Download primary and secondary substance misusers: do they differ in

Alcohol & Alcoholism Vol. 38, No. 1, pp. 54–59, 2003
doi:10.1093/alcalc/agg012, available online at www.alcalc.oupjournals.org
PRIMARY AND SECONDARY SUBSTANCE MISUSERS: DO THEY DIFFER
IN SUBSTANCE-INDUCED AND SUBSTANCE-INDEPENDENT MENTAL DISORDERS?
K. BAKKEN*, A. S. LANDHEIM and P. VAGLUM1
Centre for Addiction Issues, Department for Substance Abuse, Sanderud Hospital and 1Department of Behavioural Sciences in Medicine,
University of Oslo, Norway
(Received 18 March 2002; first review notified 9 April 2002; in revised form 9 July 2002; accepted 31 July 2002)
Abstract — Aims: This study evaluated the primary/secondary distinction among substance misusers according to comorbid mental
disorders. Methods: A consecutive sample (n = 287) of DSM-IV substance dependents from public treatment facilities in two counties
in Norway were assessed by the Composite International Diagnostic Interview. According to the debut of the first independent mental
disorder, patients were divided into primary substance use disorder (SUD) (17%), secondary SUD (76%) and SUD in the same year
as the first mental disorder (7%). Results: A lifetime substance-independent mental disorder was found in 90%. Forty-two per cent
had a combination of substance-independent and substance-induced mental disorders. Five per cent had substance-induced mental disorders only. Primary SUD patients comprised less women, and a lower number of substance-independent mental disorders. Secondary
SUD patients had more major depression, phobic disorders and obsessive-compulsive disorder. There were no differences between primary SUD and secondary SUD regarding the number of substance-induced disorders or the pattern of substance misuse. Conclusions:
Clinical differences between primary and secondary SUD were small and do not support the distinction.
INTRODUCTION
disorders that started before the establishment of the first SUD
are more easy to classify as substance-independent mental disorders, than mental disorders that commenced after establishment of the SUD. Such disorders can be both independent
of, and induced by, the SUD. Usually, in this research field,
substance-induced mental disorders are classified as those
disorders that have occurred after establishment of the SUD.
In the present study, we have separated those mental disorders
that occurred after the SUD, into substance-induced and
substance-independent mental disorders by using the Composite International Diagnostic Interview (CIDI). CIDI allows
every section to be followed by probe questions to assess whether
the mental disorder was caused directly by using medication,
drugs or alcohol (Wittchen, 1994). If the symptoms can
be explained exclusively by such causes, they are classified as
substance-induced mental disorders. If the mental disorders
are not induced by the use of substances, they are classified
as substance-independent mental disorders. Consequently,
substance-independent mental disorders may commence
before or after a SUD is established.
Prevalence rates of mental disorders among SUD patients
depend upon how mental disorders are defined. By counting
only substance-independent mental disorders (onset of mental
disorder before onset of SUD, or occurrence of a mental
disorder in a prolonged substance-free period of 3–6 months),
the comorbidity rate of SUDs and mental disorders was reduced
to 60–75% in several studies (Schuckit et al., 1990, 1997a,b;
Kadden et al., 1995). However, some researchers have argued
that the criteria for operationalizing substance-independent
mental disorders have been too restrictive in these studies
(Kushner et al., 2000), and others have not found the distinction between substance-induced and substance-independent
mental disorders clinically useful (Penick et al., 1994; Kadden
et al., 1995). Other studies do not separate mental disorders
into substance-independent and substance-induced disorders.
They usually analyse whether the mental disorder came before
or after the SUD (Driessen et al., 1996; Compton et al., 2000).
