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Drug and Alcohol Dependence xxx (2015) xxx–xxx

Contents lists available at ScienceDirect

Drug and Alcohol Dependence

journal homepage: www.elsevier.com/locate/drugalcdep

Review

Prevalence of comorbid substance use, anxiety and mood disorders in

epidemiological surveys, 1990–2014: A systematic review and
meta-analysis
Harry Man Xiong Lai a , Michelle Cleary b , Thiagarajan Sitharthan a , Glenn E. Hunt a,∗
a
Discipline of Psychiatry, University of Sydney, NSW, Australia
b
School of Nursing and Midwifery, University of Western Sydney, NSW, Australia

a r t i c l e i n f o a b s t r a c t

Article history: Background: Comorbidity is highly prevalent between substance use disorders (SUDs), mood and anxiety
Received 13 May 2015 disorders. We conducted a systematic review and meta-analysis to determine the strength of association
Received in revised form 25 May 2015 between SUDs, mood and anxiety disorders in population-based epidemiological surveys.
Accepted 27 May 2015
Methods: A comprehensive literature search of Medline, EMBASE, CINAHL, PsychINFO, Web of Science, and
Available online xxx
Scopus was conducted from 1990 to 2014. Sources were chosen on the basis that they contained orig-
inal research in non-clinical populations conducted in randomly selected adults living within defined
Keywords:
boundaries. Prevalence of comorbid SUDs, mood and anxiety disorders and odds ratios (ORs) were
Comorbidity
Prevalence extracted.
Substance use disorders Results: There were 115 articles identified by electronic searches that were reviewed in full text which
Anxiety yielded 22 unique epidemiological surveys to extract lifetime and 12-month prevalence data for psy-
Depression chiatric illness in respondents with an SUD. Meta-analysis indicated the strongest associations were
Meta-analysis between illicit drug use disorder and major depression (pooled OR 3.80, 95% CI 3.02–4.78), followed by
illicit drug use and any anxiety disorder (OR 2.91, 95% CI 2.58–3.28), alcohol use disorders and major
depression (OR 2.42, 95% CI 2.22–2.64) and alcohol use disorders and any anxiety disorder (OR 2.11, 95%
CI 2.03–2.19). ORs for dependence were higher than those for abuse irrespective to diagnoses based on
lifetime or 12-month prevalence.
Conclusions: This review confirms the strong association between SUDs, mood and anxiety disorders. The
issue has now been recognised worldwide as a factor that affects the profile, course, patterns, severity
and outcomes of these disorders.
© 2015 Elsevier Ireland Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.1. Data sources and search strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.2. Selection criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.3. Data abstraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.4. Risk of bias assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.5. Meta-analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1. Search findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.2. Study characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

∗ Corresponding author at: Discipline of Psychiatry, Concord Clinical School, Faculty of Medicine, University of Sydney, Concord Hospital, Hospital Road, Concord, 2139
NSW, Australia. Tel.: +61 2 9767 6829/8978.
E-mail addresses: man-xiong.lai@sydney.edu.au (H.M.X. Lai), m.cleary@uws.edu.au (M. Cleary), Thiagarajan.Sitharthan@sydney.edu.au (T. Sitharthan),
glenn.hunt@sydney.edu.au (G.E. Hunt).

http://dx.doi.org/10.1016/j.drugalcdep.2015.05.031
0376-8716/© 2015 Elsevier Ireland Ltd. All rights reserved.

Please cite this article in press as: Lai, H.M.X., et al., Prevalence of comorbid substance use, anxiety and mood dis-
orders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis. Drug Alcohol Depend. (2015),
http://dx.doi.org/10.1016/j.drugalcdep.2015.05.031
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3.3. Prevalence rates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

3.4. Meta-analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.1. Alcohol use disorders comorbid with anxiety and major depressive disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.2. Illicit drug use disorders comorbid with anxiety and major depressive disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.3. Understanding and treating comorbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4.4. Strengths and limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Authors disclosures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Role of funding source . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

1. Introduction large national studies have limited reporting capacity of comorbid

prevalence rates within general populations where one or both
The issue of substance use disorders (SUDs) comorbid with men- disorders are of low prevalence (such as schizophrenia and intra-
tal health disorders has gained increasing prominence in psychiatry venous drug use or methamphetamine use) where the resulting
and drug health over the last 30 years. There is overwhelm- comorbid sample size is small and variance estimates large.
ing evidence that SUDs are more prevalent among people with Many epidemiology surveys report prevalence rates for indi-
severe mental health disorders than among the general population vidual mental health and various SUDs but often do not report
(Kessler, 2004; Menezes et al., 1996; Merikangas and Kalaydjian, comorbid prevalence rates, although sometimes these are reported
2007; Regier et al., 1990; Rosenthal et al., 2012) which have con- in subsequent analyses (e.g., Merikangas et al., 1998; Swendsen
tributed to the high burden of disease worldwide (Whiteford et al., et al., 1998). Jane-Llopis and Matytsina (2006) reported comorbid
2013; Wittchen et al., 2011). Current reasoning to explain the high prevalence of mental health disorders and SUDs and their rela-
rates of comorbidity are that one mental disorder may directly tionship to be highly prevalent across high income countries. This
influence another, such as heavy alcohol use may produce depres- was not a systematic review and included only nine surveys con-
sion in persons who are alcohol dependent (Cerda et al., 2008; ducted between 1998 and 2005. However, this review found that
Hall et al., 2009). Comorbidity may also be indirectly produced people with a SUD had higher comorbid rates of mental health dis-
such as when substances are used for self-medication or for reliev- orders than vice versa and that people with illicit drug use disorders
ing distress of a mental disorder, e.g., sustained use may lead to (DUDs) had higher rates of mental health disorders than those with
dependence. A third possibility is that comorbidity may arise from alcohol use disorders (AUDs) (Jane-Llopis and Matytsina, 2006).
common shared causes through genetic predisposition or socio- The aim of this systematic review is to report and combine
economic factors, such a poverty or trauma or transmitted within the findings of surveys based on large epidemiological popula-
the family (Cerda et al., 2008; Kushner et al., 2000). The high tions reporting prevalence rates of SUDs comorbid with mood
comorbidity rates may also be due to increased access and oppor- and anxiety disorders from studies conducted between 1990 and
tunity to use illicit drugs in the community (Liang et al., 2011) 2014. We chose 1990 as a starting point to include the influen-
with the closure of large psychiatric hospitals over the last three tial Epidemiologic Catchment Area (ECA) study and subsequent
decades. surveys using similar large scale census techniques and face to
Since comorbid mental health disorders are usually associated face interviews to report prevalence rates using American Psy-
with poor treatment outcomes this leads to severe illness and high chiatric Association-Diagnostic and Statistical Manual (DSM) or
levels of health service utilisation (Kessler et al., 1994; Kessler, World Health Organisation-International Classification (WHO, ICD)
2004; Merikangas and Gelernter, 1990). Yet despite the high rates of diagnostic instruments from diverse geographic sites. Prevalence
comorbidity between substance use, mood and anxiety disorders, of mood and anxiety disorders in respondents with an SUD was
the problem remains poorly understood and is often missed as a collated for lifetime and current (1 year) abuse or dependence of
diagnosis among clinicians practising in either field (Cuffel, 1996; alcohol or illicit drugs. SUDs comorbid with any anxiety disorders
Tickell, 1999). A better understanding of comorbidity is needed included agoraphobia, generalised anxiety disorders (GAD), panic
to identify the correlational and/or potential causal relationships disorder and social phobia. Mood disorders included bipolar disor-
among symptoms, disorders and treatment in comorbid patients. der, major depression and dysthymia.
Such knowledge will also make an important contribution to treat- The odds (or odds ratio, OR) of having major depression or any
ment and prevention strategies. anxiety disorder among individuals with alcohol or illicit drug use
In epidemiologic surveys, comorbid prevalence rates can be was used in the meta-analysis because it is not affected by differ-
expressed in two ways: the prevalence of SUDs among respondents ences in calculating prevalence rates of SUDs within populations
with a mental health disorder or the prevalence of psychiatric cases with mental health disorders or vice versa. The reason comorbidity
among respondents with a SUD. The prevalence rates between rates for major depression and any anxiety disorder were selected
the two populations can vary considerably due to their frequency for the meta-analysis was that they are commonly reported and
of occurrence. Take for instance the prevalence of major depres- comorbidity for specific psychiatric diagnoses or specific sub-
sion and illicit drug dependence reported by Grant et al. (2004). stances (cannabis, heroin, cocaine, etc.) are under reported. The
Amongst respondents with any drug dependence, the prevalence current review excludes studies of clinical or treatment-seeking
of major depression was ∼40%, whereas the prevalence of any populations as these will be the subject of subsequent reviews.
drug dependence amongst respondents with major depression Studies based within these clinical setting will have greater power
was 3.5%. Conversely, the prevalence of any SUD in respondents than general population surveys to reveal associations between
with mania was ∼30% compared to the prevalence of mania (∼5%) particular mental illnesses of low prevalence (schizophrenia, bipo-
in respondents with a SUD (Grant et al., 2004). Nonetheless, even lar disorders, etc.) and licit and illicit substance dependence. Thus,

