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The American Journal on Addictions, 16: 45–56, 2007Copyright # American Academy of Addiction PsychiatryISSN: 1055-0496 print / 1521-0391 onlineDOI: 10.1080/10550490601082783 Treatment Strategies for Co-Occurring ADHDand Substance Use Disorders John J. Mariani, MD, Frances R. Levin, MD New York State Psychiatric Institute, New York, New York;Division on Substance Abuse, Columbia University College of Physicians and Surgeons, New York, New York Attention-deficit hyperactivity disorder (ADHD) is a  Describe treatment scenarios in ADHD that common co-occurring mental disorder among patients with are most likely to lead to SUD, exacerbate substance use disorders (SUD). Clinicians must be cogni- ongoing SUD, or minimize risks of SUD.
zant of the complicated nature of diagnosis and treatmentof ADHD when comorbid with SUD. Pharmacotherapy  Provide an overview of psychosocial treatments remains the mainstay of treatment for ADHD, although for ADHD and co-occurring SUD that can help complementary psychotherapeutic approaches have been optimize long-term treatment effectiveness.
developed. Psychostimulant medications are the most com-monly used medications to treat ADHD, but many clini-cians are reluctant to prescribe stimulants to patients with SUD. Recommendations for treatment planning and clinicalmanagement for patients with co-occurring ADHD andSUD are discussed. (Am J Addict 2007;16:45–56) Attention-deficit hyperactivity disorder (ADHD) is a syndrome characterized by persistent patterns of Downloaded By: [UAJA - American Journal on Addictions] At: 11:56 5 May 2007 inattention and=or impulsivity and hyperactivity that isinappropriate for a given age or developmental stage.
ADHD is the most common mental disorder in child-hood,1 with an estimated prevalence in the United States Upon completion of this activity, participants should of 5–10%.2,3 It is estimated that up to 60% of childhood cases of ADHD will continue to have clinically significant  Identify typical challenges in clinical diagnosis symptoms of ADHD as adults,4–7 and the prevalence of ADHD in adults with co-occurring SUD.
of adult ADHD in the United States is estimated to be  Explain how different types of ADHD phar- 2–5%.8–11 ADHD symptoms result in a large individual macotherapies affect the risks of SUD in speci- and public burden; it is estimated that consequences of ADHD result in the loss of 120 million days of annual  Distinguish between primary symptoms and lost work in the U.S. labor force, which is equivalent to Large-scale epidemiologic surveys in the United States  Discuss the advantages and disadvantages of have reported that substance use disorders are associated non-stimulant medications in patients with with increased rates of comorbid psychiatric disor- ADHD and co-occurring SUD, including sec- ders,9,13–16 including mood, psychotic, anxiety, personal- ity, and other classes of disorders. While it is clear thatsubstance use disorders are associated with increased Received August 29, 2006; revised September 20, 2006; rates of comorbid psychiatric disorders as compared to the general population, the converse is true as well: indi- Dr. Levin has current or past research support from Ortho- viduals with substance-independent psychiatric disorders McNeil Pharmaceuticals, Eli Lilly & Company, Shire, Astra are at an increased risk of having a substance use disor- Zeneca, and UCB Pharma, and serves or has served as a consul- tant to Shire Pharmaceuticals, AstraZeneca, Ortho-McNeil reported that among individuals with any lifetime mental Pharmaceuticals, and Cephalon=Alkermes.
Address correspondence to Dr. Mariani, 1051 Riverside disorder diagnosis, 28.9% had a lifetime substance use Drive, Unit 66, New York, New York 10032. E-mail: disorder, as compared to a rate of 13.2% for those respondents who had no history of a mental disorder.
The ECA found that having a lifetime history of any men- As the development of SUD is also linked to dopa- tal disorder was associated with more than twice the risk mine,38 there may be common factors that lead to the of having an alcohol disorder and more than four times development of ADHD and co-occurring SUD. By defi- the risk of having a drug use disorder.
nition, ADHD is present before the age of 7, and SUDs The association of ADHD and SUD has become an often develop during adolescence and early adulthood, increasing focus of investigation over the past decade. Stu- so it is likely that the increased association of ADHD dies of clinical samples of individuals with SUD seeking and SUD is the product of a developmental interaction treatment have demonstrated that ADHD is a common with ADHD symptoms (eg, impulsivity or behavior dys- co-occurring mental disorder,17–19 although historically, regulation) and the consequences of ADHD (eg, poor community-based studies have not included adult ADHD academic performance), creating an increased opportu- among the disorders surveyed.13,14,16 However, the nity for the development of a SUD. Emerging evidence recently published National Comorbidity Survey Replica- suggests that psychostimulant treatment of ADHD dur- tion (NCS-R) included ADHD in its survey and estimated ing childhood reduces the likelihood of developing a the prevalence of adult ADHD to be 4.4%.8 With regards SUD,39 although the exact mechanism of this risk reduc- to the rate of co-occurrence of ADHD and SUD, the tion is not known. The risk of initiation of substance use NCS-R found that 15.2% of individuals with adult in adolescents is related more to symptom severity (eg, ADHD met DSM-IV criteria for a SUD, as compared aggression or impulsivity) than the status of meeting cri- to 5.6% of individuals without ADHD, resulting in a sig- teria for ADHD,40 suggesting that the risk of SUD devel- nificant odds ratio of 3.0.8 Complimentary to these find- opment in adolescents with ADHD is dimensional, rather ings, the NCS-R found that among individuals with than categorical. In adolescents, the severity of atten- SUD, 10.8% met criteria for adult ADHD, as compared tional symptoms may be a more important risk factor to a prevalence of 3.8% in individuals without SUD.
