Clinical News & Knowledge: ADHD
November 1, 2008
Consultant.
No. 12
ADHD in Adults: How to Recognize—and Treat
Kevin Anthshel, PhD Steven V Faraone, PhD Arun Kunwar, MD
State University of New York
Upstate Medical University
Dr Faraone is professor of psychiatry and behavioral sciences, departments of psychiatry and behavioral sciences and neuroscience and physiology; Drs Antshel and Kunwar are assistant professors in the department of psychiatry and behavioral sciences at the State University of New York Upstate Medical University in Syracuse.
Treating Adult ADHD Pharmacotherapy. Ample data in the pediatric ADHD literature support the efficacy of stimulant medications.64 About 70% of children with ADHD will demonstrate a therapeutic response to stimulant medication.32,65 Early adult ADHD data suggested a less robust treatment response.57,62,66 However, Spencer and colleagues67 hypothesized that this may have been because of insufficient dosing. To test this hypothesis, the investigators completed a double-blind, placebo-controlled study of methylphenidate for adult ADHD that achieved an average daily dose of 1.0 mg/kg. The response rate of the stimulant-treated patients (74%) was similar to that seen in children with ADHD and was significantly greater than the 4% rate seen for placebo. The efficacy of these higher doses was confirmed by meta-analysis.30 Methylphenidate, amphetamines, and lisdexamfetamine are stimulants that are FDA-approved. (Less wellknown than methylphenidate and amphetamines, lisdexamfetamine is a pro-drug that converts to dextroamphetamine in the body.) Atomoxetine is a nonstimulant that is FDA-approved for managing adult ADHD. Both the stimulants and atomoxetine improve core symptoms of hyperactivity, inattention, and impulsivity.42,68,69 Thus, the same pharmacological agents that are effective in the pediatric ADHD population have also been demonstrated to be effective in adults with ADHD. See the Table for a summary of pharmacological approaches to managing ADHD in adults. Stimulant medications are generally started at a low dosage and titrated as needed to optimize the symptom improvement without causing significant adverse effects. Common adverse effects are dry mouth, insomnia, decreased appetite, and headache. The optimal dosage is best determined by each patient’s response. Traditionally, a trial with an immediate-release stimulant was undertaken before switching to a long-acting form; however, more recently, the American Academy of Child and Adolescent Psychiatry amended its practice parameters to recommend that long-acting agents be initiated first and titrated accordingly.70 A stimulant is effective as long as it remains in the system and does not have long-lasting cumulative effects. Because immediate- release stimulants have to be taken multiple times, compliance can be an issue, especially in a population that is known to be forgetful and disorganized.16 Atomoxetine is taken orally once or twice daily. Even with once-daily dosing, it provides full coverage in the evening with less rebound than may be observed with stimulants.71 Atomoxetine also lacks the midbrain dopamine effects that have been linked to addictive potential.72 There is also some evidence that atomoxetine may be particularly effective for adults with comorbid ADHD and depression. 73 Common adverse effects associated with atomoxetine are dry mouth, insomnia, nausea, decreased appetite, constipation, and sexual dysfunction. There is a black box warning for increased suicidal ideation in children but not in adults. While the stimulants and atomoxetine are more commonly prescribed for adult ADHD, bupropion, modafinil, and desipramine have also been described as effective for managing ADHD and may be used as second-line agents.32,74,75 Bupropion has demonstrated efficacy in open and controlled studies and may be particularly effective in adults with ADHD who have comorbid mood disorders.74,76-78 Modafinil has also been shown to be efficacious for adult ADHD in 2 double-blind, randomized, placebo-controlled studies. 75,79 Rather than affecting dopamine and norepinephrine in the striatum, modafinil alters the balance of γ-aminobutyric acid and glutamate. Desipramine has been shown to be efficacious for adult ADHD in a double- blind, placebo-controlled study.80 Findings suggest that adults with ADHD are more likely to require polypharmacy than children with ADHD.23,81-83 In addition, there is some evidence that baseline clinician ratings of ADHD symptoms are stronger predictors of pharmacotherapy treatment outcome than baseline patient reports.84 Cognitive-behavioral therapy. A psychosocial treatment component is generally recommended in addition to pharmacotherapy.85 Although cognitive- behavioral therapy (CBT) has not been shown to be effective in children with ADHD, there are reasons to be optimistic that CBT may be effective in adults with ADHD. For example, CBT is generally more effective in adolescents than in preadolescents.86 Similarly, CBT may be effective for reducing functional impairments in adults with ADHD being treated with stimulants.87 Safren and colleagues87 developed a supplemental CBT program for adults with ADHD who were receiving medication. Initial results from a