental cues, while those
with somewhat better executive functioning need less
structure and more subtle cues.2Individuals with apa-
thetic behavior benefit from environmental supports
that cue and sequence behavior, those with disinhibition
benefit most from the removal of distracting stimuli, and
those with mixed behavior benefit from a combination of
these strategies. Assessment results yield one of 6 CAT
classifications for which interventions can be targeted
(ie, apathy/poor executive function, apathy/fair executive
function; disinhibited/poor executive function, disinhi-
bited/fair executive function; mixed/poor executive func-
tion; mixed/fair executive function).
Once an individual’s CAT classification was deter-
mined, strategies for specific functional problems (med-
ication adherence, laundry, and leisure activity) were
4 withdrew consent
1 unable to complete assessments
1 changed medication
1 moved to environment unsafe for
1 demonstrated aggressive behavior
1 substance abuse
1 moved out of area
99 inpatients57 outpatients
11 were rehospitalizedand unable to transition
9 were homeless or unable to be located
8 withdrew consent
4 were incarcerated
3 were unable to complete assessments
2 demonstrated aggressive behavior
2 changed medication
1 was deceased
59 randomized 46 randomized
at least 1 Follow-up
Fig. 1. Subject Recruitment and Retention.
Environmental Supports, Adherence, and Outcome
chosen from the manual. CAT interventions were estab-
lished, trained, and maintained in the home during
weekly visits from a CAT therapist/trainer.
Problems with dressing/grooming and taking medica-
tion are described, and examples of CAT interventions
for each of these problems are presented in table 1 below.
Examples describe interventions for some of the 6 possi-
ble CAT classifications.
program, is a manual-driven treatment utilizing environ-
mental supports such as signs, checklists, and electronic
cuing devices to improve medication and treatment ad-
herence. Prior to treatment, patients received the same
set of assessments as those in Full-CAT. Interventions
in Pharm-CAT are individualized in the same manner
as those in Full-CAT treatment. However, only interven-
tions that specifically target adherence are used. Addi-
tional issues such as transportation are addressed only
if they relate to taking medication (eg, picking up pre-
scriptions at a pharmacy) or making it to clinic appoint-
ments (eg, bus passes).
Patients in Full-CAT and Pharm-CAT were seen once
weekly for 30–45 minutes. Visits in Pharm-CAT were
Pharm-CAT, a subset of the Full-CAT
necessarily shorter in duration because the focus of treat-
ment was circumscribed around the issue of adherence.
CAT and Pharm-CAT therapists were individuals with
bachelor’s or master’s degrees in psychology or related
fields trained using a combination of didactic and in
vivo strategies. Fidelity checks to ensure therapist adher-
ence to the model were made using the CAT fidelity scale
who reviewed 30% of tape recordings of home visits and
made home visits to examine the extent to which the sup-
ports established were indicated. Scores range from 0 to
100. Mean fidelity scores for a total of 18 therapists
(trained in CAT and Pharm-CAT) were 90.66 (SD =
5.14) with a range from 75.15 to 98.0.
Diagnostic and Statistical Manual for Mental Disorders
was utilized to make Diagnostic and Statistical Manual
of Mental Disorders, Fourth Edition, diagnoses. Prior
to administering this interview, all raters were trained to a
reliability of 0.95 kappa statistic for a diagnosis of schizo-
phrenia or schizoaffective disorder vs all other diagnoses.
The Structured Clinical Interview for the
Table 1. Problems in Adaptive Function and Examples of Cognitive Adaptation Training (CAT) Interventions
General Problem and CAT Classification
Based on Comprehensive AssessmentSpecific BehaviorCAT Interventions
Dressing disinhibited behavior—poor
Wears 3 shirts at once because they are
hanging in the closet and wears clothing
that is inappropriate for the weather (eg,
jackets in 90? heat).
Place complete outfits (shirt, pants,
underwear, socks) in separate plastic
containers labeled with the day of the
week. No clothes are hanging in the
closet so there is no cue to put on
additional clothing. Remove clothing
inappropriate for the weather to be
Grooming apathetic behavior—poor
Unkempt appearance, shirt not tucked in,
hair not combed, etc. Difficulty initiating
each step in a multiple step task.