The rates of ADHD co-occurrence in studies of treat- Given the common co-occurrence of ADHD with ment-seeking clinical samples of individuals with SUD SUD, clinicians working with patients with SUD must are higher than the community-based NCS-R, with the be proficient in the identification and treatment of reported prevalence of adult ADHD ranging from 10– ADHD. Due to the evolving understanding of the clinical 24%.17–19 In addition, it is estimated that more than manifestations of adult ADHD42 and the relatively recent 25% of substance-abusing adolescents meet diagnostic recognition of the elevated risk of ADHD among adults Downloaded By: [UAJA - American Journal on Addictions] At: 11:56 5 May 2007 criteria for ADHD.20–22 This disparity in rates of co- with SUD,8 clinicians working with SUD patients are occurring ADHD and substance use disorders between often unfamiliar with the assessment and management of community-based and clinical studies is likely due to ADHD. Further, because the primary treatment for Berkson’s bias,23 which is the phenomenon that patients in clinical treatment settings are more likely to exhibit a an inherent abuse potential, the treatment of ADHD in higher degree of association between two disorders. A patients with SUD is both complex and controversial.
practical outcome of this phenomenon is that clinicians This article discusses treatment planning and clinical man- in SUD treatment settings will frequently encounter co- agement of patients with co-occurring ADHD and SUD.
While the exact cause of ADHD is unknown, the avail- able evidence supports the theory that dopamine neuro-transmission dysfunction is at least partly responsible The diagnosis of ADHD in children and adults remains for the characteristic symptoms of ADHD. Evidence sup- a clinical diagnosis—there are no neuropsychiatric or porting dopamine involvement in ADHD symptomatol- laboratory tests that alone have been shown to have clin- ogy includes pharmacotherapy studies, which show that ical utility in diagnosing ADHD. In adults, the clinical stimulant medications that increase dopamine levels effec- diagnosis of ADHD remains challenging, particularly in tively treat ADHD symptoms,24–27 genetic studies, which patients with co-occurring SUD, as there is a lack of con- have linked dopamine genes to ADHD,28–30 and imaging sensus on diagnostic criteria,42 symptoms overlap with studies, which have shown abnormalities of dopamine other psychiatric disorders, and there is a need for a function and structural abnormalities in regions of the retrospective diagnosis of childhood ADHD. The criteria brain with concentrations of dopamine-producing neu- for ADHD in the Diagnostic and Statistical Manual of rons.31–33 The therapeutic effects of psychostimulants on Mental Disorders (DSM-IV-TR)43 were developed for ADHD symptoms are thought to be due to their ability diagnosing ADHD in children and are currently used for to increase extracellular dopamine,34,35 particularly in adults as well, although the validity of the criteria set is the striatum.36 Volkow and Swanson37 have postulated that psychostimulant-induced extracellular dopamine Diagnosing ADHD in patients who are actively using release in the striatum improves attention by the enhance- substances or who recently initiated abstinence is challen- ment of task-related neuronal cell firing.
ging. Substances of abuse have many acute and chronic Co-Occurring ADHD and Substance Use Disorders effects that mimic the symptoms of psychiatric disorders, including ADHD. For example, the use of stimulantscan lead to changes in attentional capacity and activity level Given the ongoing controversy over the diagnostic cri- both during intoxication and recovery, and chronic mari- teria for ADHD in adults and the complicated clinical juana use may lead to deficits in attention. In addition, issue of using ADHD pharmacotherapy in patients with many patients are unable to describe recent periods of absti- SUD, a reasonable starting point in discussing treatment nence from substance use, making the distinction between strategies is to ask, How important is it to treat ADHD in primary and substance-induced symptoms difficult.
patients with SUD? An initial approach this question is to While some authorities recommend evaluating patients consider the impact of ADHD on individuals who do not after a period of prolonged abstinence,44 this is not possi- have SUD. Adults with ADHD have less educational ble in many cases. Often a careful clinical history of symp- attainment, increased dismissals from their jobs, more toms during past periods of abstinence or prior to the traffic accidents and car license suspensions, more onset of substance use problems is the best available psychosocial problems with social deficits, and a greater method to assess whether inattention and hyperactivity frequency of divorce.12,50 The next step is to consider symptoms represent a primary disorder or are sub- the evidence that ADHD affects the development and stance-induced. Symptoms that occur during periods of course of substance use disorders: individuals with sub- active substance use are difficult to interpret, because if stance use disorders and ADHD have an earlier onset they occur exclusively in the context of active substance of substance abuse than those without ADHD, a greater use, a diagnosis of ADHD is inappropriate. Furthermore, likelihood of having continuous problem if they develop in adults, the clinical diagnosis of ADHD remains chal- substance dependence, a reduced likelihood of going lenging, because there is a lack of consensus on diagnostic into remission, and a tendency to take longer to reach criteria, particularly regarding the requirement that symp- remission.51 Despite having more treatment exposure, toms be present prior to the age of 7.42 However, because individuals who have ADHD seem to do less well with retrospective diagnoses of childhood ADHD in adults SUD treatment,51,52 although this may reflect that indivi- made on the basis of self-report tend to overdiagnosis duals with more severe symptoms are more likely to ADHD,45 a conservative approach must be maintained.
