PMHNP 7348.01 Final

After taking an antidepressant for about a week, a patient reports constipation and blurred vision, with no improvement in mood. The psychiatric and mental health nurse informs the patient:

"It takes approximately two to four weeks for depression to lessen, and side effects usually diminish over time."

Repetitive and Stereotypic Behavior: Mood Stabilizers

- Depakote- those who showed less irritability on Depakote also spent less time on repetitive behaviors

Benzodiazepine Tips: When prescribing for the first time

- Initiate with lowest recommended dose - Do not prescribe longer than 4 weeks • It is an as needed medication. Consider prescribing 20 pills if you are only prescribing daily PRN, etc.

Repetitive and Stereotypic Behavior: SSRI

- Prozac- statistically significant difference in repetitive behaviors • May be helpful for OCD like behaviors - Lexapro/Celexa- no difference between placebo

Repetitive and Stereotypic Behavior: Atypical Antipsychotics

- Risperdal- when it reduces irritability it can also be helpful for repetitive behaviors

Benzodiazepine Tips: Before prescribing:

- Very detailed drug history including alcohol - Consider and treat, if possible the underlying cause - Consider referral to other services - Consider delaying prescribing for another visit

Benzodiazepines and Pediatrics

- Xanax (alprazolam) - Klonopin (clonazepam) - Ativan (lorazepam) • Not FDA approved for use in childhood anxiety • Effect - Decreases anxiety quickly • Used - When starting SSRI's (which take longer to work) - Acute anxiety (ie-plane phobia)

Maximum recommended dose of citalopram

20 mg for patients >60 years of age, with significant hepatic insufficiency, or taking interacting medications that can increase citalopram levels. Never Exceed 40 2' Cardiac Dysrythhmias

Fluoxetine (Prozac) Depression/Anxiety Dose

20-80mg for depression/anxiety

All Immediate Release Duration Rule of Thumb

3-4 except Adderall 4-6

NAC dosing may vary between pediatric and adult populations. Which dose did Vonda say she typically started in the pediatric population?

300mg one cap PO qD

In Separation Anxiety, the fear, anxiety, or avoidance is persistent, lasting at least ____ weeks in children and adolescents.

4 weeks

How long must the symptoms of GAD be present in order to make the diagnosis?

6 months

Fluoxetine (Prozac) Bulimia Dose

60-80mg for bulimia Tablet, capsule, and oral solution) 60 mg orally once daily in the morning; may initiate at a lower dose and titrate up over several days; doses greater than 60 mg/day have not been evaluated

All Immediate Extended Duration Rule of Thumb

8-10-12

ACE score Adverse Childhood Experiences Study

>3 concerning Ie. Score of 4, seven fold increase in risk of alcoholism (700%), score >6 thirty fold increase in attempted suicide (3000%), 46x more likely to use IV drugs!!!!

kindling effect

A phenomenon in the brain that produces a heightened sensitivity to repeated administrations of some drugs, such as cocaine. This heightened sensitivity is the opposite of the phenomenon of tolerance.

Pediatric PTSD: DSM-V Criteria A.

A. Children under the age 6 have been exposed to an event involving real or threatened death, serious injury, or sexual violence in at least one of the following ways: The child directly experienced the event. The child witnessed the event, but this does not include events that were seen on television, in movies or some other form of media. The child learned about a traumatic event that happened to a caregiver. Or close friend (Violent or accidental) Experiencing repeated or extreme exposure to aversive details of the traumatic event

SSRI's Pearls Anxiety Dosing

AM dosing can make a big difference, initiate low doses w/ anxiety disorders

Dextroamphetamine and amphetamine salt combinations Extedned Release Duration

Adderall XR 4- 12

Amphetamine x3 preparations Short-acting

Adderalla 5, 7.5, 10, 12.5, 15, 20, 30 mg tab Dexedrine 5 mg cap DextroStat 5, 10 mg cap

In young children, some of the most common symptoms of depression include:

Aggression Guilt Anger Excessive crying

PTSD (Post Traumatic Stress Disorder)

An anxiety disorder characterized by haunting memories, nightmares, social withdrawal, jumpy anxiety, and/or insomnia that lingers for four weeks or more after a traumatic experience

PTSD Treatment: Medications Anti-anxiety medications

Anti-anxiety medications These drugs can relieve severe anxiety and related problems.

PTSD Treatment: Medications Antidepressants.

Antidepressants These medications can help symptoms of depression and anxiety. They can also help improve sleep problems and concentration. The selective serotonin reuptake inhibitor (SSRI) medications sertraline (Zoloft) and paroxetine (Paxil) are approved by the Food and Drug Administration (FDA) for PTSD treatment

Buspirone (BUSPAR) FDA Approved

Anxiety Disorders • Non-FDA Approved - Treatment-resistant depression (adjunctive)

There are many types of psychosocial interventions for Autism, but many use principles from

Applied Behavior Analysis

Selective Norepinephrine Reuptake Inhibitors (SNRIs) for ADHD

Atomoxetine Strattera 10, 18, 25, 40, 60, 80, 100 mg cap

Pediatric PTSD: DSM-V Criteria B.

B. The presence of at least one of the following intrusive symptoms that are associated with the traumatic event and began after the event occurred: Recurring, spontaneous, and intrusive upsetting memories of the traumatic event. ** In children older than 6y, repetitive play may occur in which themes or aspects of the trauma are expressed** 2. Recurring and upsetting dreams about the event. ** In children, there may be frightening dreams without recognizable content** 3. Flashbacks or some other dissociative response where the child feels or acts as if the event were happening again. ** In children, trauma-specific reenactment may occur in play** 4. Strong and long-lasting emotional distress after being reminded of the event or after encountering trauma-related cues. 5. Strong physical reactions, like increased heart rate or sweating, to trauma-related reminders.

Atypical Antidepressants x3

Bupropion (Wellbutrin) + Mirtazapine (Remron) + Trazadone

Risk of Neuropsychiatric Events with

Bupropion (Wellbutrin) has been reported to cause neuropsychiatric events when used for smoking cessation. Symptoms associated with these events include behavioral changes, agitation, depression, hostility, and suicidality. Patients and caregivers should be instructed to discontinue bupropion and to contact a healthcare provider if any of these symptoms occur

Atypical Antidepressants Initial Staring Dose Bupropion (Wellbutrin)

Bupropion 200 Bupropion SR 12 hour 150 Bupropion XL 24 hour 150 Bupropion hydrobromide 24 hour 174

Atypical Antidepressants Max Dose Bupropion (Wellbutrin)

Bupropion Daily Max 300 (maximum single dose 150 mg) Extreme Max 450 Bupropion SR 12 hour Daily Max 300 (maximum single dose 200 mg) Extreme Max 400 Bupropion XL 24 hr Daily Max 300 Extreme MAx 150 to 450 (United States) Bupropion hydrobromide 24 hour Daily 348 Extreme Daily 522

Antidepressant + Seizure Risk

Buproprion (Wellbutrin) The risk for seizures appears to be dose related, but is also related to patient factors, clinical condition, and concomitant medications. If a patient experiences a seizure while taking bupropion, the medication should be discontinued and should not be restarted.

Which antidepressant is used for ADHD?

Buproprion (Wellbutrin) = Atypical Antidepressant Tricyclic antidepressant (TCA), however, tricyclic antidepressants are less effective than stimulants and more poorly tolerated than stimulants, atomoxetine, or bupropion.

Pediatric PTSD: DSM-V Criteria C.

C. The child exhibits at least one of the following avoidance symptoms or changes in his or her thoughts and mood. These symptoms must begin or worsen after the experience of the traumatic event. 1. Avoidance of or the attempted avoidance of activities, places, or reminders that bring up thoughts about the traumatic event. 2. Avoidance of or the attempted avoidance of people, conversations, or interpersonal situations that serve as reminders of the traumatic event. 3. More frequent negative emotional states, such as fear, shame, or sadness. 4. Increased lack of interest in activities that used to be meaningful or pleasurable. 5. Social withdrawal. 6. Long-standing reduction in the expression of positive emotions.

SSRI's Pearls Metabolism

CYP450 system: Lexapro/Celexa not metabolized in this pathway Zoloft minimal at 2D6 & 3A4, more at 2c9/19 Paxil strong 2D6 inhibitor Prozac mild to moderate at all pathways

SNRI Pearls ADHD

Can also be helpful for ADHD symptoms

SNRI Pearls DOSE & SWITCH

Can be lethal in overdose When to switch to SNRI Methods for switching Direct switch, wean and restart, cross tapering Chart from UpToDate on comparison dosages

Bupropion (Wellbutrin) anxiety

Can cause increased anxiety

SSRI's Pearls Celexa

Celexa with FDA max 40 mg but >60 year old 20 mg max EKG for QTc prolongation

ll of the following are changes that were made to the DSM V regarding ADHD?