Please cite this article in press as: Lai, H.M.X., et al., Prevalence of comorbid substance use, anxiety and mood dis-
orders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis. Drug Alcohol Depend. (2015),
http://dx.doi.org/10.1016/j.drugalcdep.2015.05.031
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the systematic literature search used in this review also used terms
to include surveys conducted in clinical settings reporting comor-
bid prevalence rates for low prevalence SUD and mental health
disorders to be used in future reviews.
2. Methods
Methods were based on the Preferred Reporting Items for Systematic Reviews
and Meta-analysis (PRISMA) guidelines (Liberati et al., 2009; Moher et al., 2009) and
guidelines for Meta-Analysis for Observational Studies in Epidemiology (MOOSE)
(Stroup et al., 2000).
2.1. Data sources and search strategy
A computerised search of the bibliographic databases MEDLINE, PsychINFO,
EMBASE and CINAHL was conducted in September 2014 by GEH using subject
heading or free text terms to reflect differences in indexing among databases. The
following set of terms were used in the various searches: diagnosis, dual diagnosis
(psychiatry), OR comorbidity OR co-occur AND (alcohol$ or drug$ or substance$)
OR (schizophren$ or psychosis or bipolar or depression or anxiety or PTSD or
mental$) AND (epidemiology or prevalence or incidence) NOT gambl* [all fields],
limit to English language and humans and year between 1990 and 2014. Other
searches using these databases used names of surveys and abbreviation (e.g., NCS,
National comorbidity survey; NESARC, National Epidemiological Survey on Alcohol
and Related Conditions, etc.). Further searches conducted using Medline, Scopus
and Web of Science for articles or citations to major review articles or publications
authored by key authors of major surveys and reviews (e.g., Reiger, Kessler, Grant,
Merikangas, De Graaf, Degenhardt, etc.) as well as hand searches of review articles
(Crawford et al., 2003) and National surveys. All references associated with these
studies were also reviewed to identify additional relevant sources in addition to an
independent search conducted by HMXL for a recent article regarding comorbidity
prevalence rates using similar key words (Lai and Sitharthan, 2012). A final search
was completed February 23, 2015 using PREMEDLINE and Medline daily update
(PUBMED) and the above keywords for any new material published up to December
31, 2014. All of the search results were entered into a reference manager to identify
duplicates and organise the source material based on selection criteria.
2.2. Selection criteria
Two raters independently excluded source material in the first and subsequent
rounds that was not relevant to the review. First round exclusions were based on the
article’s title. Any disagreement between raters or if there was uncertainty about
excluding the source, the abstract or full article was assessed in the next round.
Sources were chosen on the basis that they contained original research (review
papers were excluded) in defined populations, had sufficient subjects in the study
to be statistically meaningful (studies with less than 100 subjects were excluded),
and appeared to be relevant to the present review as they were conducted in large
randomly selected populations living within defined boundaries (cities, states or
countries) of males and females aged between 15 and 65 + years. In many of the
included studies, householders aged 18–20 and over were surveyed regarding all
household members. Thus, some studies reported slightly different age rangers
from 15 to 18 years onwards. Consequently, studies with limited age ranges were
excluded, such as a Finnish study which did not include 18–29 year olds and also
did not report comorbid prevalence rates (Pirkola et al., 2005) and the Zurich cohort
study which included 18–19 year olds followed for 15 years (Angst et al., 1984).
The reason studies with narrow age ranges or that included only one gender were
excluded was they do not represent national populations in relation to substance
use prevalence rates.
Only studies using face-to-face interviews were included in which diagnoses
were based on clinical interviews using structured diagnostic instruments such
as the Composite International Diagnostic Interview (CIDI) or similar set of inter-
view questions (Structured Clinical Interview for Diagnostic and Statistical Manual
of Mental Disorders, SCID or Schedule for Clinical Assessment in Neuropsychiatry,
SCAN) to determine psychiatric and SUDs using DSM or WHO-ICD criteria in general
populations (Samet et al., 2004).
Studies using non-standardised diagnostic criteria for substance use (e.g., heavy
or former drinkers) or psychiatric illness not based on structured diagnostic instru-
ments (Samet et al., 2004) were also excluded such as those based on clinician
or self-reports of increased symptoms or risk of developing a psychiatric illness.
Studies reporting prevalence rates for SUDs or mental health disorders separately
were excluded as prevalence of comorbidity required both a psychiatric and SUD
diagnosis within a defined population. Studies reporting prevalence rates for vari-
ous sub-groups (gender, age or racial groups) were excluded if they did not report
overall rates for the total sample. Any disagreements between raters were resolved
between three raters (GH, MC, HL).
Articles describing restricted samples (non-consecutive sampling or sub-groups
of a trial) using limited age ranges or demographics (student samples or professional
groups), those based on medical illnesses (HIV, asthma, diabetes, heart disease, etc.),
homelessness or gender specific samples (e.g., Veterans) were excluded as were
Please cite this article in press as: Lai, H.M.X., et al., Prevalence of comorbid substance use, anxiety and mood dis-
orders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis. Drug Alcohol Depend. (2015),
http://dx.doi.org/10.1016/j.drugalcdep.2015.05.031
3
studies only reporting nicotine dependence, non-Axis 1 DSM disorders (e.g., obses-
sive compulsive or personality disorders) or disorders of children or adolescents
(e.g., ADHD, anorexia nervosa) or geriatric populations. The rationale for excluding
children and adolescents is they are normally not interviewed for large face to face
surveys due to consent issues and diagnoses normally associated with adolescents
or older persons are often not reported in adult population surveys. Lastly, stud-
ies reporting prevalence rates based on retrospective reports from medical records,
data-based registers, opinions of case managers or other health professionals (e.g.,
Graham et al., 2001) or where there was no direct contact with subjects were also
excluded.
2.3. Data abstraction
The following information was extracted in the second round by two inde-
pendent researchers using a semi-structured form: name of study, authors, titles,
journal, year survey was conducted, sample size, the use of structured or semi-
structured methods for establishing the diagnosis of substance use and mental
health disorders, study population (random sample within a defined area and
setting) and country. Data abstraction for meta-analysis included comorbidity
prevalence, OR, 95% confidence interval, type of SUD (12-month or lifetime) within
groups of patients diagnosed with any anxiety disorder (agoraphobia, generalised
anxiety disorder (GAD), panic disorder and social phobia) or mood disorder (bipolar
disorder, dysthymia or major depression).
2.4. Risk of bias assessment
We conducted an assessment of the bias of included studies using a tool devel-
oped by Hoy et al. (2012) specifically for assessment of prevalence studies. This tool
comprises 10 items assessing external (selection and non-response bias) and inter-
nal validity (measurement bias and bias related to errors in analysis) and a summary
item on overall risk of study bias. Individual items are assessed as having low or high
risk of bias and the summary item is assessed as having low, medium or high over-
all risk of bias if further research is very unlikely, likely or very likely to change
the estimate, respectively. All included studies were assessed for risk of bias inde-
pendently by two reviewers. Surveys were rated medium risk of bias if they did not
survey or report illicit drug abuse or dependence, if some subjects were interviewed
face-to-face while others were interviewed by telephone, or if response rates var-
ied significantly between sites. High bias was recorded if the survey was confined
to one city or catchment area, but unlikely to be representative of the national (or
regional) population or if the survey was a non-random sample of households, but
conducted in public places.
2.5. Meta-analysis
Comprehensive Meta-Analysis version 2 (CMA, Biostat Eaglewood, NJ) was used
to convert raw data to odds ratios (ORs) and to calculate pooled ORs for differ-
ent sub-analyses. ORs were chosen as the effect size measure because they were
reported in most of the included studies. A random effects model was chosen over
a fixed effects model as prevalence rates would likely vary between populations of
different races, ages, nationalities and availability and exposure to licit and illicit
substances. Articles reporting 12-month and lifetime prevalence rates of abuse and
dependence and ORs from the same survey were collated to avoid duplications.
Where more than one rate was reported from a survey, the original report or one
with the greater accuracy or precision (significant decimals for each level of abuse or
dependence) was used in the meta-analysis. Surveys that did not provide co-morbid
prevalence rates or rates with missing limits or confidence intervals were excluded
if these could not be computed by other means as rates by themselves could not
be included in the meta-analysis without an error term or indication of variance.
To reduce the number of subgroup analyses given the myriad of psychiatric and
SUDs we performed meta-analyses of studies based on AUDs (12 month or lifetime,
abuse, abuse/dependence or dependence) or illicit drug use and their prevalence
within populations of respondents with major depression or any anxiety disorder.
In some DUD studies, illicit substances were listed according to DSM criteria (Grant
et al., 2004) while in others it was not clear which substances were included when
reporting drug addiction (Leray et al., 2011). Graphs were produced using Systat
(Version 8.0, SPSS) or CMA software.
3. Results
3.1. Search findings
A total of 1649 titles were found after removal of duplicates
from electronic searches (Fig. 1). Among them, 1254 articles were
judged not relevant by titles by two independent reviewers leaving
395 articles to be examined for comorbid prevalence rates. Of the
395 articles, 148 articles were judged by two independent review-
ers not relevant by viewing abstract (n = 18) or full text (n = 130)
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1649 titles located after removal of duplicates from MEDLINE,

