margolese

8/19/2019 Margolese

1/11

A 12-month prospective follow-up study of patients with

schizophrenia-spectrum disorders and substance abuse:

Changes in psychiatric symptoms and substance use

Howard C. Margolese a,b,d, Juan Carlos Negrete a ,d, Raymond Tempier c,d,

Kathryn Gilla ,d,

*a Addictions Unit, McGill University Health Centre, Canada

b Clinical Psychopharmacology Unit, McGill University Health Centre, Canadac Continuing Care Service, McGill University Health Centre, Canada

d Department of Psychiatry, McGill University, Montreal, Quebec, Canada

Received 19 July 2005; received in revised form 17 November 2005; accepted 18 November 2005

Available online 7 February 2006

Abstract

While it is widely known that patients with schizophrenia-spectrum psychoses and co-occurring substance use disorders are

more difficult to manage, there is limited data on the course of their psychiatric symptoms when they remain in treatment over

time. This prospective 12-month study evaluated changes in psychiatric symptoms and substance use to ascertain if the co-

existence of substance use disorders influences ratings of psychiatric symptoms at follow-up.

147 outpatients in a continuing care program were assessed at intake and followed prospectively for 12 months. Psychiatric

symptoms were measured at baseline and 12-month follow-up using the Positive and Negative Syndrome Scale (PANSS) and

Hamilton Depression Rating Scale (HAM-D). Subjective psychological distress was rated with the Brief Symptom Inventory

(BSI) and quality of life by the Satisfaction with Life Domains Scale (SDLS). Drug and alcohol use was measured with the

Addiction Severity Index (ASI).

50.3% of patients were diagnosed with dual disorders (DD) (current and lifetime). The most common primary substances of

abuse were alcohol (35.6%) and cannabis (35.1%). DD subjects had higher baseline PANSS positive scores but experienced a

greater reduction at 12 months compared to single diagnosis (SD) patients. Severity of substance abuse as measured by ASI

composite scores did not decrease significantly between baseline and 12 months.

DD patients with schizophrenia and related psychoses treated for their psychiatric illness showed a reduction in PANSSscores over 12 months, even when their substance use remained largely unchanged. However, co-morbidity cases continued to

0920-9964/$ - see front matter D 2005 Elsevier B.V. All rights reserved.

doi:10.1016/j.schres.2005.11.019

* Corresponding author. Addictions Unit, Montreal General Hospital, 1604 Pine Avenue West, Montreal, Quebec, Canada H3G 1B4. Tel.: +1

514 934 8311; fax: +1 514 934 8262.

E-mail address: [email protected] (K. Gill).

Schizophrenia Research 83 (2006) 65–75

www.elsevier.com/locate/schres

8/19/2019 Margolese

2/11

show higher depression and anxiety ratings. Ongoing substance abuse appears to be related to levels of depression as 62.5% of

DD-current versus 34.7% of SD patients had HAM-D scores in the depressed range at 12-month follow-up. Implications for

treatment are discussed.

D 2005 Elsevier B.V. All rights reserved.

Keywords: Alcohol; Cannabis; Dual-diagnosis; Psychosis; Schizophrenia; Substance use disorders

1. Introduction

Dual diagnosis (DD) patients are known to present

more difficulties from a clinical management perspec-

tive than single diagnosis (SD) patients. Substance use

has been found to exacerbate the positive symptoms

of schizophrenia (Drake et al., 1989; Margolese et al.,2004; Negrete et al., 1986; Pulver et al., 1989) and to

increase aggression, violence (Angermeyer, 2000;

Soyka, 2000), as well as medication noncompliance

(Bhanji et al., 2004; Coldham et al., 2002; Kamali et

al., 2001; Margolese et al., 2004; Olfson et al., 2000;

Swartz et al., 1998) in the chronic mentally ill.

Furthermore, time to readmission or community

survival is significantly reduced among DD compared

to SD subjects, even when controlling for non-

compliance (Hunt et al., 2002).

Some follow-up studies have found that only a

small percentage of patients with severe mental illness

(SMI) achieve stable substance use remission over

time (Drake et al., 1996). The prevalence of active

substance use disorders changed little during a 7-year

naturalistic follow-up (Bartels et al., 1995) of a SMI

sample, suggesting that remission and new cases were

approximately equal. Another study, which found

high remission rates among dually diagnosed patients,

reported significantly higher dropout rates among

patients with schizophrenia and other psychoses

compared to patients with other diagnoses (Dixon

et al., 1998).In a retrospective 18-month study of 100 schizo-

phrenic outpatients, between 30% and 40% were

found to be using substances during each 3-month

interval (Chouljian et al., 1995). Analysis of 59 of the

subjects with complete data demonstrated that cocaine

and multiple substances increased, while problem use

of alcohol, marijuana and other drugs remained stable

(Chouljian et al., 1995).

Caspari (1999) examined the impact of cannabis

abuse on schizophrenia in a sample of 27 DD patients

compared to 26 SD controls. He found higher

rehospitalization rates and worse psychosocial func-

tioning in the cannabis abuse group at follow-up after

68.7F28.3 months. Of note, 48% of the DD patients

had ceased all substance abuse, while only 1 SD

patient started excessive alcohol use, and none

showed significant drug use. The cannabis group alsohad additional thought disturbance measured on the

Brief Psychiatric Rating Scale (BPRS) and hostility

measured on the Arbeitsgememeinscaft fur Methodik

und Dokumetation in der Psychiatrie (AMDP) (Ger-

man scale for measurement of psychotic symptoms)

compared to the control group at the follow-up

assessment (Caspari, 1999). The study design pro-

duced group comparisons for psychiatric symptoms

that were cross-sectional, rather than within-subjects

as the BPRS and AMPD were conducted only at

follow-up and not at baseline.

