Pediatric psychopharmacology - Zelan Flashcards
What does Off label use refer to?
Using a medication that has not received FDA approval for the clinical indication. Ie. using risperdal or seroquel for depression related anxiety and insomnia.
Allelic variation in CYP 2D6 can affect what?
How quickly some drugs are metabolized. Faster metabolizers need higher doses.
Poor metabolizers are at higher risk for what?
Adverse drug effects.
Borderline poor metabolizers may be more susceptible to what?
An inhibitor effect.
Rapid metabolizers are at risk for what?
Treatment failure.
What psych meds are CYP 2D6 substrates?
- TCA’s
- Prozac, luvox, paxil, trazodone, remeron
- effexor/cymbalta
- strattera, stimulants
- many antipsychotics
What psych meds are CYP 2C19 substrates?
- xanax, valium, many TCA’s
- Clozaril
- Methadone
- Perphenazine
- Zoloft, Celexa, Lexapro, Prozac, Effexor
- Thioridazine
What gene is associated with a more favorable response to SSRI’s?
The ‘long form’ of the Serotonin transporter gene - especially with 2 copies. This is not true with Asians.
There are not many studies showing how psych meds affect kids and they are often treated ‘off label’ with adult meds. What are some concerns?
- the brain continues to develop into early adulthood
- impact of adding psychoactive medications of a developing brain remains unknown
- medications safe for use in adults have had unanticipated side-effects for children
Describe some adult meds that have had unanticipated side-effects for children.
- Tetracycline - dental discoloration
- SSRI’s - suicidality
- Aspirin - Reye’s syndrome
- Cough suppressants - pneumonia
- Antiemetics - dystonic/EPS reactions
What are some things to be considered in selection of medication for children?
Target symptoms Standard of care/ Evidence-based Least risk of serious side effects FDA approval Known previous responses of patient Known previous responses of family members Dosing schedule Clinician preference
Describe how you might monitor the use of medications in children.
- Start low and go slow
- Generally continue raising dose until:
- Satisfactory remission of symptoms
- Reach upper limit of dose
- Side effects that make dosing intolerable
- Plateau in symptoms or worsening with increase in dose - Monitoring of other physical assessments:
Height/weight, P, BP, tics (stimulants)
Liver function, blood count (anticonvulsants)
Fasting blood sugar, lipids, weight, abnormal movements (antipsychotics & mood stabilizers) - monitor for target symptoms
- monitor serums levels if on lithium or anticonvulsants
What are some medication monitoring guidelines?
- During active titration, usually see weekly.
- Children on maintenance medications should be seen by their prescribing clinician no less that once every three months.
- Children in acute settings, displaying unsafe behavior, experiencing significant side-effects, or not responding to a medication trial or in an active phase of a medication trial should be seen more frequently.
List some psych med classifications.
- Anti-depressants
- Mood
- Stabilizers/Anticonvulsants
- Anti-psychotics
Traditional
Second Generation - Anxiolytics
- Sleep Agents/Hypnotics
- Stimulants
Describe some characteristics of antidepressants.
- Common antidepressants - SSRIs, atypical antidepressants, TCA, MAOIs
- SSRI’s are the most widely used anti-depressant in children
- Potential concerns: SI, mania, EKG changes, sleep problems, serotonin syndrome, sexual side effects, weight gain.
Why are SSRI’s prescribed for children and not TCA’s?
- Most studies have shown tricyclic anti-depressants to be ineffective in treating childhood depression.
- There have been several reports of sudden death in children treated with tricyclics.
- Side effects of SSRI’s generally more tolerable than those of tricyclics and MAOI’s.
- SSRI’s may be administered once daily.
- They have the potential to treat a spectrum of childhood disorders (OCD, Tourette’s, anxiety disorders, selective mutism, PTSD, eating disorders).
What are some side effects of SSRI’s?
Gastrointestinal side effects (nausea, diarrhea, decreased appetite)
Headaches
Insomnia or sedation
Serotonin syndrome (nausea, tremor, hyperthermia, rigidity or pain, ALOC, seizure)
Sexual dysfunction (delayed ejaculation, anorgasmia, decreased libido)
Discontinuation syndrome (dizziness, nausea, lethargy, irritability)
Mania
Restlessness (akathisia or agitation)
Miscellaneous side effects: sweating, anxiety, dizziness, tremors, fatigue, dry mouth.
Priapism
List the Atypical antidepressants.
Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban (buproprion) Effexor, Effexor XR (venlafaxine) Cymbalta (Duloxetine) Desyrel (trazadone) Remeron (mirtazapine)
What are the side effects of atypical antidepressants?
