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  • 1. Optimizing ADHD Treatment: The Impact of Comorbidity Russell A. Barkley, Ph.D. Clinical Professor of Psychiatry Medical University of South Carolina Charleston, SC Website: russellbarkley.org Email: drbarkley@russellbarkley.org ©Copyright by Russell A. Barkley, Ph.D., 2010Source: R. A. Barkley (2006). Attention Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. New York: Guilford. (Info@guilford.com or 800-365-7006)
  • 2. Efforts to Usefully Subtype ADHD DSM-IV has proven to be relatively useless except for the Inattentive Type in which a subset of cases appear to have Sluggish Cognitive Tempo (SCT) Using etiology (acquired vs. familial) may eventually be useful but as yet is not well-researched  Acquired cases can arise at any time, though often result from pregnancy factors  Acquired cases may not respond to stimulants as well as familial cases Molecular genetics may eventually offer ways of creating more homogeneous clinically useful subsets  Certain gene variants may predict drug and behavioral treatment response as well as adverse life course risks Comorbidity offers the most useful and best established means for deriving clinically useful subtypes currently**Ostrander, R. (2008). Journal of Clinical Child and Adolescent Psychology, 37(4), 833-847.
  • 3. Oppositional Defiant Disorder (40-80%) A pattern of hostility, anger, defiance, stubbornness, low frustration tolerance and resistance to authority (usually parental) Comprises a two-dimensional disorder  Social conflict and emotion dysregulation* ADHD cases are 11x more likely to have ODD** ADHD contributes to and likely causes ODD  This likely occurs through the impact of the hyperactive- impulsive dimension of ADHD and its strong association with emotional dysregulation (executive dysfunction)***  This can account for the well-established findings that ADHD medications reduce ODD symptoms nearly as much as they do ADHD symptoms*Hoffenaar, P. J. & Hoeksma, J. B. (2002). Journal of Child Psychology and Psychiatry, 43(3), 375-385.** Angold, A. et al. (1999). Journal of Child Psychology and Psychiatry, 40, 57-88.***Burns, G. L. & Walsh, J. A. (2002). Journal of Abnormal Child Psychology, 30(3), 245-256.
  • 4. More on ODD Some variance in ODD severity is also related to disrupted parenting  Inconsistent, indiscriminate, emotional, and episodically vacillating between harsh and permissive (lax) consequences teaches social coercion as a means of social interaction.  But timid parenting is the most important factor contributing to ODD which feeds back to make parents more reluctant to discipline  Poor parenting can partly arise from parental ADHD and other high risk parental disorders in ADHD families (e.g., depression, ASP, SUDS) Early ODD predicts persistence of ADHD and increases risk for enuresis, CD/MDD and anxiety  Emotional dysregulation component predicts later MDD; conflict component predicts later CD
  • 5. 4-Factor Model of Defiance ParentalPsychopathology Child ODD: Disrupted Parenting Social Conflict Anger-FrustrationFamily Stressors Child Factors: Negative Temperament ADHD Emotional Dysregulation Mood Disorder
  • 6. Treatment Impact of ODD Both stimulants and ATX reduce it when it is comorbid with ADHD; not when ODD is alone  Higher doses may be needed for comorbid cases Requires adjunctive parent training in behavior management methods; response is age-related:  60-75% successful for children; 25-35% treatment response after 13+ yrs. of age  May need to treat parent’s ADHD first to succeed  May need to add problem-solving communication training of teen and parents after age 14 years Severely explosive anger may be a sign of either childhood Severe Mood Dysregulation (SMD) or Bipolar Disorder (BPD)  Treat SMD with stimulants or other ADHD medications first along with behavior modification methods. If needed, employ antihypertensives or, as a last resort, atypical antipsychotics. Mood stabilizers have not been found to be useful for SMD (or even childhood BPD**Child and adolescent psychopharmacology news, Vol. 14 (6), 2009
  • 7. Conduct Disorder (20-56%) If starts early, represents a more severe disorder and possibly a unique family subtype  More severe, more persistent antisocial behavior  Worse family psychopathology  Antisocial personality, substance use disorders, major depression  Parent hostility, depression, & low warmth and monitoring interact reciprocally with child conduct problems over time to adolescence*  Greater association with ADHD (especially inattention symptoms)  Less responsive to behavioral or family interventions  Increased risk of psychopathy (20%)  Father desertion, parent divorce more common  Major depression more likely to precede/co-exist with CD* Special issue on reciprocal influence across development, Journal of Abnormal Child Psychology (2008), vol. #36 (July) .
