University of Groningen
ADHD & Addiction
van Emmerik-van Oortmerssen, Katelijne
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date: 2018
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
van Emmerik-van Oortmerssen, K. (2018). ADHD & Addiction: Prevalence, diagnostic assessment and treatment of ADHD in substance use disorder patients. Rijksuniversiteit Groningen.
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
ADHD & ADDICTION
prevalence, diagnostic
assessment and treatment
of ADHD in substance use
disorder patients
Katelijne van Emmerik-van Oortmerssen
The research described in this thesis was financially supported by Fonds NutsOhra (project number 1001-036).
ISBN: 978-94-034-0662-6
ISBN: 978-94-034-0661-9 (Electronic version)
Cover design and lay-out: Debbie Hesseling | The Fat Moose. Printed by: ProefschriftMaken.
© Copyright 2018: K. van Emmerik-van Oortmerssen, Amsterdam, the Netherlands.
All rights reserved. No part of this thesis may be reproduced, distributed, stored in a retrieval system, or transmitted in any form or by any means, without prior written permission of the author.
ADHD & Addiction
Prevalence, diagnostic assessment and treatment of ADHD in substance
use disorder patients
Proefschrift
ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen
op gezag van de
rector magnificus prof. dr. E. Sterken en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op woensdag 20 juni 2018 om 14.30 uur
door
Katelijne van Oortmerssen
geboren op 26 oktober 1978Promotores
Prof. dr. R.A. Schoevers
Prof. dr. W. van den Brink
Copromotor
Dr. E. Vedel
Beoordelingscommissie
Prof. dr. P.J. Hoekstra
Prof. dr. O.M. Tucha
Prof. dr. V.M. Hendriks
11 17 33 53 73 91 113 135 TABLE OF CONTENTS Prologue
Part I: General introduction
Chapter 1: General Introduction to this thesis
Chapter 2: An introduction to ADHD and addiction
In: Dom G, Moggi F, eds. Co-occurring addictive and psychiatric disorders: a practice-based handbook from a European perspective. Berlin: Springer-Verlag; 2015: 179-191.
Part II: Prevalence of ADHD and additional comorbidities in SUD pa-tients
Chapter 3: Prevalence of attention-deficit hyperactivity disorder in substance
In: Dom G, Moggi F, eds. Co-occurring addictive and psychiatric disorders: a practice-based handbook from a European perspective. Berlin: Springer-Verlag; 2015: 179-191.
Chapter 4: The International ADHD in Substance use disorders Prevalence
study: background, methods and study population
Int J Methods Psychiatr Res. 2013;22(3):232-244.
Chapter 5: Variability in the prevalence of adult ADHD in treatment seeking
substance use disorder patients: results from an international multi-center study exploring DSM-IV and DSM-5 criteria.
Drug Alcohol Depend. 2014;134:158-166.
Chapter 6: Psychiatric comorbidity in treatment-seeking substance use
disorder patients with and without attention deficit hyperactivity disorder: results of the IASP study
Addiction. 2014;109(2):262-272.
Part III: Diagnostic assessment and Integrated treatment of ADHD in SUD patients
Chapter 7: Investigating the efficacy of integrated cognitive behavioral
therapy for adult treatment seeking substance use disorder patients with comorbid ADHD: study protocol of a randomized controlled trial
BMC Psychiatry. 2013;13:132.
Chapter 8: Diagnosing ADHD during active substance use: feasible or
flawed?
149 169 179 199 225 229 237 243 249
Chapter 9: Integrated cognitive behavioral therapy for ADHD in adult
substance use disorder patients: results of a randomized clinical trial.
Submitted for publication
Chapter 10: Integrated cognitive behavioral therapy for patients with
Substance Use Disorder and comorbid ADHD: two case presentations
Addict Behav. 2015;45:214-217.
Chapter 11: Prediction of drop-out and outcome in integrated cognitive
behavioral therapy for ADHD and SUD: Results from a randomized clinical trial.
In preparation for submission.
Part IV: Summary and Discussion
Chapter 12: Summary and General Discussion
Epilogue Part V: Appendix
Samenvatting[Summary in Dutch]
Dankwoord[Acknowledgements in Dutch]
List of publications About the author
PROLOGUE
At the Jellinek Addiction Treatment Centre, we meet John for an intake. He has been drinking too much alcohol for a long time, and since he has less and less control of his drinking behavior, he is seeking help. John is a 34-year old single man; he finished higher education although it took considerable effort, and has had many short jobs since then. He is very talkative, restless and inpatient during intake, and confirms that he has been like this all his life. He is also suffering from concentration problems since childhood. These symptoms lead us to suspect the presence of a comorbid diagnosis of ADHD, and raise a couple of questions:
• What is the chance that John has a comorbid diagnosis of ADHD?
• If John has comorbid ADHD, does that mean that he differs from patients without ADHD in terms of complexity?
• What is the optimal timing for administering a diagnostic assessment of ADHD? • If John has a comorbid diagnosis of ADHD, what treatment can we offer him? • Do we know anything about the odds that John successfully completes treatment?
GENERAL INTRODUCTION
CHAPTER 1
GENERAL INTRODUCTION TO THIS THESIS
13 General Introduction To This Thesis
Substance use disorders (SUD) are a major public health problem worldwide. In Europe alone already 15 million people (3.4%) suffer from alcohol dependence, and more than one million
people are affected by drug dependence.1 The impact of SUD on the lives of patients who suffer
from it is huge, with often dramatic consequences for physical health, psychological wellbeing,
interpersonal relationships, and employment.2
Over the last decades, research has contributed to a better insight in the etiology and pathophysiology of SUD and revealed potential targets for treatment with for example cognitive behavioral therapy (CBT), medication, and neuromodulation. Protocolized treatment programs are available in many countries. Still, recovery from addiction is difficult and relapse is the rule rather than the exception. One of the complicating factors in SUD patients is the presence of comorbid psychiatric disorders. Attention Deficit Hyperactivity Disorder (ADHD), a neurodevelopmental
disorder associated with severe problems in several areas of functioning,3 is one of them.
During the period of my PhD research, I evaluated many adult SUD patients with ADHD symptoms at the Jellinek Addiction Treatment Centre. They told me in detail how their lives were often seriously affected by ADHD symptoms; many of them typically ended up without any diplomas in spite of sufficient intellectual capacities, had only short and under-level jobs, struggled with difficulties in relationships, had a history of failure and negative comments from others since childhood, and often had very low self-esteem. Importantly, alcohol and drugs such as cannabis were used to
calm down, but escalation of drug use often led to its own problems.4
This thesis aims to make a contribution to the epidemiology, recognition and treatment of ADHD in patients with a comorbid substance use disorder, and focuses on the following research questions: 1. What is the prevalence of ADHD in SUD patients and what are the factors that have an impact
on the prevalence?
2. Does the comorbidity profile of SUD patients with ADHD differ from SUD patients without ADHD?
3. Can ADHD be diagnosed during active substance use?
4. What is the efficacy of adding a shortened CBT specifically focusing on ADHD symptoms to regular therapy for SUD in patients with both conditions?
5. Which patient factors influence drop-out and efficacy of an integrated cognitive behavioral therapy for SUD and ADHD? Which patient factors are suitable for patient-treatment matching?
