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Home , Levomilnacipran

Update on Newer Psychiatric Medications

Teresa (Tess) Judge-Ellis DNP, FNP-BC, PMHNP-BC, FAANP Associate Lecturer, Fitzgerald Health Education Associates, North Andover, MA Clinical practice, FNP/PMHNP Winfield Community Clinic, Winfield, IA PMHNP Meadowlark Psychiatric Services, North Liberty, IA Clinical Associate Professor, University of Iowa College of Nursing, Iowa City, IA

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Disclosure

• No real or potential conflict of interest to disclose. • No off-label, experimental or investigational use of drugs or devices will be presented.

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Objectives

• Upon completion of the learning activity the participant will be able to: – Recognize clinical scenarios when newer and second line medications should be considered in the management of major depressive disorder (MDD).

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1 Objectives (continued) • Upon completion of the learning activity the participant…: (cont.) – Identify the mechanism of action of newer medication for the treatment of MDD. – Describe the mechanism of action of newer agents for .

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Major Depressive Disorder SIG E CAPS + Mood DSM-5 criteria • Sleep • Concentration • Interest* • Appetite • Guilt • Psychomotor • Energy • Suicidal thoughts

*Gateway symptoms • + mood* • One must be present + 4 other symptoms present for 2 weeks • Not due to other psychiatric or medical condition or substance use disorder

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Psychotropic Options for Major Depressive Disorder

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Generic Selective Reuptake Inhibitors (SSRI)

• The first-line medications for most mood disorders – (Celexa®) – (Lexapro®) – (Prozac®) – (Luvox®) – (Paxil®) – (Zoloft®)

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Serotonin Reuptake Inhibitors (SNRI)

Generic SNRI Branded SNRI • • (Effexor®) (Pristiq®) • • Levomilnacipran (Cymbalta®) (Fetzima®)

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Other

Generic Trade/Branded • Norepinephrine- •Serotonin modulator reuptake and stimulator inhibitor − (Trintellix®) – (Wellbutrin®) •Serotonin partial •Noradrenergic and agonist/reuptake specific serotonergic inhibitor − (Viibryd®) – (Remeron®)

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3 Newer Antidepressants

Vilazodone (Viibryd®) Vortioxetine (Trintellix®) Levomilnacipran (Fetzima®)

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What do they have in common? Serotonin

Adverse effects and cautions Attributed to increased serotonergic activity

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Adverse Effects and Precaution Common to all SSRI/SNRI

• Abnormal bleeding – Caution about increased risk of bleeding with patients on NSAIDs, aspirin, warfarin and other anticoagulants • Activation of mania/hypomania – As with all antidepressants

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Adverse Effects and Precaution Common to all SSRI/SNRI (continued) • Hyponatremia – Especially with elderly patients and those on diuretics • Angle closure glaucoma risk in patients with anatomically narrow angles due to pupillary dilation

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Adverse Effects and Precaution Common to all SSRI/SNRI (continued) • Contraindicated due to risk of serotonin syndrome – With MAOI use and within 14 days of stopping an MAOI – In patients being treated with or intravenous

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Adverse Effects and Precaution Common to all SSRI/SNRI (continued) • Boxed warning for an increase risk of suicidal thinking and behavior (suicidality) in children, adolescents and young adults (age 18−24 years) with MDD and other psychiatric disorders. • Pregnancy category C • Breastfeeding risk: Acceptable for SSRIs

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5 Adverse Effects and Precaution Serotonin Syndrome • What is it? – Over activation of the central and peripheral serotonin receptors due to high level of serotonin • Incidence is unknown. – Uncommon with low dose SSRI or SNRI and occasional use of a triptan • A diagnosis of exclusion

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Risk of Serotonin Syndrome (continued) • Caution with concomitant use of other serotonergic drugs – Examples: Triptans, TCAs, fentanyl, , , , , St John’s Wort, antidepressants, MAOIs, SGAs, • Alerts – Chronic pain, migraine history, depression or anxiety, end-stage renal disease

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Serotonin Syndrome

• Signs and symptoms – Alteration in mental status – Neuromuscular abnormalities – Autonomic hyperactivity

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6 Spectrum of Clinical Findings in Serotonin Syndrome

Boyer E and Shannon M. N Engl J Med 2005;352:1112-1120

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Findings in a Patient with Moderately Severe Serotonin Syndrome

Boyer E and Shannon M. N Engl J Med;352:1112-1120

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Intervention in Serotonin Syndrome

• Mildly ill – Hyperreflexia, tremor, afebrile • Supportive care • Removal of precipitating drugs • Benzodiazepines – Source: Boyer E and Shannon M. N Engl J Med 2005;352:1112-1120.

