adhd in adults -...

ADHD IN ADULTS

Objectives

•Apply evidence-based diagnostic techniques to the identification of adult ADHD

•Differentiate the spectrum of medications available for ADHD based on pharmacokinetic and clinical profiles

•Customize ADHD medication selection to the daily functional needs of the patients

•Integrate evidence-based nonpharmacological strategies into the overall treatment plan for patients with ADHD

PCPs and Psychiatric Presentations

• 65-80% of patients with mental health problems see the primary care physician for the first visit

• 45% remaining in treatment with the PCP

Institute of Medicine, 2003.

Undertreatment of Adult ADHD

• The 2012 or 2013 National Health and Wellness Survey (NHWS), U.S. study

• Of a total of 22,397 U.S. adults who participated in the survey, 465 self-reported a diagnosis of ADHD. ADHD-like symptoms were screened using the Adult Self-Report Scale version 1.1 (ASS-v1.1)

• In patients who self-reported an ADHD diagnosis, 62.6% reported not currently using a prescription medication to treat it

Adler LA, Faraone SV, Sarocco P, Atkins N, Khachatryan A. Symptom burden among self-reported ADHD in adults in the United States. Poster presented at: US Psych Congress: September 16-19, 2017: New Orleans, Louisiana.

Prevalence Rates of Psychiatric Disorders in Adults

Kessler RC et al. JAMA. 2003 Jan 18;278(23):3095-105;Kessler RC et al. Am J Psychiatry. 2006 Apr;63(4):415-24;Merikangas KR et al. Arch Gen Psychiatry. 2007 May;64(5):543-52.

Chart1

Major Depression

Adult ADHD

GAD

Bipolar Disorder

Schizophrenia

0.066

0.044

0.03

0.02

0.01

Sheet1

Major DepressionAdult ADHDGADBipolar DisorderSchizophrenia

6.6%4.4%3.0%2.0%1.0%

ADHD in Adults Age >50

• Adult ADHD PrevalenceLongitudinal Aging Study Amsterdam (LASA)

• Prevalence of syndromic ADHD in adults: 2.8%

• Prevalence of symptomatic ADHD in adults: 4.2%

• Men and women reported similar levels of symptoms

Michielsen M et al. Br J Psychiatry 2012;201:298-305.

Identification and Assessment of Late-Life ADHD in U.S. Memory Clinics

•ONLY 1 of 5 clinics reported screening regularly for ADHD (62 of 165 responded to survey)

•1/2 reported seeing ADHD patients

–60% reported contact with previously diagnosed ADHD patients

•ADHD symptomatology may not have been considered as pre-morbid baseline cognitive functioning

Fischer BL et al. J Att Dis 2012;16(4):333-338.

Canadian Guidelines on ADHD in Older Adults

• Recognizes ADHD in older adults

• Highlights importance in evaluation of cognitive complaints in older adults

• Medication and psychotherapies as treatments

• Consideration of medical illnesses/drug interactions when considering ADHD medication

• Consider two co-existing disorders (ADHD/MCI)

Canadian ADHD Resource Alliance (CADDRA); Canadian ADHD Practice Guidelines, 4th Ed. 2018; (www.caddra.ca) DW Goodman, MD contributor.

http://www.caddra.ca/

Diagnostic Issues

Diagnostic Difference in DSM-IV and DSM 5 for Adult ADHD

DSM-IV DSM 5Max child age threshold for symptoms

< 7

Age of Diagnosis

SYMPTOMS

IMPAIRMENTS

AGE 7 12 18 25 32 55

Child Diagnosis

Adult Diagnosis

IMPAIRMENTS

Increasing demands of Family, Work, Social

Intelligence Compensatory Skills Environmental Structure

Adult Diagnosis

ADHD

Emotionaldysregulation

Executive Dysfunction

Impairment Sources

Performance Impairment

Social Impairment

Adult ADHD and Comorbidities

National Comorbidity Survey Replication: Adult ADHD in Other Psychiatric Disorders

Major Depression Chronic Dysthymia Bipolar Disorder

ADHD 9.4%

ADHD 22.6% ADHD 21.2%

Kessler RC et al. Am J Psychiatry. 2006;163:716-723.

National Comorbidity Survey Replication: Adult ADHD in Other Psychiatric Disorders

Anxiety Disorder Substance Abuse ???

