Brain Differences Lead to Differential Treatment in ADHD and BD. Mani Pavuluri MD PhD Professor, Berger-Colbeth Chair in Child Psychiatry

Transcription

1 Brain Differences Lead to Differential Treatment in ADHD and BD Mani Pavuluri MD PhD Professor, Berger-Colbeth Chair in Child Psychiatry

2 Disclosures P Value Communications + Otsuka worked with me to develop educational slide deck: Onc Received research support from GSK, Abbott and Jansen (Medication and Matching Placebo): Once upon a time

3

4 A Assessment B c Brain Function Chemistry D Dynamics and Delivery

5 DIFFERENTIAL TREATMENT Pavuluri et al., psych Annals, In press

6 A

7

8 Longitudinal Cross sectional Population Clinic 0-19 PBD 0-33 ADHD PBD 4-98 ADHD ADHD PBD ADHD PBD 4 PBD ADHD PBD ADHD Conversion Adult BD N= <13y y 6 >18y Galanter and Leibenluft, 2008

9 Prodrome in PBD Uh! Uphill Battle at School Nothing is working Cannot Parent Stimulants prescribed They will grow out of it ] [ Age ADHD + PBD + SUD? Teen Age super imposed ADHD + PBD?! 3 rd -4 th grade: Mania-like Symptoms 2 nd -3 rd grade, work load increases, ADHD? KG: 1 st noted by Teacher, ODD or ADHD? Active since Birth Trajectory Something Different! 0 Active in Utero Singh et al 2006; Tillman & Geller, 2006; Pavuluri, 2009 AACAP

10 SYMPTOMS OF ADHD AND BPD INCREASED ACTIVITY DISTRACTIBILITY TALKATIVENESS/PRESSURE OF SP EECH DOESN T LISTEN/FOLLOW INSTR UCTIONS FIDGETING LEAVING SEAT CLIMBS EXCESSIVELY BLURTS OUT ANSWERS CAN T WAIT FOR TURN INTERRUPTS INCREASED ACTIVITY DISTRACTIBILITY TALKATIVENESS/PRESSURE OF SPEECH FLIGHT OF IDEAS ELATED MOOD/IRRITABLE MOOD INFLATED SELF-ESTEEM/ GRANDIO SITY HYPER SEXUALITY POOR SLEEP

11 Patients (%) Geller & Zimerman DISTINGUISHING BETWEEN BIPOLAR AND AD HD Bipolar 86 ADHD Elevated mood Grandiosity Flight of ideas Decreased sleep Hypersexuality

12 Affective Psychopathology MS Tolerance Alternative Choices Affective Storms MS Tolerance Alternative Choices Affective Storms 1-2 months 1-2 months SSRI Narrow Phenotype Bipolar and Related Disorder Temper Outbursts MS Tolerance Alternative Choices Affective Storms Chronic irritability 1-2 months DMDD Bipolar and Related Disorder

13 Child Mania Rating Scale, Parent Version The following questions concern your child s mood and behavior in the past month. Please place a check mark or an x in a box for each item. Please consider it a problem if it is causing trouble and is beyond what is normal for your child's age. For example, check never' if the behavior is not causing trouble. Never Sometimes Often Very Often /Rarely 1. Have periods of feeling super happy for hours or days at a time, extremely wound up and excited, such as feeling "on top of the world" 2. Feel irritable, cranky, or mad for hours or days at a time 3. Think that he or she can be anything or do anything (e.g., leader, best basketball player, rap singer, millionaire, princess) beyond what is usual for that age 4. Believe that he or she has unrealistic abilities or powers that are unusual, and may try to act upon them, which causes trouble

14 CMRS-P Total Score HC ADHD BD Only BD+ADHD 5 0 Pavuluri et al., JCAAP, 2005

15

16

17

18

19 Decoding for Families Domain Working Memory Impulse Control Executive Function Emotional Regulation Perspective & Anxiety Disorder ADHD Bipolar Disorder Anxiety Autism Spectrum Academics Reading Writing Math Spelling Parent Concerns Not listening Failing in class Excessive worrying Explosive & bullying Not enjoying play dates Labels mean only so much - Here is the true story

