SERIAL PUBLICATION 1/2015 NATIONAL OTC MEDICINES PROGRAMME NATIONAL OTC MEDICINES Serial Publication Fimea Develops, Assesses and Informs 1/2015 © Finnish Medicines Agency Fimea 2015 Publisher Finnish Medicines Agency Fimea Postal address: P.O. Box 55, FI-00034 FIMEA Telephone: +358 29 522 3341 www.fimea.fi ISBN 978-952-5624-51-9 ISSN-L 1799-7135 ISSN 1799-7135 (printed) ISSN 1799-7143 (web)
Psychiaterfriedamatthys.beInt J Ment Health AddictionDOI 10.1007/s11469-014-9496-z Guideline for Screening, Diagnosis and Treatmentof ADHD in Adults with Substance Use Disorders Frieda Matthys & Steven Stes & Wim van den Brink &Peter Joostens & David Möbius & Sabine Tremmery &Bernard Sabbe # Springer Science+Business Media New York 2014 Abstract Currently there is no guideline for the screening, diagnosis and treatment of adultattention deficit/hyperactivity disorder (ADHD) in patients with a substance use disorder(SUD). The aim was to develop such a guideline, starting out from a systematic review andbased on the methodology of the Scottish Intercollegiate Guideline Network (SIGN). Due tothe lack of scientific evidence on some of the topics, the guideline is a combination of evidencebased and practice based recommendations. Given the high prevalence of ADHD in treatmentseeking SUD patients and the availability of valid screening instruments, all treatment seekingSUD patients should be screened for ADHD. Diagnosis of ADHD should be based on clinicalobservation and history taking, including informant data. Integrated treatment of ADHD andSUD is recommended, including pharmacotherapy, psycho-education, coaching, and cognitive F. Matthys (*)University Hospital Brussels and Free University Brussels (VUB), MSOC Free Clinic, Antwerp, Belgiume-mail: firstname.lastname@example.org S. StesUniversity Psychiatric Centre at Katholieke Universiteit Leuven, Leuven, Belgium W. van den BrinkAmsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center,University of Amsterdam, Amsterdam, The Netherlands P. JoostensPsychiatric Centre Broeders Alexianen, Tienen, Belgium D. MöbiusVereniging voor Alcohol- en andere Drugproblemen, Brussels, Belgium S. TremmeryDepartment Child & Adolescent Psychiatry, University Hospitals Leuven, Leuven, Belgium S. TremmeryDepartment of Neurosciences, KU Leuven, Leuven, Belgium B. SabbeCollaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Free UniversityBrussels (VUB) and Psychiatric Hospital Sint-Norbertus, Duffel, Belgium Int J Ment Health Addiction behavioral therapy (CBT). The lack of scientific data and the overall lack of expertise inthe field are significant obstacles to the implementation of the guideline. Intensivetraining programs in the substance abuse sector need to be organized to implementthese guidelines.
Keywords Guideline . Attention deficit hyperkinetic disorder . Substance use disorder .
Comorbidity . Screening . Diagnosis . Treatment . ADHD To the best of our knowledge, no guidelines are currently available for the screening, diagnosis andtreatment of adult attention deficit/hyperactivity disorder (ADHD) in patients with a substance usedisorder (SUD). There are guidelines for ADHD in adults (Kendall et al. ; Kooij et al. )and we found several expert opinions on ADHD and SUD (Kollins ; Levin et al. ; WilensHere we present the first guideline for this population based on scientific evidence whenavailable, complemented with practice based information and clinical consensus. The need forguidelines on ADHD in addicted patients originated within the Forum for Addiction Medicine ofthe Flemish Association for Alcohol and other Drug Problems. The Vereniging voor Alcohol-enandere Drugproblemen (VAD) coordinates most of the Flemish organizations dealing with thetreatment of patients with alcohol, drug, and gambling problems.
Several studies have shown that ADHD is much more common in patients with SUD opposed to the general population, and that there is a statistically significant and clinically relevantbidirectional overlap between ADHD and addiction (Arias et al. Wilens i.e. SUDis overrepresented in patients with ADHD and ADHD is overrepresented in patients with SUD.
In a population of adults that experience ADHD, the 12 month prevalence of alcohol abuse or dependence ranges between 17 % and 45 %, whereas the prevalence of drug use disordersranges between 9 % and 30 % (Wilens and Upadhyaya ). In patients with ADHD the age ofonset of alcohol and drug use is lower (Wilens the transition from regular use to moreserious forms of abuse or dependence accelerates and there is a reduced probability of recoveryfrom an individual with SUD (Wilens et al. ). The risk of addiction problems in adults withADHD is four times higher than in adults from the general population (Fayyad et al. Once ADHD is accompanied with a comorbid disorder (e.g. depression, anxiety disorder,bipolar disorder), the risk of developing an SUD is even higher (Biederman et al. ).
In subjects with a SUD, the lifetime prevalence of adult ADHD ranges from 16 % in addicted patients not receiving treatment to 23 % in patients seeking treatment for their alcoholand/or drug use disorder (van Emmerik-van Oortmerssen et al. In a combined sample oftreatment seeking and non-treatment seeking illicit psychostimulant users, 45 % screenedpositive for adult ADHD (Kaye et al. ). In the case of cocaine or heroin dependence,ADHD is also strongly associated with other comorbid disorders, such as disruptive behaviordisorders, antisocial personality disorder, bipolar disorder and post-traumatic stress disorder(Arias et al. Finally, the combination of ADHD and SUD also makes ADHD symptomsmore marked (Farhoodi et al. Levin et al. ).
The guidelines were developed based on the methodology prescribed by the ScottishIntercollegiate Guidelines Network (SIGN) (Sign.ac.uk ). This is a recognized reference Int J Ment Health Addiction for the development of guidelines by the Belgian branch of the Cochrane Collaboration(CEBAM) (Cebam.be Guideline Development Group and Focus Groups In the composition of the Guideline Development Group, we ensured participation from allrelevant disciplines. The group consisted of Flemish specialists in ADHD in adults, ADHD inchildren, addiction medicine and addiction psychiatry both from outpatient and inpatientcenters. The director of the Belgian branch of the Cochrane Collaboration, the BelgianCenter for Evidence Based Medicine (CEBAM), provided methodological advice. In orderto keep the content of the guideline consistent with the actual needs and obstacles perceived bytherapists and patients, focus groups with patients and therapists (physicians, psychologists)were organized to gain better insight into their experiences and opinions (Fig. ) (Matthys et al.
). Based on the results of these focus groups a strategy for a systematic review ofevidence-based research was developed. Based on this review and clinical experience, thefirst version of the guideline was written and tested over a 6-month period in twelve addictiontreatment centers. The final version of the guideline was documented taking their feedback intoaccount and is electronically available: Literature Search and Data Sources The objective of the search was to reveal all relevant studies using sensitive search strategies.
An initial search was performed for guidelines and systematic reviews in the CochraneDatabase of Systematic Reviews, the NHS Guideline Finder, the Health Evidence Networkand Pubmed. A subsequent search for other studies was carried out using Pubmed, Cinahl,Psychinfo and the Web of Science between January 1994 and April 2009. For the items onwhich systematic reviews were found, the subsequent search focused on studies published afterthe systematic review. Manual searching and checking the reference lists of selected studiesenabled the inclusion of studies that were not retrieved in the initial search (Fig. ).
