British Journal of Addiction (1992) 87, 179-187
Methodological considerations in the diagnosis of
coexisting psychiatric disorders in substance
ROGER D. WEISS, STEVEN M. MIRIN & MARGARET L. GRIFFIN
Alcohol and Drug Abuse Program, McLean Hospital, 115 Mill Street, Belmont, MA 02178, and
the Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA
The authors reviewed the diagnostic methodology in 14 studies that examined the prevalence of coexisting
psychiatric disorders in substance abusers. There was widespread variation among the studies in the timing of
patient interviews, the nature of the interviews themselves, and abstinence criteria required before another
psychiatric disorder could be diagnosed. These differences were reflected in some of the study results. The
authors describe how variations in methodology can affect the diagnoses patients receive. They also suggest
more specific abstinence criteria, based on the substances of abuse and the specific disorders being diagnosed.
Several studies have shown that identification and
treatment of specific coexisting psychiatric dis-
orders in substance abusers can improve overall
prognosis.'"' Conversely, failure to diagnose these
disorders promptly and accurately may render the
use of otherwise promising pharmacotherapeutic
agents less beneficial and, in some cases, harmful.**
Approximately a decade ago, researchers pointed
out that the methodology used to diagnose coexist-
ing psychiatric disorders in substance abusers varied
widely.^'^ For example, studies of the prevalence
rate of 'depression' in alcoholics produced results
ranging from 3 to
diagnostic criteria that were instituted with DSM-
III,'' DSM-III-R^ and the Research Diagnostic
Criteria (RDC)'" were designed to make the
diagnostic process more standardized and reliable.
Unfortunately, identifying coexisting psychiatric
disorders in substance abusers presents several
specific methodological problems that can compli-
cate the diagnostic process. For example, the timing
of a diagnostic interview may affect the reliability
and validity of a patient's response. Indeed, two
studies "'' ^ have shown that repeated administration
of the same diagnostic interview to drug dependent
patients can produce poor long-term" and short-
term'- diagnostic agreement on lifetime diagnoses
that should not change during the study period.
Differences in interview techniques and diagnos-
tic criteria can also affect study results. For
example, several studies of substance abusers'*""
have compared diagnoses made as a result of clinical
interviews with those based on structured diagnostic
interviews; all have revealed areas of considerable
disagreement between the two. In addition, some
standardized interviews vary in their handling of
certain diagnostic questions that commonly arise in
drug dependent patients.'^ For example, interviews
based on the RDC (e.g. the Schedule for Affective
Disorders and Schizophrenia, or SADS") do not
diagnose antisocial personality disorder (ASPD) if
some of the symptoms of that disorder are clearly
attributable to substance abuse.'"'"' On the other
hand, structured interviews based on DSM-III or
R. D. Weiss et al.
DSM-III-R, like the Diagnostic Interview Schedule
(DIS),'* do not make this distinction, allowing the
interviewer to diagnose ASPD under circumstances
m which Research Diagnostic Criteria for that
diagnosis are not met. In addition, clinicians and
researchers who diagnose coexisting psychiatric
disorders in substance abusers must establish absti-
nence criteria, i.e. the period of time (if any) that a
patient must be drug-free before a psychiatric
disorder, other than a substance use disorder, can be
diagnosed. Variations in these criteria may lead to
differing study results.
In this paper, we will examine these methodologi-
cal issues in studies of psychiatric disorders among
substance abusers, in order to see whether the hope
of diagnostic reliability has been fulfilled in this
We conducted a computer-aided literature search to
find papers published between 1980 (when DSM-
III criteria were instituted) and 1991 that addressed
the relationship between substance abuse and psy-
chiatric disorders. We reviewed all papers that met
the following characteristics.
