Impact of adhd and its treatment on substance abuse in adults

Impact of ADHD and Its Treatment
on Substance Abuse in Adults
Timothy E. Wilens, M.D.
Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance abuse in adults. Ad- ditional psychiatric comorbidity increases this risk. ADHD is associated with different characteristicsof substance abuse: substance abuse transitions more rapidly to dependence, and lasts longer in adultswith ADHD than those without ADHD. Self-medication may be a factor in the high rate of substanceabuse in adults with ADHD. While previous concerns arose whether stimulant therapy would increasethe ultimate risk for substance abuse, recent studies have indicated that pharmacologic treatment ap-pears to reduce the risk of substance abuse in individuals with ADHD. When treating adults withADHD and substance abuse, clinicians should assess the relative severity of the substance abuse, thesymptoms of ADHD, and any other comorbid disorders. Generally, stabilizing or addressing the sub-stance abuse should be the first priority when treating an adult with substance abuse and ADHD.
Treatment for adults with ADHD and substance abuse should include a combination of addictiontreatment/psychotherapy and pharmacotherapy. The clinician should begin pharmacotherapywith medications that have little likelihood of diversion or low liability, such as bupropion andatomoxetine, and, if necessary, progress to the stimulants. Careful monitoring of patients during treat-ment is necessary to ensure compliance with the treatment plan.
(J Clin Psychiatry 2004;65[suppl 3]:38–45) tentially dampening the morbidity, disability, and poorlong-term prognosis in adolescents and adults with this co- The prevalence of attention-deficit/hyperactivity disor- morbidity.4,5 In the following sections, we will review data der (ADHD) in school-aged children is approximately 6% relevant to understanding the overlap between ADHD and to 9%.1 Data on prevalence in adults are limited, but SUD with an emphasis on ADHD as a risk factor for sub- ADHD may affect up to 5% of adults.2 Substance use disorders (SUD; denoting drug or alcohol abuse or de- Although not the topic of this report, higher rates of pendence) affect up to 27% of the adult population.3 There ADHD have been reported in adolescents and adults with is a bidirectional overlap between ADHD and substance SUD relative to controls.6,7 It is estimated that between abuse. The study of comorbidity between SUD and ADHD 15% to 25% of adults with a lifetime history of a SUD is relevant to both research and clinical practice in devel- may have ADHD.7 In adolescents, there have been 3 stud- opmental pediatrics, psychology, and psychiatry, with im- ies assessing ADHD and other disorders in substance plications for diagnosis, prognosis, treatment, and health abusing groups,8,9 including juvenile offenders,10 demon- care delivery. The identification of specific risk factors of strating an overrepresentation of ADHD (along with both SUD within ADHD may permit more targeted treatments mood and conduct disorders) in adolescents with conduct for both disorders at earlier stages of their expression, po- disorder. Studies in adults with SUD are similar to those inadolescents. When both alcohol and drug addiction are in-cluded, from 15% to 25% of adult addicts and alcoholicscurrently have ADHD.11–13 For example, Schubiner et al.11 found that 24% of 201 From the Department of Psychiatry, Harvard Medical School, and the Substance Abuse Program in Pediatric inpatients in a substance abuse treatment facility had Psychopharmacology, Massachusetts General Hospital, ADHD, and that two thirds also had conduct disorder. The This article is derived from the roundtable meeting importance of careful diagnosis, however, has been dem- “Diagnosing and Treating Attention-Deficit/Hyperactivity onstrated by Levin et al.,12 who found that while 10% of Disorder in Adults,” which was held January 17, 2003, in cocaine-dependent adults met strict criteria for ADHD Boston, Mass., and supported by an unrestricted educationalgrant from Eli Lilly and Company. (clear childhood and adult ADHD), another 11% were Corresponding author and reprints: Timothy E. Wilens, found to have ADHD symptoms only as adults.
M.D., Massachusetts General Hospital, 15 Parkman St.,WAC 725, Boston, MA 02114-3117 Conversely, ADHD is a risk factor for later SUD.
Biederman et al.2 compared 120 adults with ADHD to 268 COPYRIGHT 2004 PHYSICIANS POSTGRADUATE PRESS, INC. COPYRIGHT 2004 PHYSICIANS POSTGRADUATE PRESS, INC.