Changed age of onset to 12 CAN have Autism and ADHD and added symptoms across the lifespan since we know ADHD does not go away Can have ADHD and ODD comorbid. Also included in DSM under ADHD comorbidity- discusses that ADHD and ODD are comorbid 50% of the time modifiers were added so that the severity of the disorder (i.e., mild, moderate, or severe) can be specified and the disorder can be coded as "in partial remission"

Serotonin Reuptake Inhibtors SSRI Initial starting dose Citalopram (Celexa)

Citalopram 20

Serotonin Reuptake Inhibtors SSRI Max Dose Citalopram (Celexa)

Citalopram Max Dose 20 to 40Δ Extreme Max 40Δ Δ Maximum recommended dose of citalopram is 20 mg for patients >60 years of age, with significant hepatic insufficiency, or taking interacting medications that can increase citalopram levels.

Hyperactivity, Impulsivity and Inattention in ASD: Alpha-Agonists

Clonidine and Guanfacine- may be helpful? Mixed results - Side Effects: irritability, fatigue, hypotension

Obsessive-Compulsive Disorder: Compulsions

Compulsions: Repetitive behaviors (e.g., hand washing, ordering, checking) or ,emtal acts (e.g., praying, counting, repeating words silently) that the person feels driven to perform in response to an obsession, or according to rules that they must applied rigidly. The behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation. Can be cery excessive Time consuming (more than one hour per day)

SNRI Pearls chronic pain

Cymbalta for chronic pain but NO liver disease or hx of or current ETOH use

Pediatric PTSD: DSM-V Criteria D.

D. The child experiences at least one of the below changes in his or her arousal or reactivity, and these changes began or worsened after the traumatic event: 1. Increased irritable behavior or angry outbursts. This may include extreme temper tantrums. 2. Hypervigilance, which consists of being on guard all the time and unable to relax. 3. Exaggerated startle response. 4. Difficulties concentrating. 5. Problems with sleeping. In addition to the above criteria, these symptoms need to have lasted at least one month and result in considerable distress or difficulties in relationships or with school behavior. The symptoms also cannot be better attributed to ingestion of a substance or to some other medical condition.

Which of the following may be an appropriate form of therapy for a pediatric client with a h/o trauma or PTSD

DBT Trauma-focused CBT EMDR

ADHD treatment is associated with a ...

Decrease in accidental injury and medical utilization due to accidents and trauma

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) x5

Desvenlafaxine (Pristiq) Duloxetine (Cymbalta) Levomilnacipran (Fetzima) Milnacipran (Savella) Venlafaxine (Effexor)

2 SNRI's that cause Hypertension

Desvenlafaxine (Pristiq) + Venlafaxine (Effexor) The increase in blood pressure appears to be dose related. Patients with preexisting hypertension should have their blood pressure controlled prior to initiation of therapy with venlafaxine or desvenlafaxine, and should be routinely monitored throughout treatment. If a patient experiences an increase in blood pressure, the dose should be decreased or the medication should be discontinued.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) Initial starting dose Desvenlafaxine (Pristiq)

Desvenlafaxine 25 to 50

SNRI's Daily Max Dose Desvenlafaxine (Pristiq, Khedezla)

Desvenlafaxine Daily MAX 50 to 100 Extreme MAX 400

Adjustment disorder DSM-V

Development of emotional or behavioral symptoms in response to an identifiable stressor within 3 months of the onset of the stressor Clinically significant Marked distress out of proportion Impairment in functioning Can not meet criteria for other mental health disorder and not an exacerbation of a preexisting mental health disorder Not bereavement One stressor or consequences have been terminated, the symptoms do not persist for more than 6 months EX: divorce, job loss, empty nest

CAM ASD: Diets

Diets - GFCF- some efficacy, but poor study design, very hard to stick to - Camels milk- less fat and more nutrients- placebo controlled trials showed some efficacy

There have been reports of hepatotoxicity in patients taking which SNRI's

Duloxetine (Cymbalta) Cases of liver failure have also been reported. Duloxetine should be discontinued if jaundice develops or if there are other indications of liver dysfunction. Patients with evidence of liver disease or who consume significant amounts of alcohol should not be prescribed duloxetine.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) Initial starting dose Duloxetine (Cymbalta)

Duloxetine 30 to 60

SNRI's Daily Max Dose Duloxetine (Cymbalta)

Duloxetine Daily MAX 60 to 120 Extreme Daily MAX 120

Hyperactivity, Impulsivity and Inattention in ASD: Methylphenidate

Effective, but less effective than they are with just ADHD alone - Children with ASD prone to more irritability from stimulants - Side Effects: Increased stereotypies, GI upset, sleep problems and emotional lability

"cleanest" SSRI

Escitalopram (Lexapro)

Serotonin Reuptake Inhibtors SSRI Initial starting dose Escitalopram (Lexapro)

Escitalopram 10

Serotonin Reuptake Inhibtors SSRI MAX Dose Escitalopram (Lexapro)

Escitalopram Max Dose 10 to 20 Extreme Max 30

Anxiety disorders DSM-V: Generalized Anxiety Disorder (GAD)

Excessive anxiety and worry occurring more days than not for at least 6 months about a number or events or activities Difficulty controlling the worry Associated with 3 of more of the following : Restlessness, keyed up or on edge feelings Fatigue Difficulty concentrating or mind going blank Irritability Muscle tension Sleep disturbances Causing clinically significant distress & impairment in functioning Not do to the effects of a substance, general medical condition or other mental illness

If a child is experiencing Selective Mutism, they are usually able to speak at school amongst their friends.

False

In the treatment for cocaine use disorders, antabuse has robust efficacy in numerous peer reviewed articles.

False

Fluoxetine (Prozac) Frist line treatment x2

First line medication with Child/Adolescent Psychiatrists First line treatment for Intermittent Explosive Disorder

SSRIs and pregnancy

First trimester exposure to SSRIs is associated with a low risk of teratogenicity, and individual SSRIs as well as SSRIs as a group are not considered major teratogens. Although some data suggest that SSRIs (particularly paroxetine) may be associated with a small absolute increase in congenital heart defects, several studies have found no such association. We do not consider one SSRI to be safer or less safe than another to use during pregnancy, with the possible exception of paroxetine.

Which SSRI may be better for clients who have intermittent/poor adherence?

Fluoxetine

Fluoxetine (Prozac) + Depressed bipolar I disorder

Fluoxetine (Prozac) + Olanzapine (Zyprexa) Initial, 20 mg orally once daily in the evening in combination with olanzapine 5 mg; titrate to clinical effect and tolerability within the dose range, fluoxetine 20 to 50 mg/olanzapine 5 to 12.5 mg orally once daily each evening; safety of doses greater than fluoxetine 75 mg/olanzapine 18 mg has not been established.

Serotonin Reuptake Inhibtors SSRI Initial starting dose Fluoxetine (Prozac)

Fluoxetine 20

Serotonin Reuptake Inhibtors SSRI Max Dose Fluoxetine (Prozac)

Fluoxetine Max Dose 20 to 60 Extreme Max 80

SSRI's + Risk of Cardiac Arrhythmias w/

Fluoxetine and Citalopram Two recent FDA Drug Safety Communications have been published to notify patients and healthcare providers about the potential risk of abnormal heart rhythms with fluoxetine and with high doses of citalopram. Citalopram has been shown to cause prolongation of the QT interval and fluoxetine has been associated with reports of post-marketing cases. Patients with underlying heart conditions, hypokalemia, or hypomagnesemia are at risk of developing prolongation of the QT interval, which may lead to Torsade de Pointes.

Serotonin Reuptake Inhibtors SSRI Initial Starting Dose Fluvoxamine (Luvox)

Fluvoxamine 50 Fluvoxamine CR 100

Serotonin Reuptake Inhibtors SSRI Fluvoxamine (Luvox) Max Dose

Fluvoxamine Daily Max 50 to 200 Extreme Max 300 Fluvoxamine CR Daily Max 100 to 200 Extreme Max 300

Alprazolam is thought to exert its anxiolytic effects by acting on _________ and inhibiting activity in the _________.

