Download B-8 - New Psychiatric Medications

New Psychiatric Medications
Knowledge is Power
Gregory T. Bogart, Pharm.D., BCPP
Clinical Psychiatric Pharmacist
University of Maryland, School of Pharmacy
Springfield Hospital Center
Sykesville, MD
Jennifer Miller, Pharm.D., BCPP
Clinical Psychiatric Pharmacist
Wilkes-Barre VAMC
Wilkes-Barre, PA
Objectives
• Discuss clinical indications of new and
emerging psychiatric medications
• Compare and contrast the role of new
medications with existing medications
• Implement strategies to learn about new
psychiatric medications
Antipsychotics
Oral Antipsychotics
1st Generation
2nd Generation
Thorazine® (chlorpromazine)
Clozaril® (clozapine)
Haldol® (haloperidol)
Risperdal® (risperidone)
Prolixin® (fluphenazine)
Geodon® (ziprasidone)
Stelazine® (trifluperazine)
Seroquel® (quetiapine)
Trilafon® (perphenazine)
Zyprexa® (olanzapine)
Navane® (thiothixene)
Abilify® (aripipirazole)
Loxitane® (loxapine)
Invega® (paliperidone)
Mellaril® (thioridazine)
Fanapt® (Iloperidone)
Saphris® (Asenapine)
Latuda® (Lurasidone)
Long Acting Injectable Antipsychotics
1st Generation
2nd Generation
Haloperidol decanoate
Risperdal Consta®
Fluphenazine decanoate
Invega Sustenna®
Zyprexa Relprevv®
Abilify Maintena®
NEW ORAL ANTIPSYCHOTICS
Iloperidone
• FDA approved in 2009
• Indicated for the treatment of schizophrenia in
adults
• Mechanism of action – primarily dopamine
(D2) antagonism with some serotonin (5HT2)
antagonism
Fanapt® [package insert]. East Hanover, NJ;
Novartis Pharmaceuticals Corporation; Revised April, 2014.
Iloperidone - Efficacy
• 6-week trial with placebo and risperidone
showed superiority over placebo and
comparable efficacy of risperidone at 6 weeks
• 4-week trial with placebo and ziprasidone
found superiority over placebo and similar
efficacy to ziprasidone at 4 weeks
Fanapt® [package insert]. East Hanover, NJ;
Novartis Pharmaceuticals Corporation; Revised April, 2014.
Iloperidone – Possible Side Effects
• Metabolic changes – weight gain, ↑cholesterol
– Not as significant as other 2nd gen drugs
• Extrapyramidal symptoms (EPS)
• QTc prolongation
• Orthostasis, low blood pressure, and
dizziness
• Rarer side effects – priapism, seizure,
agranulocytosis
Iloperidone - Dosing
• Starting dose 1 mg twice daily
• Target dosage range 6-12 mg twice daily
• Increase by no more than 2 mg twice daily
every day until target range
– Slow titration due to increased risk of low blood
pressure, dizziness, and falls
• Maximum dose of 12 mg twice daily
Fanapt® [package insert]. East Hanover, NJ;
Novartis Pharmaceuticals Corporation; Revised April, 2014.
Iloperidone – Role in therapy
• New second generation antipsychotic choice
• Lower risk for EPS and weight gain than other
options
• Higher risk of orthostasis, dizziness, and falls
especially during the initial titration phase
• Slow titration phase and twice daily dosing
may be difficult for some patients to work with
Asenapine
• FDA approved in 2009
• Indications
– Treatment of schizophrenia in adults
– Acute treatment, either as monotherapy or
adjunctive, or manic or mixed episodes of bipolar
I disorder in adults
• Mechanism of action thought to be a
combination of dopamine D2 and serotonin
5HT2 receptor blockade
Saphris® [package insert]. Whitehouse Station, NJ;
Merck & Co., Inc.; Revised March, 2013.
Asenapine – Efficacy in
Schizophrenia
• Short term studies
1. A 6-week trial comparing asenapine to placebo showed
superior efficacy asenapine at 6 weeks
2. A 6-week trial comparing asenapine to placebo and
haloperidol showed asenapine to be superior to placebo,
but not haloperidol. It also showed no difference
between 5 mg twice daily and 10 mg twice daily dosing
3. A 6-weeks trial comparing asenapine to placebo
olanzapine showed that asenapine and placebo failed to
separate and that olanzapine was superior to both
Saphris® [package insert]. Whitehouse Station, NJ;
Merck & Co., Inc.; Revised March, 2013.
Asenapine – Efficacy in Bipolar I
Disorder
• Monotherapy
– Two 3-week trials of asenapine and placebo
showed that asenapine was superior to placebo
for controlling acute mania
• Adjunctive
– A 12-week trial of asenapine or placebo added to
lithium or valproic acid showed asenapine was
superior to placebo at reducing manic symptoms
at 3 weeks
Saphris® [package insert]. Whitehouse Station, NJ;
Merck & Co., Inc.; Revised March, 2013.