It seems possible that increased symptoms ex-

pressed by DD patients in some studies are accounted

for by medication non-compliance as well as the

direct effect of substances of abuse on the production

of psychiatric symptomatology. Buhler et al. (2002)

followed 29 DD and 29 SD first episode patients for 5

years. Among the patients available for follow-up

assessments, those with a DD had more positive

symptoms and less affective flattening (Buhler et al.,

2002). Once again, changes in drug use prevalence

or severity during the follow-up period were not

explored.The impact of 12 months of treatment in a general

hospital outpatient psychiatry service for patients

with severe and persistent mental illness including

schizophrenia, schizoaffective disorder and related

psy choses was explored in the present stu dy.

Changes in the expression of psychiatric symptoms

and use of substances of abuse were prospectively

evaluated to ascertain if continuing substance abuse

and dependence were associated with poorer thera-

peutic response.

H.C. Margolese et al. / Schizophrenia Research 83 (2006) 65–7566

8/19/2019 Margolese

3/11

2. Methods

2.1. Sample selection

The sample consisted of all patients with schizo-

phrenia-spectrum disorders (schizophrenia, schizoaf-

fective disorder, delusional disorder, psychosis NOS),

who were referred to the Continuing Care Service

(CCS) of the McGill University Health Centre—

Montreal General Hospital (MGH) site. The MGH is a

tertiary care hospital serving a diverse urban popula-

tion and the CCS cares for all those patients with

severe and persistent mental illness (Margolese et al.,

2004). There are no specific selection criteria for

referral to the CCS other than presence of a chronic or recurring psychotic disorder (schizophrenia and relat-

ed psychoses) and home address in a defined

geographical catchment area. The presence or absence

of substance use disorders plays no role in this

referral. The catchment area (defined by home postal

code) requires patients to obtain all psychiatric

services at the MGH. The MGH catchment area is

wide, representing a multicultural population from

both inner city and suburban regions. CCS admissions

who presented with a pure substance-induced psy-

chosis or bipolar disorder and those whose clinical

and/or hospital chart diagnosis of schizophrenia-

spectrum psychosis was not confirmed by an SCID-

P interview were excluded from the present analyses.

Characteristics of the sample (n =207) at baseline

were presented in a prior report (Margolese et al.,

2004). Briefly, there was no statistically significant

difference between DD and SD groups on age,

diagnosis, education level, living arrangements, per-

cent on social assistance (welfare), employment

status, lifetime or recent (past 2 years) number of

hospitalizations, or type of antipsychotic prescribed at

baseline (typical (oral or IM), atypical or both).Significantly more DD subjects were male and they

first received help at a younger age.

While patients were evaluated at 4-month inter-

vals, the complete set of evaluations was performed

only at study entry and study completion. Further-

more, some patients available at 12 months were not

available at some of the intervening time points, and

vice versa. Comparison of baseline to study end

point was used in order to maintain the maximum

possible sample size.

The follow-up study was designed to test the

hypothesis that DD patients with a current diagnosis

of substance abuse/dependence would fare signifi-

cantly worse than non-using SD patients on psychoticand affective symptoms, subjective psychological

distress, quality of life and medication adherence.

Power analyses were conducted in order to determine

whether the follow-up sample was adequate to test the

primary hypothesis. There are no standard methods

for power/sample size calculations in the context of

multivariate models for unbalanced repeated measures

MANOVA. Approximate power was determined by

generalizing conventional multiple linear analysis to

the case of repeated measurements of an interval-scale

dependent variable. Calculations indicated that a totalsample of 140 patients would be required to ensure

80% power in a 2-tailed test ( p = 0.05) of the

significance of the difference between current drug

abusers and other patients, after having adjusted for

potential confounders (e.g. age, gender).

At 12 months, 147 of the initial sample of 207

patients (71.0%) were still receiving services at the

MGH and agreed to the follow-up interview. Follow-

up rates were 66.1% for SD, 73.5% for DD-lifetime,

and 82.1% for DD-current subjects (v2=3.3, df = 2,

p = 0.190). Compared to those lost to follow-up,

subjects remaining in the study were significantly

older (mean age 39.6F10.4 vs. 36.2F10.9; p =0.03),

were more likely to live alone (37.0% vs. 19.7%;

p = 0.05) and had significantly lower PANSS negative

scores at intake (15.8F5.2 vs. 17.6F5.6; p =0.03).

There were no differences between subjects remaining

in the study and those lost to follow-up on any other

demographic, psychiatric, or drug use variable,

including compliance status. Regarding compliance

status, there was in fact a trend for retention to be

greater for those not compliant at intake (87.0% vs.

68.2%). All analyses were conducted on the 12-monthfollow-up sample (n =147).

2.2. Instruments

Diagnoses were confirmed through the administra-

tion of the mood, psychotic and psychoactive sub-

stance abuse sections of the Structured Clinical

Interview for DSM-IV (SCID-P). Baseline demo-

graphics including age, ethnicity, education, marital

status, and personal and family psychiatric history

H.C. Margolese et al. / Schizophrenia Research 83 (2006) 65–75 67

8/19/2019 Margolese

4/11

were recorded. Date of onset of psychiatric symptoms,

number and length of previous hospitalizations, and

medications prescribed (dose, form, compliance sta-

tus) were obtained from patient interviews and reviewof previous hospital charts.