OUTLINE OF THIS THESIS
In Chapter 2 of this thesis, an overview is presented with information on the epidemiology of ADHD in SUD patients, neurobiological aspects, the clinical presentation, the diagnostic evaluation,
treatment options and prognosis. In chapter 3, we start with a meta-regression-analysis to
establish the prevalence of ADHD in treatment-seeking SUD patients with special attention for
predictors of the ADHD prevalence in treatment-seeking SUD patients. In chapter 4, we describe
the protocol of an international multi-center study, the International ADHD in Substance use disorder Prevalence (IASP) study with the same objective: establishing a prevalence of ADHD in treatment-seeking SUD patients, and examining the factors that influence this prevalence. The
14 Part I | CHAPTER 1
results of this study are presented in chapter 5. Data from this study are also used for chapter 6,
where we take a closer look at SUD patients with ADHD and examine if they are different from
non-ADHD SUD patients with respect to other comorbid conditions. Since we conclude that ADHD is a highly prevalent condition in SUD patients, that these double diagnosis patients are more complex with respect to additional comorbidities and that standard pharmacological interventions are not very effective in the treatment of either ADHD or SUD symptoms, we hypothesize that standard psychological SUD treatments might also not suffice to treat this group of patients. Subsequently, we develop an integrated treatment with cognitive behavioral therapy (CBT) aimed at reducing both SUD and ADHD symptoms. In chapter 7, the outlines of this therapy are presented, and the protocol of a randomized controlled
trial (RCT) to test the efficacy of this new treatment is described. Within the context of the RCT, in chapter 8, we examine whether diagnostic assessment of ADHD in SUD patients
can reliably be performed early after presentation at an addiction service, even in a period of continued substance use. In chapter 9, the results of the RCT are presented. In chapter 10, we take a closer look at two patients who participated in this study, by describing the
course of treatment of a patient who completed the therapy successfully and a patient who dropped out in an early phase. In chapter 11, we try to identify factors that predict which
patients will benefit from the integrated therapy for SUD and ADHD, and which patients will drop out. Finally, in chapter 12, the main findings of this thesis and their clinical relevance
are discussed and viewed in the context of the literature on this subject. We conclude this chapter with limitations and recommendations for future research.
15 General Introduction To This Thesis
REFERENCES
1. Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jonsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21(9):655-679.
2. Degenhardt L, Whiteford HA, Ferrari AJ, Baxter AJ, Charlson FJ, Hall WD, Freedman G, Burstein R, Johns N, Engell RE, Flaxman A, Murray CJ, Vos T. Global burden of disease attributable to illicit drug use and dependence: findings from the Global Burden of Disease Study 2010. Lancet. 2013;382(9904):1564-1574.
3. Hoogman M, Bralten J, Hibar DP, Mennes M, Zwiers MP, Schweren LS, van Hulzen KJ, Medland SE, Shumskaya E, Jahanshad N, Zeeuw P, Szekely E, Sudre G, Wolfers T, Onnink AM, Dammers JT, Mostert JC, Vives-Gilabert Y, Kohls G, Oberwelland E, Seitz J, Schulte-Ruther M, Ambrosino S, Doyle AE, Hovik MF, Dramsdahl M, Tamm L, van Erp TG, Dale A, Schork A, Conzelmann A, Zierhut K, Baur R, McCarthy H, Yoncheva YN, Cubillo A, Chantiluke K, Mehta MA, Paloyelis Y, Hohmann S, Baumeister S, Bramati I, Mattos P, Tovar-Moll F, Douglas P, Banaschewski T, Brandeis D, Kuntsi J, Asherson P, Rubia K, Kelly C, Martino AD, Milham MP, Castellanos FX, Frodl T, Zentis M, Lesch KP, Reif A, Pauli P, Jernigan TL, Haavik J, Plessen KJ, Lundervold AJ, Hugdahl K, Seidman LJ, Biederman J, Rommelse N, Heslenfeld DJ, Hartman CA, Hoekstra PJ, Oosterlaan J, Polier GV, Konrad K, Vilarroya O, Ramos-Quiroga JA, Soliva JC, Durston S, Buitelaar JK, Faraone SV, Shaw P, Thompson PM, Franke B. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis. Lancet
Psychiatry. 2017;4(4):310-319.
4. Kronenberg LM, Slager-Visscher K, Goossens PJ, van den Brink W, van Achterberg T. Everyday life consequences of substance use in adult patients with a substance use disorder (SUD) and co-occurring attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD): a patient’s perspective.
CHAPTER 2
AN INTRODUCTION TO ADHD
AND ADDICTION
This chapter is published as:
Katelijne van Emmerik-van Oortmerssen, Maija Konstenius, Robert A. Schoevers. ADHD and addiction. In: Geert Dom, Franz Moggi, eds. Co-occurring addictive and psychiatric disorders: a practice-based handbook from a European perspective. Berlin: Springer-Verlag; 2015: 179-191.
ABSTRACT
Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention and/ or hyperactivity and impulsivity. It is frequently present in substance use disorder (SUD) patients; estimates of the prevalence of ADHD vary between 14% and 23% in SUD populations. The high comorbidity is partly based on communal underlying neurobiological characteristics such as a shared genetic background of the two disorders. Neuropsychological correlates of both disorders include a dysfunction of the motivational/reward system and impulsivity. In general, patients with this type of comorbidity represent a more severe subgroup of SUD patients with more additional comorbidity and a more disadvantageous prognosis and higher treatment drop-out than SUD patients without ADHD. It is important to detect and treat ADHD in SUD patients, and substance use disorder treatment centers can play an important role in this by screening for ADHD. Treatment options may include medication, although convincing evidence of effect in SUD populations is yet lacking, and cognitive behavioral therapy. As problems of SUD and ADHD can be intertwined, it is appropriate to start ADHD treatment during SUD treatment, ideally after initial stabilization of substance use. As this patient group is characterized by high complexity, further research and development of integrated treatment programs are warranted.
19 An Introduction To ADHD And Addiction
Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common psychiatric disorders in childhood, affecting approximately 4-8% of children in the general population.1
Although symptoms wane in some patients in adulthood, the majority of patients continues to be impaired by their symptoms,2 leading to a prevalence of 1-5% in adulthood.3
ADHD is characterized by symptoms of attention deficit and/ or hyperactivity and impulsivity. Three different subtypes exist: patients who exhibit mainly attention deficit symptoms have the attention deficit subtype, whereas patients experiencing mainly hyperactivity and impulsivity symptoms are diagnosed with the hyperactive/ impulsive subtype. The majority of the clinical population has symptoms in both domains, and is diagnosed with the combined subtype.4 In line with recent changes in the classification of psychiatric
disorders in which axis I and II are no longer distinguished, the difference between ADHD and personality disorders in terms of its lifelong impact can be debated, as ADHD starts at young age and its symptoms often persist in adulthood. ADHD can lead to functional impairments in all domains of life. It is associated with lower level of education, higher level of unemployment, but also higher rates of unsuccessful marriages, criminality and road traffic accidents.5, 6 Altogether, these consequences are responsible for a reduced quality of life,
which is also caused by the fact that ADHD is often accompanied by comorbid disorders. Antisocial personality disorder, borderline personality disorder, mood disorders and anxiety disorders are frequently present and have an impact on the prognosis.7, 8 Substance use
disorders (SUDs) are also an important comorbid disorders in ADHD patients, affecting 15% of adult ADHD patients.9
Several treatment options for adult ADHD exist. Pharmacological treatment with stimulants such as methylphenidate is by far the most described treatment modality, resulting in symptom improvement in a majority of patients .10 Although symptoms of for example
inattention can be improved by medication, medication offers no solution for the fact that planning and organization skills are often not developed to their full potential. Recently, therapists and researchers in the field have focused on developing a cognitive behavioral therapy (CBT) for ADHD patients, that addresses these functional skills.11 More research
is needed to corroborate their promising results, and also to investigate other treatment options.