ADHD 8.6%

ADHD 10.8%

ADHD ???%

Kessler RC et al. Am J Psychiatry. 2006;163:716-723.

Mood Disorders Schizophrenia

Hallucinations/Delusions

Diagnostic History

David W. Goodman, MD

ADHD Bipolar

Emotion Dysregulation

Executive Dysfunction

Symptomatic Overlap: Not Distinguishing Features

David W. Goodman, MD

DSM-5 Symptom Overlap: ADHD and Bipolar Disorder

Bipolar ADHD

Symptoms

Hypomanic/manic symptoms of increased talkativeness, racing

thoughts, distractibility, psychomotor agitation, increase

risky behavior

Talks too much in social situations,

difficulty maintaining attention and

distractible, fidgety and restless, impulsivity

Impairments Social/occupational distress or impairment be present

Not Diagnostic Criteria Impulsive risk-taking behavior and sleep disturbance

Emotion Dysregulation in ADHD

• Children 25-45% (7 studies)• Adults 34-70% (5 studies)

Shaw P et al. Emotional Dysregulation in Attention Deficit Hyperactivity Disorder. Am J Psych. 2014;171:276-293; Barkley RA, Fischer M: The unique contribution of emotional impulsiveness to impairment in major life activities in hyperactive children as adults. J Am Acad Child Adolesc Psychiatry 2010; 49:503–513.

Emotion Dysregulation

Persistent ADHD n=55 42-72%

Remitted ADHD n=80 23-45%Persisters have higher rates of emotion

dysregulation compared to remitters

Emotion Regulation:ADHD vs. Bipolar Adults

• A total of 150 adults ADHD, 335 adults BD subjects, and 48 controls

• Assessed using the Affective Lability Scale (ALS) (emotion lability) and the Affect Intensity Measure (AIM) (emotion responsiveness)

• Retrospective study; Swiss study• ASRS, WURS, DIVA 2.0, DIGS

Richard-Lepouriel H, et al. Similarities between emotional dysregulation in adults suffering from ADHD and bipolar patients. J Affect Dis. 2016;198:230-236.

Conclusions

• Using two self-reports, adult ADHD patients displayed emotional dysregulation with a higher mood lability and responsiveness similar to bipolar patients in comparison to controls.

• ADHD subjects essentially differ from bipolar subjects on the perceived emotional intensity, but not on emotional instability.

• Severity of ADHD was strongly correlated to AIM and ALS scores.

Richard-Lepouriel H, et al. Similarities between emotional dysregulation in adults suffering from ADHD and bipolar patients. J Affect Dis. 2016;198:230-236.

Case Presentation: Diagnostic Prioritization for Pharmacotherapy

Alcohol and substance abuseMood disorders Bipolar and MDD

Anxiety disorders Obsessive-compulsive disorder,

generalized anxiety disorder, panicADHD

Goodman D. Treatment and assessment of ADHD in adults. In: Biederman J, ed. ADHD Across the Life Span: From Research to Clinical Practice—An Evidence-Based Understanding. Hasbrouck Heights, NJ: Veritas Institute for Medical Education, Inc.2005.

Order of treatment also considers the severity of the concurrent disorders.

Research Support for Diagnostic Prioritization

“In our clinical experience, consistently with other authors, patients with ADHD-BD should be treated for BD first. Based on the current level of information, we do not recommend treatment of comorbid ADHD-BD with ADHD medications in the absence of mood stabilizers.”

Giulio Perugi MD & Giulia Vannucchi MD. The use of stimulants and atomoxetine in adults with comorbid ADHD and bipolar disorder. Expert Opinion on Pharmacotherapy. 2015.16:14;2193-2204; Asherson P, Young AH, Eich-Hochli D, et al. Differential diagnosis, comorbidity, and treatment of attention-deficit/ hyperactivity disorder in relation to bipolar disorder or borderline personality disorder in adults. Curr Med Res Opin 2014;30(8):1657-72.

Bipolar Disorder: Risk of Mania With Methylphenidate

• Swedish national registries• 2307 bipolar adults, 2006-2014• MPH with and without mood stabilizers• Mania defined: hospitalization or new

dispensation of stabilizing medication• 0-3 months and 3-6 months after medication start

following non-treated periods

Bipolar Disorder: Risk of Mania With Methylphenidate

HAZARD RATIO0-3 months 3-6 months

MPH without mood stabilizer

6.7 (95%CI-2.0-22.4)

similar

MPH with mood stabilizer

0.6 (95%CI=0.4-0.9)

similar

Viktorin A et al. The Risk of Treatment-Emergent Mania with Methylphenidate in Bipolar Disorder. Am J Psych 2016.

