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Alcohol & Drug Abuse: Practical Guidelines for the Treatment of Substance Abusers With Adult Attention-Deficit Hyperactivity Disorder
Frances R. Levin, M.D.; Suzette M. Evans, Ph.D.; Herbert D. Kleber, M.D.
Psychiatric Services 1999; doi:

With the greater acceptance of adult attention-deficit hyperactivity disorder (ADHD) as a valid clinical diagnosis, this disorder has been increasingly recognized among substance abusers seeking treatment. Because adult ADHD occurs in a substantial minority of substance abusers—from 10 to 30 percent—the question arises of whether individuals identified as having adult ADHD and substance abuse would benefit from targeted treatment interventions.

Cocaine abusers with childhood histories of ADHD are more likely to use cocaine at an earlier age and to have more exposure to treatment, but they do less well in treatment (1). Furthermore, Dansereau and associates (2) have found that methadone maintenance patients with "poor attention" do less well in treatment. Thus it seems reasonable to conclude that improving an individual's difficulties with inattention, hyperactivity, or impulsivity will increase that person's likelihood of succeeding in substance abuse treatment.

Because pharmacologic treatments have been shown to be the most effective approaches for childhood ADHD, they have been the most extensively studied treatment for adult ADHD. Among the nonstimulant medications used to treat adult ADHD, the most promising are desipramine, tomoxetine, and bupropion, and possibly venlafaxine. Whereas bupropion and venlafaxine have been evaluated and found promising only in open trials (3,4), desipramine and tomoxetine have been studied under double-blind conditions and found to reduce ADHD symptoms significantly better than placebo (5,6).

Among stimulant medications for adults with ADHD, methylphenidate has been the most widely studied. Six studies have evaluated the efficacy of methylphenidate, and three studies have evaluated the efficacy of pemoline (7). The majority of studies have reported improvement in ADHD symptoms (7).

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Nonstimulant medications

Using stimulants to treat substance abusers gives rise to concerns about safety and abuse. Thus it makes sense to consider use of nonstimulant medications first, even though little clinical information exists about their efficacy for adult substance abusers with ADHD. Although desipramine and bupropion have been studied for the treatment of cocaine abuse, they have not been studied for treating cocaine abusers with adult ADHD. Margolin and colleagues (8) found that among cocaine abusers bupropion was no more effective than placebo in reducing cocaine use. Desipramine has been widely studied for treating cocaine addiction in several double-blind placebo-controlled trials, with mixed results (9,10,11).

Desipramine is one of the few medications that has been studied under controlled laboratory conditions in combination with repeated intravenous cocaine administration among cocaine abusers not seeking treatment. Although desipramine did not produce any untoward side effects and reduced the positive effects of cocaine—that is, it decreased craving for cocaine—it did not, under these laboratory conditions, reduce the number of cocaine doses self-administered by the subjects (12).

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Stimulant medication

Few studies have addressed how to treat substance abusers with ADHD. Methylphenidate has been the most reported treatment for this group, and most studies have consisted of case reports about cocaine abusers. In a recently completed open pilot treatment study, ten patients received sustained-release methylphenidate in dosages ranging front 40 to 80 mg a day (13). Patients reported a reduction in ADHD symptoms and also reduced cocaine use, as documented by urine toxicology. Double-blind trials targeting substance abusers with ADHD using placebo and other treatment medications are under way.

A reasonable alternative to methylphenidate is pemoline, because it has lower abuse potential. One case report suggests that pemoline may improve ADHD symptoms and decrease cocaine use among cocaine abusers with adult ADHD (14). Use of stimulants in this population remains controversial because of concerns about their safety and potential for abuse.

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Safety

We have recently completed a laboratory study in which seven cocaine abusers with adult ADHD participated (15). For separate periods, they were maintained on placebo, a low dosage of sustained-release methylphenidate (40 mg a day), and a high dosage of sustained-release methylphenidate (60 mg a day). While maintained on each of the three conditions, the seven participants were given repeated doses of intravenous cocaine. Cocaine administration produced larger increases in blood pressure when participants were maintained on low and high dosages of methylphenidate than when they were on placebo. However, the increases were not clinically significant. No other adverse effects were noted.