ADHD Treatment and Substance Abuse in Adults Figure 1. Age at Onset of Substance Abuse in Individuals With
Figure 2. Risk of Abuse Following Dependence in Substance
Attention-Deficit/Hyperactivity Disordera
Abusers With and Without ADHDa,b
Reprinted with permission from Wilens et al.16 Reprinted with permission from Biederman et al.19 p ≤ .05 vs. adults without ADHD by Cox proportional hazards model.
Hazard ratio = 4.9 (95% confidence interval = 1.7 to 14.3; p = .003) for ADHD adults vs. adults without ADHD estimated using Coxregression correcting for age, sex, socioeconomic status, and otherpsychiatric comorbidity.
adults without ADHD (mean age of 40 years) and founda lifetime rate of a SUD of 52% in adults with ADHDand 27% in adults without ADHD. Similar findings were My colleagues and I18 also found that the duration of reported earlier by Shekim and colleagues.14 the substance abuse was longer in adults with ADHDthan in those without. In stratifying our data to examine substance-abusing adults with and without ADHD, we found that although the rate of remission from substanceabuse was 80% in both groups, the mean duration of sub- There appear to be important differences in the charac- stance abuse in adults with ADHD was 133.1 months, teristics of SUD in adults with ADHD relative to adults compared with 95.9 months in adults without ADHD.
without ADHD. Adults with ADHD begin to abuse sub- Biederman et al.19 investigated the effect of ADHD on stances at an earlier age and abuse substances more often transitions from substance use to abuse to dependence and than their peers without ADHD. Their substance abuse from one class of abusive agents to another. The research- continues longer, and they move from alcohol abuse to ers found that adults with ADHD (N = 239) were signifi- substance abuse more rapidly than those without ADHD.
cantly more likely to progress from an alcohol use dis- While adolescents with and without ADHD have the order to a drug use disorder than adults without ADHD same rate of substance abuse, such is not the case for (N = 268). Also, adults with ADHD were significantly adults with ADHD. In a prospective study, Biederman et more likely to go back to the less severe substance abuse al.15 found the rate of substance abuse in adolescents both from dependence than adults without ADHD, who gener- with ADHD (N = 140) and without ADHD (N = 120) to be ally fully remit from substance dependence (Figure 2).
15%. However, between adolescence and adulthood therate of substance abuse increases substantially for indi- Connections Between Substance Use and ADHD viduals with ADHD. My colleagues and I16 studied the on- The high rate of substance abuse in adults with ADHD set of SUD in adults with ADHD. We examined retrospec- is well-known, but researchers are still trying to learn the tively derived data from 120 consecutively referred adults cause. The core symptoms of hyperactivity, impulsivity, with SUD and ADHD and 268 adults with substance use and inattention, as well as the role of functioning, comor- disorder but no ADHD. The mean age at onset of sub- bidity, and overall competency, are currently being studied stance abuse was 19 years in adults with ADHD, com- as potential causal candidates in the link between ADHD pared with 22 years in adults without ADHD (Figure 1).
We found that substance abuse increased in adulthood for Researchers have undertaken studies on the role of self- approximately 48% of individuals with ADHD, compared medication in symptom control in adults with ADHD.
with approximately 30% of individuals without ADHD.
Individuals with ADHD may use specific drugs, such as Studies16,17 have found that adults with ADHD and co- cocaine, that act in a manner similar to prescribed ADHD occurring conduct or bipolar disorder are at a higher risk medications to lessen symptoms. However, Biederman for substance abuse and have an earlier onset of substance et al.2 reported that individuals with ADHD did not abuse when compared with adults with ADHD alone.
choose their drugs as selectively as originally hypoth- COPYRIGHT 2004 PHYSICIANS POSTGRADUA
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esized. Substance-abusing adults with ADHD (N = 44) Figure 3. Rate of Drug Uptake Into the Brain
and adults without ADHD (N = 29) used the same drugs insimilar ratios, with marijuana being the most frequently abused agent, followed distantly by cocaine, stimulants, and hallucinogens. Although individuals with ADHD maynot choose their drugs selectively, self-medication could still be operant. For example, Horner and Scheibe20 asked 15 substance-abusing adolescents with ADHD and 15substance-abusing adolescents without ADHD questions about substance abuse. When asked why they began toabuse substances, both the adolescents with ADHD and those without ADHD answered “to get high.” When they were asked why they continued to abuse substances, mostof the adolescents with ADHD cited the mood-altering properties of the substances, while those without ADHD cited the euphoric properties of the substances.