GABA-A, amygdala

Anxiety

GAD-7, PDSS (Panic Disorder Severity Scale) Screen patients w/ depression Patients will typically c/o anxiety symptoms (but may not depression) Associated physical symptoms Nausea, HA, muscle tension, sleep issues, GI symptoms, pain Medical history Thyroid, parathyroid, cardiac arrhythmia, COPD, asthma, CAD, epilepsy, TIA Medications and substance use Illicit drugs, caffeine, albuterol, prednisone, levothyroxine, decongestants, Withdrawal from substances

Symptoms of anxiety and panic are associated with a low level of which neurotransmitter?

Gamma-aminobutyric acid

In depressed adolescents, which therapies have evidence of efficacy from RCTs?

IPT CBT

CAM ASD: L-Carnosine

L-Carnosine - Improved receptive speech and social behavior with no side effects

Which characteristic of fluoxetine (Prozac) provides the greatest degree of safety for patients who have severe anxiety and panic attacks?

Less potential for injury with intentional overdose

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) Initial starting dose Levomilnacipran (Fetzima)

Levomilnacipran 20

SNRI's Daily Max Dose Levomilnacipran (Fetzima)

Levomilnacipran Daily Max 40 to 80 Extreme Daily 120

SSRI's Pearls safest

Lexapro and Zoloft safest

Hyperactivity, Impulsivity and Inattention in ASD: Atomoxetine (Strattera)

Limited evidence but may be effective - Side Effects: nausea, anorexia, fatigue

Vilazadone (Viibryd) FDA Approved x1 + 2

MDD Non-FDA - Anxiety - Obsessive compulsive Disorder

Citalopram (Celexa) FDA Approved x7

MDD Other uses PMDD OCD Panic Disorder GAD PTSD Social Anxiety Disorder

Vortixetine (Trintellix) FDA Approved x1 + 3

MDD • Non-FDA Approved - Generalized Anxiety Disorder - Cognitive symptoms associated with depression - Geriatric depression

Duloxetine (Cymbalta) FDA Approved x5 + 3

MDD Diabetic peripheral neuropathic pain Fibromyalgia GAD Chronic musculoskeletal pain • Non-FDA approved - Stress urinary incontinence - Neuropathic pain/chronic pain - Other anxiety disorders

Escitalopram (Lexapro) FDA Approved x2

MDD GAD • Non-FDA Approved Panic OCD PTSD Social Anxiety Disorder PMDD

Venlafaxine (Effexor) FDA Approved x4

MDD GAD Social anxiety disorder panic disorder

Paroxetine (Paxil) FDA approved x7

MDD OCD Panic Disorder Social Anxiety PTSD GAD PMDD

Fluoxetine (Prozac) FDA Approved x6

MDD Panic Disorder OCD Premenstrual Dysphoric Disorder Bulimia Nervosa Bipolar Depression (with olanzapine)

Sertraline (Zoloft) FDA Approved x8

MDD Panic Disorder PMDD PTSD Social Anxiety Disorder Social phobia OCD Generalized anxiety disorder

Bupropion FDA Approved x3 + 3

MDD Seasonal Affective Disorder Nicotine Addiction Non FDA approved Bipolar Depression ADHD Sexual Dysfunction • Immediate release, sustained action and XL formulations

Mirtazapine (Remeron) FDA Approved x1 + 3

MDD • Non-FDA Approved Panic Disorder GAD PTSD

Diagnostic Criteria for Agoraphobia include which of the following:

Marked anxiety or fear of standing in line Marked anxiety or fear of using public transportation

Social Anxiety Disorder (Social Phobia)

Marked fear or anxiety about 1 or more social situations in which the patient is exposed to possible scrutiny by others: social interactions, being observed, and performing in front of others The patient fears that they will act in a way or show anxiety symptoms that will be negatively evaluated Social situations almost always provoke fear or anxiety, avoided or endured with intense fear or anxiety, out of proportion, persistent, significant distress, not substance induced, not better explained by another mental health condition If another medical condition is present, the fear, anxiety, or avoidance is clearly unrelated or excessive (Parkinson's disease, obesity) Performance only: if the fear is restricted to speaking or performing in public

Agoraphobia

Marked fear or anxiety about 2 or more of the following: Public transportation Open spaces Enclosed spaces Standing in line or being in crowd Outside of the home alone Due to thoughts that escape might be difficult or help may not be available in the event of developing panic like symptoms or other incapacitating or embarrassing symptoms Almost always provoke fear, actively avoided or require companion, out of proportion, persistent, significant distress, If panic disorder is also present, both can be coded

Agoraphobia

Marked fear or anxiety about 2 or more of the following: Public transportation Open spaces Enclosed spaces Standing in line or being in crowd Outside of the home alone Due to thoughts that escape might be difficult or help may not be available in the event of developing panic like symptoms or other incapacitating or embarrassing symptoms Almost always provoke fear, actively avoided or require companion, out of proportion, persistent, significant distress, If panic disorder is also present, both can be coded

Specific Phobia

Marked fear or anxiety about specific object or situation Almost always provokes this fear or anxiety immediately Actively avoided or endured with intense fear or anxiety Out of proportion to actual danger Persistent, usually >6 months or longer Clinically significant distress & not explained by another mental health disorder Code based on stimulus Animals, natural environment, blood injection injury, situational, other (choking/vomiting, loud sounds, costumed characters)

Drug interactions with lithium

Medications that change renal function, salt balance, or water balance can alter lithium excretion and serum lithium concentrations. Watch HTN/diuretics

CAM ASD: Melatonin

Melatonin: Another study showed that it increased eye gaze compared to placebo - Good for reducing sleep-onset latency - Not much research but recommend taking it at least 1-2 hours before bed. Sometimes earlier

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) Initial starting dose Milnacipran (Savella)

Milnacipran 12.5

SNRI's Daily Max Dose Milnacipran (Savella)

Milnacipran Daily Max 100 to 200 Extreme Max 300

"California rocket fuel"

Mirtazapine + SNRI/Augments well with Venlafaxine (multiple mechanisms to increase NE)

Atypical Antidepressants Initial Staring Dose Mirtazapine (Remron)

Mirtazapine 15

Atypical Antidepressants Max Dose Mirtazapine (Remron)

Mirtazapine Max Daily 15 to 45 Extreme MAX60

SNRI Pearls BP

Monitor BP, especially when pushing dosages & combination w/ other meds

GAD Time Frame

More days than not for at least 6 months

Irritability in ASD Risperidone (Risperdal)

Multiple RCTs Risperdal led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior but made no changes to deficits in social interaction and communication Side effects: Increased appetite and weight gain, prolactin elevation, hyperglycemia, hyperlipidemia, drowsiness, sedation, orthostatic hypotension

CAM ASD: N-acetylcysteine

N-acetylcysteine - Can help to reduce symptoms of irritability when paired with Risperdal

N-Acetylcysteine for Refractory OCD

N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: A randomized, double- blind, placebo-controlled trial. NAC- 1.Derivative of cysteine 2.With glutamate-modulating properties, 3.Provides modest benefits to patients who are symptomatic after an initial antidepressant trial Response (≥35% reduction in Y-BOCS score) was significantly greater with NAC (53%) than placebo (15%).

Interaction of NE and Serotonin

NE can boost 5HT release via an excitatory input from the locus coeruleus projecting to the raphe and acting at alpha 1 receptors on serotonergic cell bodies and dendrites in the raphes. NE can also reduce 5HT release via an inhibitory input from NE nerve terminals acting at 5HT nerve terminals on alpha 2 receptors on serotonin axon terminals (5HT brake)

Serotonin modulators x4

Nefazodone (Serzone) Trazodone (Desyrel) Vilazodone (Viibryd) Vortioxetine (Trintellix)

Serotonin modulators Initial Starting Dose Nefazodone (Serzone)

Nefazodone 200

Serotonin modulators Max Dose Nefazodone (Serzone)

Nefazodone‡ Max Daily 300 to 600 Extreme Max 600

SSRI's and low birth weight

Observational studies of pregnant women have consistently found that exposure to SSRIs is associated with preterm birth (eg, <37 weeks gestational age), and a small reduction in gestational age at birth that is probably not clinically significant. It is not clear if SSRIs are associated with low birth weight.

Obsessive-Compulsive Disorder: Obsessions

Obsessions: Recurrent and persistent thoughts, impulses, or images that are experienced at some time during the disturbance, as intrusive and inappropriate and that caused marked anxiety or distress. - the thoughts, impulses, or images are not simply excessive worries about real-life problems - The person attempts to ignore or suppress the thoughts, impulses or images or to neutralize them with some other thought or action.

