ࡱ> E@ bjbj &{Q^^^^^^^r22223rn=33333444 < < < < < < <$`?RA\/<^44444/<^^33(=!6!6!64^3^3 <!64 <!6&!6G6:;,^^;33 @^Tp24; <>=0n=; B]5B;rr^^^^;B^; 44!644444/</<rr,2]5rr2TITLE: Attention Deficit Hyperactivity DisorderIts Treatment and Relationship to Substance Use Disorders < Slide 1> Larry Gray, MD AMSP Introduction Importance: explosion in stimulant prescriptions (1) < Slide 2> Annual rates of stimulant production rose 740% from 1991 and 2000 Amphetamine (eg. Adderall) production has risen 25-fold USA consumed 80% of methylphenidate (Ritalin) in 1999 Confusion abounds when the understanding of ADHD is based on rates of specific treatments Lecture aims regarding Attention Deficit Hyperactivity Disorder < Slide 3> Epidemiology + course Diagnosis Etiology Treatment Relationship to substance use disorders (SUD). Key points < Slide 4> Very common in the community (= 10% of boys) Central problem = poor attention and impulsivity Pharmacotherapy improves symptoms ADHD treatment may protect from later SUD ADHD Nomenclature < Slide 5> Moral deficit Early 1900s struggled with disability Focus on voluntary behavioral control Term cast aside as stigmatizing Minimal brain disorder 1930s to 1960s Term adopted from autopsy studies and emerging X-ray technology Subtle anatomic brain differences linked to disruptive behavior Attention Deficit Disorder (ADD) / Attention Deficit Hyperactivity Disorder (ADHD) (Diagnostic and Statistical Manual or DSM) 1970s to present Core symptoms of inattention and impulsivity Converging evidence from genetics and neuroanatomy supports ADHD: Epidemiology and Natural History < Slide 6> ADHD is very common (2): 6 - 9 % of school-aged children (boys and girls) Teachers est. 12 % of elementary classroom (3) Parents est. 7 % of elementary age children (3) Child psychiatrist interview < 2 % (with restricted comorbidity) National survey (NSCHN) (2003)(4) First national sample for prevalence est. National prevalence of 8 % 4.4 million school-aged children Boys: 2.5 Xs > girls 10 % boys 4 % girls Natural history < Slide 7> Behavioral symptoms often identified at school Peak prevalence: full diagnosis 9-12 years of age Symptoms change and lessen with age (5, 6) Hyperactive / impulsive symptoms lessen with age Inattention symptoms do not decrease with age Symptoms of other psychiatric disorders (eg. anxiety and conduct disorder) increase with age 65 % continue to have partial symptoms > 25 yrs Consistent with lifelong chronic disorder ADHD: Making the Diagnosis < Slide 9> DSM-IV criteria (7) (must impair or cause intense distress) Inattention (> 6 required) (not all listed on slide 9) Inattention to details / careless mistakes Difficulty sustaining attention Seems to not listen Fails to finish tasks Difficulty organizing Avoids tasks requiring sustained attention Loses things Easily distracted Forgetful Impulsivity / Hyperactivity (> 6 required) < Slide 10> Impulsivity Blurts out answers before question is finished Difficulty waiting turn Interrupts or intrudes on others Hyperactivity Fidgets Unable to stay seated Inappropriate running/climbing Difficulty engaging in activities quietly On the go Talks excessively Establishing Symptom Criteria (7) < Slide 11> Persistent pattern `" comparable developmental level Persisted > 6 months Onset < age 7 years Impairment in > 2 settings (eg., school and home) Sig. impairment in social, academic, or occupational function Not better explained by other dx (eg. conduct disorder (CD)) ADHD differential diagnosis includes: < Slide 12> Age-appropriate high activity Thyroid disorders Hearing loss or vision problem Sleep disorder Trauma / severe neglect (stressors inducing ADHD sx) (8) Learning disabilities or understimulation (high IQ) ADHD co-morbidity in school age years < Slide 13> One third have pure ADHD(9) Almost two-thirds (64 %) had comorbid condition(9) ODD alone 21 % ODD = defiant behavior toward authority Part of the disruptive behaviors spectrum Anxiety and ODD 12% Anxiety alone 10% Conduct disorder 7 % Pattern of rights of other are violated Aggression to people, animals, property Theft Serious rule violation (ie. legal trouble) Tic Disorder 10% Mood disorder 4% ADHD DSM IV Subtypes Predominantly Inattentive type > 6 inattentive criteria < 6 impulsive/hyperactive criteria