Inattention has also been found to play a role in sub- stance abuse. Tercyak et al.21 recently demonstrated an important link between the presence of attentional dys-function and the initiation and maintenance of cigarette smoking. Tapert et al.22 followed 66 youths without ADHD at a high risk for substance abuse for 8 years tolearn if attentional symptoms at baseline predicted later substance abuse. Poor attention and executive functioningat baseline predicted substance abuse at follow-up, even when results were controlled for socioeconomic status, conduct disorder, family history of substance abuse, andlearning disabilities. The youths who had low scores on neuropsychological tests of attention at baseline had greater substance use frequency than those with higherbaseline scores on attention tests.
Stimulant medications have been cited as a possible cause of the high rate of substance abuse in adults with ADHD. Research on the subject has so far been inconclu- sive, with discordant findings23–25 in the literature.
Methylphenidate is one of the most commonly pre- scribed stimulant medications for ADHD, but has been scrutinized for its pharmacologic properties, which re- semble those of cocaine. Kollins et al.,26 in their review of the literature, found that 48 (80%) of the 60 studies re- viewed concluded that methylphenidate acts in a manner similar to cocaine or produces effects indicative of abusepotential. Grabowski et al.27 conducted a study on methyl- aReprinted with permission from Volkow et al.28 phenidate as a replacement medication for cocaine.
Twenty-five individuals were given 45 mg/day of methyl-phenidate and 24 individuals were given a placebo. The and oral methylphenidate had similar pharmacokinetic two groups had no significant differences in trial retention properties. They found that both IV cocaine and IV or cocaine use, and neither group reported an increase in methylphenidate had a rapid brain (striatal) uptake but oral methylphenidate had a slow brain uptake (Figure 3). The Methylphenidate and cocaine may have similar psy- participants who were given the IV cocaine and the IV choactive properties, but the route of administration methylphenidate reported feeling a euphoria, but those controls their behavioral effects. Volkow et al.28 studied who were given oral methylphenidate did not. This lack of whether intravenous (IV) cocaine, IV methylphenidate, a high limits the abuse potential of oral methylphenidate.
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ADHD Treatment and Substance Abuse in Adults My colleagues and I25 concluded recently that the litera- Treatment of patients with ADHD and SUD necessitates ture does not support the claim that stimulant treatments multimodal involvement including empirically based SUD add to the risk of substance abuse in individuals with treatments/psychotherapy and pharmacotherapy. Psycho- ADHD. Our group reviewed 6 studies that evaluated a to- therapy is helpful in reducing substance abuse and can aid tal of 674 medicated subjects and 360 unmedicated sub- in treatment of the ADHD. Group and individual therapy jects. We found that the pooled odds ratio for the studies both have been reported to be useful in treating substance revealed a 1.9-fold reduction in risk of substance abuse for abuse.31 Reliance on 12-step programs alone may not be youths who were treated with stimulants compared with adequate, as it has been the author’s experience that adults youths who were not treated for ADHD. Only 1 study with ADHD often have difficulty following these pro- showed an increase in substance abuse in individuals grams. Researchers have demonstrated the effectiveness of treated with stimulants, 1 study showed no difference, and individual cognitive therapies, such as the empirically 4 out of the 6 studies showed a decrease in substance based strategies of A. T. Beck, in the treatment of ADHD.32 abuse. This review suggests that not only is there a lack of Cognitive-behavioral therapy may also be a particularly ef- aggregate data supporting the idea that stimulants increase fective therapy in adults with ADHD plus SUD, as special the risk of substance abuse, but stimulant pharmaco- cognitive therapy interventions, integrating relapse preven- therapy appears to decrease SUD by as much as one half tion, exist for adults with SUD. The latency to initiate phar- (compared with the general population risk for SUD).
macotherapy for ADHD in adults with ADHD plus SUDremains under study. SUD should be addressed prior to initiating pharmacotherapy. Once there is evidence of sta- bilization or solid motivation for SUD treatment, ADHDpharmacotherapy can be initiated. Medication serves an im- All adults with ADHD should be systematically queried portant role in reducing the symptoms of ADHD and other for SUD. Evaluation and treatment of comorbid ADHD concurrent psychiatric disorders. Effective agents for adults and SUD should be part of a plan in which consideration is with ADHD include the psychostimulants, noradrenergic given to all aspects of the adult’s life. Any intervention in agents, and catecholaminergic antidepressants.33 Findings this group should follow a careful evaluation of the pa- from open and controlled trials suggest that medications tient, including psychiatric, addiction, social, cognitive, used in adults with ADHD plus SUD effectively treat the educational, and family evaluations. A thorough history of ADHD but have little effect on substance use or cravings, substance use should be obtained including past and cur- and the trials are plagued by high attrition. A total of 5 stud- rent usage and treatments. Careful attention should be paid ies have been presented or reported in the adult literature: to the differential diagnoses, including medical and neuro- 4 open34–37 and 1 controlled38 (Table 1).