PsychINFO, EMBASE, CINAHL (1980 to October 2014) using search
terms: Diagnosis, Dual (Psychiatry) OR (co-morbid or co-occur) AND
(alcohol$ or drug$ or substance$) OR (Schizophren$ or psychosis or
bipolar or depression or anxiety or PTSD or mental$) AND (epidemiology
Or prevalence OR incidence) NOT gambl* [all fields], Limit to English
language and humans and yr ‘1990-2015.’ Other searches using these
databases used names of surveys and abbreviations (e.g., NCS, National
comorbidity survey; NESARC, National Epidemiological Survey on
Alcohol and Related conditions etc). Further searches using Scopus and
Web of Science for citations to major review articles or key publications
authored by e.g., Kessler, Grant, Merikangas, De Graaf, Degenhardt etc
and hand searches of review articles and National surveys 1990-2014

1254 papers judged not relevant by title by two

independent reviewers

395 abstracts or full text examined for comorbid prevalence rates

148 papers judged not relevant by abstract or full text

247 papers examined in full text and classified according

to population setting

24 papers describing prevalence rates in primary care

settings

115 papers describing 34 papers describing prevalence rates amongst persons

prevalence rates attending drug and alcohol settings
amongst general
populations or 64 papers describing prevalence rates amongst persons
households attending inpatient or outpatient psychiatric settings

10 papers describing prevalence rates amongst persons

within forensic settings
27 unique surveys
describing prevalence
rates of community,
88 papers providing supplementary material to the
national or international
populations original surveys of comorbidity prevalence rates

22 surveys provided comorbidity data for

prevalence of psychiatric disorders
among people with substance and
alcohol use disorders

Fig. 1. Flow diagram of search strategies and results.

and the remaining 247 articles were classified according to popu-
lation setting. Of the 247 articles, there were 115 articles describing
prevalence rates amongst the general populations and the rest
were populations within primary care settings, SUD clinical sett-
ings, inpatient or outpatient psychiatric settings or forensic settings
(Fig. 1). Of the 115 articles surveying general populations or house-
holds, there were 27 unique surveys describing prevalence rates of
city, national or international populations with 88 papers providing
supplementary material reporting sub-group analyses of various
topics focusing on specific drugs of abuse or psychiatric diagnoses.
After the data extraction phase, five studies were not included in the
data analysis as they did not report any usable prevalence rates of
comorbid populations or based prevalence of alcohol dependence
on consumption or risk of dependence, not on diagnostic criteria
(Bromet et al., 2005; Bulloch et al., 2012; Degenhardt et al., 2008;
Medina-Mora et al., 2007; Vega et al., 2009), leaving 22 unique
surveys which were included in the meta-analyses.
3.2. Study characteristics
Sample size, characteristics of the respondents and design fea-
tures of the twenty-two included surveys are summarised in
Table 1. Sample sizes varied between 483 and 90,277 with a total
sample size of 504,319 for the 22 included surveys. Seven national
surveys from the USA were conducted between 1990 and 2009
(ECA, NCS, NCS-R, NLAES, NHSDA, NSAL, and NESARC, Table 1, study
numbers 2–7) with sample sizes between 9090 and 90,277 per-
sons. Six surveys took place in the UK or Europe (Munich, TACOS,

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orders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis. Drug Alcohol Depend. (2015),
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Table 1
Study characteristics of included studies of drug and alcohol misuse in general populations and mental health disorders by country.

Study name and related publications by country Surveyed Setting Sample size Disorders studied and diagnostic instruments used. Risk of
years country Age (range) bias assessment

Australia
1a. National Survey on Mental Health and Wellbeing 1997 Australia 10,641 Depression, anxiety and SUDs.
(NSMHWB)-1997). Wave 1 18–65+ CIDI-A (DSM IV/ICD-10).
(Teesson et al., 2000) (Burns and Teesson, 2002) Overall risk of bias: low.
1b. National Survey on Mental Health and Wellbeing 2007 Australia 8841 Depression, anxiety and SUDs.
(NSMHWB-2007). Wave 2 16–85 Lifetime and 12 month DSM-III, DSM-IV, ICD-10 diagnoses.
(Teesson et al., 2010; McEvoy et al., 2011) Overall risk of bias: low.