receive SUD treatment. Also, both adolescents and adults A practical approach when working with adults with a are less likely to progress well in treatment or remain in SUD might be to consider ADHD likely if symptoms treatment.53–55 Therefore, the diagnosis and treatment Downloaded By: [UAJA - American Journal on Addictions] At: 11:56 5 May 2007 can be recalled as having been present since early adoles- of ADHD in patients with SUD seems to be essential to cence, but unlikely if the symptoms appeared simulta- achieve the best possible clinical outcome.
neously or subsequently to the development of theSUD. Collateral information from family or review of objective data (eg, school performance reports) can be very useful in determining whether symptoms were pre-sent during childhood.
The most commonly used pharmacotherapies for While the diagnosis of ADHD is ultimately clinically- childhood ADHD are two psychostimulants, methylphe- based, there are structured instruments and interviews nidate and analogs of amphetamine. In turn, methylphe- that can assist in the evaluation of a patient for ADHD.
nidate and amphetamine analogs have been the most A comprehensive diagnostic battery, such as might be widely studied pharmacotherapies in adult ADHD, employed in a research setting, would include, in addition although non-stimulant medications, including tricyclic to a comprehensive psychiatric interview, the Struc- antidepressants, selective serotonin reuptake inhibitors tured Clinical Interview for DSM-IV (SCID)46 and the (SSRIs), bupropion, monoamine oxidase inhibitors, aty- Conners Adult ADHD Diagnostic Interview for DSM- pical antipsychotics, clonidine, atomoxetine, and venla- IV (CAADID),47 which systematically assesses adults faxine have been studied as well. Modafinil, a novel for both childhood and adult symptoms. However, in wake-promoting agent that is chemically and pharmaco- many clinical settings, performing a SCID and CAADID logically distinct from other psychostimulants, has also is not feasible. A more practical approach is to use a semi- been investigated as a potential treatment for ADHD.
structured clinical interview using the DSM-IV TRcriteria for ADHD as a guide (ie, review symptoms in criteria set with patient). The ADHD Rating Scale-IV48 Amphetamine is a potent CNS stimulant of which the and the DSM-IV SNAP checklist49 can also be useful in effects are thought to be due to the stimulation of the cortex screening for ADHD symptoms. In any setting, it is and the reticular activating system.56 Amphetamine’s essential to gather data from other informants (eg, part- mechanism of action is primarily due to promoting dopa- ner, parent, or close friend) to better understand the mine release, although it blocks dopamine reuptake as well.
nature and severity of the symptoms and their impact Amphetamine analogs, a first-line treatment for childhood ADHD, have also been shown to be effective for the treatment of ADHD in adults.57 In the United States, both methylphenidate and amphetamine analogs demon- amphetamine analogs are used primarily for ADHD and strate characteristics associated with abuse potential.
also for narcolepsy. Commercially available amphetamine Methamphetamine, which is a commonly abused sub- analogs include methamphetamine, dextroamphetamine, stance,59 has been shown to be a positive reinforcer (ie, and mixed amphetamine salts (MAS). Methamphetamine individuals exposed to the substance are likely to choose is available only as an immediate release preparation and to be exposed again) in humans,63 providing further evi- is rarely used due to abuse and diversion concerns. Dex- dence for its abuse potential. In contrast to the data troamphetamine is available in immediate and sustained described above, a laboratory study of methylphenidate release preparations. MAS is a fixed-combination amphe- in cocaine-dependent patients receiving treatment did not tamine composed of equal amounts of dextroamphetamine increase cocaine craving nor ratings associated with abuse saccharate, dextroamphetamine sulfate, racemic ampheta- potential,64 suggesting that the context of use, in this case mine aspartate monohydrate, and racemic amphetamine therapeutic, may influence subjective effects and abuse sulfate. It is available in immediate and sustained release potential.37 Because the reinforcing effects of stimulants preparations. Side effects most commonly associated are associated with rapid changes in serum concentra- with amphetamine administration include insomnia, emo- tions37 and sustained-release preparations of methylpheni- tional lability, nausea=vomiting, nervousness, palpitations, date (which slow the rate of onset of the drug’s effect) are elevated blood pressure, and rapid heart rate. Rare, but associated with less stimulant-like drug effects (eg, serious adverse effects include severe hypertension, sei- increased ratings of ‘‘good effects’’) in healthy volun- zures, psychosis, and myocardial infarction.
teers,65,66 it is likely that delayed-release stimulant prepara- tions have lower abuse potential than immediate-release widely used in the United States for the treatment of stimulant preparations. An additional characteristic of ADHD. Methylphenidate is a piperidine derivative that delayed-release preparations that make diversion and is structurally related to amphetamine.56 The mechanism abuse less likely is that they are more difficult to use via of action of methylphenidate is primarily due to blocking a non-oral route (eg, injected or insufflated intranasally).
