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Evidence-Based Reviews


Adult ADHD: Less hyperactivity, but lingering inattention and distress

Adults with undiagnosed ADHD are probably in your office, bringing their hyperactive children to you for treatment. Now you can improve adults’ ADHD symptoms, too.

Vol. 1, No. 10 / October 2002

Attention-deficit/hyperactivity disorder (ADHD) may be the only mental disorder that was discovered in children and later acknowledged in adults. Although controlled studies of adults with ADHD are few, we know that ADHD is common in adults, it can be diagnosed reliably, and 75% of those treated respond to treatment. 1

The hallmark symptom of ADHD in children—hyperactivity—is usually attenuated in adults. In fact, some adults prefer the term ADD to ADHD because they are not hyperactive. This may be especially true of women, as their attention problems during childhood often were not recognized as ADHD (Box 1).

Box 1

WHY ADHD IS OFTEN MISSED IN GIRLS

In childhood, girls with ADHD typically present with attention problems and over-talkativeness, rather than hyperactivity. Talking too much does not disrupt the classroom as much as the larger-scale misbehavior of boys with ADHD, so the diagnosis is often missed in these girls. Overtalkativeness was added to the DSM-III-R criteria for ADHD in 1987, after it was recognized as a symptom of overactivity.

Now in midlife, many women with undiagnosed ADHD have children with ADHD. As they bring their children to treatment, these women are recognizing similar attention deficit symptoms from their own childhoods and are getting the help they need. As adults, many have low self-esteem, low energy, and weight problems. Among adults with ADHD, these women may be the most underdiagnosed.

Characteristics of adult ADHD

Adults with ADHD visit a psychiatrist for a variety of reasons. Often they are parents of children diagnosed with ADHD, and the possibility that they are similarly affected has arisen during their children’s evaluation and treatment. Sometimes they have recognized themselves in consumer articles about ADHD, or others have seen them in this light.

Adults with ADHD continue to experience their childhood difficulties in sustaining attention, listening, following instructions, and organizing tasks; inattention to details; lack of sustained mental effort; losing things; distractibility, and forgetfulness. Typical complaints include underachievement and poor adjustment at work or home. Comorbid ADHD may also be identified in patients who present with depression, anxiety, substance misuse, and mood swings.

The cognitive impairment of ADHD continues into adulthood, even in adults without hyperactive symptoms. It may be that adults are not hyperactive because the basal ganglia, which control motor activity in the brain, have over the years accommodated the problem through behavior modification or neurodevelopmental changes in late adolescence. 2

Children with ADHD have abnormal cerebrospinal fluid (CSF) and blood levels of the dopaminergic metabolite homovanillic acid (HVA), but adults with ADHD may not. The primary origin for CSF HVA is the nigrostriatum, which suggests that subcortical dopaminergic nuclei are more often affected in children than adults. 2 This may mean that compensatory changes occur as persons with ADHD mature, or perhaps the forms of ADHD that persist into adulthood have a different pathology or pathophysiology.

Comorbidities with ADHD

Rarely does one see pure ADHD; comorbidity is the rule. ADHD can be diagnosed quickly if you know what to look for. But a facile diagnosis may overlook a comorbidity that must be treated first—especially if you plan to use stimulants. Many patients with ADHD also have bipolar disorder, and a smaller proportion of patients with bipolar disorder have undetected ADHD. Placing a patient with undetected bipolar disorder on a stimulant could precipitate mania.

Table 1

COMMON COMORBIDITIES WITH ADHD

Bipolar disorder

Anxiety disorder

Depression

Drug dependence

Personality disorders

Somatoform disorders

Tourette’s disorder

Obsessive-compulsive disorder

Intermittent explosive disorder

Impulse control problems

 Addictive behaviors

 Sexual problems

 Compulsive gambling

Learning disabilities

Asperger’s syndrome

From the initial assessment, your treatment plan must address comorbid conditions (Table 1). This means taking a good history that includes corroborating information from relatives and data from the past, if possible. The case will then be much easier to manage, and quality of care greatly enhanced.

Stimulants: Usual first-choice therapy

In most cases, adult ADHD responds well to stimulant medications, although most available evidence is limited to studies in children. Several nonstimulant medications are also available, and the FDA is considering a new-drug application for a medication indicated for adult ADHD. Stimulants produce significant improvement in 30% of patients and mixed results in another 40%. Comorbidities may account for the 10 to 30% of patients who do not respond to stimulant therapy.

Methylphenidate, taken multiple times daily, is the most common treatment for ADHD. Dextroamphetamine and mixed salts of amphetamine also are used (Table 2).3 Patients usually respond to either methylphenidate or an amphetamine, and typically 25% of those who do not respond to one will respond to the other. When the clinical efficacy of amphetamines diminishes over time, many psychiatrists rotate medications. Replacing one amphetamine with another often eliminates the need to slowly increase the dosage and allows the clinician to maintain a relatively stable regimen.

When administering stimulants to adults, consider the individual’s total dosage requirement and daily schedule. Will he or she fare better with multiple daily dosing or a sustained-release form? How long is his or her average day? Does the patient have to be alert for 12 hours—or longer?