logic conditions whose symptoms may overlap with The first line of pharmacologic treatment for adults with ADHD (e.g., hyperthyroidism) or be a result of SUD (e.g., ADHD and SUD, based on the risk for medication diversion protracted withdrawal, intoxication, and hyperactivity).
and misuse, should be the nonstimulants, such as Current psychosocial factors contributing to the clinical bupropion, tricyclic antidepressants, and atomoxetine.
presentation need to be explored thoroughly. Although no Second-line agents for ADHD in adults with comorbid SUD specific guidelines exist for evaluating the patient with ac- include the stimulants: pemoline, methylphenidate, and tive SUD, in our experience at least one month of absti- amphetamines (Table 2). Because of its high likelihood for nence is useful in accurately and reliably assessing for abuse, methamphetamine should be avoided.
ADHD symptoms. Semistructured psychiatric interviewsor validated rating scales of ADHD29,30 are invaluable aids for the systematic diagnostic assessments of this group.
Tricyclic antidepressants, such as desipramine and Adults with ADHD and SUD have special treatment imipramine, have been tested for effectiveness in adults considerations. If possible, the first priority in treatment with ADHD. A randomized, placebo-controlled study39 of should be to address the SUD, i.e., to stabilize the SUD desipramine in adults with ADHD found significant reduc- either to abstinence or to a stable low-use pattern.13 By tion in symptoms of ADHD from baseline to endpoint.
treating the SUD first, treatment retention is improved and Forty-one adults were given 200 mg/day of desipramine the effectiveness of treatments for ADHD is increased.
for 6 weeks. Sixty-eight percent of participants treated with After the addiction has been addressed, the clinician desipramine responded positively to treatment, while none should reevaluate the patient and establish a treatment of the participants given the placebo showed a positive re- hierarchy based on the relative impairment from the sponse. The literature is limited, however, in studies of tri- patient’s disorders. For example, if a patient has ADHD cyclic antidepressants and current substance abuse in pa- and major depressive disorder, then the depression should be treated first if it has a greater negative effect on the Studies that have evaluated the newer antidepressant bupropion in the treatment of ADHD with comorbid sub- COPYRIGHT 2004 PHYSICIANS POSTGRADUA
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Table 2. Medications Available for the Treatment
of ADHD Plus Substance Abuse Disorders
Norepinephrine reuptake inhibitor (promising) aIn order of increasing abuse potential.
stance abuse have generally found bupropion to be effec- tive. Riggs et al.40 examined the use of bupropion in treat- ing ADHD in adolescents with substance abuse and con- duct disorder. The open, 5-week trial in 13 adolescents (all completed) in residential treatment resulted in moderate reductions in ADHD symptoms and mild reduction in sub- stance abuse and craving. The mean score on the ConnersHyperactivity Index declined by 13%, mean score on the Daydream Attention score declined by 10%, and mean score on the Clinical Global Impressions-Severity of Ill- Solhkhah et al.41 conducted an open, 6-month study of the effectiveness of bupropion sustained release, up to a maximum of 400 mg/day, in 14 adolescents with ADHD, substance abuse, and mood disorders. The researchers found moderate reductions in ADHD symptoms, sub- stance abuse, and cravings in the 13 completers. Partici- pants’ scores on the Drug Use Screening Inventory- ders (SUD)
Revised declined 39% from baseline to endpoint, and scores on the ADHD Symptom Checklist declined 43% from baseline to endpoint. There were no serious adverseevents in the group.