In a recent review, Wittchen et al. (1996) reported that
80–90% of substance misusers possibly developed the other
There is a strong co-occurrence of substance use disorders
(SUDs) with other mental disorders in the general population
(Regier et al., 1990; Kessler et al., 1997; Merikangas et al.,
1998) and an even stronger relationship within clinical groups
(Hesselbrock et al., 1985; Helzer and Pryzbeck, 1988; Ross
et al., 1988; Tomasson and Vaglum, 1995; Driessen et al., 1996,
1998; Kokkevi et al., 1998; Compton et al., 2000). However,
there is far less empirical evidence regarding the actual mechanism of this co-occurrence (Winokur, 1990; Kessler and
Price, 1993; Mueser et al., 1998; Kushner et al., 2000). It is of
both theoretical and clinical importance to clarify further these
possible relationships.
An important approach to the investigation of the association between SUDs and mental disorders has been the
classification of mental disorders among SUD patients into
substance-independent and substance-induced mental disorders. Substance-induced mental disorders are characterized
by their development in close connection with the use of substances, their presence only when the person uses substances,
and their supposed improvement during the initial weeks of
abstinence, even without specific treatment (Akiskal, 1995;
Kadden et al., 1995). The identification of mental disorders
that are independent of SUDs is mainly based on the argument
that if such a disorder was manifested (lifetime prevalence)
before the onset of any SUD, it is likely that the mental disorder is independent of the substance misuse. Consequently,
such mental disorders may need to be treated differently from
those that have been induced by the use of substances (Brown
et al., 1995; Goodwin and Guze, 1996).
Concerning the classification of comorbid mental disorders,
it is always difficult to do such classification with a retrospective design. Retrospective information depends on the patient’s
capability to recall. The best would be to have a prospective
design, but it is difficult to carry out such studies. Axis I mental
*Author to whom correspondence should be addressed at: Department for
Substance Abuse, Sanderud Hospital, Postboks 68, 2312 Ottestad, Norway.
54
© 2003 Medical Council on Alcohol
MENTAL DISORDERS IN PRIMARY AND SECONDARY SUD
mental disorder before SUD onset. A German study that
used the CIDI in a sample of 100 alcoholics found that 80% of
those with a mental disorder developed the condition before
the onset of SUD (Driessen et al., 1996).
Concerning the classification of substance misusers, it
has been customary to classify substance misusers as primary
misusers (primary SUD) if the first Axis I mental disorder began
after the SUD, and as secondary misusers (secondary SUD) if
the Axis I mental disorder(s) were manifested before the SUD.
The term secondary SUD does not imply that the SUD is
caused by the mental disorder, only that it started some time
after the mental disorder. One important, but still unsolved,
question is whether primary and secondary SUD patients
really differ with regard to the prevalence and type of both
substance-independent mental disorders and substanceinduced mental disorders. Until now, most of the studies have
been done in the USA in highly selective clinical samples, and
the validity of generalizing these findings is unclear. There
is therefore a need for studying this important question outside
the USA, where the drug scene is different. Such studies should
examine samples representing the heterogeneity of the SUD
population, and explore whether there are clinically important
differences in comorbid disorders between the primary and
secondary SUD groups. In addition, it is also of interest, in
clinically representative samples, to examine more specifically the subgroup of patients who have exclusively substanceinduced mental disorders, so as to identify the magnitude of the
mental disorder as well as other characteristics of this subgroup.
Since it may be difficult in retrospective studies to clearly
know when the first SUD/Axis I disorder started we excluded
those patients who got both disorders in the same year.
With this background, we have conducted a cross-sectional
study, completing personal interviews with a consecutive sample
of treatment-seeking SUD patients from public treatment
facilities for SUD patients in two neighbouring counties in
Norway (with a total population of approximately 290 000
people aged over 18 years). To our knowledge, this is the first
study of its type in Scandinavia. The questions we explored
are: (1) what is the prevalence of substance-induced and
substance-independent mental disorders in this consecutive
sample?; (2) are there any differences in sociodemographic
variables or SUDs between patients with substance-induced,
and those with substance-independent, mental disorders?; (3)
among patients with substance-independent mental disorders,
what is the prevalence of primary and secondary SUDs?; (4)
are there any differences between primary and secondary SUD
patients regarding sociodemographic variables, substance use
and the prevalence of Axis I disorders?
