MH‐ID: Misuse of Psychotropic Medications
Jarrett Barnhill MDUNC School of Medicine
Jarrett [email protected] 19, 2013
Goals
• To explore the complex relationship between challenging behaviors and psychiatric disorders
• To look into the relationship between psychopharmacological and behavioral interventions‐ behavioral pharmacology
• Use findings from both to address the problems of treatment resistance
What We Know?
• Basic elements of brain development• Earlier onset has a greater impact of subsequent
development• Challenging behaviors are heterogeneous
conditions• Psychiatric disorders pose real challenges for
children with ID
What We Don't Know
• Causes of mental disorders and IDD • Exact mechanisms of drug action ‐ we know what
we have studied and can measure• Long term impact on brain development, especially
in young children
What We Need to Remember
• The brain is adaptive organ, is constantly rewiring itself, functions in an integrated, hierarchical fashion
• No single transmitter or lesion• Psychopharmacological agents are generally "dirty"
agents whose effects are still under investigation
Developmental Issues
• Primer on brain development ‐ it matters what, where, and when something goes awry
• Problems with defining psychiatric disorders ‐hitting a moving target
• Pharmacokinetic v. pharmacodynamics• Placebos, families, and learning curves
IDD ‐ Brain Development
• Mild ID ‐ environmental stimulation, nutrition, gestational problems, exposure to toxins (FAS), genetic disorders
• Severe ID ‐ frequent brain developmental abnormalities, epilepsy, motor disorders are more common
• Degenerative disorders may cross boundaries
Behavior and Brain Abnormalities
• Disruption of emerging skills ‐ deficits• Decreased top down regulation of affect or impulse
control ‐ excesses• Temperamental factors ‐ lesions less relevant today
than coherence issues• Behavioral phenotypes ‐ effects of specific genetic
disorders on substrate
Brain and Psychiatric Disorders
• Dual heterogeneity of psychiatric disorders, epigenesis
• Multiple brain networks and systems are involved ‐lesions rarely reproduce a primary psychiatric disorder
• Single neurotransmitter abnormalities are not causes of psychiatric disorders
• Brains disorders presentation, course, and prognosis
Another Look at Antecedents and Behavior
• Antecedents or trigger events, positive/negative experience, setting, memory, conditioning experiences, social factors
• Classical conditioning (initiating)‐ CS/CR impact motivation (escape); intensity of reward potential (approach); Temperamental and presence of psychiatric disorders
• Fear conditioning‐ LTP (panic disorder)
Other Factors Affecting Consequences
• Ease of conditioning, extinction, reversal learning• Operant learning‐ valence of reinforcer• Extinction‐ LTD (long term depression)• Extinction spurt or increased appetitive behaviors • Multiple layers of conditioning‐ panic disorder with
agoraphobia
Analysis of Function
• Function of behavior‐ arousal, reactivity, motivational state, approach‐avoidance, autonomic regulation
• Drive or craving, reward potential, hedonic drive• Neuroticism‐ emotional reactivity• Behavioral inhibition, conflict• Escape behaviors‐sensitivity, threat perception
Analysis of Functional Behavioral Analysis
• Function: approach‐avoidance, intensity of drive, valence of reinforcement, arousal, positive negative affective state
• Antecedents: assessment of stimulus/setting, pos/negaffective valence
• Behaviors: careful subtyping• Consequences: ease of reinforcement; resistance to extinction
Pharmacology of Learning
• Motivational states‐ reward potential (BFS), inhibition (BIS)• Linkage to VTA‐n accumbens: reward pathways• Septo‐hippocampal system, memory circuitry, LTP/LTD• MPF/orbital cortex‐ top down regulation • Attachment/social pathways
Theories
• Intrinsic reinforcement‐ shift from positive to negative maintenance strategies; what happens to endorphins
• Factors that trigger SIB‐ stress, urge to act, balance between aggression and SIB when restricted; craving and HPA axis
• Problem with extinction‐ requires learning at a molecular biological level, LTD; Glutamate/NMDA activity; ACTH/AVP
Challenging Behavior‐ Treatment Issues
• Limited success finding drugs for specific behaviors• Most challenging behaviors are extremely heterogeneous
conditions• Functional Behavioral Analysis is a critical step but more
information is needed• Relationship between brain function, neurochemistry, and
target behavior
Challenging Behaviors and Syndromes
• SIB• Aggression• ADHD• Tic ‐ repetitive behavior spectrum• Anxiety disorders• Mood disorders• Psychoses
SIB: A Diverse Collection of Behaviors
• Topography, typology, intensity, frequency, setting and trigger events
• Functional Behavioral Analysis is a critical tool but has limits• Relationship to genetic disorders‐ specific topographies• Developmental models‐ do not always address special
vulnerabilities
SIB: Behavioral Pharmacological Dissection
• Why do some people develop progressive SIB when others in the same environment don’t?