A 12-week study by Levin et al.42 on the effectiveness of bupropion in 11 adults with ADHD seeking treatment for cocaine abuse found similarly positive results. Of the11 patients, 10 completed the study. Study participants were given 250 to 400 mg/day of bupropion and concur- rent psychotherapy. ADHD and cocaine use decreased considerably over the course of the trial. The mean scores ith ADHD Plus Substance Use Disor
on the ADHD Rating Scale declined by half from baseline to the close of the trial. Cocaine craving, as measured by a visual analog scale, decreased by a mean of 46%, and the number of days of cocaine use, as measured by the Addic- tion Severity Index, declined by 91% from baseline to Prince et al.43 studied bupropion sustained release, in doses up to 200 mg/day, to investigate whether it success- fully treated ADHD in adults with substance abuse while reducing the substance abuse. They conducted an open,6-week trial comprising 32 adults diagnosed with ADHD and substance abuse. Subjects were referred for SUD able 1. Medication Studies of Adults W
treatment. Only 19 individuals completed the study, a 41% COPYRIGHT 2004 PHYSICIANS POSTGRADUATE PRESS, INC. COPYRIGHT 2004 PHYSICIANS POSTGRADUATE PRESS, INC.
ADHD Treatment and Substance Abuse in Adults dropout rate. However, the study showed significant reduc- Of interest, no evidence exists to suggest that treating tions in ADHD symptoms and only minor reduction in sub- ADHD pharmacologically during an active SUD exacer- stance abuse in adults treated with bupropion. The study bates the SUD. In particular, studies of bupropion40–43 participants whose ADHD responded to treatment showed show no increased substance use or craving in general, the most improvement in substance abuse; conversely, or cocaine use in particular. Moreover, methylphenidate 60% of participants whose substance abuse diminished treatment did not increase cocaine use or cocaine craving also showed a decline in symptoms of ADHD. No reports according to subjective and objective data. These findings of drug interactions with substances of abuse emerged.
are consistent with those of Grabowski et al.,27 who sys-tematically evaluated methylphenidate as a potential co- caine-blocking agent by studying cocaine addicts without Another medication that has been found effective in the ADHD and administering methylphenidate or placebo.
treatment of ADHD in adults is atomoxetine. Atomoxetine, While methylphenidate was not effective in reducing co- a nonstimulant, is a highly specific noradrenergic reuptake caine use or craving compared with placebo, there was no inhibitor that is not associated with substance abuse patho- evidence that methylphenidate exacerbated any aspect of physiology or neural networks. Michelson et al.44 recently the cocaine addiction. Similar findings have been reported reported on two 10-week, double-blind, controlled studies in a pilot study using dextroamphetamine in adult amphet- on atomoxetine in adults with ADHD (N = 536) showing amine abusers48 in which no exacerbation of the stimulant significant reductions in symptoms on both the self-rated abuse or craving emerged during the 12-week randomized and investigator-rated versions of the Conners Adult ADHD Rating Scale. Atomoxetine is unscheduled and hasso far shown no signs of abuse potential. For example, one study by Heil et al.45 systematically evaluated the abuseliability of atomoxetine and demonstrated that no abuse Concerns still exist about the safety of pharmaco- liability in adults exists at therapeutic dosing. Very recent therapy in adults with ADHD and SUD. Medications with data on atomoxetine in adults with ADHD and SUD show known drug interactions with substances of abuse (e.g., an absence of acute liability in this group (data on file, Eli marijuana and tricyclic antidepressants49) should be Lilly and Co., Indianapolis, Ind.). Atomoxetine is clearly avoided. Patients should be monitored for compliance promising as a first-line agent given its lack of abuse liabil- with the treatment plan, misuse or abuse of medication, ity and relative freedom from drug interactions with sub- and reselling of medication. Also, patients may believe stances of abuse. Moreover, atomoxetine may also be use- that pharmacologic treatment conflicts with the drug-free ful in addressing any additional psychiatric comorbities, ideology they are being taught, but they should be re- such as anxiety and mood disorders, reported in adults in minded that they are taking prescribed medication, not Monitoring of adults in treatment for ADHD and sub- stance abuse requires frequent follow-up questionnaires, Stimulants, such as methylphenidate and amphet- objective toxicology screens, and contingency plans. Cli- amines, are considered second-line agents for adolescents nicians need to know what they plan to do if the individual and adults with ADHD and SUD. When prescribing stimu- they are treating continues to abuse substances. Gradual lants, the clinician should begin with a medication with a steps must be taken with patients who cannot control their low abuse liability, such as pemoline or methylphenidate.