Place a full-length mirror in an obvious
location. Attach a comb to the mirror
with a string and a sign, ‘‘Is my hair
combed? Is my shirt tucked in?’’
Taking medication disinhibited
behavior—fair executive functioninga
Takes too much medication, uses old
medications, and combines them with
over-the-counter medications without
checking with physician.
Clear out all old prescriptions and over-the-
counter medications to be stored
elsewhere (eg, in a container under the
bed). Place a sign on the box ‘‘Do not
take without checking with Dr X at 555-
5555.’’ Assist patient in placing current
medicines in daily use containers, labeled
with date and time.
Apathetic behavior—fair executive
Forgets to take medication. Would not get
out of bed to take AM medications and
misses 50% of prescribed doses due to
Use a voice alarm recorded in the patient’s
own voice reminding ‘‘It’s time to take
medication.’’ If no children are present or
visit, place AM medications on a stand by
the bed with bottled water.
aThese interventions are available in both Full-CAT (CAT focused on many aspects of community adaptation including grooming, care
of living quarters, leisure skills, social and role performance, and medication adherence) and Pharm-CAT (CAT focused only on
medication and appointment adherence).
D. I. Velligan et al.
cent adherence derived from unannounced pill counts
conducted in participants’ homes twice during each 3
months during the study. Asking patients to bring pills
into clinic appointments biases data by collecting of
more complete data on subjects with greater adherence.29
The researcher making the visit requested that he or she
be given all pills available to be counted. An adherence
percent was (the number of pills missing from the bottle
sessment of medication adherence using unannounced,
in-home pill counts is innovative in schizophrenia re-
search. The method required some initial preparation
including asking patients to save all empty medication
bottles (providing a sign and empty box) and bagging
and stapling old bottles of medication so that the re-
bottles. Specific procedures to address multiple bottles,
samples of medication, and other problems associated
with pill counts are available from D.I.V. Pill counts
could not be blinded due to the obvious nature of envi-
Pharmacy records were examined as a secondary mea-
sure of adherence that would not be impacted by the ob-
vious nature of environmental supports in the participants’
homes. Pharmacy percent adherence [(number of pills
supplied/number days in period) 3 100] was calculated.
Pharmacy records that overlapped assessment periods
were included in the assessment period in which the ma-
jority of prescription days fell.
Our primary measure was per-
Symptom, Relapse, and Functional Assessment
Symptom and functional assessments were administered
quired to reach a criterion of 0.80 intraclass correlation
coefficient on a combination of video-recorded and live
addition, all raters were observed administering multiple
assessments to ensure standardized and competent ad-
ministration of all scales. Checks on rater competency
were conducted throughout the study, and regular meet-
ings were held to prevent rater/scorer drift.30
expanded version of the BPRS.31The psychosis factor
score, calculated as the mean of items assessing halluci-
nations, unusual thought content, suspiciousness, and
conceptual disorganization, was utilized as a measure
of positive symptoms.32,33Higher scores indicate higher
levels of symptomatology.
Symptoms were assessed using the
based upon the work of Nuechterlein et al36and
Schooler,35we developed an index for relapse in remit-
ted/partially remitted patients. For subjects to be
Hospital use is influenced by social, economic,
counted as at least partially remitted, scores on 3 of
the 4 BPRS psychosis items had to be 4 or lower indicat-
ing moderate symptoms only. A relapse was scored if
scores on any of the 4 items increased a minimum of 2
points to a score of 5 or higher, if the patient was suicidal,
if the patient was hospitalized, or if the patient was un-
using the Social and Occupational Functioning Scale
(SOFAS).23This instrument assesses the overall level
of functioning on a scale from 1 to 100 based upon social,
school, and work functioning. Higher scores indicate bet-
ter adaptive function. The SOFAS score was based upon
all information obtained about adaptive and social func-
tioning during a lengthy semistructured interview adap-
ted from multiple validated functional measures covering
independent living skills and social and role functioning.
To increase the validity of ratings, collateral information
was obtained from caregivers and relatives.
Global functioning was assessed
In an effort to maintain treatment blinds, all subjects and
neither to divulge information about any visits made by
staff of the research project nor to refer to any items they
mayhave receivedaspartofthe study.If blindswere bro-
ken, alternative raters blind to group assignment com-
pleted the remaining assessments.
