ADHD Throughout the Lifespan

From the 14th Annual Psychopharmacology Update, presented by the University of Nevada, School of Medicine, and the Nevada Psychiatric Association

Educational Objectives

The goal of this program is to improve the diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD) throughout the lifespan. After hearing and assimilating this program, the clinician will be better able to:

Describe the trajectory of ADHD from childhood to adulthood.

Differentiate between ADHD and other psychiatric disorders with overlapping symptoms.

Adapt the children’s criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) to adults.

Explain treatment considerations for adolescents with ADHD.

Compare the efficacies of stimulant medications and atomoxetine in treating children and adolescents with ADHD.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed:  Dr. Young is on the advisory boards of Eli Lilly and Shire, has received grants and/or research support from Eli Lilly, Novar­tis, and Shire, and is on the Speakers’ Bureaus of AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Mc­Neil, Novartis, Noven, sanofi-aventis, Sepracor, Shire, and Wyeth. Dr. Childress is a consultant to Shire and Novartis, has received grant support from Eli Lilly, Novartis, Ortho-McNeil, and Shire, and is on the Speakers’ Bureau for Novar­tis. The planning committee reported nothing to disclose. In their lectures, both speakers discussed the off-label use of medications.

Acknowledgements

Drs. Young and Childress were recorded at the 14th Annual Psychopharmacology Update, held February 12-14, 2009, in Las Vegas, NV, and sponsored by the University of Nevada, Medical School, and the Nevada Psychiatric Association. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

ADHD in Adolescents and Adults

Joel L. Young, MD, Medical Director, Rochester Center for Behavioral Medicine, and Clinical Assistant Professor of Psy­chiatry, Wayne State University School of Medicine, Detroit, MI

Introduction: types of attention-deficit/hyperactivity disorder (ADHD) include predominantly hyperactive/impul­sive, predominantly inattentive, and combined (most common); occurs worldwide; estimated prevalence in children 4% to 12%, in adults 4% (controversial; adult prevalence may be closer to 7%-9%); estimated persistence into adulthood 30% to 60%; considered most heritable of all psychiatric conditions; study found 25% of relatives of children with ADHD also had ADHD, vs 5% of controls

Trajectory of ADHD from childhood to adulthood: adolescents and children with ADHD (compared to those with­out) more likely to encounter juvenile justice system; more likely to experiment with substances, including nico­tine; more likely to get pregnant at early age; more likely to be injured; adults with ADHD (compared to those without) have higher rates of unemployment; often first to be laid off in poor economy and likely to experience long-term unemployment; more likely to be homeless; less likely to qualify for disability benefits

Inattentive symptoms: in childhood, include difficulty sustaining attention in school and at home, losing things, ap­pearing not to listen, and difficulty with follow-through and organization; in adulthood, include difficulty sustain­ing attention at work, procrastination, difficulty budgeting time (and arriving at work on time), inefficiency, slowness in getting things done, and difficulty with follow-through and organization

Hyperactive/impulsive symptoms: in childhood, include squirming, fidgeting, inability to stay in seat, inability to wait turn, blurting out answers, running and climbing excessively, inability to work or play quietly, intruding on or interrupting others; in adulthood, include inability to sit through meetings, inability to wait in line, interrupting oth­ers, fearing boredom, driving too fast, road rage, self-selection of very active job, making inappropriate comments (no “mental filter” to control social presentation)

Presentation: formerly believed that ADHD did not persist into adulthood, so Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) has no criteria for adults, and criteria for children must be adapted to adults (DSM-V will have criteria for adult); children usually present when school advises parents that child’s behav­ior unacceptable, and if child not treated, he or she can no longer attend that school; adults present less with behav­ioral complaints, more with inattention, distractibility, low energy, fatigue, or problem with motivation, and ADHD must be differentiated from major depression

Quality-of-life issues for adults with ADHD: symptoms may lead to low self-esteem, frustration, hopelessness, de­pression, anxiety, fatigue, and/or substance abuse; inability to control impulses may lead to arguments, accidents, increased spending, legal difficulties, substance use, disappointing partner with forgetfulness and lack of follow-through, higher rate of divorce (28%, compared to 15% of controls); controlled studies show that adults with ADHD more likely to be divorced or separated, do not fit in with peers, do not have good relationships with par­ents, more likely to be addicted to substances, over-represented in criminal justice system, and have higher rates of motor vehicle violations

Money management: adults with ADHD often have poor credit rating, exceed credit limit, have no savings, miss rent payments, and/or engage in impulse buying

Intelligence and ADHD: ADHD not more common in people with lower intelligence; intelligence is independent variable; high IQ can compensate for impairments of ADHD and forestall diagnosis; girls and women often diag­nosed later because they do not manifest behavioral issues of boys and men (do not come to attention of teachers or other authorities); “they’re just quietly underperforming”; individuals with higher IQ and girls and women often initially misdiagnosed with bipolar disorder, dysthymia, or personality disorder