In this chapter, we will provide an overview of the epidemiology of SUD patients with comorbid ADHD, and of the neurobiological correlates of this type of comorbidity. We will then focus on the clinical presentation, treatment and prognosis of these patients, and end with recommendations for future research.
EPIDEMIOLOGY OF ADHD IN SUD PATIENTS
Several studies have shown that children with ADHD have a greater risk of developing SUD later in life than children without ADHD.12 Not surprisingly, the prevalence of ADHD in SUD
patients is much higher than in the general population; a meta-analysis of predominantly American studies estimated the prevalence of ADHD in SUD patients to be 23.1%13 and in
20 Part I | CHAPTER 2
the largest study so far in 3558 SUD patients in 10 mostly European countries, prevalence rates ranged from 5.4 to 31.3% depending on country.14 The latter study found significant
differences between countries, with Scandinavian countries having a higher ADHD prevalence than for example southern European countries. Also, differences were found between patients with different types of SUD, as a lower ADHD prevalence was found among alcohol dependent patients compared to illicit drug dependent patients. Altogether, these findings suggest that ADHD is a frequently present comorbid disorder in SUD patients. Several factors contribute to this high co-occurrence of both disorders. In the next paragraph, genetic and neurobiological mechanisms explaining the high comorbidity are discussed.
NEUROBIOLOGY OF ADHD
Pathophysiology underlying ADHD has been extensively investigated in the past two decades and the field is growing rapidly. Along with technical advances, exciting results from both genetic and brain imaging studies are emerging. This section briefly presents important findings regarding the neurobiological underpinnings in ADHD.
Genetic factors
ADHD has a strong heritable component. The mean estimated heritability is 76 % in twin studies.15 In familial studies, parents and siblings of ADHD patients show increased risk of
ADHD. This risk is more strongly associated in index patients with persisting ADHD compared to remitted ADHD.16 A number of risk genes for ADHD have been identified but results have
yet been inconsistent. The most replicated findings involve dopamine (DA) and serotonin transmission.17
To date research has shown that ADHD involves multiple genes of moderate effect in complex interaction with environmental factors. For example health complications early in life may modulate the genetic risk for ADHD.18
ADHD subtypes based solely on DSM-IV symptom criteria have been criticized as providing too heterogeneous samples for the purpose of genetic studies. Identifying endophenotypes based on neuropsychological deficits is suggested to offer more well-defined subtypes of ADHD16 (for definition of endophenotypes see Castellanos and Proal).19
Neuropsychological functioning
Over the years, several theories about core cognitive deficits in ADHD have been formulated based on results from neuropsychological studies and behavioural observations; focussing for example on deficits in executive functioning20 or a dual pathway model of executive
function deficits and reward deficiency.21 Barkley proposed that executive function deficits
seen in children with ADHD are secondary to failure in inhibition.22
Meta-analysis of studies investigating neuropsychological functioning in ADHD show that, compared to controls, individuals with ADHD most consistently display differences in
21 An Introduction To ADHD And Addiction
response inhibition, vigilance, spatial working memory, signal detection (arousal), set shifting and some measures of planning.23
Results from imaging studies
Results from both structural24 and functional imaging studies25 have repeatedly shown
involvement of fronto-striatal-cerebellar networks in the neurobiology of ADHD, implicating neurotransmission involving DA and noradrenaline (NA). Prefrontal cortex (PFC) is rich in DA and NA receptors and has a vital role in cognitive control by regulating information received from sensory cortices and attention based on the relevance of incoming information. PFC is also important for sustaining attention over delay and shifting attention based to task demands. In addition, it has an important role in regulating behaviour and emotion.26
Functional brain imaging studies have initially investigated subjects performing cognitive tasks challenging e.g. attention, working memory and response inhibition thus activating brain areas of interest, comparing individuals with ADHD to controls or medicated individuals to non-medicated. Recently, interesting results are emerging from imaging studies investigating brain activity during resting state suggesting a more diffuse connectivity between functional networks in individuals with ADHD.27
Few imaging studies have been able to prospectively follow up individuals, who were diagnosed with ADHD as children, from childhood to adulthood. In a prospective study of 59 boys (aged 6 – 12 when diagnosed with ADHD) and 80 comparisons who underwent MRI after approximately 33 years of initial diagnosis, a reduction in brain gray matter was found in areas involved in attention, emotion regulation and motivation.28 These results
were independent of current diagnosis and the authors suggest that remission in ADHD is linked to compensatory maturation of prefrontal, cerebellar and thalamic circuitry.
Recently, based on findings from brain imaging studies, involvement of several large-scale brain systems in ADHD has been proposed instead of focusing mainly on the influence of prefrontal brain regions.19 The suggested brain systems include: 1) the fronto-parietal
network, also referred to as an executive control circuit involved in goal directed behaviour, 2) the dorsal and ventral attentional networks, which form the key components of the attention regulatory system; especially the dorsal attentional network is implicated in ADHD, 3) the visual network, which is important in sustained attention and interacts with the dorsal attentional network, 4) the motor network; ADHD children often exhibit motoric hyperactivity, and 5) the default network, the activity of which is diminished during a task and increased during rest. Diminished suppression of the default network during tasks is related to lapses in attention (for a detailed account see Castellanos and Proal).19
Disruptive externalizing disorders (CD, ODD, SUD and ADHD) that commonly co-exist share behavioural symptoms and neuropsychological dysfunctions and it has been suggested that they involve common genetic networks.29 Brain circuits involved in addiction vulnerability
include those of reward, memory, executive function, and motivation, all of which play a role in ADHD as well. Deficient DA transmission reported in ADHD is also implicated in
22 Part I | CHAPTER 2
vulnerability to addiction.30
To conclude, ADHD is a highly heritable disorder and its pathophysiology involves fronto-striatal-cerebellar networks and DA and NA neurotransmission (while not excluding other potential neurophysiological mechanisms). Results from imaging studies also support the notion that ADHD and SUD share some common neurobiological underpinnings.
CLINICAL PRESENTATION OF ADHD
Table 1 lists the ADHD symptoms of inattention and hyperactivity/ impulsivity. A DSM5 ADHD diagnosis in adulthood can be established if a patient (retrospectively) meets all criteria in childhood as well as in adulthood. These criteria are: symptom criterion (i.e. at least 6 symptoms of inattention and /or 6 symptoms of hyperactivity and impulsivity in childhood, and 5 symptoms of inattention and/ or hyperactivity/ impulsivity in adulthood); age criterion (age of onset before 12); pervasiveness criterion (symptoms are present in at least two domains of life); impairment criterion (symptoms lead to a significant impairment); and diagnostic category (symptoms are not better explained for by the presence of another disorder).
While the core symptoms of inattention, hyperactivity and impulsivity are well pronounced in children, the presentation is generally more subtle in adults. Hyperactivity at an adult age for instance is not expressed in running and climbing excessively, but rather as inner restlessness, inability to relax, over talkativeness, or avoiding going to theatres etc. This makes it more difficult to recognize the symptoms, especially since the description of symptoms in the DSM is sometimes more suitable for a childhood situation than for adults.