We examined distributions for normality and homogene-
ity of variance and used transformations where necessary
to meet the assumptions of the statistical models. We ex-
amined group differences in medication adherence (pill
counts and pharmacy refill data), symptomatology
(BPRS positive symptom score), and functional outcome
(SOFAS score) over time (3, 6, 9, 12, 15 months) by treat-
ment group (CAT, Pharm-CAT, TAU) using mixed-
effects regression with repeated measures (SAS PROC
MIXED).37A random subject effect was included mod-
eling intercept, linear, and quadratic trend components.
As described by Kraemer and Blasey,38we utilized cen-
tering to ensure that the regression coefficient tested was
relevant to the research question. When baseline scores
were available (eg, functional outcome, symptoms),
these were used as covariates in the model. Group differ-
ences were tested by estimating group means at each of
the assessment points from the model using an overall
F test and pairwise t tests at points of interest. Graphs
of outcome variables depict lines generated from ran-
dom regression model estimates. Specific data points
at each time period are plotted around these lines.
For time to relapse, 3-month intervals were examined
utilizing a proportional hazard regression model with
Environmental Supports, Adherence, and Outcome
DISCRETE option to deal with ties. The graph was pre-
pared utilizing LifeTest.
To investigate whether statistically significant effects
were clinically meaningful, effect sizes were calculated
utilizing the SD for the outcome variable in the control
we report number needed to treat to reach a clinically
meaningful difference for the control vs each of the
Table 2 presents the demographic and baseline variables
by treatment group. There were no statistically signifi-
cant group differences with respect to demographic or
baseline data. The numbers of subjects available at
each assessment point differed slightly by measure. For
symptom and functional measures, the number of sub-
jects with data at each time point was as follows: baseline
n = 95; 3-month n = 94, 6-month n = 87, 9-month n = 81,
12-month n = 67, and 15-month n = 61. For pill count and
pharmacy records, respectively, 90 and 83 subjects had
available data at baseline and at least one follow-up.
We examined differential dropout by treatment group
using a proportional hazards regression model. Individ-
uals in Pharm-CAT were more likely to drop out of the
ment phase, 2 individuals dropped in CAT treatment and
TAU (6% and 7%, respectively), while 9 individuals
(28%) in the Pharm-CAT group dropped from study.
2= 14.01; P < .0009). During the active treat-
With respect to pill count adherence, the mixed-effects
regression model yielded a significant quadratic by group
interaction and a trend for linear by group interaction in-
dicating that the effects of the treatment differed over
time. Although the size of the treatment effect varied,
both CAT and Pharm-CAT were significantly better
than standard treatment at all time points throughout
formal treatment and the follow-up period. Differences
between CAT and Pharm-CAT treatments were not sig-
nificant at any time point (all P#s > .85). Figure 2 depicts
estimated means derived from the regression model at
specified time points by treatment group. P values of
the differences between experimental and standard treat-
ments are shown for each time point.
Averaged across the time points, the effect sizes for
CAT and Pharm-CAT compared with TAU were 1.09
and 1.05, respectively, values that correspond to number
needed to treat of 1.79 and 1.84, respectively.39For spe-
cific time points, these effects sizes varied from 0.53 at 3
months to 1.43 at 12 months. Beginning with 6 months of
treatment and for the remainder of the study, all effect
sizes for CAT or Pharm-CAT vs standard treatment
were over 1. According to Cohen’s conventions,40these
are large treatment effects.
amined prescription refill rates. The mixed-effects regres-
sion model yielded a significant main effect of group
(F2,105= 3.93, P < .02). There were neither significant
effects of time nor significant interactions. Patients in
CAT were significantly more adherent thanthose in stan-
dard treatment, and there was a nonsignificant trend for
patients in the Pharm-CAT group to be more adherent
than those in standard treatment (F2,98= ?2.85 P <
.006 and F2,102= ?1.81, P < .07, respectively). Averaged
across time points, the effect sizes for CAT and Pharm-
CAT vs the control for refill adherence were 0.51 and
Table 2. Baseline Characteristics by Treatment Group
Usual (n = 29)
(n = 32)
(n = 34)
% Male62.0743.75 64.71
% Hispanic 27.5938.71 29.41
% Non-Hispanic White 44.8338.71 29.41
Age, y39 (SD = 22.1)40 (SD = 11.1)37 (SD = 9.4)
Education11.7 (SD = 2.3) 11.3 (SD = 2.6)12.1 (SD = 2.3)
BPRS psychosis factor2.7 (SD = 2.34) 2.6 (SD = 1.47)2.5(SD = 1.34)
Social and occupational
45.6 (SD = 8.07)45.5 (SD = 8.90)45.9 (SD = 8.19)
Note: No significant group differences (all P#s with one exception >.40; trend for fewer males in Pharm-CAT [CAT focused only on
medication and appointment adherence] P < .08). CAT, cognitive adaptation training; BPRS, Brief Psychiatric Rating Scale.
