ADHD and Beyond…

Shaw Wendi Fortuchang, M.D. Board certified in

Child & Adolescent, Adult, and Forensic Psychiatry

Overview • Use of medications in children

• How do medications work in the brain?

• Risperdal?

• Polypharmacy (multiple medications)?

• How much is too much?

• Best ones for Anxiety Disorders?

• Best ones for Depressive Disorders?

• ADHD?

• What works best and with the fewest side effects?

• Diagnosis of psychiatric disorders in children

• Most common diagnoses?

• Early diagnosis?

• How to differentiate amongst similar diagnoses

• Hallucinations in young children

• Do rating scales help?

• How can psychologists and other therapists help assist MD in the diagnosis?

4 Major Anatomic Systems

• Thalamus • Relays sensory information to the cortex

• Association cortex • Sensory information processing

• Medial temporal lobe • Including hippocampus and amygdala

• Basal ganglia • Voluntary motor movements

Neuron

Neurons (Nerve Cells)

• Cell Body • Where neurotransmitters and other proteins

are made

• Axon • the “output station” of the cell

• Dendrites • Provides the cell body with input from other

cells

4 Major Neurons

• Cholinergic neurons (acetylcholine) • In basal forebrain and brain stem

• Dopaminergic neurons (dopamine) • In substantia nigra and ventral tegmental area

• Noradrenergic neurons (norepinephrine) • In locus ceruleus

• Serotonergic neurons (serotonin) • In raphi nuclei

Acetylcholine

• Modulates attention, novelty seeking and memory

• Anticholinergic delirium and Alzheimer’s Dementia are examples of a cholinergic deficit state

Dopamine

• Associated with the “reward center” of the brain

• Both older and newer antipsychotics involve blockade of DA transmission, since psychosis is associated with INCREASED dopamine activity

• Methylphenidate and Amphetamine enhance the release of dopamine from the ventral tegmental area, since ADHD is associated with DECREASED dopamine activity

Serotonin

• Modulation of its receptors and the reuptake site have been beneficial in treating depression, anxiety, OCD, and schizophrenia

• Plays important roles in sleep, mood, appetite, perception, and hormone secretion, as well as neurodevelopment

Norepinephrine

• Modulates sleep cycles, appetite, mood, and cognition by targeting the thalamus, limbic structures and cortex

Diagnoses

ADHD

• Involves inattention and distraction, with or without hyperactivity-impulsivity

• 6 or more symptoms for at least 6 months, occurring in more than 1 setting, and prior to age 12

• Symptoms do not occur exclusively during a psychotic disorder, and are not better explained by another Dx

• Studies indicate both DA and NE deficiencies in these patients

• Family and twin studies strongly indicate the inheritability of the disorder

Depressive Disorders • Disruptive Mood Dysregulation Disorder

• Major Depressive Disorder

• Persistent Depressive Disorder (Dysthymia)

• Premenstrual Dysphoric Disorder

• Substance/Medication-Induced Depressive D/O

• Depressive D/O Due to Another Medical Condition

• Other Specified Depressive Disorder

• Unspecified Depressive Disorder

Major Depressive Disorder

• SSIGECAPS • Suicidal thoughts • Sad or depressed mood • Interest and pleasure markedly decreased • Guilt, worthlessness • Energy markedly decreased, fatigue • Concentration/thinking difficulties • Appetite decreased OR increased; or wt loss or gain • Psychomotor changes (agitation or retardation) • Sleep (insomnia or hypersomnia)

Depressive Disorders

• Childhood Clinical Presentation • Irritability, low frustration tolerance, temper

tantrums, somatic complaints, social withdrawal, “acting out,” school refusal, FTT

• Adolescent Clinical Presentation • Anger, academic problems, behavioral changes,

recklessness, social withdrawal, giving away valuables, frequent school absences, more melancholic symptoms, more suicide attempts and delusional symptoms than seen in children