Diagnostic process: make thorough differential diagnosis; several screening tests available (speaker favors Adult Self-Report Scale, available from World Health Organization), although some must be normalized for adults; ask when symptoms first began and obtain thorough history; review old report cards, if available; young people, es­pecially adolescent men, may not have much insight into self, so collateral input important; ask why patient pre­senting now; obtain family history (unusual to have patient with ADHD without similarly affected family members); medical mimics include hypothyroidism and iron-deficiency anemia

Differential diagnosis: symptoms of ADHD overlap with other psychiatric disorders, including bipolar disorder and major depression; comorbidity common (45% to 50% of adolescents with ADHD also have diagnosis of conduct disorder, 33.5% have anxiety disorder, 45% have depression); many (perhaps most) have substance abuse disor­der; treatment protocol for patients with comorbid psychiatric disorder suggests treating substance abuse first, then mood and anxiety disorders, and finally ADHD

Therapy: short-acting stimulants more likely to be abused or diverted than long-acting; many stimulants associated with weight loss, which adults frequently consider advantageous for themselves, but not for their children; medi­cations approved by Food and Drug Administration (FDA) for adolescents and adults include atomoxetine (Strat­tera), extended-release (XR) dexmethylphenidate (Focalin XR), mixed amphetamine salts XR (Adderall XR), methylphenidate (Concerta), and lisdexamfetamine (Vyvanse); medications not specifically approved for adults include short-acting mixed amphetamine salts (Adderall), short-acting methylphenidate (eg, Methylin, Ritalin, Focalin), dextroamphetamine (eg, Dexedrine, Dexedrine Spansules, Dextrostat), and methylphenidate transder­mal system (Daytrana)

Psychotherapy: cognitive behavioral therapy (CBT) plus stimulant medication better than stimulants alone

Conclusions: ADHD high-prevalence disorder; symptoms in adults can lead to low self-esteem, frustration, hope­lessness, functional impairment, depression, anxiety, fatigue, and/or substance abuse; prioritize treatment in pa­tients with multiple diagnoses; consider long-acting stimulants to minimize abuse and diversion potential; ADHD cannot be cured, but symptoms can be controlled

ADHD in Children and Adolescents

Ann Childress, MD, Volunteer Assistant Professor of Psychiatry, University of Nevada, School of Medicine, Las Vegas; President, Center for Psychiatry and Behavioral Medicine, Las Vegas, NV

ADHD defined: triad of inattention, concentration problems, and hyperactivity/impulsivity; DSM-IV requires that some symptoms present before 7 yr of age, but that requirement may be dropped in DSM-V (many adults cannot re­member exact age when childhood events occurred); patient must have some impairment in ³2 settings (eg, school, home, work); symptoms cannot be better accounted for by another mental health condition; ADHD is chronic dis­order, symptoms of which may persist into adolescence and adulthood; in adults, hyperactive and impulsive symp­toms may decrease at higher rate than inattention

Prevalence of ADHD in children and adolescents: ADHD affects 3% to 6% of children and adolescents, although some estimates as high as 16%; prevalence believed to be underestimated because 1) comorbidities may mask diag­nosis, 2) girls with inattentive symptoms tend to be underrecognized, underdiagnosed, and undertreated, 3) primary diagnosis difficult in adolescents

ADHD in adolescents: excessive motor activity tends to decrease; have sense of inner restlessness rather than being hyperactive; school work disorganized and shows poor follow-through; exhibit risky behaviors; have difficulty with authority figures, including teachers; have poor self-esteem and difficulty with peer relationships; prone to anger and emotional lability

Psychosocial challenges for adolescents with ADHD: increasing demands in school (eg, multiple teachers, long-term assignments, college applications, board examinations); family stress; peer pressure; driving responsibilities; substance abuse and/or diversion; increasing desire for autonomy

Treatment considerations for adolescents with ADHD: adolescents neither children nor adults; often need to feel in control of their treatment, which leads to problems with negotiating treatment alliance and with adherence to treatment regimen; when selecting medication, tailor treatment to fit adolescent’s schedule; keep treatment pri­vate and out of school; consider and discuss risk for substance abuse and medication misuse and diversion

Pharmacotherapy vs psychotherapy: study showed that medication more efficacious than psychotherapy;  combina­tion most efficacious; medication alone least expensive, then psychotherapy alone, then combination; if parents reluctant to put children on medication, advise them that studies show improvement with medication within hours

FDA-approved medications for ADHD: nonstimulant  —atomoxetine; immediate-release stimulants  —  methylphenidate; mixed amphetamine salts; dexamphetamine; dexmethylphenidate; long-acting stimulants  —  osmotic-release oral system (OROS); methylphenidate; methylphenidate long-acting (Ritalin LA); methylpheni­date sustained-action (Metadate CD); XR dexmethylphenidate; methylphenidate transdermal system; lisdexamfet­amine; mixed amphetamine salts XR

Mechanism of action: amphetamine and methylphenidate prevent reuptake of catecholamines; amphetamine also causes release of catecholamines

