Heterogeneity in adhd

comorbidity , learning disability,anxiety, depression, tourette syndrome, autism spectrum disorder, treatment , amphetamine, atomoxetine ,behavior therapy, alternative treatment , megavitamins, ginkgo biloba

1. Heterogeneity in ADHD: neuropsychological pathways, comorbidity and symptom domains. Heba Essawy , MD Prof Of Psychiatry Ain Shams University

2. Roadmap What is ADHD? Prevalence of ADHD. ADHD mimicry. ADHD Comorbidity. Treatment of ADHD and Comorbidities

3. Introduction ADHD is a complex disorder of higher brain functioning, characterized by inattention, motor over-activity and difficulty inhibiting impulsive behaviors ADHD is one of the most prevalent disorders in childhood and adolescence, affecting an estimated 3-9% of school-age children

4. Introduction Symptoms occur at an early age, occur in most areas of a child’s life, and persist over time, frequently into adulthood The precise constellation of symptoms changes as children grow and develop

5. Introduction ADHD is often inherited Imaging, electrophysiological and neuropsychological tests, and now, genetic analysis, all point to disturbances in specific neurotransmitter systems, affecting specific areas of the brain

6. Introduction ADHD is frequently associated with other psychiatric and learning problems, which complicate diagnosis, treatment and prognosis ADHD is a heterogeneous disorder with many known causes, all of which mediate similar or identical effects on brain functioning

7. Prevalence of ADHD in Children and Adolescents The world wide prevalence of ADHD in children and adolescents is 5.29% 1 Children: 5%-8% Adolescents: 2.5%-4% The pooled prevalence of DSM-IV ADHD is (5.9%-7.1%) 2 Inattentive is the most common subtype (3.4%-3.6%) followed by combined (2.2%-2.3%) impulsive subtypes (1.1%-1.3%) Higher prevalence in males than females ( 2.4:1) Polanczyk et al. Am J Psychiatry 2007;164(6):942-8. Willcutt . Neurotherapeutics 2012;9(3):490-9.

8. Prevalence of ADHD Across the World by Age and Gender a 22 studies of subtypes (total N = 52,622) b 10 studies of subtypes (total N = 10,882) Willcutt. Neurotherapeutics 2012;9(3):490-9. Age Range Total Studies (Total N) Total ADHD ADHD-C ADHD-H ADHD-I % M:F % M:F % M:F % M:F 3-5 years 12 (9,339) 10.5 1.8:1 2.4 2.5:1 4.9 1.9:1 2.2 1.0:1 6-12 years 24 (56,088) a 11.4 2.3:1 3.3 3.6:1 2.9 2.3:1 5.1 2.2:1 13-18 years 6 (5,010) 8.0 2.4:1 1.1 5.6:1 1.1 5.5:1 5.7 2.0:1 19+ years 11 (14,081) b 5.0 1.6:1 1.1 2.0:1 1.6 1.4:1 2.4 1.7:1

9. ADHD Mimicry In assessing and diagnosing ADHD, it is important to consider that there are a variety of conditions that can mimic ADHD. These include both physical conditions and psychological problems .

10. Conditions that Can Mimic ADHD Symptoms Sensory Impairments Medication side effects Phenobarbital Dilantin Some Asthma Medications Seizure Disorder RTH (Resistance to Thyroid Hormone) PTSD Bipolar Disorder Anxiety Disorders Depressive Disorders

11. What is Comorbidity? A variety of definitions of comorbidity have been offered. From a medical epidemiology perspective, Feinstein has defined comorbidity as any distinct additional entity that has existed or that may occur during the clinical course of a patient who has the index disease under study. Blashfield has referred to comorbidity as the co-occurrence of different diseases in the same individual . Likewise, Caron and Rutter have defined comorbidity as the simultaneous occurrence of two or more unrelated conditions .

12. Number of Comorbidities in US Children with ADHD Larson et al. Pediatrics 2011;127(3):462-70 ADHD alone ADHD alone 31% At least one 33% Two 16% N = 5028 Three or more ADHD 33% 18%

13. Comorbid Conditions and ADHD A number of these conditions will be considered : Learning Disabilities Oppositional Defiant and Conduct Disorder Anxiety Disorders Mood Disorders ASD Tourette’s Syndrome Other Related Characteristics

14. Learning Disabilities Children with ADHD show problems in the academic environment. These problems include behaviors that interfere with learning, lowered levels of school achievement , specific learning disabilities . They show more grade repetitions and more frequent placement in special classes. Follow-up studies have also found that the academic and learning problems of such children often persists into adolescence and are associated with chronic underachievement and school failure.