Asenapine – Possible Side Effects
• Metabolic changes and weight gain
– Not as significant as other 2nd gen drugs
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EPS – higher rates of akathisia
QTc prolongation
Sedation or somnolence
Headache
Rarer side effects – agranulocytosis, seizures,
and orthostasis
Saphris® [package insert]. Whitehouse Station, NJ;
Merck & Co., Inc.; Revised March, 2013.
Asenapine - Dosing
• Asenapine is supplied as sublingual tablets
– Do not swallow tablets
– Dissolve under the tongue
– No food or drink for 10 minutes after dose
Indication
Starting Dose
Dosage Range
Maximum
Schizophrenia
5 mg twice daily
5-10 mg twice daily
10 mg twice daily
Acute Bipolar I
10 mg twice daily
5-10 mg twice daily
10 mg twice daily
Saphris® [package insert]. Whitehouse Station, NJ;
Merck & Co., Inc.; Revised March, 2013.
Asenapine – Role in Therapy
• Can be utilized in both schizophrenia and
bipolar disorder
• Unique sublingual administration
• Relatively small metabolic side effects
• Higher rates of sedation and akathisia than
other agents
Lurasidone
• FDA approved in 2010
• Indications
– Treatment of schizophrenia in adults
– Treatment of depressive episodes in bipolar
disorder in adults as both monotherapy and
adjunctive therapy
• Mechanism of action thought to be a
combination of dopamine D2 and serotonin
5HT2 receptor blockade
Latuda® [package insert]. Marlborough, MA;
Sunovion Pharmaceuticals, Inc.; Revised July, 2013.
Lurasidone – Efficacy in
Schizophrenia
• Five total trials, all 6 weeks long
– Two trials of fixed dose lurasidone vs. placebo showed
superior efficacy of lurasidone
– One trial of 40 mg, 80 mg, and 120 mg lurasidone vs.
placebo showed that only the 80 mg dose was superior to
placebo
– One trial of lurasidone, olanzapine and placebo showed
that both lurasidone and olanzapine were superior to
placebo
– One trial of lurasidone, quetiapine ER, and placebo
showed both lurasidone and quetiapine ER were superior
to placebo
Latuda® [package insert]. Marlborough, MA;
Sunovion Pharmaceuticals, Inc.; Revised July, 2013.
Lurasidone – Efficacy in Bipolar
Depression
• As monotherapy
– A 6-week trial vs placebo for symptom reduction in bipolar
depression showed that both doses of lurasidone studied
were superior to placebo at 6 weeks
• As an adjunct
– A 6-week trial of patients who were still symptomatic on
lithium or valproic acid were given placebo or lurasidone.
At 6 weeks, there was a superior symptom reduction in
the lurasidone group vs. the placebo group
Latuda® [package insert]. Marlborough, MA;
Sunovion Pharmaceuticals, Inc.; Revised July, 2013.
Lurasidone – Possible Side Effects
• Metabolic changes and weight gain
– Possibly the most weight and metabolic neutral
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EPS – akathisia more common than others
QTc prolongation
Sedation or somnolence
Nausea and vomiting
Rarer side effects – agranulocytosis, seizures,
and orthostasis
Latuda® [package insert]. Marlborough, MA;
Sunovion Pharmaceuticals, Inc.; Revised July, 2013.
Lurasidone - Dosing
• For schizophrenia, starting dose is 40 mg/day
with a range of 40-160 mg/day
• For bipolar depression, starting dose is 20
mg/day with a range of 20-120 mg/day
• All doses should be taken with a meal of at
least 350 calories to improve absorption
• Dosing is recommended in the evening due to
the possibility of sedation and somnolence
Latuda® [package insert]. Marlborough, MA;
Sunovion Pharmaceuticals, Inc.; Revised July, 2013.
Lurasidone – Role in Therapy
• Can be utilized in schizophrenia and bipolar
depression
• Has a very favorable long-term metabolic
profile
• Once daily dosing is most patient friendly
• Appears to be the most rigorously studied of
the newer agents
LONG ACTING INJECTIONS
(LAIS)
Rationale
• LAIs are options to improve compliance
– Less frequent administration than oral agents
– Doses converted from stable oral regimens
– Guaranteed drug level in the body post-injection
– Improved clinician contact
Available Options
1st Generation
2nd Generation
Haloperidol decanoate
Risperdal Consta®
Fluphenazine decanoate
Invega Sustenna®
Zyprexa Relprevv®
Abilify Maintena®
Zyprexa Relprevv®
• FDA approved in 2009
• Long acting intramuscular injection of
olanzapine intended for gluteal injection only
• Indicated for the treatment of schizophrenia
• Designed to be initiated after a stable regimen
of olanzapine is established
Zyprexa Relprevv® [package insert]. Indianapolis, IN;
Eli Lilly and Company; Revised July, 2011.