D. I. Velligan et al.
0.33, respectively. According to Cohen’s conventions,40
these are moderate and small effect sizes, respectively.
line symptom scores used as covariates yielded no signif-
icant main effects or interactions (all P#s > .09).
Complete a total of 69 participants met criteria for remis-
sion at baseline (21/29 for standard, 23/32 for Pharm-
CAT, and 25/34). There were no significant differences
in the numbers of patients remitted in the 3 treatment
groups at baseline (v(2)
lapse differed by treatment group based on the propor-
tional hazards regression model (v(2)
.004). Differences between CAT and standard treatment
tively). Over 65% of patients in CAT and Pharm-CAT
treatments survived the 15 months without a relapse vs
only 19% of individuals in the standard treatment group.
There were no differences between active treatments. The
survival curves for each treatment group over time are
presented in figure 3.
2= 0.24; P < .89). The time to re-
= 11.09; P <
2= 8.29; P < .004 and (v(2)
2= 8.20; P < .005, respec-
For SOFAS scores, results of a mixed-effects regression
model yielded a significant group effect (F1,147= 22.01;
P < .0001) and significant group by linear and group
by quadratic interactions (F1,303= 4.85; P < .009; and
F2,290= 3.51; P < .04, respectively). Figure 4 depicts esti-
mates and means at each time point. Pharm-CAT dif-
fered significantly from standard treatment at 3 and 6
months (P#s < .05) but not at any time point thereafter.
CAT was significantly better than standard treatment at
all assessment points during the treatment period (all
P#s < .0001). CAT was significantly better than TAU
in the first 3 months of follow-up (P < .0001), but there
was only a nonsignificant trend for patients in CAT to do
better than those in standard treatment by the end of
6-month follow-up (P < .07). CAT was significantly bet-
ter than Pharm-CAT at all time points (P#s < .0004) with
Time in Treatment
3 months 6 months9 Months
Treatment PeriodFollow-up Period
Pill Count Adherence Percent100
12 months 15 months
CAT Treatment as UsualPharmCAT
Fig. 2. Adherence Derived From Unannounced Pill Counts in the
2.85; P < .06; visits by visits by group (quadratic)—F2,2515 3.46p
P < .033). P values for cognitive adaptation training (CAT) vs
Pharm-CAT (CAT focused only on medication and appointment
All othertimepoints hadP valuesof.0001.No differences between
CAT and Pharm-CAT (CAT focused only on medication and
appointment adherence) were found at any time point.
Fig. 3. Time to Relapse or Significant Exacerbation by Treatment
Group. Proportional hazards regression model for time to relapse
(v(2)25 11.09; P < .004).
3 months 6 months 9 Months12 months15months
Treatment Period Follow-up Period
Treatment as UsualPharmCAT
Fig.4. Social andOccupational FunctioningScale Score (SOFAS)
Over Time by Treatment Group. Main effect of group—F2,1475
113.38; P < .0001; visits by group (linear)—F2,2025 4.85; P < .009;
visits by visits by group (quadratic)—F2,2905 3.51; P < .032. P
values for cognitive adaptation training (CAT) vs standard
values for Pharm-CAT (CAT focused only on medication and
appointment adherence) vs standard treatment were <.014 at 3
CAT vs Pharm-CAT were .004, .0001, .0001, .0004, and .37 for
3,6,9,12, and 15 months, respectively.