CAM ASD: Omega 3s

Omega 3s - When given during childhood have not had a benefit - But what about if we give them to preemies?

ASD Pharm: Only 2 FDA approved medications

Only 2 FDA approved medications - Risperdal and Abilify

PTSD Info

Only 2 FDA drugs: sertraline and paroxetine Development depends on severity of stressor, support systems, etc. Many other used off label SSRIs, SNRIs Mirtazapine Propranolol, prazosin (alpha 1 blocker: dosage 1-4 mg qhs) Therapy CBT, EMDR "trauma therapy", exposure therapy, trauma focused therapy in kids

All of the following are differences between Schizophrenia and Autism

Only children with autism are diagnosed before 3 years of age Onset of schizophrenia occurs in adolescence or adulthood, not in very early childhood Children with autism have an increased risk of having mental retardation Schizophrenia develops after a period of normal behavior. It's more of a regression. The prodromal period of schizophrenia can have some symptoms that are similar to ASD, problems with social communication which on the inside may be due to hallucinations but on the outside just looks strange.

CAM ASD

Oxytocin Melatonin Diets Omega 3s N-acetylcysteine L-Carnosine Probiotics

CAM ASD: Oxytocin

Oxytocin: Mediates social behavior in rats so has been proposed as a treatment for ASD One study showed sig improvement on affective comprehension tasks and social memory

Anxiety Disorders DSM-5

Panic Disorder Agoraphobia Specific Phobia Social Anxiety Disorder Generalized Anxiety Disorder

Serotonin Reuptake Inhibtors SSRI Initial Starting Dose Paroxetine (Paxil)

Paroxetine 20 Paroxetine CR 25

Serotonin Reuptake Inhibtors SSRI Max Dose Paroxetine (Paxil)

Paroxetine Max Dose 20 to 40 Extreme Max 50 Paroxetine Max Dose 25 to 50 Extreme Max 62.5

SSRI's Pearls Most Sedating

Paxil most sedating

Social (Pragmatic) Communication Disorder

Persistent difficulties in the social use of verbal and nonverbal communication **New diagnosis for DSM V to capture children who do not have stereotyped or restricted interests**

PTSD Treatment: Medications Prazosin

Prazosin While several studies indicated that prazosin (Minipress) may reduce or suppress nightmares in some people with PTSD Other medications that may assist with nightmares are Clonidine.

CAM ASD: Probiotics

Probiotics - significant improvement in eye contact and correct recognition of human emotion

A 45 year old female presents to your office for an initial intake appointment with complaints of depression. She is being treated for HTN and asthma by her primary care provider. Knowing that certain medications can cause or exacerbate depression, you obtain a complete medication history and determine which of the following medications should be considered as a possibility of worsening depression?

Propranolol

SSRI's Pearls most activating

Prozac most activating, followed by Zoloft

Panic Disorder DSM-V

Recurrent UNEXPECTED panic attacks At least one attack has been followed by ONE month or more of: Additional worry or concern for subsequent panic attacks or their consequences A significant related change in behavior (ie avoidance) Not attributable to a substance Not explained by another mental health disorder Ie reminders of traumatic events in PTSD

First-line medication treatment for GAD in children and adolescents are

SSRI

Most effective for treatment of Anxiety Disorders (although not all FDA approved)

SSRI's

What are our first line medicines in unipolar depression?

SSRI's

SSRI's and Postpartum hemorrhage

SSRIs do not appear to be associated with an elevated risk of miscarriage, and do not appear to greatly increase the risk for hypertensive disorders of pregnancy. However, SSRIs are associated with postpartum hemorrhage.

Only medications approved by the FDA for PTSD

SSRIs sertraline and paroxetine are the only medications approved by the FDA for PTSD.

Seizures have been associated with other antidepressant medications.

SSRIs, SNRIs, TCAs, mirtazapine, nefazodone, and vilazodone warn that they should be used with care when antidepressant therapy is initiated in a patient with a known seizure disorder.

Depakote Safety/Monitoring

Safety/Monitoring . Therapeutic Drug Levels Epilepsy: 50-100 mcg/mL (valproic acid); Mania: 50-125 mcg/mL (valproic acid); Toxic Levels: >175 mcg/mL; Timing: just before morning dose; Time to Steady State: 2-4 days; Info: draw free levels if hypoalbuminemia Monitoring Parameters LFTs at baseline, then frequently, especially during 1st 6mo or if suspected hereditary mitochondrial dz; CBC w/ diff, coagulation tests at baseline, then periodically, also before planned surgery, during pregnancy; serum drug levels; ammonia; s/sx depression, behavior changes, suicidality

Reasonable alternatives to SSRIs for the initial treatment of major depression include?

Second-generation antidepressants, such as serotonin-norepinephrine reuptake inhibitors, Atypical antidepressants Serotonin modulators

Serotonin modulators Black Box Warning for Hepatotoxicity

Serotonin modulators Nefazodone (Serzone) Life-threatening liver failure has been reported with nefazodone. A boxed warning has been added to alert patients and providers to this risk

Serotonin Reuptake Inhibtors SSRI Initial Starting Dose Sertraline (Zoloft)

Sertraline 50

Serotonin Reuptake Inhibtors SSRI Max Dose Sertraline (Zoloft)

Sertraline Daily Max 50 to 200 Extreme Max 300

Level 3 "Requiring very substantial support" Social Communication

Severe deficits in verbal and nonverbal social communication skills cause severe impairments in functioning, very limited initiation of social interactions, and minimal response to social overtures from others. For example, a person with few words of intelligible speech who rarely initiates interaction and, when he or she does, makes unusual approaches to meet needs only and responds to only very direct social approaches.

Short-acting vs long-acting Stimulant child/adolescent

Short-acting are easier to titrate, then may wish to switch to long-acting Often start with short-acting in child, long- acting in adolescent

Amphetamine preparations Short-acting considerations

Short-acting stimulants often used as initial treatment in small children (<16 kg/35 lb), but have disadvantage of b.i.d.-t.i.d. dosing to control symptoms throughout day

Methylphenidate preparations Short-acting considerations

Short-acting stimulants often used as initial treatment in small children (<16 kg/32lb) but have disadvantage of b.i.d.-t.i.d. dosing to control symptoms throughout day

Irritability in ASD Aripriprazole (Abilify)

Study looked at tantrums, aggression, and self-injury Side effects: sedation, dizziness, insomnia, akathisia, N/V and weight gain (though theoretically not as severe)

Before modern conceptions of depression in children, it was thought that their ______ would prevent them from developing depression.

Super-ego

Which of the following statements are correct?

Symptoms of panic attacks may include cardiac related, dysphagia, diaphoresis, & neurological symptoms

Vilazodone (Viibryd) = VIIBREAD

TAKE WITH FOOD

Lithium Half Life

The half-life of lithium is approximately 24 hours. Thus, it takes at least four or five days for serum lithium concentrations to reach steady state after the dose is changed.

Which neurochemicals are hypothesized to be involved in the pathophysiology of depression?

The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. Serotonin is the most extensively studied neurotransmitter in depression.

Applied Behavior Analysis (ABA)

The science in which tactics derived from the principles of behavior are applied to improve socially significant behavior and experimentation is used to identify the variables responsible for the improvement in behavior.

Lithium Starting dose

The starting dose of lithium is usually 300 mg two or three times daily. The total daily dose is then increased by 300 to 600 mg every one to five days based upon response, tolerability, and body mass index. The goal is to reach a therapeutic serum level, which generally occurs with a dose of 900 mg to 1800 mg per day. Dose increases generally occur more frequently at the beginning of treatment and less often as clinicians approach the target dose.

Target serum levels for lithium

The target serum level for acute phase management and maintenance treatment is between 0.8 and 1.2 mEq/L (0.8 and 1.2 mmol/L), and levels should usually not exceed 1.2 mEq/L (1.2 mmol/L) Patients who cannot tolerate a level of 0.8 mEq/L (0.8 mmol/L) may respond to a level of 0.6 mEq/L (0.6 mmol/L)

Acute Stress Disorder 1st line

Therapy 1st line treatment: Cognitive behavioral therapy, trauma focused

Serotonin modulators Initial Starting Dose Trazodone (Desyrel)

Trazodone 100 200 to 400 100 to 600

Serotonin modulators Max Dose Trazodone (Desyrel)

Trazodone Max Daily 200 to 400 Extreme Max 600

Clomipramine/Anafranil is a TCA and, thus, has serotonergic and noradrenergic actions.