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7 Intervention in Serotonin Syndrome (continued) • Moderately ill – Aforementioned findings, fever, cardiorespiratory abnormalities • Aggressive correction of cardiorespiratory and thermal abnormalities • Administration of 5-HT2A antagonists such as cyproheptadine (Periactin®) with a dose range=12−32 mg/24h so that up to 95% of serotonin receptor sites are occupied – Source: Boyer E and Shannon M. N Engl J Med;352:1112-1120.

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Vilazodone (Viibryd®) • Indication – For the treatment of major depressive disorder in adults age ≥18 years • Mechanism of action – Increases CNS serotonergic activity • SSRI • Partial 5-HT1A receptor agonist • Cost=$140 per month

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Vilazodone (Viibryd®) (continued) • How supplied – 10 mg, 20 mg, and 40 mg tablets • Recommended daily dose – Start with an initial dose of 10 mg once daily with food for 7 days – Then increase to 20 mg once daily with food – Increase up to 40 mg once daily with food after a minimum of 7 days between doses

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8 Vilazodone (Viibryd®) (continued) • Take with food – Taking on an empty stomach can decrease availability by 50−60%

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Vilazodone (Viibryd®) Adverse Effects • Most common adverse effects – Diarrhea, , – Insomnia – Headache, dizziness • No reported weight gain in clinical trials • Minimal reported sexual adverse reactions

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Vilazodone (Viibryd®) Niche

Comorbid depression and anxiety Weight gain worriers Sexual adverse effect concerns

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9 Case Example

• Mr. R., a 25-year-old graduate student, recently moved to your town to begin graduate studies. He has a history of major depressive disorder and generalized anxiety disorder. His anxiety is worse and he is feeling depressed. His current medication is sertraline 100 mg. PHQ-9=16; GAD-7=12

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Case Example (continued) • You increase his sertraline to 150 mg and recommend counseling. • He returns in 2 months with continued mild depression (PHQ- 9=14; GAD-7=12) and worsening anxiety symptoms of rumination, muscle tension and occasional difficulty with middle insomnia.

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Case Example (continued) • He is also unhappy with the sexual adverse effects, specifically difficult and delayed orgasm, that he attributes to the sertraline. • You start vilazodone 10 mg daily with breakfast and reduce the sertraline to 100 mg.

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10 Case Example (continued) • During week 2 you reduce the sertraline to 50 mg daily and increase vilazodone to 20 mg daily. • During week 3 the sertraline was discontinued and the vilazodone was increased to 40 mg daily.

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Case Example (continued) • Mr. R. tolerated this transition well. After a month his depression had improved (PHQ-9=10) and his anxiety symptoms were improved (GAD-7=7). • While he still has some delay to orgasm, this is much improved and he opts to continue on vilazodone (Viibryd®) 40 mg.

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Vortioxetine (Trintellix®)

• Indication – For treatment of major depressive disorder in adults age ≥18 years • Cost – About $240/month

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11 Vortioxetine (Trintellix®) September, 2013 • What is it? – “Multi-modal” antidepressant or a “serotonin modulator and stimulator” • Selective serotonin (SSRI) • Serotonin receptor agonist (5-HT1A) • Partial agonist (5-HT1B) • Antagonist (5-HT3A, 5HT7, 5-HT1D)

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Vortioxetine (Trintellix®) (continued) • How supplied – 5 mg, 10 mg, 15 mg, and 20 mg tablets • Recommended daily dose – 10 mg starting dose without regards to meals • If 10 mg is tolerated, dosage can be increased to 20 mg/day. • Consider 5 mg/day for those unable to tolerate higher doses

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Vortioxetine (Trintellix®) (continued) • Elderly study – 155 adults age 64−88 years with MDD • Diagnosed with MDD recurrent • No comorbid cognitive impairment; MMSE score>24 – Vortioxetine 5 mg or – Significant improvement in the HAMD-24