  • 8. Conduct Disorder One pathway to early onset CD is through ADHD and its impulsivity perhaps when combined with adverse social environments*  Explains why most ADHD does not get CD but most early CD cases have ADHD School drop out, drug use, and teen pregnancy are more likely in comorbid cases than in ADHD alone** ODD is not so much a precursor to or predictor of CD but develops in parallel with it if CD has an early onset. If CD starts late (>12), it may be related to social disadvantage, family disruption, & affiliation with deviant peers. BUT, recent research shows reduced amygdala and insula volume in both CD types*** so some neurobiological factors are involved in late onset CD too.*Beauchaine, T. et al. (2010). Clinical Psychology: Science and Practice, 17, 327-336.**Barkley, R. A. et al. (2008). ADHD in Adults: What the Science Says. New York: Guilford.*** Fairchild, G. et al. (2011). American Journal of Psychiatry, 168, 624-633.
  • 9. Treatment Impact of CD Stimulants and ATX reduce aggressive behavior and antisocial acts but stimulants may work more rapidly to gain case control  Higher doses often required in comorbid cases  Stimulant effectiveness may deteriorate with duration of treatment (3+ yrs) in this subset of ADHD cases (MTA study) Parent and family interventions often required to address family issues  Problem-solving, communication training and parent BMT  Multi-systemic therapy where available  Treatment of parental depression and other psychiatric disorders  Family relocation to better neighborhoods advisable If psychopathy (callous-unemotional traits) is present there is limited or no response to behavior therapy alone – medication is necessary first, then follow up with behavioral treatments* Avoid group treatment due to deviancy training by aggressive peers Involvement of social service and juvenile justice agencies is highly likely – educate them about comorbidity As in ODD, treat with ADHD medications and behavior modification first. Then follow-up with antihypertensives or, rarely, atypicals may be needed for highly aggressive/explosive cases or BPD. Mood stabilizers are often unhelpful.*Waschbusch, D. A. et al. (2007). Journal of Clinical Child and Adolescent Psychology, 36(4), 629-644.
  • 10. Anxiety Disorders (10-40%) Considered a stealth or hidden comorbidity in child ADHD cases if only parents are interviewed about child anxiety symptoms. High comorbidity with adult ADHD (30%+) Related in part to emotional dysregulation in ADHD (& ODD) This is evident more as negative affectivity rather than fear/worry Also risk for real anxiety disorders(risk increases with age) Most common are simple phobias or separation anxiety in early childhood; GAD becomes more common with age Risk is related to:  earlier inattention more than to impulsive-hyperactive symptoms*  greater disruptive and stressful life events  presence of autistic spectrum disorders and chronic multiple tics**  parental anxiety disorders Comorbid cases often show lower levels of impulsiveness but are still more impaired than ADHD alone cases Comorbid cases have more sleep problems (bedtime resistance and night waking); anxiety contributes to these besides ADHD Anxiety contributes additionally to social impairment besides ADHD*Reinke, W., & Ostrander, R. (2008). Journal of Abnormal Child Psychology, 36(7), 1109-1122.** Gadow, K. et al. (2009). Journal of Attention Disorders, 12(5), 474-485.
  • 11. Role of Parent Anxiety Disorders Anxiety disorders more likely in parents and family* (18%+ of parents have significant symptoms of anxiety or depression)** Child and parental anxiety are associated with low rates of positive parental behavior, over- protectiveness of the child, less autonomy for the child, lower child self-sufficiency, and parent modeling of anxiety. This excess parental control may increase child perceptions of threat, decrease children’s sense of controlling threats, and decreased opportunity for experience with managing threats****Pfiffner, L. & McBurnett, K. (2006). Journal of Abnormal Child Psychology, 34, 725-735.*Kepley, H., & Ostrander, R. (2007). Journal of Attention Disorders, 10, 317-323.** Vidair et al. (2011). J Amer. Acad. Child. Adolesc. Psychiatry, 50(5), 441-450.*** van der Bruggen, C. O. et al. (2008). (meta-analysis) Journal of Child Psychology and Psychiatry, 49(12), 1257-1269.