In a recent double-blind placebo-controlled trial, Grabowski and associates (15) used methylphenidate (45 mg a day) to treat cocaine abusers without ADHD. Although methylphenidate did not produce a significant reduction in cocaine use compared with placebo, no untoward medical side effects were noted.

The safety of using pemoline with substance abusers has been less well evaluated. Given pemoline's increased risk, albeit small, for hepatotoxicity, its safety among substance abusers remains unclear.

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Potential for abuse

The other major concern about the use of stimulant medication for substance abusers with adult ADHD is the risk of abuse, as well as the possibility that a stimulant medication might increase craving for cocaine or other stimulants. Although other stimulant medications such as dextroamphetamine and methamphetamine would probably reduce ADHD symptoms among substance abusers with adult ADHD, the higher likelihood of abuse of these medications compared with pemoline and methlyphenidate has limited their use for treating substance abusers with adult ADHD.

Several questions have yet to be answered. Do stimulants work more effectively than other medications for substance abusers with ADHD? Do the benefits of stimulant medications outweigh the risks of possible abuse? The literature on childhood ADHD suggests that stimulants are more likely to be effective in treating ADHD symptoms than other medications; antidepressants are often considered a second-line approach. However, this may not be the case with adult substance abusers. The choice of medication needs to be based on the specific clinical situation.

Because desipramine and bupropion pose less risk of abuse by patients and by their family members or friends, these medications should be considered first-line approaches for the treatment of adult substance abusers with ADHD.

More data exist about the safety of using desipramine for substance abusers in outpatient clinical settings than about the safety of using bupropion. Although both medications appear to be safe for use with substance abusers, these individuals often combine prescribed medication with drugs of abuse. Because an additive or synergistic risk of seizure may exist when bupropion is combined with cocaine or other drugs of abuse, this medication should be avoided or used cautiously with substance abusers who have a history of seizures. Of note, dosages of desipramine and bupropion used to treat depression appear to be similarly effective for adult ADHD.

For individuals who do not respond to an antidepressant, methylphenidate, particularly the sustained-release preparation, may be an effective alternative if prescribed in a well-controlled manner. There are several ways to monitor a patient's use of stimulants and thus limit the potential for abuse. First, the physician should limit the number of pills given with each prescription and keep a log of the pills prescribed. Generally, during the first few weeks of treatment, no more than a one-week supply should be given. Second, frequent patient contact is important because it allows the physician to review whether the stimulant medication is benefiting the patient and also to look for any evidence of stimulant misuse or abuse.

A third way to limit the potential for abuse of stimulants is by documenting improvements, preferably by using established instruments such as the Adult Behavior Checklist (17). If improvements are not noted after an adequate trial of medication (four weeks), then continued use is unlikely to help. Fourth, urine toxicology tests should be routinely done during the first four weeks of medication treatment and then done randomly, about once a month, after that. Patients should also be asked at each visit about their alcohol and drug use. If they do not substantially reduce or cease drug use, then stimulant medications should be discontinued, and the patient should be referred for more intensive substance abuse treatment.

It is critical that the patient safeguard the stimulant medication. Although the patient may not abuse the medication, other family members, particularly adolescents, may do so. In addition, it is preferable if the medication can be given in the context of family support and monitoring.

Finally, the use of a sustained-release preparation of methylphenidate might be preferable to the standard formulation because of its slower onset of action, which inherently reduces its abuse potential, and because it can be administered twice a day rather than several times a day. Although clinical lore suggests that the sustained-release preparation is less clinically effective than the standard preparation, this conclusion may be related to inadequate dosing. In our experience, dosages of up to 1 mg per day per kg of body weight are often necessary to effectively treat adult ADHD and substance abuse; however, inadequate dosages, similar to those frequently prescribed for children, are sometimes given to adults.