Selection of Studies Inclusion and exclusion criteria were defined before the selection procedure: adults with ADHDwith SUD. In the absence of data, studies on adults with ADHD but without SUD were alsoincluded. Further selection was based on the specific questions from focus groups (Fig. ). OnlyEnglish and Dutch language studies were selected from January 2000 until April 2009. Studieswere selected based on the titles and provided abstracts. Two independent assessors subse-quently assessed the selected studies. Irrelevant studies were excluded and full texts werescreened for the presence of answers to questions from Fig. In cases of doubt, the GuidelineDevelopment Group made the decision. A flow chart of the search can be found in Fig. below.
Quality Assessment All of the selected studies were evaluated for methodological quality using checklists. Forassessing guidelines, the Appraisal of Guidelines for Research and Evaluation (AGREE) Int J Ment Health Addiction Fig. 1 Topics from the focus groups instrument from the AGREE Collaboration (Agreecollaboration.org ) for assessingguidelines was used. The SIGN checklist was used for assessing systematic reviews, random-ized control trials (RCTs) and cohort case studies.
The data from valid studies was tabulated in evidence tables and summarized by level ofevidence. In accordance with the SIGN grading system, (Sign.ac.uk (Fig. ) ourrecommendations are graded from A to D. These grades match the strength of the supportingevidence from Levels of Evidence 1 to 4. If no relevant research evidence was found,recommendations were based on clinical judgment and consensus of the GuidelineDevelopment Group to what extent constitutes good practice.
The first version of the guideline was tested over a 6-month period in 12 addiction treatment centers.
Physicians and psychologists gave feedback on scope, quality, clarity and usefulness. The GuidelineDevelopment Group then considered the responses. An independent expert committee, following theCEBAM external validation procedure, officially approved the final guidelines in September 2011.
Levels of Evidence We selected 66 studies to support our recommendations, including three meta-analyses, onesystematic review, 11 RCTs, 16 non-systematic reviews, 12 cohort studies, eight open trials,four case reports/series, eight cross-sectional surveys, two prevalence studies, and one studyprotocol.
Int J Ment Health Addiction Fig. 2 Flow chart for the literature search on ADHD and SUD Only 38 of the 66 studies contained specific information about the target group (adults with ADHD and SUD), eight of which were non-systematic literature reviews. We found noguidelines for the target group of patients with SUD and ADHD. As a consequence, some
Int J Ment Health Addiction LEVELS OF EVIDENCE
1++ High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias Meta-analyses, systematic reviews, or RCTs with a high risk of bias 2++ High quality systematic reviews of case control or cohort studies High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal Well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal Non-analytical studies, e.g. case reports, case series GRADES OF RECOMMENDATIONS
At least one meta-analysis, systematic review, or RCT rated as 1++, and directly applicable to the target population or A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results or Extrapolated evidence from studies rated as 1++ or 1+ A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results or Extrapolated evidence from studies rated as 2++ Evidence level 3 or 4 or Extrapolated evidence from studies rated as 2+ Fig. 3 SIGN grading system of the recommendations were derived from research in other populations, such as youngpeople with ADHD and SUD as well as adults with ADHD but without SUD. We markedthese recommendations with ⓘ.
Findings Screening and Diagnosis It is generally assumed that a good diagnosis comprises a number of necessary steps: mappingthe current symptoms and the symptoms during childhood, family history, school and Int J Ment Health Addiction vocational history, relationships, physical signs and investigation of comorbidity (Upadhyaya(L. Adler and Cohen ) ⓘ. 3 Although there is no specific evidence on when the diagnostic process in individuals with an addiction problem should be started, experts mention an abstinence period of 1 month foran accurate and valid diagnosis (Wilens Other sources argue that the patient should atleast be approachable to obtain adequate information about the life course in an interview(Glind et al. Our group of experts and practitioners rejected a 1-month abstinencerequirement. They concluded that this recommendation could not be generalized in view of thegreat variation in the history, the type of substance use and the nature of the treatment setting.
In addition, it was emphasized that for a correct diagnosis of ADHD in adults with SUD,expertise with regard to both disorders is required (Glind et al. 4 The high prevalence of ADHD in patients with SUD and the impact of ADHD on the course ofSUD symptoms are important reasons for screening (West et al. 3 Early detection andtreatment of ADHD in a population with SUD is significant for successful treatment of thesepatients (Kalbag and Levin The screening should be done with a validated questionnaire based on the eighteen DSM-IV symptoms of ADHD. However, until recently, only one screening instrument for ADHD wastested in a population of young adults with addiction problems: Conners' Adult ADHD RatingScale (CAARS) (Cleland et al. 2+ At the time of the development of the guideline, theFlemish version of the Adult ADHD Self-Report Scale (ASRS) had not yet been validated inthis patient group. However, experts felt that the CAARS and the ASRS can be used, providedthat the results are interpreted with caution. This screening gives an indication of the presence ofADHD. However, the specificity of such questionnaires is generally limited, resulting in asubstantial number of false positives and thus over-diagnosis of ADHD (Upadhyaya ). 3 Under-Diagnosis and Over-Diagnosis The stringency of the DSM-IV criteria, at least six of the nine symptoms currently and thepresence of symptoms before the age of seven, can complicate the diagnosis of ADHD in adults,which may lead to an under-diagnosis of ADHD in the adult population (Levin and Upadhyaya). 3 It is often wrongly assumed that in the presence of anxiety disorders, depression or otherpsychiatric disorders, ADHD should not be diagnosed. If ADHD exists together with other axis-Idisorders, all disorders should be taken into account (Kalbag and Levin ). Since the DSM-IVcriteria was originally developed for children, the absence of age-specific symptoms can also leadto underdiagnosis. Patients with addiction problems combined with ADHD often have difficultiesin recalling the presence of ADHD symptoms in childhood which is necessary for properdiagnosis (Levin and Upadhyaya . Moreover, the patient may be reluctant in givinginformation, while the family may not be willing to cooperate either (Kalbag and Levin ).
3 Ultimately, if a patient with SUD is not diagnosed with ADHD as a child, it is highly unlikelythat current behavioral problems will be linked to ADHD. Social problems such as poor schoolresults, job loss, etc., are easily attributed to existing substance abuse issues. In addition, manyadults with ADHD have developed compensatory strategies to mask the negative impact of theirADHD symptoms in daily functioning (Adler and Cohen ) (Culpepper and Mattingly ) ⓘ. 3 Therefore, if an adult with SUD is examined, it is also important to take into account theoverall clinical picture and to interpret reasonably, but critically, the age limit of 7 years as well asthe requirement of six of the nine symptoms. In the DSM-V, the age limit of 7 years is raised to Int J Ment Health Addiction 12 years and the number of symptoms required for the diagnosis of adult ADHD is reduced fromsix to five (American Psychiatric Association ).
Differential diagnosis with bipolar disorder or borderline personality disorder can be difficult, but should be taken seriously in order to prevent misdiagnosis. Checking thecontinuity of the symptoms from early childhood to adulthood and their appearance indifferent settings and situations can give further insights. Over-diagnosis of ADHD can alsooccur due to symptoms of drug dependence or drug use itself being mistaken for ADHDsymptoms (Kalbag and Levin ; Levin and Upadhyaya ; Wilson and Levin 3Therefore, it is highly recommended to consider developmental history, psychiatric co-morbidity and family history of the patient while focusing on drug-free and alcohol-freeepisodes in the patient's life. (Sullivan & Rudnik-Levin ). 3 Another risk of over-diagnosis can occur when patients exaggerate experienced ADHD symptoms and try toinfluence the diagnosis in order to obtain stimulant medication (Upadhyaya ). 3 Diagnostic Instruments Self-report questionnaires based on the DSM-IV criteria for ADHD can be useful but areinsufficient for an accurate diagnosis (Adler and Cohen However, only two instrumentswere tested in a population of young adults with addiction problems (Cleland et al. ; Westet al. ) 2+: CAARS and Attention Deficit Scales for Adults (ADSA). Both instruments arereliable and valid in determining which patients with addiction problems should receive a morein-depth diagnostic examination (Adler et al. West et al. , 3 ⓘ.