As mentioned before, ADHD is often accompanied by comorbid disorders. This is also true for SUD patients with ADHD: in comparison to SUD patients without ADHD they even suffer more often from additional psychiatric disorders, such as antisocial personality disorder, borderline personality disorder, depression or anxiety disorders. In fact, the majority of SUD patients with ADHD have at least one more comorbid disorder31 which contributes to the
fact that this is a subgroup of SUD patients with more severity.
Although in childhood, ADHD is more often recognized in boys, the rates of ADHD for men and women are more equal in adult populations and are equal in adult SUD populations as well.
SCREENING AND DIAGNOSTIC ASSESSMENT OF ADHD
Typically, in many SUD patients with ADHD the disorder has not been identified by health care workers, so substance abuse treatment centers may often be the first to recognize the ADHD symptoms and perform diagnostic assessment. Screening and diagnostic assessment is however hampered by a number of important difficulties. As an example, ongoing substance use can mask ADHD symptoms, but it may also mimic ADHD symptoms that are no longer present when the effects of substance use have faded. The same holds
23 An Introduction To ADHD And Addiction
Table 1: ADHD symptoms of inattention and hyperactivity/impulsivity.
Inattention symptoms
1 Often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities.
2 Often has difficulty sustaining attention in tasks or play activities. 3 Often does not seem to listen when spoken to directly.
4 Often does not follow through on instructions and fails to finish schoolwork or duties in the workplace (not due to oppositional behavior or failure to understand).
5 Often has difficulty organizing tasks or activities.
6 Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (like schoolwork or homework).
7 Often loses things necessary for tasks or activities (e.g. toys, school assignments, pencils, books, or tools).
8 Is often easily distracted by extraneous stimuli. 9 Is often forgetful in daily activities.
Hyperactivity/impulsivity symptoms
1 Often fidgets with hands or feet or squirms in seat.
2 Often leaves seat in classroom or in other situations in which remaining in seat is expected. 3 Often runs about or climbs excessively in situations in which it is not appropriate (in
adolescents and adults, may be limited to subjective feelings of restlessness). 4 Often has difficulty playing or engaging in leisure activities quietly.
5 Is often “on the go” or often acts as if “driven by a motor”. 6 Often talks excessively.
7 Often blurts out answers before the questions have been completed. 8 Often has difficulty awaiting turn.
9 Often interrupts or intrudes on others (e.g., butts into conversations and games).
for withdrawal symptoms such as restlessness and concentration problems. Several ADHD screening instruments exist, of which the ASRS-v1.1 has been validated in a population of SUD patients.32 It is important to remember that a diagnosis cannot be based on a simple
screening, so in case of a positive result of the screening instrument, diagnostic assessment is indicated. This is usually postponed until after a period of several weeks of abstinence when interfering intoxication/ withdrawal symptoms have been minimized. However, valuable information can also be obtained if careful attention is given to childhood ADHD symptoms, and to ADHD symptoms in past periods of abstinence, even if a patient is not abstinent at the time of assessment. It is generally recommended to involve an informant,
24 Part I | CHAPTER 2
such as a parent, to collect additional information on childhood symptoms; similarly, a partner or other significant person can shed light on adulthood symptoms. Structured interviews such as the Conners’ Adult ADHD Diagnostic Interview for DSM-IV (CAADID)33 and
DIVA34 are helpful in obtaining all necessary diagnostic information in a standardized way.
ADHD symptoms need not only be differentiated from substance use disorders, but also from bipolar disorders, depressive and anxiety disorders, and borderline personality disorder, all of which share overlapping symptoms with ADHD. For example, adults with ADHD often exhibit low self-esteem, low mood, affective lability and irritability, which may be confused with dysthymia, bipolar disorder or borderline personality disorder.35 Diagnosing
ADHD is further complicated by the fact that these differential diagnoses can also be present as comorbidities.
Although ADHD is associated with deviations in neuropsychological functions when groups of ADHD patients and normal controls are compared, these deviations are relatively unspecific and neuropsychological tests are not sensitive enough as diagnostic tools on an individual level. They may, however, provide useful information about a person’s cognitive functioning that is important for treatment planning. This is apparent for example in patients with severe learning difficulties.
TREATMENT OF ADHD IN SUD PATIENTS
An important first step in the treatment of ADHD in SUD patients is psycho-education about the disorder. For patients who have experienced ADHD-related problems from childhood on, it is a relief to learn that there is a condition explaining these problems. Often they have been told that they are lazy and they may have developed a low self-esteem because of failing tasks. Realizing that ADHD is involved in the origin of these difficulties is very valuable information for many patients. It is important to explain that ADHD is a lifelong condition, and treatment is aimed at reducing symptoms and learning how to cope with symptoms. In this paragraph, treatment options for ADHD are described, as well as their efficacy in SUD patients with ADHD.
Pharmacological treatment
Stimulant medications such as methylphenidate are an effective treatment option for adults with ADHD.10 Methylphenidate blocks the dopamine transporters in the brain, which leads
to enhanced dopamine levels and reduced ADHD symptoms. Dextroamphetamine, which is also a stimulant, exerts its effect through increased synaptic dopamine release. Although stimulant medication is effective in 70% of adult ADHD patients,35 the effect of stimulant
medication is not as clear in SUD patients with ADHD. Most randomized controlled trials to date did not find a convincing effect of methylphenidate on ADHD symptoms or SUD problems (e.g. Levin et al., Konstenius et al.).36, 37 The reasons for this putative lack of effect
are not yet clear, but a possible explanation could be that direct toxic effects of drugs have altered dopamine neurotransmission in such a way that methylphenidate is not able to exert
25 An Introduction To ADHD And Addiction
its effect anymore.38 It has also been suggested that higher doses may be warranted in a SUD
population.36 This is supported by results from a recent study showing that methylphenidate
in doses up to 180 mg improved ADHD-symptoms, reduced relapse and improved retention to treatment in amphetamine dependent men recently released from prison.39
Thus, although the first choice pharmacological therapy for ADHD is methylphenidate, it is important to realize that this medication may not be effective in many SUD patients with ADHD. Still a treatment with methylphenidate can be considered if a patient wants to try the option. In that case, it is important that a patient first becomes abstinent of substances, so the effect of medication is not disturbed by intoxication or withdrawal from substances, and that agreements are made in advance on how long the effect is monitored before deciding if there is any effect or not.
The regular treatment dose of methylphenidate is 0.5-1.0 mg/kg/day. Before starting treatment, a somatic check-up is required with specific attention for cardiac problems, epilepsy, thyroid problems, and registration of blood pressure and heart frequency, which is repeated during treatment. Methylphenidate is available as immediate-release and several forms of sustained release. Immediate release preparations have a short effect span and should be administered four to five times a day. One of the side effects of this type of stimulants is the rebound effect: ADHD symptoms worsen as the medication effect declines. The sustained-release formula is prescribed once or twice daily, which is more convenient and feasible for most patients. Rebound effects occur less frequent and less pronounced. Another advantage of this medication formula is the lower abuse liability, in contrast to the immediate release form which can be inhaled through the nose or injected. Compared to oral administration, sniffing or injecting methylphenidate results in a faster increase of extracellular dopamine, which evokes a reinforcing ‘high’. In patients where abuse is a particular concern, it is probably wiser to prescribe the sustained release form. Other medication options for the treatment of ADHD include atomoxetine and bupropion. Atomoxetine inhibits noradrenaline re-uptake and is considered an appropriate second-line alternative for stimulants. There is only limited information on the effects of atomoxetine in SUD patients with ADHD, but the scarce studies to date showed disappointing effects on ADHD symptoms. Only one double-blind RCT found that atomoxetine treatment was superior to placebo in improving ADHD symptoms in recently abstinent alcohol-dependent adults with ADHD.40 The usual dosage for atomoxetine is 80-100 mg/day, and it is prescribed
once daily. Bupropion is an inhibitor of catecholamines re uptake. It has antidepressive effects but it is also used in the treatment of ADHD. However, its use has hardly been studied in double-diagnosis patients with SUD and ADHD. Bupropion is dosed 300-450 mg/ day, divided over 1 or 2 doses.