For individuals with adult ADHD who do not use drugs or alcohol, it is less clear what should be the first-line medication treatment. Some might suggest that antidepressants are still the preferred treatment because they have a lower abuse potential. We would agree that if an individual has a depressive disorder along with symptoms of ADHD, then desipramine or bupropion are good first choices, However, because little evidence exists that methylphenidate increases craving for other drugs and because it has been the most widely used and most effective medication for childhood and adult ADHD, we would recommend its use, with the precautions described above, as a first-line treatment for individuals with no ongoing substance use disorder.

Although these guidelines have focused on pharmacologic interventions, simply providing medication without other treatment interventions is unlikely to change ingrained drug-taking behavior. Other strategies such as 12-step models, contingency management, and relapse prevention have been shown to be effective for treating substance abuse. These approaches, in conjunction with one of the medications mentioned above, are the best current methods for treating comorbid ADHD and substance abuse.

However, because many questions remain, these guidelines should be considered preliminary, and they need to be tempered by the clinical situation and the physician's ability to adequately monitor the patient's response to treatment.

This work was supported by grants K20-DA-000214 and P50-DA-09236 from the National Institute on Drug Abuse.

The authors are affiliated with the department of psychiatry at Columbia University and New York State Psychiatric Institute, 722 West 168th Street, Unit 66, New York, New York 10032 (e-mail frl2@columbia.edu). Richard J. Frances, M.D., is editor of this column.

Carroll KM, Rounsaville BI: History and significance of childhood attention deficit disorder in treatment-seeking cocaine abusers. Comprehensive Psychiatry 34:75-86,  1993
 
Dansereau DF, Joe GW, Simpson DD: Attentional difficulties and the effectiveness of a visual representation strategy for counseling drug-addicted clients. International Journal on Addictions 30:371-386,  1995
 
Wender PH, Reimherr FW: Bupropion treatment of attention-deficit hyperactivity disorder in adults. American Journal of Psychiatry 147:1018-1020,  1990
 
Adler LA, Resnick S, Kunz M, et al: Open-label trial of venlafaxine in adults with attention deficit disorder. Psychopharmacology Bulletin 31:785-788,  1995
 
Wilens TE, Biederman J, Prince J, et al: Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder. American Journal of Psychiatry 153:1147-1153,  1996
 
Spencer T, Biederman J, Wilens T, et al: Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder. American Journal of Psychiatry 155:693-695,  1998
 
Wilens TE, Biederman J, Spencer TJ, et al: Pharmacotherapy of adult attention deficit disorder: a review. Journal of Clinical Psychopharmacology 15:270-279,  1995
 
Margolin A, Kosten TR, Avants SK, et al: A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients. Drug and Alcohol Dependence 40:125-131,  1995
 
Gawin FH, Kleber HD, Byek R, et al: Desipramine facilitation of initial cocaine abstinence. Archives of General Psychiatry 46:117-121,  1989
 
Kosten TR, Morgan CM, Falcione J, et al: Pharmacotherapy for cocaine-abusing methadone-maintained patients using amantadine or desipramine. Archives of General Psychiatry 49:894-898,  1992
 
Arndt IO, Dorozynsky L, Woody GE, et al: Desipramine treatment of cocaine dependence in methadone-maintenance patients. Archives of General Psychiatry 49:888-993,  1992
 
Fischman MW, Foltin RW, Nestadt G, et al: Effects of desipramine maintenance on cocaine self-administration in humans. Journal of Pharmacology and Experimental Therapeutics 253:760-770,  1990
 
Levin FR, Evans SM, McDowell D, et al: Methylphenidate treatment for cocaine abusers with adult attention-deficit/hyperactivity disorder: a pilot study. Journal of Clinical Psychiatry 59:300-305,  1998
 
Weiss RD, Pope HG, Mirin SM: Treatment of chronic cocaine abuse and attention deficit disorder, residual type, with magnesium pemoline. Drug and Alcohol Dependence 15:69-72,  1985
 