True

Clozapine has shown superior efficacy compared to other atypical antipsychotics for the treatment of psychosis.

True

The single most predictive factor for developing MDD is high family loading for the disorder.

True

When considering Metformin for antipsychotic-associated weight gain, it would be prudent to discuss the benefits of lifestyle changes along with medication management.

True

Lisdexamfetamine (Vyvanse) 30, 50, 70 mg cap

Typical Starting Dose 30 mg q.d. FDA Max 70 mg

Obsessive Compulsive Disorder

Typically starts in childhood/adolescence YBOCS, gold standard Obsessions or compulsions, or both, DSM-V Intrusive or unwanted thoughts, images, or urges & attempts to suppress, ignore, or improve w/ another thought or behavior Repetitive behaviors or mental acts in order to suppress the above Aimed at reducing anxiety or distressing thoughts but are clearly defined as excessive or not realistic Time consuming >/= 1 hour a day Significant distress

A 50 year old male patient has been diagnosed with MDD and placed on fluoxetine 20 mg for his depression. For the PMHNP to effectively monitor his use of the medication, which of the following actions should be part of ongoing care?

Use of a standardized rating scale for depression

SNRI Pearls perimenopausal & vasomotor symptoms

Venlafaxine (Effexor) for perimenopausal & vasomotor symptoms

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) Initial starting dose Venlafaxine (Effexor)

Venlafaxine 37.5 to 75 Venlafaxine XR 37.5 to 75

SNRI's Daily Max Dose Venlafaxine (Effexor)

Venlafaxine Daily Max 75 to 375 Extreme Max375 Venlafaxine XR Daily Max75 to 225 Extreme Max 375

SPARI Serotonin Partial Agonist Reuptake Inhibitor

Vilazodone (Viibryd) FDA: MDD in adults Off label: anxiety, OCD Dual acting partial agonist reuptake inhibitor and 5HT1A partial agonist ie. SSRI + buspar Partial agonists actions at postsynaptic serotonin 1A receptors may theoretically reduce sexual SE May have earlier onset of action Starter pack 10 mg x 7 days, then 20 mg x 7 days, then 40 mg thereafter TAKE WITH FOOD = VIIBREAD

Serotonin modulators Initial Starting Dose Vilazodone (Viibryd)

Vilazodone 10

Serotonin modulators Max Dose Vilazodone (Viibryd)

Vilazodone Daily Max 40

Serotonin modulators Initial Starting Dose Vortioxetine (Trintellix)

Vortioxetine 10

Serotonin modulators Max Dose Vortioxetine (Trintellix)

Vortioxetine Max Dose 20

Depakote Divalproex (Valproic Acid) labs

When to Draw Level: Within 30 minutes before dose Time to Steady State(when concentrations remain constant): 2-3 days Usual reference range 50-125 mg/L check hepatic function

Acute Stress Disorder DSM-V

Within the first 30 days of experiencing a traumatic event as described The acute phase 9 or more from any category of the above symptoms Many patients recover completely If >1 month, termed PTSD Therapy 1st line treatment Cognitive behavioral therapy, trauma focused Pharmacotherapy Limited role in ASD, SSRIs not effective, propranolol, Vistaril, benzos

Level 1 "Requiring substantial support" Social Communication

Without supports in place, deficits in social communication cause noticeable impairments. Difficulty initiating social interactions, and clear examples of atypical or unsuccessful responses to social overtures of others. May appear to have decreased interest in social interactions. For example, a person who is able to speak in full sentences and engages in communication but whose to-and-fro conversation with others fails, and whose attempts to make friends are odd and typically unsuccessful.

The only bupropion product that is FDA-approved for smoking cessation.

Zyban is the only bupropion product that is FDA-approved for smoking cessation.

SSRI's Pediatric not approved

citalopram not approved for children paroxetine not approved for children or adolescents

SSRI's Pediatrics

citalopram not approved for children escitalopram MDD 12 & up fluoxetine Depression 8 & up, OCD 7 & up fluvoxamine OCD 8 & up paroxetine not approved for children or adolescents sertraline OCD 6 & up

A PHQ-9 score of 15 would warrant _______.

pharmacotherapy

SSRI's Pediatric OCD + SSRI's

sertraline OCD 6 & up fluoxetine OCD 7 & up fluvoxamine OCD 8 & up

Rett Syndrome

x-linked progressive neurological developmental disorder featuring constant hand-wringing, intellectual disability, and impaired motor skills

Prevalence of ASD

• 1% - Increased rate of diagnoses due to true increase in frequency of ASD?, increased awareness?, better services/treatment (people seeking diagnoses)?, better detection of genetic disorders? and more • Boys are diagnosed 4x as often as girls - May be due to differences in presentation rather than actual differences

Pathophysiology of ASD: Environmental

• Advanced maternal or paternal age, maternal gestational bleeding, gestational diabetes, first-born child • Low birth weight, umbilical cord complications, birth trauma, fetal distress, small for gestational age, low 5- minute Apgar scores, congenital malformation, ABO blood group system or Rh factor incompatibility and hyperbilirubenemia

Mirtazapine (Remeron)

• Alpha 2 Antagonist • NaSSA - Noradrenaline and specific serotonergic agent • Commonly used for sleep - Only lower doses help with sleep - 7.5mg - 15mg • May help with anxiety early on • Augments well with Venlafaxine - "California Rocket Fuel"

Citalopram (Celexa) INFO

• Dose range - 20-40mg • Adults <60yo - Doses greater than 40mg not recommended (QTc Prolongation)

Escitalopram (Lexapro) INFO

• Dosing - 10-20mg • "cleanest" SSRI - Fewest drug interactions - Fewest side effects

Duloxetine (Cymbalta) INFO

• Dosing 40-60mg in 1-2 doses for depression • 60mg once daily for pain disorders and GAD • 40mg BID for stress urinary incontinence • Early norepinephrine reuptake so there is therapeutic norepinephrine at initial dose.

Venlafaxine (Effexor) INFO

• Dosing Range - 37.5mg - 225mg • PTSD may have doses higher than 225mg if tolerated - Norepinephrine reuptake is at 150mg • Dosing schedule to ...

Generalized Anxiety Disorder (GAD)

• Excessive anxiety or worry occurring more days than not for at least 6 months about a number of events or activities • Difficulty controlling worry • 3 of 6 symptoms are present for more days than not: (** Only 1 item required in Children) • restlessness, easily fatigued, difficulty concentrating, irritability, muscle tension, sleep disturbance • The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. • The disturbance is not attributable to the physiological effects of a substance (i.e. drug of abuse, a medication) or another medical condition (e.g., hypothyroidism)

Trazodone FDA Approved

• FDA Approved - Depression • Non-FDA Uses - Insomnia, anxiety • Mostly used as augmenting agent • Lacks sexual dysfunction side effects

BIPOLAR Pathophysiology: Genetics

• Genetics can explain around 60-93% of the variability in adults with bipolar disorder from twin studies (shared environment account for 10-40%) • Relatives of individuals with the early- onset, narrow phenotype, are more often diagnosed with Bipolar Spectrum Disorders - 1/3 - 1⁄2 of family members with a first-degree relative have BSP have BSP • First-degree is key!!

Buspirone (BUSPAR) INFO

• Mechanism - Partial agonist at Serotonin 1A • Which other drug does this? • Dosing - 20-30mg/day - 60mg/day maximum - Dosed 2-3x daily • Start at 15mg BID - Increase in 5mg increments every 2-3 days • Takes 2-4 weeks to work • NOT a PRN medication

Vilazadone (Viibryd) INFO

• Mechanism of Action - Blocks serotonin reuptake pump - Partial agonist actions at serotonin 1A • Thought that this will diminish sexual dysfunction caused by serotonin reuptake inhibition but still cause sexual SFX • Dose = 40mg - 10mg first week - 20mg second week - 40mg next week • Take with food

Vortixetine (Trintellix) INFO

• Multimodal • Blocks serotonin reuptake • 5-HT1 Agonist • 5-HT1B partial agonist • 5-HT1D antagonist - Pro-cognitive actions • 5-HT3 Antagonist - Enhance noradrenergic and glutamatergic activity. - Pro-cognitive actions • 5-HT7 Antagonist - Pro-cognitive actions

SNRI Class Overview

• Newer generation of antidepressants • Mechanism of Action - Norepinephrine and serotonin reuptake - Going back to making more of a "pseudo" tricyclic without the side effects. • Unique class side effects - Dose dependent hypertension - Activation • Commonly prescribed for chronic pain

Bupropion (Wellbutrin) (NDRI) INFO

• Notable Side Effects - Dry mouth, constipation, nausea, weight loss - Insomnia, dizziness, H/A, agitation, anxiety - Hypertension • Life Threatening Side Effects - Rare seizures • Immediate release, highest risk - Hypomania (Less • Often used as augmenting agent - Relieves sexual side effects - Adds a more "tricyclic effect" with an SSRI • May be effective if there is SSRI "poop- out" • Improve cognitive slowing/pseudodeme ntia • Not effective in ...