Cognitive behavioral therapy and coaching
Only recently, research has focused on Cognitive Behavioral Therapy (CBT) as treatment option for adults with ADHD. Even if medication is effective in a patient, for example by improving attention, many patients have never been able to learn basic planning and
26 Part I | CHAPTER 2
organizing skills. Moreover, the accumulation of failure experiences in the past may still have an impact on patient’s functioning. CBT addresses these issues, by training planning and organization skills on one hand, and teaching the patient to tackle automatic negative thoughts on the other hand. Several randomized trials have studied the effect of CBT in adult ADHD patients, and found a remarkable effect which also lasted at follow-up (e.g. Safren et al.).11 Unfortunately, CBT for ADHD has not yet been studied in SUD patients
with ADHD. At the present an integrated CBT treatment which addresses both SUD and ADHD is being investigated in a randomized controlled design in the Netherlands.41 SUD
and ADHD symptoms can exacerbate one another, for example substances are sometimes used to alleviate ADHD symptoms (e.g. of restlessness), and at the same time substance use can worsen ADHD symptoms (e.g. concentration problems or impulsivity). The authors hypothesize that treating SUD and ADHD at the same time may result in better treatment outcomes for both SUD and ADHD. The integrated treatment incorporates both protocollized addiction treatment and elements of the CBT protocol for ADHD treatment by Safren and colleagues.42 After initial stabilization of substance use, sessions on addiction treatment
alternate with sessions ADHD treatment. Basic planning skills are trained by instructing patients to use a calendar and task list, and ample attention is paid to prioritizing tasks and managing overwhelming tasks by cutting them into small parts. Reducing distractibility and coping with negative automatic thoughts are also part of the treatment protocol. Results of the study are not yet available at the moment of writing this chapter, but are expected in 2016.
Order of treatments
In treating SUD patients with ADHD, it is important to start with ADHD treatment as soon as possible. Symptoms of ADHD and addiction exacerbate each other and treatment of both disorders is therefore required. After initial stabilization of substance use, ADHD treatment in the form of psycho education and CBT or coaching can be taken up. In case of medication treatment, treatment should only be started once the patient is abstinent from substances. Investing in a stable work alliance between patient and therapist is of extra importance in order to prevent patients from dropping out of treatment. Apart from this, extra efforts could be useful to help these, generally chaotic, patients to remember their treatment appointments. Scheduling appointments on a fixed day and time, and sending a reminder text message before the appointment for example, can be very helpful.
PROGNOSIS
As stated earlier, SUD patients with ADHD represent a more severe subgroup of patients than patients with SUD only. They more often suffer from additional psychiatric comorbidities, and in general their SUD problems are more severe compared to SUD patients without ADHD. Furthermore, SUD patients with comorbid ADHD start abusing substances at a younger age, use more substances and are hospitalized more often than SUD patients without ADHD.43 ADHD is also associated with higher relapse rates after SUD treatments.44
27 An Introduction To ADHD And Addiction
On top of that, pharmacological treatment of ADHD symptoms has limited effect,45 and
results of CBT approaches have not yet been described in this patient group.
A
ll in all, treatment of these double diagnosis patients should include not only addiction care, but also diagnostic assessment and treatment for ADHD symptoms to optimize the prognosis. Still, treatment of SUD patients with ADHD is challenging because these patients are often struggling with many long-existing problems, and developing tailored treatment programs should be a focus of future research. A more extensive treatment is generally necessary in comparison to patients with uncomplicated SUD, and can offer these patients a chance to overcome SUD problems and ADHD related problems in their lives. Successful treatment may result in better quality of life and large health gains for these patients.28 Part I | CHAPTER 2
REFERENCES
1. Faraone SV, Sergeant J, Gillberg C. The worldwide prevalence of ADHD: is it an American condition? World
Psychiatry. 2003;2:104-113.
2. Faraone SV, Biederman J, Mick E. The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med. 2006;36:159-165.
3. Simon V, Czobor P, Bálint S, Mészáros A, Bitter I. Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. Br J Psychiatry. 2009;194:204-211.
4. Wilens TE, Biederman J, Faraone SV, Martelon M, Westerberg D, Spencer TJ. Presenting ADHD symptoms, subtypes, and comorbid disorders in clinically referred adults with ADHD. J Clin Psychiatry. 2009;70:1557-1162.
5. Biederman J, Faraone SV, Spencer TJ, Mick E, Monuteaux MC, Aleardi M. Functional impairments in adults with self-reports of diagnosed ADHD: A controlled study of 1001 adults in the community. J Clin
Psychiatry. 2006;67:524-540.
6. Shaw M, Hodgkins P, Caci H, Young S, Kahle J, Woods AG, Arnold LE. A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: effects of treatment and non-treatment.
BMC Medicine. 2012;10:99.
7. Wilens T, Faraone SV, Biederman J. Attention-deficit/hyperactivity disorder in adults. JAMA. 2004;292:619-623.
8. Barkley RA, Brown TE. Unrecognized attention-deficit/hyperactivity disorder in adults presenting with other psychiatric disorders. CNS Spectrums. 2008;13:977-984.
9. Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, Faraone SV, Greenhill LL, Howes MJ, Secnik K, Spencer T, Ustun TB, Walters EE, Zaslavsky AM. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006;163:716-723.
10. Mészáros A, Czobor P, Bálint S, Komlósi S, Simon V, Bitter I. Pharmacotherapy of adult attention deficit hyperactivity disorder (ADHD): a meta-analysis. Int J Neuropsychopharmacol. 2009;12:1137-1147. 11. Safren SA, Sprich S, Mimiaga MJ, Surman C, Knouse L, Groves M, Otto MW. Cognitive behavioral therapy vs
relaxation with educational support for medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. JAMA. 2010;304:875-880.
12. Charach A, Yeung E, Climans T, Lillie E. Childhood attention-deficit/hyperactivity disorder and future substance use disorders: comparative meta-analyses. J Am Acad Child Adolesc Psychiatry. 2011;50:9-21. 13. van Emmerik-van Oortmerssen K, van de Glind G, van den Brink W, Smit F, Crunelle CL, Swets M,
Schoevers RA. Prevalence of attention-deficit hyperactivity disorder in substance use disorder patients: A meta-analysis and meta-regression analysis. Drug Alcohol Depend. 2012;122:11-19.
