3/19/18. Medications Used In the Mental Health Care of Children. General Pediatric Psychopharmacology Overview

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1 Medications Used In the Mental Health Care of Children American Academy of Pediatrics Critical Issues in School Health March 22 nd 2018 Jennifer Zajac, D.O. Saachi Tarr, M.D. Vanessa Katon, D.O. Institute of Living/ Hartford Hospital General Pediatric Psychopharmacology Overview Psychopharmacology studies are limited in children. Off label use of medications common Children metabolize differently Developmental Aspects of Medication Management in Pediatric Population Basic pharmacokinetic processes are absorption, distribution, metabolism, and excretion: Children have smaller body size, but greater proportion of liver/kidney parenchyma when adjusted to body weight They have more body water, less fat, and less plasma albumin 1

2 Developmental Aspects of Medication Management in Pediatric Population Because of these differences in children compared to adults: There is smaller volume of distribution for drugs (higher risk for sensitivities because of higher peak plasma concentrations) Greater drug extraction during 1 st pass metabolism (less drug that actually makes it to metabolism phase) Lower bioavailability (less drug available to utilize) Faster metabolism and elimination of the drug Developmental Aspects of Medication Management in Pediatric Population This leads typical Start Low and Go Slow prescribing to avoid potential for sensitivities. However, because of faster metabolism, etc. it is common to prescribe at higher dosages and/or more frequent dosing schedules to achieve optimum benefits. Antidepressants Several different types of antidepressants: SSRIs (Selective Serotonin Reuptake Inhibitors) SNRIs( Serotonin-Norepinephrine Reuptake Inhibitors) MAOIs (Monoamine Oxidase Inhibitors) TCAs (Tricyclic antidepressants) Other: Wellbutrin, Mirtazapine 2

3 Antidepressants: SSRIs SSRIs are a group of antidepressants that selectively inhibit serotonin reuptake First-line to treat depression and anxiety Require minimum of 4-6 weeks to discern maximum benefit of current dose Commonly Used SSRIs Citalopram (a.k.a. Celexa) Typical starting dose 5-10 mg daily Typical Dosage Range mg daily Not FDA approved in children Commonly used to treat: Social phobia, depression, GAD Lexapro (a.k.a. Escitalopram) Typical starting dose 5-10 mg daily Typical dosing range mg daily FDA approved for MDD in ages 12 and up Also commonly used to treat anxiety symptoms Commonly Used SSRIs Fluoxetine (a.k.a. Prozac) Typical starting dose 10 mg daily (AM) Typical dosing range mg daily (AM) FDA approved to treat MDD in ages 8 and up Also used to treat OCD, GAD, Separation Anxiety, Social Phobia Known CYP450 2D6 inhibitor-can impact metabolism of any other medication processed by this enzyme Long half-life Paroxetine (a.k.a. Paxil) Typical starting dose 10 mg daily Typical dosing range mg daily Not FDA approved in pediatrics Less frequently used given significant withdrawal side effects quickly after abrupt cessation May still be seen at times to treat depression, Separation Anxiety, and Social Anxiety 3

4 Commonly Used SSRIs Fluvoxamine (a.k.a Luvox) Typical starting dose 25 mg daily Typical dosing range mg daily More rare to see used in this population, but may come across this medication for treatment of OCD, GAD, Separation Anxiety, and Social Anxiety in select few Sertraline (a.k.a. Zoloft) Typical starting dose mg daily Typical dosing range mg daily (some young people require as high as 300 mg however) Commonly used to treat depression, OCD, Panic Disorder Side Effects of SSRIs Typically SSRIs are very well tolerated Most often, any side effects experienced typically subside with time and/or reduction in dosage and/or change in dosing frequency More common side effects experienced include: GI upset (e.g. nausea/vomiting) Insomnia (e.g. Fluoxetine) Sedation (e.g. Paroxetine, Fluvoxamine) Anxiety/Agitation ( e.g. Fluoxetine) Headache Side Effects of SSRIs Rare but more serious side effects include: Serotonin Syndrome Increased suicidality (a.k.a. Black Box warning) 4

