Pharmacotherapy of ADHD
Just as with children, stimulants and atomoxetine(Drug information on atomoxetine) are the mainstay treatment for adults with ADHD. FDA-approved medications for ADHD treatment in adults include mixed amphetamine salts, dexmethylphenidate, and atomoxetine. Please see the Table for a summary of specific FDA-approved medications for adults with ADHD. Package inserts should be reviewed for complete prescribing details. All other medications discussed here are off-label. The mechanism of action for medications used to treat ADHD is thought to involve the neurotransmission of dopamine and/or norepinephrine(Drug information on norepinephrine). Nicotinic agonists may hold some promise and histaminergic systems have been hypothesized to be involved in the pathophysiology of ADHD.
Summary of FDA-approved medications for
adults with attention-deficit/hyperactivity disorder
|Medication||Starting dosage||Maximum dosage||Common adverse effects|
|Amphetamine salts-XR||20 mg/d||60 mg/d||Dry mouth, loss of appetite, insomnia, |
weight loss, headache, nausea, anxiety, agitation,
dizziness, tachycardia, diarrhea
|Dexmethylphenidate-XR||10 mg/d||20 mg/d||Headache, dry mouth, anxiety, dyspepsia, |
pharyngolaryngeal pain, feeling jittery, dizziness
|Atomoxetine||40 mg/d (increase to 80 mg/d after 3 days)||100 mg/d||Constipation, dry mouth, nausea, decreased appetite, dizziness, insomnia, decreased libido, ejaculatory problems, impotence, urinary problems, dysmenorrhea|
XR, extended release.
Source: FDA Web site.
Amphetamine salts and methylphenidate(Drug information on methylphenidate) preparations have established efficacy in adults with ADHD.2,13,14 The mechanism of action for stimulants is thought to be primarily mediated through dopamine(Drug information on dopamine)rgic neurotransmission.15 Effective dosages in adults should be based on weight and may be significantly higher than the dosages known to be effective in children. For example, a recent study on the use of osmotic-release oral system methylphenidate in adults suggested an optimal dosage of 1.3 mg/kg/d.13 Adults in this study had a higher incidence of anorexia, dry mouth, moodiness, anxiety, insomnia, cardiovascular complaints, and dizziness.13
Cardiovascular complaints may be of concern in adults more so than in children. Because of the higher incidence of cardiovascular disease, including hypertension, routine monitoring is strongly recommended.2,13 In addition, the high rate of comorbidity in adults with ADHD is a factor, because stimulants can worsen psychosis, mood, and anxiety. The use of stimulant medication in adults with comorbid substance use disorders is particularly problematic given the potential for abuse. However, long-acting formulations are a reasonable option with less potential for abuse.13
Multiple studies have confirmed the efficacy of atomoxetine in treating adults with ADHD. Atomoxetine is primarily a norepinephrine reuptake inhibitor, although it may secondarily affect dopamine levels.15 It may be particularly useful in adults with ADHD, because it can alleviate anxiety symptoms and has no abuse potential.15 Atomoxetine may be considered first in adults with comorbid substance use disorders, anxiety disorders, or mood disorders.16 It is generally well tolerated; common adverse effects observed in adults include insomnia and GI and genitourinary symptoms.15 Increases in blood pressure and pulse have been observed in adults; therefore, atomoxetine should be used with caution in the context of cardiovascular risk factors such as hypertension.15
Numerous antidepressant medications have been used to treat ADHD. However, there is limited data supporting their use and published trials typically involved small numbers and high dropout rates.17
Perhaps the strongest evidence supports the use of desipramine, which has been found to have similar efficacy to stimulants.17 The results of a 6-week, double-blind, placebo-controlled trial showed desipramine to be effective in the treatment of adult ADHD; however, adverse effects and potential for overdose lethality limit its usefulness.18
Bupropion is frequently used to treat ADHD. A few small studies support its use in adults. Bupropion's mechanism of action is unclear but may be related to indirect agonism of norepinephrine and dopamine.19
A double-blind, placebo-controlled, randomized trial of 40 adults with ADHD20 and a recent, larger study involving 162 adults over an 8-week treatment period21 supported its use. The latter study used once-daily dosing of bupropion extended-release (XL) and demonstrated effect sizes similar to those seen with atomoxetine for the treatment of adult ADHD.21 The study excluded adults with comorbid mood or anxiety disorders, suggesting that the benefit attained with bupropion was independent of any antidepressant or anxiolytic effect, and bupropion-XL was generally well tolerated with no serious adverse events.21 The demonstrated efficacy of bupropion in the treatment of depression suggests that it may be used as monotherapy in patients with comorbid ADHD and depression.
In a preliminary study, venlafaxine was shown to effectively treat ADHD in adults with comorbid ADHD and depression.22 Venlafaxine alone was found to be comparable in efficacy to a combination of stimulants and antidepressants, suggesting that venlafaxine may also be an option as monotherapy for patients with comorbid depression and ADHD.22 There are no controlled studies using venlafaxine for the treatment of ADHD and more research is needed.
Monoamine oxidase inhibitors and other tricyclic antidepressants besides desipramine have been used to treat ADHD with varying levels of success, but their use is limited by problematic adverse effects. There is little evidence supporting the use of SSRIs, possibly because of their lack of activity on norepinephrine and dopamine systems.2
The central α-agonists clonidine(Drug information on clonidine) and guanfacine(Drug information on guanfacine) are often used in the treatment of ADHD, but there is little data to support their use, particularly in adults. Potential adverse effects include rebound hypertension, dizziness, and transient sedation.2,23 Cardiovascular monitoring is recommended.