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12 Vortioxetine (Trintellix®) Adverse Effects and Precaution • Vortioxetine is metabolized by CYP2D6. −Reduce vortioxetine dose by 50% when co-administrated with a strong CYP2D6 inhibitor (e.g., bupropion, fluoxetine, paroxetine, quinidine). −Consider increasing the vortioxetine dose when co-administered with a strong CYP2D6 inducer (e.g., rifampicin, carbamazepine, phenytoin)

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Vortioxetine (Trintellix®) Adverse Effects and Precaution (continued) • Vortioxetine is metabolized by CYP2D6. (cont.) −Maximum recommended dose of vortioxetine is 10 mg/day in known CYP2D6 poor metabolizers.

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Vortioxetine (Trintellix®) Adverse Effects and Precaution • Most common adverse effects – Nausea, , vomiting, dry mouth • Dose related • Mostly in the first week – Sexual dysfunction/adverse effects – Dizziness – Minimal reported weight gain

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13 Vortioxetine (Trintellix®) Adverse Effects and Precaution (continued)

• Taper off vortioxetine is recommended to avoid transient discontinuation symptoms of headache and muscle tension. • Individualize taper- generally 2‒4 weeks

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Vortioxetine (Trintellix®) Niche

Elderly with depression Concern will be with insurance coverage. Depression where cognitive “fog” is a dominant concern

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Case Example

• Norma is an 82-year-old woman with a history of major depressive disorder. She was hospitalized at age 70 and 76 years. Her symptoms had been managed well with citalopram 60 mg.

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14 Case Example (continued) • Past psychiatric medication tried and failed: Fluoxetine, citalopram, and bupropion. • After FDA warnings about prolonged QT interval with citalopram, she was tapered off citalopram and onto sertraline. Currently she is on sertraline 150 mg daily.

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Case Example (continued) • Depressive symptoms of decreased interest, lack of motivation and energy remain, which keep her from going out with friends and socializing. PHQ-9=17

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Case Example (continued) • Norma agreed to a medication change. –Week 1: Sertraline 100 mg daily –Week 2: Sertraline 50 mg and vortioxetine 5 mg –Week 3: Sertraline 25 mg and vortioxetine 5 mg –Week 4: Vortioxetine 5 mg

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15 Case Example (continued) • She tolerated the switch without difficulty. • Return visit at 2 months where she reported improvement in interest and “ambition.” PHQ=12 • Vortioxetine is increased to 10 mg. She returns in 6 weeks and feels “back to my old self.” PHQ=8

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Levomilnacipran (Fetzima®) July, 2013 • Indication – For the treatment of major depressive disorder in adults age ≥18 years • Cost – $200 per month

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Levomilnacipran (Fetzima®)

• Mechanism of action –Serotonin and norepinephrine reuptake inhibitor • Relatively more selective for norepinephrine reuptake inhibition (NRI) compared with serotonin reuptake inhibition (SRI) –>10-fold greater selectivity for NRI than SRI compared with duloxetine or venlafaxine

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16 Levomilnacipran (Fetzima®)

• Mechanism of action (cont.) –Serotonin and norepinephrine...(cont.) • Relatively more… (cont.) –Could offer more targeted treatment of NE deficiency MDD symptoms (e.g., concentration, physical slowing, decreased self-care) • Could be considered a NSRI

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Levomilnacipran (Fetzima®) (continued) • How supplied – 20 mg, 40 mg, 80 mg, 120 mg ER capsules • Recommended daily dose – Start at 20 mg daily, increase to 40 mg daily after 2 days – Based on efficacy and tolerability, increase by increments of 40 mg/d every 2 or more days up to a maximum dose of 120 mg daily • Take with or without food

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Levomilnacipran (Fetzima®) Adverse Effects and Precaution • Elevated and – Measure blood pressure and pulse prior to initiating levomilnacipran and periodically throughout treatment. • Mean change from baseline after one year of levomilnacipran – SBP was 3.9 mm Hg – DBP was 3.1 mm Hg – Control pre-existing hypertension before starting levomilnacipran.

