N I "M T ?": Ewer Typical Ntipsychotics

3/27/2013
OBJECTIVES
NEWER ATYPICAL Discuss new antipsychotics approved within the last five years
ANTIPSYCHOTICS: Review new formulations of previously approved

antipsychotics
NOVEL IDEAS OR Recognize the clinical utility of new antipsychotic agents for
the treatment of schizophrenia
ME TOOS?
Sanaz Farhadian, Pharm.D., BCPP
Clinical Psychiatric Pharmacist
2
Veterans Affairs Healthcare System, San Diego, CA
PRE-TEST: QUESTION 1 PRE-TEST: QUESTION 2

Blockade of which receptor makes lurasidone a novel Which of the following antipsychotics is NOT available as a
antipsychotic, due to the belief that it improves cognition? long-acting injectable?
A. 5-HT7 A. Olanzapine
B. 5-HT2A B. Aripiprazole
C. 5-HT1A C. Paliperidone
D. D2 D. Quetiapine
3 4
1
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PRE-TEST: QUESTION 3 BACKGROUND

Which of the following is a black box warning for Zyprexa Antipsychotics introduced in 1950s to treat psychosis
Relprevv (olanzapine), requiring that a patient be observed
Atypical antipsychotics gained popularity in 1990s
for at least 3 hours after administration?
More efficacious than typical agents
A. Acute dystonia
Decreased risk of movement disorders
B. Post-injection delirium/sedation syndrome
C. Hyperglycemia New atypical entities and formulations continue to be approved
D. Increased mortality in elderly patients with
Account for large portion of pharmaceutical market share
dementia-related psychosis
5 6
AVAILABLE ATYPICALS SCHIZOPHRENIA PATHOPHYSIOLOGY

GENERIC BRAND
Clozapine* Clozaril Abnormal
Risperidone* Risperdal Neurotransmission
Olanzapine* Zyprexa DA
Quetiapine* Seroquel 5-HT
Ziprasidone* Geodon Glu
Aripiprazole Abilify GABA
Paliperidone Invega
Iloperidone Fanapt
Asenapine Saphris
Lurasidone Latuda 7 8
* Available generically
2
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DOPAMINE BRAIN PATHWAYS SCHIZOPHRENIA CORE SYMPTOMS

POSITIVE NEGATIVE COGNITIVE
Limbic cortex
Nucleus accumbens Alogia
Hallucinations Anergia Difficulty with:
2
Substantia nigra 3 1 Delusions Avolition Attention
Disorganization Anhedonia Learning
4
Paranoia Restricted affect Memory
Tegmentum Combative/hostile Executive function
Social withdrawal
Unusual behavior Psychomotor
Pituitary
retardation
9 10
1 Mesolimbic 3 Nigrostriatal
2 Mesocortical 4 Tuberoinfundibular
ATYPICAL ANTIPSYCHOTICS COMMON ADVERSE SIDE EFFECTS

Postsynaptic D2 receptor blockade with limbic specificity Involuntary movements Metabolic abnormalities
Mesolimbic pathway decreased positive symptoms Extrapyramidal symptoms Weight gain
Tuberoinfundibular pathway decreased risk of hyperprolactinemia Tardive dyskinesia Hyperglycemia and diabetes
Dyslipidemia
Presynaptic 5-HT2A autoreceptor blockade increases Hyperprolactinemia
dopamine release that overcomes the postsynaptic blockade
of the D2 receptors in: Sedation
Mesocortical pathway decreased negative symptoms
Nigrostriatal pathway decreased risk of EPS Orthostasis
Cause blockade of 1, H1, and mACh receptors Anticholinergic side effects

11 12
Risk of metabolic side effects
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RARE ADVERSE SIDE EFFECTS BLACK BOX WARNINGS

Tachycardia Neuroleptic malignant syndrome Increased mortality in elderly patients with dementia-related
psychosis due to cardiovascular or infectious causes
QTc prolongation Photosensitivity All atypical antipsychotics
Seizures Thermoregulation Suicidality in children and young adults due to depression

indications
Cerebrovascular events Hepatic dysfunction Aripiprazole
Quetiapine
Leukopenia, neutropenia,
agranulocytosis Myocarditis, seizures, agranulocytosis, orthostasis ( syncope)
Clozapine
13 14
FANAPT
WHERE DO NEW AGENTS FIT IN? (ILOPERIDONE)
Oral tablet
APPROVAL DATE ANTIPSYCHOTIC BRAND
1mg, 2mg, 4mg, 6mg, 8mg, 10mg, 12mg
May 2009 Iloperidone Fanapt
July 2009 Paliperidone IM Invega Indication: acute treatment of schizophrenia
Injection Sustenna
August 2009 Asenapine SL Saphris Antagonist at 2C receptors
December 2009 Olanzapine IM Zyprexa
Injection Relprevv Twice daily dosing
October 2010 Lurasidone Latuda 95% protein bound
February 2013 Aripiprazole IM Abilify Well absorbed, peak plasma concentrations 2-4 hours post-dose
Injection Maintena Metabolized by CYP2D6 and CYP3A4 into P88 and P95
February 2013 Clozapine Oral Versacloz Elimination half-life: 18-33 hours for parent drug; 23-37 hours for
15 16
Suspension metabolites
Fanapt package insert.
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3/27/2013
FANAPT: DOSING FANAPT: ADVERSE EFFECTS