1. A major topic of the study was the prevalence
rate of comorbid Axis I psychiatric disorders
in a study population of patients with primary
substance use disorders. We focused primarily
on Axis I disorders rather than personality
disorders because of the particular difficulty
involved in distinguishing between addiction-
related symptoms and enduring personality
traits.''*'^" In papers that diagnosed both Axis I
and Axis 11 disorders, we included only
antisocial personality disorder (ASPD) among
the latter group, since this diagnosis has been
subject to the most extensive validity and
reliability testing among the personality dis-
2. Patients were diagnosed as the result of
3. DSM-III, DSM-III-R, and/or Research Diag-
nostic Criteria were utilized in making diag-
If a group of investigators wrote a series of papers
that met the above criteria, we selected the one
paper that most clearly described the diagnostic
We reviewed 14 papers'^'-*-'*-^^""'- that met the
aforementioned criteria (see Table 1). Six focused
exclusively on alcoholics, four on mixed populations
of drug abusers, three on cocaine abusers and one on
opioid addicts. In addition to characterizing the size
and nature of the patient populations described, we
compared the following study characteristics.
1. When were patients interviewed?
2. How were diagnoses made, i.e. how were
patients interviewed and what diagnostic
criteria were utilized?
3. What abstinence criteria were used? That is,
what was the period of time that a patient had
to be drug-free before a psychiatric diagnosis,
other than a substance use disorder, could be
In answering each of these questions, we also
examined the question of whether methodological
differences in the diagnostic process led to divergent
When were patients interviewed?
There was substantial variation among studies
regarding the timing of diagnostic interviews. Most
commonly, such interviews began during the first
week after admission,'^'^'^^'^'-^^'^^ although two
studies administered diagnostic interviews during
the second-*^ and third"' weeks, respectively. Three
studies'^'^-^^ began the diagnostic process within
the first week, but conducted repeated interviews
during the next 2-4 weeks. The timing of the
diagnostic interview was not specified in two
reports.^*'^^ Some of the patients interviewed may
have been drug-free for variable periods of time
prior to entering treatment, thus making their length
of abstinence prior to being interviewed longer than
In two studies, the same diagnostic assessment
was carried out at two separate times. Dackis et al.^^
found that the prevalence rate of current major
depression in hospitalized alcoholics was signifi-
cantly lower when patients were interviewed with
the SADS-C after 2 weeks of abstinence, as
compared with these same patients when given the
same interview within 5 days of admission. In a
study of hospitalized cocaine abusers, Rounsaville et
aV^ administered the lifetime version of the SADS
to a subsample of their study population during the
first week after admission and again after approxi-
mately 3 weeks of hospitalization. They reported
kappa values" for the two interviews ranging from
Diagnostic methods in substance abusers 181
0.36 to 0.46, depending on the diagnosis. The kappa
statistic measures chance-corrected degree of agree-
ment, ranging in value from —1, for complete
disagreement, through 0, for chance agreement, to a
maximum of +1, for perfect agreement; these
findings thus suggest that during early abstinence,
making reliable current or even lifetime psychiatric
diagnoses in patients with substance use disorders is
How were diagnoses made?
Imerview techniques varied widely across studies.
Most commonly, a single standardized struc-
tured interview such as the DIS, SADS or
SCID^^"^*-^*'^''^' was administered. However, other
researchers utilized repeated standardized inter-
views,'-'^^ a structured clinical interview/" a semi-
structured clinical interview,^'' or a single clinical
interview using a DSM-III checklist.'- In two
studies, patients were diagnosed by two different
methods.'^'* The DIS was compared in one study
with repeated clinical interviews conducted by two
psychiatrists;'-' in the other study, patients received
DIS and SADS-L diagnoses.'"
We found that neither the type of interview
administered nor the diagnostic criteria utilized
affected study results m any consistent pattern.
However, the studies in which patients were diag-
nosed by more than one method revealed substantial
variation in the prevalence rates of comorbid
disorders. For example, Rounsaville et a/.'- found
that 33% of their sample of cocaine abusers met
DSM-III-R criteria for antisocial personality dis-
order, whereas only 8% met the more restrictive
Research Diagnostic Criteria for this diagnosis. In
addition, kappa values reflected relatively poor
agreement between DIS and SADS diagnoses of
anxiety disorders and ASPD,'* and substantial
disagreement between clinical and DIS diagnoses of
mood disorders, anxiety disorders and ASPD.''
