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Column   |    
Alcohol & Drug Abuse: Long-Acting Stimulants for the Treatment of Attention-Deficit Disorder in Cocaine-Dependent Adults
Ricardo Castaneda, M.D.; Robert Levy, M.D.; Marcos Hardy, M.D., Ph.D.; Manuel Trujillo, M.D.
Psychiatric Services 2000; doi: 10.1176/appi.ps.51.2.169

This column offers recommendations about the diagnosis and treatment of attention-deficit hyperactivity disorder (ADHD) among cocaine-dependent adults based on our year-long study of long-acting stimulants in the treatment of patients with these disorders. The lack of phenomenological information about these comorbid disorders hinders diagnostic and treatment efforts by clinicians.

Not surprisingly, ADHD among cocaine addicts is frequently unrecognized in clinical settings. Moreover, even when correctly diagnosed, ADHD generally goes untreated because physicians managing this patient population face a treatment quandary (1). Specifically, the treatment of ADHD generally involves stimulants, yet physicians are reluctant to prescribe them in addicted populations due to a fear of perpetuating or "priming" the use of cocaine and of drawing the attention of governmental agencies. As we describe here, these concerns may not be justified in the management of patients who are in full remission from their addiction.

ADHD, which is characterized by hyperactivity, disorganization, impulsivity, emotionality, unstable personality, fidgetiness, and inability to relax (2,3), has been reported to be present in 17 percent to 40 percent of various cocaine-dependent populations (1,2,4,5). Less well known is the fact that cocaine modifies these symptoms, thus making it more difficult to correctly diagnose such patients. We have reported that one reliable indicator of the presence of ADHD among adult cocaine-dependent subjects is the history of a "paradoxical" reaction to cocaine use (1). A carefully obtained clinical history confirms that despite eventual deterioration as cocaine dependence develops, patients with ADHD initially derive symptomatic improvement from the use of cocaine and may resort to this readily available stimulant for self-medication (1,6).

Instead of the excitation (4) and exacerbation of psychiatric symptoms (7) observed in cocaine-using populations without ADHD, cocaine induces a constellation of beneficial effects in the ADHD population; they include relaxation, anxiolysis, mood stabilization, improved focus and ability to think, and increased capacity to engage in productive activity, all in the relative absence of a euphoric response (1,4). Whether some individuals with ADHD could continue to use cocaine for symptomatic relief without actually abusing it has not been investigated, although it appears unlikely.

Both cocaine and methylphenidate bind to and compete for the transporters that remove dopamine from the synaptic cleft (8). The inference that psychostimulants derive their effects on ADHD from bolstering levels of dopamine in the frontal lobes has led to the general assumption that ADHD arises from intrinsic dopaminergic deficiencies (2,9). This view is further supported by the observation that haloperidol, which blocks dopamine receptors, negates the pharmacological actions of methylphenidate (10). An alternative view is that ADHD may develop from alterations in glutamatergic-dopaminergic interactions because both cocaine and amphetamine also activate dopamine-controlled glutamatergic circuitry (11).

Although cocaine and various formulations of stimulants can alleviate ADHD symptoms, these agents present differential liabilities for abuse and self-administration. It has been suggested that the differences in the speed of clearance from the brain between cocaine (20 minutes) and methylphenidate (90 minutes) and in the level and rate of dopamine transporter blockade are the key factors accounting for differences in the rate of self-administration of these compounds (8). If this suggestion is correct, then slow-release amphetamine-like compounds might be even less likely to be abused and more effective in preventing cocaine relapse in comorbid ADHD populations.

Our year-long treatment study of patients dually diagnosed with ADHD and cocaine dependence demonstrated that long-acting stimulants were highly effective in suppressing symptoms of severe ADHD, with minimal side effects and rare relapses to cocaine use (1). We administered long-acting stimulants rather than shorter-acting preparations despite reports of the efficacy of short-acting agents (12,13). Our aim was to minimize the risk of medication abuse (14) or cocaine relapse based on the rationale described above.

The population studied consisted of 19 patients who were seen in weekly or biweekly outpatient treatment and who agreed to participate in the 1997–1998 study. All patients met both DSM-IV criteria for cocaine dependence in complete remission and also met narrow DSM-IV criteria for adult attention-deficit hyperactivity disorder (3). They also were positive for six of the eight diagnostic Utah Criteria for Adult ADHD (15).

We employed an algorithm in which medications were introduced in an order inversely related to their expected degree of stimulant effects. Thus patients were placed on a treatment schedule that featured the progressive introduction of fluoxetine, bupropion, pemoline (2), slow-release methylphenidate, dextroamphetamine, and methamphetamine. Among the stimulants, we introduced the least expensive one, slow-release methylphenidate, first and reserved the most expensive one, methamphetamine, for the final step in the algorithm. We increased dosages of partially effective medications, progressively added others, and promptly discontinued any ineffective medication until we identified one medication regimen that suppressed each patient's ADHD symptoms for one year.