Diagnostic Overlap

Intelligence

LearningDisabilitiesADHD

ExecutiveFunction

NeuropsychologicalDiagnoses

BehavioralDiagnosis

Executive Function

• Response inhibition• Working memory• Set shifting• Interference control

Seidman LJ. Neuropsychological functioning in people with ADHD across the lifespan. Clinical Psychology Review 2006. 26;466-485.

30-50% of ADHD patients have executive dysfunction vs. 5-10% in controls

EF Associated With Other Disorders

Executive Disorder

ADHD30-50% with EF

BipolarDisorder

Autism

Schizophrenia

LearningDisorders Chronic SUD

MajorDepression GAD

NeurologicDisorders

TBI, MCI, CVA, CNS tumors,Degenerative

GeneticDisorder

Klinefelter’s(47, XXY)

GeneralPopulation

5-10% with EF

Can EF neuropsychological tests detect ADHD?

These studies have examined male and female youth, as well as adults, and found that most measures of EFs have good positive predictive power for ADHD (characterized by adequate sensitivity), but poor negative predictive power (poor specificity).

That is, abnormal scores on measures of EFs are generally predictive of the diagnosis; however, normal scores cannot rule out the diagnosis.

Siedman L. Clinical Psychology Review 2006;36:207-226.

“Understanding the Cognitive Effects of Stimulants” Swanson et al, 2011

In well-controlled studies using batteries, stimulant-related cognitive enhancements were more prominent on tasks without an executive function component (complex reaction time, spatial recognition memory reaction time, and delayed matching-to-sample) than on tasks with an executive function component (inhibition, working memory, strategy formation, planning, and set-shifting).

Swanson J et al. Understanding the Effects of Stimulant Medications on Cognition Individuals with Attention-Defict Hyperactivity Disorder: A Decade of Progress. Neuropsychopharmacology 2011. 36:207-226.

Treatment Options and Medication

Treatment Options

•Diagnoses (what’s there, what’s not)•Education (what this is, what it’s not)•Environmental changes (academic, occupational, social, family)•Psychopharm/Psychotherapies

• Behavior, social, individual, family, couples• Support associations (www.CHADD.org)

Methylphenidate PreparationsGeneric methylphenidate 2-3 hrs tablet

Methylin liquid 2-3 hrs liquid

MPH SR LA

4 hrs wax matrix8 hrs beaded

OROS MPH 12 hrs OROS

MPH ER 6-8 hrs beaded

MPH CD 8 hrs beaded

DexMPHXL

3 hrs tablet10 hrs beaded

MPH ER liquid 12 liquid

MPH-ODT ER 12 dissolvable tab

MPH transdermal patch 12 hrs patch

Amphetamine PreparationsPreparation Duration of Action

Liquadd 2-3 hrs liquid

Dextrostat 2-3 hrs tabletDextroamphetamine

spanules4 hrs tablet6 hrs beaded

Amphetamine (racemic) 6 hrs tablet

Mixed AMPH saltsXR

6 hrs tabletUp to 12 hrs beaded

d-Amphetamine-ODT ER 12 Dissolvable tab

d-Amphetamine ER 12 liquid

Lisdexamfetamine Up to 14 hrs prodrug

Non-Stimulants

• Atomoxetine approved for children/adolescents

• Guanfacine ER• Clonidine ER Off-label:• Bupropion (positive controlled adult trials)• Desipramine (positive adult trial)• Modafinil (child study positive, adult study negative)

FDA-Approved Medications for Adults With ADHD

Medication Child dosing

Adolescent dosing

Adult dosing

U.S. trials (adult)

Atomoxetine 0.5 mg/kg (

CYP450 Inhibitory Effects of ADHD Medications

00000Desipramine

?+++???Bupropion00*000Atomoxetine00000Methylphenidate00000Amphetamine

3A42D62C192C91A2Medication

Cytochrome P450 Isoenzymes

Goodman D. (2006), In: ADHD Across the Life Span: From Research to Clinical Practice—An Evidence-Based Understanding; Biederman J, ed. Hasbrouck Heights, NJ: Veritas Institute for Medical Education, Inc.; Devane L et al. (2003), Poster presented at the 156th Annual Meeting of the APA; San Francisco: May 17-22.