These variations were most likely due, in part, to
differences between RDC and DSM-III in their
definitions of ASPD (see above) and specific
anxiety disorders. For example, RDC requires fewer
symptoms than DSM-IH to make a diagnosis of a
panic attack. However, Hasin and Grant'*' also
reported that discrepancies in phobia diagnoses
between the SADS-L and the DIS resulted pri-
marily from patients reporting different fears to
different interviewers. This underlines the difficulty
inherent in obtaining reliable information regarding
psychiatric symptoms from this population in a
What abstinence criteria were utilized?
Abstinence criteria also varied markedly across
studies. Four investigators diagnosed psychiatric
disorders even when patients were engaged in active
substance abuse,'---''"-'- while four others'-'-*'-'^-'"*
distinguished between diagnoses made during peri-
ods of abstinence and those made during periods of
substance use or abuse. Among the latter group of
studies, however, abstinence criteria varied mark-
edly. For example, Rounsaville et aV- diagnosed
comorbid disorders in cocaine addicts in the context
of abstinence or steady-state substance use, but not
during periods of changmg use patterns; Griffin et
a/." (using the DIS interview) and Ross et al.
diagnosed concurrent psychiatric disorders only if
patients believed that their symptoms were not
explained by substance abuse. Hesselbrock et al}^
used similar criteria, although they did not specify
whether that judgment (i.e. that symptoms were not
due to substance abuse) was made by the patient or
by the interviewer. Hendriks-'* did not specify how
this distinction was made in his study.
When we compared three studies that examined
the prevalence rate of major depression in hospital-
ized alcoholics, we found considerable variation in
the abstinence criteria employed. Schuckit'" did not
diagnose affective disorder in alcoholics unless they
had either experienced symptoms prior to the onset
of heavy drinking or during a period of abstinence
lasting 3 months or more. Dackis et al.,~^ on the
other hand, diagnosed major depression in alcoholics
after only 2 weeks of sobriety, and Willenbring'^
diagnosed patients as depressed regardless of the
relationship of their depressive symptomatology
to drinking. Herz et al.-'^ were not specific about
their abstinence criteria. Not surprisingly, the
study conducted by Schuckit,'" which imposed the
strictest abstinence criteria, reported the lowest
prevalence rate of affective disorder. Interestingly,
however, the Willenbring study," which had no
exclusionary criteria, had a lower rate of depression
than that reported by Dackis et al?'^
Finally, studies varied substantially in how they
dealt with specifi,c diagnostic entities. For example,
some authors'^'^''•^* eschewed the diagnosis of dys-
thymia because of their belief that this disorder was
too difficult to distinguish from the low mood that
frequently occurs in substance abusers. Other au-
thors^' diagnosed dysthymia, but did not diagnose
atypical depression for the same reason.
R. D. Weiss et al.
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Diagnostic methods in substance abusers 183
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R. D. Weiss et al.
In reviewing studies of the prevalence of psychiatric
disorders in substance abusers, we found that the
diagnostic methodology used in these reports varied
substantially. Despite widespread agreement on the
importance of accurate diagnosis, our review re-
vealed little consensus about how to make additional
psychiatric diagnoses in patients with substance use
disorders, when to make them, or even which
diagnoses can be made at all.