15. Learning Disabilities Biederman , et al found the degree of overlap between ADHD and “learning disabilities” ranged from a low of 10 % to a high of 92% (??). Barkley (1998) has suggested that the best estimate of comorbidity is likely to be 19 to 26 % when learning disability is “conservatively” defined (i.e., significant delay in reading, math, or spelling relative to IQ, with achievement in one of these areas at or below the 7 th percentile

16. Learning Disabilities With a more lax criterion, (e.g. achievement levels at least two grades below current grade placement) comorbidity estimates as high as 80% are found. C hildren with ADHD also show other types of developmentally related difficulties that can impair school functioning. S peech and language disorders which occur in as many as 30 to 64 % of children diagnosed with ADHD.

17. Oppositional Defiant and Conduct Disorder The finding of high levels of comorbidity with oppositional defiant disorder and conduct disorder is very common Available data suggests as many as 50% of children with ADHD show evidence of oppositional defiant disorder (Johnson, Alvarez & Johnson, 2009)

18. Oppositional Defiant & Conduct Disorder 30 to 50 % of children with ADHD are consistent with a clinical diagnosis of conduct disorder (Johnson, et al, 2009) W hen ODD or CD occurs with ADHD the clinical picture is one of increased severity compared to children/ adolescents with ADHD alone .

19. Oppositional Defiant & Conduct Disorder Children with combined ADHD and ODD seem to represent an intermediate group in terms of symptom severity when compared to ADHD only children, who show less severe problems , and children with ADHD and CD, who show more severe problems . Biederman et al have noted that “ ... children with attention deficit hyperactivity disorder plu s conduct disorder appear to have a particularly severe form of attention deficit hyperactivity disord er .”

20. Oppositional Defiant & Conduct Disorder These investigators indicate that “... subgrouping based on comorbidity with conduct disorder may be of potential value in determining which children with attention deficit hyperactivity disorder have M ore serious prognosis D ifferent family-genetic risk factors R equire specialized comprehensive therapeutic interventions.” What are the pros and con’s of diagnostic subgrouping??

21. ANXIETY DISORDERS ADHD has not only been found to be related to disruptive behavior disorders. It is related to internalizing problems such as anxiety disorders and depression. 25 and 30 % of children with ADHD show evidence of some type of anxiety disorder (Johnson, et al, 2009). Rates between 23 and 58.8% have been found in general population studies.

22. ANXIETY DISORDERS Here, children diagnosed attention deficit disorder- primary inattentive type have been found to show the highest degree of comorbidity with regard to anxiety disorders. C omorbid anxiety may serve to reduce the impulsiveness often associated with ADHD .

23. Mood Disorders The combination of the two disorders appears to suggest a subgroup of children who show an especially poor long term outcome . C omorbidity with bipolar disorder are somewhat more controversial , The small number of studies in this area suggest that the degree of overlap between ADHD and bipolar disorder is in the range of 11 to 22 per-cent (Johnson, et al , 2009)

24. Mood Disorders This apparent comorbidity may be partially an artifact due to the fact that similar symptoms (e.g., attentional problems, poor judgment, high activity level) are a diagnostic indicators of both disorders The relationship between ADHD and bipolar disorder is unidirectional . That is, the presence of bipolar disorder seems to suggest an increased risk for ADHD , while the presence of ADHD does not seem to suggest an increased risk of developing bipolar disorder. (cite Katie’s dissertation research).

25. Mood Disorders Additional research is needed to further investigate the precise relationship between ADHD and bipolar disorder.

26. Tourette’s Disorder Individuals with Tourette’s disorder, somewhere between 40 and 50 % show features of ADHD . ADHD children who develop Tourette’s syndrome is 7%. Children displaying both disorders may be more likely to be referred for assessment and/or treatment than children who show either of the disorders alone .

27. Tourette’s Disorder L ower rate of ADHD diagnoses (12%) in children with Tourette’s disorder. Additional studies in this area are necessary to more carefully ascertain the degree of comorbidity and the nature of the underlying relationships between ADHD and Tourette’s Disorder.