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17 Levomilnacipran (Fetzima®) Adverse Effects and Precaution (continued) • Urinary hesitancy or retention – Use with caution in patients prone to obstructive urinary disorders. – Consider new onset of urinary hesitancy, or dysuria a possible drug-related effect.

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Levomilnacipran (Fetzima®) (continued) • Do not exceed 80 mg once daily when used with strong CYP3A4 inhibitors. – Ketoconazole, clarithromycin, ritonavir • Renal dosing – Moderate renal impairment (GFR 30−59 mL/min/1.73 m2) • Dose should not exceed 80 mg once daily – Severe renal impairment (GFR 15–29 mL/min/1.73 m2) • Dose should not exceed 40 mg once daily – Not recommended with end-stage renal disease

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Levomilnacipran (Fetzima®) (continued) • Most common adverse effects – Nausea, constipation, vomiting – – Heart rate increase, – • Pregnancy category C • Lactation risk unknown

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18 Levomilnacipran (Fetzima®)Niche

Comorbid chronic pain and depression Renal dosing

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Case Example

• Marjorie, 53-years-old, has fibromyalgia and depression. Her previous antidepressants include fluoxetine, duloxetine, citalopram, and sertraline. She takes 20 mg at bedtime for fibromyalgia and sleep. Some days are better than others with regards to her fibromyalgia.

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Case Example (continued) • She has not taken any antidepressants for several years, but would like to restart because of worsening depression symptoms. PHQ was 16. • You recommend returning to her counselor and starting on levomilnacipran (Fetzima®).

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19 Case Example (continued) • She starts levomilnacipran 20 mg/d for 2 days, then 40 mg daily for 5 days. • After one month she returns and her depression is improved but not 100% relieved. PHQ score is 12. She believes her pain is improving.

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Case Example (continued) • You increase the levomilnacipran to 80 mg. • One month later, PHQ is at 8. She feels happier and relates her pain is less of an issue.

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New Second Generation Indication for MDD Augment (Rexulti®)

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20 SGAs for MDD Augment

• XR (Seroquel XR®) • (Abilify®)

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Brexpiprazole (Rexulti®) July, 2015 • Indication – For schizophrenia and adjunctive treatment for major depressive disorder • Cost – $867 per month

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Brexpiprazole (Rexulti®) (continued) • Mechanism of action – 5-HT1A receptor partial agonist – D2 receptor partial agonist – 5-HT2A receptor antagonist – α1A receptor antagonist – α1D receptor antagonist

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21 Brexpiprazole (Rexulti®) (continued) • How supplied – 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg tablets • Recommended daily dose for MDD augment – 0.5 mg or 1 mg daily – Titrate increases at weekly interval to the patient’s clinical response and tolerability

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Brexpiprazole (Rexulti®) (continued)

• Recommended daily dose for MDD augment (cont.) – Target dose 2 mg daily; maximum daily dose 3 mg • Take with or without food

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Brexpiprazole (Rexulti®) (continued) • Dose adjustments with moderate to severe hepatic impairment (<2 mg daily) • Dose adjustments for renal impairment GFR≤60 mL/min/1.73 m2 (2 mg/day)

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22 Brexpiprazole (Rexulti®) (continued) • Dosing adjustments recommended – Patients who are known CYP2D6 poor metabolizers – Patients taking CYP3A4 inhibitors, or CYP2D6 inhibitors or strong CYP3A4 inducers

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Brexpiprazole (Rexulti®) (continued) • In clinical trials, brexpiprazole dosing was not adjusted for strong CYP2D6 inhibitors: Paroxetine, fluoxetine – However start low, 0.5 mg and wait longer between dosage adjustments

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Brexpiprazole (Rexulti®) Boxed Warnings • Increased mortality in elderly patients with dementia-related psychosis – Common to all SGAs • Suicidal thoughts and behaviors in children, adolescents, and young adults – Common to all antidepressants

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23 Brexpiprazole (Rexulti®) Antipsychotic Adverse Effects • Neuroleptic malignant syndrome • Tardive dyskinesia • Extrapyramidal adverse effects • Metabolic changes – Hyperglycemia/diabetes, dyslipidemia, weight gain