Disruptive Mood Dysregulation Disorder

• Was created and added to the DSM-V to better encapsulate a subset of children with persistent, chronic, consistently irritable mood WITHOUT a previously diagnosed manic/hypomanic episode

• Was done following an upswing in the numbers of pediatric bipolar disorder diagnoses with the DSM-IV TR and earlier

Bipolar Disorders • Bipolar I Disorder

• Bipolar II Disorder

• Cyclothymic Disorder

• Substance/Medication-Induced Bipolar and Related Disorder

• Bipolar and Related Disorder Due to Another Medical Condition

• Other Specified Bipolar and Related Disorder

• Unspecified Bipolar and Related Disorder

Mania and Hypomania

• DIGFAST • Distractibility • Increased goal-directed activity or psychomotor

agitation • Grandiosity • Flight of ideas, racing thoughts • Activities with high potential for negative

consequences • Sleep • Talkativeness

Anxiety Disorders • Most common of all childhood psychiatric diagnoses

• 15-20% of children will develop anxiety if their parents have it (anxious parents tend to beget anxious children)

• Preschool • Separation Anxiety Disorder

• School Age • Specific Phobia (fearful of dark, monsters, insects) • GAD • Selective Mutism • OCD

• Adolescence • Social Anxiety Disorder • Panic Disorder

Behavioral Disorders

• Oppositional Defiant Disorder

• Conduct Disorder

• Other Specified Disruptive, Impulse-Control and Conduct Disorder

• Unspecified Disruptive, Impulse-Control, and Conduct Disorder

Schizophrenia Spectrum and Other Psychotic Disorders

• Delusional Disorder

• Brief Psychotic Disorder

• Schizophreniform Disorder

• Schizophrenia

• Schizoaffective Disorder

• Substance/Medication-Induced Psychotic D/O

• Psychotic Disorder Due to Another Medical Condition

• Other Specified Schizophrenia Spectrum and Other Psychotic D/O

• Unspecified Schizophrenia Spectrum and Other Psychotic Disorder

Psychotic Disorders

• Delusions are less complex in children versus adults

• Hallucinations are less elaborate in children

• Most children who report hallucinations do NOT have schizophrenia

• Childhood onset cases resemble poor-outcome adult cases • Gradual onset and prominent negative symptoms

• These children are more likely to have experienced nonspecific emotional-behavioral disturbances and psychopathology, intellectual and language alterations, and subtle motor delays

Autism Spectrum Disorder

• With or without accompanying intellectual impairment

• With or without accompanying language impairment • 25% begin talking after diagnosis; 75% remain severely impaired

• Social Interaction

• Social Communication

• Behaviors

• Varying degrees of severity • Level 1 • Level 2 • Level 3

• Adolescents and adults are prone to anxiety and depression

Anxiety versus Depression

• GAD and worry are common features of depressive, bipolar and psychotic disorders, and should NOT be separately diagnosed if excessive worry occurs during the course of these conditions

MDD versus ADHD

• Both can have distractibility and low frustration tolerance, but if criteria are met for both, then both diagnoses should be made

• Caution should be taken not to overdiagnose a MDE in children with ADHD whose mood disturbance is irritability versus sadness or loss of interest

ADHD versus Bipolar D/O

• ADHD is common in preadolescents, whereas bipolar disorder is rare in this age group

• Children with ADHD may exhibit significant mood changes within the same day, which is different from mood lability associated with mania, which must last 4 days or longer for the bipolar disorder diagnosis

DMDD versus Bipolar D/O

• Should not be diagnosed for the first time younger than age 6 yrs or older than age 18 years

• Consistent pattern of irritable mood, not episodic mood changes like with Bipolar Disorder

• DMDD cannot be diagnosed in a child who has ever experienced a manic/hypomanic episode lasting > 1 day or a full manic/hypomanic episode