28. Sleep Problems Children with ADHD have a higher sleep problems than normals . As many as 56% of children with ADHD have problems falling asleep (compared to 23% of normal children). Up to 39% of ADHD children show problems of night time awakening. Resistance to going to bed and fewer total hours of sleep seem to be a major problem with many children with ADHD (and likely add to their difficulties in school functioning). Studies of sleep patterns do not, suggest specific difficulties with the nature of sleep itself in these children

29. Speech Difficulties There is a tendency for children with ADHD to be more delayed in talking t han non ADHD children. Studies generally suggest that ADHD children are likely to have problems with expressive language but not receptive language. Here, anywhere from 10 to 54% of children have speech/language problems compared from 2 to 25 percent of normal children. Often have problems on tasks of verbal fluency.

30. Motivational Deficits Children with ADHD are often characterized by their apparent low level of sustained motivation . This is especially true on tasks that require repetitive responding that involves little or no reinforcement. Multiple studies have documented an impairment in persistence of effort in laboratory tasks in children with ADHD. It is not clear whether this is due to the lack of sensitivity of the ADHD child to reinforcement, unless it is continuous, or due to some other type of deficit

31. Motivational Deficits Barkley has suggested that the problem may relate to the fact that, while normal children have the capacity to bridge temporal delays across times when rewards are sparse, children with ADHD are delayed in this ability . He suggests the problem is not that ADHD children are not sensitive to reward or dominated by the tendency to seek immediate rewards. Instead they have a diminished capacity to bridge delays in reinforcement and permit the persistence of goal directed acts (rule governed behavior?).

32. Types of Comorbidities in Children with ADHD * p<.05 for  2 test a Relative risks were adjusted for child age, gender, race/ethnicity, parent education, household income, and family structure Larson et al. Pediatrics 2011;127(3):462-70 ARR a 5.12 7.79 12.58 7.45 8.04 4.42 8.72 2.77 3.93 1.47 10.7 Proportion of Patients (%) * * * * * * * * * * *

33. ADHD Comorbidity: Relevance Comorbidity has important implications for the understanding, assessment, and treatment of children with ADHD. First, the findings reported here suggest that children with ADHD frequently show evidence of significant comorbidity. Indeed, many children with ADHD display Learning Disabilities, ODD or CD, Anxiety Disorders, and Depressive Disorders, while still others may show evidence of co-occurring tic disorders and perhaps bi-polar disorder.

34. Relevance of Comorbidity Some show multiple comorbid disorders. These patterns of comorbidity have been interpreted by Biederman, et al as suggesting that “...attention deficit hyperactivity disorder is most likely a group of conditions with potentially different and modifying risk factors and different outcomes rather than a single homogeneous clinical entity.” (multiple conditions or ADHD with multiple comorbidities???) The presence of comorbid conditions likely has significant implications for long term outcome .  

35. Relevance of Comorbidity Simply treating symptoms of ADHD is not enough ! Appropriate case management involves addressing the full range of clinical problems displayed. E ffective treatments for children with ADHD and comorbid conditions are likely to be multimodal and multidisciplinary in nature and necessarily more extensive and complex that treatments for children with “uncomplicated” ADHD.

36. Treatment Of ADHD & CD Stimulant medication or ATX decrease : - Physical aggression -Verbal aggression -Negative social interaction Antihypertensive , atypical AP for highly aggressive , explosive cases Mood stabilizers are unhelpful Behavioural management techniques are employed Spencer T, et al Pediatr Clin North Am. 1999;46(5):915-927.

37. Treatment of ADHD & A nxiety Prioritize treatment Reduced response to stimulants Stimulants make anxiety worse ? Stimulants make some cognitive abilities worse in combined cases ATX and GUANFACINE xr do not worsen anxiety in comorbid cases SSRI may be effective for anxiety disorders B uspirone , high-potency benzodiazepines for anxiety Spencer T, et al. Pediatr Clin North Am. 1999;46(5):915-927. Conners CK J Attn Disord . 2001;4( suppl 1):30.

38. Treatment ADHD& Depression Combination therapy often required Stimulants effective in treating ADHD but not mood SSRIs may be effective in treating depression but not ADHD Noradrenergic agents ATX may treat both Antihypertensive , Atypical AP and Mood stabilizer are useful. Spencer T, et al. Pediatr Clin North Am. 1999;46(5):915-927.