dopamine reuptake in the striatum. Methylphenidate has The use of stimulants and non-stimulant medications been one of the first-line treatments for ADHD in chil- has been studied in patients with co-occurring adult ADHD dren for decades and has been demonstrated to be effec- and SUD. Methylphenidate has been shown to be effective in uncontrolled trials in reducing ADHD symptoms and Downloaded By: [UAJA - American Journal on Addictions] At: 11:56 5 May 2007 Methylphenidate is available in multiple immediate and cocaine use.67,68 A three-arm double-blind placebo-con- sustained release preparations, using a variety of strate- trolled trial of bupropion and methylphenidate for the gies for delaying absorption. The most common side treatment of ADHD in cocaine-dependent patients receiv- effects of methylphenidate are insomnia, nervousness, ing methadone maintenance treatment for opioid depen- tachycardia, and hypertension. As with amphetamines, dence found no benefit of bupropion or methylphenidate rare but serious adverse effects include severe hyperten- on ADHD symptoms or cocaine use outcomes.69 A dou- sion, seizures, psychosis, and myocardial infraction.
ble-blind placebo-controlled trial of methylphenidate inthe treatment of adult ADHD patients with comorbid cocaine dependence found that methylphenidate improved Methylphenidate and amphetamine analogs are widely ADHD symptoms on some measures but not others, and it used in the treatment of ADHD; however, concern exists did not show a reduction in cocaine use.26 Consistent with with respect to their abuse potential, particularly in this, Levin et al.70 found that sustained-release methylphe- patients with SUD. The phenomenon of nonmedical use nidate did not demonstrate an improvement in cocaine use of stimulant medications has been documented in large- in cocaine-dependent individuals with ADHD. An uncon- scale survey studies; according to the National Survey trolled trial of bupropion for the treatment of cocaine on Drug Use and Health (NSDUH), 8.8% of Americans dependence and adult ADHD in 11 patients reported that aged 12 years or older reported having used prescription- ADHD and cocaine use symptoms decreased signifi- type stimulants non-medically at least once in their life- cantly.71 In none of the trials using stimulants was abuse time.59 Therefore, the risks of using these potentially abu- of prescribed stimulant medication reported.
sable medications in a vulnerable population must be Additionally, psychostimulants, including amphetamine analogs, methylphenidate, and modafinil, have been studied There is a limited body of laboratory and clinical evi- for the treatment of cocaine dependence. The results of these dence to consider when assessing the risks of using stimu- studies have been mixed with regard to the effects on cocaine lant medications in patients with SUD. In a laboratory use outcomes, with the most consistent effects reported for double-blind choice procedure, individuals with ADHD dextroamphetamine.72,73 Dextroamphetamine has also been significantly chose methylphenidate over placebo,60 while studied for the substitution treatment of amphetamine other measures of abuse potential were not elevated. In dependence74,75 and this approach has been found to be laboratory studies of patients with61 and without62 SUD, feasible. Despite concerns that psychostimulants use may Co-Occurring ADHD and Substance Use Disorders lead to increased craving and cocaine use, this has not been Modafinil, a novel wake-promoting agent that is FDA- reported in controlled clinical trials.26,69,70,72,73,76 approved for narcolepsy and shift work sleep, has recently In summary, while stimulants are clearly diverted for been shown to be effective for the treatment of ADHD in nonmedical use, clinical data suggest that the use of children and adolescents,87–89 and more limited evidence delayed-release preparation and the context of therapeu- suggests that it may be effective for adult ADHD as well.90 tic risk may reduce the potential for abuse.
Because there is limited evidence that modafinil may havepotential as a treatment for cocaine dependence,91 it is deserving of further study in the treatment of co-occurring Nonstimulant pharmacotherapies for ADHD include a ADHD and SUD. Although modafinil has some stimu- heterogeneous group of medications, which with the lant-like properties (eg, promoting wakefulness), it has exception of atomoxetine are off-label and typically minimal abuse potential, so for the purposes of discussion considered second line treatments. However, there are it is being grouped with non-stimulants.
certain instances where non-stimulant medications wouldbe considered first line, such as if a motor tic disorder is Choice of Pharmacotherapy for Co-Occurring present or in the case of cardiovascular disease.
Atomoxetine is a recently FDA-approved nonstimu- The treatment of adult ADHD in patients with SUD lant agent for the treatment of ADHD in children, adoles- has been controversial, as the primary pharmacotherapy cents, and adults. Atomoxetine is a noradrenergic for ADHD is psychostimulants and, historically, there reuptake inhibitor with efficacy for treating the symptoms has been reluctance on the part of clinicians to use these of ADHD.77,78 The effects of atomoxetine are more gra- medications in patients with addictive disorders. How- dual than those experienced with stimulant medications.
ever, although non-stimulant medications have been Common side effects of atomoxetine include sedations, shown to have efficacy for ADHD, these agents have appetite suppression, nausea, vomiting, and headache.
not been demonstrated to have comparable efficacy to Rare but serious side effects reported in children and the psychostimulants.92 Some authorities93,94 have pro- adolescents include increased suicidal ideation and posed approaches that emphasize medications with a hepatotoxicity. Atomoxetine has no known abuse poten- lower risk of abuse, such as antidepressants or clonidine, tial, so it is an attractive candidate medication for study before using traditional stimulant medications such as in the treatment of ADHD in patients with substance methylphenidate or amphetamine analogs. However, clin- Downloaded By: [UAJA - American Journal on Addictions] At: 11:56 5 May 2007 use disorders, though published studies are presently ical trials of methylphenidate26,67,70,95 and dextroamphe- The antidepressants are off-label and considered sec- dependence or ADHD in patients with co-occurring ond-line treatments for ADHD. Tricyclic antidepressants, SUD have shown that stimulant medications can be used which block the reuptake of norepinephrine in addition to safely in patients with SUD and have a relatively low risk other neurotransmitters, have some efficacy in reducing of abuse under monitored conditions.