Meets impairment criteria 27 % Predominantly Hyperactive/Impulsive type > 6 impulsive/hyperactive criteria < 6 inattentive criteria Meets impairment criteria 18 % ADHD Combined type > 6 inattentive criteria > 6 impulsive/hyperactive criteria Meets impairment criteria 55% Diagnostic Limitations ADHD is profile of behaviors Diagnosis is based on clinical history which can be subjective Symptoms are difficult to distinguish from normal behavior Temperament or individual differences is hard to assess DSM IV No special category for severe cormorbidities like conduct disorder Allows conduct disorder as comorbid condition like anxiety or major depression Other diagnostic systems (used in Europe for example) use conduct disorder as basis for main subdivision Aims to recognize as many diagnoses as symptoms permit Results in a broad range of symptoms in ADHD diagnosis Clinical presentation of ADHD Most frequently present for eval. at 6 12 yrs (5) Variety of behavioral symptoms(10) Distracted Too talkative Described as immature acts younger than chrono. age History of repeating a grade Presentation in the adolescent (12 18 yrs) Inner sense of restlessness rather than hyperactivity Organization becomes priority in school work Executive or managing skills get overwhelmed (11) Driving skills reveal executive impairment (ADHD vs. non-ADHD) > 12 moving violations ( 20 % vs 3 %) > 5 speeding tickets (21 % vs 3 %) > 3 car accidents ( 27 % vs 9 % ) ADHD = 3 Xs the dollar amount in damages Pathophysiology of ADHD Searches for biological basis to explain neuropsychological impairments Anatomical abnormalities in frontal lobes and basal ganglia Genetic molecular differences in the dopamine neurochemical pathways Environmental risk factors that may stress developing CNS Environmental /acquired risk may damage developing neurons(17) Prenatal factors related to decreased fetal well-being Low birth weight Exposure to alcohol Exposure to nicotine Postnatal factors CNS infections and trauma Environmental lead exposure Severe marital discord Maternal mental health disorder Not the focus of this talk Genetic influences Twin Studies Heritability estimate from frequency of ADHD in twins Monozygotic (identical) twins 100% of their genes Fraternal (dizygotic) twins 50 % shared genes Identical twins have > concordance than fraternal twins 0.50 -.0.76 for dizygotic 0.80 0.98 for monozygotic Mean heritability estimate = 76%(18) Molecular genetic studies 7 candidate genes emerged from twin studies (18) Top gene candidates are dopamine D4 receptor (DRD4) and dopamine transporter gene (DAT1) Dopamine D4 receptor (DRD4) gene is associated with a subsensitive postsynaptic receptor <slide 22> Dopamine transporter gene (DAT1) !expression of the dopamine transporter Results in hre-uptake of dopamine out of synaptic cleft <slide 22> Supporting evidence Animal studies: knockout mice lacking dopamine transporter Have ! motor activity Reduced locomotor response (19) Mechanism of drugs used to treat ADHD (eg methylphenidate) Blocks the dopamine transporter Causes an accumulation of dopamine in synaptic cleft Caution must be used in translating any genetic / anatomic study to DSM-IV ADHD phenotype (see diagnostic limitations) Treatment of ADHD Proven effective therapies Therapy based on behavioral principles Pharmacotherapy Combination therapy Behavioral Therapy(20) Based on use of rewards and consequences Uses behavioral techniques of reinforcement and punishment Examples: Behavioral parent training Behavioral classroom training Not effective: nonspecific family, individual, or cognitive therapies Pharmacotherapy Stimulants Methylphenidate (Ritalin) (eg. 5 to 20 mg three times a day) D-amphetamine salts (Adderall) (eg. 5 to 15 mg three times a day) Once-a-day dosing increases compliance and decreases missed doses Methylphenidate = Concerta D-amphetamine salts = Adderall XR Acts similar to cocaine Similar chemical structure (21-23) Enters brain more slowly Less addictive potential (less reinforcing) (24) Successful tx = rating scales = low or 0 behaviors 25 = normalized Controlling symptoms `" function Multimodal Treatment of ADHD Study (MTA)(26) <slide 26> Success rates approach 90% with two main stimulants (27) Clinically meaning benefits = ! in impairment