Environmental Supports, Adherence, and Outcome
the exception of the 6-month follow-up. The effect size
ment to 0.50 at the 6-month follow-up following with-
drawal of home visits. During the treatment phase, the
1.0. According to Cohen’s conventions40this is a large
effect size during treatment that decreases to a moderate
effect size 6 months after withdrawal of home visits. The
Number Needed to Treat (NNT) for CAT vs standard
and was 1.8 and 2.3 during follow-up. The effect size for
Pharm-CAT varied from 0.42 and 0.44 at 3 and 6 months
of treatment to 0.22 at 6-month follow-up.
Environmental supports targeted at global functional
outcome improved global community functioning in
individuals with schizophrenia. Environmental supports
targeted at medication adherence alone improved adher-
ence to antipsychotic medications in schizophrenia as
assessed by unannounced, in-home pill counts. Data sup-
port that individually tailored environmental supports
improve targeted behaviors.
This is the first randomized trial to demonstrate that
the systematic application of individually tailored envi-
ronmental supports in CAT and Pharm-CAT improve
adherence to oral antipsychotic medication in individuals
CAT and Pharm-CAT as compared with TAU during
treatment and 6 months after home visits were with-
drawn. The average level of medication adherence in
close to 80%. CAT/Pharm-CAT treatment and perhaps
the continued use of these previously provided supports
after the withdrawal of home visits can sustain an impor-
tant behavior change that has major public health impli-
cations.11It is important to note that supports improved
adherence to medication whether or not they were em-
bedded in the context of a CAT program that targeted
multiple additional areas of functional outcome. Mainte-
nance of medication adherence gains in CAT and Pharm-
CAT may result from the formation of habit behavior
with the repeated use of environmental cues.
Adherence data obtained from unannounced, in-home
pill counts suggested more robust treatment effects than
data obtained from pharmacy records. Differences may
reflect that filling a prescription only ensures that medi-
cation is available to be taken. Larger samples may be
needed when using pharmacy refill data to examine the
efficacy of interventions. This study provides important
support for the feasibility of conducting in-home pill
counts and their sensitivity to change with targeted be-
While there were not significant differences in positive
symptoms across treatment groups, rates of relapse uti-
lizing a composite measure as suggested by Schooler
et al35were significantly lower with CAT and Pharm-
CAT treatment compared with TAU. This finding corre-
sponds to published data indicating that poor adherence
is a significant predictor of relapse.11Moreover, medica-
tion adherence has been characterized as a foundation
upon which the rehabilitation and recovery process is
CAT improved functional outcome as compared with
TAU and to Pharm-CAT. This finding replicates what
was found in our previous trials. The number needed
to treat to improve functional outcome compared with
TAU was 1.4 during treatment. This is important in
that CAT is a fairly labor intensive treatment. A low
NNT indicates that the intensity of treatment may be jus-
tified by clinically important outcomes. Surprisingly,
statistically significant improvement in functioning was
noted for Pharm-CAT over TAU. While Full-CAT treat-
ment made a far more robust and longer standing impact
upon functional outcome, it is possible that better med-
ication adherence in the Pharm-CAT group may have
been a platform which allowed minimal functional im-
provement to occur even in the absence of a comprehen-
sive rehabilitation program. However, results clearly
indicate that the Full-CAT program has significant ben-
efits for functional outcomes over a program targeting
only medication adherence. It is important to determine
whether limiting the goals of treatment to improving
medication adherence and preventing relapse is enough.
during the last part of treatment. It may be that to keep
individuals involved in intensive treatment, functional
goals important to the individual need to be targeted.
to help the individual achieve a broader range of goals.
Moreover, when an individual is resistant to working on
medication adherence, working on other issues can keep
them engaged in treatment so that adherence can be
approached again at a later point. Such individuals are
likely to drop out of a treatment targeting adherence
only. Because home visits can be labor intensive, it
may make more sense to get more out of each visit by
targeting the broad range of adaptive behaviors. This ap-
proach is likely to produce the best results with little ad-
ditional financial burden.
Functional gains in CAT were sustained throughout
the first 3 months after the withdrawal of home visits
but the CAT group was no longer significantly better
vironmental supports for complex functional behaviors
may need more individual tailoring, adjustment, and re-
inforcement in a changing environmental context than
a relatively circumscribed behavior such as adherence.