Stimulant comparisons: most studies done in laboratory classrooms that simulate school classrooms; screening in­struments include Swanson, Kotkin, Alger, M-Flynn, and Pelham (SKAMP) rating scale and Permanent Product Measure of Performance (PERMP); SKAMP  —  13-item rating scale completed and scored by trained observers; PERMP  —  400-question math test that measures how many addition and subtraction problems child can com­plete in given time

OROS vs modified-release methylphenidate (MPH): OROS has 22% immediate-release overcoat, 78% controlled-release bilayer core; modified-release MPH has 30% immediate-release methylphenidate beads, 70% extended-release methylphenidate beads coated with controlled-release polymer; on SKAMP, modified-release MPH supe­rior at 1.5 to 4.5 hr; OROS superior at 12 hr

Methylphenidate long acting (MPH-LA) vs OROS: MPH-LA superior early on, OROS superior at 12 hr

Dexmethylphenidate XR vs placebo: dexmethylphenidate XR separates from placebo early on

OROS vs dexmethylphenidate: dexmethylphenidate XR superior to OROS for first 6 hr, then OROS becomes supe­rior through twelth hour

Atomoxetine vs mixed amphetamine salts XR: 70% of children on mixed amphetamine salts XR had ³25% im­provement on SKAMP scores, compared with only 38% of those on atomoxetine

Lisdexamfetamine: FDA approved for children and adults, but not yet for adolescents; prodrug (must be activated by enzymes in gut); inability to separate chemical components outside of body discourages abuse; long-lasting; time to maximum concentration occurs at 4.5 to 6 hr; still 50% of maximum at 12 hr (as opposed to mixed amphetamine salts XR, which metabolizes at variable rates, thus necessitating twice-daily dosing in some children)

Methylphenidate transdermal system (MTS): approved only for children 6 to 12 yr of age; patch (placed on hip) releases fixed amount of methylphenidate each hour for 9 hr; peak concentration occurs at 6 to 8 hr; in study, SKAMP scores in children on MTS higher than those on placebo through twelfth hour

Off-label therapeutic options for ADHD: modafinil  —  did not get FDA approval and manufacturer decided not to pursue approval; bupropion XR  —  small study showed minimal efficacy (in adults, scores on ADHD rating scale same for bupropion and placebo); clonidine/guanfacine  —long-acting forms of both under development; guanfa­cine works mostly as a_2a agonist; clonidine works on all a₂ receptors; guanfacine immediate-release has proven ef­ficacy in children with ADHD and comorbid tic disorder; guanfacine XR approved and should be released soon

Before prescribing medication for children and adolescents: obtain thorough history, including patient’s personal and family history of cardiovascular problems; assess heart rate and blood pressure; electrocardiography and Holter monitor assessment not recommended; if cardiovascular concerns present, obtain consultation from pediatric cardi­ologist

On the horizon: nicotinic acid receptor drugs; memantine; drugs to enhance cognition

Suggested Reading

Adler LA: Clinical presentations of adult patients with ADHD. J Clin Psychiatry 65(Suppl 3):8, 2004; Barkley RA et al: ADHD in Adults: What the Science Says. New York: Guilford Press, 2008; Barkley RA: Driving impairments in teens and adults with at­tention-deficit/hyperactivity disorder. Psychiatr Clin North Am 27:233, 2004; Biederman J et al: Functional impairments in adults with self-reports of diagnosed ADHD: A controlled study of 1001 adults in the community. J Clin Psychiatry 67:524, 2004; Biederman J et al: Age-dependent decline of symptoms of attention deficit hyperactivity disorder: impact of remission definition and symptom type. Am J Psychiatry 157:816, 2000; Burket RC et al: Personality comorbidity in adolescent females with ADHD. J Psychiatr Pract 11:131, 2005; Faraone SV et al: The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med 36:159, 2006; González MA et al: Methylphenidate bioavailability from two extended-release formulations. Int J Clin Pharmacol Ther 40:175, 2002; Jensen PS et al: Findings from the NIMH Multimodal Treatment Study of ADHD (MTA): implications and applications for primary care providers. J Dev Behav Pediatr 22:60, 2001; Kessler RC et al: The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Sur­vey Replication. Am J Psychiatry 163:716, 2006; Markowitz JS et al: Pharmacokinetics of methylphenidate after oral adminis­tration of two modified-release formulations in healthy adults. Clin Pharmacokinet 42:393, 2003; Swanson JM et al: COMACS Study Group. A comparison of once-daily extended-release methylphenidate formulations in children with attention-deficit/hy­peractivity disorder in the laboratory school (the Comacs Study). Pediatrics 113:e206, 2004; Weiss M, Murray C: Assessment and management of attention-deficit hyperactivity disorder in adults. CMAJ 168:715, 2003; Young JL: ADHD Grownup: Evalu­ation, diagnosis, and treatment of adolescents and adults. London: W.W. Norton, LTD, 2007.