• DMDD is not associated with grandiosity and expansive or elevated mood

DMDD versus ODD

• DMDD children have mood symptoms not typically seen in children with ODD

• While most children with DMDD have symptoms consistent with ODD, the reverse is not true

• In children with diagnostic criteria for both disorders, only the diagnosis for DMDD should be made

Comorbidities

• ADHD • ODD, CD, DMDD, SUD, specific learning disorder

• Depressive Disorders • SUD, Panic D/O, OCD, AN, BN, Borderline PD

• Anxiety Disorders • Other Anxiety D/O, MDD, SUD

• Bipolar Disorder • Anxiety D/O, ADHD, Disruptive Impulse Control D/O, CD, SUD

• Psychotic Disorders • SUD (++nicotine), Anxiety D/O (++OCD and Panic D/O)

Sleep plays a major role!

• Poor sleep negatively impacts mood, concentration, frustration tolerance, cognitive abilities/academic performance, appetite, level of motivation and psychomotor movement

• Poor sleep can mimic and mask various psychiatric diagnoses

• GOOD SLEEP HYGIENE IS ESSENTIAL

Use of Psychotropic Medication in Children

START LOW AND

GO SLOW!

Effects of Medication

• Pharmacokinetics • Describes what the body does to a drug • ADME (absorption, distribution, metabolism,

excretion)

• Pharmacodynamics • Describes what the drug does to the body • Involves the short and long-term effects of

drugs on neuronal function and structure

ADHD Medications

• Stimulants • Gold Standard for treatment of ADHD

• Non-Stimulants • Use when patient cannot tolerate a stimulant

Stimulants

• Methylphenidate • Dexedrine • Ritalin • Focalin • Concerta • Daytrana patch

• Amphetamines • Adderall • Vyvanse • Amphetamine salts

Methylphenidate VS Amphetamines

• Both enhance the release of DA

• Amphetamines also inhibit the reuptake of DA

• Typical side effects of stimulants: • Appetite suppression weight loss • Insomnia • Mild headache

Non-Stimulant Meds

• Strattera • Selectively blocks reuptake of NE • NE reuptake inactivates DA, therefore can increase

DA transmission in the frontal cortex NOT limbic areas

• 0.5-1.2mg/kg/day in children up to 70kg • 40-100mg/day in adults • Typical side effects • Sedation and fatigue • Decreased appetite • Can also autonomic effects of increased NE (BP,HR)

Non-Stimulant Meds

• Blood Pressure Medications

• Work by acting on post-synaptic alpha-2 receptors in the prefrontal cortex

• Typical side effects are dry mouth, sedation, dizziness, rebound effects if not tapered slowly • Clonidine • 0.1-0.4mg/day in divided doses

• Tenex • 1-2mg/day

• Intuniv (long-acting formulation) • 1-4mg/day

Antipsychotics

• Typically used for mood stabilization and anger in children, but also for psychosis, Tic Disorders and irritability associated with Autism Spectrum Disorders • Risperdal • Abilify • Zyprexa • Seroquel • Haldol • Geodon

Abilify

• DA partial agonist

• Reduces DA output when levels are high improving positive symptoms of schizophrenia

• Increases DA output when levels are low improving cognitive, negative and mood symptoms

• Blockade of serotonin receptors improve cognitive and affective symptoms

Abilify

• FDA-approved for schizophrenia ages 13 >, acute and mixed mania ages 10>, autism-related irritability ages 6-17

• Typical side effects: • Dizziness, insomnia, akathisia, activation, NV

• 15-30mg/day for schizophrenia and mania

• 2-10mg/day when used with SSRI or SNRI

• Remember, LOW AND SLOW with children

Risperdal

• Second-generation, atypical antispychotic

• Most commonly used antipsychotic in children

• FDA-approved for schizophrenia (ages 13>), manic and mixed-manic states (ages 10>), and irritability associated with ASD in children (ages 5-16)