SUBJECTS AND METHODS
A consecutive sample (n = 287) of DSM-IV (American
Psychiatric Association, 1994) substance dependents from
three out-patient (n = 116) and six in-patient public facilities
(n = 171) were assessed by the Norwegian National Client
Assessment form (sociodemographic and substance use variables) and the structured interview CIDI (Axis I disorders).
The response rate was 42%. In spite of this relatively low response rate, the sample appears to be reasonably representative
for treatment-seeking SUD patients. Compared with a national
55
sample of treated substance misusers (n = 5000) in Norway,
the main difference was only that our sample included rather
fewer young drug misusers. In the analyses, we did not distinguish between substance misuse and substance dependence.
All patients fulfilled DSM-IV criteria for at least one substance dependence. With regard to the onset of SUD, we chose
as age of onset the first time the person fulfilled either a
dependence or a misuse diagnosis.
The assessment with the CIDI was conducted at the earliest
4 weeks after discontinuation of substances among in-patients.
This was more difficult to carry out among out-patients, and
we included such clients if they were sober in the assessment
situation.
About one third of the patients received medications because
of mental problems during the last month before assessment.
Psychiatric Axis I disorders were evaluated using the
Norwegian version of the CIDI, Lifetime version, the computer version of CIDI-M 1.1. CIDI is a structured psychiatric
interview based on DSM-IV criteria and the corresponding
diagnosis in ICD-10. CIDI focuses on both lifetime symptoms
as well as those of the last 12 months, age of onset and recency.
In this study, we used the version of the CIDI examining
symptoms over the lifespan. The time of onset (and recency)
of a disorder are assessed in relation to the year when a sufficient number of criteria of a specific diagnosis was fulfilled
for the first and most recent time. For the purpose of this study,
we used a non-hierarchical diagnostic system.
The CIDIs were mostly conducted by the two researchers
(K.B. and A.S.L.), who had taken part in the training workshops by The National WHO Training Centre (Munich). One
third of the interviews were conducted by trained clinicians
(psychiatrists, social workers psychiatric nurses). The two
researchers in the project trained these interviewers using a
standardized 4-day training programme. Structured diagnostic
interviews, such as CIDI, usually possess higher test–retest
reliability than clinical interviews (Robins et al., 1989). The
CIDI has shown good feasibility in general populations, high
inter-rater reliability, and has been subjected to tests of reliability
and validity with satisfactory results (Janca et al., 1992a,b;
Williams et al., 1992; Wittchen, 1994). Further information
about sampling, subjects, methods and data analyses is described
in another paper (Landheim et al., 2003).
RESULTS
Prevalence of substance-induced and substance-independent
mental disorders
In all, 259 patients (90%) fulfilled the criteria for at least
one lifetime substance-independent mental disorder, and 15
patients (5%) had exclusively substance-induced mental disorders. Another 13 subjects (5%) were without any additional
mental disorder and were excluded from the analyses. In all,
120 patients (42%) had one or more substance-induced mental disorders in addition to one or more substance-independent
mental disorders (Table 1).
Differences between substance-induced and
substance-independent mental disorders
The subgroup exhibiting only substance-induced mental
disorders did not differ significantly from patients with
56
K. BAKKEN et al.
Table 1. Prevalence of substance-induced and substance-independent mental disorders
Substance-induced mental disorders
Yes
Substance-independent mental disorders
Yes
No
Total
No
Total
n
%
n
%
n
%
120
15
135
41.8
5.2
47.0
139
13
152
48.5
4.5
53.0
259
28
287
90.2
9.8
100.0
substance-independent mental disorders with regard to sociodemographic variables (Table 2) and substance use (main substance, mean number of substances, duration of dependency).
