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 = Fanapt
FDA approved in 2009
Indicated for the treatment of schizophrenia in
adults
Mechanism of action primarily dopamine
(D2) antagonism with some serotonin (5HT 2)
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=saphris
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

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=latuda
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

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 Relprevvafter 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 Irenka DR
(duloxetine)

Lexapro (escitalopram)

Effexor (venlafaxine)

Prozac Sarafem (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 Oleptro
(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

FDA.gov
Drugs.com
MedlinePlus
Narsad.org