- Wellbutrin-insomnia, CNS stimulation, headache, constipation, dry mouth, nausea, tremor, seizure (rare)
- Trazodone-sedation, weight gain, hypotension, dry mouth, priapism
- Effexor-hypertension, insomnia, anxiety, nausea, sweating, dizziness, high incidence of discontinuation syndrome
- Remeron-increased appetite, sedation, dry mouth, constipation
List some common mood stabilizers.
- Common mood stabilizers - Lithium,
Depakote (Valproic Acid), Lamotrigine, Tegretol (affects blood count), Trileptal (better tolerated than tegretol but less effective), lamictal (safer in pregnancy), topomax (not used for bipolar, does not cause weight gain) - Alternatives to traditional mood stabilizers - second generation antipsychotics
What is the association between priapism and psychiatric meds?
- Probably under-reported and under estimated, not well studied b/c trazodone is very old drug.
- Can also occur with other psychiatric drugs, though lower rate usually.
- Risk increases with various medical conditions that increase hypercoagulability or otherwise alter hemodynamics.
- Many contributing risks may be occult.
- can occur in females, though is more rare
What are some of the causes of priapism?
- illness - hematologic, metabolic, neoplastic, neurological
- trauma
- drugs
What are some issues in prescribing Trazodone to men?
- If you do prescribe, careful history taking is essential, since past hx of delayed detumescence is present in 50% with priapism.
- Lower doses are not protective.
- Duration of treatment not relevant.
- While the risk has been quoted as ranging from 1:10,000 to 1:1000, one small study in 2001 found 19% of the 74 participants had priapism.
What should you consider when choosing a mood stabilizer?
- Consider side effect profile/ease of use vs. research data (Current trend towards prescribing antipsychotics as first-line mood stabilizer despite more data for Lithium and Depakote)
- Involve the family in the discussion and choice.
- For bipolar disorder, you may be forced to use multiple medications.
- Understand that bipolar disorder in pediatrics is highly controversial.
List some names of meds that are lithium meds.
- lithobid
- eskalith
- lithonate
- eskalith CR
List some characteristics of mood stabilizers.
- Baseline labs important (chemistry panel, TFTs, CBC, pregnancy test)
- Renal excretion
- Capsule and liquid form (lithium citrate syrup)
- Follow lithium levels (range 0.8-1.2mEq/L); dangerous if toxic levels
- Therapeutic effect may take weeks(4-6 weeks on average)
What are the side effects of Lithium?
- GI distress (nausea, vomiting), weight gain, fine tremor, cognitive impairment (“fuzzy thinking”).
- Polyuria with polydipsia (20% of patients)
- Hypothyroidism (monitor TSH a few times a year)
4.Cardiovascular - Dermatological (acne, rash, itching, psoriasis)
Hematologic (leukocytosis—elevated white count) - Neurologic-muscles weakness, slurred speech, headache
What are the potential life threatening risks for Lithium?
- serotonin syndrome
- neuroleptic malignant syndrome (NMS)
- these syndromes may be variants of drug induced central hyperthermia
What are some symptoms of serotonin syndrome?
- mydriasis
- diaphoresis
- agitation
- tachycardia
- autonomic instability - often includes hypertension
- clonus - greater in lower extremities
- tremor - greater in lower extremities
- hyperreflexia - greater in lower extremities
- increased bowel sounds and possible diarrhea
What meds increase risk for serotonin syndrome?
- Anti-migraine medications such as triptans, tegretol and Depakote
- Pain medications Flexeril, fentanyl, Demerol, tramadol, talwin,
- Illicit drugs, including LSD, Ecstasy, cocaine and amphetamines
- Herbal supplements, including St. John’s wort, ginseng and nutmeg
- Over-the-counter cough and cold medications esp. with dextromethorphan, but caution with all OTC cough meds
- Anti-nausea medications such as granisetron, reglan, droperidol, Zofran
- Linezolid
- Ritonavir
- Buprenorphine, oxycodone, hydrocodone
What is the difference between NMS and serotonin syndrome?
- NMS usually seen more with antipsychotics (esp older ones) and chronic schizophrenia, but not exclusively.
- SS is sudden (within 24 hrs of starting med), NMS is slower (within days of starting med)
- SS symptoms include agitation and diarrhea, NMS includes dysphagia, hyper salivation and incontinence
- Signs of SS are dilated pupils, myoclonus, hyperreflexia, NMS signs include hyper thermal, akinesia, extrapyramidal ‘lead pipe’ rigidity, rhabdomyoloysis
- SS deaths are rare and NMS deaths - 15-20%
Lithium toxicity can be caused by what?
Can be caused by: decreased fluid intake, increased fluid loss (sweating excessively/diuretics), reduced salt intake, medications that act on the renal system (NSAIDS/ACE inhibitors), taking too much Lithium!
What are the symptoms of lithium toxicity?
- Symptoms: GI (nausea, vomiting, diarrhea), coarse tremor, ataxia, slurred speech, confusion, arrythmias.