In addition, there are two semi-structured diagnostic interviews for adults available to assess current and past symptoms, the Diagnostic Interview for ADHD in Adults (DIVA) (Kooij )and the Conners' Adult ADHD Diagnostic Interview for the DSM-IV (CAADID) (Epstein et al.
). The DIVA was only available in Dutch at the time the guideline was developed and neitherof the interviews had been validated in a population with ADHD and comorbid SUD.
Gender and Socio-Economic Situation The investigator should take into account the environment of the patient. Attention deficit, impulsive-ness, easy distraction, overreacting etc., can also be the result of living in a stressful and unpredictablesubstance abusing environment rather than being symptoms of ADHD (Gingerich et al. ⓘ.
The clinical appearance of ADHD may differ between men and women. Women with ADHD are more likely to suffer from mood and anxiety disorders and low self-esteem (Arciaand CONNERS ; Biederman et al. ; Katz et al. ) ⓘ. 2 Unlike the findings fromresearch in girls, in which the inattentive type is diagnosed more often than in boys, in aclinical trial, adult women were diagnosed more often with the combined type than men(Robison et al. ) ⓘ. 2 Other authors suggest women with ADHD generally do not exhibitsymptoms of hyperactivity, but rather less obvious symptoms such as restlessness, forgetful-ness and disorganization (Quinn Waite ) ⓘ. 3 As in other pathologies, it is important to know the cultural background of the patient (importance of individuality, family loyalty and honor, performance orientation, etc.) inorder to assess whether the behavior is abnormal. Cultural differences can have an influenceon the signs and treatment access of ADHD (Rohde et al. ⓘ. 1+ Although theprevalence of ADHD seems similar in different countries (Faraone et al. cross-national research shows a lower prevalence of ADHD in lower-income countries (1.9 %)compared with higher-income countries (4.2 %) (Fayyad et al. ). Within a population ofyoung adults with ADHD the association between socio-economic class and comorbid Int J Ment Health Addiction addiction problems is U-shaped, with an increased risk of substance abuse in both thehighest and lowest social classes (Monuteaux et al. 2+ Co-morbidity complicates the diagnosis of ADHD, because there can be an overlap insymptoms as well as associated features with SUD (Kalbag and Levin (hypo)mania(Kim and Miklowitz ) ⓘ or other axis I and axis II disorders. Moreover, the combinationof ADHD and SUD is associated with an increased risk of mood and anxiety disorders (Wilenset al. 2+ Finally, intoxication and/or withdrawal from alcohol or drugs can mimic thesymptoms typical associated with ADHD (Faraone et al. ). 2+ Recommendations Screening and Diagnosis General Principals D The diagnosis should not be exclusively based on self-report questionnaires and/or semi-structured interviews covering the current situation. In addition to the current symptoms, dailylife observation, symptoms present in early childhood, lifetime presence of symptoms andsubstance abuse should also be considered. The clinician should, on an individual basis,determine the minimal duration of the abstinence needed before screening and diagnosis canbe initiated, taking into account the history of the patient, the setting in which the patient istreated and the substance of abuse. Interviewing the patient and his/her family can be startedeven when the patient has not been fully stabilized. Any physician who has had comprehensivetraining in the differential diagnosis of ADHD can make the formal diagnosis of ADHD. Thephysician should also have sufficient experience in substance abuse treatment and with apopulation of young adults with ADHD.
Given the high prevalence of ADHD in patients with SUD, screening for ADHD is important.
C Since there is no screening tool validated in Dutch, the physician will have to rely on clinicalexperience when choosing a valid instrument. Further diagnostic examination can be started ifthe screening is positive but also when the history of the patient or the clinical observationsuggests that ADHD is a possible diagnosis. D Diagnostic Examination A comprehensive clinical interview with the patient and family is necessary, preventingpotential over-diagnosis or under-diagnosis. C The use of validated questionnaires and semi-structured interviews is an ideal starting point. For the selection of diagnostic instruments, thephysician should base his/her choice on his/her clinical experience. C A timetable of the use of alcohol and drugs (duration, frequency and pattern of use, route of administration, type of substance) matching the appearance of ADHD symptomscan help to differentiate between ADHD symptoms and similar drug induced symptoms.
Moreover, this feedback can make the patient aware of his/her problems. During theclinical interview, it is appropriate to focus on the abstinent/clean episodes in thepatient's life. D Int J Ment Health Addiction The involvement of the patient's parents (or siblings) is significant in collecting information about the patient's childhood, though intentionally or unintentionally, family members canunderestimate or exaggerate his or her symptoms. C Additional observer information can begathered from school reports (if available), with special attention to the evolution of thepatient's performance and any added comments from teachers. C For systematic data collection (current and childhood), diagnostic interviews such as CAADID and DIVA can be used. D Gender aspects and cultural backgrounds should be included in the diagnostic assessment, as well as the socio-economic status (SES) of the patient. C Most patients have more than two comorbid conditions, therefore it is important to look for other psychiatric problems in the patient's personal and family history, D screening for moodand anxiety disorders. C In case of planning, organizational or memory dysfunctions, neuropsychological examina- tion can be useful to determine cognitive deficits. D Findings Treatment A Complex Problem Requires Complex Treatment Presently, there is a general consensus that proper treatment of ADHD in people with SUDcomprises several components: psycho-education and medication need to conjoin with indi-vidual and/or group therapy, as well as peer support (Goossensen et al. 3 It has beenindicated that combined interventions (medication + behavioral therapy) have a better outcomeopposed to medication alone (Safren et al. ) ⓘ 1 (Rostain and Ramsay ⓘ.2Abstinence is not an absolute precondition to start treatment (Wilens ) 3, but substanceuse must be stabilized, e.g. occasional moderate alcohol consumption, moderate cannabis use,fixed dose methadone or buprenorphine. The treatment of ADHD should be integrated into thetreatment of addiction, which is vital considering ADHD symptoms (such as impulsivity anddisturbed planning and organization) may interfere with the addiction treatment (Mariani andLevin ). 3 There is no consensus about the order of treatment of comorbid disorders.
