PsychopharmacologyUpdate - 2018Annual Conference

Kimberly Roberts, MSN,ARNP, PMHNP-BC

Objectives

• Review evidence-based treatment to common pediatric mental health disorders

• Review when & what psychotropic meds to use based on target symptoms & diagnosis

• Review side effects & monitoring of commonly used psychotropic meds

• Discuss common challenges in pediatric psychiatry

Mental Health Report Card

• Access/receiving mental health care– Iowa ranked 49th Adults, 40th children

• 30% children & teens have a diagnosable psychiatric disorder

• 20% of those children receive mental health care, often PCP

Prescriptions Written• Off label use

– 75% pediatric psych meds– Cost prohibitive

• How many Rx are not taken correctly or not even filled?– Cost, taste, time of dosing, parent– Misinformation: Internet, other parents, family

members, community– Medicaid: foster care, Prior authorization

www.fda.gov/cder/drugsatfda

General principles• Children are not small adults (usually)• Establish diagnosis/diagnostic category• Collaboration is key – family/caregiver, teachers,

therapist• Combined treatment regardless of severity yields

better outcomes• Goal in behavioral health is control, not cure

Evaluation Tools

Clinical interview

History

ScalesMedical Records

Testing

Differential Diagnosis

• Thyroid, caffeine, seizures, asthma, and allergy medications

• Other psychiatric disorders (anxiety, ADHD, akathisias, bipolar, autism, learning disorders, substance abuse)

Principles of prescribing

• Target system approach• Start low and go slow• Efficacy vs. side effects• Patience • Establish baseline• PRN prescriptions with caution

When should you consider medication?

• Negative impact on functioning• Safety issues• Poor response to other interventions• Probability of efficacy for target symptoms

*selection should be based on past history of response, side effect profile, & co-existing medical conditions

• Lipophilic medications– most psychotropic meds are highly lipophilic– Different volumes of fat for drug storage at

different ages• CYP450

– Drug-metabolizing enzyme levels often exceed adult levels, declining after puberty

Antidepressants

Indications: bipolar depression, mood disorders, schizoaffective disorder, GAD, OCD, panic, social phobia, PTSD, PMDD, & impulsivity assoc. with personality disorders

SSRI SDNRI SNRI TCA MAOI

Black Box Warning

• Black Box Warning (2004, 2007revised)– Incr. risk of suicide in children and adolescents

with major depressive disorder or other psychiatric disorders within the 1st month

– No complete suicides in any studies– Liability in NOT treating too

SSRI

Selective serotonin reuptake inhibitor: affects release and reuptake of pre- and post-synaptic receptors

Differences between SSRIs

Fluoxetine, escitalopram, sertraline, citalopram, fluvoxamine, paroxetine

SSRI

Common side effects Headache GI issues sedationInsomnia sexual dysfunction

Rare side effects Activation Black Box Warning serotonin syndrome (hyper-reflexia, fever, flu-like sx, seizures, coma)

Cardiac (celexa over 20mg, EKG indicated)

Uses: Depression, Anxiety, OCD, PTSDOther: rigid thinking associated with autism

NDRI

Norepinephrine dopaminergic reuptake inhibitor

Uses: MDD, seasonal affective d/o, ADHD, nicotine addiction, and chronic pain

Affects the release and reuptake of brain NTs serotonin, norepinepherine, dopamine

NDRI

Buproprion (good for augmenting, ‘meh’)

Common side effectsDry mouth anorexiaConstipation insomniaNausea tremorWeight loss sweating

Rare side effectsRisk or seizuresActivation

* Avoid in TBI and eating disorders

SNRI

Serotonin Norepinephrine Reuptake Inhibitor

Affects the release and reuptake of brain NTs serotonin, norepinepherine.

