Diagnosis and Management of Adhd in Adults

Educational Objectives

The goal of this program is to improve the diagnosis and management of attention-deficit/hyperactivity disorder (ADHD) in adults. After hearing and assimilating this program, the clinicians will be able to:

1. Identify factors that contribute to the development of ADHD in adults.
2. Diagnose adults with ADHD based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
3. Devise a treatment plan for ADHD in adults using pharmacologic and nonpharmacologic strategies.
4. Recognize the differences in presentation of ADHD in adults and children.
5. Treat psychiatric comorbidities that mimic ADHD in adults, eg, anxiety, depression.

Summary

Attention-deficit/hyperactivity disorder (ADHD): worldwide prevalence of ADHD is 6% to 9% in children ages 8 to 15 yr and 4% to 5% in adults; a chronic disorder (≈50% of children carry diagnosis into adulthood); found to be associated with high degrees of psychiatric comorbidities (eg, anxiety, depression); reverse is also true, with high rates of ADHD in patients receiving treatment for such disorders, predominantly substance use disorder (SUD); can lead to impairments in multiple domains; not a cosmetic disorder; persons with ADHD have different feelings from others, cannot sit through meetings, and have short attention spans; adult ADHD is a relatively new diagnosis; though first described in the 1700s, ADHD was not systematically studied until the 1990s; Dr. Paul Wender and Dr. Fred Reimer started “mapping out” adults with ADHD and describing different treatments; until the 1990s, it was believed that one grows out of ADHD between the ages of 12 and 18 yr; many adults with ADHD have not received treatment because they were never diagnosed

Factors causing ADHD: ADHD applies biologically in adults and children; there is a genetic component; compared with other heritable psychiatric disorders (eg, autism), ADHD is nearly the same (0.75); not all ADHD is inherited; in some cases, ADHD is preventable; in addition to genetic factors, mothers with ADHD who smoke increase risk for ADHD in their children; studies performed on rats show that exposure to nicotine during pregnancy leads to ADHD-like symptoms in offspring (child) as well as the next generation of offspring (grandchild)

Role of catecholaminergic system (CAS) in ADHD: at synapse level, ADHD is defined as underproduction or undertransmission of catecholamines, in particular dopamine and norepinephrine; there are insufficient amounts of these neurotransmitters postsynaptically; most drugs act by making more of dopamine or norepinephrine available in the intrasynaptic cleft; glutamate and γ-aminobutyric acid (GABA) also are involved; in general, CAS seems to be the driver of ADHD; in brain imaging (specifically functional magnetic resonance imaging) studies, patients are given a task (Stroop test), eg, what color is painted on a board with the written name of a different color (one tends to say the color rather than reading the word, as it takes extra executive operations); when performed in a person who does not have ADHD, this causes the activation of the anterior cingulate cortex; however, in a person with ADHD, it reaches an entirely different part of the brain; ADHD medications essentially convert the functionality of the brain to direct it back to the anterior cingulate cortex where these cognitive tasks are supposed to be completed

Diagnosing ADHD: compared with individuals without ADHD, those with ADHD have less capacity to complete high school and college, lower income, higher rate of poverty, more substance use and difficulties in employment, higher rates of separation and divorce, and more criminality; good treatment helps to reverse most of these issues; criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), is adequate for diagnosing ADHD; no neuropsychological testing or special scales are required; this systematic checklist for ADHD helps in drawing a good conclusion about the individual; most adults with ADHD meet criteria in the attentive realm, eg, failing to pay attention to details, problems in sustaining attention, not listening, not following through on instructions, difficulty with organization, avoiding tasks, losing things, and being easily distracted and forgetful; ≥5 of these 9 criteria and a track from childhood are required for diagnosis; these features are often present and associated with impairment; 98% of adults with ADHD have core cognitive symptoms as well as problems with hyperactivity and impulsivity; symptoms may or may not be present during the conducted sessions; some individuals blurt out answers, interrupting or intruding during the canter of the discussion; 5 of 9 symptoms of inattention or hyperactivity/impulsivity are needed

Differentiating and screening for ADHD: ADHD usually starts before age 12 yr and persists; differential diagnoses include mimic disorders, anxiety, current active depression, and substance disorders; interference with daily living should be present; consider symptoms that affect >2 settings (eg, work, interpersonal, school); most adults have predominantly inattentive or combined subtype (inattentive/hyperactive/impulsive); various rating scales (many derived from DSM-5) are available