However, researchers claim that serious psychiatric disorders that significantly affect func-tioning (such as psychosis or depression) should be treated first. When symptoms of an SUDare too serious or when housing is unstable, time-limited in-patient treatment is recommended(Wilens . 3 Treat the Patient, not the Illness Most adults with ADHD have two requests to reduce their symptoms: developing copingmechanisms to handle symptoms and a decrease of the emotional and functional problems thataccompany ADHD (Ramsay and Rostain ). Combined with an addiction problem, therewill be two additional objectives: to keep the patient in treatment and to influence the SUD in apositive way (Carpentier et al. Most young adults with ADHD suffer from a negative self-image and low self-esteem. If the diagnosis of ADHD is first recognized and made in adulthood, patients often experience aperiod of anger and grief for how different the outcome of life could have been if the diagnosishad been made earlier (Murphy ). 3 Involving families in the treatment process isrecommended: when members of the family are well informed and educated on the issue,coping mechanisms are easily developed and utilized towards the patient. Essentially, family- Int J Ment Health Addiction patient coping strategies allow for proper supervision in medication use to avoid abuse (Wilens3 There is sufficient evidence about the effect of medication on ADHD in adults. In placebo-controlled trials, stimulants have larger effect-sizes than atomoxetine (Peterson et al. ) ⓘ. 1Certain antidepressants (desipramine, a metabolite of imipramine, and bupropion) have anobvious effect on ADHD symptoms, but the effect is still smaller than that of stimulants(Maidment ; Verbeeck et al. ⓘ. 1 All products have a smaller effect in adults thanin children (Mészáros et al. ⓘ, 1 perhaps partly due to inadequate dosing (Dodson ⓘ.
However, data on adult ADHD in a population of substance users is much more limited. A number of case reports and open-label investigations suggest a positive effect of medication onADHD symptoms in addicts (Castaneda et al. Levin et al. ; Mann and Bitsios ;Riggs et al. ; Solhkhah et al. Somoza et al. ; Vaiva et al. ; Wilens et al.
Winhusen et al. 3 However, most double-blind and placebo-controlled studies,albeit with small groups and of short duration (Upadhyaya Wilens et al. showlittle or no improvement in ADHD symptoms. 2 In several of the studies, however, there is animprovement in ADHD symptoms in all groups, indicating a strong placebo effect, or an effectdue to the accompanying psychotherapy. In one study, the treatment of ADHD and co-occurring alcohol dependence with atomoxetine showed a significant effect on ADHDsymptoms with an effect size of 0.48. This is comparable to a study with atomoxetine in adultADHD patients without SUD (Wilens et al. Does ADHD Treatment Decrease Substance Abuse in Comorbid Patients? Since ADHD generally precedes SUD and since ADHD is considered a complicating factor inthe treatment of addiction, it was expected that the reduction of the ADHD symptoms wouldmake the addiction easily treatable. Initially, there was a great deal of optimism about the effectsof ADHD treatment on substance abuse (Levin et al. However, optimism was based on theresults from open label trials in small samples and without a control group, it could not beconfirmed in RCTs (Levin et al. , Szobot et al. Wilens et al. 1 It should be noted, however, that there is hardly any evidence for a worse substance use outcome in comorbid patients treated for their addiction. ADHD is a risk factor for an earlier onset of asubstance use disorder (Biederman et al. ) and adults with ADHD have a more prolongedcourse of SUD (Wilens but severity of drug dependency seems to be a more importantpredictor of comorbid ADHD in patients that dropout of treatment (Levin et al. ). 3 Does ADHD Treatment Prevent Substance Use Disorder? Children with ADHD are at increased risk for developing an addiction problem. In severalstudies it is shown that the treatment of childhood ADHD with stimulants does not increase therisk of SUD (Faraone and Wilens Kollins ) (Wilson 1 Other studies showthat treating childhood ADHD with stimulants results in a 50–70 % reduction of addiction(Wilens ). However, a prospective study in which children with ADHD were studied for10 years, results showed that short-term treatment with stimulants had no effect on the risk ofthe onset of substance abuse (Biederman et al. ). 2 Some authors have, therefore,concluded that stimulant treatment of childhood ADHD does not prevent the developmentof addiction. However, it is proposed that this is only true for short-term medical treatment and Int J Ment Health Addiction that treatment with medicine and/or psychotherapy, should be continued until young adulthoodin order to definitively prevent addiction in patients with ADHD.
Misuse of the Medication Patients being treated for ADHD often see treatment as a sign of recognition of their problems, thisfurther increases their treatment compliance. 4 Therefore, medication with a delayed effect (e.g.
atomoxetine) often causes dropout in extremely impatient individuals. However, in addictiontreatment centers there is often great concern about prescribing stimulants given their abusepotential in patients with SUD. Although methylphenidate should have less abuse potential thancocaine because of its pharmacological properties (slower uptake) when administered in thera-peutic doses (Kollins Volkow and Swanson 3 it remains a product that can be abusedby the patients themselves or by someone in their surroundings. In research, 16.5 % of thosesurveyed in an ADHD treatment center affirmed that they shared medication with others (Bright). 3 Products with immediate release effects are more likely to be abused than the modifiedreleased stimulants. Modafinil can also be abused (Turner et al. ). Atomoxetine, on the otherhand, has no abuse potential (Jasinski et al. ; Wilens et al. ), but has a delayed effect. 1 There is limited evidence about the effectiveness of psychotherapeutic treatment of ADHD inadults. However, there is some evidence on a positive effect of cognitive behavioral therapy(CBT) (Rostain and Ramsay ; Safren et al. Virta et al. ) ⓘ and structured skillstraining (Solanto et al. ⓘ . There are indications of a positive effect of psycho-educationand peer support (Murphy ) ⓘ, dialectical behavioral therapy (DBT) (Hesslinger et al.
Philipsen et al. ⓘ, and mindfulness training (Zylowska et al. ) ⓘ . Most ofthese methods are also part of the standard treatment in addiction and for some of them, suchas cognitive behavioral therapy (CBT), considerable evidence is available (Kleber et al. ;Rigter ). There is no evidence on the effects of any of these treatments in addicted patientswith ADHD. Only expert opinions are available (Goossensen et al. Levin et al. ). 4 Because of the chronic nature of both ADHD and addiction, with repercussions in all life domains, combining as many interventions as possible is recommended. According to theexperts in the focus groups, many therapeutic methods are appropriate for both the addictionproblem and the ADHD, e.g. providing structure, teaching time management and planningand learning to cope with impulsivity and mood swings. In an inpatient program, there issufficient time and manpower for these intensive therapies. In an outpatient setting, patientcontacts are often fragmentary and too short. Yet even in this setting, a combination ofindividual with group-based training and peer support seems to be the best answer to theproblem.
General Principles The treatment of ADHD in addicts can be started when the addiction problem is stabilized. DCombining medication with psychotherapy D and using an integrated approach to substanceabuse and ADHD (and to any other mental disorder present) are recommended. C Peer andfamily support enhances the effect of the treatment. D Int J Ment Health Addiction Pharmacological Treatment C Atomoxetine is preferred since it lacks abuse potential but the delayed effect can be a problemfor patients that express little patience in recovering. Methylphenidate (extended release) maybe prescribed, on the assumption that delivery and administration are sufficiently supervised.
Imipramine and bupropion are possible alternatives for the treatment of ADHD. Due to abusepotential, methylphenidate (immediate release) only has a place in an inpatient setting and inthe startup phase to assess its impact.
Extended release dexamphetamine can, in high doses, have a positive effect on cocaine use, but is not recommended at the moment. D A multimodal treatment is preferable. The first phase consists of psycho-education. In thesecond phase, cognitive behavioral therapy (CBT) and skills training (individually or group-based), C individual coaching and peer support are recommended in addition to medication. DDialectical behavior therapy (DBT) and mindfulness training can also be helpful. Relationshiptherapy should be considered. D Remaining comorbid disorders should be treated. S The guideline was approved by the Belgian Centre for Evidence-Based Medicine BelgianBranch of the Dutch Cochrane Centre (CEBAM) in September 2011. The literature search onwhich we based the development of our guidelines was completed in April 2009. In themeantime, some new research findings have been published. For this reason we carried out anew literature search with the same terms and using the same sources for the period May2009—July 2013. Eventually we selected three studies on screening and five on pharmaco-logical treatment trials (three RCT's and two open trials) in adults with ADHD and SUD. Thedata from these new studies have either confirmed or nuanced some of our findings andrecommendations.