Benefits are quick to appear (ie days to weeks) Behavioral therapy (BT) not as effective as stimulant meds only(27) Intensive BT expensive Intensive BT not widely available Benefits take longer to appear (weeks to months) Multimodal treatment (Meds + BT) = hed benefit with sig. comorbidity(27) Three year MTA follow-up has revealed (48) 83% followed up; now 10-13 years old MTA medication treatment groups (Meds + Comb) lost advantage All 4 study groups show age-related ADHD symptom decline Can stimulant medications be stopped? Did children doing well stop meds? Did children doing poorly start meds? ADHD and Substance Use DisordersA Complex Relationship Adolescent Substance UseMonitoring the Future Study Annual nationwide survey of behaviors and attitudes in teens 2005 data from 50,000 8th, 10th, 12th graders 50% high school seniors = alcohol use in last month; 25 % = tobacco Some illicit drug use: 25 % of high school seniors accessed at: http://www.monitoringthefuture.org/ Risk factors for SUD Retrospective studies suggest: ADHD hed in adolescents and adults with SUD (30-35)<slide 30> Up to 50 % of adolescents with SUD have ADHD 25% of adults with SUD have ADHD Development of conduct disorder mediates risk of alcohol use disorders <slide 31> Via early expression of antisocial behavior(36) <slide 32> ADHD w/o CD is `"! risk for future antisocial behaviors(37) SUD has 2 year earlier onset in ADHD compared to those without ADHD (38) Persistence of symptoms in adolescence ! s risk of alcohol use (39) Alcohol abuse and dependence studies <slide 33> All SUD not the same (eg nicotine `" alcohol dependence) San Diego Prospective Study of Alcoholism Study of genetic and environmental influences in alcoholism 165 children of sons of alcoholics (ie. family history of AUD) Now 14-25 years of age (separated into two groups) Group 1 ( + CD or + ADHD) Group 2 ( absence of CD or ADHD) Results of comparison Family Hx of AUD `" predict ADHD or CD CD strongly correlated to SUD (18X s Risk) ADHD (w/o CD) did not inc risk for SUD ADHD Studies of SUD <slide 34> ADHD with comorbidity (eg. conduct disorder) !! risk of SUD Accelerates the development to more severe SUD Persistence of ADHD symptoms in adolescence(39) ADHD persisters with no conduct disorder 2.5 X s > risk of Alcohol Problem Score > 1 3 X s > to be drunk 2 times or > in past 6 mths ADHD persisters with conduct disorder 5 X s > risk of Alcohol Problem Score > 1 4 X s > to be drunk 2 times or > in past 6 mths Persistence and severity of ADHD symptoms ! alcohol misuse Inattention symptoms predict better than childhood antisocial behaviors Poorer scores on tests of attention were prospectively associated with greater substance use frequency(40) Emerging relationship of treatment of ADHD to SUD <slide 35> Unmedicated children with ADHD = hed risk for SUD (44-46) ADHD compared to controls report using substances to Attenuate mood i Restlessness Assist with sleep (35) Meta-analysis of 12 studies : stimulant treatment does not lead to SUD in adults (21) Early medication treatment for ADHD matters Meta-analysis of 6 studies: Tx significantly ies the risk for subsequent SUD Pharmacotherapy of ADHD= 85% ! risk for SUD in ADHD youth (45, 47) 3-fold decreased risk for SUD outcome in substance and alcohol(46) <slide 36> 75 % of unmedicated ADHD ! SUD 25 % of medicated ADHD ! SUD Medicated ADHD same SUD rate as controls Summary (We have reviewed:) ADHD is very common (= 10% of boys) Central problem = poor attention and impulsivity Pharmacotherapy improves symptoms ADHD treatment may protect from later SUD References 1. Zito JM, Safer DJ, dosReis S, Gardner JF, Boles M, Lynch F. Trends in the prescribing of psychotropic medications to preschoolers. JAMA. 2000 February 23;283:1025-30. 2. Committee on Quality Improvement,Subcommittee on Attention-Deficit/Hyperactivity Disorder,. Clinical practice guideline: Diagnosis and evaluation of the child with attention-Deficit/Hyperactivity disorder. Pediatrics. 2000 May 1;105:1158-70. 3. Wolraich ML. Examination of DSM-IV criteria for attention Deficit/Hyperactivity disorder in a county-wide sample. Journal of developmental behavioral pediatrics. 1998;19:162-8. 