USA
2. Epidemiologic Catchment Area (ECA). 1980–1984 USA 20,291 SUDs and various mental disorders. DSM-III for lifetime
(Regier et al., 1990; Swendsen et al., 1998) Wave-II 18–65 and 6-month prevalence.
1985 Overall risk of bias: low.
3a. National Comorbidity Survey (NCS). 1991–1992 USA 8098 Lifetime and 12-month prevalence of substance or alcohol
(Kessler et al., 1996; Swendsen and Merikangas, 15–54 abuse/dependence and affective or anxiety disorders, CIDI,
2000) DSM-III-R.
Overall risk of bias: low.
3b. NCS replication (NCS-R). Kessler, 2003 (Kessler et al., 2001–2002 USA 9090 SUDs, major depression and anxiety disorders. WMH-CIDI,
2003, 2005; Merikangas et al., 1998, 2007) 18–60+ ICD-10 and DSM-IV.
Overall risk of bias: low.
4. National Longitudinal Alcohol Epidemiologic Survey 1992 USA 42,862 SUDs, major depression and anxiety disorders. DSM-IV.
(NLAES). (Grant, 1995) (Grant and Harford, 1995) 18–65+ Overall risk of bias: low.
(Hanna and Grant, 1997)
5a. National Household Survey on Drug Abuse (NHSDA) 1994–1996 USA 39,994 Depressive, anxiety, SUD syndromes or dependence.
(Kandel et al., 2001) (1997) 18–65+ Screening scales based on modified CIDI, DSM-III-R and
DSM-IV.
Overall risk of bias: low.
5b. NHSDA changed name to National Survey on Drug 2001–2002 USA 90,277 Serious mental health illness and SUD. DSM-IV, CIDI-SF,
Use and Health (NSDUH). 18–65+ Keesler Psychological Distress Scale (K6).
(Swartz and Lurigio, 2006) Overall risk of bias: low.
6. Collaborative Psychiatric Epidemiology Studies (CPES): 2000–2003 USA 19,729 Prevalence of lifetime mental disorders among individuals
Combined three surveys the National Study of 18–65+ with AUD, DUD or SUD. Racial comparisons among
American Life (NSAL), NCS-R and National Latino and Caucasian, Asian, Latino and Black Americans. Overall risk
Asian American Study (NLAAS); (Jackson et al., 2004; of bias: Medium; some interviews were conducted face to
Alegria et al., 2004; Mericle et al., 2012) face others via telephone.
7a. National Epidemiological Survey on Alcohol and 2001–2002 USA 43,093 Lifetime comorbidity of DSM-IV mood and anxiety
Related Conditions (NESARC) (Grant et al., 2004, (Wave 1) 18–65+ disorders.
2005a,b; Hasin et al., 2005; Conway et al., 2006; Overall risk of bias: low.
Compton et al., 2007)
7b. National Epidemiological Survey on Alcohol and 2004–2005 USA 34,653 DSM-IV Substance, mood and anxiety disorders. Wave 1
Related Conditions (NESARC). Wave 2 (Grant et al., (Wave 2) 21–65+ subjects are re-interviewed for wave 2.
2009) Overall risk of bias: low.

Racial populations within USA and other countries

8. Household survey, Puerto Rico (USA territory) 1984 Puerto 1551 DSM-III alcoholism, anxiety and depressive disorders using
(Canino et al., 1987; Swendsen et al., 1998) Rico 17–64 Spanish version, DIS
Overall risk of bias: Medium. Did not report separate
prevalence rates for alcohol abuse, dependence, only ORs.
Did not survey comorbid illicit drug use.
9. Mexican American Prevalence and Services (MAPS) Latino Fresno 2874–3012 WHO-CIDI/DSM-III-R lifetime mood or anxiety disorder.
Study (Vega et al., 1998, 2003; Merikangas et al., population (USA) 18–59 Compared native-born Latinos and immigrants with other
1998) ICPE subsample 1997 Hispanic samples.
Overall risk of bias: High as only one city sampled which
may not be representative of other Latino populations.
10. Korean Epidemiologic Catchment Area (KECA) (Cho 2000–2002 South 6275 Lifetime and 12 month DSM-IV disorders using
et al., 2007; Jeon et al., 2007; Chou et al., 2012) Korea 18–64 Korean-CIDI and AUD. Compared Native Koreans with
residents living in the USA, NESARC. Overall risk of bias:
Medium. Did not survey illicit drug use, only 12 month
AUDs. Did not report comorbid prevalence rates for AUD,
only ORs.

Canada
11. Mental Health Supplement to the Ontario Health 1990–1991 Ontario, 6902 Alcohol abuse/dependence with depression and anxiety,
Survey (OHS/OMHS) (Offord et al., 1996; Gratzer Canada 15–64 CIDI, alcohol use assessment and DSM-III-R.
et al., 2004; Merikangas et al., 1998). ICPE subsample Overall risk of bias: low.
12. Canadian Community Health Survey (CCHS 1.2): 2002 Canada 36,984 12 month prevalence of MDD and SUD.
Mental Health and Well-Being (Currie et al., 2005; 15–65+ Overall risk of bias: low.
Rush et al., 2008)

European countries
13. Munich follow-up study, phase 1 and 2 (Wittchen 1974 and Munich, 483 DSM-III, RDC and ICD-9 DIS interview, lifetime and 6
et al., 1992; Merikangas et al., 1996) 1981 Germany 25–65 month prevalence of affective, anxiety and SUDs. Seven
year follow-up of a random sample from West Germany.
Overall risk of bias: high; small follow-up sample unlikely
to be representative of all West Germans, no longer
relevant after re-unification of Germany.

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orders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis. Drug Alcohol Depend. (2015),
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Table 1 (Continued)

Study name and related publications by country Surveyed Setting Sample size Disorders studied and diagnostic instruments used. Risk of
years country Age (range) bias assessment

14. Transitions in Alcohol Consumption and Smoking 1996–1997 Germany 4074 DSM-IV, WHO CIDI alcohol use, abuse, dependence and
(TACOS) (Meyer et al., 2000; Bott et al., 2005) 18–64 any mental, affective or anxiety disorder. Overall risk of
bias: high, interviews were limited to one catchment area
in Northern Germany, Lubeck; excluded non-German
nationalities and did not survey illicit drug use.
15. Netherlands Mental Health Survey and Incidence 1996 Netherlands7076 12 month co-morbidity of mood, anxiety, psychotic and
Study (NEMESIS-wave 1 and 2) (Bijl et al., 1998; De Wave-2, 18–64 SUDs. CIDI, DSM-III-R. Wave-2 reported changes over time
Graaf et al., 2002; Merikangas et al., 1998; Ravelli 2007–2009 and incidence.
et al., 1998; Marquenie et al., 2007) Overall risk of bias: low.
16. The British Psychiatric Morbidity Survey (Farrell 1990–2000 United 10,018 Depression, anxiety and SUDs. Revised Clinical Interview
et al., 2001; Jenkins et al., 1997) King- 16–64 Scale (CIS-R), DIS and ICD-10.
dom Overall risk of bias: low.
17. France, Mental health in General Population 1999–2003 France 36,105 Face to face interviews from people recruited in street or
(MHGP) (Leray et al., 2011) 18–55+ public places using MINI, ICD-10 diagnoses of current or
last 6 months of anxiety disorders, major depressive
episode, alcohol abuse and drug addiction. Overall risk of
bias: high. Not a random sample of households, refusals in
public places were replaced by others. SUDs not well
defined as drug addiction and dependence are used
interchangeably and types of illicit drug use surveyed not
reported.

Other national or international surveys

18. Household survey, Brazil (Almeida-Filho et al., 2001 Salvador, 2306 Alcohol on anxiety and depression. Psychosomatic
2007) Brazil 20–55+ Anxiety-Depression (PSAD) subscale for DSM-III-R. Overall
risk of bias: high. Only one city in Brazil was surveyed,
poor external validity and DUDs were not surveyed.
19. Mexico: Epidemiology of Psychiatric Comorbidity 1995 Mexico 1734 Household survey using CIDI and DSM-III-R.
Project (EPM) (Caraveo-Anduaga and Bermudez, City 18–65 Response rate 60.4% and excluded non-urban areas.
2002; Merikangas et al., 1998) ICPE subsample Overall risk of bias: high. Low response rate and only one
city in Mexico was surveyed which excluded non-urban
and rural areas.
20. Thai National Mental Health survey (Suttajit et al., 2008 Thailand 17,140 Various mental disorders on alcohol or illicit drug use.
2012) 15–59 MINI International Neuropsychiatric Interview, DSM-IV.
Overall risk of bias: low. ORs reported here had to be
manually calculated.
21. Singapore Mental Health Study (Subramaniam 2009–2010 Singapore 6616 12month and lifetime prevalence of AUDs, MDD, BPD and
et al., 2012, 2013) 18–65+ anxiety disorders using CIDI, DSM-IV.
Overall risk of bias: medium. Did not survey DUDs and ORs
had to be manually calculated.
22. European Study of the Epidemiology of Mental 2000 Spain, 21,425 12 month mood, anxiety, AUDs. Computer assisted
Disorders (ESEMeD) (Alonso et al., 2004, 2007, 2011) Phase 2 France, 18–65+ WMH-CIDI providing DSM-IV and ICD-10. Overall risk of
2003 Belgium, Phase 2 bias: medium. Did not survey DUDs and due to low
Italy 8796 numbers, co-morbidities were combined for some
Germany, 18–65+ analyses. Mean response rate was 61.2% and varied
the between countries (46–79%).
Netherlands

AUD, alcohol use disorder; BPD, bipolar disorder; CIDI-A, automated version of the Composite International Diagnostic Interview (CIDI); CIDI-SF (short form); DIS, diagnostic
interview schedule; GAD, generalised anxiety disorder; MDD, major depressive disorder; SUD, substance use disorder; WMH-CIDI, World Mental Health-CIDI. For consistency,
some studies used modified age ranges (e.g., 18–54) when comparing multiple surveys.