• Why does it persist in spite of pain, tissue destruction?• What initiates and maintains this particular typography?• What gets in the way of extinction‐ self‐restraint?
Behavioral Pharmacology of Self‐Injurious Behaviors
• Complex relationship between SIB, behavioral phenotypes, and environment
• Gene expression is continually influenced by environmental events and learning
• Temperamental style influences helps shape life experiences and learning environment
• Think in terms of an ecosystem
Behavioral Pharmacology of Self‐Injurious Behaviors
• Complex relationship between SIB, behavioral phenotypes, and environment
• Gene expression is continually influenced by environmental events and learning
• Temperamental style influences helps shape life experiences and learning environment
• Think in terms of an ecosystem
Basics of psychopharmacology
• Drug mechanisms‐more complex than originally described• Pharmacokinetics‐ how do the drugs get there; genetic
differences in rates• Pharmacodynamics‐ what the drugs do when they get there;
genetics of receptor variability• Pharmaco‐genomics
Anxiety Disorders
Anxiety: Fear
• Anxiety ‐ a ubiquitous human affective ‐cognitive response to threat
• Fears change during development• Life experiences plus temperament shape
personality• Neurobiology of threshold, reactivity, self ‐
regulation, sensitivity to distress
Anxiety Disorders
• Development, age of onset, severity • Duration or frequency of symptoms• Genetic risk ‐ OCD, panic disorder • Trauma, abuse/neglect, attachment• Regulation ‐ top down regulation of limbic system,
cortical activation
Common Anxiety Disorders
• Separation anxiety ‐ exaggerated attachment distress, age limits?
• Social anxiety ‐ social cues• Phobias ‐panic attacks‐ PTSD: fear conditioning,
sensitization• OCD, repetitive behaviors, tics• PTSD
Treatment Issues
• Attachment behaviors• Panic ‐fear ‐phobia• Anticipatory, conditioned fear• Hypervigilance GAD, social anxiety, BDD, AN• Avoidance behaviors• Mood disorders
Mood Disorders
Mood Disorders
• Biological risk factors ‐ family history, early losses • Gender differences, effects of puberty• Genetic risks ‐ BD>MDD• Polarity, severity, comorbidity, longitudinal course• Psychopharmacology
Major Depressive Disorder (MDD)
• High rates of comorbidity with anxiety disorders, CD/ADHD, trauma
• Neg affect plus anhedonia in MDD• M=F prior to puberty, high rates ADHD• 50 ‐75% relapse within 5 years• 20% develop BD
MDD‐ID
• Recognition ‐ irritability and endocrine, cortical asymmetry, epilepsy and RX
• Primary sleep v mood disorders• Life experiences, temperament, self ‐regulation,
educational/social stresses• Recurring disorder ‐ SAD, comorbid anxiety,
externalizing symptoms• Parent recognition
Treatment Approaches
• Medication trials, high placebo response, cognitive ‐interpersonal Rx
• Environmental/ecological, iatrogenic issues• SSRIs mainstay, drug interactions, disinhibition, ?
prolonged Rx course• Recurrence, duration of RX, remission
Psychotic Disorders
What are Psychoses?
• Severe disturbances in brain function• Disorders of thought, mood, behavior, motivational
states• Hallucinations, delusions, bizarreness, affective
changes• Genetic risk, timing of insults• Continuity with adult disorders
Schizophrenias
• Childhood onset forms ‐ rare • Common features with autistic spectrum disorders• Ontogeny of symptoms ‐ emergence of secondary
features• Genetic risk• Temporal profile ‐ clinical course
Treatment Issues
• Positive symptoms ‐ APDs work best • Negative symptoms ‐ EPS ‐related v. core features
schiz, cognition, chronicity• Comorbidity ‐ OC, anxiety, mood disorders,
aggression, SIB• Complications ‐ obesity, TD
What exactly is a nonresponder?
• Wrong person, wrong diagnosis or learning model, wrong drug or intervention
• Incomplete functional behavioral analysis• Incomplete understanding of the bio‐behavioral issues• Drug issues‐ wrong dose; theory of drug effect and connection
between it and behaviors is incomplete
Conclusions
• The assessment is the most important part of psychopharmacology
• Medication selection‐ evidence, experience• Limited knowledge of neuropharmacology• There are no cures, improvement is far more common than
remission‐ there are no silver bullets• More is not better• All drugs are poison with positive side effects.