ADHD over time: ADHD looks different in adults than in children; hyperactivity and impulsivity reduce with aging; core cognitive issues (inattention, distractibility, forgetfulness) and some issues in executive functioning persist; adults have less hyperactive symptoms and more attentional symptoms

Assessment: common symptoms in adult ADHD include being easily distracted by internal thoughts or surrounding voices, and difficulty in sustaining attention, staying focused, and following instructions; among hyperactive symptoms, the most common is blurting out answers in conversations or meetings; when considering ADHD diagnosis, it is important to ask whether the patient is, in some manner, compensating for symptoms, eg, a person who blurts out answers may sit on their hands to counter the urge to raise a hand for answering, and in doing so, the patient struggles with symptoms but is not manifesting them; make specific inquiries about compensatory strategies; ask about life history; adults often underreport childhood symptoms; mental status examination is recommended to identify other psychiatric issues; rating scales can be helpful for identifying symptoms; medical history should be reviewed and include cardiac and neurologic pathology, blood pressure, and pulse (become critical when considering treatment); if the medical history is unremarkable, laboratory and neurologic testing are unnecessary; look for psychosocial comorbidities and cognitive issues

Treatment plan: may depend on the patient’s current life situation, eg, in school or work; occupational considerations and special assessments may be necessary; patients may require some kind of accommodation at work; individual support and support groups can be helpful; some people are reluctant to take medications; cognitive behavioral therapy (CBT) has been demonstrated in multiple trials to be effective for ADHD in adults, particularly for mild to moderate symptoms; in the United States, medications are considered first-line treatment for adults with ADHD; studies have shown that telehealth can be helpful as individuals, eg, do not need to take time off work; CBT has been shown to be most effective in individuals who are already taking medication for ADHD and have residual symptoms; addition of CBT in medicated individuals with residual issues improves outcomes (consider effect size, eg, that of a multisite national study was 0.5 to 0.6 [very healthy effect size]); CBT is recommended in individuals with self-repetitive or self-sabotaging behavior, certain behavioral patterns, or residual symptoms, especially in executive functions

Medication: many stimulant and noradrenergic agents have been approved by the US Food and Drug Administration (FDA); many medications that have not been approved by the US FDA are also found to be effective; methylphenidate and amphetamine class agents are mainstay for ADHD treatment in adults; methylphenidate (MPH; eg, Concerta, Metadate, Ritalin) — Ritalin (short-acting) lasts ≈4 hr, Metadate (intermediate-acting) requires ≈8 hr preparation, and Concerta (extended release [ER]) lasts ≈12 hr; the speaker recommends familiarizing with 3 agents (one of each category) from the 14 listed preparations; amphetamine (AMP) — has 9 different preparations; Dexedrine is short-acting (lasts for 3-5 hr); Dexedrine Spansule and Adderall (a mix of amphetamine salts) are intermediate-acting; Adderall XR is an ER form (lasts 12 hr); Vyvanse (lisdexamfetamine) lasts longer

Newer agents: combined serdexmethylphenidate and dextromethylphenidate (Azstarys; 12-14 hr preparation) has lower abuse liability as it is a prodrug; 16-hr ER forms, eg, extended mix of AMP (Mydayis) or MPH (Adhnasia), are available; the choice of stimulant (MPH or AMP) for initial treatment is at the clinician’s discretion; in the speaker’s clinic, ≈40% of adults who started one medication ultimately switched to a different drug; switch rate is higher with MPH taken first than with AMP first, but preference is given to MPH as it has fewer side effects

Common side effects of stimulants: insomnia — it is important to note whether it is baseline or worsened by the stimulant; encourage the patient to follow good sleep hygiene; melatonin, mirtazapine, and tricyclic antidepressants (imipramine, amitriptyline) have efficacy for ADHD in addition to helping with sleep issues and work with stimulants to improve outcomes; dry mouth — one of the most common side effects; frequent cleanings, keeping the mouth wet by drinking water, and avoiding sugar candies is recommended; if severe, consider involving the patient’s dentist to formulate a mouthwash; pilocarpine solution stimulates saliva; grinding — a night guard can be used to protect damage to the teeth and the temporomandibular joint; consider β-blockers; mood and irritability — less common; ask whether it is occurring with the medication, in which case, consider changing the preparation or treatment and/or address mood with additional treatment