Mirtazapine (Remeron) SFX

• Notable Side Effects - Sedation - Dry mouth, constipation, increased appetite, dry mouth, weight gain - Hypotension - Abnormal dreams • Life threatening S/E - Rare seizures - Rare induction of mania

Fluoxetine (Prozac) INFO

• P-450 inhibition/Drug-Drug interactions • Long acting SSRI - Half life 4-6 days (parent drug) - Half life 9.3 days (metabolite)

Treatment of Panic Disorder in Children

• Pharmacologic Treatment - Borrowed from adult research - Not FDA approved for children - Acute, short term use of benzodiazepines - Longer term use of SSRI's

Trazodone (Desyrel) INFO

• SARI - Serotonin 2 antagonist/reuptake inhibitor • Notable Side Effects - Nausea, vomiting, edema, blurred vision, constipation, dry mouth - Dizziness, sedation, fatigue, headache - Hypotension, syncope - Occasional sinus bradycardia • Dangerous Side Effects - Rare Priapism - Rare Seizures - Rare induction of mania - Rare activation of suicidal ideation

Lab Monitoring in ASD

• Same lab monitoring for atypical antipsychotics • Same lab monitoring for stimulants • Same lab monitoring for depakote Initial Assessment: • Physical exam • Hearing screen • Wood's lamp for signs of tuberous sclerosis • Genetic testing: chromosomal analysis, fragile X, G-banded karotype • EEG when relevant

Paroxetine (Paxil) INFO

• Short Half Life - ~21 hours • Unique Side Effects - Sedation, weight gain, constipation • Most sexual side effects

Benzodiazepine Tips

• Should not be generally be prescribed longer than 1 month • Short term relief of anxiety and related symptoms when it is disabling and severe resulting in significant distress or problems in social functioning. • If used for sleep limit to between 2 and 4 weeks and prescribe intermittently

OCD: Drug Treatments

•Clinical trials have shown that drugs that impact on serotonin can significantly decrease OCD symptoms. •Examples of these SRIs include the following; -clomipramine (Anafranil) -flouxetine (Prozac), -fluvoxamine (Luvox), -Paroxetine (Paxil) -sertraline (Zoloft).

Medications that May increase or decrease lithium level

•Loop diuretics •Calcium channel blockers

Medications that Decreases lithium level

•Potassium-sparing diuretics •Theophylline

Medications that Increases lithium level

•Thiazide diuretics • NSAIDS Nonsteroidal anti-inflammatory drugs except aspirin • ACE/Angiotensin converting enzyme inhibitors •Antibiotics tetracyclines and metronidazole

Atomoxetine (Strattera)

- BBW > Risk of suicidal ideation; monitor for suicidal thinking or behavior, worsening, or unusual behavior - Contraindications > Glaucoma, pheochromocytoma, MAO I use within past 14 days - Warning > Rare, but severe hepatotoxicity (most within 120 days of start of treatment) SE > Headache, insomnia, *somnolence*, dry mouth, nausea, abdominal pain, decrease in appetite, nausea, etc. > Priapism NOTE > * do not open capsule * - irritant > CYPD 2D6 substrate > watch out for *LIVER PROBLEMS *

ASD: Social Communication and Social Interaction Deficits (manifested by all of the following) x3

1) Deficits in social-emotional reciprocity 2) Deficits in nonverbal communication behaviors used for social interaction 3) Deficits in developing, maintaining, and understand relationships

Persistent difficulties in the social use of verbal and nonverbal communication as manifested by all of the following:

1) Deficits in using communication for social purposes, such as greeting and sharing information, in a manner that is appropriate for the social context. 2) Impairment of the ability to change communication to match context or the needs of the listener, such as speaking differently in a classroom than on a playground, talking differently to a child than to an adult, and avoiding use of overly formal language. 3) Difficulties following rules for conversation and storytelling, such as taking turns in conversation, rephrasing when misunderstood, and knowing how to use verbal and nonverbal signals to regulate interaction. 4) Difficulty understanding what is not explicitly stated (e.g., making inferences) and nonliteral or ambiguous meaning of language (e.g., idioms, humor, metaphors, multiple meanings that depend on the context for interpretation).

Diagnosis of Social (Pragmatic) Communication Disorder x4

1) Persistent difficulties in the social use of verbal and nonverbal communication as manifested by all of the following 2) The deficits result in functional limitations in effective communication, social participation, social relationships, academic achievement, or occupational performance, individually or in combination. 3) The onset of symptoms is in the early developmental period. 4) The symptoms are not better accounted for by another mental disorder and are not due to a general medical or neurological condition, or to low abilities in the domains of word structure and grammar, and are not better explained by autism spectrum disorder, intellectual disability, or global developmental delay.

ASD: Restricted, repetitive patterns of behavior, interests, or activities, as manifested by at least two of the following, currently or by history x4

1) Stereotyped or repetitive motor movements, use of objects, or speech 2) Insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior 3) Highly restricted, fixated interests that are abnormal in intensity or focus (e.g., strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interests). 4) Hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment

Diagnosis of ASD 2 Major Categories

2 Major Categories A. Persistent deficits in social communication and social interaction across multiple contexts B. Restrictive and repetitive behaviors and/or stereotyped patterns of interest that are abnormal in their intensity of focus

Atomoxetine (Strattera) Pediatric dosing and dose form [6 yo and older, <70 kg]

6 yo and older, <70 kg Dose: 1.2 mg/kg/day PO divided qd-bid Start: 0.5 mg/kg PO qam for at least 3 days; Max: 1.4 mg/kg/day; Info: in CYP2D6 poor metabolizers, start 0.5 mg/kg PO qam x4wk; do not open cap; periodically reassess need for tx

Long acting x3 Methylphenidate preparations

Concerta 18, 27, 36, 54 mg cap Daytrana patch 10, 15, 20, 30 mg patches Focalin XR 5, 10, 15, 20 mg cap

ASD: Deficits in developing, maintaining, and understand relationships

Deficits in developing, maintaining, and understand relationships, ranging, for example, from difficulties adjusting behavior to suit various social contexts; to difficulties in sharing imaginative play or in making friends; to absence of interest in peers.

ASD: Deficits in nonverbal communicative behaviors used for social interaction

Deficits in nonverbal communicative behaviors used for social interaction, ranging, for example, from poorly integrated verbal and nonverbal communication; to abnormalities in eye contact and body language or deficits in understanding and use of gestures; to a total lack of facial expressions and nonverbal communication.

ASD: Deficits in social-emotional reciprocity

Deficits in social-emotional reciprocity, ranging, for example, from abnormal social approach and failure of normal back-and-forth conversation; to reduced sharing of interests, emotions, or affect; to failure to initiate or respond to social interactions.

Amphetamine x3 preparations long acting

Dexedrine Spansule 5, 10, 15 mg cap Adderall XR 5, 10, 15, 20, 25, 30 mg cap Lisdexamfetamine (Vyvanse) 30, 50, 70 mg cap

ASD Differential Diagnosis

Differential Diagnoses • Rett Syndrome • Selective Mutism • Language Disorders • Social (Pragmatic) Communication Disorder • Intellectual Disability • Stereotypic movement disorder • ADHD • Schizophrenia (Childhood Onset?)

Hyperactivity/Impulsivity Fidgets

Difficultly remaining seated Runs or climbs excessively (feelings restless in adolescents or adults) Difficulty engaging quietly "on the go" "driven by a motor" Talks excessively Blurts out answers Difficult waiting turn Interrupts or intrudes

Which of the following symptom is the MOST frequent reason for referral in child psychiatry clinics?

Disruptive behavior "disruptive behavior disorders being the most frequent referral problem for youth, accounting for one-third to half of all cases seen in mental health clinics" and slide 43 and 44 I mentioned this during the lecture.