ADHD symptoms, but are considered less effective than While the treatment literature for ADHD in patients the stimulant medications.79 The dopaminergic antide- with SUD is not well developed, the emerging trend is pressant bupropion has been reported to be effective in that medications effective for adult ADHD may be effec- the treatment of ADHD,80–82 although when studied in tive for adults with ADHD and co-occurring SUD, but patients with SUD, it offered no benefit over placebo.69 the therapeutic benefit may be less or non-existent if sub- Venlafaxine, a norepinephrine-serotonin reuptake inhibi- stance use is ongoing.82 Several possible causes of this tor antidepressant medication, has limited evidence of efficacy in ADHD in uncontrolled clinical trials.83,84Monoamine oxidase inhibitors have been shown to have  patients with ongoing SUD do not reliably efficacy for ADHD, but the potential for hypertensive crises associated with tyramine-containing foods and  patients with SUD may require higher doses medications (both illicit and prescribed) limit their utility, (ie, higher tolerance) than administered in clin- and should be considered contraindicated in patients  ongoing SUD makes detection of a therapeutic Clonidine, a noradrenergic alpha-2 agonist antihyper- tensive agent, is effective for the treatment of ADHD,particularly among adolescents with hyperactivity and As in children, the available evidence supports the use aggressiveness.85 Side effects includes sedation, dry mouth, of stimulant medications over non-stimulant medications depression, confusion, electrocardiographic changes, and for adult ADHD, although direct comparisons are lack- hypertension with abrupt withdrawal. Guanfacine, also a ing. While stimulant medications, such as methylpheni- norepinephrine alpha-2 agonist, has limited evidence sup- date and amphetamine analogs, have the potential for porting its efficacy as a treatment for ADHD.86 abuse, which is a heightened clinical concern in patients with comorbid SUD, the available evidence suggests that considerably between patients, and needs to be assessed this risk is relatively low under monitored conditions, such clinically rather than be defined categorically. Factors as in clinical trials. However, it should be expected that a such as ongoing substance use, prior history of misuse proportion of patients with ADHD comorbid with SUD of stimulant medication, other co-occurring psychiatric will misuse, abuse, or divert stimulant medications,96–98 disorders, and overall clinical stability should be taken particularly in less structured treatment settings. A related into account. For a patient who is abstinent from sub- clinical concern, that stimulant treatment would worsen stance use and has good social functioning, a trial of sti- SUD outcomes, has not been observed in clinical trials, mulant medication probably represents a low risk and in children, stimulant treatment of ADHD has been intervention, whereas if a patient is using substances or associated with reduced risk of developing SUD.39 is otherwise clinically compromised, the use of stimulant The primary approach to the treatment of ADHD pharmacotherapy must be approached more cautiously.
remains pharmacotherapy; thus, a rational treatment plan The individualized risk assessment should also dictate for a patient with ADHD co-occurring with ADHD will other elements of clinical management, such as the fre- most likely include pharmacotherapy. For patients without quency of office visits or urine toxicology testing.
SUD, stimulant medications are the first line treatment When the decision to use stimulant pharmacotherapy is choice; however, given the risk of misuse and diversion made, the choice of formulation should be considered of stimulant pharmacotherapy, which may be heightened carefully. Most clinicians experienced in the treatment of in patients with SUD, the decision to use stimulant medica- ADHD in patients with SUD would likely recommend tions must be undertaken carefully. In some cases, nonsti- the use of sustained-release preparations of stimulants to mulant pharmacotherapy would be more a more desirable reduce the potential for misuse, although clinical data are alternative. The decision to use stimulant pharmacother- lacking to support this approach. Novel delivery systems apy in a patient with ADHD and co-occurring SUD such as the crush-resistant shell of Concerta (Alza Corpora- requires an individualized risk-benefit assessment.
tion, Fort Washington, Pennsylvania, USA)99 or the The assessment of risk in using stimulant pharma- recently FDA-approved methylphenidate skin patch, are cotherapy in a patient with SUD is a broad consideration more resistant to abuse and may be desirable alternatives of the patient’s clinical condition, past history, and overall in patients with co-occurring ADHD and SUD.
functional status. A conservative approach for treating A final consideration regarding choice of medication is co-occurring ADHD and SUD would be to begin treat- that of combination pharmacotherapy. While there is very Downloaded By: [UAJA - American Journal on Addictions] At: 11:56 5 May 2007 ment with a non-stimulant pharmacotherapy, but if an minimal data to guide choices with regard to combina- adequate response is not obtained, stimulant pharma- tions of ADHD pharmacotherapies, nonetheless, clini- cotherapy should be considered. While this approach cians will often be faced with clinical situations that call would minimize the risk of diversion and the misuse of for the consideration of combination pharmacotherapy.