We recognize that we may have excluded some
studies on this subject that met our inclusion
criteria. Some potentially appropriate studies may
have been left out because we did not identify them
durmg our computer-aided literature search; one
recent study'* reported that computer searches may
fail to identify approximately one-third of appropri-
ate articles on a particular subject. We eliminated
still other studies that did not, in our judgment,
focus primarily on the prevalence of Axis I disorders
in substance abusing patients. Nonetheless, al-
though ours was not a very large sample of studies,
and may not have been comprehensive, the degree
of disagreement among the reports we reviewed was
This variability in diagnostic technique has oc-
curred despite great effort to refine this process. For
example, many of the aforementioned studies used
standardized structured interviews to make diag-
noses. The advantage of standardized interviews is
that their systematic and comprehensive approach
enhances reliability. Unfortunately, using standar-
dized instruments is only one step in clarifying the
relationship between substance use disorders and
coexisting psychiatric disorders. For example, inter-
viewers using the Diagnostic Interview Schedule are
instructed to ask all patients (not just substance
abusers) whether their symptoms have 'always been
explainable by the effects of medication, drugs or
alcohol, or by withdrawal from any of those'.'^ The
Schedule for Affective Disorders and Schizophre-
nia" and the Standardized Clinical Interview for
DSM-III-R^^ contain similar questions. These 'ex-
clusionary' or 'probe' questions are designed to
differentiate an independent coexisting psychiatric
disorder from a drug-induced disorder. However,
since these interviews do not clearly define how this
distinction is to be made, the timing of the interview
and the abstinence criteria established are likely to
produce reporter and interviewer bias, respectively.
The influence of the timing of a diagnostic
interview on patient response is illustrated by the
poor long-term concordance over time for lifetime
diagnoses in opioid addicts" and only low to
moderate short-term diagnostic concordance in
cocaine abusers.'- One potential explanation for
these findings is that an individual's recollection of
his or her past experiences may be influenced by
current emotions and attitudes, which are subject to
change during the treatment process. For example, a
depressed alcoholic who cannot clearly recall the
exact chronology of the onset of his two disorders
may enter treatment believing:
(1) that his drinking is symptomatic of his
(2) that receiving treatment for his depression
will allow him to return to controlled drink-
If administered a standardized diagnostic interview
upon entry into treatment, such an individual would
not attribute his depressive symptoms to drinking.
Since he would not meet exclusionary criteria, he
would receive a diagnosis of major depression. If
such a patient became actively involved in treat-
ment for his alcoholism, part of which might include
attendance at Alcoholics Anonymous meetings, he
might be told that his wish to return to controlled
drinking was evidence of his 'denial' of the severity
of his alcoholism. He might also be told that his
depression was probably a result of his alcoholic
drinking, and that his mood would improve if he
became sober. If he subsequently believed this
alternative viewpoint, a repeat interview might
reveal a different diagnosis, since he would now be
more likely to say that his depressive symptoms
occurred in the context of heavy drinking. This
patient would then meet exclusionary criteria and
would, therefore, not receive a diagnosis of major
Since one major goal of many substance abuse
treatment programs is to confront 'denial' and
encourage patients to recall the numerous adverse
consequences of their substance abuse, it can be
argued that an indirect result of patients' compli-
ance with such treatment programs may be their
changing their views of their histories. This can
obviously affect the diagnostic process, and may
limit the utility of any single diagnostic interview in
substance abusing patients early in the course of
In addition to potential changes in patient atti-
tudes over time, reporter and interviewer biases
regarding abstinence criteria can influence study
results. For example, one patient or interviewer
might interpret an episode of depression that
Diagnostic methods in substance abusers 185
occurred 2 months after stopping drinking as
alcohol-related, while another patient or interviewer
might consider a depressive episode that began 2
weeks subsequent to stopping drinking to be unre-
lated to alcohol. Although individual investigators
may establish guidelines for dealing with such
situations, there is no clear consensus within the
field on the duration of abstinence necessary before
specific signs and symptoms can be attributed to
'non-alcohol'-related causes. This has contributed
to substantial variation in the prevalence of comor-
bidity from one center to another, despite the use of
identical diagnostic interviews. Thus, the study'"
that requires the longest period of abstinence before
diagnosing comorbid depression in alcoholics also
reports the lowest prevalence rate of this disorder.