NEMESIS, British Psychiatric Morbidity Survey, France (MHGP) and
ESEMeD (Table 1 studies 13–17, and 22). There were two Cana-
dian surveys, one in Ontario (OHS/OMHS) and another in several
provinces (CCHS 1.2) (Table 1, studies 11 and 12) and one in
Australia (NSMHWB) with surveys conducted in 1997 and 2007
(Table 1, study 1a and 1b). Other included surveys were of people
living in Puerto Rico, Mexican-Americans living in Fresno, sam-
ples from South Korea (KECA), Brazil (Salvador), Mexico City (EPM),
Thailand and Singapore (Table 1, studies 8–10, 18–21). Five surveys
were repeated using different subjects over two time points (e.g.,
Australia, wave 1 and 2 (study 1a and 1b), NCS, NSC-R (3a, 3b),
NHSDA, study 5a, 5b) and two re-surveyed the same subjects over
time (NESARC, 2002 and 2005 (study 7a, 7b); NEMESIS 1996 and
2008, study 15). Prevalence rates are reported for individual sites
within collaborative studies such as the International Consortium
in Psychiatric Epidemiology (ICPE) (Merikangas et al., 1998). Risk
of bias is reported on the last column of Table 1. Ten surveys were
rated as having low risk of bias, six with medium risk and 6 with
high risk of bias. The inter-rater reliability of assessing overall risk
of bias was high, with a kappa value of 0.86.
3.3. Prevalence rates
Fig. 2 shows 12 month and lifetime prevalence rates of AUDs
for various anxiety and mood disorders from the included stud-
ies. Many of the included studies reported comorbid prevalence
for a limited number of substances or psychiatric diagnoses which
are represented here to gauge the range of variability. Some of the
psychiatric diagnoses have narrow comorbid prevalence rates, for
example agoraphobia, general anxiety disorder (GAD), panic disor-
der, dysthymia and bipolar disorder while others show a wide range
of prevalence rates, for example AUDs and any anxiety disorder,
major depression or any mood disorder. There was a lot of overlap
of prevalence rates between alcohol use, abuse and dependence.
Fig. 3 shows 12 month and lifetime prevalence rates of illicit
DUDs for various anxiety and mood disorders. Some of the surveys
included a limited range of illicit substances (usually cannabis
and a combination of others) while others reported individual
prevalence rates for each illicit drug. Similar to alcohol use,
comorbid illicit drug use prevalence rates had a relatively narrow
range for anxiety disorders, dysthymia and bipolar disorders and

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orders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis. Drug Alcohol Depend. (2015),
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Fig. 2. Prevalence estimates of mood and anxiety disorders of community respon-
dents with AUDs. Each circle, square or diamond represents an estimate from a
survey for alcohol use, abuse or dependence respectively. Open symbols indicate 12
month estimates and filled symbols indicate lifetime estimates.
Fig. 3. Prevalence estimates of mood and anxiety disorders of community respon-
dents with DUDs. Each circle, square or diamond represents an estimate from a
survey for any illicit drug use, abuse or dependence disorder, respectively. Open
symbols indicate 12 month estimates and filled symbols indicate lifetime estimates.
relatively wide rates for major depression or any anxiety or mood
disorder.
3.4. Meta-analysis
Fig. 4 shows the forest plots and ORs for AUDs (abuse,
abuse/dependence and dependence) and any anxiety disorder.
Meta-analysis found the pooled OR of any anxiety disorder and
alcohol abuse of 1.636 (95% confidence interval (CI) 1.317–2.031),
for abuse/dependence the OR was 2.088 (95% CI 2.007–2.172) and
for alcohol dependence it was 2.532 (95% CI 2.243–2.859). The point
estimate for the 31 studies indicated a pooled OR of 2.111 (95% CI
2.034–2.190, Z = 39.62, P < 0.0001) for AUDs and any anxiety dis-
order. ORs based on lifetime AUDs (15 studies, OR 2.048, 95% CI
1.859–2.257) were similar to 12-month AUD estimates (16 studies,
OR 2.195, 95% CI 1.894–2.544, P = 0.443).
Fig. 5 shows the forest plots and ORs for AUDs (abuse,
abuse/dependence and dependence) and major depression.
Please cite this article in press as: Lai, H.M.X., et al., Prevalence of comorbid substance use, anxiety and mood dis-
orders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis. Drug Alcohol Depend. (2015),
http://dx.doi.org/10.1016/j.drugalcdep.2015.05.031
7
Meta-analysis found the pooled OR of major depression and
alcohol abuse of 1.532 (95% CI 1.203–1.951), for abuse/dependence
it was 2.53 (95% CI 2.291–2.796) and for alcohol dependence it
was 3.094 (95% 2.377–4.027). The point estimate for the 34 studies
indicated a pooled OR of 2.423 (95% CI 2.222–2.644, Z = 19.95,
P < 0.001) for AUDs and major depression. ORs based on lifetime
AUDs (13 studies, OR 2.032, 95% CI 1.62–2.54) were not signifi-
cantly different to 12-month AUD estimates (21 studies, OR 2.648,
95% CI 2.265–3.095, P = 0.058).
Fig. 6 shows the forest plots and ORs for illicit drug use disor-
ders (abuse, abuse/dependence and dependence) and any anxiety
disorder. Meta-analysis found the pooled OR of any anxiety dis-
order with illicit drug abuse of 2.355 (95% CI 2.016–2.752), for
abuse/dependence the OR was 2.144 (95% CI 1.171–3.927) and for
drug dependence it was 4.194 (95% 3.447–5.104). The point esti-
mate for the 16 studies indicated a pooled OR of 2.907 (95% CI
2.58–3.277, Z = 17.49, P < 0.001) for illicit drug use and any anxiety
disorder. ORs based on lifetime DUDs (10 studies, OR 3.083, 95% CI
2.662–3.572) were similar to 12-month DUD estimates (6 studies,
OR 2.748, 95% CI 1.90–3.975, P = 0.570).
Fig. 7 shows the forest plots and ORs for illicit DUDs (abuse,
abuse/dependence and dependence) and major depression. Meta-
analysis found the pooled OR of major depression with illicit drug
abuse of 2.601 (95% CI 1.715–3.944), for abuse/dependence it was
4.319 (95% CI 3.082–6.054) and for drug dependence it was 4.825
(95% 3.013–7.725). The point estimate for the 18 studies indicated
a pooled OR of 3.803 (95% CI 3.024–4.782, Z = 11.428, P < 0.001) for
illicit drug use and major depression. ORs based on lifetime DUDs
(10 studies, OR 3.032, 95% CI 2.114–4.349) were lower compared
to 12-month estimates (8 studies, OR 5.390, 95% CI 3.901–7.447,
P = 0.020).
4. Discussion
This systematic review and meta-analyses found strong associ-
ations between co-occurring SUDs with major depression and any
anxiety disorder. The strongest associations were found between
illicit drug use and major depression (pooled OR 3.803), followed
by illicit drug use and any anxiety disorder (pooled OR 2.907), alco-
hol use and major depression (pooled OR 2.423) and alcohol use
and any anxiety disorder (pooled OR 2.111). Sub-analyses indicated
ORs for AUDs and DUDs were higher for dependence than those for
abuse for major depression and any anxiety disorder, irrespective
of diagnoses based on lifetime or 12-month prevalence.
4.1. Alcohol use disorders comorbid with anxiety and major
depressive disorders
Anxiety disorders are highly associated with AUDs and this was
confirmed in the meta-analysis (Fig. 4). The OR for any anxiety dis-
order and alcohol abuse was 1.636 and the association was stronger
for alcohol dependence (OR 2.532). Closer inspection of the for-
est plots show five of the 31 estimates reported non-significant
associations (ORs or 95% CIs ≤ 1.0) which included one study from
South Korea for abuse and dependence estimates (Chou et al.,
2012), and three studies conducted in Germany (Bott et al., 2005),
the Netherlands (NEMESIS) (Merikangas et al., 1998; Ravelli et al.,
1998) and USA (NESARC) (Grant et al., 2004).
Major depression and alcohol dependence have been found
to co-occur at higher than expected rates in many epidemiologi-
cal studies (Kessler et al., 1994; Merikangas and Gelernter, 1990;
Regier et al., 1990; Ross et al., 1988). Lifetime prevalence of AUDs
in respondents with major depressive disorders has been reported
to be as high 40% (Grant and Harford, 1995; Hasin et al., 2005) and
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Alcohol use and any anxiety disorder