Classification in primary and secondary SUD groups
Among those patients with a substance-independent mental
disorder, 43 patients (17%) were classified as primary SUD.
These individuals had a SUD at least 1 year before the emergence of any other mental disorder. Furthermore, 198 patients
(76%) were classified as secondary SUD, as they developed a
mental disorder at least 1 year before the first SUD diagnosis.
In 18 patients (7%), the SUD and the mental disorder emerged
during the same year, thereby making it difficult to decide which
was the initial disorder. Subsequently, these patients were excluded from comparisons between the primary and secondary
SUD groups.
Differences between primary and secondary SUD patients
The only significant sociodemographic difference between
the primary and secondary SUD groups was that of gender
(Table 2). More than one third of the secondary SUD group
were women, compared with only 9% (n = 4) among those
with primary SUD. Because of this large gender difference, we
controlled for gender when we compared primary and secondary
SUD.
Concerning the length, extent and severity of the substance
use, there was only one significant difference as shown in
Table 3. As expected, patients with primary SUD more often
had an early average onset of SUD, compared with secondary
SUD patients (17.8 vs 22.9 years, P = 0.003). For each misused
substance, the primary SUD group had a higher frequency of
use than the secondary SUD group, but the differences were
not significant. The mean number of SUD diagnoses was
quite similar in the primary and secondary SUD groups (2.8 vs
2.5). To further examine differences between groups, we
conducted a series of multivariate analyses using logistic
regression, controlling for gender. In the series of analyses,
each disorder was treated as a dependent variable, while
primary/secondary SUD and gender were independent
variables. These analyses did not change any of the differences
between primary SUD and secondary SUD, which are shown
in Tables 2 and 3.
Table 2. Sociodemographic variables in primary and secondary SUD groups
Parameter
Women
Married/cohabiting
Only elementary schoola
Employed
Mean age (SD) (years)
Primary SUD (n = 43)
%
Secondary SUD (n = 198)
%
Significance (P)
9.3
34.1
50.0
30.3
38.1 (10.1)
36.7
33.7
51.1
23.6
38.2 (11.0)
<0.001
NS
NS
NS
NS
NS, not significant.
Education 9 years.
a
Table 3. Substance use disorders (SUDs) (DSM-IV) and substance use variables in primary and secondary SUD groups
Alcohol misuse and/or dependence
Opioid misuse and/or dependence
Cannabis misuse and/or dependence
Sedative/hypnotic misuse and/or dependence
Cocaine misuse and/or dependence
Amphetamine misuse and/or dependence
Hallucinogen misuse and/or dependence
Inhalant misuse and/or dependence
Earlier treatment for substance misuse
Mean age of onset SUD (SD) (years)
Mean number of SUDs (SD)
NS, not significant.
Primary SUD (n = 43)
%
Secondary SUD (n = 198)
%
Significance (P)
88.4
37.2
39.5
37.2
9.3
44.2
16.3
11.6
69.0
17.8 (5.6)
2.8 (2.2)
84.6
33.8
33.3
35.8
6.5
32.3
11.4
9.5
70.7
22.9 (10.9)
2.5 (2.0)
NS
NS
NS
NS
NS
NS
NS
NS
NS
0.003
NS
MENTAL DISORDERS IN PRIMARY AND SECONDARY SUD
Axis I disorders were significantly more prevalent in the
secondary SUD group (4.4 vs 2.4, P = 0.003; Table 4). When
comparing the primary and secondary SUD groups, the
secondary SUD group had a significantly higher incidence of
major depression and three anxiety disorders: social phobia,
simple phobias and obsessive-compulsive disorder. The
primary SUD group had a significantly higher prevalence of
substance-induced mental disorders. When controlling for
gender, however, this difference became non-significant.
