copyright © the reach institute. all rights reserved. adverse effects and monitoring of atypicals

Copyright © The REACH Institute. All rights reserved.

Adverse Effects and Monitoring of Atypicals

http://www.thereachinstitute.org/


Learning ObjectivesLearning ObjectivesIn order to effectively manage adverse effects (AEs) associated with antipsychotics, participants will learn to:

1) How to ask about AEs

2) Guidance for monitoring of atypicals (eg vital signs and metabolic labs)

3) With respect to AEs, atypicals are not all the same

4) Tips on the management of AEs

5) Importance of communication and collaboration with involved specialists

6) Use of Abnormal Involuntary Movements Scale (AIMS)


Monitoring Adverse Effects• General (e.g., “What’s Up?”)

• Quick but misses things• “Is there anything that is bothering you? I hear some

kids say…• It makes me too tired• It messes up my sleep• It makes me constipated or have diarrhea• I am eating more or less• I have noticed breast enlargement “man boobs” or leakage• I’m drooling• I’m shaking”

• Then circle back to, “Anything that you’ve noticed that’s different that is bothering you that you haven’t mentioned yet that you’ve wondered about”


Monitoring Side Effects

• Antipsychotic Use in Children and Adolescents: Minimizing Adverse Effects to Maximize Outcomes. – Correll, C. Journal of the American Academy

of Child & Adolescent Psychiatry. 47(1):9-20, January 2008

• BMI Percentile Calculator– http://apps.nccd.cdc.gov/dnpabmi/Calculator.a

spx, T-MAY Tool Kit

http://apps.nccd.cdc.gov/dnpabmi/Calculator.aspx

http://apps.nccd.cdc.gov/dnpabmi/Calculator.aspx


Atypical Antipsychotics• Risperidone (Risperdal)

– FDA indication for bipolar disorder, Acute Mania for children 10-17 – Also has indication for schizophrenia for children ages 13-17 and

the irritability symptoms of autistic disorder in children ages 5-16

• Aripiprazole (Abilify)– FDA indication for bipolar disorder, Acute Mania for children 10-17 – Also has indication for schizophrenia for children ages 13-17 and

the irritability symptoms of autistic disorder in children ages 6-17

• Quetiapine (Seroquel)– FDA indication for bipolar disorder, Acute Mania for children 10-17– Also has indication for schizophrenia for children ages 13-17

• Olanzapine (Zyprexa)– FDA indication for bipolar disorder, manic or mixed episodes , ages

13-17– Also has indication for schizophrenia for children ages 13-17

• Evidence also for aggression but must weigh side effects and consider general principles (thorough diagnostic eval, treat primary disorder, etc)


Adapted from: Pappadopulos EA et al. Schizophr Bull. 2002;28:111-121. Marder et al, 2003; Potkin et al, 2003.

Safety and Tolerability of Atypical Antipsychotics (AP)

Safety and Tolerability of Atypical Antipsychotics (AP)

Medication Antichol-inergic

Elevated Prolactin EPS Ortho-

stasisQTc

Increase Sedation Weight Gain

Aripiprazole (Abilify) 0 0 0 + 0 + +

Risperidone (Risperidal) 0 +++ ++ ++ 0 + ++

Quetiapine (Seroquel) + + + ++ + +++ ++

Olanzapine (Zyprexa) ++ ++ + ++ 0 +++ ++++

Ziprasidone (Geodon)

+ + + + +++ + 0

Clozaril(Clozapine) ++++ + 0 ++++ + ++++ ++++


Adapted from: Pappadopulos EA et al. Schizophr Bull. 2002;28:111-121. Marder et al, 2003; Potkin et al, 2003.

SEE T-MAY Reference Guide

Antichol-inergic

Elevated prolactin EPS

Ortho-stasis

QTcIncrease Sedation

Weight Gain

Clozapine ++++ 0/+ 0/+ +++ + ++++ ++++

Risperidone + ++++ ++ ++ + + +++

Olanzapine ++ ++ + ++ + +++ ++++

Quetiapine + 0/+ 0/+ ++ + ++ ++

Ziprasidone + + + + ++ + 0/+

Aripiprazole* 0/+ 0/+ + + 0 + 0/+

Safety and Tolerability ofAtypical Antipsychotics


Atypical Antipsychotics: Optimal Dosing/Titration for Children & Adolescents*

200-600 mg**150-300 mg**200-600 mg150-300 mg1-2x starting dose(18-20 days)