substance abuse. For example, a patient whose urine tests A study27 has suggested that methylphenidate does not positive for substances might be referred to a self-help encourage preexisting substance addictions, but diversion group such as Alcoholics Anonymous or Narcotics Anony- and abuse of the medication itself is still a concern, espe- mous. If the patient continues to use substances, the clini- cially in the ADHD and comorbid SUD population. The cian might insist that he or she seek outpatient substance use of extended-release stimulant preparations is recom- abuse treatment. If the outpatient treatment is not effec- mended because they may reduce the risk of medication tive, the clinician could ask the patient to consider In the largest study to date, Schubiner et al.38 conducted a 12-week controlled trial of methylphenidate in 48 adults with ADHD and cocaine abuse. Despite the high attritionrate, they found a significant reduction in symptoms of Adults with ADHD are at a higher risk for substance ADHD with no change in cocaine craving or use. An open abuse than adults without ADHD, especially when comor- trial of methylphenidate in 12 adults with ADHD and co- bid conditions are present. ADHD also changes the course caine abuse47 found a reduction in symptoms of ADHD and of substance abuse in adults. Self-medication has been ex- cocaine craving and use from baseline to endpoint.
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abuse in adults with ADHD, as has treatment with stimu- 14. Shekim WO, Asarnow RF, Hess E, et al. A clinical and demographic lants. Research on these subjects is inconclusive, but re- profile of a sample of adults with attention deficit hyperactivity disorder,residual state. Compr Psychiatry 1990;31:416–425 cent studies have indicated that pharmacotherapy reduces, 15. Biederman J, Wilens T, Mick E, et al. Is ADHD a risk factor for psycho- not increases, the risk of substance abuse in adults with active substance use disorders? findings from a four-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry 1997;36:21–29 16. Wilens TE, Biederman J, Mick E, et al. Attention deficit hyperactivity Treatment for adults with ADHD and substance abuse disorder (ADHD) is associated with early onset substance use disorders.
should begin by addressing substance abuse initially and throughout the treatment for the ADHD. Psychotherapy 17. Wilens TE . Substance abuse and ADD. Syllabus and Proceedings Summary of the 156th Annual Meeting of the American Psychiatric and pharmacotherapy are both important in the treatment Association; May 22, 2003; San Francisco, Calif. Abstract 103C:179 of adults with ADHD and substance abuse. Several medi- 18. Wilens TE, Biederman J, Mick E. Does ADHD affect the course of cations are effective in reducing symptoms of ADHD, substance abuse? findings from a sample of adults with and withoutADHD. Am J Addict 1998;7:156–163 including the antidepressant bupropion, the nonstimulant 19. Biederman J, Wilens TE, Mick E, et al. Does attention-deficit hypera- atomoxetine, and the stimulants. Stimulants with abuse ctivity disorder impact the developmental course of drug and alcohol potential should be sequenced after nonstimulant trials.
abuse and dependence? Biol Psychiatry 1998;44:269–273 20. Horner BR, Scheibe KE. Prevalence and implications of attention-deficit hyperactivity disorder among adolescents in treatment for substance Drug names: atomoxetine (Strattera), bupropion (Wellbutrin), desipra- abuse. J Am Acad Child Adolesc Psychiatry 1997;36:30–36 mine (Norpramin), dextroamphetamine (Dexedrine, Dextrostat, and 21. Tercyak KP, Lerman C, Audrain J. Association of attention-deficit/ others), imipramine (Tofranil, Surmontil, and others), methamphet- hyperactivity disorder symptoms with levels of cigarette smoking in a amine (Desoxyn), methylphenidate (Ritalin, Concerta, and others), community sample of adolescents. J Am Acad Child Adolesc Psychiatry 22. Tapert SF, Baratta MV, Abrantes AM, et al. Attention dysfunction predicts Disclosure of off-label usage: The author of this article has determined substance involvement in community youths. J Am Acad Child Adolesc that, to the best of his knowledge, bupropion and desipramine are not approved by the U.S. Food and Drug Administration for the treatment 23. Lambert NM, Hartsough CS. Prospective study of tobacco smoking and of attention-deficit/hyperactivity disorder (ADHD) and substance use substance dependencies among samples of ADHD and non-ADHD disorders; dextroamphetamine, methylphenidate, and pemoline are not participants. J Learn Disabil 1998;31:533–544 approved for the treatment of ADHD in adults; and imipramine is not 24. Biederman J, Wilens T, Mick E, et al. Pharmacotherapy of attention- approved for the treatment of ADHD in adults and adolescents.
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