DISCUSSION
Approximately 90% of all patients had developed a
substance-independent mental disorder at some point in their
lives. In addition, nearly 50% of patients had suffered from
one or more substance-induced mental disorders. About 40%
of patients had both substance-induced and substanceindependent mental disorders, thus demonstrating the problem
of classifying SUD patients based on this distinction. The
treatment system must obviously be able to diagnose and treat
both types of disorders, even when they occur in the same
person. Only 5% had exclusively substance-induced mental
disorders, and this small number makes it difficult to find
significant differences between this group and the group with
independent mental disorders.
It is important to note that three quarters of the patients with
comorbid mental disorders developed their first independent
mental disorder before the onset of any SUD (secondary SUD
group). Only 17% had a primary SUD, a percentage that may
be somewhat underestimated because of the composition of
our sample. However, it does accord well with the review
by Wittchen et al. (1996), and it shows that regardless of the
presence of substance-induced mental disorders, the majority
of substance misusers also had independent mental disorders
that required specific treatment. For some, early and adequate
treatment might possibly have prevented the development of a
secondary SUD, or might have made the course of the SUD
less serious. Our findings highlight the importance of evaluating and treating psychiatric disorders in substance misusers
57
being treated for their dependence for the first time, and to
evaluate substance misuse in general patients with a first-onset
psychiatric disorder.
The primary and secondary SUD groups were very similar
with regard to sociodemographic variables, except for gender.
Accordingly, it is well established that the onset of psychiatric
disorders precedes the onset of SUD more often in women
than in men (Brady and Randall, 1999).
Also as expected, the primary SUD group had an earlieronset
of SUD (mean = 17.8 years) than the secondary SUD group
(mean = 22.9 years). However there were small differences with
respect to the other substance use variables. Differences in
substance use could not explain differences in the prevalence of
mental disorders between the groups. Neither was there a
difference in substance-induced mental disorders between the
groups. The results from other studies vary in this regard.
Most studies report an earlier onset of alcoholism and more
severe substance misuse among primary alcoholics (Roy et al.,
1991; Tsuang et al., 1995; Driessen et al., 1996; Schuckit et al.,
1997b); however, Merikangas and Gelernter (1990) found few
clinical differences between primary and secondary alcoholics.
Concerning Axis I disorders, the secondary SUD group had
significantly more Axis I disorders than the primary SUD
group (4.4 vs 2.4, P = 0.003). Major depression, social phobia,
simple phobia and obsessive-compulsive disorder were more
frequent in the secondary SUD group, with this difference
remaining after controlling for gender. These are well defined
psychiatric disorders with effective treatment methods, so
SUD patients should also receive such treatment. Even if the
SUD patients become abstinent, the independent mental disorders may persist. With regard to dysthymia, the differential
diagnosis versus substance-induced mood disorder may be
difficult. However, the prevalence of dysthymia was the same
in the primary SUD and secondary SUD groups (44.2 vs 45.4%).
About one third of the patients received medications when
they were assessed. Such medication may have modified the
presence of symptoms of psychiatric disorders at the time of
evaluation, but have possibly not influenced the age of onset
of SUD or the differences in prevalence of psychiatric disorders
between the primary and secondary SUD groups.
Table 4. Lifetime Axis I disorders (ICD-10) in primary and secondary SUD groups
Parameter
Substance-induced disorders
All affective disorders
Bipolar
Major depression
Dysthymia
All anxiety disorders
Agoraphobia with/without panic
Social phobia
Generalized anxiety disorder
Simple phobia
Obsessive-compulsive disorder
PTSDa
Somatoform disorder
Eating disorder
Mean number of Axis I disordersb (SD)
NS, not significant.
a
Post-traumatic stress disorder.
b
Only substance-independent disorders.
