Evidence-Based Reviews

Adult ADHD: Less hyperactivity, but lingering inattention and distress

Current Psychiatry. 2002 October;1(10):34-43

References

1. Gadrow KD, Weiss M. Attention-deficit/hyperactivity disorder in adults: beyond controversy. Arch Gen Psychiatry 2001;58(8):784-5.

2. Ernst M, Zametkin AJ, Matochik JA, Jons PH, Cohen RM. DOPA decarboxylase activity in attention deficit hyperactivity disorder adults. A [fluorine-18]fluorodopa positron emission tomographic study. J Neurosci 1998;18(15):5901-7.

3. Spencer T, Wilens T, Biederman J, Faraone SV, Ablon JS, Lapey K. A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention-deficit hyperactivity disorder. Arch Gen Psychiatry 1995;52:434-43.

4. Spencer T, Biederman J, Wilens T, et al. Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2001;58(8):775-82.

5. Swanson J, Wigal S, Greenhill L, et al. Objective and subjective measures of the pharmacodynamic effects of Adderall in the treatment of children with ADHD in a controlled laboratory classroom setting. Psychopharmacol Bull 1998;34(1):55-60.

6. Wilens TE, Biederman J, Spencer TJ, et al. Controlled trial of high doses of pemoline for adults with attention-deficit/hyperactivity disorder. J Clin Psychopharmacol 1999;19(3):257-64.

7. Wilens TE, Biederman J, Mick E, Spencer TJ. A systematic assessment of tricyclic antidepressants in the treatment of adult attention-deficit hyperactivity disorder. J Nerv Ment Dis 1995;183(1):48-50.

8. Findling RL, Schwartz MA, Flannery DJ, Manos MJ. Venlafaxine in adults with attention-deficit/hyperactivity disorder: an open clinical trial. J Clin Psychiatry 1996;57(5):184-9.

9. Wender PH, Reimherr FW. Bupropion treatment of attention-deficit hyperactivity disorder in adults. Am J Psychiatry 1990;147(8):1018-20.

10. Wilens TE, Spencer TJ, et al. A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry 2001;158(2):282-8.

11. Grabowski J, Roache JD, Schmitz JM, Rhoades H, et al. Replacement medication for cocaine dependence: methylphenidate. J Clin Psychopharmacol 1997;17(6):485-8.

12. Levin FR, Evans SM, McDowell DM, Kleber HD. Methylphenidate treatment for cocaine abusers with adult attention-deficit/hyperactivity disorder: a pilot study. J Clin Psychiatry 1998;59(6):300-5.

13. Biederman J, Wilens T, Mick E, Spencer T, Faraone SV. Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder. Pediatrics 1999;104(2):e20.-

14. Zametkin AJ, Nordahl TE, Gross M, et al. Cerebral glucose metabolism in adults with hyperactivity of childhood onset. N Engl J Med 1990;323(20):1361-6.

15. Spencer T, Biederman J, Wilens T. Effectiveness and tolerability of atomoxetine in adults with attention deficit hyperactivity disorder. Am J Psychiatry 1998;155(5):693-5.

16. Noven Pharmaceuticals. The Science of Noven. Research and development. Transdermal technology. Available at: http://www.noven.com/research.htm.

Concerta is delivered in 18-mg and 36-mg tablets. The immediate-release coating on the tablets delivers medication within the first hour. The drug inside then dissolves in the GI tract and is released at a controlled rate by osmotic pressure. The indigestible tablet is passed in the stool.

Concerta was investigated in children ages 6 to 12 and provides 10 to 12 hours of sustained medication. From child studies, we know that when a patient takes a 36-mg tablet at 6 AM, blood levels decline in late afternoon. An 18-mg dose at noon covers the 4 to 6 hours needed for evening chores.

Adderall XR is an extended-release, once-daily form of mixed amphetamine salts. No controlled trials of this formulation are available in adults with ADHD. Its efficacy was established after two clinical trials of children aged 6 to 12 who met DSM-IV criteria for ADHD.

Individualized and flexible dosing improves symptom control and compliance when treating adults with ADHD. For some patients, once-daily dosing is more convenient than multiple doses, while others prefer the immediate-release form because they like its midday “pause” and bid dosing. The immediate-release tablet allows the flexibility of bid or tid dosing, depending on the day’s requirements.

Antidepressants: Another choice

Antidepressants are usually considered second-line treatment for ADHD because of concerns about efficacy and side effects. The few available studies show antidepressants work as well as stimulants but more slowly. It is good practice, therefore, to advise patients that—unlike feeling the effect of a stimulant in 60 minutes—they will not feel an effect from an antidepressant for days or weeks, and that achieving an optimal effect may take 4 to 6 weeks.

Antidepressants have several advantages over stimulants. They are not classified as narcotics, work without the on-off effects of stimulants, and can treat comorbid depression and anxiety. For adult ADHD, the most effective agents work on the catecholamine systems—norepinephrine and/or dopamine. This includes the tricyclic antidepressants, MAO inhibitors, bupropion, and venlafaxine. The serotonin reuptake inhibitors have not shown promise in ADHD, nor have mirtazapine or nefazodone demonstrated much effect.

Desipramine, a tricyclic antidepressant, is a strong inhibitor of norepinephrine reuptake. In a double-blind, controlled study in 41 adults with ADHD, 68% of patients receiving desipramine, 200 mg/d, responded positively, compared with no patients who took a placebo.⁷

When venlafaxine was given in standard dosages to 10 adults with ADHD in an open, 8-week clinical trial, an effect was seen by week two. Of the nine patients who completed the study, seven were considered responders. Symptoms were reduced significantly with venlafaxine treatment, and most side effects were mild.⁸

In an open study, bupropion treatment resulted in moderate to marked response in 74% of 19 patients. Ten of those patients who responded chose to continue bupropion rather than their previous medication.⁹ In a 6-week controlled study of 40 patients, bupropion use was associated with a 42% reduction in ADHD symptoms in the 38 patients who completed the study. Patients who received a placebo showed only a 24% reduction in symptoms. According to the CGI, 52% of patients who received bupropion reported being “much improved” or “very improved” compared with 11% of those receiving a placebo.¹⁰

Other treatment options that have shown mixed results include modafinil, alpha-2a agonists, acetylcholinesterase inhibitors, and the histaminergic agents.

Managing adverse effects

Substance abuse Stimulant abuse has been a concern, but it has not become the problem many feared. In fact, some studies have found that methylphenidate may help stanch the craving for cocaine in adults with ADHD.^11,12 Treating ADHD with pharmacotherapy also has been shown to reduce the risk for substance abuse in adolescence by 85%.¹³

With careful screening, you can usually identify drug-seeking behavior in adult patients. For patients with substance abuse problems, you can prescribe the nonstimulants.

Tics that can occur with stimulant medications usually can be suppressed by reducing the dosage, being vigilant, and waiting it out. Tics may ameliorate over weeks to months.

Cardiac and cognitive effects Long-term use of stimulant medications at high dosages has been associated with cardiac and cognitive toxicity, as noted in the 1998 NIH consensus statement on diagnosis and treatment of ADHD. It is important to provide patients with this information as part of their informed-consent briefing. (See “Related resources,” to view the consensus statement.)

Nonpharmacologic management

Nonpharmacologic treatments such as EEG biofeedback; psychoeducational approaches; and individual, family, and group psychotherapy are widely used to treat adults with ADHD. Clinicians and patients often perceive these interventions as beneficial, although none have been tested in randomized, placebo-controlled studies.