Psychiatric symptomatology was assessed at base-

line and 12-month follow-up using the Positive and

Negative Syndrome Scale (PANSS) (Kay et al., 1988,

1989) and the Hamilton Depression Rating Scale

(HAM-D) (Hamilton, 1960); subjective psychological

distress was measured with the Brief Symptom

Inventory (BSI) (Derogatis and Melisaratos, 1983);

while quality of life (QOL) was measured by the

Satisfaction with Life Domains Scale (SDLS) (Baker

and Intagliata, 1982). The PANSS is a 30-itemstandardized instrument that measures positive symp-

toms (e.g. hallucination, delusions), negative symp-

toms (e.g. affective blunting, emotional withdrawal),

and general symptoms (e.g. motor retardation, anxi-

ety, disorientation) using a semi-structured interview

and chart review (Kay et al., 1988, 1989). The HAM-

D is a 23-item clinician administered scale that rates

cognitive, affective, somatic, and vegetative symp-

toms of depression (Hamilton, 1960). The BSI is a 53-

item self-rating questionnaire that evaluates psycho-

logical distress in nine areas (e.g. hostility, depression,

somatization, anxiety) over the past week (Derogatis

and Melisaratos, 1983). A global severity index (GSI)

score is also obtained from the nine dimensions

providing an indication of overall distress. The SDLS

is a 7-point scale wherein stylized faces are used to

rate patients’ feelings about relationships, autonomy,

leisure activities, health and housing (Baker and

Intagliata, 1982). It has been widely used with

mentally ill patients (Baker and Intagliata, 1982;

Mercier et al., 1992) and it has been demonstrated

to have good psychometric properties in terms of

reliability, internal consistency, and convergent andcontent validity (Horley, 1985; Kamman et al., 1983;

Larsen et al., 1985).

The Addiction Severity Index (ASI) was used to

determine current and lifetime drug and alcohol use

levels (McLellan et al., 1980, 1985). The ASI was

found reliable and valid for assessing drug-related

behaviours and consequences in mentally ill patients

(Carise et al., 2001; el Guebaly and Hodgins, 1992). It

assesses the number of days and routes of adminis-

tration of specific drug (e.g. cannabis, cocaine,

amphetamines, etc.) and alcohol use during the past

30 days, as well as the number of days of drug

abstinence and extent of substance abuse treatment.

Composite scores range from 0 (abstinent) to 1 (dailyuse with significant impairment and intoxication).

2.3. Treatment during the follow-up period

The CCS provides long-term care with a focus on

improving quality of life, encouraging community

living, prevention of hospitalizations and increased

autonomy. Clients are treated by a multidisciplinary

team that includes a psychiatrist, social worker, nurse

and occupational therapist. A case manager who

becomes the primary contact person for both theclient and family follows each client. A number of

services were offered during treatment including

medication and side-effect management, supportive

psychotherapy, crisis intervention, social skills train-

ing, as well as linkage with community services

related to general health care, housing, finances,

vocational training and recreation. Case managers

were not specifically trained to address substance use

but used the standard case management approach to

help each patient. Thus, general encouragement to

reduce substances of abuse and psychoeducation on

the harmful effects of substance use was discussed

with those patients whose case manager was aware of

their ongoing substance use. This program contained

no specific component focussed on co-morbid sub-

stance use disorders; it was not an integrated treatment

program.

2.4. Statistical analysis

Data for each patient across all variables including

demographic and diagnostic information was coded

and entered into a database using Microsoft ExcelR.Statistical analysis was conducted using the micro-

computer version 10.0 of SPSSR. Fisher’s exact tests

and chi-square tests of association were used to assess

differences in categorical variables between groups.

Comparisons between groups for continuous variables

were conducted using independent t -tests and Anal-

ysis of Variance (ANOVA) techniques, including

multivariate tests (MANOVA). Comparisons between

baseline and follow-up time points were performed

using repeated measures analyses. All post-hoc tests


8/19/2019 Margolese

5/11

were conducted using t -tests with a Bonferroni

correction.

Linear hierarchical multiple regression analysis

was performed to examine the relationships among

drug use and psychiatric symptomatology (e.g.

PANSS scores) at follow-up. Variables with signifi-

cant individual correlations, as well as key variables

of interest (PANSS scores) were entered into hierar-

chical multiple linear regression using the following

model: Step 1: Baseline ASI alcohol or drug severity

composite scores; Step 2: demographics (age and

sex); Step 3: mood variables at follow-up (HAM-D,BSI, antidepressant status); Step 4: variables related to

psychosis at follow-up (PANSS, antipsychotic type).

3. Results

The patients in this cohort were chronically ill with

approximately 16 years since first diagnosis. Subjects

with a DD were more likely than SD to be male, non-

compliant with medications at intake and younger

when they first received psychiatric treatment (Table

1). There were no significant differences between SD

and DD patients on any other demographic variable.