stimulants, given that nonstimulants do not appear to These clinical situations can broadly be categorized into have equivalent efficacy to stimulants, this increased four groups: partial response, dose-limiting side effects, assurance in terms of misuse may come at the expense associated disorders, and comorbid diagnoses. Potential of ADHD symptom response. The available evidence approaches to these clinical situations include combina- does not support differing degrees of risk based on type tions of stimulants and non-stimulant medications, combi- of SUD (eg, cannabis dependence vs. cocaine dependence) nations of non-stimulant medications, and combinations or even current substance use, because, as discussed of immediate- and delayed-action stimulants.
previously, stimulant pharmacotherapy has been usedsuccessfully in patients with active cocaine depen- dence.26,67,69,70,72–74,76,95 Perhaps the only absolute con- traindication to stimulant pharmacotherapy in a patientwith SUD would be current abuse of prescription stimu- Although pharmacotherapy is the cornerstone of treat- lants or a clear indication that the patient would sell or ment for ADHD, a variety of psychosocial treatments can be employed in combination with medication to optimize While it would be desirable to provide clear-cut recom- the long-term management of this chronic disorder.
mendations or an algorithm (eg, when patient has charac- Unfortunately, little controlled research has been under- teristic X, give drug Y), the data are lacking to provide taken on psychosocial treatments for adults with ADHD.
such guidance. Instead, clinicians must consider all of Data on treatments for children are not likely to be the available clinical information and make the best initial directly relevant, given that those interventions typically decision, with the understanding that the treatment emphasize parent training100 and, in some cases, show plan may need to be modified over time. The known no additive benefit of psychosocial treatment to patients efficacy of psychostimulants must be balanced against the risk of diversion or misuse, and although this risk is An important element of the treatment of ADHD is likely heightened in patients with SUD, it likely varies psychoeducation. Having the patient learn about the Co-Occurring ADHD and Substance Use Disorders disorder and its pervasive effects on their functioning can The use of psychostimulants in patients with substance help to set the stage for developing an effective therapeu- use disorders requires careful monitoring, including urine tic alliance. Providing educational literature or referrals toxicology testing. Relapse or worsening of substance use to community education=support groups, such as Chil- may necessitate re-assessing the appropriateness of stimu- dren and Adults with Attention Deficit Disorder lant pharmacotherapy. Careful documentation of all (CHADD; http://www.chadd.org) or the Attention Def- prescriptions must be maintained in order to monitor the icit Disorder Association (ADDA; http://www.add.org), amount and frequency of the drug being prescribed.
can be very useful for patients and families in gaining Repetitive requests to replace ‘‘missing,’’ ‘‘lost,’’ or ‘‘stolen’’ medication should be cause for concern, as should similar Cognitive behavioral therapy (CBT) has been shown to requests for dose increases when not clinically supported.
be effective in reducing symptoms of adult ADHD.102 Delayed-release preparations are preferred to reduce the Modifications of CBT such as structured skills training103 rate of change of drug blood levels, which is less reinforcing, or cognitive remediation104 have also been shown to be as well as to discourage non-oral use. Patient visits should effective. However, in patients receiving CBT for SUD, be frequent. Despite all mechanisms in place to reduce the there is evidence that cognitive deficits, such as those risk of diversion, misuse, or abuse of stimulants, it should associated with ADHD, are associated with low treat- be expected that a small percentage of patients with ADHD ment retention,105 suggesting that retaining patients with comorbid with substance use disorders will do so, and that cognitive deficits in CBT-based SUD treatment is diffi- careful clinical monitoring will detect such nontherapeutic cult, and that individualized treatment strategies may use early and minimize its adverse effects.
Rating scales, such as the Conners Adults Attention- Additional behavioral strategies for ADHD that are Deficit Rating Scale,106 can be useful for monitoring used clinically but not studied in controlled trials in adults symptom severity over time in response to prolonged include coaching and behavior modification. Coaching is abstinence or ADHD pharmacotherapy. One important a collaborative relationship between the patient and a caveat is that ADHD rating scales administered to professional to develop strategies for managing problems patients who have not yet achieved a prolonged period such as procrastination, time-management, and organiza- of abstinence will capture substance-induced symptoms tion. Behavior modification is a technique used mainly for of inattention and hyperactivity in addition to possible children where desired behaviors are positively reinforced symptoms due to ADHD. In such cases, sequential rating Downloaded By: [UAJA - American Journal on Addictions] At: 11:56 5 May 2007 scale administration over time can help resolve the diag-nosis; substance-induced symptoms should improve with abstinence, whereas symptoms due to ADHD will be stable in the absence of treatment. Rating scales help pro-vide benchmarks from which the efficacy of therapy can The management of patients with co-occurring ADHD be measured, particularly if multiple trials of medications and SUD requires a comprehensive approach to assessing are required to achieve a clinical response.