Zyprexa Relprevv® - Dosing
Oral dose of olanzapine
Dose of Zyprexa
Relprevv® for the first 8
weeks
Maintenance dose of
Zyprexa Relprevv®after 8
weeks
10 mg/day
210 mg every 2 weeks or
405 mg every 4 weeks
150 mg every 2 weeks or
300 mg every 4 weeks
15 mg/day
300 mg every 2 weeks
210 mg every 2 weeks or
405 mg every 4 weeks
20 mg/day
300 mg every 2 weeks
300 mg every 2 weeks
Note: No oral medication overlap is required
Zyprexa Relprevv® [package insert]. Indianapolis, IN;
Eli Lilly and Company; Revised July, 2011.
Adverse Events
• Adverse events are similar to oral olanzapine
– Metabolic syndrome and weight gain
– Sedation
– Orthostasis and dizziness
• Also has Post-Injection Delirium/Sedation
Syndrome (PDSS) risk
Zyprexa Relprevv® [package insert]. Indianapolis, IN;
Eli Lilly and Company; Revised July, 2011.
PDSS
• Signs and symptoms associated with olanzapine
overdose
– Sedation and/or delirium possibly leading to coma
– Dizziness, confusion, disorientation, slurred speech,
weakness, difficulty walking
– Occurred in <0.1% of all injections, 2% of all patients
treated in 46 months
– Most patients recovered with supportive care within 72
hours
– Lead to the creation of a REMS program
Zyprexa Relprevv® [package insert]. Indianapolis, IN;
Eli Lilly and Company; Revised July, 2011.
Zyprexa Relprevv® REMS
• Prescriber, patient, facility, and pharmacy must all
register
• Medication cannot be dispensed directly to patient
• Medication must be administered in a registered facility
with access to emergency response services
• Patients must be observed by a healthcare worker for at
least 3 hours after injection for signs of PDSS
• Patients may not leave the facility by themselves
• Patients should not drive the remainder of the day
Zyprexa Relprevv® [package insert]. Indianapolis, IN;
Eli Lilly and Company; Revised July, 2011.
Abilify Maintena®
• FDA approved in 2013
• Long acting intramuscular injection of
aripiprazole intended for gluteal injection only
• Indicated for the treatment of schizophrenia
• Designed to be initiated after a stable regimen
of aripiprazole is established
Abilify Maintena® [package insert]. Tokyo, Japan;
Otsuka Pharmaceutical Co. Ltd; Revised February, 2013.
Abilify Maintena® Dosing
• Recommended starting dose in 400 mg
monthly
• Continuation of oral aripiprazole 10-20
mg/day is necessary for 14 days after initial
injection
• Maintenance dose is also 400 mg monthly
– Dose reduction to 300 mg can be used if 400 mg
dose is intolerable
Abilify Maintena® [package insert]. Tokyo, Japan;
Otsuka Pharmaceutical Co. Ltd; Revised February, 2013.
Adverse Events
• Very similar to oral aripiprazole
– Slight metabolic changes
– Some EPS – mostly akathisia
– Anxiety
– Headache
– Orthostasis
Abilify Maintena® [package insert]. Tokyo, Japan;
Otsuka Pharmaceutical Co. Ltd; Revised February, 2013.
Antidepressants
Antidepressants
Selective Serotonin Reuptake
Inhibitors (SSRIs)
Serotonin Norepinephrine
Reuptake Inhibitors (SNRIs)
Celexa® (citalopram)
Cymbalta® (duloxetine)
Lexapro® (escitalopram)
Effexor® (venlafaxine)
Prozac® (fluoxetine)
Pristiq® (desvenlafaxine)
Paxil® (paroxetine)
Savella® (milnacipran)
Luvox® (fluvoxamine)
Fetzima® (levomilnacipran)
Zoloft® (sertraline)
Brintellix® (vortioxetine)
Viibryd® (vilazodone)
Antidepressants
Tricyclic Antidepressants
Atypical
Antidepressants
Monoamine Oxidase
Inhibitors (MAOIs)
Elavil® (amitriptyline)
Wellbutrin® (bupropion)
Nardil® (phenelzine)
Anafranil® (clomipramine)
Remeron® (mirtazapine)
Parnate® (tranylcypromine)
Tofranil® (imipramine)
Serzone® (nefazodone)
Eldepryl® (selegiline)
Pamelor® (nortriptyline)
Desyrel® (trazodone)
Marplan® (isocarboxazid)*
Norpramin® (desipramine)
Sinequan® (doxepin)
Vivactil® (protriptyline)
NEW ORAL ANTIDEPRESSANTS
Viibryd® (Vilazodone)
• Year Approved
– 2011
• Indication
– Major Depressive Disorder
Viibryd ® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;
Revised December, 2012.