5 Serotonin Syndrome Hyperthermia Muscle Rigidity Myoclonus Tremors Agitation Confusion Rare if SSRI taken as prescribed Can occur in: overdose, taking SSRI with another serotonergic agent, recent MAOI use Black Box Warning FDA issued public warning indicating individuals younger than 25 years of age treated with an antidepressant are at increased risk of suicidal thoughts or behavior. However, review of evidence still suggests that benefits of antidepressant medications likely outweigh their risks to children and adolescents with major depression and anxiety disorders If increase suicidal behavior is to be observed in relation to antidepressants, it is most likely to occur following initiation or dosage increase. Antidepressants: SNRIs Selectively inhibit serotonin and norepinephrine reuptake Require minimum of 4-6 weeks to discern maximum benefit of current dose Often 2 nd or 3 rd in line to treat anxiety and depressive disorders Can be beneficial in treating symptoms of anhedonia/low motivation related to depression 5

6 Commonly Used SNRIs Venlafaxine (a.k.a. Effexor) Typical starting dose 37.5 mg q AM Typical dosing range mg q AM Frequently used to treat Social Anxiety, GAD, Separation Anxiety, and depression Typically prescribed in XR formulation, but may occasionally see short acting formulation requiring BID dosing Desvenlafaxine (a.k.a. Pristiq) Typical starting dose 25 mg daily Typical dosing range mg daily Not yet FDA approved in pediatrics population, but used to treat depression and anxiety disorders Duloxetine (a.k.a. Cymbalta) Typical starting dose mg q AM Typical dosing range mg q AM Not FDA approved in pediatric population; may more commonly see this prescribed in individuals suffering from pain issues (e.g. fibromyalgia) May see used to treat anxiety and depressive disorders Side Effects of SNRIs Most often, any side effects experienced typically subside with time and/or reduction in dosage and/or change in dosing frequency SNRIs can be very well tolerated and potential side effects overlap with those of SSRIs, but due to increase in NE, there is less likely to be sedation. More common side effects experienced include: GI upset (e.g. nausea/vomiting) Insomnia Anxiety/Agitation Headache Side effect of SNRIs Due to increases in NE from the selective reuptake of SNRIs, individuals may also experience: Increased blood pressure Tachycardia Reduced appetite and associated weight loss 6

7 Antidepressants: Tricyclics (TCAs) Tricyclic Antidepressants Less commonly used in pediatric populations due to anticholinergic effects and cardiac risks in overdose. It is advised to get baseline ECG and periodic ECG when taking these medications. Clomipramine Typical dosing range mg/kg daily Used to treat OCD Imipramine Typical dosing range mg/kg daily Used to treat GAD, Panic Disorder, Nocturnal Enuresis Side Effects of TCAs 7

8 Antidepressants: MAOIs Through the inhibition of Monoamine Oxidase, serotonin, norepinephrine, and dopamine are increased. Old class of medications used to treat depression and anxiety Monoamine Oxidase Inhibitors are very rarely ever used in pediatric population due to their known number of potential side effects including risk of hypertensive crisis from excess tyramine build up. A special diet is required. Antidepressants: Other Bupropion (a.k.a. Wellbutrin SR & Wellbutrin XR) Some minimal impact on SE and NE levels as well impact on increasing DA Used to treat depressive disorders, smoking cessation, ADHD Typical starting dose SR & XR formulations 100 mg q AM & 150 mg q AM) Dosing ranges: Wellbutrin SR mg BID Wellbutrin XR mg q AM Antidepressants: Other Mirtazapine (a.k.a. Remeron) Dosing ranges between mg Not FDA approved in pediatric population Acts by antagonizing the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as by blocking 5-HT2 and 5-HT3 receptors. Because of its strong sedative effects, often given at night and may be prescribed to assist in sleep difficulties 8

9 Antidepressants Mood Stabilizing Agents Medications with mood stabilizing properties include atypical antipsychotics, antiepileptics, and lithium. Mood stabilizers are used to treat bipolar mania/depression, augment unipolar depression, as well as potentially be used in other circumstances of disruptive/aggressive behavior (e.g. DMDD) Mood Stabilizing Agents: Lithium Lithium is FDA approved in children over 12 years of age for Bipolar mania and maintenance. Also can be used to augment in depression One of two medications known to reduce suicidality Mechanism of action unknown exactly and overall complex but includes: Alteration in sodium transport across cell membranes Alteration of neurotransmitters including catecholamines and serotonin 9