Primary SUD (n = 43)
%
Secondary SUD (n = 198)
%
Significance (P)
65.1
53.5
2.3
21.5
44.2
84.2
47.5
34.2
23.8
21.4
0.0
16.7
21.4
4.9
2.4 (1.5)
41.9
74.9
6.3
53.7
45.4
92.9
53.8
57.6
20
62.1
10.6
22.3
32.3
11.5
4.4 (2.6)
0.006
0.005
NS
<0.001
NS
NS
NS
0.010
NS
<0.001
0.026
NS
NS
NS
0.003
58
K. BAKKEN et al.
The majority of the patients had independent mental disorders. The substance-independent/induced distinction did not
reduce the number of patients with comorbid mental disorders,
as was the case in some American studies (Schuckit et al.,
1990, 1997a,b; Kadden et al., 1995). The primary SUD group
did not display more severe substance use, and, even if they
had fewer mental disorders, they were of the same type as in
the secondary SUD group. Therefore, it is difficult to use the
primary/secondary distinction to select a group of substance
misusers that do not need psychiatric treatment. Our results
question the clinical validity of differentiating between primary
and secondary SUD patients. Even though it seems to be of
clinical interest in some studies, these samples differ in many
ways from our sample. Compared with many clinical studies
from the USA and Europe our sample was less educated and
with a lower proportion employed (Kadden et al., 1995; Tomasson
and Vaglum, 1995; Driessen et al., 1996, 1998; Schuckit et al.,
1997a,b; Kokkevi et al., 1998). Our sample was drawn from
public institutions and not private clinics that may be supposed
to have a somewhat less sick clientele.
Nevertheless, the distinction between substance-independent
and substance-induced mental disorders should still be used
with respect to the actual disorder of the patient. However,
because many patients have both types of mental disorders,
the terms ‘substance-independent’ and ‘substance-induced’
should be used to classify disorders, but not patients.
The current study has certain limitations. Our methods are
retrospective, and recall bias is always an important problem.
The accuracy of self-reported age of onset is generally poorer
among older adults, and older subjects may tend to report an
older age of depression onset (Prusoff et al., 1988). The subjects using illicit substances could easily recollect when they
started use/misuse of different substances, whereas pure alcoholics described a more gradual development. The co-occurrence
of disorders also introduces complications regarding accurate
assessment and diagnosis (Blanchard, 2000). The validity of
structured interviews, such as the CIDI, can also be questioned,
which is a general problem for all epidemiological research.
Our findings are, however, in good accordance with studies
from other countries. The strength of the CIDI in substance
misuse research is that it has a formal training programme
for interviewers. Furthermore, the CIDI has a system which
excludes psychiatric symptoms that are clearly elicited by the
use of substances.
A further limitation is that only 42% of the patients participated in the study. Our comparisons with dropouts from
the sampling process and the clients from the national
sample indicate that we have an under-representation of
young drug misusers. From several other studies, we know
that poly-substance misusers have a higher prevalence of
symptom disorders than pure alcoholics (Ross et al., 1988).
Furthermore, it is well documented that young substance
misusers have a higher prevalence of psychiatric disorders
than older substance misusers (Tomasson and Vaglum, 1995;
Merikangas et al., 1998). Given a better representation of
young drug misusers in the sample, we could expect to
find an even higher prevalence of Axis I disorders. The
strength of the study, however, is the treatment populationbased sample, the heterogeneity of treatment institutions
included, and the use of structured interviews with well
established reliability.
In conclusion, we found no differences between primary
and secondary misusers with regard to substance misuse or
substance-induced mental disorders. Secondary SUD patients
were more often women, and had a higher prevalence of
substance-independent mental disorders, especially anxiety
disorders. However, the need for treatment of substanceindependent mental disorders was present in both the primary
and secondary SUD groups, and the distinction in primary and
secondary SUD groups seems to be no longer clinically valid.
The distinction between substance-independent and substanceinduced mental disorders was useful in this study, but since
40% of the misusers had both, it is not possible to use this
distinction to classify substance misusers with regard to the
need for psychiatric services.
Acknowledgements — This project has been partly financed with the aid of
EXTRA funds from the Norwegian Foundation for Health and Rehabilitation
and by The Norwegian Board of Health.
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