Image from www.viibryd.com
Viibryd® (Vilazodone)
• Mechanism of Action
– Selective Serotonin Reuptake Inhibitor (SSRI)
– Activity at serotonin receptor
• Effectiveness
– Decreased depressive symptoms in 8 week trials
better than placebo
Viibryd ® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;
Revised December, 2012.
Viibryd® (Vilazodone)
• Safety
– Contraindications
• Use with MAOI
– Warnings
• Serotonin syndrome, suicidality, seizure, mania, bleed,
low sodium, sudden discontinuation
Viibryd ® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;
Revised December, 2012.
Viibryd® (Vilazodone)
• Safety
– Drug interactions
– Adverse Effects
• Nausea, diarrhea, dizziness, sleep disturbance, sexual
dysfunction
Viibryd ® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;
Revised December, 2012.
Viibryd® (Vilazodone)
• Considerations for Use
– Take with food
– Dose titration
– No dose adjustment for age
– Pregnancy, nursing, or children
• Medication Role
– No clear advantage over SSRIs for depression
Viibryd ® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;
Revised December, 2012.
Fetzima® (Levomilnacipran)
• Year Approved
– 2013
• Indication
– Major Depressive Disorder
Fetzima® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;
Revised July, 2013.
Image from www.fetzima.com
Fetzima® (Levomilnacipran)
• Mechanism of Action
– Serotonin Norepinephrine Reuptake Inhibitor
(SNRI)
• Effectiveness
– Decreased depressive symptoms in 8 week trials
better than placebo
Fetzima® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;
Revised July, 2013.
Fetzima® (Levomilnacipran)
• Safety
– Contraindications
• Allergic reaction, uncontrolled narrow-angle glaucoma,
use with MAOI
– Warnings
• Serotonin syndrome, suicidality, seizure, mania, bleed,
low sodium, sudden discontinuation
Fetzima® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;
Revised July, 2013.
Fetzima® (Levomilnacipran)
• Safety
– Warnings (cont.)
• High blood pressure & heart rate, narrow-angle
glaucoma, urinary hesitation or retention
– Drug interactions
– Adverse Effects
• Nausea, vomiting, constipation, sweating, increased
blood pressure & heart rate, sexual dysfunction
Fetzima® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;
Revised July, 2013.
Fetzima® (Levomilnacipran)
• Considerations for Use
– Adjust dose for kidney impairment
– No dose adjustment for age
– Pregnancy, nursing, children
• Medication Role
– No clear advantage over SNRIs for depression
– No established effectiveness for fibromyalgia/
pain
Fetzima® [package insert]. St. Louis, MO; Forest Laboratories, Inc.;
Revised July, 2013.
Brintellix® (Vortioxetine)
• Year Approved
– 2013
• Indication
– Major Depressive Disorder
Brintellix® [package insert]. Deerfield, IL; Takeda Pharmaceuticals
America, Inc.; Revised July, 2014.
Image from us.brintellix.com
Brintellix® (Vortioxetine)
• Mechanism of Action
– SSRI
– Activity at various serotonin receptors
• Effectiveness
– Decreased depressive symptoms in 6-8 week
trials & longer time to recurrent depression in 64
week trial better than placebo
Brintellix® [package insert]. Deerfield, IL; Takeda Pharmaceuticals
America, Inc.; Revised July, 2014.
Brintellix® (Vortioxetine)
• Safety
– Contraindications
• Allergic reaction, use with MAOI
– Warnings
• Serotonin syndrome, suicidality, mania, bleed, low
sodium
Brintellix® [package insert]. Deerfield, IL; Takeda Pharmaceuticals
America, Inc.; Revised July, 2014.
Brintellix® (Vortioxetine)
• Safety
– Drug interactions
– Adverse Effects
• Nausea, vomiting, constipation, dizziness, sexual
dysfunction
Brintellix® [package insert]. Deerfield, IL; Takeda Pharmaceuticals
America, Inc.; Revised July, 2014.
Brintellix® (Vortioxetine)
• Considerations for Use
– Avoid in severe liver impairment
– No dose adjustment for age
– Pregnancy, nursing, children
• Medication Role
– No clear advantage over SSRIs for depression
Brintellix® [package insert]. Deerfield, IL; Takeda Pharmaceuticals
America, Inc.; Revised July, 2014.
Miscellaneous
Medications
Miscellaneous Medications
Images taken from www.quillivantxr.com; www.intermezzorx.com;
www.zubsolv.com
Learning Strategies
Resources
• NAMI.org
– Medication fact sheets
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FDA.gov
Drugs.com
MedlinePlus
Narsad.org