Medication compliance rates differed markedly at

baseline, but were similar among the 3 groups at

follow-up, with a higher percentage of DD subjects

compliant at follow-up versus baseline and a lower

percentage of SD subjects compliant at follow-up

Table 1

Demographics (n =147)

Variable SD (n = 73) DD-lifetime (n = 50) DD-current (n =24)

Age (meanFS.D.) 40.4F10.4 40.1F9.7 38.6F10.8% Male 47.9 74.0* 79.2*

Diagnosis at intake

% Schizophrenia 63.0 66.0 58.3

% Schizoaffective 26.0 24.0 16.7

% Other (delusional disorder, psychosis NOS) 11.0 10.0 25.0

% Married 9.6 12.0 12.5

% Caucasian 89.0 90.0 95.8

Living arrangements

% Alone 32.9 42.9 37.5

% Institutiona 24.7 22.0 25.0

% With other people 49.7 36.0 37.5

Education: % above high school 65.8 52.0 58.3

% Employed 5.5 2.0 0

% On welfare 65.8 68.0 70.8

Age first received help (meanFS.D.) 24.2F7.9 21.2F9.4 22.0F9.2

Age first hospitalized b (meanFS.D.) 28.2F9.0 25.6F8.6 29.4F9.4

Number of hospitalizations at baseline (meanFS.D.) 4.6F4.4 4.8F5.4 3.9F3.0

% With history of medical problems 54.8 52.0 58.3

% With current medical problems 42.5 28.0 37.5

% Non-compliant at baseline 5.6 20.8* 25.0*

% Non-compliant at follow-up 10.9 12.0 12.5

S.D.= standard deviation.a Institution includes any supervised living setting. b For age first hospitalized, n =67 for SD, n =45 for DD-lifetime, and n = 20 for DD-current as some patients were never hospitalized.

* DD group significantly different than SD group, v 2 or Fisher’s Exact Test, p b0.05 corrected for multiple comparisons.

Fig. 1. Non-compliance at baseline and follow-up.


8/19/2019 Margolese

6/11

versus baseline (Fig. 1). At baseline, 41.5% of the

sample were prescribed typical antipsychotics, 37.4%

atypicals, 17.0% both and 4.1% none. The percentage

of patients prescribed different antipsychotic types

(typical, atypical, both) did not differ significantly

between SD and DD patients. Furthermore, there waslittle shift over time so that similar percentages of

patients were receiving typicals, atypicals or both

antipsychotic types at follow-up.

Only 15% (22/147) of patients required hospitali-

zation during the follow-up period and most needed

either 1 ( N =14) or 2 ( N =6) hospitalizations. There

were no significant differences between groups (SD,

DD-current, DD-lifetime) with respect to hospitaliza-

tion rates.

Primary substance of abuse for DD-current and

DD-lifetime patients is shown in Table 2. A higher percentage of DD-lifetime subjects used cannabis

while a lower percent used both alcohol and cocaine

compared to DD-current subjects. These differences

were not statistically significant. Of the 74 patients

with current or lifetime diagnoses of DD, 58 were

actively abusing substances at baseline. At follow-up,

36.2% (21/58) were abstinent from their primary drug

during the month prior to evaluation. However, 7 of

these 21 patients were using substances of abuse other

than their identified primary drug of abuse. Thus,

severity of substance use as measured by thecomposite scores on the ASI did not differ signifi-

cantly when comparing baseline to 12-month follow-

up measures. There were no significant t ime

[ F (1,135)=1.42, p = 0.24] or group time interac-

tions [ F (2,135)=0.34, p =0.72]. This lack of change

in overall substance use was also observed for alcohol

(all p valuesN0.3) (Fig. 2) and drug (all p val-

uesN0.2) (Fig. 3) use measures separately.

During the course of psychiatric outpatient treat-

ment, DD subjects experienced a greater reduction in

PANSS positive symptom measures compared to SD patients at 12 months (Fig. 4). Repeated measures

ANOVA with group (3 levels) and time (2 levels)

yielded significant effect of time [ F (1,140)=47.50,

p =0.0001] and a significant group time interaction

Table 2

Primary substance of abuse for current and lifetime DD patients at

12 months

Substance of abuse

DD-lifetime(n =50)

DD-current (n =24)

Total sample(n =74)

Alcohol (%) 29.2 40.0 36.5

Cannabis (%) 38.5 32.0 35.1

Cocaine (%) 12.5 20.0 17.6

Other (%) 16.7 8.0 10.8

Fig. 2. ASI alcohol composite severity scores.

Fig. 3. ASI drug composite severity scores.

Fig. 4. PANSS positive scores.


8/19/2019 Margolese

7/11

[ F (2,140)=3.97, p =0.021]. Post-hoc analysis failed

to reveal a statistically significant between group

difference at 12 months. In other words, 12 months of

routine outpatient treatment caused all groups to look more similar in terms of positive symptom expression.

HAM-D total scores were analyzed using repeated

measures ANOVA with group (3 levels) and time (2

levels) yielding a significant main effect for group

[ F ( 2 , 1 3 8 ) = 5 . 4 1 , p = 0 . 0 0 5 ] a n d t i m e

[ F (1,138)=4.92, p =0.028] but no significant group- time interaction [ F (2,138)=0.379, p =0.685]. Post-

hoc analysis indicated that DD-current subjects

remained significantly ( pb0.05) more depressed than

SD at both baseline and 12 months. Substance abuse

appeared to impact on rates of clinically significant depression as 62.5% of DD-current and 50% of DD-

lifetime versus 34.7% of SD patients had HAM-D

scores in the depressed range of 12 or more at follow-

up (v2=0.039, df =2). Most of the patients who did

receive concomitant antidepressants received an SSRI

(19/31, 61.3%).

While there was an absolute significant difference

between SD versus DD-current and DD-lifetime

subjects on changes in total subjective QOL scores

(Table 3), the result was no longer significant after

individual items were considered (i.e. after correction

for multiple comparisons).