Evans SM, Levin FR, Kleber HD: The effects of cocaine alone and in combination with sustained-release methylphenidate in cocaine abusers with ADHD. Presented at the annual meeting of the American College of Neuropsychopharmacology, Waikoloa, Hawaii, Dec 8-12, 1997
 
Grabowski J, Roache JD, Schmitz JM, et al: Replacement medication for cocaine dependence: methylphenidate. Journal of Clinical Psychopharmacology 17:485-488,  1997
 
Murphy KR, Barkley RA: Prevalence of DSM-IV symptoms of ADHD in adult licensed drivers. Journal of Attention Disorders 1:147-161,  1996
 
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References

Carroll KM, Rounsaville BI: History and significance of childhood attention deficit disorder in treatment-seeking cocaine abusers. Comprehensive Psychiatry 34:75-86,  1993
 
Dansereau DF, Joe GW, Simpson DD: Attentional difficulties and the effectiveness of a visual representation strategy for counseling drug-addicted clients. International Journal on Addictions 30:371-386,  1995
 
Wender PH, Reimherr FW: Bupropion treatment of attention-deficit hyperactivity disorder in adults. American Journal of Psychiatry 147:1018-1020,  1990
 
Adler LA, Resnick S, Kunz M, et al: Open-label trial of venlafaxine in adults with attention deficit disorder. Psychopharmacology Bulletin 31:785-788,  1995
 
Wilens TE, Biederman J, Prince J, et al: Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder. American Journal of Psychiatry 153:1147-1153,  1996
 
Spencer T, Biederman J, Wilens T, et al: Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder. American Journal of Psychiatry 155:693-695,  1998
 
Wilens TE, Biederman J, Spencer TJ, et al: Pharmacotherapy of adult attention deficit disorder: a review. Journal of Clinical Psychopharmacology 15:270-279,  1995
 
Margolin A, Kosten TR, Avants SK, et al: A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients. Drug and Alcohol Dependence 40:125-131,  1995
 
Gawin FH, Kleber HD, Byek R, et al: Desipramine facilitation of initial cocaine abstinence. Archives of General Psychiatry 46:117-121,  1989
 
Kosten TR, Morgan CM, Falcione J, et al: Pharmacotherapy for cocaine-abusing methadone-maintained patients using amantadine or desipramine. Archives of General Psychiatry 49:894-898,  1992
 
Arndt IO, Dorozynsky L, Woody GE, et al: Desipramine treatment of cocaine dependence in methadone-maintenance patients. Archives of General Psychiatry 49:888-993,  1992
 
Fischman MW, Foltin RW, Nestadt G, et al: Effects of desipramine maintenance on cocaine self-administration in humans. Journal of Pharmacology and Experimental Therapeutics 253:760-770,  1990
 
Levin FR, Evans SM, McDowell D, et al: Methylphenidate treatment for cocaine abusers with adult attention-deficit/hyperactivity disorder: a pilot study. Journal of Clinical Psychiatry 59:300-305,  1998
 
Weiss RD, Pope HG, Mirin SM: Treatment of chronic cocaine abuse and attention deficit disorder, residual type, with magnesium pemoline. Drug and Alcohol Dependence 15:69-72,  1985
 
Evans SM, Levin FR, Kleber HD: The effects of cocaine alone and in combination with sustained-release methylphenidate in cocaine abusers with ADHD. Presented at the annual meeting of the American College of Neuropsychopharmacology, Waikoloa, Hawaii, Dec 8-12, 1997
 
Grabowski J, Roache JD, Schmitz JM, et al: Replacement medication for cocaine dependence: methylphenidate. Journal of Clinical Psychopharmacology 17:485-488,  1997
 
Murphy KR, Barkley RA: Prevalence of DSM-IV symptoms of ADHD in adult licensed drivers. Journal of Attention Disorders 1:147-161,  1996
 
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