Uses: MDD, anxiety, OCD, ADHD, chronic pain

SNRI

Duloxetine, Venlafaxine, Desvenlafaxine

Common side effectsHeadache GI Sweating urinary retentionsomnolence

Rare side effects SeizuresDiscontinuation syndrome

TCA

Tricyclic Antidepressants

Increase serotonin and norepinephrine availability

Uses: depression, ADHD, social phobia, panic, PTSD, eating disorders, enuresis, sleep, chronic pain, OCD (clomipramine only)

TCA

Clomipramine, Amitriptyline, Imipramine

Common side effects Anti-cholinergic (dry mouth,sedation, constipation, urinary retention)

Rare side effects DeliriumHeart arrythmiaDeath in OD

BuspironeSerotonin agonist, decreases serotonin levels in specific areas of the brain while increasing DA & NE. also weak antagonist of D2 receptor

Not good by itself, better paired with SSRI

Uses: anxiety, ADHD, irritability, aggression

Side Effects: dizziness, headaches

Mirtazapine Adrenergic antagonist and serotonin, tetracyclic antidepressant

MDD, Anxiety, PTSD, appetite stimulant, weight gainer

Side effects: hypotension, mania, photosensitivity, discontinuation syndrome

Dose 15-45mg/hs

Benzodiazepines

Increases GABA

GAD, sleep and panic disordersAlso used for agitation, alcohol withdrawal

Short term use, abuse potential

Benzodiazepines

Lorazepam, clonazepam, alprazolam, diazepamCommon side effects

SedationCognitive issuesDecreased libidodepression

Rare side effects Addiction SeizuresDeliriumBlurred vision

Mood Stabilizers

Bipolar, disruptive behaviors disorder, aggression, DMDD

MOA unknown, possibly inhibits neuronal signaling and alters sodium transport

Lithium, valproic acid, lamotrigine, topiramate

Lithium

Gold standard mania, mood disorder, depression, schizophrenia

Common side effects: nauseam dizziness, weight gain, tremors, acne

Serious side effects: arrhythmia

Valproic acid

Affects GABA by blocking sodium channels and inhibit histone enzymes

Seizure mgmnt, migraines, mood disorder, impulsivity, pain control, aggression

Occassional labs (LFT, platelets)

Side effects: weight gain, sedation, Polycystic ovary disease, pancreatitis

Lamotrigine

Controls glutamate release, activates serotonin

Depressive phase of bipolar, epilepsy

Start 25-50mg/day, titrate up to 500mg BID

Fatigue, blurred vision, nightmares, dry mouth, Stevens Johnson Rash

TopiramateInhibits glutamate and enhances GABA

Seizures, migraines, chronic pain, alcohol cravings, aggression, impulsiveness

Side effects: brain fog, N/V, sedation,delirium, hot flashes (no weight gain)

Labs: LFTs, CBC/diff

Propanolol

Blocks epinephrine and norepinephrine

Migraine, performance anxiety

Nausea, constipation. Worsen depression

Contraindicated in those with heart issues

Alpha2-agonistsStrengthens working memory/connectivity in PFCClonidine (0.025-4mg/day)

– ADHD, tics, sleep problems, aggression– Side effects: bradycardia, sedation

Guanfacine (1-4mg/day) – ADHD, tics, sleep problems, aggression– Intuniv (extended release)– Side effects: sedation, somnolence, trigger depression

PsychostimulantsLong acting are safe to start in most kids Block reuptake of DA and NEADHD, off label MDD

Common side effects: loss of appetite, insomnia, irritability, emotionality, tics Rare side effects: mani, hallucinations, hypertension

Vanderbilt, Connors gauge severity. EKG if family heart hx

Newest Stimulants

• Methylphenidate: Quillichew, Cotempla-ODT, Aptensio

XR

• Amphetamine: Myadyis, Dynavel XR, Adzenys-ODT

• Amphetamine mixed salts : Evekeo

• Lisdexamfetamine: Vyvanse

Memantine

Partial antagonist of the NMDA receptor, downregulates activity of glutamate

Controversial use in autism (mixed results)

Studies in anxiety and ADHD

First Generation Antipsychotics

Haloperidol, thioridazine, pimozide, chlorpromazine

Blocks receptors of dopamine

Treats psychosis, schizophrenia, bipolar, depression, aggression, tourettes, sleep, anxiety

First Generation Antipsychotics

Common side effects: sedation, dry mouth, constipation, increased hunger, restlessness, metabolic issues (Diabetes, lipids), sexual side effects

Rare side effects: prolonged QT interval, EPS, TD, NMS (rigid, high fever, unstable autonomic system), increase prolactin, pseudoparkinsonism

Second Generation Antipsychotics

Post-synaptic blockage of dopamine D2 receptors.