small-scale study of this manualized therapy have been showing significant benefits beyond those achieved by medication alone.87 Ramsay and Rostain88 have also created a CBT program for adults with ADHD. In their open study, 43 adults with ADHD were treated for 6 months with a combination of pharmacotherapy and CBT. Findings from this study suggest that the combined treatment approach was effective across both symptom and functional parameters. Future Directions Despite our increased understanding of adults with ADHD, there is much that we still do not know. For example, most of the adult ADHD research has used samples of college students or adults under the age of 40. Thus, we know far less about ADHD in middle age and beyond. Following persons longitudinally across their life spans also presents a unique method of tracking not only interindividual change but also intra-individual change. The use of cross-sectional research designs limits our ability to assess these parameters. As Barkley, Biederman, and others’ longitudinal samples continue to age, we will know more about the continuation of ADHD in middle and late adulthood. Pediatric ADHD is more common in boys than in girls.89 This sexbased difference, however, appears less marked in adult ADHD.58,90,91 Relative to boys with ADHD, lower rates of externalizing disorders in girls have been found.89,92 The presence of an externalizing comorbid condition increases the likelihood that a child will be clinically referred for ADHD. Referral biases are possibly less salient for adults who, unlike children, can refer themselves for treatment. While this hypothesis has intuitive appeal, future studies should consider possible sex-based differences in ADHD across the life span. Further research is needed to clarify whether the DSM-IV approach to ADHD should be modified for adults. DSM-IV recognizes developmental changes in the expression of ADHD in several ways. It cautions diagnosticians that with maturation, symptoms become less conspicuous. Older children may be restless and fidgety but not overly hyperactive. With age, inattention may predominate as tasks at school require increasing levels of attention. DSM specifies that symptoms are considered present only if they are maladaptive and inconsistent with developmental level. DSM-IV includes the category of ADHD in partial remission for persons (especially adolescents and adults) who currently have symptoms but no longer meet full criteria. The net effect of developmental changes is to make it more difficult for children with ADHD to meet criteria for the disorder as they get older. Although this reflects the true remission of the disorder to some extent, it may also be because of the use of insensitive diagnostic criteria. For example, Barkley and colleagues23 examined the utility of DSM criteria for ADHD when used with adults, and they showed that only 6 to 8 symptoms were required to diagnose ADHD in adults. (DSM-IV stipulates that 12 symptoms must be present to diagnose ADHD.) The single symptom of "often being distractible" was sufficient to differentiate ADHD from typically developing adults while 5 to 7 more symptoms were needed to discriminate those with ADHD from clinic-referred adults. Inattention and verbal impulsivity symptoms were the best discriminators between patients with ADHD and clinical controls. 23 Barkley’s work as well as the work of others on the developmental sensitivity of ADHD symptoms has clear implications for the development of DSM-V. Also relevant to DSM-V, the ageat- onset criterion (onset before 7 years) has virtually no empirical support. 56 Other investigators have argued that the onset criterion should be broadened to include midadolescence or more generically phrased as "onset in childhood."23 Finally, as a function of educational and occupational impairments, clinicians may be asked to make recommendations concerning the need for and types of accommodations for those settings. In addition to a need for the clinician to be familiar with the standards of the Americans with Disabilities Act, which is required for obtaining such accommodations, it will also be important for future research to consider which accommodations are effective. For as often as they are used, there is remarkably little evidence that "extra time on tests" and/or "testing in a quiet, nondistracting environment" are effective for adults with ADHD. Therapeutic Agents in This Article Atomoxetine (Strattera) Bupropion (Wellbutrin, Zyban) D-amphetamine (Dexedrine) D,L-amphetamine (Adderall) D,L-amphetamine ER (Adderall XR) Desipramine (Norpramin, Pertofrane) Dexmethylphenidate (Focalin) Dexmethylphenidate ER (Focalin XR) Lisdexamfetamine (Vyvanse) Methylphenidate (Ritalin) Methylphenidate ER (Ritalin LA, Metadate CD, Concerta, Daytrana) Modafinil (Provigil)
REFERENCES:
1. Hill JC, Schoener EP. Age-dependent decline of attention
deficit hyperactivity disorder. Am J Psychiatry. 1996;153:1143-1146.
2. Spencer T, Biederman J, Wilens T, Faraone SV.
Is attention-deficit hyperactivity disorder in adults a
valid disorder? Harv Rev Psychiatry. 1994;1:326-335.
3. Faraone SV, Biederman J, Spencer T, et al.
Attention-deficit/hyperactivity disorder in adults: an
overview. Biol Psychiatry. 2000;48:9-20.