Self-rating of symptoms, as measured by the BSI,

was different between SD, DD-lifetime and DD-

current groups (Table 3). While all groups had some

reduction in their levels of distress (Global SeverityIndex scores) these remained the most elevated for

DD-current subjects [ F (2,139)=9.39, p b0.001]. Fur-

thermore, while all three groups had some reduction

in their Positive Symptom Total (PST) scores, the DD-

current group remained the most symptomatic, fol-

lowed by the DD-lifetime group [ F (2,142)=10.30,

pb0.001].

The relationship between psychiatric symptomatol-

ogy and alcohol/drug abuse severity at follow-up was

examined using hierarchical multiple regression. ASI

alcohol and drug severity composite scores at follow-up were predicted using a model that included

variables related to baseline ASI composite scores,

demographics, psychological distress and psychotic

symptoms. Results of the regression demonstrated that

alcohol and drug severity at intake largely predicted

severity at follow-up (Table 4). ASI alcohol composite

severity scores at follow-up were predicted by severity

at intake ( R2change, F 1,135=75.73, p b0.001). Similarly,

drug severity at follow-up was predicted by drug

severity at baseline ( R2change, F 1,130=84.53, p b0.001).

Younger age also predicted alcohol, but not drug ASI

severity scores. No additional variance in alcohol or

Table 3

Psychiatric and substance use measures at baseline and follow-up

Variable SD (n = 73) DD-lifetime (n = 50) DD-current (n =24)

Baseline Follow-up Baseline Follow-up Baseline Follow-up

PANSS

Positive 14.01F5.36 12.16F5.45 15.22F5.16 12.72F5.16 18.17F5.44 13.04F5.43

Negative 16.10F5.26 14.92F6.63 15.22F5.05 15.11F5.92 15.29F4.93 15.63F5.26

Total 59.90F13.82 54.52F17.52 61.70F13.15 55.96F15.66 66.83F13.53 59.54F16.74

HAM-D Total score 11.7F6.90 9.5F7.7 14.4F8.4 11.7F8.0 15.4F7.5 14.7F7.1

ASIAlcohol Comp score 0.02F0.06 0.04F0.08 0.06F0.08 0.09F0.15 0.20F0.20 0.19F0.20

Drug Comp Score 0.006F0.02 0.003F0.008 0.02F0.05 0.02F0.07 0.11F0.11 0.13F0.13

SDLS Total score 91.9F18.5 98.6F20.7 88.1F17.7 89.7F20.3 85.3F19.6 86.6F22.3

BSI

GST 0.80F0.57 0.55F0.55 1.05F0.64 0.84F0.56 1.30F0.72 1.05F0.56

PST 22.7F12.4 17.4F13.5 27.8F12.8 25.6F14.4 33.2F12.6 29.7F14.7

PSDI 1.72F0.68 1.45F0.54 1.88F0.55 1.53F0.43 2.06F0.60 1.74F0.44

PANSS=Positive and Negative Syndrome Scale; HAM-D=Hamilton Depression Rating Scale; ASI=Addiction Severity Index; SDLS=Sa-

tisfaction with Life Domains Scale; BSI = Brief Symptom Inventory, GST = global symptom total, PST= positive symptom total, PSDI= positive

symptom distress index.

For none of the above variables was DD-current or DD-lifetime group significantly different from SD group, or DD-current group significantly

different from DD-lifetime group, p b0.05 corrected for multiple comparisons.


8/19/2019 Margolese

8/11

drug severity at follow-up was accounted for by the

severity of psychosis or depression. The presence or

absence of antidepressant medications and the type of

antipsychotic medication prescribed during treatment

did not add to understanding the variance in alcohol/

drug abuse severity at follow-up.

4. Discussion

The present study demonstrates that when DD

patients are adequately treated for their psychiatric

illness there is considerable amelioration in their

psychotic symptoms. Moreover, the reduction in

psychosis does not appear to be related to the type

of antipsychotic prescribed (typical vs. atypical). The12-month follow-up rate of 71% was considered to be

reasonable for a chronic psychosis population in an

ambulatory care setting. While the numbers did not

reach statistical significance, there was a trend for

higher retention among the current (82.1%) and

lifetime DD (73.5%) groups compared to the SD

group (66.1%). This finding was unexpected, as it is

often assumed that DD patients tend to drop out of

treatment more readily. BootsMiller et al. (1998), for

instance, reported that dual diagnosis subjects have a

higher attrition rate and are more difficult to track in

follow-up studies.

This study replicates the often-reported finding of

poor treatment compliance among DD subjects; they

were more likely to be non-compliant with prescribed

medications at baseline. However, 12 months later all

groups showed similar compliance rates; largely due

to considerable improvement in the dual diagnosis

groups. This change for the better can be seen as a

measure of success for the case management approach

adopted by the CCS program, and the significant

impact of this approach on treatment compliance

among DD subjects confirms current best-practices

recommendations (Drake et al., 2004).

Alcohol and cannabis were the most commonly

abused substances in the present cohort, and overallseverity of substance use, as measured by ASI

composite scores, did not change significantly over

the 12-month follow-up period. While 36.2% of DD

patients abstained from using their primary drug over

the month preceding follow-up evaluation, 1/3 of

them substituted another substance of abuse. There

was little change in drug/alcohol dependence over the

follow-up period.