Tics, bipolar mania, schizophrenia, severe behavior disturbances, sleep, irritability associated with autism

Second Generation Antipsychotics

Risperidone (Risperdal) - Side effects are dose dependent- Weight gain and sedation very commonOlanzaoine (Zyprexa, Zydis)- Weight gain very common & Metabolic labsQuetiapine (Seroquel)- Sedation & Weight gain common - Hangover effect

Second Generation Antipsychotics

Ziprasidone (Geodon)- Prolonged QT- No associated weight gain- Good for aggression and bipolar- Take with foodAsenapine (Saphrys)- sublingual (no food/drink x 10 min)- rapid action, BID dosing, start at therapeutic dose

Second Generation Antipsychotics

Aripiprazole (Abilify)- D2 partial agonist- Low EPS, low QT, low sedation, With fluoxetine- possible activation

Lurasidone (Latuda)- Daily with food, can start at therapeutic dose, rapid onset- No prolonged QT, no weight gain

FGA/SGA lab monitoring

• Every visit: height, weight, BMI, AIMS• Baseline, 3 months, then annually

– hgbA1c, fasting glucose, fasting lipids– Prolactin – LFTs

Anticholinergics

Facilitates dopamine

Treats EPD, TD• Benztropine, trihexyphenidyl, diphenhydramine• Anticholinergic side effects: dry out

Complimentary and Alternative Medicine

Vayarin (Omega 3s/6s) 2 capsules dailyEPA/DHA (brain health) 250-500mg dailyN-acetylcysteine (trichotillomania)SAM-e 400-1600mg dailyL-methylfolate 3-15mg daily

CAM

• Investigational studies on the horizon– Electroconvulsive therapy– Transcranial magnetic stimulation– Deep brain stimulation

Pharmacogenetic Testing

• How well certain medications may be tolerated and effective

• Limitations – cannot determine how you will respond to all medications

• No tests for many over the counter medications• MTHFR assists in converting essential amino acids• Saliva sample• No covered by all insurance

Take home points• Know what you are treating and any comorbid diagnosis

(often can get 2 birds / 1 stone)• Diagnosis may unfold over time• Step back and rethink your plan • Drug-drug interactions• Decrease stigma through education • Collaborate and connect with others (Medications do not

replace family support, safety, parenting, friends, hobbies, self-esteem, etc)

Thank You!

Helpful websites & resources• http://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm

143565.htm• REACH Institute: designed to provide pediatric primary care

practitioners with evidence-based instruction and mentoring around treatment of behavioral/mental health disorders http://www.thereachinstitute.org/primarycareprofessionals. html

Helpful websites– AIMS: http://www.psychiatrictimes.com/clinical-scales-

movementdisorders/clinical-scales-movement-disorders/aims-abnormal-involuntarymovement-scale

– AACAP’s Resources for Primary Care: http://www.aacap.org/AACAP/Resources_for_Primary_Care/Hom e.aspx?hkey=59bfdf7f-149f-43fd-babb-a6a77c5e8caf

– NAPNAP’s Developmental Behavioral & Mental Health Special Interest Group: http://www.dbmhresource.org/

– Massachusetts Child Psychiatry Access Project https://www.mcpap.com/Default.aspx

Helpful websites– National Network of Child Psychiatry Access Projects

http://www.nncpap.org/ – http://www.aacap.org/AACAP/Families_and_Youth/Fact

s_for_Families/Facts_for_families_Pages/Psychiatric_Medication_For_Children_And_Adolescents_Part_II_Types_Of_Medications_29.aspx

– Healthy Children.org https://www.healthychildren.org/English/Pages/d efault.aspx

References • AACAP. (2014). AACAP Workforce Fact Sheet. Retrieved from

http://www.aacap.org/AACAP/Resources _for_Primary_ Care/Workforc e_Issues.aspx

• APA. (2013).Retrieved from http://www.dsm5.org/documents/changes %20from%20dsm-iv-r%20to%20dsm-5.pdf

• AAP Policy statement, March 2014 http://pedoatrocs.aapublications.org/content/133/3/563

References• American Academy of Pediatrics, Subcommittee on Quality

Improvement, Subcommittee on Attention-Deficit/Hyperactivity Disorder, Steering Committee on Quality Improvement and Management: ADHD Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics 2011;128:1007-1022.