Other newer medications for ADHD: viloxazine (Qelbree) — a newer drug that has been approved by the US FDA for ADHD in children and adolescents; has an application in adults; studies investigating use of ≤600 mg/day have demonstrated efficacy, with significant and rapid improvement in severity; caveat is that over-the-counter items, eg, caffeine, can accumulate and caution must be exercised with drugs like duloxetine; α-agonists (guanfacine [Intuniv, Tenex]) — ≤7 mg/day of ER form shows ≈50% response, with improved inattention and hyperactivity/impulsivity; no serious adverse effects have been noted, however, 1 in 5 patients discontinue because of blood pressure dropping; manifesting syncopal or presyncopal symptoms indicate discontinuation

Medications not approved by the US FDA for ADHD: bupropion (eg, Aplenzin, Wellbutrin, Zyban) — 5 controlled trials have been conducted in adults, with response rate of 50% to 60%; effect size of 0.5 (not as effective as stimulants); helpful with moodiness in patients with ADHD or those with smoking issues; can be used with stimulant medications; tricyclic antidepressants — desipramine is largely used; in studies, most common dose is 150 mg/day; have high effect size of 0.7 to 0.8; effective in adults who have depression or anxiety

Monitoring treatment: typically includes serum level and electrocardiography after titrating up to an effective dose for 6 to 8 wk; further testing is infrequent at the clinician’s discretion; overdose is the greatest concern; tricyclic antidepressants are used less frequently because of safety margins; prolonged treatment from adolescence to adulthood and older age does not seem to cause neurotoxicity; abusive stimulants, eg, methamphetamine may cause neurotoxicity when misused; rates of depression and bipolar disorder are lower in treated vs untreated patients; this same trend is seen in suicidality; large-scale study by Quinn et al (2017) — followed nearly 3 million individuals (≤42 yr of age) with ADHD; found that, during ADHD treatment, there was a 30% reduced risk of developing SUD compared with the same individual when untreated; compared with untreated group, the overall treated group had 50% reduction in likelihood of new-onset SUD; driving — studies have shown reductions in aberrant driving and motor vehicle accidents in treated vs untreated groups

Adverse outcomes in ADHD: there is concern about the impact of these drugs on cardiovascular (CV) and cerebrovascular function; Habel et al (2011) found no increase in the risk for adverse CV or cerebrovascular stroke claims in treated vs untreated individuals; the speaker’s group has not found significant changes in blood pressure in patients with treated hypertension after initiation of ADHD treatment; assess hypertension, palpitations, chest pain, rhythm disturbances, and seizures and address any identified issues before initiating ADHD treatment

Resolving cognitive executive functions: problems, eg, time management and organization, can be addressed by online ADHD coaches; various organizational trainings are available online; noradrenergic agents, eg, atomoxetine (α-agonist) can be used alone or with a stimulant; experimental use of memantine (Alzheimer medication) seems helpful

Anxiety: one of the most common mimics and comorbidities of ADHD; can be treated with atomoxetine, which has been shown to be helpful in children and adults; study by Adler et al (2009) — showed improvement in ADHD and significant improvement in anxiety; effect was similar to that of selective serotonin reuptake inhibitors (SSRIs) or serotonic and norepinephrine reuptake inhibitors (SNRIs); stimulants — some data show that stimulants reduce anxiety, particularly if the anxiety manifests as avoidance or phobias; however, panic attacks and generalized anxiety can worsen; SSRIs — not effective for ADHD; however, in cases with comorbidity of depression or anxiety, there is a trend toward improvement in mood and anxiety with paroxetine alone or combined with AMP

Bipolar disorder: mood must be stabilized first with antipsychotic agents and/or mood stabilizers; if the patient is euthymic, a stimulant can be added; good data supports successful treatment of ADHD with stimulants in patients with stabilized mood disorders