Atomoxetine (Strattera) Adult dosing and dose form

Dosage forms: CAP: 10 18 25 40 60 80 100 mg ADHD [80 mg/day PO divided qd-bid] Start: 40 mg PO qam for at least 3 days Max: 100 mg/day; Info: may incr. to 100 mg/day after 2-4wk; in CYP2D6 poor metabolizers, start 40 mg PO qam x4wk; do not open cap; periodically reassess need for tx

Atomoxetine (Strattera) Pediatric dosing and dose form 6 yo and older, >70 kg

Dose: 80 mg/day PO divided qd-bid Start: 40 mg PO qam for at least 3 days; Max: 100 mg/day; Info: may incr. to 100 mg/day after 2-4wk; in CYP2D6 poor metabolizers, start 40 mg PO qam x4wk; do not open cap; periodically reassess need for tx

Stimulants have a black box warning for:

Drug Dependence The U.S. Food and Drug Administration (FDA) reviewed the prescribing information on stimulants in an effort to clarify risks and benefits. After this careful review, the only black box warning for stimulants concerns their abuse potential" Screen for cardiac concerns.

Dextroamphetamine Extended Release Duration

Extended Release Rule of Thumb 8-12 Dexedrine spansules 8 Evekeo 10 Adzenys XR (ODT) 10-12 Vyvanse 12-14

Methylphenidate Extended Release Duration

Extended Release Rule of Thumb 8-12 Ritalin SR 8 Concerta 12 Metadate 12 CD 8 Metadate ER 8 Ritalin LA 8-12 Daytrana 8-12 Focalin XR 12 Quillivant XR Quillichew ER 8 Aptensio XR 12

Inattention criteria ADHD

Fails to give close attention to details or makes careless mistakes in schoolwork, at work, or during other activities Difficulty sustaining attention in tasks or play activities Does not seem to listen when spoken to directly Does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace Difficulty organizing tasks and activities Avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort Often loses things necessary for tasks or activities Easily distracted by extraneous stimuli Forgetful in daily activities

Which of the following is true regarding psychostimulants?

First line treatment for ADHD Stimulants are first line treatment for ADHD in children, adolescents and adults. They are the most studied (Dulcan).

Methylphenidate x3 preparations Short-acting

Focalin 2.5, 5, 10 mg cap Methylin 5, 10, 20 mg tab Ritalin 5, 10, 20 mg

Guanfacine (Intuniv=ADHD, Tenex=Hypertension)

Guanfacine is a non-stimulant medication used to treat symptoms of attention deficit disorder (ADHD or ADD). a2 agonist that shares the central a adrenoceptor stimulating effects of clonidine.

Dextroamphetamine Immediate Release Duration

Immediate Release Rule of Thumb 3-4 Dexedrine 3-4

Methylphenidate Immediate Release Duration

Immediate Release Rule of Thumb 3-4 Ritalin 3-4 Methylin 3-4 Focalin 3-4

Dextroamphetamine and amphetamine salt combinations Immediate Release Duration

Immediate Release Rule of Thumb 4-6 Adderall 4-6

Level 1 "Requiring substantial support" Restricted Repetitive Behavior

Inflexibility of behavior causes significant interference with functioning in one or more contexts. Difficulty switching between activities. Problems of organization and planning hamper independence.

Level 2 "Requiring substantial support" Restricted Repetitive Behavior

Inflexibility of behavior, difficulty coping with change, or other restricted/repetitive behaviors appear frequently enough to be obvious to the casual observer and interfere with functioning in a variety of contexts. Distress and/or difficulty changing focus or action.

Level 3 "Requiring very substantial support" Restricted Repetitive Behavior

Inflexibility of behavior, extreme difficulty coping with change, or other restricted/repetitive behaviors markedly interfere with functioning in all spheres. Great distress/difficulty changing focus or action.

Amphetamine preparations long acting considerations

Longer acting stimulants offer greater convenience, confidentiality, and compliance with single daily dosing but may have greater problematic effects on evening appetite and sleep Adderall XR cap may be opened and sprinkled on soft foods

Intermediate-acting Methylphenidate preparations considerations

Longer acting stimulants offer greater convenience, confidentiality, and compliance with single daily dosing but may have greater problematic effects on evening appetite and sleep Metadate CD and Ritalin LA caps may be opened and sprinkled on soft food

Level 2 "Requiring substantial support" Social Communication

Marked deficits in verbal and nonverbal social communication skills; social impairments apparent even with supports in place; limited initiation of social interactions; and reduced or abnormal responses to social overtures from others. For example, a person who speaks simple sentences, whose interaction is limited to narrow special interests, and who has markedly odd nonverbal communication.

Intermediate-acting x5 Methylphenidate preparations

Metadate ER 10, 20 mg cap Methylin ER 10, 20 mg cap Ritalin SR 20 mg Metadate CD 10, 20, 30, 40, 50, 60 mg Ritalin LA 10, 20, 30, 40 mg

Start with MPH or AMP

No evidence to suggest one over the other If one stimulant is not effective, try the other (MPH vs AMP)

Selective Norepinephrine Reuptake Inhibitors (SNRIs) for ADHD considerations

Not a schedule II medication Consider if active substance abuse or severe side effects of stimulants (mood lability, tics); give q.a.m. or divided doses b.i.d. (effects on late evening behavior); do not open capsule; monitor closely for suicidal thinking and behavior, clinical worsening, or unusual changes in behavior

Paroxetine (Paxil) and atomoxetine (Strattera)

Paroxetine (Paxil) is an inhibitor of CYP450 2D6 and atomoxetine (Strattera) is metabolized by CYP450 2D6, so the dose of atomoxetine should be decreased. Strattera as it is metabolized (get rid of d and c)by the P450 CYP 2D6, which many other psychiatric medications are also metabolized by. Specifically if you look under epocrates for interactions you will find "avoid combo, combo may increase atomoxetine levels, risk adverse effects" therefore you'd want to decrease the Strattera dose (or not use the combo)

ASD Pharmacotherapy

Pharmacology • Treatment is aimed at behavioral symptoms rather than core symptoms - Irritability, aggression, injurious behaviors, hyperactivity, inattention, impulsivity, temper tantrums, anxiety • Reducing these symptoms may make it easier for children to participate in behavioral treatments • Overall we have mostly small open trials, with limited RCT data • Only 2 FDA approved medications - Risperdal and Abilify

Which of the following is a risk factor for the development of Conduct Disorder

Poor family functioning child maltreatment, overly harsh and abusive parenting or inconsistent parenting, neglectful parenting

ADHD specifiers

Specify if • Combined • Predominately Inattentive • Predominantly Hyperactive/Impulsive • In partial remission- fully criteria were previously met, but fewer symptoms are present now • Mild- few if any symptoms in excess of normal

ASD specifiers

Specify if • With or without accompanying intellectual impairment • With or without accompanying language impairment • Associated with a known medical or genetic condition or environmental factor • Associated with another neurodevelopmental, mental, or behavioral disorder • With catatonia

Treatment Algorithm with ADHD

Stage 1: Stimulant (either MPH or AMP preparation) Stage 2: Alternative stimulant Stage 3: Atomoxetine or α2 agonist Stage 4: Combination of α2 agonist or atomoxetine with stimulant

Stimulant Practical Considerations in Ohio

Stimulants cannot be refilled- but can give multiple prescriptions at once (total 90 days worth) - Can give a prescription that can only be given at a future date using "Do Not Fill Before" or (DNFB) • Do not give undated prescription of prescriptions dated ahead

Common Stimulant Side Effects

Stomachaches, headaches, nausea - May only occur the first day they take it, may persist but are tolerable, may necessitate a medication switch • Insomnia - Never take too late in the day (after 4 pm), take earlier in the day, switch to immediate release formulation, assess/practice good sleep hygiene at home (NO SCREENS IN BEDROOM)

Long acting x3 Methylphenidate preparations considerations

Swallow whole with liquids Nonabsorbable tablet shell may be seen in stool.

Guanfacine (Intuniv=ADHD)

The starting dosage of guanfacine is 1 mg per day. The dosage can be titrated up in increments of 1 mg per week to a maximum dosage of 4 mg per day.

Which of the following is true regarding cortical brain development in children with ADHD compared to healthy controls?