Daily starting dosages of fluoxetine were 20 mg; bupropion, 100 mg; pemoline, 37.5 mg; methylphenidate, 20 mg; dextroamphetamine, 10 mg; and methamphetamine, 15 mg. Incremental increases in dosages rarely exceeded doubling of the initial dose. Methylphenidate was increased up to 120 mg daily. Dextroamphetamine was increased to 60 mg a day and pemoline to 75 mg a day. To assess treatment efficacy, Utah scores were obtained at least weekly or within two days after any treatment modification. Urine toxicology screens were also monitored weekly.

Treatment proved very effective in suppressing ADHD symptoms, and relapses to cocaine use were rare. Eighteen of the 19 patients studied had a fully effective response, described as suppression of 80 percent of their initial ADHD symptoms. After one year of treatment, mean Utah scores for the sample decreased from 7.4 to 1.6. Only one patient (4 percent) did not derive any improvement in her ADHD symptoms from treatment with stimulants or antidepressants. The majority of patients (12, or 60 percent) eventually attained symptom suppression on only one drug, generally a long-acting stimulant. However, seven patients (36 percent) required drug combinations or alternating treatment regimens.

Despite dosage increases, the two antidepressants proved to be of very limited utility as monotherapy (15). The most effective treatment regimen consisted of monotherapy with a long-acting stimulant, usually slow-release methylphenidate. The second highly efficacious regimen included one long-acting stimulant in combination with either an antidepressant or pemoline. Finally, fluoxetine augmentation enhanced the effectiveness of various drug regimens, including pemoline, methylphenidate, and dextroamphetamine, and helped to maintain high levels of symptom suppression for an entire year.

The study had limitations, including lack of a placebo control group and a small number of subjects relative to the large number of treatments administered. Despite these limitations, a high degree of effectiveness of long-acting stimulants for ADHD symptoms was found. Further studies should be undertaken to replicate our findings. To minimize the risk of misdiagnosis or exacerbation of the underlying cocaine abuse problem, we recommend that diagnosis and treatment be initiated only when a patient has attained at least a partial remission from cocaine abuse.

Treatment response to long-acting stimulants among addicted and nonaddicted ADHD patients is immediate. An effective dose will induce subjective feelings of calm and emotional stability and will also increase attention and ability to focus. The type and dosage of long-acting stimulant medication must be tailored to each patient, because the effective dosages vary greatly among individuals and do not correlate with body weight or severity of ADHD symptoms. For example, in adults the effective dose of monotherapy with methylphenidate ranges from 40 to 220 mg a day. We have found that the patient's subjective response is the best guide for determining dosage and frequency of medication. In most cases the dosage that was initially effective will require upward titration within the first six months of treatment. Although most patients have a satisfactory response to one treatment regimen for at least a year, others require rotation of two or more effective treatment regimens.

Although medication abuse was not observed in our study or in our clinical practice, the possibility of abuse exists, and careful monitoring should be employed to prevent it. As patients achieve symptomatic stability through psychopharmacological treatment, it is important to address in psychotherapy several key aspects of the patient's emotional functioning. ADHD patients have confronted key developmental landmarks while they have suffered from disordered attention and motor function. They have frequently developed distorted self-images and feelings of fragility, which create narcissistic vulnerabilities. Optimum psychotherapeutic management of these patients requires integration of the new, healthier self-images and development of internal sources of organization and planning. Psychotherapy is also needed to help the patient discover and practice deeper relationships. These patients need to grieve the loss of some aspects of the ADHD that have been experienced positively, such as their capacity to easily respond to many emotional stimuli. They need to learn to appreciate mellower states and deeper emotional experiences as new sources of pride and personal satisfaction.

The authors are affiliated with the department of psychiatry at Bellevue Hospital- New York University Medical Center, 550 First Avenue, New York, New York (e-mail, castar01@popmail.med.nyu.edu). Richard Frances, M.D., is editor of this column.