MPH-Guanfacine XR in Adults

Roesch B et al. Drugs R D 2013;13:53-61.

35 healthy adult

MPH-Guanfacine XR in Adults

35 healthy adult

Roesch B et al. Drugs R D 2013;13:53-61.

Side Effects With Stimulant Medication• Insomnia• GI upset• Decreased appetite• Weight loss• Headaches• Dry mouth• Constipation• Hand tremors• Jittery

• Research on individual stimulants has generally shown no dose relationship with side effects in group data1, 2

• Some research has shown side effects may be more likely in stimulant naïve patients3

1Weisler RH et al. (2006), CNS Spectr 11(8):625-639; 2Adler L et al. (2005), Presented at the 158th Meeting of the American Psychiatric Association, May 21-25; 3Goodman DW et al. (2005), CNS Spectr 10(Suppl 20):26-34.

Safety Concerns

Medical Illness Considerations

• Hypertension• Hypo- or Hyperthyroidism• Diabetes Mellitus• Cardiac: Post MI, post-stent placement,

arrthymias, electrical/structural abnormalities• Seizure disorder• Substance Use: caffeine, alcohol, illicit drugs• Pregnancy

Congenital Abnormalities

• In the U.S., 3% of infants are born with a major birth defect

• Risk of congenital heart defects in general population: 8.2 per 1000 births

Byatt N et al. Acta Psychiatr Scand 2013;127:94-114.

Cardiovascular Risk: Stimulants in Pregnancy

• Cohort study of the Medicaid-insured population in the United States nested in the 2000-2013 U.S. Medicaid Analytic eXtract

• Nordic Health Registries, 2003-2013 (Denmark, Finland, Iceland, Norway, and Sweden)

• Relative risks were estimated accounting for underlying psychiatric disorders and other potential confounders

Huybrechts et al. Association between methylphenidate and amphetamine use in pregnancy and risk of congenital malformations, a cohort study from the International pregnancy safety study consortium, JAMA Psychiatry, JAN2017.


Malformations

Per 1

000

infa

nts


In the US data, of the 1,813,894 pregnancies evaluated

Chart1

CongenitalCongenitalCongenital

CardiacCardiacCardiac

Controls

Methylphenidate

Amphetamine

35

45.9

45.4

12.7

18.8

15.4

Sheet1

ControlsMethylphenidateAmphetamine

Congenital3545.945.4

Cardiac12.718.815.4

To resize chart data range, drag lower right corner of range.



methylphenidate using the Nordic data including 2 560069 pregnancies

Chart1



Methulphenidate

Amphetamines

Nordic Data

1.11

1.05

1.28

1.28

0.96

1.28

Sheet1

MethulphenidateAmphetaminesNordic Data

Congenital1.111.051.28

Cardiac1.280.961.28

Category 33.51.83

Category 44.52.85


Chart1



Methulphenidate

Amphetamines

Nordic Data

1.11

1.05

1.28

1.28

0.96

1.28

Sheet1

MethulphenidateAmphetaminesNordic Data

Congenital1.111.051.28

Cardiac1.280.961.28

Category 33.51.83

Category 44.52.85


Stimulant Pregnancy Risk

• Pregnancies exposed to amphetamine-dextroamphetamine (n=3331), methylphenidate (n=1515) monotherapy in early pregnancy were compared with 1,461,493 unexposed pregnancies. Among unexposed women, the risks of the outcomes were 3.7% for preeclampsia, 1.4% for placental abruption, 2.9% for small-for-gestational age, and 11.2% for preterm birth

• The adjusted risk ratio for stimulant use was 1.29 for preeclampsia (95% CI 1.11-1.49), 1.13 for placental abruption (0.88-1.44), 0.91 for small-for-gestational age (0.77-1.07), and 1.06 for preterm birth (0.97-1.16)

• Compared with discontinuation (n=3,527), the adjusted risk ratio for continuation of stimulant use in the latter half of pregnancy (n=1,319) was 1.26 for preeclampsia (0.94-1.67), 1.08 for placental abruption (0.67-1.74), 1.37 for small-for-gestational age (0.97-1.93), and 1.30 for preterm birth (1.10-1.55)

Cohen JM et al. Placental complications associated with psychostimulant use in pregnancy. Obstet Gynecol. 2017 Dec;130(6):1192-1201.