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Brexpiprazole (Rexulti®) Antipsychotic Adverse Effects (continued) • Leukopenia, neutropenia, agranulocytosis • Orthostatic hypotension/syncope • Body temperature dysregulation • Dysphagia • Cognitive and motor impairment

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Brexpiprazole (Rexulti®) Antipsychotic Metabolic Syndrome Monitoring Recommendations • Baseline – BMI, waist circumference, Hgb A1C, fasting plasma glucose, fasting lipid profile • 1 month – BMI, waist circumference • 2 months – BMI, waist circumference

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24 Brexpiprazole (Rexulti®) Antipsychotic Metabolic Syndrome Monitoring Recommendations (continued) • 3 months – BMI, waist circumference, Hgb A1C, fasting plasma glucose, fasting lipid profile • 6 months – BMI, waist circumference • Annually – BMI, waist circumference, Hgb A1C, fasting plasma glucose, fasting lipid profile Fitzgerald Health Education Associates 73

Brexpiprazole (Rexulti®) Niche Recurrent MDD Adjunctive System for monitoring

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Suvorexant (Belsomra®)

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Sleep Architecture Naturally Occurring Sleep’s 2 Stages

1. Non-rapid eye movement (NREM) – Stage 1 − Transitional – Stage 2 − Light sleep – Stage 3 − Deep sleep – Stage 4 − Deepest sleep 2. Rapid eye movement (REM)

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Non-REM: Stages 1 and 2

• Stage 1 – Easily awakened “muscle jump” (hypnic myoclonia) • Stage 2 – Heart rate slows, body temperature drops – 50% of total sleep time

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Non-REM: Stage 3

• Stage 3 – Delta waves (slow waves) – Moving to deeper sleep

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26 Stage 4: “Deep Sleep”

•Stage 4 – Delta waves exclusively • Difficult to arouse • No eye movement or muscle activities – When interrupted • “Groggy and disoriented” – Stage of bedwetting, night terrors or sleep walking occur during deep sleep

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REM Sleep: 20% of Adult Sleep • Rapid, irregular and shallow breathing • Rapid eye jerks in various directions • Temporary paralysis of limb muscles • Increased HR, BP • Penile erections • Most vivid dreams

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Sleep Stages Movement Through 5 Stages

• Adults actively move through the sleep process from NREM stages 1−4 to REM – Complete cycle typically 90−100 minutes – Complete 4−5 cycles per night

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Sleep Stages Movement Through 5 Stages (continued) • Length of REM sleep becomes progressively longer and time in deep sleep decreases throughout the night

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Potential Influence of Sleep Aids on Sleep Architecture: Potential Increase in Stage 1, Stage 2, Sleep Potential Reduction in Stage 3,

Stage 4, REM Sleep Consider as short -term therapy!

Source: http://www.medscape.com/viewarticle /723907_2

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Circadian Rhythm

•Biologic “internal clock” –Housed in suprachiasmatic nucleus in anterior hypothalamus –Fully developed by age 25 years – Source: http://www.howsleepworks.com/ how_circadian.html

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28 Sleep-Wake Homeostasis

• The pressure to sleep – Also known as sleep drive • Unable to overcome – With use of stimulants, can only mask need to sleep – With medications, can mildly promote or enhance sleep drive

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Pharmacology of Insomnia Treatment Therapeutic Approaches • Stimulate/activate sleep promoting system – GABA • Inhibitory neurotransmitter (NT) • Main hypothalamic NT, projects to several sleep regulating centers of the brain – Increase in GABA inhibits (“blocks”) the wake- promoting chemicals – Melatonin

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Pharmacology of Insomnia Treatment Therapeutic Approaches (continued) • Suppress the wake-promoting systems – Histamine – Cholinergic – Serotonin – Orexin

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29 Suvorexant (Belsomra®) Novel Mechanism of Action • What is it? – Orexin-receptor antagonist • Any drug that occupies a receptor site and prohibits its activation is an antagonist. • First drug in this class FDA approved to treat insomnia

Source of image: https://en.wikipedia.org/wiki/Orexin#/ media/File:1CQ0_crystallography.png

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Suvorexant (Belsomra®) Mechanism of Action (continued) • Blocking the binding of neuropeptides orexin A and orexin B to receptors OX1R and OX2R=Thought to suppress the wake drive

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Suvorexant (Belsomra®) C-IV

• Indication – For treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults age ≥18 years • What would you expect for PK?