A recent paper (Dakwar et al. confirmed that various ADHD screening instruments, recommended in our guideline, have adequate sensitivity and specificity in SUD population.
Especially the ASRS has been investigated in this population by several researchers (Chiassonet al. ; van de Glind et al. ), and was found to be useful with good sensitivity butlimited specificity. The data of van de Glind et al. also show that there is no differencein the screening results when patients are interviewed in the withdrawal stage or after a fewweeks of abstinence.
The support for the effect of medication on ADHD in patients with SUD is still limited.
However, some new open trials with sustained-release bupropion and atomoxetine are prom-ising (Wilens et al. ) (Adler et al. ). Furthermore, in an RCT with high dose osmoticrelease oral system methylphenidate there was a significant reduction of both ADHD-symptoms and the risk for relapse to substance use in criminal offenders with a co-diagnosisof ADHD and amphetamine dependence (Konstenius et al. In contrast, an RCT withatomoxetine in adolescents did not show any difference with the placebo group (Thurstoneet al. ; Wilens et al. Finally, the evidence for the effect of cognitive behavioral therapy (CBT) and dialectical behavioral therapy (DBT) in patients with ADHD (without SUD) is now stronger (Hirvikoskiet al. Safren et al. Solanto et al. ).
Int J Ment Health Addiction This is the first evidence-based guideline for the diagnosis and treatment of ADHD in adultswith SUD. Only limited evidence was found for screening, diagnosis and treatment. Whenevidence was not available, our recommendations are based on expert consensus. Fear of bothover-diagnosis and under-diagnosis is common. The diagnostic rules are often too strict, e.g.
regarding information from early childhood and the requirement for complete abstinence.
Especially in an inpatient setting observation may provide more information than self-reportquestionnaires and interviews. Standard neuropsychological examination may be useful toobjectify and measure deficits in executive functioning.
We found strong evidence for the effect of pharmacological treatment of ADHD in adults without SUD, but not for ADHD patients with a comorbid substance use disorder. Perhaps thedosages in this population need to be increased (Konstenius et al. ). Considering thespecific vulnerability of our patients and the misuse of medication, caution is needed whenprescribing stimulants. Although there is only limited evidence for the effectiveness of non-pharmacological treatment in ADHD patients with a comorbid addiction, there are indicationsthat the combination with the evidence-based treatments from addiction care may be effectivein this population with some adaptation. However, more research is needed for the develop-ment of integrated treatments that target both ADHD and substance abuse in order to gobeyond standard treatment.
Contemporary research does not lead to new conclusions. Major differences were not found between the group treated with medication and the placebo group. It was interesting to find, asit was already mentioned in our findings, that both groups (who also receive motivationalintervention and cognitive behavioral treatment) have a high treatment response. We thereforelook forward to the results of research into integrated cognitive behavioral therapy (CBT) forwhich a protocol was recently published (van Emmerik-van Oortmerssen et al. We hope this guideline will help practitioners to make their approach more effective and will encourage the scientific community to start new research efforts in this area. A strategyshould be developed to implement the guideline in treatment centers.
Weaknesses and Strengths of the Guideline This guideline is based on a limited number of studies. A potential limitation of this review isthe possibility of missing articles despite our attempt to include all pertinent articles and to becomprehensive by checking the reference lists of selected studies. Nevertheless, studies thatwere in a language other than English and Dutch were not reviewed. Due to the lack ofscientific evidence in this patient group, the guideline is a combination of evidence- based andpractice-based recommendations. Even though the evidence base was limited, the recommen-dations in this guideline were systematically developed.
Acknowledgments We are grateful to the Forum of Addiction Medicine, the Guideline Development Groupand all the participants of the focus groups. The study was funded by the Belgian Federal Public Service (FPS)Food Chain Safety and Environment (Health.belgium.be Role of Funding Sources The study was funded by the Belgian Federal Public Service (Health, Food ChainSafety and Environment). The Federal Public Service had no role in the study design, collection, analysis orinterpretation of the data, writing the manuscript, or the decision to submit the paper for publication.
Conflict of Interest All authors declare that they have no conflicts of interest.
Int J Ment Health Addiction Adler, L., & Cohen, J. (2004). Diagnosis and evaluation of adults with attention-deficit/hyperactivity disorder.
Psychiatric Clinics of North America, 27(2), 187–201.
Adler, L. A., Faraone, S. V., Spencer, T. J., Michelson, D., Reimherr, F. W., Glatt, S. J., et al. (2008). The reliability and validity of self- and investigator ratings of ADHD in adults. Journal of Attention Disorders,11(6), 711–719.
Adler, L., Guida, F., Irons, S., & Shaw, D. M. (2010). Open label pilot study of atomoxetine in adults with ADHD and substance use disorder. Journal of Dual Diagnosis, 6(3–4), 196–207. do.
Agreecollaboration.org. (2003). Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project. Qual Saf Health Care,12(1), 18–23.
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.).
Arlington: American Psychiatric Publishing.
Arcia, E., & CONNERS, K. C. (1998). Gender differences in ADHD? Journal of Developmental & Behavioral Pediatrics, 19(2), 77–83.
Arias, A. J., Gelernter, J., Chan, G., Weiss, R. D., Brady, K. T., Farrer, L., et al. (2008). Correlates of co-occurring ADHD in drug-dependent subjects: prevalence and features of substance dependence and psychiatricdisorders. Addictive Behaviors, 33(9), 1199–1207.
Biederman, J., Wilens, T., Mick, E., Milberger, S., Spencer, T. J., & Faraone, S. V. (1995). Psychoactive substance use disorders in adults with attention deficit hyperactivity disorder (ADHD): effects of ADHDand psychiatric comorbidity. American Journal of Psychiatry, 152(11), 1652–1658.
Biederman, J., Wilens, T. E., Mick, E., Faraone, S. V., & Spencer, T. (1998). Does attention-deficit hyperactivity disorder impact the developmental course of drug and alcohol abuse and dependence? Biological Psychiatry,44(4), 269–273.
Biederman, J., Monuteaux, M. C., Mick, E., Spencer, T., Wilens, T. E., Klein, K. L., et al. (2006).
Psychopathology in females with attention-deficit/hyperactivity disorder: a controlled, five-year prospectivestudy. Biological Psychiatry, 60(10), 1098–1105.
Biederman, J., Monuteaux, M. C., Spencer, T., Wilens, T. E., & Faraone, S. V. (2009). Do stimulants protect against psychiatric disorders in youth with ADHD? A 10-year follow-up study. Pediatrics, 124(1), 71–78.
Bright, G. M. (2008). Abuse of medications employed for the treatment of ADHD: results from a large-scale community survey. The Medscape Journal of Medicine, 10(5), 111.
Carpentier, P. J., Knapen, L. J., van Gogh, M. T., Buitelaar, J. K., & De Jong, C. A. (2012). Addiction in developmental perspective: influence of conduct disorder severity, subtype, and attention-deficit hyperac-tivity disorder on problem severity and comorbidity in adults with opioid dependence. Journal of AddictiveDiseases, 31(1), 45–59.