It is a common practice to examine whether behavioral
improvements with psychosocial treatments are main-
tained when the treatment is withdrawn. This is not
D. I. Velligan et al.
a standard applied to medication treatments, and is likely
most applicable to psychosocial treatments that focus on
systematic teaching of skills which are anticipated to be
sustained after treatment is withdrawn. For a treatment
such as CAT which is expected to bypass cognitive prob-
whether treatment should be withdrawn. It may make
more sense after an initial treatment period to decrease
controlling the costs of treatment, or to train family
gains and comparing the costs and benefits of CAT with
skills training programs would be important to pursue.
Contrary to the results of previous studies, mean levels
Pharm-CAT groups in comparison to those in TAU.
These findings may suggest that in effect, taking medica-
tion as prescribed prevented relapse but did not result in
a statistically significant reduction in symptoms. There
are several possible interpretations of this finding.
Symptoms of psychosis were mild on average at base-
line. Further improvement may have been difficult to
demonstrate with this starting point. It could also be
able to treating psychiatrists may make it difficult for
them to optimize medication regimens to produce the
best outcomes in terms of symptomatology. In a recent
study, we found that among partially adherent outpa-
tients with schizophrenia, adherence as measured with
Medication Event Monitoring (MEMS; caps that record
day and time opened) was not correlated with either
symptoms or symptom improvement over a 12-week pe-
riod.42These findings raise interesting questions. What is
the right amount of medication for an individual patient?
How can the right dose be determined in the context of
limited or no information about the patient’s adherence?
How adherent is adherent and over what time period?
in an effort to optimize dose may be needed.
It is important to note that symptom scores did not
worsen in CAT even though patients were more involved
in social and role functioning. Increased social and role
demands may increase stress. Stress in turn can worsen
symptoms. Better functional status in the context of sta-
ble psychotic symptoms translates to a positive outcome
for CAT patients.
Pharm-CAT is a new treatment that improves
adherence to medication and reduces rates of relapse.
Pharm-CAT and CAT add to the growing number of
interventions targeting this problem for individuals
with schizophrenia. Clinical experience suggests that
Pharm-CAT is likely to be best suited for individuals
who are willing to take medication but who may miss
doses due to distraction, memory problems, poor plan-
ative symptoms. For individuals with more ambivalence
toward medication, CAT treatment may be able to help
them to connect medication adherence to improvements
in functional outcomes. For individuals refusing medica-
tions altogether, interventions such as cognitive behavior
therapy,43family therapy,44or compliance therapy45may
be important precursors to Pharm-CAT. Willingness to
take medication may be a necessary but not sufficient
condition to improve actual adherence to medication.
Combining treatments focusing on changing attitudes
and insight with the use of environmental supports to
change behavior may lead to improved adherence
outcomes for a broader range of individuals.
These results must be examined within the context of
the study’s methodological limitations. A significant
number of inpatient recruits did not make it to the point
of randomization into treatment for this outpatient treat-
ment study. Results can only apply to those individuals
treated as outpatients or inpatients who have successfully
tus. Participants in the study had been ill on average for
more than a decade. The extent to which these techniques
would be helpful to individuals with a more recent onset
of schizophrenia should be examined in future research.
In future studies including a baseline period of assess-
ment for medication adherence prior to randomization
would be important. In-home pill counts could not be
conducted by blinded observers given the nature of envi-
ronmental supports. However, pharmacy records were
not subject to observer bias. It is also likely that more
adherent individuals agreed to participate in the study;
a common problem in adherence research. Moreover,
assessments of medication adherence involve error that
may overestimate or underestimate actual adherence.
Methodological problems with pill counts and pharmacy
records are outlined elsewhere.29The fact that medication
adherence improved, while psychotic symptoms did not
suggests that our notions about adequate adherence and
optimal dosing may have been formed in the ambiguous
environment of partial adherence or negotiation and may
Despite these methodological limitations, the study
provides strong support for the benefits of CAT and
Pharm-CAT with respect to improving medication ad-
herence and for the benefits of CAT for improving func-
National Institutes of Health (R01 MH62850, R01
MH61775 to D.I.V.).
We wish to thank the participants and staff from the San
Antonio State Hospital (Superintendent: Robert Arizpe)
and the Center for Health Care Services (Executive
Environmental Supports, Adherence, and Outcome
Director: Leon Evans) for their ongoing support of our
research program. We wish to thank Nina Schooler for
consulting on this research.
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Environmental Supports, Adherence, and Outcome