The Benefits and Limitations of Medication Treatment for Executive Dysfunctions and ADHD

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1 The Benefits and Limitations of Medication Treatment for Executive Dysfunctions and ADHD Damon Korb, MD Behavioral and Developmental Pediatrician Director of the Center for Developing Minds Los Gatos, California November 4, 2017

2 Executive Functioning The executive functions are a set of processes that all have to do with managing oneself and one's resources in order to achieve a goal. An umbrella term for the neurologically-based skills involving mental control and selfregulation.

3 Brain Functioning

4 Phineus Gage Gage s Exhumed Skull Path of Tamping Rod

5 Executive Functions

6 Grouping Executive Functions Inhibi&on Self Monitoring Shi* Organiza&on of Materials Executive Functions Emo&onal Control Planning Ini&a&on Working Memory

7 Neurotransmitters Dopamine Attention Motivation Reward Pleasure Appetite Aggression Alertness Mood Anxious Mood Mood Compulsion Norepinephrine Serotonin

8 Neurotransmitters Dopamine Norepinephrine

9 ADHD: Model of Attention Language and Visual Processing Arousal Control Sensory Detection Saliency Determination Filter Distractions Satisfaction Control Access to Prior Knowledge

10 ADHD: Model of Self-Control Learning Recognizing Norms or Rules Planning Actions Inhibition Self- Monitoring Memory Social Cognition Language Organization Previewing Language Impulse and Tempo Control Social Cognition Sensory Recognition

11 Attention Medications S"mulants Non- S"mulants Amphetamines Dexadrine Evekeo Adderall Adderall XR Adzenys Vyvanse Mydayis Methylphenidates Ritalin Ritalin SR StraOera, Provigil, Wellbutrin Ritalin LA Methlyn Alpha Adrenergic Metadate CD Tenex Focalin XR Clonidine Daytrana Intuniv Concerta Kapvay Daytrana Quillivant XR/ Quillichew

12 Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation 824 MRI of 223 children with ADHD and 223 Controls; Longitudinal data; mean interval btwn scans 2.8 years Greater than 2 years delay 0 to 2 years delay P. Shaw et al, Proc Natl Acad Sci, 2007, 104:

13 MPH Normalizes Under activation in ADHD - 2 Error Detection task On MPH Frontocingulate activates Off MPH More occipital activation See Rubia K et al Meta-analysis of MPH on ADHD; Biological Psych 2013

14 Lisdexamfetamine Affect of Lisdexamfetamine on Executive Functioing Before Lisdexamfetamine After Lisdexamfetamine Before Placebo After Placebo

15 Alpha Adrenergic Agonists and antagonists and SSRI s Selective Serotonin Reuptake Inhibitors fluoxetine, sertraline, etc. Alpha 2 Agonists clonidine, guanfacine Antagonists Atypical antipsychotics: risperidone, aripiprazole Neuroleptics: gabapentin, lamotrigine

16 Cognitive Flexibility

17 Cognitive Flexibility Perspective Social Cognition Shifting Gears Anticipation

18 Stimulants Cause Cognitive Inflexibility Paradoxical effects of psychomotor stimulant drugs in hyperactive children from the standpoint of behavioral pharmacology T.W.Robbins 1 B.J.Sahakian 2

19 Selective Serotonin Reuptake Inhibitors Citalopram (Celexa) Escitalopram (Lexapro) Paroxetine (Paxil) Fluoxetine (Prozac) Fluvoxamine (Luvox) Sertraline (Zoloft) The anxiety medications can reduce the anxiety around needing to shift gears and indirectly increase cognitive flexibility The medications listed in white are more commonly used as treatments for Obsessions and Compulsions

20 Executive Function Disorders Conditions with fairly consistent EF deficits ADHD FAS ASD Conditions with less consistent EF deficits PTSD Depression Alzheimer s ODD

21 Overview of Common Medications

22 References Antidepressant Medication and Executive Dysfunction: A Deleterious Interaction in Late-Life Depression Joel R. Sneed, Ph.D.1,2, Michelle E. Culang1,2, John G. Keilp, Ph.D.2, Bret R. Rutherford, M.D.2, D. P. Devanand, M.D.2, and Steven P. Roose, M.D.2 Am J Geriatr Psychiatry February ; 18(2): 128 Hosenbocus et al.a Review of Executive Function Deficits and Pharmacological Management in Children and Adolescents J Can Acad Child Adolesc Psychiatry, 21:3, August 2012 P. Shaw et al, Proc Natl Acad Sci, 2007, 104: Rubia K et al Meta-analysis of MPH on ADHD; Biological Psych 2013