14. van de Glind G, Konstenius M, Koeter MW, van Emmerik-van Oortmerssen K, Carpentier PJ, Kaye S, Degenhardt L, Skutle A, Franck J, Bu ET, Moggi F, Dom G, Verspreet S, Demetrovics Z, Kapitany-Foveny M, Fatseas M, Auriacombe M, Schillinger A, Moller M, Johnson B, Faraone SV, Ramos-Quiroga JA, Casas M, Allsop S, Carruthers S, Schoevers RA, Wallhed S, Barta C, Alleman P, IASP Research Group, Levin FR, van den Brink W. Variability in the prevalence of adult ADHD in treatment seeking substance use disorder patients; Results from an international multi-center study exploring DSM-IV and DSM-5 criteria. Drug
Alcohol Depend. 2014;134:158-166.
15. Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005;57:1313-1323.
29 An Introduction To ADHD And Addiction
Haavik J, Lesch KP, Cormand B, Reif A, International Multicentre persistent AC. The genetics of attention deficit/hyperactivity disorder in adults, a review. Mol Psychiatry. 2012;17:960-987.
17. Cortese S, Castellanos FX. Neuroimaging of attention-deficit/hyperactivity disorder: current neuroscience-informed perspectives for clinicians. Curr Psychiatry Rep. 2012;14:568-578.
18. Plomp AS, Bergen AA, Florijn RJ, Terry SF, Toonstra J, van Dijk MR, de Jong PT. Pseudoxanthoma elasticum: Wide phenotypic variation in homozygotes and no signs in heterozygotes for the c.3775delT mutation in ABCC6. Genet Med. 2009;11:852-858.
19. Castellanos FX, Proal E. Large-scale brain systems in ADHD: beyond the prefrontal-striatal model. Trends
Cogn Sci. 2012;16:17-26.
20. Pennington BF, Ozonoff S. Executive functions and developmental psychopathology. J Child Psychol
Psychiatry. 1996;37:51-87.
21. Sonuga-Barke EJ. The dual pathway model of AD/HD: an elaboration of neuro-developmental characteristics. Neurosci Biobehav Rev. 2003;27:593-604.
22. Barkley RA. Attention-deficit/hyperactivity disorder, self-regulation, and time: toward a more comprehensive theory. J Dev Behav Pediatr. 1997;18:271-279.
23. Nigg J. Neuropsychologic Theory and Findings in Attention-Deficit/Hyperactivity Disorder: The State of the Field and Salient Challenges for the Coming Decade. Biol Psychiatry. 2005;57:1424-1435.
24. Castellanos FX, Lee PP, Sharp W, Jeffries NO, Greenstein DK, Clasen LS, Blumenthal JD, James RS, Ebens CL, Walter JM, Zijdenbos A, Evans AC, Giedd JN, Rapoport JL. Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA. 2002;288:1740-1748.
25. Bush G, Frazier JA, Rauch SL, Seidman LJ, Whalen PJ, Jenike MA, Rosen BR, Biederman J. Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop.
Biol Psychiatry. 1999;45:1542-1552.
26. Durston S, van Belle J, de Zeeuw P. Differentiating frontostriatal and fronto-cerebellar circuits in attention-deficit/hyperactivity disorder. Biol Psychiatry. 2011;69:1178-1184.
27. Swanson J, Baler RD, Volkow ND. Understanding the effects of stimulant medications on cognition in individuals with attention-deficit hyperactivity disorder: a decade of progress. Neuropsychopharmacology. 2011;36:207-226.
28. Proal E, Reiss PT, Klein RG, Mannuzza S, Gotimer K, Ramos-Olazagasti MA, Lerch JP, He Y, Zijdenbos A, Kelly C, Milham MP, Castellanos FX. Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood. Arch Gen Psychiatry. 2011;68:1122-1134. 29. Arcos-Burgos M, Velez JI, Solomon BD, Muenke M. A common genetic network underlies substance use
disorders and disruptive or externalizing disorders. Hum Genet. 2012;131:917-929.
30. Volkow ND, Wang GJ, Fowler JS, Tomasi D. Addiction circuitry in the human brain. Annu Rev Pharmacol
Toxicol. 2012;52:321-336.
31. van Emmerik-van Oortmerssen K, van de Glind G, Koeter MW, Allsop S, Auriacombe M, Barta C, Bu ET, Burren Y, Carpentier PJ, Carruthers S, Casas M, Demetrovics Z, Dom G, Faraone SV, Fatseas M, Franck J, Johnson B, Kapitany-Foveny M, Kaye S, Konstenius M, Levin FR, Moggi F, Moller M, Ramos-Quiroga JA, Schillinger A, Skutle A, Verspreet S, IASP Research Group, van den Brink W, Schoevers RA. Psychiatric comorbidity in treatment-seeking substance use disorder patients with and without attention deficit hyperactivity disorder; results of the IASP study. Addiction. 2014;109:262-272.
32. van de Glind G, van den Brink W, Koeter MW, Carpentier PJ, van Emmerik-van Oortmerssen K, Kaye S, Skutle A, Bu ET, Franck J, Konstenius M, Moggi F, Dom G, Verspreet S, Demetrovics Z, Kapitany-Foveny
30 Part I | CHAPTER 2 M, Fatseas M, Auriacombe M, Schillinger A, Seitz A, Johnson B, Faraone SV, Ramos-Quiroga JA, Casas M, Allsop S, Carruthers S, Barta C, Schoevers RA, IASP Research Group, Levin FR. Validity of the Adult ADHD Self-Report Scale (ASRS) as a screener for adult ADHD in treatment seeking substance use disorder patients. Drug Alcohol Depend. 2013;132:587-596.
33. Epstein JE, Johnson DE, Conners CK. Conners’ Adult ADHD Diagnostic Interview for DSM-IV (CAADID). Technical
Manual. Toronto: MHS; 2001.
34. Kooij JJS, Francken MH. Diagnostisch Interview voor ADHD bij volwassenen (DIVA). Den Haag: DIVA foundation; 2010.
35. Kooij SJ, Bejerot S, Blackwell A, Caci H, Casas-Brugue M, Carpentier PJ, Edvinsson D, Fayyad J, Foeken K, Fitzgerald M, Gaillac V, Ginsberg Y, Henry C, Krause J, Lensing MB, Manor I, Niederhofer H, Nunes-Filipe C, Ohlmeier MD, Oswald P, Pallanti S, Pehlivanidis A, Ramos-Quiroga JA, Rastam M, Ryffel-Rawak D, Stes S, Asherson P. European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD. BMC Psychiatry. 2010;10:67.
36. Levin FR, Evans SM, Brooks DJ, Garawi F. Treatment of cocaine dependent treatment seekers with adult ADHD: double-blind comparison of methylphenidate and placebo. Drug Alcohol Depend. 2007;87:20-29. 37. Konstenius M, Jayaram-Lindstrom N, Beck O, Franck J. Sustained release methylphenidate for the
treatment of ADHD in amphetamine abusers: a pilot study. Drug Alcohol Depend. 2010;108:130-133. 38. Crunelle CL, van den Brink W, Veltman DJ, van Emmerik-van Oortmerssen K, Dom G, Schoevers RA, Booij
J. Low dopamine transporter occupancy by methylphenidate as a possible reason for reduced treatment effectiveness in ADHD patients with cocaine dependence. Eur Neuropsychopharmacol. 2013;23:1714-1723.
39. Konstenius M, Jayaram-Lindström N, Guterstam J, Beck O, Philips B, Franck J. Methylphenidate for attention deficit hyperactivity disorder and drug relapse in criminal offenders with substance dependence: a 24-week randomized placebo-controlled trial. Addiction. 2014;109:440-449.
