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.
Cardiovascular Risk: Stimulants in Pregnancy
Malformations
Per 1
000
infa
nts
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.
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.
Cardiovascular Risk: Stimulants in Pregnancy
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.
methylphenidate using the Nordic data including 2 560069 pregnancies
Chart1
CongenitalCongenitalCongenital
CardiacCardiacCardiac
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
To resize chart data range, drag lower right corner of range.
Chart1
CongenitalCongenitalCongenital
CardiacCardiacCardiac
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
To resize chart data range, drag lower right corner of range.
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