symptom burden and functional impairment. The simulta- Assessment for malingering is an important component neous treatment of both conditions is likely to be the opti- of managing a patient with co-occurring ADHD and mal approach because ADHD symptoms (eg, impulsivity, SUD, given that the mainstay of treatment for ADHD poor planning) will interfere with SUD treatment, and sub- are stimulants that are potentially abusable. Because inat- stance use will limit the benefit of ADHD treatment.
tention symptoms tend to predominate in adults with When using psychostimulant pharmacotherapy for ADHD and symptom assessment is almost entirely based ADHD in patients with SUD, careful attention to the on self-report, the potential for patients with substance use clinical frame and boundaries of treatment needs to be disorders attempting to mislead clinicians in an effort to made. It should be discussed explicitly with the patient obtain stimulants is always present. Efforts to obtain col- that the use of stimulant medication carries an inherent lateral data from family and other sources should be risk of misuse or abuse, and that if evidence of such devel- made, including childhood school records.
ops, the appropriateness of stimulant use will be reconsid-ered. Emphasis should be placed on the adherence to the prescribed medication regimen, and that medicationshould not be taken on an ‘‘as needed’’ basis. It should ADHD and SUDs frequently co-occur, particularly in be made clear to the patient, and ideally the family, that SUD treatment settings. The etiology of the increased if it becomes apparent that prescribed stimulant medica- association of ADHD and SUD is unknown, although tion is being misused, abused, or diverted, that there is one possible cause is that substance use represents an no obligation on the part of the physician to continue attempt to ‘‘self-medicate’’ ADHD symptoms. Untreated treatment. Fortunately, stimulant medications can be dis- ADHD leads to significant consequences and may continued abruptly without dangerous sequelae.
impair a patient’s ability to benefit from SUD treatment.
Pharmacotherapy remains the mainstay for the treatment function of reporting source and definition of disorder. J Abnorm of ADHD, and psychostimulants continue to be first-line 7. Kessler RC, Adler LA, Barkley R, et al. Patterns and predictors of treatments. Several non-stimulant medications have attention-deficit=hyperactivity disorder persistence into adulthood: shown promise for the treatment of ADHD, but their role results from the national comorbidity survey replication. Biol for patients with co-occurring SUDs has not yet been determined. While stimulant medications have the poten- 8. Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates tial for abuse and must be used cautiously in patients with of adult ADHD in the United States: results from the NationalComorbidity Survey Replication. Am J Psychiatry. 2006;163:716–723.
substance use disorders, the available evidence suggests 9. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE.
that stimulant medications administered under monitored Prevalence, severity, and comorbidity of 12-month DSM-IV disor- conditions can be safe and effective in patients with sub- ders in the National Comorbidity Survey Replication. Arch Gen stance use disorders. However, ongoing substance use can limit the efficacy of stimulant pharmacotherapy, and 10. Weiss M, Murray C. Assessment and management of attention-def- icit hyperactivity disorder in adults. CMAJ. 2003;168:715–722.
there is an irreducible risk of misuse, abuse, and diversion 11. Murphy K, Barkley RA. Attention deficit hyperactivity disorder of stimulant medications when used to treat ADHD adults: comorbidities and adaptive impairments. Compr Psychiatry.
comorbid with substance use disorders. A conservative approach for treating co-occurring ADHD and SUD 12. Kessler RC, Adler L, Ames M, et al. The prevalence and effects of would be to begin treatment with a non-stimulant phar- adult attention deficit=hyperactivity disorder on work performancein a nationally representative sample of workers. J Occup Environ macotherapy, but if an adequate response is not obtained, 13. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental regarding the use of stimulant medications for a patient disorders with alcohol and other drug abuse. Results from the with ADHD and a co-occurring substance use disorder Epidemiologic Catchment Area (ECA) Study. JAMA. 1990;264: should be made on the basis of a broad clinical assess- 14. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month ment and an individual risk-benefit analysis. For many prevalence of DSM-III-R psychiatric disorders in the United patients, psychostimulants can be used safely and effec- States. Results from the National Comorbidity Survey. Arch Gen tively; however, careful monitoring during treatment is essential to ensure prescribed stimulants are being used 15. Grant BF, Harford TC. Comorbidity between DSM-IV alcohol use in a therapeutic manner, and in the case of worsening sub- disorders and major depression: results of a national survey. DrugAlcohol Depend. 1995;39:197–206.
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rence of substance use disorders and independent mood and anxi-ety disorders: results from the National Epidemiologic Survey on Please turn to page 55–56 for the post-test and evalua- Alcohol and Related Conditions. Arch Gen Psychiatry. 2004; 17. Levin FR, Evans SM, Kleber HD. Prevalence of adult attention- deficit hyperactivity disorder among cocaine abusers seeking treat- Work on this manuscript was supported in part by ment. Drug Alcohol Depend. 1998;52:15–25.
grants K23 DA021209 (Dr. Mariani) and K02 DA00465 18. Clure C, Brady KT, Saladin ME, Johnson D, Waid R, Rittenbury (Dr. Levin) from the National Institute on Drug Abuse, M. Attention-deficit=hyperactivity disorder and substance use: symptom pattern and drug choice. Am J Drug Alcohol Abuse. 1999;25:441–448.