Group by Study name Statistics for each study Odds ratio and 95% CI
use vs dependence
Odds Lower Upper
ratio limit limit
Abuse NESARC-Grant 2004a 1.100 0.915 1.322
Abuse France-Leray 2001a 1.700 1.422 2.032
Abuse Korea, KECA-Chou 2012a 1.830 0.650 5.156
Abuse Fresno, MAPSS-Merikangas 19981.800
b 1.325 2.446
Abuse Mexico, EPM-Merikangas 1998b 1.700 1.106 2.614
Abuse NEMESIS-Merikangas 1998b 1.000 0.784 1.275
Abuse Ontario,-Merikangas 1998b 2.200 1.831 2.644
Abuse NCS-Merikangas 1998b 2.100 1.819 2.425
Abuse Germany, TACOS-Bott 2005b 1.330 0.839 2.108
Abuse Australia-Teesson 2010e 3.000 1.464 6.148
Abuse 1.636 1.317 2.031
Abuse/dependence Australia-Burns 2002c 3.300 2.238 4.866
Abuse/dependence Australia-Teeson 2010c 2.600 1.916 3.529
Abuse/dependence ECA-Swendsen 1998c 2.100 2.060 2.140
Abuse/dependence NCS-Swendsen 1998c 2.380 1.773 3.195
Abuse/dependence Puerto Rico-Swendsen 1998c 3.260 1.777 5.980
Abuse/dependence NESARC-Grant 2004c 1.700 1.472 1.963
Abuse/dependence Korea, KECA-Chou 2012c 2.230 1.029 4.834
Abuse/dependence Thailand-Suttajit 2012c 1.790 1.314 2.438
Abuse/dependence ECA-Swendsen 1998d 2.080 2.040 2.120
Abuse/dependence NCS-Swendsen 1998d 2.160 1.809 2.579
Abuse/dependence Puerto Rico-Swendsen 1998d 2.490 1.433 4.328
Abuse/dependence 2.088 2.007 2.172
Dependence NHSDA-Kandel 2001e 4.000 2.905 5.509
Dependence NESARC-Grant 2004e 2.600 2.227 3.036
Dependence Korea-KECA-Chou 2012e 2.320 0.896 6.009
Dependence Brazil-Almeida-Filho 2007e 2.860 1.229 6.655
Dependence Fresno, MAPSS-Merikangas 1998f2.700 2.041 3.572
Dependence Mexico, EPM-Merikangas 1998f 2.700 1.989 3.665
Dependence NEMESIS-Merikangas 1998f 1.800 1.353 2.394
Dependence Ontario-Merikangas 1998f 2.500 2.058 3.037
Dependence NCS-Merikangas 1998f 2.200 1.918 2.524
Dependence Germany, TACOS-Bott 2005f 2.680 1.770 4.059
Dependence 2.532 2.243 2.859
Overall 2.111 2.034 2.190
0.1 0.2 0.5 1 2 5 10

No alcohol use Alcohol use

Fig. 4. Forest plot of the random effects meta-analysis of AUDs and any anxiety disorder. Comparisons are made between subgroups based on severity of alcohol use.
Summary statistics are indicated by filled diamonds for studies reporting alcohol abuse (a, b), abuse/dependence (c, d) and dependence (e, f). Estimates for 12 month (a, c, e)
and lifetime (b, d, f) estimates were pooled within each diagnostic group.

within respondents with alcohol disorder a prevalence as high as
35% has been reported (Mericle et al., 2012).
The pooled OR for major depression and alcohol abuse was 1.532
(95% CI 1.203–1.951) and the association was strongest for alcohol
dependence (OR 3.094, 95% CI 2.377–4.027) (Fig. 5). Eight of the 34
studies contributing to this meta-analysis reported non-significant
associations which included one study from South Korea for 12
month alcohol abuse and dependence (Chou et al., 2012), the sec-
ond wave of the Australian survey for 12 month abuse/dependence
and dependence (Teesson et al., 2010), surveys from the USA for12
month (NESARC) (Grant et al., 2004) and lifetime alcohol abuse
(NCS) (Swendsen and Merikangas, 2000) and one study from Puerto
Rico (Swendsen et al., 1998) and another from Munich (Merikangas
et al., 1996) who reported non-significant associations between
alcohol abuse/dependence and major depression.
the second wave Australian national survey (McEvoy et al., 2011).
All of the other prevalence studies reported significant associa-
tions between illicit drug abuse and dependence and any anxiety
disorder.
Major depression and illicit drug use have been shown to have
the strongest associations based on surveys conducted in general
populations (Conway et al., 2006; Grant et al., 2004; Swendsen and
Merikangas, 2000). All of the 18 studies used in the meta-analysis
reported significant associations between illicit drug use and major
depression. The pooled OR for illicit drug use and major depression
was 3.803 (95% CI 3.024–4.782) and the association was strongest
for drug dependence (OR 4.825, 95% CI 3.013–7.725).
4.3. Understanding and treating comorbidity

Comorbidity is important because it is the rule rather than the

4.2. Illicit drug use disorders comorbid with anxiety and major
depressive disorders
Anxiety disorders are highly associated with illicit drug use
especially in those with lifetime drug dependence where almost
50% have a comorbid disorder (Fig. 3) (Merikangas et al., 1998)
and this was confirmed in the meta-analysis (Fig. 6). The pooled
OR for illicit drug use and any anxiety disorder was 2.907 (95% CI
2.58–3.277) and the association was strongest for drug use depend-
ence (OR 4.194, 95% CI 3.447–5.104). Closer inspection of the forest
plots show that only one of the 16 studies reported a non-significant
association and this was for 12 month drug abuse/dependence from
exception with mental health disorders. Internalising disorders
such as anxiety and depression function from childhood to adult-
hood and comorbidity seems to be a function of age (Eaton et al.,
2013). In terms of externalising disorders, substance abuse shows
a strong pattern of development from substance use to abuse or
dependence starting in early adolescence and young adulthood in
some individuals that may influence the timing of the onset of a
comorbid disorder (Cerda et al., 2008). The strength of the causal
link depends on whether the two disorders persist after accounting
for other risk factors (Kushner et al., 2000). Understanding why and
how different disorders co-occur may provide new information for
prevention to intervene to reduce their use of alcohol and other