4. Kessler RC, Adler L, Barkley R, et al. The prevalence
and correlates of adult ADHD in the United
States: results from the National Comorbidity Survey
Replication. Am J Psychiatry. 2006;163:716 723.
5. Faraone SV, Perlis RH, Doyle AE, et al. Molecular
genetics of attention-deficit/hyperactivity disorder.
Biol Psychiatry. 2005;57:1313-1323.
6. Faraone SV, Biederman J, Mick E. The agedependent
decline of attention deficit hyperactivity
disorder: a meta-analysis of follow-up studies.
Psychol Med. 2006;36:159-165.
7. Biederman J, Faraone SV, Knee D, Munir K.
Retrospective assessment of DSM-III attention deficit
disorder in nonreferred individuals. J Clin Psychiatry. 1990;51:102-106.
8. Biederman J, Faraone SV, Spencer T, et al. Patterns
of psychiatric comorbidity, cognition, and
psychosocial functioning in adults with attention
deficit hyperactivity disorder. Am J Psychiatry. 1993;
150:1792-1798.
9. Millstein RB, Wilens TE, Biederman J, Spencer
TJ. Presenting ADHD symptoms and subtypes in
clinically referred adults with ADHD. J Atten Disord. 1997;2:159-166.
10. Downey KK, Stelson FW, Pomerleau OF, Giordani
B. Adult attention deficit hyperactivity disorder:
psychological test profiles in a clinical population. J Nerv Ment Dis. 1997;185:32-38.
11. Heiligenstein E, Keeling RP. Presentation of
unrecognized attention deficit hyperactivity disorder
in college students. J Am Coll Health. 1995;43:
226-228.
12. Heiligenstein E, Conyers LM, Berns AR, Miller
MA. Preliminary normative data on DSM-IV attention
deficit hyperactivity disorder in college students.
J Am Coll Health. 1998;46:185-188.
13. Murphy K, Barkley RA. Attention deficit hyperactivity
disorder adults: comorbidities and adaptive
impairments. Compr Psychiatry. 1996;37:393-401.
14. Biederman J, Mick E, Faraone SV. Age-dependent
decline of symptoms of attention deficit hyperactivity
disorder: impact of remission definition and
symptom type. Am J Psychiatry. 2000;157:816-818.
15. Eaton WO, McKeen NA, Campbell DW. Waxing
and waning of movement: implications for psychological
development. Dev Rev. 2001;21:205-223.
16. Weiss MD, Weiss JR. A guide to the treatment
of adults with ADHD. J Clin Psychiatry. 2004;65
(suppl 3):27-37.
17. Conners CK, Epstein JN, March JS, et al. Multimodal
treatment of ADHD in the MTA: an alternative
outcome analysis. J Am Acad Child Adolesc
Psychiatry. 2001;40:159-167.
18. Biederman J, Newcorn J, Sprich S. Comorbidity
of attention deficit hyperactivity disorder with
conduct, depressive, anxiety, and other disorders.
Am J Psychiatry. 1991;148:564-577.
19. Borland BL, Heckman HK. Hyperactive boys
and their brothers: a 25-year follow-up study. Arch
Gen Psychiatry. 1976;33:669-675.
20. Morrison J. Adult psychiatric disorders in parents
of hyperactive children. Am J Psychiatry. 1980;
137:825-827.
21. Heiligenstein E, Guenther G, Levy A, et al.
Psychological and academic functioning in college
students with attention deficit hyperactivity disorder. J Am Coll Health. 1999;47:181-185.
22. Shekim WO, Asarnow RF, Hess E, et al. A clinical
and demographic profile of a sample of adults
with attention deficit hyperactivity disorder, residual
state. Compr Psychiatry. 1990;31:416-425.
23. Barkley RA, Murphy KR, Fischer M. ADHD in
Adults: What the Science Says. New York: Guilford
Press; 2007.
24. Lahey BB, Applegate B, McBurnett K, et al.
DSM-IV field trials for attention deficit hyperactivity
disorder in children and adolescents. Am J Psychiatry. 1994;151:1673-1685.
25. Biederman J, Mick E, Faraone SV, et al. Influence
of gender on attention deficit hyperactivity
disorder in children referred to a psychiatric clinic.
Am J Psychiatry. 2002;159:36-42.
26. Faraone SV, Perlis RH, Doyle AE, et al. Molecular
genetics of attention-deficit/hyperactivity disorder.
Biol Psychiatry. 2005;57:1313-1323.
27. Faraone SV, Biederman J, Milberger S. An
exploratory study of ADHD among second-degree
relatives of ADHD children. Biol Psychiatry. 1994;35:
398-402.