6.25-25 mgClozapine(Clozaril)

12.5-20 mg7.5-12.5 mgNDANDA2.5 mg(9-16 days)

2.5 mg for children 2.5-5 mg for adolescents

Olanzapine(Zyprexa)

300-600 mgNDANDANDA25-50 mg to 150 mg then 50-100 mg (18-33 days)

12.5 mg for children25 mg for adolescents

Quetiapine(Seroquel)

3-6 mg3-4 mg2-4 mg1.5-2 mg0.5-1 mg (18-20 days)

0.25 mg for children0.50 mg for adolescents

Risperidone(Risperdal)

NDA; (In adults, 160-180 mg)

NDANDANDA10-20 mg10 mg for children20 mg for adolescents

ZiprasidoneGeodon

5-30 mg2.5-15 mg5-15 mg2.5-15 mg2.5-5 mg (7-10 days)

2.5-5 mgAripiprazole(Abilify)

CHILDADOLESCENTCHILD

Usual Daily Dose Rangein Psychosis

Usual Daily Dose Range in Aggression*

Titration Dose Increase q3-4 days (~Min. days to antipsychotic dose)

Starting Daily-Dose

AtypicalAntipsychotic

NDA = no data available.*There is little information to guide dosing strategies for aggression. However, for aggressive children treated with risperidone, doses are about half the usual AP dose.**In treatment resistant schizophrenic adults, a serum clozapine level (of the parent compound) greater than 350mg/dl is generally required for efficacy.

SEE T-MAY Reference Guide

ADOLESCENT



Cardiometabolic Risk of Second-Generation Antipsychotic Medication During First-Time

Use in Children and Adolescents

Significant Changes in Metabolic Parameters Over Time

Total Cholesterol (mg/dl)

Triglycerides (mg/dl)

Non-HDL Cholesterol (mg/dl)

TG:HDL Ratio

Olanzapine 15.58 24.34 16.81 0.59

Quietiapine 9.05 36.96 9.93 1.22

Risperidone NS 9.74 NS NS

Aripiprazole NS NS NS NS

Correll, Manu, Olshanskiy, et al. JAMA. 2009;302(16):1765-1773


Rare, Life Threatening, or Highly Medically Concerning (see pg 23 of TMAY)

Rare, Life Threatening, or Highly Medically Concerning (see pg 23 of TMAY)

Side Effect First Line Options Additional Considerations

Neuroleptic Malignant Syndrome (NMS)

D/C APEmergency consult/ER

Different AP once NMS resolves

↓d ANC Repeat labHeme consultD/C AP

Start different AP once ANC returns to normal

Agranulocytosis Emergency heme consult Immediately D/C APRepeat lab

Start different AP once agranulocytosis resolves

Increased Liver Function Tests

Repeat labConsider D/C APInternal Med/Peds consult

↓ doseIf continues, D/C APOnce resolved reconsider need for AP


Extrapyramidal SymptomsExtrapyramidal Symptoms

Side Effect First Line Options

Additional Considerations

Akathisia ↓ dose Add beta adrenergic antagonist; Switch AP

Akinesia ↓ dose Add anticholinergic; Switch AP

Tremor ↓ dose Add anticholinergic; Switch AP

Muscle Rigidity Add anticholinergic ↓ dose

Add dopamine agonist; Switch AP

Dystonia Add anticholinergic Add lorazepam

↓ dose

Tardive Dyskinesia Neurology consult D/C AP

Reconsider need for APSwitch AP


Cognitive Side EffectsCognitive Side Effects


Confusion Assess for medical illness + illicit drug use; ↓ dose; neuro consult

Obtain serum levelsD/C AP; Switch AP

Headache Add analgesic; Wait for improvement; Rule-out tension headache

↓ doseConsider specialist consult

Memory Problems

↓ dose Neuro + neuropsychology consult; Meds HS; Switch AP

Sedation/Hypersomnia

Give med HS; Discontinue other sedating meds; ↓ dose

Switch AP

Seizures EEG; Neuro consult; ↓ dose; Review other meds, Switch AP; (Increase MS dose)

D/C medication


Cardiac Side EffectsCardiac Side Effects


Slightly prolonged QTc Interval (>450 & <500 msecs)