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orders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis. Drug Alcohol Depend. (2015),
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Alcohol use and major depression

Group by Study name Statistics for each study Odds ratio and 95% CI
use vs dependence
Odds Lower Upper
ratio limit limit
Abuse NLAES-Grant 1995a 2.240 1.741 2.882
Abuse NESARC-Grant 2004a 1.200 0.980 1.470
Abuse Korea, KECA-Chou 2012a 4.140 0.899 19.057
Abuse ESEMeD-Alonso 2004a 2.600 1.766 3.827
Abuse NCS-Swendsen 2000b 0.900 0.687 1.178
Abuse NLAES-Swendsen 2000b 1.700 1.510 1.913
Abuse NESARC-Hasin 2005b 1.200 1.104 1.305
Abuse 1.532 1.203 1.951
Abuse/dependence Australia-Burns 2002c 3.400 2.306 5.013
Abuse/dependence Australia-Teeson 2010c 1.200 0.710 2.028
Abuse/dependence ECA-Swendsen 1998c 3.010 2.897 3.127
Abuse/dependence NCS-Swendsen 1998c 2.270 1.727 2.984
Abuse/dependence Puerto Rico-Swendsen 1998c 1.250 0.459 3.403
Abuse/dependence NLAES-Grant 1995c 3.650 3.120 4.270
Abuse/dependence NESARC-Grant 2004c 2.300 2.017 2.622
Abuse/dependence Korea, KECA-Chou 2012c 3.630 1.073 12.277
Abuse/dependence Thailand-Suttajit 2012c 1.890 1.448 2.467
Abuse/dependence ECA-Swendsen 1998d 2.920 2.865 2.976
Abuse/dependence NCS-Swendsen 1998d 2.070 1.700 2.520
Abuse/dependence Puerto Rico-Swendsen 1998d 2.800 1.181 6.637
Abuse/dependence NLAES-Grant 1995d 3.560 3.287 3.856
Abuse/dependence NESARC-Hasin 2005d 1.900 1.709 2.112
Abuse/dependence Munich-Merikangas 1996d 1.100 0.635 1.905
Abuse/dependence Singapore-Subamaniam 2012d 3.100 1.790 5.369
Abuse/dependence 2.530 2.291 2.796
Dependence Australia-Teesson 2010e 1.500 0.574 3.921
Dependence NLAES-Grant 1995e 4.240 3.507 5.126
Dependence NHSDA-Kandel 2001e 4.100 3.001 5.602
Dependence NESARC-Grant 2004e 3.700 3.106 4.408
Dependence Korea-KECA-Chou 2012e 2.960 0.751 11.661
Dependence Canada, CCHS-Currie 2005e 2.300 1.703 3.106
Dependence Brazil-Almeida-Filho 2007e 4.100 1.773 9.479
Dependence ESEMeD-Alonso 2004e 6.700 3.120 14.390
Dependence NCS-Swendsen 2000f 2.000 1.569 2.550
Dependence NLAES-Swendsen 2000f 3.800 3.469 4.163
Dependence NESARC-Hasin 2005f 1.900 1.709 2.112
Dependence 3.094 2.377 4.027
Overall 2.423 2.222 2.644
0.1 0.2 0.5 1 2 5 10

No alcohol use Alcohol use

Fig. 5. Forest plot of the random effects meta-analysis of AUDs and major depression. Comparisons are made between subgroups based on severity of alcohol use. Summary
statistics are indicated by filled diamonds for studies reporting alcohol abuse (a, b), abuse/dependence (c, d) and dependence (e, f). Estimates for 12 month (a, c, e) and lifetime
(b, d, f) estimates were pooled within each diagnostic group.

Illicit drug use and any anxiety disorder

Group by Study name Statistics for each study Odds ratio and 95% CI
use vs dependence
Odds Lower Upper
ratio limit limit
Abuse NESARC-Grant 2004a 1.700 1.307 2.212
Abuse France-Leray 2011a 2.100 1.782 2.475
Abuse Frenso, MAPSS-Merikangas 1998b 3.100 2.192 4.384
Abuse Mexico, EPM-Merikangas 1998b 2.800 1.080 7.262
Abuse NEMESIS-Merikangas 1998b 2.000 1.339 2.987
Abuse Ontario-Merikangas 1998b 2.900 2.401 3.502
Abuse NCS-Merikangas 1998b 2.500 2.177 2.870
Abuse 2.355 2.016 2.752
Abuse/dependence Australia,McEvoy 2011c 1.500 0.900 2.500
Abuse/dependence NESARC-Grant 2004c 2.800 2.270 3.454
Abuse/dependence 2.144 1.171 3.927
Dependence NESARC-Grant 2004e 6.200 4.409 8.718
Dependence NHSDA-Kandel 2001e 4.400 3.319 5.833
Dependence Fresno, MAPSS-Merikangas 1998f 4.000 2.661 6.012
Dependence Mexico, EPM-Merikangas 1998f 4.600 1.401 15.107
Dependence NEMESIS-Merikangas 1998f 5.200 3.319 8.147
Dependence Ontario-Merikangas 1998f 3.400 2.480 4.662
Dependence NCS-Merikangas 1998f 3.300 2.746 3.966
Dependence 4.194 3.447 5.104
Overall 2.907 2.580 3.277
0.1 0.2 0.5 1 2 5 10

No drug use Drug use

Fig. 6. Forest plot of the random effects meta-analysis of illicit DUDs and any anxiety disorder. Comparisons are made between subgroups based on severity of drug use.
Summary statistics are indicated by filled diamonds for studies reporting drug abuse (a, b), abuse/dependence (c, d) and dependence (e, f). Estimates for 12 month (a, c, e)
and lifetime (b, d, f) estimates were pooled within each diagnostic group.

Please cite this article in press as: Lai, H.M.X., et al., Prevalence of comorbid substance use, anxiety and mood dis-
orders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis. Drug Alcohol Depend. (2015),
http://dx.doi.org/10.1016/j.drugalcdep.2015.05.031
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Illicit drug use and major depression

Group by Study name Statistics for each study Odds ratio and 95% CI
use vs dependence
Odds Lower Upper
ratio limit limit
Abuse NLAES-Grant 1995a 5.300 3.970 7.076
Abuse NESARC-Grant 2004a 2.500 1.897 3.295
Abuse NCS-Swendsen 2000b 1.600 1.131 2.263
Abuse NLAES-Swendsen 2000b 3.300 2.833 3.844
Abuse NESARC-Hasin 2005b 1.700 1.510 1.913
Abuse 2.601 1.715 3.944
Abuse/dependence NLAES-Grant 1995c 7.200 5.723 9.059
Abuse/dependence NESARC-Grant 2004c 4.200 3.396 5.194
Abuse/dependence NLAES-Grant 1995d 5.240 4.732 5.802
Abuse/dependence NESARC-Hasin2005d 2.000 1.600 2.500
Abuse/dependence ECA-Merikangas 1996d 4.100 3.331 5.047
Abuse/dependence Munich-Merikangas 1996d 5.600 2.535 12.371
Abuse/dependence 4.319 3.082 6.054
Dependence NLAES-Grant 1995e 11.160 8.030 15.510
Dependence NHSDA-Kandel 2001e 4.200 3.233 5.456
Dependence NESARC-Grant 2004e 9.000 6.439 12.580
Dependence CCHS-Currie 2005e 4.300 2.710 6.824
Dependence NCS-Swendsen 2000f 2.000 1.519 2.633
Dependence NLAES-Swendsen 2000f 6.900 6.052 7.867
Dependence NESARC-Hasin 2005f 2.500 2.092 2.988
Dependence 4.825 3.013 7.725
Overall 3.803 3.024 4.782
0.1 0.2 0.5 1 2 5 10