Pregnancy and Stimulants

•Category C-Amphetamines, methylphenidates, atomoxetine-Animal reproduction studies have shown an adverse effect on the fetus. There are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

Available at www.fda.gov Accessed January 15, 2008.

http://www.fda.gov/

Breastfeeding and Amphetamimes

•Amphetamine

•Detectable in breast milk

•In infants’ urine

•Methylphenidate

•Detectable in breast milk

•American Academy of Pediatrics considers amphetamines and methylphenidate a contraindication for breastfeeding

Ilett KF et al. (2007), Br J Clin Pharmacol 63(3):371-375; Steiner E et al. (1984), Eur J Clin Pharmacol 27:123-124; Spigset O, Brede WR et al. (2007), Am J Psychiatry 164(2):348; Hackett LP, Kristensen JH et al. Ann Pharmacother 2006;40(10):1890-1891.

Psychotherapies

Psychotherapies for ADHD

• Education

• Patients and family members

• Books and websites

• Cognitive behavior therapy

• Structure routines

• Audio and visual cues

• Consistent consequences for behavior

• Individual

• Self-esteem issues

• Social skills and relationship issues

• Academic and occupational accommodations

52

When to Refer

• Presenting with symptoms of a major mental illness, serious mood disorder, substance dependence, or other complex comorbid psychiatric symptoms that are beyond your level of clinical competence and/or comfort level

• Confused about the patient’s presentation, unsure about ADHD, and uncomfortable about the idea of prescribing ADHD medication for this person

• Suspect drug-seeking behavior

• Patient not responding to medications or expresses sensitivity to drug side effects

• Treatment seems to require multiple psychiatric medications

Summary

ADHD is highly prevalent in both children and adults -screen regardless of age Diagnostic accuracy is enhanced by considering:

• Presenting symptoms• Age of onset• Longitudinal course: chronic, pervasive, impairing• Family psychiatric history Use symptom checklists for baseline target symptoms and change with treatment Look for psychiatric comorbidities and prioritize accordingly Education, behavioral changes, and cognitive therapies are effective

ADHD in AdultsObjectivesPCPs and Psychiatric PresentationsUndertreatment of Adult ADHDPrevalence Rates of Psychiatric Disorders in AdultsADHD in Adults Age >50 �Identification and Assessment of Late-Life ADHD in U.S. Memory ClinicsCanadian Guidelines on ADHD in Older AdultsDiagnostic IssuesDiagnostic Difference in DSM-IV and DSM 5 for Adult ADHDAge of DiagnosisImpairment SourcesAdult ADHD and ComorbiditiesNational Comorbidity Survey Replication: Adult ADHD in Other Psychiatric DisordersNational Comorbidity Survey Replication: Adult ADHD in Other Psychiatric DisordersDiagnostic HistorySymptomatic Overlap: �Not Distinguishing FeaturesDSM-5 Symptom Overlap: ADHD and Bipolar DisorderEmotion Dysregulation �in ADHDEmotion Regulation:�ADHD vs. Bipolar AdultsConclusionsCase Presentation: Diagnostic Prioritization for PharmacotherapyResearch Support for Diagnostic PrioritizationBipolar Disorder: Risk of Mania With Methylphenidate Bipolar Disorder: Risk of Mania With Methylphenidate Diagnostic OverlapExecutive FunctionEF Associated With Other DisordersCan EF neuropsychological tests detect ADHD?“Understanding the Cognitive Effects of Stimulants” Swanson et al, 2011Treatment Options and MedicationTreatment OptionsMethylphenidate PreparationsAmphetamine PreparationsNon-StimulantsFDA-Approved Medications for Adults With ADHD CYP450 Inhibitory Effects of �ADHD MedicationsMPH-Guanfacine XR in AdultsMPH-Guanfacine XR in AdultsSide Effects With Stimulant MedicationSafety ConcernsMedical Illness ConsiderationsCongenital AbnormalitiesCardiovascular Risk: �Stimulants in PregnancyCardiovascular Risk: �Stimulants in PregnancyCardiovascular Risk: �Stimulants in PregnancyStimulant Pregnancy RiskPregnancy and StimulantsBreastfeeding and AmphetamimesPsychotherapiesPsychotherapies for ADHDWhen to Refer Summary

adhd in adults -...

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