Repeat EKG↓ dose

Cardiology consult; D/C AP; start different AP once QTc returns to normal

Very prolonged QTc Interval (> 500 Msecs)

Repeat EKG; cardiology consult; D/C AP

Start different AP once QTc returns to normal

Tachycardia Cardiology consult; ↓ dose

Switch AP

Orthostatic Hypotension

Teach patient to change posture slowly; increase hydration; ↓ dose

Cardiology consult; switch AP


Weight Gain, Metabolic Dysregulation and Diabetes Risk

Weight Gain, Metabolic Dysregulation and Diabetes Risk

Side Effect First Line Options Additional

Considerations

Weight gain (5-10% of baseline weight or 5- 10% rise in BMI%)

Nutrition consult; Implement diet/exercise program;

Switch AP

Metabolic Deregulation

Monitor fasting glucose, non-HDL cholesterol and triglycerides at baseline and follow up

Switch AP

Diabetes Endocrine consult; Symptom-management education; Referral for weight management program

Switch AP


Endocrine SymptomsEndocrine Symptoms


Hyperprolactinemia

No action needed in absence of symptomsProlactin levels not needed

Galactorrhea ↓ dose; Obtain prolactin levels; Endocrine consult

Switch AP

Amenorrhea Rule out pregnancy; Prolactin levels; Gynecology consult

Wait to see if resolves; ↓ dose; Switch AP

Gynecomastia (males)

Prolactin levels; Endocrine consult

Switch AP


Anticholinergic Side EffectsAnticholinergic Side Effects


Constipation High fiber diet; fluids; Bulk laxatives or stool softener; ↓ dose

Switch AP

Dry Mouth Sugarless gum or hard candy; ↓ dose

Switch AP


Other Side EffectsOther Side Effects


↓d libido; Erectile dysfunction

↓ dose; D/C meds with sexual side effects

Switch AP

Enuresis Void before sleep; ↓evening fluids; ↓dose; Wake to void at night

Use behavior intervention; Switch AP

Hypersalivation ↓dose; Sleep in lateral decubitus position; Towel over pillow

Switch AP; If due to EPS, add anticholinergic; If due to Clozapine, add alpha agonist

Insomnia Evaluate and treat for depression/ anxiety; total or larger AP dose HS; Add sleep aid; If due to AP, consider ↓ dose

Switch AP

Nausea/Vomiting Wait 1-2 days; ↓dose; Add temporary antiemetic

Switch AP

Rash D/C AP; Dermatology consult if severe

Switch AP/MS once rash resolves


Monitoring for Children and Adolescents on APs

Assessments Frequency

Lifestyle monitoring Baseline, every visit

Height, weight, BMI percentile Baseline, every visit

Somnolence/sedation Baseline, every visit

Sexual symptoms/signs Baseline, titration and q 3 mo

EPS, akathisia Baseline, titration, 3 mo and annually

Blood pressure, pulse Baseline, 3 months and 6-monthly

Fasting glucose, lipids Baseline, 3 months and 6-monthly

Liver function tests Baseline, 3 months and 6-monthly

Dyskinesia/TD Baseline, 3 months and annually

Electrolytes, blood count, renal function Baseline and annually (unless on CLO)

Personal and Family History Baseline and Annually

Prolactin Only when symptomatic

EKG If on ZIP, during titration, at max dose

Correll, JAACAP, 2008


Q & AQ & A


Summary of Adverse Effects in Atypicals Monitoring

Summary of Adverse Effects in Atypicals Monitoring

• Systematic Monitoring of AEs crucial to safe and effective treatment

• Monitor for potential side effects with AIMS

• Importance of communication and collaboration with involved specialists

• Educate youth and family, and ask about side effects! You won’t know, otherwise


REMINDER: Please fill out Unit N

evaluation


Resource Slide: ADA/APA Recommended Monitoring Protocol

for Patients on AP’s

Resource Slide: ADA/APA Recommended Monitoring Protocol

for Patients on AP’sBaseline

4 Weeks

8 Weeks

12 Weeks

Quarterly Annually5

Years

Personal/ Family History x

Weight/ BMI x x x x x

Waist Circumference x x

Blood Pressure x x x

Fasting Plasma Glucose x x xFasting Lipid Profile x x xDiabetes Care 27:596-601, 2004

copyright © the reach institute. all rights reserved. adverse effects and monitoring of atypicals

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