Some patients cannot sleep unless they take their last stimulant dose at bedtime. Others will have insomnia if a last dose is taken too late in the afternoon, especially with a sustained-release formulation.

When starting a patient on stimulants, begin with a 12-hour day and titrate the dosage—usually up, sometimes down—depending on response and side effects. Educating patients about their medications enables them to participate in decision-making.

Common side effects of stimulants include insomnia, decreased appetite, upset stomach, headache, anxiety, agitation, and increased pulse rate and blood pressure. The increase in blood pressure is usually less than 10%, but patients with poorly controlled hypertension should not be treated with stimulants until their blood pressure is well controlled. Until more is known about long-term effects, periodic assessment of blood pressure may be warranted.

Table 2

STIMULANT THERAPY FOR ADULTS WITH ADHD

Stimulants

Starting dosage

Titration rate

Usual dosing interval

Maximum dosage in adults

Methylphenidate

Short-acting

d, l-methylphenidate (Ritalin, Methylin)

5 mg qd or 5 mg bid

5 to 10 mg every 3 to 5 days

Every 3 to 4 hours Usually bid-tid

Average oral dosage 0.92 mg/kg/d; best response to 1.0 mg/kg/d16

Intermediate-acting

d, l-methylphenidate (Ritalin SR, Metadate ER, Methylin ER)

20 mg Ritalin SR; 10 mg Methylin ER or Metadate ER

10 to 20 mg per week

qd to bid

 

d-methylphenidate (Focalin)

2.5 mg bid

2.5 to 5 mg per week

bid, at least 4 hours apart

 

Long-acting

d, l-methylphenidate (Concerta)

18 mg qd

18 mg every 3 to 5 days

12+ hours, usually qd

 

d, l-methylphenidate (Metadate CD)

20 mg qd

20 mg per week

qd

 

Amphetamine

Short-acting

(Dexedrine, Dextrostat)

2.5 to 5 mg qd

2.5 to 5 mg every 3 to 5 days

Every 4 to 6 hours Usually bid-tid

 

Intermediate-acting

Mixed salts (Adderall)

5 mg qd or 5 mg bid

5 to 10 mg every 3 to 5 days

Every 4 to 6 hours Usually qd to bid

Average dosage 54 mg/d divided in two doses; maximum 30 mg bid

(Dexedrine Spansule)

5 or 10 mg qd

5 mg per week

qd

 

Long-acting

(Adderall XR)

10 mg qd

10 mg per week

qd

 

Stimulant

Pemoline (Cylert)

37.5 mg qd

18.75 mg per week

qd; typical range 56.25 to 75 mg qd

Maximum dosage 112.5 mg/d

Box 2

NONDRUG THERAPIES FOR ADULTS WITH ADHD

  • Organized and orderly home and working environment
  • Designated work/study space at home
  • Designated coach to supervise work/study
  • Healthy meals at regularly scheduled times
  • Regular exercise

Adults with ADHD have been treated with mixed amphetamine salts with positive results. In a 7-week controlled, crossover study, 27 adults with ADHD received an average of 54 mg/d administered in two doses. Symptoms improved significantly—a 42% decrease on the ADHD Rating Scale. The medication was well-tolerated, and 70% of those receiving mixed amphetamine salts improved, compared with 7% of those who received a placebo. 4

Duration of action of mixed salts of amphetamine has been measured at 3.5 hours with a 5-mg dose and 6.4 hours with a 20-mg dose. 5 With methylphenidate, a dose of 12.5 mg worked for 4 hours. The maximum recommended dosage of mixed salts of amphetamine is 40 mg/d in divided doses.

Stimulant medications are well-tolerated. Addiction and the need for increased dosages can occur over long-term use (months to years). Reducing the dosage or switching from methylphenidate to an amphetamine variant can usually prevent these problems.

The FDA recently approved a single-enantiomer form of methylphenidate. It contains only the active “d” enantiomer, whereas the racemic mixture contains both the “d” and “l” enantiomers. Because the “l” enantiomer is inert, the resulting medication is more potent and may be prescribed at half the dosage of the racemic mixture.

Pemoline, a once-daily stimulant, is considered a second-line treatment because of reports of hepatic failure in some patients. Its use requires written informed consent and liver function tests at baseline and every 2 weeks. In a controlled trial, pemoline at high dosages (120 to 160 mg/d) was found moderately effective in adults with ADHD. 6

Newer options: Longer-acting stimulants

Newer forms of slow-release methylphenidate and mixed amphetamine salts with sophisticated delivery systems are available.

Metadate CD is delivered in capsules containing beads with polymer coatings that dissolve and release their contents at different times. The capsules contain a 30:70 ratio of immediate- and extended-release beads.

Metadate CD has not been tested for adults in controlled clinical trials. In children ages 6 to 15, a single morning dose has been shown to be clinically effective in the morning and afternoon. A supplemental immediate-release capsule can be given in the morning if a patient’s medication levels need to be increased quickly. Dosage supplementation may also be required later in the day.

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

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