40. Wilens TE, Adler LA, Weiss MD, Michelson D, Ramsey JL, Moore RJ, Renard D, Brady KT, Trzepacz PT, Schuh LM, Ahrbecker LM, Levine LR, Atomoxetine ASUDSG. Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders. Drug Alcohol Depend. 2008;96:145-154.
41. van Emmerik-van Oortmerssen K, Vedel E, Koeter MW, De Bruijn K, Dekker JJ, van den Brink W, Schoevers RA. Investigating the efficacy of integrated cognitive behavioral therapy for adult treatment seeking substance use disorder patients with comorbid ADHD: Study protocol of a randomized controlled trial.
BMC Psychiatry. 2013;13:132.
42. Safren SA, Sprich S, Perlman CA, Otto MW. Mastering your adult ADHD: A cognitive-behavioral therapy
approach. New York: University Press; 2005.
43. Arias AJ, Gelernter J, Chan G, Weiss RD, Brady KT, Farrer L, Kranzler HR. Correlates of co-occurring ADHD in drug-dependent subjects: prevalence and features of substance dependence and psychiatric disorders. Addict Behav. 2008;33:1199-1207.
44. Ercan ES, Coskunol H, Varan A, Toksoz K. Childhood attention deficit/hyperactivity disorder and alcohol dependence: a 1-year follow-up. Alcohol Alcohol. 2003;38:352-356.
45. Castells X, Ramos-Quiroga JA, Rigau D, Bosch R, Nogueira M, Vidal X, Casas M. Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis. CNS Drugs. 2011;25:157-169.
PART II:
PREVALENCE OF ADHD AND
ADDITIONAL COMORBIDITIES
IN SUD PATIENTS
Katelijne van Emmerik - van Oortmerssen, Geurt van de Glind, Wim van den Brink, Filip Smit, Cleo L. Crunelle, Marije Swets, Robert A. Schoevers.
Drug and Alcohol Dependence. 2012;122(1-2):11-19.
CHAPTER 3
PREVALENCE OF ATTENTION-DEFICIT
HYPERACTIVITY DISORDER IN SUBSTANCE
USE DISORDER PATIENTS: A META-ANALYSIS
AND META-REGRESSION ANALYSIS
ABSTRACT
Context: Substance use disorders (SUD) are a major public health problem. Attention deficit
hyperactivity disorder (ADHD) is a comorbid condition associated with both onset and prognosis of SUD. Prevalence estimates of ADHD in SUD vary significantly.
Objective: To obtain a best estimate of the prevalence of ADHD in SUD populations.
Data sources: A literature search was conducted using MEDLINE, PsycINFO and EMBASE. Search terms
were ADHD, substance-related disorders, addiction, drug abuse, drug dependence, alcohol abuse, alcoholism, comorbidity, and prevalence. Results were limited to the English language.
Study Selection: After assessing the quality of the retrieved studies, 29 studies were selected. Studies
in which nicotine was the primary drug of abuse were not included.
Data Extraction: All relevant data were extracted and analysed in a analysis. A series of
meta-regression analyses was performed to evaluate the effect of age, primary substance of abuse, setting and assessment procedure on the prevalence of ADHD in a variety of SUD populations.
Data synthesis: Overall, 23.1% (CI: 19.4% - 27.2%) of all SUD subjects met DSM-criteria for comorbid
ADHD. Cocaine dependence was associated with lower ADHD prevalence than alcohol dependence, opioid dependence and other addictions. Studies using the DICA or the SADS-L for the diagnosis of ADHD showed significantly higher comorbidity rates than studies using the KSADS, DISC, DIS or other assessment instruments.
Conclusions: ADHD is present in almost one out of every four patients with SUD. The prevalence
35 Prevalence Of Attention-Deficit Hyperactivity Disorder In Substance Use Disorder Patients: A Meta-Analysis And Meta-Regression Analysis INTRODUCTION
Substance use disorders (SUD) are a major public health problem. The Epidemiologic Catchment Area Study reports a lifetime prevalence for alcohol use disorders of 13.5% and for other drug use disorders of 6.1%,1 and in the Netherlands Mental Health Survey
and Incidence Study-2 a lifetime prevalence of 19.1% for any substance use disorder was found.2 Patients with SUD constitute a large proportion of mental health service users, and
are overrepresented in general medical care.3
Attention Deficit Hyperactivity Disorder (ADHD) is a major risk factor for the development of substance use disorders,4-6 either directly7 or mediated by conduct disorder.8 Comorbid
ADHD has a negative effect on the course of SUD. Patients with both ADHD and SUD become addicted at a younger age, use more substances and are hospitalized more often than SUD patients without ADHD.9 ADHD is also associated with higher relapse rates after
successful addiction treatment.10 Moreover, treatment studies have consistently shown
that pharmacological treatment of ADHD with methylphenidate or atomoxetine is not as effective in ADHD patients with SUD compared to those without this comorbidity.11-17 Only
one study reported a decrease in self-reported ADHD symptoms after treatment in SUD patients.18 Other treatment strategies such as cognitive behavioural therapy19 have not
been studied in this population.
In order to develop optimal treatment programs for patients with ADHD and SUD, it is important to adequately recognize and diagnose these disorders. This may be complicated by overlapping symptoms, such as effects of drug intoxication or withdrawal.20 While the
prevalence of ADHD among children in the general population is approximately 5%,21 and in
adults around 4%,22 it is often assumed that the ADHD prevalence in SUD patients is higher.
However, prevalence estimates in the literature vary considerably and range from 2% in a study by Hannesdottir and colleagues23 to 83% in a study by Matsumoto and colleagues.24 It
is currently unclear whether differences in substance of abuse, in ADHD or SUD assessment, or between SUD populations may explain this variation in prevalence estimates. The current study aims to establish a best estimate of the prevalence of comorbid ADHD in adolescents and adults with SUD, using data from high quality studies in a statistical and meta-regression analysis. Differences between studies in terms of patient population, primary substance of abuse, setting and assessment procedure are taken into account. A meta-analytic review of the existing studies to date is important to obtain a more accurate estimate of the comorbidity of ADHD and SUD, as a first step in developing adequate diagnostic and treatment programs for this patient population.
METHOD
Data sources
We conducted a systematic literature search to identify studies reporting on the prevalence of comorbid ADHD in SUD populations using MEDLINE, PsycINFO and EMBASE. Key words
36 Part II | CHAPTER 3
for the search were: ADHD, substance-related disorders (Mesh term MEDLINE), addiction (subject heading in EMBASE), drug abuse, drug dependence, alcohol abuse, alcoholism (key words PsycINFO), comorbidity, and prevalence. English language and human studies were used as limits. Databases were searched from 1966 until January 2010. In addition, cross-references of the retrieved articles were checked.
Study selection
Titles and, if needed, abstracts were screened. All articles reporting on the prevalence of comorbid ADHD within a substance use disorder population were fully assessed by two authors independently (KvE-vO, GvdG) in order to assess eligibility. Differences between these authors were resolved by discussion with the last author (RAS).
The following criteria for inclusion in this meta-analysis were used:
• Studies reporting on the prevalence of comorbid ADHD in a SUD population. Articles with a different focus, but providing information from which the prevalence of ADHD in a SUD population could be extracted, were also included.