10 Mood Stabilizing Agents: Lithium Typical dose range mg/kg/day Often started around mg daily and titrated by mg every 5-7 days. Maximum dosing 1800 mg/day Typically divided in BID or even TID dosing Narrow therapeutic window ( ) Excessive sweating, vomiting, diarrhea all could impact lithium level and lead to toxicity NSAIDs should be avoided (only acetaminophen) Frequent blood draws upon initiation and then every 3-6 months once stable level achieved Lithium level TSH/T4 Electrolytes including Ca Renal Panel Side Effects of Lithium Common side effect associated with Lithium include: Weight gain Tremor Acne Increased thirst Polyuria Hypothyroidism/Euthyroid/Goiter Sedation Lithium Toxicity Ataxia Confusion Renal failure Cardiac arrhythmia Significant tremor Vomiting Is deadly if not treated; Lithium should be stopped immediately if toxicity occurs 10

11 Mood Stabilizing Anti-epileptics Carbamazepine (a.k.a. Tegretol) Typical dosing range 400-1,200 mg/day; mg/kg/day if under the age of 6 years Used to treat seizure disorders, some pain syndromes, Bipolar Disorder/Mood lability Acts through voltage gated sodium channels to inhibit release of glutamate Induces its own metabolism through CYP450 3A4 enzyme often requiring upward dose adjustment of itself, but also potentially any other medications metabolized through this enzyme. Baseline labs and periodically Common side effects include: Sedation Dizziness GI upset Blurred vision Benign leukopenia-transient in up to 10% Rash-not to be confused with Steven s Johnson s Weight gain can occur but less associated than other agents Mood Stabilizing Anti-epileptics More rare but life-threatening side effects include: Aplastic anemia Unusual bleeding and bruising Mouth sores Fever Sore throat Infections Severe skin reactions (e.g. Steven s Johnson s) Fever Unexplained widespread skin pain A red or purple skin rash that spreads Blisters on your skin and the mucous membranes of mouth, nose, eyes and genitals Shedding of your skin within days after blisters form Generalized flu-like symptoms SIADH w/ associated hyponatremia Mood Stabilizing Anti-epileptics Valproate (a.k.a. Depakote, Depakene, Depakote ER) Typical dosing range mg/kg/day MOA largely unknown but believed to work through voltage-sensitive sodium channels as well as having mechanism to increase GABA Used to treat seizure disorders, Bipolar Disorder/Mood lability, and aggressive/disruptive behaviors Baseline labs and routine monitoring of Platelet counts, LFTs, Lipids, Ammonia, Depakote Level 11

12 Mood Stabilizing Anti-epileptics Depakote side effects more commonly include: Sedation Weight gain and associated metabolic syndrome GI upset Controversial, less common side effects include: Alopecia, PCOS, Decreased Bone Density Frequently given as BID or even TID dosing to avoid SE Mood Stabilizing Anti-epileptics Rare but more life-threatening side effects of Depakote include: Hepatotoxicity Pancreatitis Elevated Ammonia Mood Stabilizing Anti-epileptics Lamotrigine (a.k.a. Lamictal) Typical dosing roughly 4.5 mg/kg/day Requires very slow titration to avoid potential risk of Steven s Johnsons Attenuates glutamate release via Na+, K+, and Ca+2 channels Used to treat seizure disorders, Bipolar Disorder, augment in MDD Fairly well tolerated: Does not require lab monitoring Not typically associated with weight gain or sedation Side effect most commonly associated but is very rare with proper titration is Steven s Johnsons Syndrome. Pediatric population at higher risk, but still very rare Along with severe rash, associated with multi-organ failure If purpuric, widespread, tender rash with systemic sx develops-stop Lamictal, go to ED 12