39. ADHD: Comorbid Depression (cont.) ADHD treatment Noradrenergic antidepressants Stimulants Depression treatment SSRIs Bupropion Venlafaxine

40. Treatment ADHD& Bipolar Disorder Juvenile mania is highly comorbid and frequently mixed with depressive features, ADHD, anxiety, and ODD/CD Prioritize treatment First treat mania or psychosis Mood stabilizers Atypical neuroleptic ADHD

41. Treatment of ADHD & Tourette's Tics develop in 1-2% of ADHD receiving high dose of Amphetamine but not Methylphenidate  Stimulant medication is not contraindicated If unable to tolerate stimulants, consider alternative ADHD medication ( Atx or TCA) Adjunctive agents for tic control can be successfully combined with stimulants (alpha agonist, risperidone , pimozide )

42. Treatment Of ADHD & ASD 20- 25% of ADHD have ASD. 20- 5-% of ASD have ADHD. ADHD medication can be used to treat ADHD symptoms effectively in context of ASD

43. Treatment ofADHD & ODD Both stimulants and ATX reduce ODD with ADHD but not ODD alone. Requires adjunctive parents training in behavior management . Response is aged related: -60-75% successful for children -25-35% treatment response after 13 ys of age .

44. TREATMENT Of ADHD &learning Disorders Comorbid reading , spelling and math disorder do not improve from stimulants Reading ability improve on ATX

45. ADHD: Alternative Therapies Effective in ADHD children : Fish oil Lithium Zinc Arnold LE. J Affn Disord . 1999;3(l):30.

46. ADHD: Alternative Therapies Limited data Ineffective or dangerous EPA Megavitamin therapy Flax seed oil Megamineral therapy Ginko preparation Caffeine EEG biofeedback Primrose oil L- carnitine DHA Mg- VIT B6- VIT C Arnold LE. J Attn Disord . 1999;3(1):30.

47. Summary: Treatment of ADHD In treatment planning targeting major areas of impairment and comorbidities . Treatment may employ balance of behavioral and medical intervention Stimulant medications are the gold standard for medical intervention if no comorbidity is associated Apply Low- Slow- GO approach to titrating doses

48. THANK YOU

49. Hyperactivity, impulsivity and inattention are the final common pathway of virtually all psychiatric disorders in childhood. The specific constellation of symptoms and the course of a child's difficulties distinguish one disorder from another. This brings up an important point. An accurate diagnostic assessment does more than determine the presence or absence of ADHD; it also assesses for the presence, absence or co- occurence of other psychiatric and developmental disorders. Approximately 2/3 of children with ADHD have an additional diagnosis; approximately 20% have 2 diagnoses. About 50% of children with ADHD have a disruptive behavioral disorder such as ODD or CD; 20-30% will have a learning disability; 34% will have an Anxiety D/O; 6% will have a depressive D/O. There's been a lot of press lately about the association of ADHD and juvenile BPD. Two groups reported that 19% of Kids w/ ADHD also have BPD, and that nearly 90% of kids w/ BPD meet criteria for ADHD @ some point in their clinical course. Kids w/ ADHD are 2x more likely to develop a substance abuse disorder as they get older, esp. if they also have CD or BPD. An accurate assessment also includes a physical examination to rule out medical disorders that can cause, or can mimic ADHD. Ultimately, ADHD may prove to be a group of disorders with different etiologies, risk factors and outcomes, rather than a single entity.

50. ADHD: Childhood Common Comorbid Diagnoses Biederman J, et al. J Am Acad Child Adolesc Psychiatry. 1996;35(3):343-351. Pllszka SR. J Clin Psychiatry. 1998;59( surppl 1,50-58. Biederman J, at al. J Am Acad Child Adolesc Psychiatry. 1999;38(8):966-975. Spencer T, et al. Pediatr Clin North Am. 1999;46(5):915-927.

51. Treatment Impact of anxiety Probe more for physical or sexual abuse or bulling at school More responsive to behavioral therapy ( MTA) Better response to social skill training

52. Treatment ADHD & Depression Highly prevelant from 20 to 45% Severe explosive anger may be a sign of either childhood severe mood dysregulation (SMD) or Bipolar disorder