- Can check blood levels: Mild to moderate toxicity (1.5-2.0mEq/L). Severe toxicity (>2.5mEq/L). Death may occur (>4mEq/L). Treatment may involve stopping lithium, hydration, and hemodialysis.
Describe some characteristics of Depakote.
- Capsules, oral suspension, tablets
- Avoid in patients with hepatic (liver) disease
- Screening labs (CBC, LFTs, pregnancy test)
- Check serum levels 7 days after first dose, then continue to monitor
- Therapeutic effect 2-4 weeks
- Side effects: sedation, dizziness, nausea, vomiting, abnormal LFTs.
- Other rarer side effects: hepatitis, pancreatitis, hematological (decreased platelets), dermatological (rash), neurological (tremor, ataxia).
Lactimal is used for Bipolar. It includes the risk for what?
Risk for Steven-Johnson’s syndrome.
Describe some characteristics of Steven’s-johnson syndrome.
- Can progress to toxic epidermal necrolysis – medical emergency, sometimes ICU level (resemble severe burns).
- Fever and rash, especially involving mucous membranes.
- Rash may be preceeded by flu like symptoms (fever, sore throat, fatigue, cough).
- Rash can be painful and involving blisters.
WHat are some causes of Steven’s-johnson syndrome?
- acute infection
- medications - especially anticonvulsants like Lamictal
- PCN
- meds like ibuprofen, tylenol, naproxen, allopurinol
- radiation therapy
What are the justifiable uses of antipsychotics in children?
- Childhood Schizophrenia
- Childhood Bipolar Disorder
- Autistic Spectrum Disorders
- Tourette’s Disorder
- Substance Induced Psychosis
List some atypical antipsychotic drugs.
- aripiprazole
- olanzapine
- quetiapine
- risperidone
- ziprasidone
These are the second generation.
What are the side effects of the 2nd generation anti-psychotics?
- Abilify (aripiprazole): GI effects, headache, sedation (higher dosages).
- Geodon (ziprasidone): cardiac effects (caution in those with cardiac history), dizziness, nausea, sedation (IM).
- Zyprexa, Zydis (olanzapine): metabolic syndrome, weight gain, dry mouth, akathisia, insomnia, GI effects, tremor, lightheadedness.
- Seroquel (quetiapine): sedation, metabolic syndrome, weight gain, orthostatic hypotension, GI effects, and dry mouth.
- Risperdal (risperidone): orthostatic hypotension, weight gain, elevated prolactin levels.
- Clozaril (clozapine): hematological changes (agranulocytosis), orthostatic hypotension, sedation, constipation, hyperthermia, hypersalivation, seizure (higher dosages), myocarditis.
What are some adverse effects of the first generation antipsychiotics?
CV effects such as arrythmia and hypotension.
What are some conditions that compound the CV risk factor of anti-psychotics?
Female gender Hypokalemia, hypomagnesaemia CV disease History of prolonged QTc Other medications on board that can prolong QTc
What medical urgencies/emergencies are associated with anti-psychotic drugs?
- Parkinsonianism - tremor, rigidity, bradykinesia
- Acute dystonia - brief or prolonged muscle contraction
- Acute akathisia - restlessness, can’t be still, agitated
- Tardive dyskinesia (TD) - involuntary muscle movement
- Neuroleptic malignant syndrome (NMS)
What are psychostimulants used to treat?
ADHD, narcolepsy. Be careful of Bipolar - don’t want to stimulate a manic episode.
Name some psychostimulants.
- ritalin
- metadate
- focalin
- adderall
- Concerta
What are some alternative meds to treat ADHD?
- Strattera - atomoxatine
- Wellbutrin - buproprion
- older drugs are tenex and clonidine- not really used because of sedating effects and hypotension
Describe some issues when treating anxiety pharmacologically.
- Fast acting anxiolytics may have more of a reinforcing effect on the illness, due to immediate relief of aversive emotional experiences, but also because they wear off fast, causing emotional “roller coaster” effect. Will also disrupt sleep due to these effects.
- BZDs (xanax, ativan, klonopin, valium) tend to cause tolerance and increasing demand.
- BZD withdrawal like alcohol withdrawal can be life threatening.
- I prefer less reinforcing medications like SSRI or if needed for short period, atypical antipsychotic.
- Behavioral therapy is mandatory, and most effective.
What are some things to consider when treating sleep disorders in children?
- Assess why difficult to sleep
- Start with medications with low side effects/interaction potential
e. g. Benadryl or Atarax, Remeron, Melatonin - In young adults, can consider sonata
Which neurophych meds have been historically safe and effective for children?
In order of most safest/efficacious:
- stimulants
- SSRI’s
- mood stabilizers
- anti-psychotics
What is safer monopharmacy or polypharmacy?
Monopharmacy.