13 Mood Stabilizing Anti-epileptics Oxcarbamazepine (a.k.a. Trileptal) Frequently further down the line with less evidence to support mood stabilizing properties; off-label in kids Benefits include minimal need for lab monitoring Some increased risk for hyponatremia that may check Na+ levels every 3-6 months Generally well tolerated in terms of levels of sedation and weight gain Some association with drug rashes including Stevens- Johnsons, but very rare Mood Stabilizing Anti-epileptics Topiramate (a.k.a. Topamax) Little evidence to truly support its use as a mood stabilizer, but may be still be used as adjunctive treatment for mood stabilization Takes several weeks to discern if benefits can be seen More likely to see this used in seizure disorders, migraine prophylaxis, bingeeating, and weight management Common side effects include: Appetite suppression Sedation Blurred and/or double vision Confusion Memory problems Psychomotor retardation General fatigue Increased risk for kidney stones ADHD Medications used to treat inattentive behavior hyperactivity explosively irritability impulsivity Medication types: Stimulants, alpha agonists, stimulant like medications 13

14 Role of treatment Help improve attention, focus, and concentration Decrease hyperactivity, fidgeting, and impulsivity May increase academic performance and peer interactions Improve peer relationships Variety of formulations Formulations of pills: IR = Immediate Release XR = Extended Release ER = Extended Release SR = Sustained Release LA = Long-Acting CD = Controlled-Dispense Liquid Patches Alpha-2-Adrenergic Agonists (Alpha-2-agonists) Also used: tic disorders, substance withdrawal, ADHD, PTSD, social anxiety, irritability, and situations that include anxiety and impulsivity. Traditionally used to treat HTN. Clonidine (IR) Typical starting dose 0.05 mg q HS Typical dosing range mg/day in divided doses Works centrally on post-synaptic alpha 2 receptors in the prefrontal cortex Clonidine HCL extended release tablets (ER) (commercially: Kapvay) Clonidine Patch qweekly though can be more frequent, during titration may briefly have oral dose 14

15 Alpha-2-Adrenergic Agonists (Alpha-2-agonists) Guanfacine IR (aka Tenex) More selectivity at alpha receptors such that sedation frequent. Similar side effect profile otherwise Regular monitoring of blood pressure recommended Typical starting dose 0.05mg Dose range 0.05mg-2mg/day in divided doses (daily, BID, 4x day) Guanfacine ER (aka Intuniv) Typical starting dose: 0.05mg Dose Range 0.05mg-4mg (though can be higher) Side Effects Alpha-2-agonists Constipation Sedation or fatigue Low blood pressure Low heart rate Fever Weakenss Nausea and vomiting Nervousness or agitation Headache High-blood pressure if med suddenly discontinued (without tapering off) Long-acting formulations may cause dry mouth and require student to drink plenty of water Stimulants Modulate NE and dopamine levels in the CNS Two broad categories: Amphetamine Derivatives Methylphenidate Derivatives Quick Response Can make quicker dose adjustments No withdrawal from missed doses 15

16 Stimulants Stimulants Methylphenidate Long Acting Concerta Daytrana Patch Intermediate Acting Metadata ER Metadata CD Ritalin LA Ritalin SR Short Acting Methylin (liquid or chewable) Quillivant XR (liquid available) Ritalin 16

17 Amphetamine Derivatives Short Acting Evoke Zenzedi Adderall ProCentra (liquid) Long Acting/ER Vyvanse (can remixed with yogurt/oj/water) Adderall XR (capsule can be opened and sprinkled on applesauce) Dexedrine Spansule Focalin - short-acting Focalin XR long-acting psules_novartis.html Notes on Stimulants Can have XR then IR dosing Can have IR BID dosing Can have XR BID dosing May have stimulant + alpha-2-agonist combination High abuse potential Stimulant can be stopped suddenly alpha-2-agonist MUST TITRATE 17

18 Daytrana Patch Newer formulation-transdermal Available: 10/15/20/30mg patch Patch should not be on more than 9 hours Dose can be adjusted by length of patch use Do not reapply used patch Generally apply to hip Alternate hip each day and rotate sites Stimulant Side Effects Anxiety Decreased appetiteà weight loss à delayed growth Pediasure Diarrhea or constipation HTN Tachycardia Dizziness Dry mouth Irritability Nausea Headache Trouble sleeping Possible worsening of tics Rash (Daytrana patch) Paranoia/psychosis Rarely: arrhythmia Non-stimulant Atomoxetine (aka Strattera) Mechanism of Action: Unclear,? inhibition of presynaptic norepinephrine re-uptake in the prefrontal cortex Small changes within 2 weeks 4-6 weeks to see significant improvements May help improve attention and reduce hyperactivity/impulsivity The most common side effects include: Constipation Dry mouth Nausea Decreased appetite Dizziness Problems urinating Low abuse potential 18

