Alcohol & Drug Abuse: Long-Acting Stimulants for the Treatment of Attention-Deficit Disorder in Cocaine-Dependent Adults

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, [email protected]). Richard Frances, M.D., is editor of this column.