• Blocks DA disinhibition of prolactin hyperprolactinemia breast enlargement and galactorrhea

• At high doses, functions like Haloperidol

Risperdal

• Blocks alpha 1 receptors dizziness, sedation, hypotension

• Blocks DA2 in striatum motor side effects

• Blocks DA2 receptors in pituitary gland elevations in prolactin

• Usual dose range for children is 0.5-2mg/day

• Like all atypical antipsychotics, can result in the development of Metabolic Syndrome

Metabolic Syndrome

• A group of risk factors associated with atypical antipsychotics that increase a patient’s chances of heart disease, DM, stroke, etc

• Need at least 3 risk factors for the diagnosis: • Large waistline • Increased triglycerides in blood • Decreased HDL (the “good” cholesterol) • Increased blood pressure • Increased fasting blood glucose

Antidepressants

• SSRI’s are gold standard, and are the most researched in children • Prozac, Celexa, Lexapro, Paxil, Zoloft

• 2 have been FDA-approved • Prozac • Lexapro

• Wellbutrin, Remeron, Effexor, Pristiq

FDA-approval for acute treatment of

Bipolar 1 Disorder, Mixed or Manic Episode

• Abilify (10 years and older)

• Risperdal (10 years and older)

• Seroquel (10 years and older)

• Lithium (12 years and older)

• Zyprexa (13 years and older)

Mood Stabilizers

• Lithium • Gold Standard for Bipolar Disorder

• Anti-Convulsant Medications • Depakote • Lamictal • Trileptal

• Anti-Psychotic Medications • Abilify • Risperdal • Zyprexa

FDA-Indications

• Zoloft • OCD, 6 years and older

• Prozac • OCD, 7 years and older • MDD, ages 8 and older

• Luvox • OCD, 7 years and older; both formulations • SAD; CR formulation

• Clomipramine • OCD, 10 years and older

• Lexapro • MDD, ages 12 years and older

Anxiolytics

• SSRIs medication class of choice in children • Prozac • Zoloft • Lexapro • Luvox

• Clomipramine

• Buspar

• Benzodiazepines • Treatment of last resort

Clinical Research and Evidence-Based Treatment

TADS Study

• Treatment for Adolescents with Depression Study

• Study involving the improvement/response rate of CBT with and without fluoxetine

• Revealed that both CBT + fluoxetine demonstrated the best treatment outcome

• By week 18 of the trial, CBT alone and fluoxetine alone had comparable response rates

• By week 36, all three parameters had similar response rates

TORDIA Study

• Treatment of SSRI-Resistant Depression in Adolescents

• CBT + meds was superior than meds alone

• No overall difference between SSRI and Venlafaxine

CAMS Study

• Child/Adolescent Anxiety Multimodal Treatment Study

• Similar in structure to TADS

• Indicated that combined treatment (CBT + sertraline) was superior to both meds alone and CBT alone

POTS Study

• The Pediatric OCD Treatment Study

• Combined treatment (CBT + meds) superior to either meds alone or CBT alone

• Weeks 4-8 indicated sertraline was more effective than CBT

• By week 12, CBT was slightly more effective than sertaline alone

How can we help?

• Rating scales

• Knowing what to look for

• MSE pertinent positives

• Rapport with patient to establish trust

• Your endorsement of medication-- if needed

References • Martin A, Volkmar FR: Lewis’ Child and Adolescent Psychiatry, A

Comprehensive Textbook. Philadelphia: Lippincott, Williams and Wilkins; 2007

• American Physician Institute for Advanced Professional Studies: Beat The Boards! 2012 Child and Adolescent Psychiatry Part 1 Exam Prep Course.

• Schatzberg AF, Nemeroff CB: Essentials of Clinical Psychopharmacology. Arlington: American Psychiatric Publishing; 2013

• Stahl SM: Stahl’s Essential Psychopharmacology Prescriber’s Guide. New York: Cambridge University Press; 2014

• DSM-V