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87. Biederman J, Swanson JM, Wigal SB, Boellner SW, Earl CQ, 106. Conners CK. Clinical use of rating scales in diagnosis and treat- Lopez FA. A comparison of once-daily and divided doses of mod- ment of attention-deficit/hyperactivity disorder. Pediatr Clin North afinil in children with attention-deficit=hyperactivity disorder: a Co-Occurring ADHD and Substance Use Disorders TREATMENT STRATEGIES FOR CO-OCCURRING ADHD AND SUBSTANCE USE DISORDERPost-testPlease select only one answer for each question. Circle the letter corresponding to the correct answer on the answer form on the back page.
1. Retrospective diagnoses of childhood ADHD in adults made on the basis of self-reports tend to ______________ a. Underdiagnose ADHDb. Overdiagnose ADHDc. Confuse ADHD with bipolar disorderd. Never be done 2. The therapeutic benefit of medications for adult ADHD is more effective when the SUD is ongoing 3. Compared to the community-based National Comorbidity Survey Reports, clinical samples tend to report____________of co-occurring ADHD in individuals with SUDa. A lower rateb. The same ratec. A higher rate 4. Which of the following has NOT been shown in individuals who have both ADHD and SUD compared to SUD cases without ADHD? a. Earlier onset of SUDb. Better response to SUD treatment in adults compared to adolescentsc. Reduced likelihood of going into remissiond. Longer time to reach remission 5. The effects of atomoxetine in treatment of ADHD are more gradual than those with stimulants 6. Although clinical data are lacking, it is rational to assume that medication misuse in ADHD patients with SUD would be least likely with: a. Immediate-release stimulantsb. Intravenous stimulant formulationsc. Sustained-release stimulants Downloaded By: [UAJA - American Journal on Addictions] At: 11:56 5 May 2007 7. Which of the following is the most rare adverse effect associated with amphetamine treatment of ADHD? a. Emotional labilityb. Severe hypertensionc. Nausea=vomitingd. Insomnia 8. The mechanism of action of methylphenidate is primarily due to blocking dopamine reuptake in the striatum 9. Which of the following types of antidepressant is contraindicated in patients with SUD? a. Norepinephrine-serotonin reuptake inhibitorsb. Dopamine=norepinephrine reuptake inhibitorsc. Monoamine oxidate inhibitorsd. Tricyclics 10. Most controlled trials have shown that methylphenidate use for ADHD does not reduce cocaine use in those with comorbid cocaine dependence 11. Based on clinical studies, which of the following has been most effective in treatment of cocaine use? a. Methylphenidateb. Dextroamphetaminec. Bromocriptined. Atomoxetine 12. When treating with stimulants, an important component of managing a patient with co-occurring ADHD and SUD is: a. Polypharmacyb. Sequential rating scale administrationc. Assessment of malingeringd. Self-reports TREATMENT STRATEGIES FOR CO-OCCURRING ADHD AND SUBSTANCE USE DISORDERSuccessful completion of the posttest examination (at least 75% correct) and activity evaluation is required to earn a maximum of one (1) AMA PRACategory 1 CreditTM. Physicians should only claim credit commensurate with the extent of their participation in the activity. Statements of Credit willbe awarded upon successful completion of the posttest and evaluation.
please mail or fax this completed form to: Please circle the appropriate rating in answer to the questions that follow: Extent to Which this Activity Met the Identified Objectives Upon completion of this activity, participants should be able to: 1. Identify typical challenges in clinical diagnosis of ADHD in adults There is no fee for certificate processing.
2. Explain how different types of ADHD pharmacotherapies impact the risks of SUD in specific patients types.
3. Distinguish between primary symptoms and substance-induced (Circle the correct answer to each question) 4. Discuss the pros=cons of non-stimulant medications in patients with ADHD and co-occurring SUD, including second-line medications.
5. Describe treatment scenarios in ADHD that are most likely to lead to SUD, exacerbate ongoing SUD, or minimize risks of SUD.
6. Provide an overview of psychosocial treatments for ADHD and co- occurring SUD that can help optimize long-term treatment effectiveness.
To receive credit, you must answer 9 of the 12 post-test questions correctly, complete all forms, and submit them by January 31, Are there any comments you would like to communicate directly to theauthors? Downloaded By: [UAJA - American Journal on Addictions] At: 11:56 5 May 2007 1. Objectives were related to overall purpose=goal(s) of activity.
4. Will help me improve patient care.
5. Stimulated my intellectual curiosity.
6. Overall, the activity met my expectations.
Was the information in this activity presented in an unbiased manner? Will the information presented cause you to make any changes in your practice? If YES, please describe any change(s) you plan to make in yourpractice as a result of this activity.
______________________________________________________How committed to making these changes?Not At All Committed 1 I certify that I have completed this CME activity. The actual amount of time I spent on this activity was: Do you feel future activities on this subject are necessary and=or Please list any other topics that would be of interest to you for future Co-Occurring ADHD and Substance Use Disorders

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Leitlinie: Aktinische Keratose Inhaltverzeichnis Definition, Ätiologie und Epidemiologie Klinik und Histologie Diagnostik Therapie 4.3. Kürettage mit oder ohne Elektrodesikkation Prävention Verfahren zur Konsensbildung Definition der Evidenzebenen Literaturverzeichnis Leitlinie Aktinische Keratose 09/2004 Prof. Dr. med. Eggert Stockfleth, Berlin Pro


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