Substance use disorders: consider treatment of ADHD in context of SUDs; patients with less severe substance use can be treated for ADHD; patients who use daily or have impairment or functional issues require focus on the SUD; ADHD treatment may or may not need to be withheld while addressing SUD; CBT should be done first, with focus on the SUD, followed by treatment of ADHD with nonstimulant medications because of abuse liability; if stimulants are to be used, ER stimulants (ERS) should be used; trials with ERS in patients with SUD have shown low misuse and good outcomes; higher doses may be required, especially in an addiction setting; do not delay too long in treating ADHD; a paper by the speaker’s group showed that ADHD patients receiving treatment for SUD tripled the retention in treatment when ADHD was treated, particularly within the first 90 days, and with use of stimulant medications; stimulants can be misused, especially in young adults; studies have shown a 10% to 20% prevalence of misuse, largely in college students; the primary source for college students seems to be a reservoir of stimulants from overprescription; limiting prescription to an appropriate monthly supply can reduce the available reservoir; primary motivation for misuse is concentration and alertness; misuse and diversion primarily involves immediate-release preparations; the speaker prefers ERS for this population

Readings

Adler LA, Liebowitz M, Kronenberger W, et al. Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder and comorbid social anxiety disorder. Depress Anxiety. 2009;26(3):212-221. doi:10.1002/da.20549; Biederman J. Attention-deficit/hyperactivity disorder: a life-span perspective. J Clin Psychiatry. 1998; 59:4-16; Biederman J, Monuteaux MC, Doyle AE, et al. Impact of executive function deficits and attention-deficit/hyperactivity disorder (ADHD) on academic outcomes in children. J Consult Clin Psychol. 2004; 72:757; Guha M. Diagnostic and statistical manual of mental disorders: DSM-5. Reference Reviews. 2014; Habel LA, Cooper WO, Sox CM, et al. ADHD medications and risk of serious cardiovascular events in young and middle-aged adults. JAMA. 2011; 306:2673-2683; Quinn PD, Chang Z, Hur K, et al. ADHD medication and substance-related problems. Am J Psychiatry. 2017; 174:877-885; Safren SA, Otto MW, Sprich S, et al. Cognitive-behavioral therapy for ADHD in medication-treated adults with continued symptoms. Behav Res Ther. 2005; 43:831-842; Sibley MH. Empirically-informed guidelines for first-time adult ADHD diagnosis. J Clin Exp Neuropsychol. 2021;43(4):340-351. doi:10.1080/13803395.2021.1923665; Solanto MV, Marks DJ, Mitchell KJ, et al. Development of a new psychosocial treatment for adult ADHD. J Atten Disord. 2008 May; 11(6):728-36; Spencer TJ, Biederman J, E. Ciccone P, et al. PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short-and long-acting oral methylphenidate. Am J Psychiatry. 2006; 163:387-395; Stevens JR, Wilens TE, Stern TA. Using stimulants for attention-deficit/hyperactivity disorder: clinical approaches and challenges. Prim Care Companion CNS Disord. 2013 Mar 28;15(2):PCC.12f01472. doi: 10.4088/PCC.12f01472; Wilens TE, Spencer TJ. Understanding attention-deficit/hyperactivity disorder from childhood to adulthood. Postgrad Med. 2010; 122:97-109; Wilens TE, Vitulano M, Upadhyaya H, et al. Cigarette smoking associated with attention deficit hyperactivity disorder. J Pediatr. 2008 Sep 1; 153(3):414-419; Wilens TE. Mechanism of action of agents used in attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2006; 67:32; Wilens TE. Pharmacotherapy of ADHD in adults. CNS Spectrums. 2008; 13:11-13; Zulauf CA, Sprich SE, Safren SA, et al. The complicated relationship between attention deficit/hyperactivity disorder and substance use disorders. Curr Psychiatry Rep. 2014 Mar;16(3):436. doi: 10.1007/s11920-013-0436-6.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Wilens has financial relationships with Arbor Pharmaceuticals (now a subsidiary of Azurity Pharmaceuticals), Ironshore Pharmaceuticals and Vallon Pharmaceuticals; and is a consultant, and the fees charged went to Massachusetts General Hospital; no direct financial benefit has been availed by Dr. Wilens; and he has shared Intellectual Property (IP) and is a consultant with Gravin Foundation, Bay Cove Human Services, US National Football League (ERM Association), US Minor/Major League Baseball for Clinical Consulting and with White Rhino/3D. Members of the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Wilens was recorded exclusively for Audio Digest. Audio Digest thanks Dr. Wilens for his cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.75 CE contact hours.

Lecture ID:

PS511301

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.