Castaneda, R., Levy, R., Hardy, M., & Trujillo, M. (2000). Long-acting stimulants for the treatment of attention- deficit disorder in cocaine-dependent adults. Psychiatric Services, 51(2), 169–171.
Cebam.be. (2013). Default. [online] Retrieved from: Chiasson, J. P., Stavro, K., Rizkallah, E., Lapierre, L., Dussault, M., Legault, L., et al. (2012). Questioning the specificity of ASRS-v1.1 to accurately detect ADHD in substance abusing populations. Journal of AttentionDisorders, 16(8), 661–663. doi.
Cleland, C., Magura, S., Foote, J., Rosenblum, A., & Kosanke, N. (2006). Factor structure of the Conners adult ADHD rating scale (CAARS) for substance users. Addictive Behaviors, 31(7), 1277–1282.
Culpepper, L., & Mattingly, G. (2008). A practical guide to recognition and diagnosis of ADHD in adults in the primary care setting. Postgraduate Medicine, 120(3), 16–26.
Dakwar, E., Mahony, A., Pavlicova, M., Glass, A., Brooks, D., Mariani, J. J., et al. (2012). The utility of attention-deficit/hyperactivity disorder screening instruments in individuals seeking treatment forsubstance use disorders. The Journal of Clinical Psychiatry, 73(11), e1372–e1378. doi: Dodson, W. W. (2005). Pharmacotherapy of adult ADHD. Journal of Clinical Psychology, 61(5), 589–606.
Epstein, J.N., Johnson D.E., & C.K., C. (2001). CAADID, the Conner's Adult ADHD Diagnostic Interview for DSM-IV. Multi-Health Systems. New York: North Tonawanda.
Faraone, S. V., & Wilens, T. (2003). Does stimulant treatment lead to substance use disorders? American Journal of Clinical Psychiatry, 64(Suppl 11), 9–13.
Faraone, S. V., Sergeant, J., Gillberg, C., & Biederman, J. (2003). The worldwide prevalence of ADHD: is it an American condition? World Psychiatry, 2(2), 104–113.
Faraone, S. V., Wilens, T. E., Petty, C., Antshel, K., Spencer, T., & Biederman, J. (2007). Substance use among ADHD adults: implications of late onset and subthreshold diagnoses. The American Journal on Addictions,16(Suppl 1), 24–32. quiz 33–34.
Int J Ment Health Addiction Farhoodi, F., Rostami, R., Abdolmanafi, A., & Amiri, M. (2010). A study and comparison of the symptoms of attention deficit hyperactivity disorder (ADHD) among patients with substance use disorder and normalpeople. Procedia-Social and Behavioral Sciences, 5, 892–895.
Fayyad, J., De Graaf, R., Kessler, R., Alonso, J., Angermeyer, M., Demyttenaere, K., et al. (2007). Cross– national prevalence and correlates of adult attention–deficit hyperactivity disorder. The British Journal ofPsychiatry, 190(5), 402–409.
Gingerich, K. J., Turnock, P., Litfin, J. K., & Rosen, L. A. (1998). Diversity and attention deficit hyperactivity disorder. Journal of Clinical Psychology, 54(4), 415–426.
Glind, G. van de, Kooij JJS, Duin, D. van, Goossensen, A., & Carpentier, PJ (2004). Protocol ADHD bij verslaving. Screening, diagnostiek en behandeling voor de ambulante en klinische verslavingszorg.
Goossensen, M. A., van de Glind, G., Carpentier, P. J., Wijsen, R., van Duin, D., & Kooij, J. J. (2006). An intervention program for ADHD in patients with substance use disorders: preliminary results of a field trial.
Journal of substance abuse treatment, 30(3), 253–259.
Health.belgium.be. (2014). Fps health. [online] Retrieved from: Hesslinger, B., van Elst, L. T., Nyberg, E., Dykierek, P., Richter, H., Berner, M., et al. (2002). Psychotherapy of attention deficit hyperactivity disorder in adults. European archives of psychiatry and clinical neuroscience,252(4), 177–184.
Hirvikoski, T., Waaler, E., Alfredsson, J., Pihlgren, C., Holmstrom, A., Johnson, A., et al. (2011). Reduced ADHD symptoms in adults with ADHD after structured skills training group: results from a randomizedcontrolled trial. Behavior Research and Therapy, 49(3), 175–185. doi.
Jasinski, D. R., Faries, D. E., Moore, R. J., Schuh, L. M., & Allen, A. J. (2008). Abuse liability assessment of atomoxetine in a drug-abusing population. Drug and Alcohol Dependence, 95(1–2), 140–146.
Kalbag, A. S., & Levin, F. R. (2005). Adult ADHD and substance abuse: diagnostic and treatment issues.
Substance Use & Misuse, 40(13–14), 1955–1981.
Katz, L. J., Wood, D. S., Goldstein, G., Auchenbach, R. C., & Geckle, M. (1998). The utility of neuropsycho- logical tests in evaluation of Attention-Deficit/ Hyperactivity Disorder (ADHD) versus depression in adults.
Assessment, 5(1), 45–52.
Kaye, S., Darke, S., & Torok, M. (2013). Attention deficit hyperactivity disorder (ADHD) among illicit psychostimulant users: a hidden disorder? Addiction, 108(5), 923–931. doi: Kendall, T., Taylor, E., Perez, A., Taylor, C., & THOMPSON, A. (2008). Diagnosis and management of attention-deficit/hyperactivity disorder in children, young people, and adults: summary of NICE guidance.
Commentary. BMJ. British medical Journal, 337(7672), 751–754.
Kim, E. Y., & Miklowitz, D. J. (2002). Childhood mania, attention deficit hyperactivity disorder and conduct disorder: a critical review of diagnostic dilemmas. Bipolar Disorders, 4(4), 215–225.
Kleber, H. D., Weiss, R. D., Anton, R. F., Jr., George, T. P., Greenfield, S. F., Kosten, T. R., Regier, D. (2007).
Treatment of patients with substance use disorders, second edition. American Psychiatric Association. Am JPsychiatry, 164(4 Suppl), 5–123.
Kollins, S. H. (2003). Comparing the abuse potential of methylphenidate versus other stimulants: a review of available evidence and relevance to the ADHD patient. Journal of Clinical Psychiatry, 64, 14–18.
Kollins, S. H. (2008). ADHD, substance use disorders, and psychostimulant treatment: current literature and treatment guidelines. Journal of Attention Disorders, 12(2), 115–125. doi.
Konstenius, M., Jayaram-Lindstrom, N., Guterstam, J., Beck, O., Philips, B., & Franck, J. (2013).
Methylphenidate for ADHD and drug relapse in criminal offenders with substance dependence: A 24-week randomized placebo-controlled trial. Addiction. doi Kooij, J. S. (2012). Adult ADHD: Diagnostic assessment and treatment. London: Springer.
Kooij, S. J., Bejerot, S., Blackwell, A., Caci, H., Casas-Brugué, M., Carpentier, P. J., et al. (2010). European consensus statement on diagnosis and treatment of adult ADHD: the European Network Adult ADHD. BMCPsychiatry, 10(1), 67.
Levin, F. R., & Upadhyaya, H. P. (2007). Diagnosing ADHD in adults with substance use disorder: DSM-IV criteria and differential diagnosis. Journal of Clinical Psychiatry, 68(7), e18.