Castaneda R, Sussman N, Levy R, et al: A treatment algorithm for attention-deficit hyperactivity disorder in cocaine-dependent adults: a one-year private practice study with long-acting stimulants, fluoxetine, and bupropion. Substance Abuse 20:55-67,  1999
 
Weiss RD, Pope HG, Mirin SM: Treatment of cocaine abuse and attention deficit disorder, residual type, with magnesium pemoline. Drug and Alcohol Dependence 15:69-72,  1985
 
Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC, American Psychiatric Association, 1994
 
Carroll KM, Rounsaville BJ: History and significance of childhood attention deficit disorder in treatment-seeking cocaine abusers. Comprehensive Psychiatry 34:75-81,  1993
 
Wilens TM, Spencer TJ, Biederman J: Role of medication in the treatment of adult attention-deficit disorder, in Attention-Deficit Hyperactivity Disorder Through the Lifespan. Edited by Nadeau KG. New York, Brunner/Mazel, 1994
 
Castaneda R, Lifshutz H, Galanter M, et al: An empirical assessment of the self-medication hypothesis. Comprehensive Psychiatry 2:180-184,  1994
 
Khantzian EJ: The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. American Journal of Psychiatry 142:1259-1264,  1985
 
Volkow ND, Wang G-F, Fowler JS, et al: Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. American Journal of Psychiatry 155:1325-1331,  1998
 
Hunt RD: Nosology, neurobiology, and clinical patterns of ADHD in adults. Psychiatric Annals 27:572-581,  1997
 
Levy F, Hobbes G: Does haloperidol block methylphenidate? Motivation or attention? Psychopharmacology 126:70-74,  1996
 
Reid MS, Hsu Jr K, Berger SP: Cocaine and amphetamine preferentially stimulate glutamate release in the limbic system: studies in the involvement of dopamine. Synapse 27:95-105,  1997
 
Wood RD, Reimherr FW, Wender PH, et al: Diagnosis and treatment of minimal brain dysfunction in adults. Archives of General Psychiatry 33:1453-1460,  1976
 
Spencer T, Wilens TE, Biederman J, et al: A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention-deficit hyperactivity disorder. Archives of General Psychiatry 52:350-353,  1995
 
Callahan PM, Appel JB, Cunningham KA: Dopamine D1 and D2 mediation of the discriminative stimulus properties of d-amphetamine and cocaine. Psychopharmacology 103:50-55,  1991
 
Wender PH: Attention-Deficit Hyperactivity Disorder in Adults. New York, Oxford University Press, 1995
 
Barrickman L, Noyes R, Kuperman S: Treatment of ADHD with fluoxetine: a preliminary trial. Journal of the American Academy of Child and Adolescent Psychiatry 30:762-767,  1991
 
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References

Castaneda R, Sussman N, Levy R, et al: A treatment algorithm for attention-deficit hyperactivity disorder in cocaine-dependent adults: a one-year private practice study with long-acting stimulants, fluoxetine, and bupropion. Substance Abuse 20:55-67,  1999
 
Weiss RD, Pope HG, Mirin SM: Treatment of cocaine abuse and attention deficit disorder, residual type, with magnesium pemoline. Drug and Alcohol Dependence 15:69-72,  1985
 
Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC, American Psychiatric Association, 1994
 
Carroll KM, Rounsaville BJ: History and significance of childhood attention deficit disorder in treatment-seeking cocaine abusers. Comprehensive Psychiatry 34:75-81,  1993
 
Wilens TM, Spencer TJ, Biederman J: Role of medication in the treatment of adult attention-deficit disorder, in Attention-Deficit Hyperactivity Disorder Through the Lifespan. Edited by Nadeau KG. New York, Brunner/Mazel, 1994
 
Castaneda R, Lifshutz H, Galanter M, et al: An empirical assessment of the self-medication hypothesis. Comprehensive Psychiatry 2:180-184,  1994
 
Khantzian EJ: The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. American Journal of Psychiatry 142:1259-1264,  1985
 
Volkow ND, Wang G-F, Fowler JS, et al: Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. American Journal of Psychiatry 155:1325-1331,  1998
 
Hunt RD: Nosology, neurobiology, and clinical patterns of ADHD in adults. Psychiatric Annals 27:572-581,  1997
 
Levy F, Hobbes G: Does haloperidol block methylphenidate? Motivation or attention? Psychopharmacology 126:70-74,  1996
 
Reid MS, Hsu Jr K, Berger SP: Cocaine and amphetamine preferentially stimulate glutamate release in the limbic system: studies in the involvement of dopamine. Synapse 27:95-105,  1997
 
Wood RD, Reimherr FW, Wender PH, et al: Diagnosis and treatment of minimal brain dysfunction in adults. Archives of General Psychiatry 33:1453-1460,  1976
 
Spencer T, Wilens TE, Biederman J, et al: A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention-deficit hyperactivity disorder. Archives of General Psychiatry 52:350-353,  1995
 
Callahan PM, Appel JB, Cunningham KA: Dopamine D1 and D2 mediation of the discriminative stimulus properties of d-amphetamine and cocaine. Psychopharmacology 103:50-55,  1991
 
Wender PH: Attention-Deficit Hyperactivity Disorder in Adults. New York, Oxford University Press, 1995
 
Barrickman L, Noyes R, Kuperman S: Treatment of ADHD with fluoxetine: a preliminary trial. Journal of the American Academy of Child and Adolescent Psychiatry 30:762-767,  1991
 
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