On average, the severity of psychotic symptoms as

measured by the PANSS, did diminish over the 12-

Table 4

Hierarchical multiple regression predicting ASI composite severity ratings for alcohol and drug abuse at follow-up

Predictors ASI alcohol severity at 12 months ASI drug severity at 12 months

R R2 R2 change ba R R2 R2 change ba

Step 1 0.60 0.36 0.36, 0.63 0.39 0.39,

Baseline ASI alcohol or drug

severity composite scores

p b0.0001* 0.60* p b0.0001* 0.63*

Step 2: demographics 0.62 0.39 0.03, 0.63 0.40 0.002,

Age p =0.06 0.16* p =0.77 0.02

Sex 0.02 0.04

Step 3: mood variables 0.64 0.41 0.24, 0.64 0.42 0.02,

HAM-D total p =0.39 0.03 p = 0.58 0.03

BSI depression 0.03 0.07

BSI anxiety 0.16 0.12

BSI GSI 0.04 0.01

Any antidepressant use 0.03 0.07

Step 4: psychosis variables 0.65 0.42 0.10, 0.66 0.44 0.23,PANSS positive p = 0.73 0.11 p =0.30 0.27

PANSS negative 0.01 0.28

PANSS total 0.12 0.54

Antipsychotic type 0.09 0.10

a b weights are standardized.

* pb0.05.


8/19/2019 Margolese

9/11

month treatment period. All groups benefited from

treatment, but the gains were most marked in the DD

despite the fact that they continued to use substances of

abuse during the follow-up period.It would appear that DD patients in this cohort

did no worse than SD patients with respect to

positive and negative psychiatric symptoms, living

arrangements, hospitalizations, and employment

status over the 12-month follow-up. This observa-

tion is somewhat at odds with previous reports,

mostly from the United States. The relatively low

rates of cocaine use—a more potent psychotomi-

metic—in this Montreal sample; may help explain

the difference. There are, nonetheless, other follow-

up studies that found that substance disorders donot impact negatively on psychiatric status. Blow et

al. (1998) explored inpatient service use and general

functioning over 2 years in 632 veterans with an

Axis 1 psychotic disorder, 90% of whom had

schizophrenia, 7.7% an affective psychosis and

198 (29%) a co-morbid substance use disorder.

They found that Brief Psychiatric Rating Scale

(BPRS) (Overall and Gorman, 1962) scores were

consistently lower (i.e. better) among DD compared

to SD subjects. Clinical rated Global Assessment of

Functioning scores were higher (better) for DD

compared to SD groups and all mean group GAF

scores increased between baseline and follow-up.

Similar to our findings, DD patients reported less

satisfaction with life compared to SD patients on a

subjective measure of life satisfaction (Blow et al.,

1998). However, the sample differs from the present

study in that they were all veterans and 96.8% of them

were male. Moreover, Blow et al. did not evaluate

changes in substance use measures over time, nor

specify the types of substances that were abused. Bell

et al. examined patients with schizophrenia in a work

rehabilitation program in the United States (Bell et al.,2002). 80% of the group was classified as DD-

lifetime, as opposed to DD-current, on the ASI. At 1-

year follow-up, most patients were classified as

remaining in stable remission, and substance use

was found not to influence work participation rates

(Bell et al., 2002). Thus the impact of substance abuse

on social functioning as measured by work, was

minimal. Unfortunately, this paper did not report

changes in PANSS or ASI scores over time although

these data were collected.

Evidence suggests that several different patient

profiles exist among the DD population. For example,

some have higher symptom levels and poor social

skills; others lower symptom levels, especially nega-tive symptoms, and even better social skills compared

to non-abusing schizophrenia patients (Arndt et al.,

1992; Dixon et al., 1991; Salyers and Mueser, 2001).

Joyal et al. (2003) compared 16 DD to 14 SD men

discharged from a forensic inpatient unit. The DD

group had fewer negative symptoms and less frontal

impairment as measured by soft signs and perfor-

mance on the WCST (Wisconsin Card Sorting Test)

and COWAT (Controlled Oral Word Association

Test). They suggest that planning and organization

skills are required to obtain substances of abuse andmaintain substance use. Therefore, these patients are

able to continue their addiction in part because of their

better cognitive function and fewer negative symp-

toms. Thus these different patient profile types may

help to explain some of the differential findings

between studies as this variance is not yet accounted

for in most published studies to date.

The only major between group-differences at

follow-up were the greater percentage of current and

lifetime DD patients who had clinically significant

depression. However, there was no statistically

significant difference in mean group HAM-D scores.

Subjective positive and global symptoms (i.e., BSI

results) were higher among DD patients. Thus, it is

quite evident that DD patients experience more severe

internal distress than their SD counterparts. Similar to

the general population without severe mental illness

(Kendler et al., 1996; Kessler et al., 1994; Regier et

al., 1990), substance use disorders are associated with

higher levels of stress, depression and anxiety among

those with dual disorders. Among this cohort, these

higher rates of clinically significant depression were

seen despite improved antipsychotic and concomitant medication compliance, suggesting that medication

compliance does not have a strong impact on

depression and anxiety symptoms when patients

continue to use substances of abuse. This is likely

because substance abuse and dependence can increase

or even induce states of depression and anxiety

(Kendler et al., 1996; Kessler et al., 1994; Regier et

al., 1990).

The data from this cohort imply that severity of

psychosis and drug and alcohol use at follow-up


8/19/2019 Margolese

10/11

varied independently, and that 12 months of routine

outpatient treatment for schizophrenia and related

psychotic disorders did not significantly impact

levels of alcohol and drug use. All groups experi-enced a reduction in objective positive symptoms of

psychosis. In fact, objective positive symptoms

decreased more for DD-current than DD-lifetime

than SD patients. This may be related to the fact that

those patients who remained in treatment wanted

help and thus made an effort to be compliant with

treatment. Thus, antipsychotic medication compli-

ance despite ongoing substance use may result in a

reduction of positive symptoms. Patients that were

lost to follow-up may have continued to escalate

their drug use and/or were more likely to bemedication noncompliant.