  • 12. Treatment Impact of Anxiety Disorders Probe more carefully in child cases for child physical or sexual abuse or bullying at school  Bully-victims have high rates of psychosomatic symptoms* More responsive to behavioral therapies (MTA Study) May respond better to social skills training (and possibly cognitive-behavioral therapies)  But CBT outcomes are poor if parental anxiety remains high and if paternal rejection and depression are present** Family counseling may be required to limit family induction of anxiety by other anxious members Focus parent BMT on increasing positive parenting behavior and reducing over-protectiveness and less so on parent discipline tactics*Gini, G. & Pozzoli, T. (2009). Pediatrics , 123(3), 1059-1065.**Liber, J. et al. (2008). Journal of Clinical Child and Adolescent Psychology, 37(4), 747-758.
  • 13. Impact of Anxiety on Med Management Anxiety (or high internalizing symptoms) has been associated in some studies with reduced response to stimulants. 4 issues arise here:  Do stimulants make ADHD worse in mixed cases? No  Do stimulants result in less improvement in ADHD symptoms in these comorbid cases? Maybe – findings are conflicting here*  Do stimulants make anxiety worse? Maybe – results are conflicting here also  Do stimulants make some cognitive abilities worse in mixed cases? Probably***Pliszka, S. (1989). Journal of the American Academy of Child and Adolescent Psychiatry, 28, 882-887. Biutelaar, J. et al. (1995). Journal of the American Academy of Child and Adolescent Psychiatry, 34, 1025-1032. Abikoff, H. et al. (2005). Journal of the American Academy of Child and Adolescent Psychiatry, 44(5), 418-427. Pliszka, S. (2003). Paediatric Drugs, 5(11), 741-750.**Blouin, B. et al. (2009). Journal of Attention Disorders, 13(4), 414-419. Pliszka, S. (1989) [see above]. Tannock, R. et al. (1995). Journal of the American Academy of Child and Adolescent Psychiatry, 34 , 886-889. Bedard, A. & Tannock, R. (2008). Journal of Attention Disorders, 11(5), 546-557.
  • 14. More Impact of Anxiety on Med Mgmt Atomoxetine (ATX) and guanfacine XR do not worsen anxiety in comorbid cases. AACAP and CADDRA Practice Guidelines recommend both stimulants and ATX as first choice treatments in comorbid cases
  • 15. Major Depression (0-45%) Likely genetic linkage to ADHD Genes create a vulnerability to MDD MDD expressed upon exposure to repeated social and emotional distress, physical trauma, etc. Also related to presence of earlier ODD and CD in child or adult patient & family Often manifest low self-esteem in childhood in contrast to other ADHD cases Full MDD onset may not be until adolescence or later In adults with ADHD, MDD is related to higher GAD and social phobia but lower SUDS and school disciplinary actions and grade repetitions in history**Fischer, A. et al. (2007). Journal of Psychiatric Research, 41, 991-996.
  • 16. More on Impact of MDD Parental depression is elevated in these child cases (18%+ have elevated depression or anxiety)* Depressed parents:  show decreased positive parenting and nurturance, greater irritability and expressed emotion, irritability and open hostility, erratic use of discipline tactics, child rejection, and poor child monitoring – these are associated with increased later risk for child ODD and also internalizing problems**  Parental MDD linked directly to child ODD risk; parental DBD with MDD increases risk for child ADHD, CD, and mania*** Evaluate carefully for presence of child physical or sexual abuse or victimization by bullying in child cases Increased suicidal ideation (4x) and attempts (2x) in ADHD cases during peak risk years in high school* Vidair et al. (2011). J Amer. Acad. Child. Adolesc. Psychiatry, 50(5), 441-450.**Elgar et al. (2007). Journal of Abnormal Child Psychology, 35, 943-955.**Gerdes, et al. (2007). Journal of Abnormal Child Psychology, 35, 705-714.*** Hirshfeld-Becker, D. R. et al. (2008). Journal of Affective Disorders, 111, 176-184.