A final problem inherent in diagnosing coexisting
psychiatric disorders in substance abusers is the fact
that different substance use disorders may cause
symptoms resembling some psychiatric syndromes,
but not others. For example, prolonged drinking and
alcohol withdrawal can cause symptoms of depres-
sion that may closely resemble those of a primary
mood disorder.-""'^' Moreover, many of these symp-
toms have been shown to spontaneously improve
without antidepressant treatment.^^ On the other
hand, it is less clear as to whether intoxication and
withdrawal symptoms in opioid addicts may mimic
symptoms of major depression.'"'^^ Rounsaville et
al.^* have reported that these syndromes are distin-
guishable, while Dackis et aO'^ have found more
similarity in the two disorders, particularly in
patients dependent upon methadone. Abstinence
criteria, then, should vary according to the diagnosis
being made and the substance(s) that the patient is
abusing. One model that proposes such specificity
has been outlined by Rounsaville,""* who suggests
that diagnoses of psychotic disorders or mood
disorders not be made if symptoms have occurred
only during extended periods of stimulant, halluci-
nogen, or phencyclidine use. The high prevalence
rate of polysubstance abuse among patients seeking
treatment*" can, unfortunately, complicate this pro-
cess, since patients may simultaneously use drugs
that cause very different intoxication and with-
drawal syndromes, e.g. cocaine and heroin.
Obviously, not all variations in diagnostic studies
are attributable to methodological differences. In-
deed, the prevalence of rate of depression in the
three aforementioned studies of alcoholics'^'^"-*-^ did
not vary merely according to the strictness of the
abstinence criteria that they used. Rather, differ-
ences in patient populations can also affect results.
Although we do not suggest that there is a single
optimal way to diagnose psychiatric disorders in
substance abusers, we can offer several guidelines.
First, it is important to recognize that substance
abusers early in treatment are undergoing rapid
physical, psychiatric and attitudinal changes. Thus,
any single interview conducted during this time of
acute turmoil may yield incomplete or biased
information. Conducting a longitudinal evaluation
rather than relying on any one interview may,
therefore, improve the diagnostic process. In addi-
tion, one can obtain corroborating data from family
members, who may be able to inform clinicians
regarding longstanding patient behaviors and alti-
tudes; use of an extended observation period,
coupled with multiple data sources, has been shown
to enhance validity in research,•*^"'*"'
Another strategy that can improve the reliability
and validity of the diagnostic process involves
delaying the evaluation inierview(s) until the pa-
tient is physically and psychiatrically stable and not
experiencing significant intoxication or withdrawal
symptoms.*"* The time course involved in this
process may vary from patient to patient, but would
most likely be approximately 2 weeks after admis-
sion in most cases. Finally, the most reliable clinical
and/or research interviews are likely to be con-
ducted by clinically trained personnel who can
recognize potential manifestations of reporter bias,
and who understand specific short- and long-term
psychiatric effects of the drugs of abuse. Since
substance abuse programs often have few profes-
sional staff members, screening questionnaires may
have some utility in identifying patients with
possible psychiatric comorbidity.'-''^''* However,
instruments such as the SADS and the SCID, which
need to be administered by clinically sensitive
interviewers, appear to offer the most valid assess-
ments of the relationship between substance abuse
It is important lo consider the potential implica-
tions of the current lack of consensus regarding this
diagnostic process. Studies of the efficacy of antide-
pressant treatment in 'depressed alcoholics' would
be difficult to replicate if investigators used differ-
ent abstinence criteria to define their target study
populations. Jaffe and Ciraulo"*^ have pointed out
that methodological problems such as this have
limited the generalizability of the findings of many
such studies. Perhaps further research on the natural
history of recovery from substance abuse will allow
us to be able to reach agreement on how to diagnose
psychiatric disorders in this population.
R. D. Weiss et al.
Supported by Grant 1 R29 DA-05944 from the
National Institute on Drug Abuse; BRSG Grant
RR05484 awarded by the Biomedical Research
Support Program, Division of Research Resources,
National Institutes of Healthi and a grant from the
Engelhard Foundation. The authors would like to
thank Harrison G. Pope, Jr MD, for his helpful
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