The timing of cortical maturation is different Peak thickness of cortex delayed (typically occurs around 7, may not happen until 10 for kids with ADHD)

Metadate ER 10, 20 mg cap

Typical Starting Dose 10 mg q.a.m. FDA Max 60 mg OFF Label Max Daily >50 kg: 100 mg

Methylin ER 10, 20 mg cap

Typical Starting Dose 10 mg q.a.m. FDA Max 60 mg OFF Label Max Daily >50 kg: 100 mg

Ritalin SR 20 mg

Typical Starting Dose 10 mg q.a.m. FDA Max 60 mg OFF Label Max Daily >50 kg: 100 mg

Concerta 18, 27, 36, 54 mg cap

Typical Starting Dose 18 mg q.a.m. FDA Max 72 mg OFF Label Max Daily 108 mg

Metadate CD 10, 20, 30, 40, 50, 60 mg

Typical Starting Dose 20 mg q.a.m. FDA Max 60 mg OFF Label Max Daily >50 kg: 100 mg

Ritalin LA 10, 20, 30, 40 mg

Typical Starting Dose 20 mg q.a.m. FDA Max 60 mg OFF Label Max Daily >50 kg: 100 mg

Dexedrine (dextroamphetamine) 5 mg cap

Typical Starting Dose 3-5 y: 2.5 mg q.d. Typical Starting Dose >6 y: 5-10 mg q.d.-b.i.d. spansule

Methylin 5, 10, 20 mg Tab

Typical Starting Dose 5 mg b.i.d. FDA Max 60 mg OFF Label Max Daily >50 kg: 100 mg

Ritalin (methylphenidate) 5, 10, 20 mg

Typical Starting Dose 5 mg b.i.d. FDA Max 60 mg OFF Label Max Daily >50 kg: 100 mg

Focalin XR 5, 10, 15, 20 mg cap

Typical Starting Dose 5 mg q.a.m FDA MAX 30 mg OFF Label Max 50 mg

ADDERALL (XR), amphetamine and dextroamphetamine salts 5, 10, 15, 20, 25, 30 mg cap

Typical Starting Dose >6 y: 10 mg q.d FDA Max 30 mg Off Label Max Daily >50 kg/100lb: 60 mg

Dextrostat (Dextroamphetamine) 5, 10 mg cap

Typical Starting Dose >6 y: 5 mg q.d.-b.i.d

Dexedrine Spansules (dextroamphetamine) 5, 10, 15 mg cap

Typical Starting Dose >6 y: 5-10 mg q.d.-b.i.d FDA Max 40 mg Off Label Max Daily >50 kg/100lb: 60 mg

Daytrana patch 10, 15, 20, 30 mg patches

Typical Starting Dose Begin with 10 mg patch q.d., then titrate up by patch strength FDA MAX 30 mg OFF Label Max Not yet known

Atomoxetine Strattera 10, 18, 25, 40, 60, 80, 100 mg cap

Typical Starting Dose Children and adolescents <70 kg/140lb: 0.5 mg/kg/day for 4 days; then 1mg/kg/day for 4 days; then 1.2 mg/kg/day FDA MAX Lesser of 1.4 mg/kg or 100 mg OFF Label Max Daily Lesser of 1.8 mg/kg or 100 mg

Adderall 5, 7.5, 10, 12.5, 15, 20, 30 mg tab

Typical starting Dose 3-5 y: 2.5 mg q.d. >6 y: 5 mg q.d.-bid FDA Max 40 mg Off Label Max Daily >50 kg/100lb: 60 mg

Macrocephaly

abnormally large skull

Focalin 2.5, 5, 10 mg cap

dexmethylphenidate Typical Starting Dose 2.5 mg b.i.d. FDA Max 20 mg Off Label Max Daily 50 mg

ASD: Hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment

e.g. apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement.

ASD: Insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior

e.g., extreme distress at small changes, difficulties with transitions, rigid thinking patterns, greeting rituals, need to take same route or eat same food every day.

ASD: Stereotyped or repetitive motor movements, use of objects, or speech

e.g., simple motor stereotypes, lining up toys or flipping objects, echolalia, idiosyncratic phrases.

ASD: Highly restricted, fixated interests that are abnormal in intensity or focus

e.g., strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interests.

ASD Comorbid Conditions

• Anxiety Disorders - Specific phobia 44% - OCD 37% - Social Anxiety 29% - Separation Anxiety 12% • ADHD 31% • MDD 10% • ODD 28% **Around 57% have a comorbid condition**

ASD Screening Tools

• Children should be screened routinely at psychiatric evaluations and during developmental assessments (well-child) • If screening bring up any significant findings the child should be referred for a full evaluation • M-CHAT (Modified Checklist for Autism in Toddlers) - 23 items rated yes or no • CAST (Childhood Asperger's Syndrome Test) - 37 items rated yes or no - Children ages 4-11

CAM in ADHD

• Common Complementary therapies in ADHD: - Modified diet (eliminating sugar, food dyes) - Vitamins and/or minerals (fish oil, iron, Ginkgo biloba) - Dietary supplements - Aromatherapy - Chiropractic care - Neurofeedback • No conclusive evidence that food can alter ADHD symptomatology

Stimulant Black Box Warning

• Drug dependance/abuse potential - Caution if emotionally unstable incling hx of drug dependence of alcoholism - Chronic abuse can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior - Frank psychotic episodes can occur - Typically snorted or injected so greater risk with IR formulations that can be crushed - Concern that use in adolescents can increase risk of abuse, BUT studies have

Pathophysiology of ASD: Neurophysiological

• EEG abnormalities or seizure activity is present in 20-25% of children with ASD • 4-32% have a grand mal seizure at some time

ASD Biomarkers:

• Elevated serotonin in whole blood, specifically in platelets • Abnormal signaling in the Mammalian target rapamycin-linked (mTOR) synaptic plasticity mechanisms • Alterations in GABA

Pathophysiology of ASD: Genetics

• Heritability estimates range from 37-90% • 15% of cases may be associated with known genetic mutations • Multiple genes are involved (polygenic) • Chromosomes 2 and 7 and 16 and 17 may contain genes linked to ASD • Fragile X - X-linked recessive disorder that is present in 2-3% of children with autism

Pathophysiology of ASD: Neuroanatomical

• Increased total brain volume in children younger than 4 - Even when neonatal head circumference was normal • By age 5 15-20% develop macrocephaly • Amygdala may be larger for the first few years, then begins to decrease in size • Increase in size of the straitum which correlates with frequency of repetitive behaviors • According to fMRI studies children with ASD scan faces differently - Focus more on the mouth rather than the eyes

Clinical features of ASD

• Intellectual Disability - 1/3 have an intellectual disability, however adaptive functional skills may be low even in those with average or high intelligence • Deficits in pragmatic communication (social aspects of communication) - Sometimes also have deficits in vocab and grammar and with pronouns • Disturbance in language development and usage - Babbling may be absent - No longer a core criteria however langauge delays can be present, especially in more severe cases - Exchanges of pronouns "You want the toy" when they mean "I" • Hypersensitivity to sounds, bright lights, touch, or taste • Gross and fine motor deficiencies - odd gait, clumsiness, and other abnormal motor signs (e.g., walking on tiptoes) • Irritability - Aggression, self-injurious behaviors, severe tempter tantrums • Precocious Skills - "savants"- hyperlexia, special memory skills, musical skills and more • Insomnia

Non-Stimulant Medications Atomoxetine (Strattera)

• Norepinephrine uptake inhibitor (selective inhibition of presynaptic norepinephrine transporter) so increases DA and NE in prefrontal cortex • Usually administered BID • Can be good for mood too- even alone • Metabolized by P450 (CYP) 2D6- check for interactions

Comorbidities of ADHD

• ODD/CD/Anxiety - 25-33% or 40-70% • Learning/language disorders - 25% • MDD - 11% (from MTA) or 15-35% • Bipolar Disorder - 16% • Emotional Dysregulation (Chronic **Comorbidity is the rule in ADHD** irritability, reactive aggressive outbursts

Pathophysiology of ASD: Neurochemical

• Serotonin - Elevation of peripheral levels - 5HT is involved in brain development so problems in its regulation may lead to alternations in brain growth • Dopamine - Antipsychotics appear to be helpful so DA must be involved somehow!

Diagnostic Criteria of ADHD

• Several inattentive or hyperactive- impulsive symptoms were presents prior to age 12 years • Several inattentive or hyperactive- impulsive symptoms are present in 2 or more settings (home, school, work, etc) • There is clear evidence that the symptoms interfere with, or reduce the quality of social, academic, or occupational functioning

Diagnosis of ASD

• Symptoms must be present in early development - Often noticed around 12-24 months, but can be sooner or later • Must be impairing in social, occupational, or other important areas of functioning • The symptoms are not better explained by Intellectual Disability (ID) or Global Developmental Delay - ID and ASD can co-occur