Limitations of this study include the design whereby

psychiatric symptoms were only measured at two time

points. Since psychiatric symptoms vary and are

expected to vary with the pattern of substance use,

the intimate relationship between use and expression of

psychiatric symptoms was not adequately explored in

this study. As well, clinical samples that use a

naturalistic follow-up are by their very nature biased.

However, this sample was from a large catchment area

and both the initial baseline refusal rate (14%) and the

portion lost to follow-up (29%) were relatively low,

thus reducing the impact of the inherent bias in the

study design. This study relied on self-report data,

some key measures such as medication compliance and

current substance abuse were not independently

confirmed; thus some patients may have been incor-

rectly classified as SD instead of DD.

Although this study suggests that standard psychi-

atric treatment is sufficient to reduce psychosis,

specific substance-related interventions may be re-

quired to reduce alcohol and drug consumption and

improve quality of life in this population.

Acknowledgements

The authors would like to thank Drs. Allan

Fielding, Richard Montoro and Warren Steiner for

their assistance in patient recruitment. This research

was supported by a grant awarded to K.G. from the

National Health Research and Development Program

(Canada).

References

Angermeyer, M.C., 2000. Schizophrenia and violence. Acta

Psychiatr. Scand., Suppl. 102, 63 – 67.Arndt, S., Tyrrell, G., Flaum, M., Andreasen, N.C., 1992.

Comorbidity of substance abuse and schizophrenia: the role of

pre-morbid adjustment. Psychol. Med. 22, 379 – 388.

Baker, F., Intagliata, J., 1982. Quality of life in the evaluation of

community support systems. Eval. Program Plann. 5, 69– 79.

Bartels, S.J., Drake, R.E., Wallach, M.A., 1995. Long-term course

of substance use disorders among patients with severe mental

illness. Psychiatr. Serv. 46, 248–251.

Bell, M., Greig, T., Gill, P., Whelahan, H., Bryson, G., 2002. Work

rehabilitation and patterns of substance use among persons with

schizophrenia. Psychiatr. Serv. 53, 63 – 69.

Bhanji, N.H., Chouinard, G., Margolese, H.C., 2004. A review of

compliance, depot intramuscular antipsychotics and the new

long-acting injectable atypical antipsychotic risperidone inschizophrenia. Eur. Neuropsychopharmacol. 14, 87 – 92.

Blow, F.C., Barry, K.L., BootsMiller, B.J., Copeland, L.A., McCor-

mick, R., Visnic, S., 1998. Longitudinal assessment of inpatient

use and functioning of seriously mentally ill veterans with and

without co-occurring substance use disorders. J. Psychiatr. Res.

32, 311–319.

BootsMiller, B.J., Ribisl, K.M., Mowbray, C.T., Davidson, W.S.,

Walton, M.A., Herman, S.E., 1998. Methods of ensuring high

follow-up rates: lessons from a longitudinal study of dual

diagnosed participants. Subst. Use Misuse 33, 2665–2685.

Buhler, B., Hambrecht, M., Loffler, W., an der, H.W., Hafner, H.,

2002. Precipitation and determination of the onset and course of

schizophrenia by substance abuse—a retrospective and pro-

spective study of 232 population-based first illness episodes.

Schizophr. Res. 54, 243–251.

Carise, D., McLellan, A.T., Cacciola, J., Love, M., Cook, T.,

Bovasso, G., Lam, V., 2001. Suggested specifications for a

standardized Addiction Severity Index database. J. Subst. Abuse

Treat. 20, 239–244.

Caspari, D., 1999. Cannabis and schizophrenia: results of a follow-

up study. Eur. Arch. Psychiatry Clin. Neurosci. 249, 45–49.

Chouljian, T.L., Shumway, M., Balancio, E., Dwyer, E.V., Surber,

R., Jacobs, M., 1995. Substance use among schizophrenic

outpatients: prevalence, course, and relation to functional status.

Ann. Clin. Psychiatry 7, 19–24.

Coldham, E.L., Addington, J., Addington, D., 2002. Medication

adherence of individuals with a first episode of psychosis. ActaPsychiatr. Scand. 106, 286– 290.

Derogatis, L.R., Melisaratos, N., 1983. The Brief Symptom

Inventory: an introductory report. Psychol. Med. 13, 595 – 605.

Dixon, L., Haas, G., Weiden, P.J., Sweeney, J., Frances, A.J., 1991.

Drug abuse in schizophrenic patients: clinical correlates and

reasons for use. Am. J. Psychiatry 148, 224–230.

Dixon, L., McNary, S., Lehman, A.F., 1998. Remission of substance

use disorder among psychiatric inpatients with mental illness.

Am. J. Psychiatry 155, 239–243.

Drake, R.E., Osher, F.C., Wallach, M.A., 1989. Alcohol use and

abuse in schizophrenia. A prospective community study. J. Nerv.

Ment. Dis. 177, 408–414.


8/19/2019 Margolese

11/11

Drake, R.E., Mueser, K.T., Clark, R.E., Wallach, M.A., 1996. The

course, treatment, and outcome of substance disorder in

persons with severe mental illness. Am. J. Orthopsychiatry

66, 42–51.