28. Manshadi M, Lippmann S, O’Daniel RG,
Blackman A. Alcohol abuse and attention deficit disorder.
J Clin Psychiatry. 1983;44:379-380.
29. Biederman J, Faraone SV, Mick E, et al. High
risk for attention deficit hyperactivity disorder among
children of parents with childhood onset of the disorder:
a pilot study. Am J Psychiatry. 1995;152:431-435.
30. Biederman J, Faraone SV, Monuteaux MC,
et al. Gender effects on attention-deficit/hyperactivity
disorder in adults, revisited. Biol Psychiatry. 2004;55:
692-700.
31. Faraone SV, Biederman J, Monuteaux MC.
Toward guidelines for pedigree selection in genetic
studies of attention deficit hyperactivity disorder.
Genet Epidemiol. 2000;18:1-16.
32. Biederman J, Faraone S, Milberger S, et al. A
prospective 4-year follow-up study of attention-deficit
hyperactivity and related disorders. Arch Gen
Psychiatry. 1996;53:437-446.
33. Faraone SV, Biederman J, Feighner JA,
Monuteaux MC. Assessing symptoms of attention
deficit hyperactivity disorder in children and adults:
which is more valid? J Consult Clin Psychol. 2000;68:
830-842.
34.Wilens TE, Dodson W. A clinical perspective of
attention-deficit/hyperactivity disorder into adulthood. J Clin Psychiatry. 2004;65:1301-1313.
35. Weiss G, Hechtman L, Milroy T, Perlman T. Psychiatric
status of hyperactives as adults: a controlled
prospective 15-year follow-up of 63 hyperactive children.
J Am Acad Child Psychiatry. 1985;24:211-220.
36. Schubiner H, Tzelepis A, Milberger S, et al.
Prevalence of attention-deficit/hyperactivity disorder
and conduct disorder among substance abusers.
J Clin Psychiatry. 2000;61:244-251.
37. Hinshaw SP. Interventions for social competence
and social skill. In: Weiss G, ed. Child and
Adolescent Psychiatric Clinics of North America. Vol 1. Philadelphia: WB Saunders; 1992:539-552.
38. Semrud-Clikeman M, Biederman J, Sprich-
Buckminster S, et al. Comorbidity between ADHD
and learning disability: a review and report in a
clinically referred sample. J Am Acad Child Adolesc
Psychiatry. 1992;31:439-448.
39. Biederman J, Faraone SV, Spencer TJ, et al.
Functional impairments in adults with self-reports of
diagnosed ADHD: a controlled study of 1001 adults
in the community. J Clin Psychiatry. 2006;67:524-540.
40. Able SL, Johnston JA, Adler LA, Swindle RW.
Functional and psychosocial impairment in adults
with undiagnosed ADHD. Psychol Med. 2007;37:
97-107.
41. Faraone SV, Biederman J, Spencer T, et al. Diagnosing
adult attention deficit hyperactivity disorder:
are late onset and subthreshold diagnoses valid?
Am J Psychiatry. 2006;163:1720-1729.
42. Spencer T, Biederman J, Wilens T, et al. Effectiveness
and tolerability of tomoxetine in adults
with attention deficit hyperactivity disorder. Am J
Psychiatry. 1998;155:693-695.
43. Wilens TE, Prince JB, Biederman J, et al.
Attention-deficit hyperactivity disorder and comorbid
substance use disorders in adults. Psychiatr Serv. 1995;46:761-763, 765.
44. Wilens TE. Attention-deficit/hyperactivity disorder
and the substance use disorders: the nature
of the relationship, subtypes at risk, and treatment
issues. Psychiatr Clin North Am. 2004;27:283-301.
45. Biederman J, Wilens T, Mick E, et al. Psychoactive
substance use disorders in adults with attention
deficit hyperactivity disorder (ADHD): effects of
ADHD and psychiatric comorbidity. Am J Psychiatry. 1995;152:1652-1658.
EVIDENCE-BASED REFERENCES:
•Adler L, Dietrich A, Reimherr FW, et al. Safety
and tolerability of once versus twice daily atomoxetine
in adults with ADHD. Ann Clin Psychiatry.
2006;18:107-113.
•Spencer T, Biederman J, Wilens T, et al. A large,
double-blind, randomized clinical trial of methylphenidate
in the treatment of adults with attentiondeficit/
hyperactivity disorder. Biol Psychiatry.
2005;57:456-463.
|
|
SearchMedica Search Result
Find peer-reviewed literature and websites for practicing medical professionals
|