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30 Suvorexant (Belsomra®) PK Information • Peak plasma time • Zolpidem (Ambien®) – 2 h post dose – T ½=2.6 h – With high fat meal= • 2.6 h × 3=7.8 h, take 1.5 h delay at 10 PM, approx. 12.5% of dose on • T ½=12 h board at 6 AM – As a result, when – Time to Cmax=1.6 h taking at 10 PM, 50% of the dose still on board at 10 AM

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Suvorexant (Belsomra®) Recommended Dose • How supplied – 5 mg, 10 mg, 15 mg, and 20 mg tablets • Recommended daily dose – 10 mg, taken ≥30 mins prior to bedtime, only if ≥7 h of sleep time available, only 1 dose per night • If 10 mg dose is well-tolerated but not effective, dose can be increased up to a maximum dose of 20 mg daily.

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Suvorexant (Belsomra®) Precaution Do we have this information on older meds? • Per FDA required study – Exposure to suvorexant increased in obese compared to nonobese patients • AUC and Cmax increased by 46% and 25% respectively compared to nonobese females. – Women compared to men • Consistent with warnings about other sleep aids including zolpidem (Ambien®)

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31 Suvorexant (Belsomra®) Adverse Effects and Precaution (continued) • Patient advised about these in handout provided with medication. – CNS depressant effects and daytime impairment – Abnormal thinking and behavioral changes – Worsening of depression/suicidal ideation – Sleep paralysis, hallucinations, cataplexy- like symptoms

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Newer ADHD Medications

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ADHD Symptom Clusters DSM-5 • Inattention – Off task, lacking persistence, difficulty sustaining focused, disorganized • Hyperactivity – Excessive motor activity when it is not appropriate, excessive fidgeting, tapping, talkativeness

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32 ADHD Symptom Clusters (continued) • Impulsivity – Hasty actions without forethought and with high potential for harm, desire for immediate rewards, inability to delay gratification

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Stimulants: First-line Medication in the Treatment of ADHD Safe and Effective • Mechanism of action – Increased norepinephrine and dopaminergic activity in the prefrontal cortex and other areas in the brain is thought to explain it’s efficacy. • How they differ?

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Stimulants: First-line Medication in the Treatment of ADHD Safe and Effective (continued) • (e.g., Ritalin®, Methylin®, Ritalin® LA, Concerta®) – Inhibits the reuptake of dopamine and norepinephrine • salts (Adderall®) – Inhibits the reuptake of dopamine and norepinephrine – Releases dopamine and norepinephrine from the presynaptic neuron

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33 Dopamine and Norepinephrine Pathways and ADHD  Prefrontal cortex –Inhibitory control •Ability to block out irrelevant stimuli to focus on the relevant

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Dopamine and Norepinephrine Pathways and ADHD (continued)  Executive function –Relates to task completion – Analyze, plan, organize, develop timelines, adjust or shift, complete

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Dopamine and Norepinephrine Pathways and ADHD (continued)  Dorsal striatum and motor response in ADHD –ADHD variable reaction time • Quick motor and long-delayed motor responses • Results in trouble executing motor component of a task

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34 Dopamine and Norepinephrine Pathways and ADHD (continued)  Ventral striatum and response to reward in ADHD –ADHD and difficulty with delaying gratification –Arousal adjustment in response to the emotional

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Dopamine and Norepinephrine Pathways and ADHD (continued)  Cerebellum and motor timing in ADHD –Children with ADHD have a difficult time with tasks that require time estimation or time discrimination.