19 Anti-psychotics Used for: aggression, augmentation for depression or anxiety treatment, irritability, psychosis, Bipolar DO, OCD, behaviors related to autism One of the first categories of psychiatric medications: Chlorpromazine (1950) Dosage can be divided throughout the day Two Broad Categories Side Effects First Generation AP Chlorpromazine, Haloperidol, Perphenazine in children (Thorazine/Haldol/Trilafon) Anticholinergic: constipation, blurred vision, dry mouth, urinary retention Antihistaminic: Sedation Anti alpha 1: orthostatic hypotension Hyperprolactonemia- Galatorrhea/Gynecomastia Extrapyramidal Side Effects (EPS) Also risk for QTc prolongation 19

20 EPS Hours to days: Acute dystonia (sustained muscle contraction), tremor Laryngeal dystonic reaction!! Days to weeks: Akathisia (inner feeling not restlessness, very disturbing) Weeks to months/years: Parkinsonism, Tarydive Dyskinesia Side Effects Second Generation Antipsychotics Risperidone, Aripiprazole, Quetiapine, Ziprasidone May have SE of typical AP but rarer Increased risk for Metabolic Syndrome: weight increase, particularly abdominal girth hyperlipidemia Increase insulin resistance Diabetes Mellitus Sedation/Fatigue Sometimes Activating/increase irritability Risperidone: Hyperprolactinemia Dosage ranges substantially vary: Risperidone 0.25mg - 6mg daily, Quetiapine 12.5mg to 900mg daily Neuroleptic Malignant Syndrome 20

21 Long Acting Injectables IM delivery of antipsychotics Slow release allows for qweekly to q 3 monthly dosing Individuals with significant psychosis Both Typical and Atypical Antipsychotics May have overlap with oral medications during initiation of injectable Once steady state is reached, no more oral medications Increases compliance Risk of same side effects Miscellaneous May come across other medications used to treat mental health disorders. Prazosin o Prescribed to address trauma symptoms: nightmares, flashbacks, hypervigilance o Typically given at night o May cause hypotension Hydroxyzine (a.k.a. Vistaril) o May see as scheduled or PRN for episodes of anxiety in conjunction with other anxiolytic medications Buspirone (a.k.a. Buspar) o BID, TID dosing o May be used to address anxiety Benzodiazepines (e.g. Lorazepam, Clonazepam) o Regular, long-term use typically avoided o Potential for abuse, tolerance, and dependence o Sometimes prescribed scheduled and/or PRN for acute agitation episodes, panic episodes, or for catatonia Trazodone o Typically prescribed mg q HS to address sleep issues o However, not FDA approved for sleep and is only FDA approved for MDD in adults Benadryl o May be prescribed as PRN for acute agitation or sleep o Ideally would avoid long-term use due to sedation and anticholinergic effects Miscellaneous Trazodone o Typically prescribed mg q HS to address sleep issues o However, not FDA approved for sleep and is only FDA approved for MDD in adults Benadryl o May be prescribed as PRN for acute agitation or sleep o Ideally would avoid long-term use due to sedation and anticholinergic effects 21

22 Take Home Points Children metabolize medications differently Medication Emergencies: Serotonin Syndrome NMS Laryngeal Spasm ADHD treatment varies a great deal Important to keep an eye on vital signs Also include psychiatric vital signs: worsening irritability, increase in depression Bibliography Diagnostic And Statistical Manual of Mental Disorders : DSM-5. Arlington, VA :American Psychiatric Publishing, Print. North Shore LIJ, Children s Medical Center NY ADHD Medication Guide Chart. Stahl, Stephen M. Stahl s Essential Psychopharmacology: Neuroscientific Basis and Practical Application. Cambridge University Press, Stahl, Stephen M. The Prescriber's Guide: Stahl's Essential Psychopharmacology. Cambridge University Press, Zajac, Jennifer. ADHD Medications 4 Dec PowerPoint File. 22