  • 17. Suicidality in Childhood Follow-up study of 127 ADHD cases from age 8 to 14 years* 8 have seriously considered suicide (6.3%)  One teen went on to try once, but was not treated ; one went on to try more that once and was treated. The latter teen had self-harmed 5 times. 10 teens had intentionally injured themselves (7.9%) (self-cutting, etc. 1-6x over 1 year); 5 of these cases had considered or attempted suicide• R. Schachar, M.D., Hospital for Sick Children (2009, personal communication)
  • 18. Suicidality in Teens & Adults ADHD is associated with a greater risk for suicidal ideation & attempts*  Ideation in high school (33 vs. 22%)  Attempts in high school (16 vs. 3%)  Attempts are worse (46% vs. 11% hospitalized)  Ideation after high school (25% vs. 12%), attempts 6 vs 3%); risks for ideation found even at age 27  Associated with comorbid MDD (4x), CD (somewhat), and more severe ADHD  Evaluate carefully for child physical or sexual abuse or victimization by bullying *Barkley, R. A. & Fischer, M. (2005). The ADHD Report, 13 (6), 1-4. *Barkley, R. A., Murphy, K. R., & Fischer, M. (2008). ADHD in adults: What the science says. New York:Guilford
  • 19. Treatment Impact of MDDUse ADHD drug first if: ADHD is chief complaint ADHD symptoms are more disabling MDD is mild: Little or no current functional impairment from depression; dysthymia or demoralization are present Neuro-vegetative signs are mild or absent ADHD symptoms clearly preceded MDD symptomsStart with Antidepressant first if: MDD symptoms are chief present complaint Prominent neuro-vegetative signs or health is compromised Present of suicidal ideation ADHD symptoms are mild, have a late onset, or are coincident with MDD onset. Clear history that depression was non-responsive to ADHD drugs
  • 20. More Impact of MDD May require mixed ADHD/SSRI therapy  Stimulants and atomoxetine do not treat MDD May need cognitive-behavioral therapy Assess for parental induction of depression in children and exaggeration of child ODD symptoms given higher maternal depression Parent depression may require separate treatment In parent training use a “go slow” approach to punishment so as not to contribute to depressive cognitive schemas (self-statements) or to already excessive parental use of criticism and discipline  start with all reward programs initially until MDD symptoms lift then introduce mild, selective punishments.
  • 21. Child Bipolar Disorder (BPD) (2-6%) Overlap with ADHD is controversial (2-27% incidence in ADHD cases across studies)  Prevalence rates differ: ADHD = 5-8%, BPD = 1.2-1.6% Comorbidity can arise from several problems with DSM  Some cases are misdiagnosed BPD when they are ADHD/ODD  ADHD symptoms overlap with bipolar symptoms in DSM  Irritability could substitute for mania in children in DSM-IV – this is an error to be corrected in DSM-5 (could be ODD)  No requirement for cycling or periods of remission in children  DSM-V will likely require mixed moods (bipolarity), cycling between them, grandiosity, mania and other typical cognitive BPD symptoms SMD is more likely to co-exist with ADHD – irritability with explosive/aggressive behavior but no mania Overlap probably represents a one-way comorbidity  2-6% of ADHD cases have BPD; 80-97% of child BPD have ADHD but only 15-20% of adult onset BPD cases have ADHD.
  • 22. More on BPD Risk for BPD is not elevated in follow-up studies of ADHD kids (2-6%) or in studies of clinic referred ADHD adults1,2 Childhood BPD has 7-8x family risk of BPD than does ADHD or adult onset BPD; BPD not elevated in ADHD families Parental BPD associated with 8x greater risk for ADHD in offspring and for subthreshold mood and manic symptoms3 BPD unlikely to be fully evident before age 10 years but can be prodromal in offspring of BPD adults, especially if ADHD and ODD develop3  Sequence: Age 4 (hyper); 6 (ADHD), 12-22 (BPD+ADHD); adulthood (BPD, less ADHD) Neuro-imaging results differ between ADHD and BPD  Larger caudate in BPD; smaller in ADHD  Anterior cingulate affected in both but subgenua ventral region more involved in BPD while dorsal ACC is less active in ADHD 1. Barkley, R. A. (2006). Attention deficit hyperactivity disorder: A handbook for diagnosis and treatment (3rd ed.). New York: Guilford Press. 2. Barkley, R. A. et a. (2008). ADHD in adults: What the science says. New York: Guilford Press. 3. Birmaher, B. et al. (2010). American Journal of Psychiatry, 167(3), 321-330.