4. Centers for Disease Control and Prevention (CDC). Mental health in the united states. prevalence of diagnosis and medication treatment for attention-deficit/hyperactivity disorder--united states, 2003. MMWR Morb Mortal Wkly Rep. 2005 Sep 2;54:842-7. 5. Faraone SV. The age-dependent decline of attention deficit hyperactivity disorder: A meta-analysis of follow-up studies. Psychological medicine. 2006;36:159-65. 6. Mannuzza S, Klein RG, Bessler A, Malloy P, LaPadula M. Adult psychiatric status of hyperactive boys grown up. American Journal of Psychiatry. 1998 April 1;155:493-8. 7. American Psychiatric Association, American Psychiatric Association. Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders : DSM-IV-TR. 4th , text revision ed. Washington, DC: American Psychiatric Association; 2000. 8. Baumgaertel A. Practice guideline for the diagnosis and management of attention deficit hyperactivity disorder. Ambulatory child health. 1998;4:45-58. 9. Jensen PS. ADHD comorbidity findings from the MTA study: Comparing comorbid subgroups. Journal of the American Academy of Child Adolescent Psychiatry. 2001;40:147-58. 10. Brown TE. Attention-deficit disorders and comorbidities in children, adolescents, and adults. 1st ed. Washington, D.C.: American Psychiatric Press; 2000. 11. Robin AL. Attention-deficit/hyperactivity disorder in adolescents: Common pediatric concerns. The Pediatric clinics of North America. 1999;46:1027-38. 12. Dulcan M. Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child Adolescent Psychiatry. 1997;36:85-121S. 13. Ferguson JH. National institutes of health consensus development conference statement: Diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD). Journal of the American Academy of Child Adolescent Psychiatry. 2000;39:182-193. 14. Pliszka SR. The texas children's medication algorithm project: Revision of the algorithm for pharmacotherapy of attention-deficit/hyperactivity disorder. Journal of the American Academy of Child Adolescent Psychiatry. 2006;45:642-57. 15. Perrin JM. Clinical practice guideline: Treatment of the school-aged child with attention-deficit/hyperactivity disorder. Pediatrics. 2001;108:1033-44. 16. Foy JM, Earls MF. A process for developing community consensus regarding the diagnosis and management of attention-Deficit/Hyperactivity disorder. Pediatrics. 2005 January 1;115:e97-104. 17. Biederman J. Family-environment risk factors for attention-deficit hyperactivity disorder: A test of rutter's indicators of adversity. Archives of general psychiatry. 1995;52:464-70. 18. Faraone SV. Molecular genetics of attention-deficit/hyperactivity disorder. Biological Psychiatry. 2005;57:1313-23. 19. Spielewoy C. Hypolocomotor effects of acute and daily d-amphetamine in mice lacking the dopamine transporter. Psychopharmacology. 2002;159:2-9. 20. Pelham Jr. WE. Empirically supported psychosocial treatments for attention deficit hyperactivity disorder. Journal of clinical child psychology. 1998;27:190-197. 21. Barkley RA. Does the treatment of attention-deficit/hyperactivity disorder with stimulants contribute to drug use/abuse? A 13-year prospective study. Pediatrics. 2003;111:97-109. 22. Wise RA. Neural mechanisms of the reinforcing action of cocaine. NIDA research monograph. 1984;NO. 50:15-33. 23. Wise RA. Brain reward circuitry: Insights from unsensed incentives. Neuron. 2002;36:229-240. 24. Volkow ND, Ding YS, Fowler JS, Wang GJ, Logan J, Gatley JS, et al. Is methylphenidate like cocaine? studies on their pharmacokinetics and distribution in the human brain. Arch Gen Psychiatry. 1995 June 1;52:456-63. 25. Biederman J. Normalized functioning in youths with persistent attention- deficit/hyperactivity disorder. The Journal of pediatrics. 1998;133:544-51. 26. Jensen Pr- 7 q { MP~Q[lo 6MXLWps  03RVXYders !!h"B*phh"mH sH h"6] h"H*h"6CJ]aJh" h"5\QW}~# \ 9 O Y b m  3 ^ _ d^edqjl d^edqjldedqjl`edqjledqjl_ |  & g ' : h "Q,^edqjl =d^=edqjl^edqjl d^edqjl d^edqjldedqjl,Ndnx Q 6\.DZdedqjl =d^=edqjl d^edqjl d^edqjl @ d^@ edqjl!9Zhp8X'Yw d^edqjl @ d^@ edqjl d^edqjl =d^=edqjlw&Xt 1Fn )Cf @ d^@ edqjl d^edqjl d^edqjl =d^=edqjlf 6Yswx(ajg @ d^@ edqjl d^edqjl d^edqjl =d^=edqjl4Yes7e /Q{|# h @ d^@ edqjl =d^=edqjl d^edqjl d^edqjldedqjl %!6!J!_!q!!!!!!"%"[""""#.#S#m### @ d^@ edqjl =d^=edqjl d^edqjl d^edqjl!!! ""N#R######t$$$$$H%^%`%%%&&(())**F+G+b+i+j+++++++,,.,,,-&-b.j.