20

21 Neurocognitive Function: ADHD Comorbidity Healthy Control PBD Only Comb. PBD+ADHD -2 Visual Mem Verbal Mem Attention Exec Function Motor skills Visuo-Spac Percep Working Mem Pavuluri et al., AMJ, 2006

22 Pavuluri et al, 2009, JACAAP

23 B

24

25 Pavuluri, in Press (Book by Stratowski et al)

26 Pavuluri, in Press (Book by Stratowski et al)

27

28 Image source:

29 Brain Emerging Model: Core regions of five circuits mapped Pavuluri and Sweeney, 2008

30 ADHD Brain vs. Bipolar Brain

31

32

33 Evaluative Affective+ Inhibitory Circuit: Cortical Emotional Regions are Highly Engaged to Get the Job Done Risperidone engaged insula Divalproex engaged subgenual cingulate cortex With Change in YMRS (p=.03) With Change in CDRS (p=.01) Pavuluri et al., Behav Brain Res, 2012

34 RISP AND DVPX: REACTIVE AFFECTIVE CIRCUITRY DURING IMPULSE CONTROL Amygdala is engaged poorly even after treatment Pavuluri et al., Behav Brain Res, 2012

35 DIVALPROEX RISPERIDONE LAMOTRIGINE Response Inhibition DLPFC Posttreatment activity; and change overtime vs.hc (except striatum) MPFC VLPFC PACC SACC Connectivity in affective inhibitory circuit from baseline patients vs. HC Insula VStr PCC Connectivity in affective inhibitory circuit from baseline patients and vs. HC Emotional areas are deployed during cognitive performance Affective Inhibitory Circuit Pavuluri, AACAP., 2014

36 RISPERIDONE DIVALPROEX LAMOTRIGINE Working Memory under Negative Emotional Challenge MPFC MTL Posttreatment activity; and change overtime vs.hc VLPFC SACC Replication among antiepileptic drugs Posttreatment activity; and change overtime vs.hc Posttreatment activity; and change overtime vs.hc Pavuluri, Neuropsychopharmacology, in press

37 Executive Function under Negative Emotional Challenge LMG RISP Post - treatment; Change towards lower activity vs. HC MPFC DLPFC PACC SACC MTL Amyg. RIGHT AMYGDALA LMG Still shows activity post LMG in short term (6-8 weeks), but connectivity Post Standardized Algorithm in long term (4-6 months). LMG RISP. DVPX activity with treatment vs. HC PFC Changes First: Normalized activity of DLPFC, VLPFC and MPFC on short term treatment, followed by the amygdala on long term treatment. Pavuluri, AACAP., 2014

38 Connecting the dots Affective circuits are impaired in mood dysregulation: Hyperactive amygdala and impaired VLPFC: Underlie mania, reactivity, dysregulation Severe: VLPFC is switched off Moderate, Mild or medicated: VLPFC appears to be overactive Ouch! Broken!

39 from what we know Negative or Intense Provocative Stimuli are the best probes to elicit dysfunction PFC is more plastic than subcortical structure to change with intervention Affective and cognitive circuitry impairments coexist, interface and are dynamic Prognostic factors: PFC/amygdala pathology at baseline non specific if you understand pathophysiology?

40 C

41 Principles MDPAAS Pavuluri et al., 2004 and live white paper

42 ALGORITHM PART I: MOOD STABILIZATION Medication* Second Generation Antipsychotic Mood stabilizer First Choice Risperidone or Aripiprazole Quetiapine Lithium Choices Risperidone Aripiprazole Quetiapine Ziprasidone Olanzapine Li/DVPX, CBZ Lamotrigine Oxcarbazepine Topiramate *Any history of a drug that had negative or no effect was not prescribed

43 Algorithm Part II: Problem Solving Break-through Symptoms Depression Lamotrigine or Lithium LMG + Lithium Escitalopram In Small Dose

44 Algorithm Part II: Break-through Symptoms Psychosis SGA as monotherapy Add SGA if partial response to other mood stabilizer Choose in an order of choice or base d on tolerability

45 Algorithm Part II: Break-through Symptoms Aggression and hyper-arousal Maximize Mood stabilizer dose Add SGA Treat like treatment resistant case Add Guanfacine Propranolol

46 Algorithm Part II: Treatment Resistance Alternative Therapy Combination Therapy Triple Therapy Clozapine?

47 Algorithm Part II:Sleep Difficulties Melatonin Quetiapine Alpha Agonists Move to PM: Sedating meds

48 ALGORITHM PART II: COMORBID ADHD Focalin XR or Concerta Mixed Amphetamine Salts Methylphenidate Dexamphetamine Atomoxetine

49 Algorithm Part II: Comorbid Anxiety CBT First choice SSRI Small doses Propranolol For performance anxiety Benzodiazepines Long acting ones first!