Levin, F. R., Evans, S. M., & Kleber, H. D. (1999). Practical guidelines for the treatment of substance abusers with adult attention-deficit hyperactivity disorder. Psychiatric Services, 50(8),1001–1003.
Levin, F. R., Evans, S. M., McDowell, D. M., Brooks, D. J., & Nunes, E. (2002). Bupropion treatment for cocaine abuse and adult attention-deficit/hyperactivity disorder. Journal of Addictive Diseases,21(2), 1–16.
Levin, F. R., Evans, S. M., Vosburg, S. K., Horton, T., Brooks, D., & Ng, J. (2004). Impact of attention-deficit hyperactivity disorder and other psychopathology on treatment retention among cocaine abusers in atherapeutic community. Addictive Behaviors, 29(9), 1875–1882.
Int J Ment Health Addiction Levin, F. R., Evans, S. M., Brooks, D. J., Kalbag, A. S., Garawi, F., & Nunes, E. V. (2006). Treatment of methadone-maintained patients with adult ADHD: double-blind comparison of methylphenidate, bupropionand placebo. Drug and Alcohol Dependence, 81(2), 137–148.
Levin, F. R., Evans, S. M., Brooks, D. J., & Garawi, F. (2007). Treatment of cocaine dependent treatment seekers with adult ADHD: double-blind comparison of methylphenidate and placebo. Drug and AlcoholDependence, 87(1), 20–29.
Levin, F. R., Bisaga, A., Raby, W., Aharonovich, E., Rubin, E., Mariani, J., et al. (2008). Effects of major depressive disorder and attention-deficit/hyperactivity disorder on the outcome of treatment for cocainedependence. Journal of Substance Abuse Treatment, 34(1), 80–89.
Levin, F. R., Mariani, J. J., Secora, A., Brooks, D., Cheng, W. Y., Bisaga, A., et al. (2009). Atomoxetine treatment for cocaine abuse and adult attention-deficit hyperactivity disorder (ADHD): a preliminary opentrial. Journal of Dual Diagnosis, 5(1), 41–56.
Maidment, I. D. (2003). The use of antidepressants to treat attention deficit hyperactivity disorder in adults.
Journal of Psychopharmacology, 17(3), 332–336.
Mann, N., & Bitsios, P. (2009). Modafinil treatment of amphetamine abuse in adult ADHD. Journal of Psychopharmacology, 23(4), 468–471.
Mariani, J. J., & Levin, F. R. (2007). Treatment strategies for co–occurring adhd and substance use disorders. The American Journal on Addictions, 16(s1), 45–56.
Matthys, F., Joostens, P., Stes, S., Tremmery, S., & Sabbe, B. (2013). The construction of the first validated (evidence based) guideline for dual diagnosis of ADHD and SUD; data from focus groups. InternationalJournal of Mental Health and Addiction, 11(5), 557–567. doi Mészáros, A., Czobor, P., Bálint, S., Komlósi, S., Simon, V., & Bitter, I. (2009). Pharmacotherapy of adult attention deficit hyperactivity disorder (ADHD): a meta-analysis. The International Journal ofNeuropsychopharmacology, 12(08), 1137–1147.
Monuteaux, M. C., Wilens, T. E., & Biederman, J. (2007). Does social class predict substance problems in young adults with ADHD? The American Journal on Addictions, 16(5), 403–409.
Murphy, K. (2005). Psychosocial treatments for ADHD in teens and adults: a practice-friendly review. Journal of Clinical Psychology, 61(5), 607–619.
Peterson, K., McDonagh, M. S., & Fu, R. (2008). Comparative benefits and harms of competing medications for adults with attention-deficit hyperactivity disorder: a systematic review and indirect comparison meta-analysis. Psychopharmacology, 197(1), 1–11.
Philipsen, A., Richter, H., Peters, J., Alm, B., Sobanski, E., Colla, M., et al. (2007). Structured group psychotherapy in adults with attention deficit hyperactivity disorder: results of an open multicentre study.
The Journal of Nervous and Mental Disease, 195(12), 1013–1019.
Quinn, P. O. (2008). Attention-deficit/hyperactivity disorder and its comorbidities in women and girls: an evolving picture. Current Psychiatry Reports, 10(5), 419–423.
Ramsay, J. R., & Rostain, A. L. (2005). Adapting psychotherapy to meet the needs of adults with attention- deficit/hyperactivity disorder. Psychotherapy: Theory, Research, Practice, Training, 42(1), 72–84.
Riggs, P. D., Leon, S. L., Mikulich, S. K., & Pottle, L. C. (1998). An open trial of bupropion for ADHD in adolescents with substance use disorders and conduct disorder. Journal of the American Academy of Child &Adolescent Psychiatry, 37(12), 1271–1278.
Rigter, H. (2006). What drug policies cost: drug policy spending in the Netherlands in 2003. Addiction, 101(3), Robison, R. J., Reimherr, F. W., Marchant, B. K., Faraone, S. V., Adler, L. A., & West, S. A. (2008). Gender differences in 2 clinical trials of adults with attention-deficit/hyperactivity disorder: a retrospective dataanalysis. The Journal of Clinical Psychiatry, 69(2), 213–221.
Rohde, L. A., Szobot, C., Polanczyk, G., Schmitz, M., Martins, S., & Tramontina, S. (2005). Attention-deficit/ hyperactivity disorder in a diverse culture: do research and clinical findings support the notion of a culturalconstruct for the disorder? Biological Psychiatry, 57(11), 1436–1441.
Rostain, A. L., & Ramsay, J. R. (2006). A combined treatment approach for adults with ADHD–results of an open study of 43 patients. Journal of Attention Disorders, 10(2), 150–159.
Safren, S. A., Otto, M. W., Sprich, S., Winett, C. L., Wilens, T. E., & Biederman, J. (2005). Cognitive-behavioral therapy for ADHD in medication-treated adults with continued symptoms. Behavior Research and Therapy,43(7), 831–842.
Safren, S. A., Sprich, S., Mimiaga, M. J., Surman, C., Knouse, L., Groves, M., et al. (2010). Cognitive behavioral therapy vs relaxation with educational support for medication-treated adults with ADHD and persistentsymptoms: a randomized controlled trial. Jama, 304(8), 875–880.
Sign.ac.uk. (2001). Scottish intercollegiate guidelines network (SIGN). SIGN 50: A guideline developer's handbook. Retrieved from: .
Int J Ment Health Addiction Solanto, M. V., Marks, D. J., Mitchell, K. J., Wasserstein, J., & Kofman, M. D. (2008). Development of a new psychosocial treatment for adult ADHD. Journal of Attention Disorders, 11(6), 728–736.
Solanto, M. V., Marks, D. J., Wasserstein, J., Mitchell, K., Abikoff, H., Alvir, J. M., et al. (2010). Efficacy of meta-cognitive therapy for adult ADHD. American Journal of Psychiatry, 167(8), 958–968. doi Solhkhah, R., Wilens, T. E., Daly, J., Prince, J. B., Van Patten, S. L., & Biederman, J. (2005). Bupropion SR for the treatment of substance-abusing outpatient adolescents with attention-deficit/hyperactivitydisorder and mood disorders. Journal of Child & Adolescent Psychopharmacology, 15(5),777–786.
Somoza, E. C., Winhusen, T. M., Bridge, T. P., Rotrosen, J. P., Vanderburg, D. G., Harrer, J. M., et al. (2004). An open-label pilot study of methylphenidate in the treatment of cocaine dependent patients with adult attentiondeficit/hyperactivity disorder. Journal of Addictive Diseases, 23(1), 77–92.