////00!00011 2 2222244N4\4p455 66(666h"OJQJh"CJOJQJaJh"OJQJh"CJaJ h"H* h"6]h"B*phh"M#$$H%%%p&&&V''(x(((((()<)x)) d^edqjldedqjl =d^=edqjl d^edqjl d^edqjl @ d^@ edqjl)))****h*** +/+G+j++++D,F,,(---l... @ d^@ edqjl d^edqjl d^edqjl =d^=edqjl.F//"0G00001<1u111 2d2222r4455*66 d^edqjldedqjl @ d^@ edqjl d^edqjl =d^=edqjl6(7077788;<D=L=4A:t:::0;;;;<<<N=== d^edqjl @ d^@ edqjl =d^=edqjl d^edqjl d^edqjl=\>>>`??h@>A@AA0BBBBB CCDD2EE d^edqjl^edqjl d^edqjl d^edqjl =d^=edqjl @ d^@ edqjl d^edqjlEFJFFFG~GG HHHHIlJiK LLM@NNO#P Q d^edqjl $^a$edqjl d^edqjldedqjl =d^=edqjl QRRSLTUUVVpWWBXYYh@Ń@τoiZ*و{# d^edqjlS. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. Archives of general psychiatry. 1999;56:1073-86. 27. Jensen PS. Findings from the NIMH multimodal treatment study of ADHD (MTA): Implications and applications for primary care providers. Journal of developmental behavioral pediatrics. 2001;22:60-73. 28. Greenhill LL. Impairment and deportment responses to different methylphenidate doses in children with ADHD: The MTA titration trial. Journal of the American Academy of Child Adolescent Psychiatry. 2001;40:180-7. 29. Stein MA, Sarampote CS, Waldman ID, Robb AS, Conlon C, Pearl PL, et al. A dose-response study of OROS methylphenidate in children with attention-Deficit/Hyperactivity disorder. Pediatrics. 2003 November 1;112:e404. 30. Schubiner H. Prevalence of attention-deficit/hyperactivity disorder and conduct disorder among substance abusers. The Journal of clinical psychiatry. 2000;61:244-51. 31. DeMilio L. Psychiatric syndromes in adolescent substance abusers. The American journal of psychiatry. 1989;146:1212-4. 32. Eyre . History of childhood hyperactivity in a clinic population of opiate addicts. Journal of Nervous and Mental Disease. 1982;170:522-9. 33. Carroll KM. History and significance of childhood attention deficit disorder in treatment-seeking cocaine abusers. Comprehensive psychiatry. 1993;34:75-82. 34. Levin FR. Prevalence of adult attention-deficit hyperactivity disorder among cocaine abusers seeking treatment. Drug and alcohol dependence. 1998;52:15-25. 35. Wilens TE. Attention-deficit/hyperactivity disorder in adults. JAMA. 2004;292:619-23. 36. Brassett-Harknett A. Attention-deficit/hyperactivity disorder: An overview of the etiology and a review of the literature relating to the correlates and lifecourse outcomes for men and women. Clinical psychology review. 2007;27:188-197. 37. Lilienfeld SO. The relation between childhood attention-deficit hyperactivity disorder and adult antisocial behavior reexamined: The problem of heterogeneity. Clinical psychology review. 1990;10:699-715. 38. Wilens TE. Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders. Journal of nervous and mental disease. 1997;185:475-82. 39. Molina BSG. Childhood predictors of adolescent substance use in a longitudinal study of children with ADHD. Journal of abnormal psychology. 2003;112:497-507. 40. Tapert SF. Attention dysfunction predicts substance involvement in community youths. Journal of the American Academy of Child Adolescent Psychiatry. 2002;41:680-6. 41. Milberger S. ADHD is associated with early initiation of cigarette smoking in children and adolescents. Journal of the American Academy of Child Adolescent Psychiatry. 1997;36:37-44. 42. Levin ED. Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology. 1996;123:55-65. 43. Biederman J. Is cigarette smoking a gateway to alcohol and illicit drug use disorders? A study of youths with and without attention deficit hyperactivity disorder. Biological psychiatry. 2006;59:258-64. 44. United States. Public Health Service. Office of the Surgeon General, Center for Mental Health Services, National Institute of Mental Health. Mental health : A report of the surgeon general. Rockville, Md.; Pittsburgh, PA: Dept. of Health and Human Services, U.S. Public Health Service; For sale by the Supt. of Docs.; 1999. 45. Wilens TE. Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics. 2003;111:179-85. 46. Biederman J. Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder. Pediatrics. 1999;104:e20. 47. Faraone SV. Does stimulant treatment lead to substance use disorders? Journal of Clinical Psychiatry. 2003;64:9-13. 48. Jensen PS. 3-year follow-up of the NIMH MTA study. 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