No drug use Drug use

Fig. 7. Forest plot of the random effects meta-analysis of illicit DUDs and major depression. Comparisons are made between subgroups based on severity of drug use.
Summary statistics are indicated by filled diamonds for studies reporting drug abuse (a, b), abuse/dependence (c, d) and dependence (e, f). Estimates for 12 month (a, c, e)
and lifetime (b, d, f) estimates were pooled within each diagnostic group.

drugs before abuse and dependence develop (Kendler et al., 2011;
Kushner et al., 2012).
There are numerous guidelines and reviews summarising the
management and treatment of patients with a dual diagnosis
which include psychosocial or integrated share-care approaches
or treatment in parallel systems (Drake et al., 2008; Horsfall et al.,
2009; Mills et al., 2009; Tiet and Mausbach, 2007). Comorbidity
in patients with serious mental illness is difficult to treat as there
are many service barriers that need to be overcome (McGovern
et al., 2006; Mills et al., 2012). Obviously there is no “one-size-fits-
all” treatment package for patients with a dual diagnosis (Torrens
et al., 2012), but there are a number of guiding principals that
include, engagement, adopting a non-judgemental attitude, holis-
tic approach that is client-centred (Mills et al., 2009). Frequently,
service delivery to patients are often managed by different sets
of clinicians or treating teams, some focussing on optimal medi-
cation treatment for mental health and others for substance use
issues depending upon conditions requiring the most immediate
attention (Pettinati et al., 2013). A recent Cochrane review found
no compelling evidence to support any one psychosocial treat-
ment over another for people with both severe mental illness and
substance misuse (Hunt et al., 2013) suggesting more research is
required in these difficult to treat patients.
4.4. Strengths and limitations
The epidemiological studies used in these meta-analyses show
consistently strong associations between SUDs, mood and anxiety
disorders. This meta-analysis was facilitated by relatively consis-
tent methods conducting large surveys, using random sampling of
households, face-to-face interviews and standardised methods to
formulate SUDs and psychiatric diagnoses. There are several lim-
itations common to the above studies that have been noted by
Kessler et al. (2011) which include; diagnoses were often based
on lay interviews which are unable to clarify differential diagno-
sis leading to inflated estimates of prevalence and comorbidity
between disorders. Data were combined across countries with very
different cultures and across surveys with different response rates,
which could have introduced selection bias. Lifetime diagnoses
were based on retrospective reports rather than prospective assess-
ments that may under estimate prevalence. As with all population
surveys, it could not take into account treatment history which may
influence prevalence rates through early intervention programmes.
This could interrupt the progression of co-morbidity and thereby
distort estimates of predictive associations (Kessler et al., 2011). In
addition, some of the prevalence estimates were adjusted for demo-
graphic and socioeconomic variables while others were not and
rates for genders and age groups were combined so care needs to
be taken when generalising results to specific populations as males,
on average, have higher 12-month and lifetime rates of alcohol and
other SUDs than females and illicit drug use is more common in
early adulthood (Grant, 1995; Kessler et al., 1994).
Although the selected studies employed high-quality methodol-
ogy with reasonably large samples, or used statistical techniques to
correct regional and other sampling variations, there are no estab-
lished standards for evaluating observational studies such as those
that are available for the evaluation of study quality in interventions
research (Dickersin, 2002). The risk of bias assessment showed that
ten of the studies were given an overall low risk of bias inferring
that further research is very unlikely to change the confidence in
the estimates of prevalence for a given population within the time-
frame it was conducted (Hoy et al., 2012). However, others were
given a medium to high risk of bias beause of procedural flaws in
the design, conduct or size of the sample population that limit the
generalisability and accuracy of the study findings and this may
have contributed to some heterogeniety of the studies. In addition,
these studies used various methodologies to formulate diagnoses
using different versions of DSM or ICD diagnostic criteria and the
quality of the interviews varied from the more comprehensive
interviews using the CIDI that may be less accurate in diagnosing
SUDs and specific psychiatric disorders criteria (Rosenthal et al.,
2012). Morevoer, some studies were more comprehensive when
combining diagnoses used for reporting prevalence rates for any
anxiety disorder; e.g., some included PTSD while some reported
lifetime psychiatric disorders and 12 month SUDs when reporting
comorbidity that may be prone to selective reporting and do not

Please cite this article in press as: Lai, H.M.X., et al., Prevalence of comorbid substance use, anxiety and mood dis-
orders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis. Drug Alcohol Depend. (2015),
http://dx.doi.org/10.1016/j.drugalcdep.2015.05.031
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H.M.X. Lai et al. / Drug and Alcohol Dependence xxx (2015) xxx–xxx
take into consideration temporal patterns for SUDs. Moreover, all
included studies were cross-sectional and so onset and causuality
can not be determined.
Meta-analysis on individual anxiety disorders (agoraphobia,
GAD, panic disorder and social phobia) and mood disorders (bipo-
lar disorder, dysthymia) comorbid with AUDs and specific DUDs
are not reported here or people attending drug and alcohol sett-
ings, inpatient or outpatient psychiatric settings or those within
forensic settings as they will be subject of subsequent reviews. In
addition, this analysis grouped illicit substances together without
taking into consideration types of substance use may differ widely
between countries and over time. For example, worldwide cannabis
is the most widely used illicit substance, however this may not be
true for all countries as shown in Thailand where kratom leaves
(Mitragyna speciosa Korth) were the most commonly used illicit
substance followed by methamphetamine and cannabis (Suttajit
et al., 2012). Finally, the results do not take into consideration an
individual may have more than one comorbidity, such as having
both AUD and a DUD, or major depression and an anxiety disorder,
or other combinations as these disorders tend to cluster in some
people (Rosenthal et al., 2012).
5. Conclusion
This systematic review of epidemiological studies in general
populations over the last 25 years shows comorbidity between
SUDs, mood and anxiety disorders are highly prevalent across
countries. The meta-analysis revealed that people with an alco-
hol use disorder (abuse or dependence) were 2.1 times of greater
risk of having any anxiety disorder compared to those without an
AUD and this association was higher for AUDs and major depres-
sion showing that the risk of having major depression is 3.10 more
likely for a person with alcohol dependence compared to someone
without an AUD. The literature shows substantial recent progress in
investigating the patterns and implications of comorbidity between
mental health disorders and SUDs. The issue has now been recog-
nised worldwide as a factor that affects the profile, course, patterns,
severity and outcomes of these disorders. In addition, there is an
urgent need for more prospective data on the full range of dis-
orders and specific subtypes as little attention has been paid to
broaden patterns of comorbidity in studies examining the associa-
tion between specific psychiatric and comorbid SUDs (Hall et al.,
2009; Kessler, 2004). Further surveys are needed using DSM-5
criteria given the continuum of severity of AUDs and DUDs will be
rated mild, moderate and severe rather than a simple binary split
between abuse and dependence. Furthermore, prospective studies
are needed to help understand comorbidity and course of illness to
assess temporal patterns and causal relationships between disor-
ders to help develop better interventions in treating persons with
comorbid disorders.
Authors disclosures
Authors have nothing to disclose.
Role of funding source
No financial support was received for this study. Portions of
these data were used for the submission of a dissertation by HL
for a doctorate of philosophy.
Contributors
HL and GH were responsible for the development of the research
question, article searching, interpretation of the data and writing
Please cite this article in press as: Lai, H.M.X., et al., Prevalence of comorbid substance use, anxiety and mood dis-
orders in epidemiological surveys, 1990–2014: A systematic review and meta-analysis. Drug Alcohol Depend. (2015),
http://dx.doi.org/10.1016/j.drugalcdep.2015.05.031
11
the draft manuscript. HL, GH and MC were responsible for screening
articles and data extraction. GH and MC conducted the assessment
of bias. GH performed the meta-analysis and produced the figures.
TS was responsible for the development of the research question,
critical revision of the manuscript and was the primary supervisor
of the project. All authors have reviewed and approved the final
manuscript.
Conflict of interest
No conflict declared.
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