  • 23. Differential diagnosis from ADHD All ADHD symptoms are more severe in BPD cases but ADHD cases do not show the typical mood regulation features of BPD. Focus on mood, thought, and hypersexuality.  Irritability: 95% (BPD) vs. 65% (Disruptives)  Elation: 73% vs. 15%  Grandiosity: 80% vs. 10%  Excessive talking: 92% vs. 38%  Racing thoughts: 30% vs. 5%  Flight of ideas: 69% vs. 14%  Decreased need for sleep: 42% vs. 12% (ADHD kids have sleep problems)  Pressured speech/motor: 84% vs. 35%  More active: 85% vs. 43%  Uninhibited socializing: 32% vs. 3%  Hypersexual: 53% vs. 3%From Luby & Belden, 2006, Development and Psychopathology, 18, p. 971
  • 24. C-BPD Diagnostic Keys Grandiosity, elated mood, psychotic-like thinking (paranoia, delusions, auditory hallucinations, disjointed thought) , decreased need for sleep and hyper-sexuality are involved in C-BPD but not in ADHD.  Inattention, high energy, distractibility are NOT helpful signs for differential diagnosis Depressed-irritable mood is also a major problem and moods are often severe (i.e., rage attacks, violence, destructive). Classify as SMD if mania is absent Mood states are not related to immediate environmental events in a rational sense (irrational and inconsistent)  ADHD kids have rational but somewhat excessive emotions Disruptive (aggressive) behavior rated as 3+SDs on rating scales like the CBCL (85 or higher) goes with CBPD, not with ADHD BPD is significantly more prevalent in biological relatives
  • 25. Treatment Impact of BPD1 Medical management of bipolarity should be done first before managing ADHD symptoms with ADHD drugs But expect mania not to be as responsive to BPD drugs when ADHD is a comorbidity2 Often requires poly-pharmaceutical management for long- term (mood stabilizers, atypicals, anticonvulsants likely) Often requires periodic hospitalization for safety (suicidality or violence) and stabilization Special education (ED) programs are likely to be needed SUDs are likely by adolescence (monitor/manage) Suicidality is increasingly problematic at adolescence  15-20% completed suicide rate  30x population rate for attempts1. See special issues of Development and Psychopathology, 2006, 18. Entire issue is on childhood BPD, diagnosis, and management.2. Consoli et al. (2007). Canadian Journal of Psychiatry, 52(5), 323-328.
  • 26. More Treatment Impact of BPD Consider all-reward or non-confrontational parent training programs (Greene & Ablon’s Explosive Child) Interventions also must focus on parental coping with explosive episodes rather than expecting remediation of disruptive behavior ADHD/BPD have highest rates of physical abuse/PTSD of all ADHD cases Counsel parents on stress management; periodic respite care as needed
  • 27. Autistic Spectrum Disorders 20-25% of ADHD children have autistic spectrum symptoms or disorder  20-54% of ASD kids have ADHD Overlap may be partially due to risk genes shared between the two disorders  Both disorders are highly heritability (70-80%) Poor inhibition is linked to ADHD not to ASD symptoms while inattention is shared by both disorders; ASD is more related to social and language impairments ADHD medications can be used to treat ADHD symptoms effectively in context of ASD
  • 28. Learning Disabilities (24-70%) Not due to ADHD:  Reading (8-39%); (effect size (ES) = 0.64)  Spelling (12-30%) (ES = 0.87)  Math (12-27%) (ES = 0.89) Result from ADHD or correlated with it  Handwritingproblems (60%+)  Comprehension deficits  Reading, listening, & viewing deficits  Due to adverse impact of ADHD on working memory
  • 29. Treatment Impact of LDs Comorbid Reading, Spelling and Math Disorders do not improve from stimulants  Reading ability improves on atomoxetine Additional educational interventions will be needed for these comorbid disorders Comorbid handwriting and comprehension deficits are likely to improve from stimulants if secondary to ADHD itself ADHD cases with comorbid math disorder may be less likely to respond to stimulants (37%) than those with reading disorder (67%) or no LD (75%)**Grizenko et al. (2006). Journal of Psychiatry & Neuroscience, 31(1), 46-51.
  • 30. Conclusions Comorbidity is very common in both child and adult ADHD Comorbidity produces additional impairments in major life activities Comorbidity affects life course Comorbidity may require adjustments to ADHD treatments  Choice of meds is related to presence of anxiety, sleep problems, tics/TS and OCD, risk for diversion or abuse, and urgency of care Comorbid disorders often require separate interventions from ADHD treatments