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Newest ADHD Medications “Me-too”

Methylphenidate ER (QuilliChew ER®, Quillivant XR®, Aptensio XR®) (Adzenys XR-ODT® Dyanavel® XR, Evekeo®)

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35 Methylphenidate Extended-Release All with IR/ER onset of action Methylphenidate ER Administration Duration of medications with Once daily Action (approx.) IR/ER action QuilliChew® ER Cherry tablet 8 hours Quillivant® XR Oral suspention 12 hours Aptensio® XR Whole or sprinkled 12 hours Concerta® Whole 12 hours Ritalin® LA Whole or sprinkled 6‒9 hours on applesauce Metadate® CD Whole or sprinkled 6‒9 hours on applesauce

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Amphetamines Amphetamines Administration Duration of ER Once daily action (approx) Adderall® XR Whole or 10‒12 hours (mixed sprinkled on amphetamine applesauce salts) Adzenys XR- Sublingual 10‒12 hours ODT® orally (amphetamine) disintegrating Dyanavel XR® Suspension At least 12 hours (amphetamine)

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Amphetamines (continued) Amphetamine Administration Duration of 1‒3 times per day action Additional doses at (approx.) 4‒6 hours Adderall® IR Whole 6 hours (mixed amphetamine salts) Evekeo® Whole At least 9.25 (mixed hours amphetamine salts)

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36 Decision Making in ADHD Medications

• Choice of medication – Onset of action – Duration of action – Ease of taking medication – Adverse effects – Dosing – Cost

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End of Presentation Thank you for your time and attention.

Tess Judge-Ellis DNP, FNP-BC, PMHNP-BC, FAANP

www.fhea.com [email protected]

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References

• Anderson, S. & VandeGriend, J (2014) Quetiapine for insomnia: A review of the literature. American Journal of Health-Syestem Pharmacists, 71, 394- 402 • Coe, H. & Hong, I. (2012). Safety of Low Doses of Quetiapine when Used for Insomnia. The Annals of Pharmacotherapy;46:718-722.

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37 References (continued) • Belsomra (suvorexant) Product Insert, http://www.merck.com/product/usa/pi_circulars/b /belsomra/belsomra_pi.pdf • Brintellix (vortioxetine) Product Insert, http://general.takedapharm.com/content/file.aspx ?applicationcode=396066C6-E50F-4113-ABAD- 54FE9525BF7E&filetypecode=BRINTELLIXPI&cach eRandomizer=3dae8368-2480-4331-bf59- 1fe9c7f9eb54

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References (continued) • Dopheide, J. & Pliszka, S. (2009) Attention-Deficit- Hyperactivity Disorder: An Update. Pharmacotherapy, 29 (6); 656-679. • Elmaadawi, A., Singh, N., Reddy, J., Nasr, S., (2015) Prescriber’s guide to using 3 new antidepressants: Vilazodone, levomilnacipran, vortioxetine. Current Psychiatry (2015) 14(2): 28- 29, 32-36. • Fetzima (levomilnacipran) Product Insert, http://www.allergan.com/assets/pdf/fetzima_pi#p age=1

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References (continued) • Prescriber’s Letter; March 2016; Vol: 23. New ADHD Stimulant Formulations • Prescriber’s Letter; September 2013; ADHD Stimulant FAQs • Prescriber’s Letter: February 2015; Vol: 31. Role of Suvorexant (Belsomra) for Insomnia. • Solanto, M. (1998) Neuropsychopharmacological mechanisms of stimulant drug action in attention- deficit hyperactivity disorder: a review and integration. Behavioural Brain Research 94 (1998), 127-152

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38 References (continued) • Seier, K., Connell, R., Resche, W., Thomas, C. (2013). Recommendations for lab monitoring of atypical . Current Psychiatry, 12(9):51-54. • http://www.ninds.nih.gov/disorders/brain_basics/und erstanding_sleep.htm • http://www.howsleepworks.com/types_rem.html • Viibryd (vilazodone) Product Insert, http://www.allergan.com/assets/pdf/viibryd_pi • Volpi-Abadie, J., Kaye, A.M., Kaye, A.D. (2013). Serotonin Syndrome. The Ochsner Journal 13: 533- 540

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• Images/Illustrations: Unless otherwise noted, all images/ illustrations are from open sources, such as the CDC or Wikipedia or property of FHEA or author. • All websites listed active at the time of publication.

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39 Statement of Liability

• The information in this program has been thoroughly researched and checked for accuracy. However, clinical practice and techniques are a dynamic process and new information becomes available daily. Prudent practice dictates that the clinician consult further sources prior to applying information obtained from this program, whether in printed, visual or verbal form. • Fitzgerald Health Education Associates disclaims any liability, loss, injury or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents of this presentation.

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Fitzgerald Health Education Associates

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