50 Algorithm Part II: Adverse Events Weight gain: EPS: GI symptoms: Sedation:

51 DIFFERENTIAL TREATMENT Pavuluri et al., psych Annals, In press

52 D

53 The best has gotten to be Brain and Environmental Training Towards Emotional Resilience: BETTER And get the children and families to be in a better place!!

54 Keep the score! YOU= Brain+ People (Mind, Body and Soul) People to manage= you, child, partner, school, family, friends, child s peers and sibs

55 Shielding children from allostatic load

56 Ingredients Domains EF WM IC Ph Rx PT CFF- CBT Mot At EpM CR SS IT Flex EA EmM Ment Tut Sib EmR Emp ERe FT Ed Sch The SPICE PERSONALIZED MEDICINE = TREATMENT PRECISION 56

57 OUTINE FFECT CONTROL CAN DO IT O NEGATIVE THOUGHTS; LIVE IN THE NOW E A GOOD FRIEND: BALANCED LIFESTYLE H! HOW CAN WE SOLVE IT?! AYS TO GET SUPPORT West et al., JACAAP, in press

58 Priority: Laser beam focus! Multiple, different and equal for all! In reality, 20 things hit at you Make the list of things 1. Self Instruction 2. Things to do 3. Mindfully give it time Centered, keep steadily busy=behavioral activation, do not rush, schedule less busy times and people times

59

60 What to say and what not to say is half the skil Wisdom+Warm th+dignity = East meets West It is not all about logic!!!

61 Dead pan Compassionate A bit sad Cheerful

62 Systems Perspective: People Skills PERK up!! Patience Empathy Respect Kindness How fast can you solve it?

63 Frustration: You Nagging Bi..ch Negative Inability stimuli Poor executive function, Frustration 0 to 100 to do it! reactivity Things to be done Parent asks-fair! EAR Full- Extra Parents- must accept that this requires their EXTRA effort due to illness

64 Zero to 100! Ouch!!! Disengage Reboot Humor Distraction Lighten up Chill Leave the room and lie down Mindful focus on outside world Think of a role model would they do it? Put on dead pan face till you recover Speed bumps: Think about good times and get the strength Find constructive things to do- relax or release energy Decreasing ANS activation= Mind+Body+Soul= DLPFC+ Insula+MPFC= Thinking+Comfort+Feeling

65 Which one are you: Cold, critical, compassionate, quiet, illogical, passive, rigid, optimal?

66

67 Friendly, consistently

68 Nothing falls from the sky, y all!

69 3Ts: Teacher, Tiny work, Time

70 CEOs DLPFC EDUCATING FAMILIES Nucleus accumbens Amygdala Frontline workers OFC VLPFC Subcortical Cortical TAKING IT TO THE TABLE WITH REAL PATIENTS AND PARENTS

71 EDUCATING FAMILIES Frontline workers CEOs Nucleus accumbens DLPFC Amygdala OFC Cortical VLPFC Insula Subcortical Threat vs. Trust Knob TAKING IT TO THE TABLE WITH REAL PATIENTS AND PARENTS

72 cognitive skills:

73

74 HAVE A GAME PLAN FOR DISTRACTIONS also Trick is parents must have non digital skills of engagement

75 EVERYTHING IN MODERATION But how? Sleep deprivation with media in their room : Checking the computer or smart phones in with parents if harder to stop

76 The Real Deal! Multi domain-multi system functionality Experience and Brain as partners Eg. Nature-nurture: Change is primarily possible through Envn. vs Fixed Genes; So larger longitudinal studies chasing repair sounds promising Science can better itself in embracing what can be applied in real life. Eg. Affect Sensitive Learning So, can we start early?

77 Now, the business of life and managing!

78

79

80 BRAIN CENTER ACTIVE PATIENTS: 529 CATCHMENT: 29 States + Canada 80 UIC

81 Feel BETTER!?