Drake, R.E., Mueser, K.T., Brunette, M.F., McHugo, G.J., 2004. A

review of treatments for people with severe mental illnesses and

co-occurring substance use disorders. Psychiatr. Rehabil. J. 27,

360–374.

el Guebaly, N., Hodgins, D.C., 1992. Schizophrenia and substance

abuse: prevalence issues. Can. J. Psychiatry 37, 704 – 710.

Hamilton, M., 1960. A rating scale for depression. J. Neurol.

Neurosurg. Psychiatry 23, 56 – 62.

Horley, J.L.B.R., 1985. Affective and cognitive components of

global subjective well-being measures. Soc. Indic. Res. 17,

189–197.

Hunt, G.E., Bergen, J., Bashir, M., 2002. Medication compliance

and comorbid substance abuse in schizophrenia: impact on

community survival 4 years after a relapse. Schizophr. Res. 54,253–264.

Joyal, C.C., Halle, P., Lapierre, D., Hodgins, S., 2003. Drug abuse

and/or dependence and better neuropsychological performance

in patients with schizophrenia. Schizophr. Res. 63, 297 – 299.

Kamali, M., Kelly, L., Gervin, M., Browne, S., Larkin, C.,

O’Callaghan, E., 2001. Psychopharmacology: insight and

comorbid substance misuse and medication compliance among

patients with schizophrenia. Psychiatr. Serv. 52, 161–3, 166.

Kamman, R., Farry, M., Harbison, P., 1983. The analysis and

measurement of happiness as a sense of well-being. Soc. Indic.

Res. 15, 91–115.

Kay, S.R., Opler, L.A., Lindenmayer, J.P., 1988. Reliability and

validity of the Positive and Negative Syndrome Scale for

schizophrenics. Psychiatry Res. 23, 99–110.Kay, S.R., Opler, L.A., Lindenmayer, J.P., 1989. The Positive and

Negative Syndrome Scale (PANSS): rationale and standardisa-

tion. Br. J. Psychiatry Suppl., 59–67.

Kendler, K.S., Gallagher, T.J., Abelson, J.M., Kessler, R.C., 1996.

Lifetime prevalence, demographic risk factors, and diagnostic

validity of nonaffective psychosis as assessed in a US

community sample. The National Comorbidity Survey. Arch.

Gen. Psychiatry 53, 1022–1031.

Kessler, R.C., McGonagle, K.A., Zhao, S., Nelson, C.B., Hughes,

M., Eshleman, S., Wittchen, H.U., Kendler, K.S., 1994. Lifetime

and 12-month prevalence of DSM-III-R psychiatric disorders in

the United States. Results from the National Comorbidity

Survey. Arch. Gen. Psychiatry 51, 8 – 19.

Larsen, R.J., Diener, D., Emmons, R.A., 1985. An evaluation of

subjective well-being measures. Soc. Indic. Res. 17, 1 – 17.

Margolese, H.C., Malchy, L., Negrete, J.C., Tempier, R., Gill, K.,

2004. Drug and alcohol use among patients with schizophrenia

and related psychoses: levels and consequences. Schizophr. Res.

67, 157–166.

McLellan, A.T., Luborsky, L., Woody, G.E., O’Brien, C.P., 1980.

An improved diagnostic evaluation instrument for substance

abuse patients. The Addiction Severity Index. J. Nerv. Ment.

Dis. 168, 26–33.

McLellan, A.T., Luborsky, L., Cacciola, J., Griffith, J., Evans, F.,

Barr, H.L., O’Brien, C.P., 1985. New data from the Addiction

Severity Index. Reliability and validity in three centers. J. Nerv.

Ment. Dis. 173, 412–423.

Mercier, C., Tempier, R., Renaud, C., 1992. Community services

and quality of life: a study of the impact in a remote region. Can.

J. Psychiatry 37, 553–563.

Negrete, J.C., Knapp, W.P., Douglas, D.E., Smith, W.B., 1986.Cannabis affects the severity of schizophrenic symptoms: results

of a clinical survey. Psychol. Med. 16, 515–520.

Olfson, M., Mechanic, D., Hansell, S., Boyer, C.A., Walkup, J.,

Weiden, P.J., 2000. Predicting medication noncompliance after

hospital discharge among patients with schizophrenia. Psychiatr.

Serv. 51, 216–222.

Overall, J.E., Gorman, D.R., 1962. The brief psychiatric rating

scale. Psychol. Rep. 10, 799–802.

Pulver, A.E., Wolyniec, P.S., Wagner, M.G., Moorman, C.C.,

McGrath, J.A., 1989. An epidemiologic investigation of

alcohol-dependent schizophrenics. Acta Psychiatr. Scand. 79,

603–612.

Regier, D.A., Farmer, M.E., Rae, D.S., Locke, B.Z., Keith, S.J.,

Judd, L.L., Goodwin, F.K., 1990. Comorbidity of mentaldisorders with alcohol and other drug abuse. Results from the

Epidemiologic Catchment Area (ECA) Study. JAMA 264,

2511–2518.

Salyers, M.P., Mueser, K.T., 2001. Social functioning, psychopa-

thology, and medication side effects in relation to substance use

and abuse in schizophrenia. Schizophr. Res. 48, 109–123.

Soyka, M., 2000. Substance misuse, psychiatric disorder and violent

and disturbed behaviour. Br. J. Psychiatry 176, 345–350.

Swartz, M.S., Swanson, J.W., Hiday, V.A., Borum, R., Wagner,

H.R., Burns, B.J., 1998. Violence and severe mental illness: the

effects of substance abuse and nonadherence to medication. Am.

J. Psychiatry 155, 226–231.


margolese

Documents