• A SUD diagnosis is made in all subjects by means of a validated diagnostic instrument, such as the SCID-I. If specific information on diagnostic procedures for SUD was not available, but the study involved a sample of patients from an addiction treatment centre, we assumed that these patients would qualify for a SUD diagnosis on clinical grounds. • We included all types of substance use disorders (for example abuse or dependence
of alcohol, cocaine, opiates, cannabis, or polysubstance disorders). However, studies reporting on subjects with nicotine dependence as the primary substance of abuse were not included.
• The presence of ADHD was established by means of a (semi) structured diagnostic instrument or a systematic DSM-based clinical interview. Self report questionnaires were not considered to be sufficient for this purpose. Studies were only selected if a clear diagnostic procedure for ADHD was described, and diagnoses were made according to DSM-III or DSM-IV criteria. A lifetime diagnosis of ADHD thus includes a retrospective childhood diagnosis (symptoms starting before age 7), irrespective of symptoms in adulthood. A current diagnosis of ADHD implies a childhood onset ADHD with persisting symptoms in adulthood that currently meet DSM-criteria. Studies in which the age of onset criterion for ADHD was not available were not included.
• Studies on both adults and adolescents were included. Studies on inpatients and outpatients of addiction treatment centres were included (treatment seeking samples), as well as studies based upon community samples (currently not in treatment for addiction problems).
The following exclusion criteria were used:
37 Prevalence Of Attention-Deficit Hyperactivity Disorder In Substance Use Disorder Patients: A Meta-Analysis And Meta-Regression Analysis
characterised by delinquent behaviour, which in turn is associated with ADHD.25-27
• Studies involving patients in treatment for a psychiatric disorder who had comorbid SUD were also excluded for reasons of sample selection.
• Studies that included different members of the same family, because subjects are not independent in these samples.
• Studies using imputation techniques to estimate the ADHD prevalence. • Studies lacking information necessary for our analysis.
Data extraction
The following data were extracted from the included studies: sample size, primary substance of abuse, diagnostic procedure for ADHD and SUD, timeframe of ADHD diagnosis (retrospective childhood diagnosis or current diagnosis with persisting symptoms), information on recruitment of the sample, setting and demographic characteristics of the sample, period of abstinence before diagnostic assessment, availability of other informant (for example parent) in ADHD assessment, and information on the prevalence of ADHD. Data synthesis and statistical analysis
The variable of interest was the prevalence of ADHD in SUD populations. Data on this outcome measure were analysed using Comprehensive Meta-analysis software Version 2. We expected the results to be quite heterogeneous as we included studies with different demographic characteristics, settings, primary substances of abuse, time frame, and assessment procedure. A test of heterogeneity (Q test) was used to determine whether the differences in prevalence estimates across studies were indeed larger than expected by chance. Heterogeneity was also assessed by the I2 metric, i.e. the percentage of between
study variance due to systematic heterogeneity rather than chance.28 A random-effects
model was used for the meta-analysis, as a fixed effect model is likely to produce misleading results in the presence of significant heterogeneity.29 In addition, heterogeneity was further
explored using a series of meta-regression analyses, in which we evaluated the effect of age, primary substance of abuse, setting and assessment procedure on the prevalence of ADHD in the various SUD populations. These meta-regression analyses were performed using SPSS 17 software with macros provided by Lipsey and Wilson.30
The following a priori defined variables were used for meta-regression: percentage males in the sample, mean age of the sample, setting (treatment seeking versus community), primary substance of abuse, recruitment of the sample (random/consecutive inclusion versus unknown way of inclusion), length of abstinence before diagnosing ADHD (at least 4 days of abstinence or less/unknown), type of adult ADHD diagnosis (lifetime or current), ethnicity (percentage Caucasians in sample), type of diagnostic instrument for ADHD (KSADS, DISC, DICA, systematic clinical interview using DSM criteria, SADSL, DIS or other instrument; abbreviations are explained at the bottom of table 1), and age group of sample (adolescents versus adults). For primary substance of abuse, we created dummy variables
38 Part II | CHAPTER 3
for cocaine, alcohol and opioids, as studies on these substances were the most frequent. If a study sample consisted of for example subjects with cannabis addiction, or a mixed group of SUD patients, the sample was classified as ‘other substance’ and was used as the reference category relative to the three dummies for cocaine, alcohol and opioids. Dummy variables were also used for the instrument that was used for ADHD diagnosis. The KSADS, DISC, DICA, DSM-list, SADSL and DIS were used as dummy variables for this purpose, with any other instrument as the reference category. Subsequently, a back-step procedure was employed, in which the least significant variable was deleted after every step. Finally, the remaining statistically significant (p<0.05) variables were retained in the regression model.
RESULTS
Results of literature search
Figure 1 shows the process of identifying and selecting relevant articles. Searches in MEDLINE, PsycINFO and EMBASE yielded a total of 1040 non-duplicate articles. After screening of titles and abstracts, 59 articles were fully studied by two authors on eligibility, and an additional nine studies were added for eligibility assessment from cross-references. A total of 39 of the 68 studies were excluded for various reasons, which resulted in a final inclusion of 29 articles. A more detailed list of the excluded studies and reasons for exclusion can be obtained from the first author.
Table 1 gives an overview of all selected studies. A total of 29 studies are included, involving 6,689 subjects (4,054 adolescents and 2,635 adults) from 6 countries. 26 studies involved treatment seeking samples. In terms of primary substance of abuse, 5 studies concerned alcohol dependent subjects, 6 studies described cocaine dependent subjects, 3 studies opioid dependent subjects, 1 study involved a cannabis dependent sample, and 14 studies included subjects with various types of SUD (not restricted to one specific substance). Different instruments were used to make ADHD and SUD diagnoses. For the ADHD diagnosis, the K-SADS was the most frequently used diagnostic instrument. For the SUD diagnosis, 9 of the 29 studies did not report the use of a specific instrument, but reported that a diagnosis was made based on a clinical interview using DSM criteria. Among the studies that used a diagnostic instrument for the SUD diagnosis, the SCID was most frequently used. Four studies (14%) reported no specific diagnostic instrument but concerned patients from an addiction treatment center.
ADHD prevalence rates in the included studies ranged from 8% 40 to 44.3% 7 in the
adolescent populations and from 9.9% 47 to 54.1% 52 in adult populations. The study by
Carroll and Rounsaville10 reported on two subgroups: a sample of 298 treatment-seeking
cocaine abusers (in- and outpatients from a drug abuse clinic), and a community sample of 101 cocaine abusers. The same treatment seeking sample was also reported in the article by Rounsaville and colleagues.53 Therefore, from Carroll’s article we only used the
39 Prevalence Of Attention-Deficit Hyperactivity Disorder In Substance Use Disorder Patients: A Meta-Analysis And Meta-Regression Analysis
FIGURES AND TABLES Figure 1 : Flow diagram study selection.
MEDLINE 598 records PsycINFO 163 records EMBASE 650 records Records after removing duplicates n = 1040 Screening titles and, if necessary, abstracts Full-text articles n = 59 Articles excluded because diagnostic procedure for ADHD was not sufficient (n = 18) Articles excluded because prevalence data were not available (n = 6) Articles excluded because the sample was inadequate (e.g. juvenile offenders) (n = 9) Articles retrieved by cross-references n = 9 Full-text articles assessed for eligibility n = 68 Articles excluded because SUD criterium was not met (n = 3) Articles excluded because lack of information which was necessary for our research question (e.g. the size of the SUD population was not reported) (n = 3) Studies included in this meta-analysis n = 29