• Bridge, J. Clinical Response and Risk for Reported Suicidal Ideation and Suicide Attempts in Pediatric Antidepressant Treatment. JAMA 2007; 297:15: 1683-96.

References• Center for Mental Health Services in Pediatric Primary Care. (2016). A

Guide to Psychopharmacology for Pediatricians. Retrieved from: http://web.jhu.edu/pedmentalhealth/Psychopharmacolog%20use.html

• Choice, T. (2016). Clinical conversations: Depression in pediatric primary care. MCPAP. Retrieved from: https://www.mcpap.com/Docs/March%20Clinical%20Conversations% 20-%20Depression.pdf

• Chugani DC et al. Efficacy of low-dose buspirone for restricted and repetitive behavior in young children with ASD: a randomized trial. J Pediatr 2016; 170:45–53.e4

References

• Daughton, J.M. & Kratchovil, C.J. (2009). Review of ADHD Pharmacotherapies. Journal of the American Academy of Child and Adolescent Psychiatry, 48(3), 240-248.

• Fanton J, Gleason MM.Psychopharmacology and preschoolers: a critical review of current conditions. Child Adolesc Psychiatric Clin N Am 2009; 18: 753–771.

• Faraone, Comparing the efficacy of stimulants for ADHD in children and adolescents using a meta-analysis. Eur Child and Adolescent Psychiatry (2010)19; 353-364

References• FDA (2007). Revised Black Box Warning. http://www.fda.gov/

CDER/Drug/antidepressants/antidepressants_label_change_2007.pdf

• Fibinger, H. C. (2012). Psychiatry, the pharmaceutical industry, and the road to better therapeutics. Schizophrenia Bull., 38, 649-650

• Gurnani T,Ivanov I, Newcorn J. Pharmacotherapy of aggression in child and adolescent psychiatric disorders. J Child AdolescPsychopharm 2016;26: 65-73.

References• March J. Expert Consensus guidelines: treatment of obsessive

compulsive disorder. J. Clinical Psychiatry. 1997; 58(1-72).• Olfson M, Marcus, S (2009) National Patterns in

Antidepressant Medication Treatment Arch Gen Psychiatry. 2009;66(8):848-856

• Olfson, et al. (2006). Antidepressant Drug Therapy and Suicide in Severely Depressed Children and Adults A Case-Control Study. Arch Gen Psychiatry, 63, 865-872.

References

• Rockhill C, Kodish I, DiBattisto C, Macias M, Varley C, Ryan S. Anxiety disorders in children and adolescents. Curr Probl Pediatr Adolesc Health Care 2010 Apr;40(4):66-99

• Sharma, T., et al. (2016). Suicidality and aggression during antidepressant treatment…..British Medical Journal, 2016:352:i65/doi:10.1136/bmj.i65

References

• Sparks JA,Duncan BL. Outside the black box: re-assessing pediatric antidepressant prescription. J Can Acad Child AdolescPsychiatry. 2013 Aug; 22(3): 240–246.

• Stroeh O, Trivedi HK. Appropriate and judicious use of psychotropic medications in youth. Child Adolesc Psychiatric ClinN Am 2012; 32:703-711.

• Survey of Commonwealth of PA Medicaid findings (also published NEJM 1 Sept 2015).

References

• Treatment of Resistant Depression in Adolescents (TORDIA): week 24 outcomes. Am J Psychiatry. 2010 Jul;167(7):782-91.

• Van Cleave J, Leslie LK. Approaching ADHD as a chronic condition: implications for long-term adherence. Journal of Psychosocial Nursing & Mental Health Services 2008;46(8):28-36.