Sullivan, M. A., & RUDNIK–LEVIN, F. R. A. N. C. E. S. (2001). Attention deficit/hyperactivity disorder and substance abuse. Annals of the New York Academy of Sciences, 931(1), 251–270.
Szobot, C. M., Shih, M. C., Schaefer, T., Júnior, N., Hoexter, M. Q., Fu, Y. K., et al. (2008). Methylphenidate DAT binding in adolescents with attention-deficit/hyperactivity disorder comorbid with substance usedisorder-a single photon emission computed tomography with [Tc <sup> 99m</sup>] TRODAT-1 study.
Neuroimage, 40(3), 1195–1201.
Thurstone, C., Riggs, P. D., Salomonsen-Sautel, S., & Mikulich-Gilbertson, S. K. (2010). Randomized, con- trolled trial of atomoxetine for attention-deficit/hyperactivity disorder in adolescents with substance usedisorder. Journal of the American Academy of Child & Adolescent Psychiatry, 49(6), 573–582.
Turner, D. C., Clark, L., Dowson, J., Robbins, T. W., & Sahakian, B. J. (2004). Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder. Biological Psychiatry, 55(10), 1031–1040.
Upadhyaya, H. P. (2006). Managing attention-deficit/hyperactivity disorder in the presence of substance use disorder. The Journal of Clinical Psychiatry, 68, 23–30.
Vaiva, G., De Lenclave, M. B., & Bailly, D. (2002). Treatment of comorbid opiate addiction and attention-deficit hyperactivity disorder (residual type) with moclobemide: a case report. Progress inNeuropsychopharmacology and Biological Psychiatry, 26(3), 609–611.
van de Glind, G., van den Brink, W., Koeter, M. W., Carpentier, P. J., van Emmerik-van Oortmerssen, K., Kaye, S., et al. (2013). Validity of the adult ADHD self-report scale (ASRS) as a screener for adult ADHD intreatment seeking substance use disorder patients. Drug and Alcohol Dependence. doi.
van Emmerik-van Oortmerssen, K., van de Glind, G., van den Brink, W., Smit, F., Crunelle, C. L., Swets, M., et al. (2012). Prevalence of attention-deficit hyperactivity disorder in substance use disorder patients: Ameta-analysis and meta-regression analysis. Drug and Alcohol Dependence, 122(1–2), 11–19.
van Emmerik-van Oortmerssen, K., Vedel, E., Koeter, M. W., de Bruijn, K., Dekker, J. J. M., van den Brink, W.
et al. (2013). Investigating the efficacy of integrated cognitive behavioral therapy for adult treatment seekingsubstance use disorder patients with comorbid ADHD: study protocol of a randomized controlled trial. BMCPsychiatry, 13. doi: Verbeeck, W., Tuinier, S., & Bekkering, G. E. (2009). Antidepressants in the treatment of adult attention-deficit hyperactivity disorder: a systematic review. Advances in Therapy, 26(2), 170–184. doi: Virta, M., Vedenpää, A., Grönroos, N., Chydenius, E., Partinen, M., Vataja, R., et al. (2008). Adults with ADHD benefit from cognitive—behaviorally oriented group rehabilitation a study of 29 participants. Journal ofAttention Disorders, 12(3), 218–226.
Volkow, N. D., & Swanson, J. M. (2003). Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD. American Journal of Psychiatry, 160(11), 1909–1918.
Waite, R. (2007). Women and attention deficit disorders: a great burden overlooked. Journal of the American Academy of Nurse Practitioners, 19(3), 116–125.
West, S. L., Mulsow, M., & Arredondo, R. (2003). Factor analysis of the attention deficit scales for adults (ADSA) with a clinical sample of outpatient substance abusers. The American Journal on Addictions, 12(2), 159–165.
West, S. L., Mulsow, M., & Arredondo, R. (2007). An examination of the psychometric properties of the attention deficit scales for adults with outpatient substance abusers. The American Journal of Drug andAlcohol Abuse, 33(5), 755–764.
Wilens, T. E. (2004a). Attention-deficit/hyperactivity disorder and the substance use disorders: the nature of the relationship, subtypes at risk, and treatment issues. Psychiatric Clinics of North America, 27(2), 283–301.
Wilens, T. E. (2004b). Impact of ADHD and its treatment on substance abuse in adults. Journal of Clinical Psychiatry, 65(Suppl 3), 38–45.
Wilens, T. E., & Upadhyaya, H. P. (2007). Impact of substance use disorder on ADHD and its treatment. The Journal of Clinical Psychiatry, 68(8), e20.
Int J Ment Health Addiction Wilens, T. E., Biederman, J., Mick, E., Faraone, S. V., & Spencer, T. (1997). Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders. The Journal of Nervous & MentalDisease, 185(8), 475–482.
Wilens, T. E., Kwon, A., Tanguay, S., Chase, R., Moore, H., Faraone, S. V., et al. (2005). Characteristics of adults with attention deficit hyperactivity disorder plus substance use disorder: the role of psychiatric comorbidity.
The American Journal on Addictions, 14(4), 319–327.
Wilens, T. E., Adler, L. A., Weiss, M. D., Michelson, D., Ramsey, J. L., Moore, R. J., et al. (2008). Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders. Drug & Alcohol Dependence, 96(1–2),145–154.
Wilens, T. E., Prince, J. B., Waxmonsky, J., Doyle, R., Spencer, T., Martelon, M., et al. (2010). An open trial of sustained release bupropion for attention-deficit/hyperactivity disorder in adults with ADHD plus substanceuse disorders. Journal of ADHD & related disorders, 1(3), 25–35.
Wilens, T. E., Adler, L. A., Tanaka, Y., Xiao, F., D'Souza, D. N., Gutkin, S. W., et al. (2011). Correlates of alcohol use in adults with ADHD and comorbid alcohol use disorders: exploratory analysis of a placebo-controlled trial of atomoxetine. Current Medical Research & Opinion, 27(12), 2309–2320. doi Wilson, J. J. (2007). ADHD and substance use disorders: developmental aspects and the impact of stimulant treatment. The American Journal on Addictions, 16(s1), 5–13.
Wilson, J. J., & Levin, F. R. (2001). Attention deficit hyperactivity disorder (ADHD) and substance use disorders.
Current Psychiatry Reports, 3(6), 497–506.
Winhusen, T., Somoza, E., Singal, B. M., Harrer, J., Apparaju, S., Mezinskis, J., et al. (2006). Methylphenidate and cocaine: a placebo-controlled drug interaction study. Pharmacology Biochemistry and Behavior, 85(1), 29–38.
Zylowska, L., Ackerman, D. L., Yang, M. H., Futrell, J. L., Horton, N. L., Hale, T. S., et al. (2008). Mindfulness meditation training in adults and adolescents with ADHD: a feasibility study. Journal of Attention Disorders,11(6), 737–746.
FOCUS ON CLINICAL ELECTROPHORESIS: Progress Report as of October 2005 THERAPEUTIC UP-DATING ON BLOOD DISEASES MANAGEMENT OF MONOCLONAL GAMMAPATHIES Assessment of Monoclonal Gammapathies COMPARATIVE ECONOMIC COSTS CELLOGEL: what is it and how is it used? The use of Cellogel EQUIPMENT FOR ELECTROPHORESIS ON CELLOGEL Electrophoretic tank for Cellogel Bridges for Cellogel tank