(ILOPERIDONE) (ILOPERIDONE)
Slow titration required due to orthostasis risk Hyperprolactinemia
Initial dose: 1mg PO BID, titrating by 1-2mg BID daily Orthostasis
Target dose: 6-12mg PO BID Medium metabolic risk
Maximum dose: 24mg/day in divided doses QTc prolongation (~11.4 msec)
Dosage adjustments reduce by 50% Priapism

CYP2D6 poor metabolizers
Strong CYP2D6 or CYP3A4 inhibitor
Hepatic impairment: NOT recommended
17 18
Fanapt package insert. Fanapt package insert.
FANAPT: EFFICACY FANAPT: CLINICAL UTILITY

(ILOPERIDONE) (ILOPERIDONE)
All studies were randomized, double-blind, placebo-, active controlled PROS CONS
STUDY ILOPERIDONE ACTIVE PRIMARY OUTCOME
DURATION REGIMEN COMPARATOR (BASELINE TO ENDPOINT) Low EPS risk Slow titration
4 weeks 24mg/day Ziprasidone PANSS-T in ilo vs plac (p<0.019) and zipr vs
160mg/day plac (p<0.05) BID dosing
6 weeks 4, 8 , or 12 Haloperidol PANSS-T in ilo 12mg/day vs plac (p=0.047)
mg/day 15mg/day and halo vs plac (p<0.001)
QTc prolongation
6 weeks 4-8mg/day Risperidone BPRS-d in all ilo groups and risp
10-16mg/day 4-8mg/day Sign. improv. in both ilo groups vs plac
6 weeks 12-16mg/day Risperidone BPRS-d in all ilo groups and risp
20-24mg/day 6-8mg/day Sign. improv in ilo 20-24mg vs plac (p=0.01)
Ilo = iloperidone, zipr = ziprasidone, halo = haloperidol, risp = risperidone, plac = placebo,
sign. improv = significant improvement
19 20
PANSS-T = Positive and Negative Symptom Scale, Total
BPRS = Brief Psychotic Rating Scale
BPRS-d = PANNS-derived BPRS Fanapt package insert.
Caccia et al. Drug Des Devel Ther 2010;4:33.
5
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INVEGA SUSTENNA INVEGA SUSTENNA: DOSING

(PALIPERIDONE PALMITATE) (PALIPERIDONE PALMITATE)
Long-acting formulation of paliperidone Must establish efficacy/tolerability on risperidone or oral
39mg/0.25ml, 78mg/0.5ml, 117mg/0.75ml, 156mg/1.0ml, paliperidone first
234mg/1.5ml
First two doses must be given in deltoid
Indication: acute and maintenance treatment of schizophrenia Day 1: 234mg IM; Day 8: 156mg IM
Once monthly injection Then, 117mg IM (deltoid or gluteal) q4 weeks

74% protein bound Maintenance dose may range from 39-234mg
Paliperidone palmitate hydrolyzed to paliperidone
Metabolized by CYP2D6 and CYP3A4 to 9-hydroxyrisperidone Dosage adjustments
Peak plasma concentrations at 13 days CrCl 50-79mL/min: day 1 - 156mg, day 8 - 117mg, q4 weeks - 78mg
Elimination half-life: 25 days (39mg), 48 days (234mg) 21
CrCl 49mL/min: NOT recommended 22
Strong CYP3A4 inducer: decrease paliperidone dose
Invega Sustenna package insert. Invega Sustenna package insert.
SWITCHING TO INVEGA SUSTENNA INVEGA SUSTENNA: ADMINISTRATION

Oral antipsychotic to paliperidone palmitate Visually inspect prefilled syringe for particles/discoloration
Stop oral antipsychotic, initiate as discussed on previous slide White to off-white suspension
If switching from oral paliperidone, use following conversion
for maintenance dose Shake syringe vigorously for at least 10 seconds
PO QDAY IM Q4 WEEKS Attach appropriate needle based on injection site

3mg 39-78mg
6mg 117mg
9mg 156mg
12mg 234mg
Long-acting injection to paliperidone palmitate Hold syringe upright to de-aerate by moving plunger rod forward
If at steady state, initiate with maintenance dose q4 weeks 23 24
when next injection is due Inject entire contents IM slowly into selected muscle
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INVEGA SUSTENNA: ADVERSE EFFECTS INVEGA SUSTENNA: EFFICACY

Injection site reaction 13-week randomized, double-blind/-dummy, non-inferiority trial
Long-acting paliperidone 78-234mg
Dose-related EPS
Long-acting risperidone 25-50mg with oral risperidone x3 weeks
Hyperprolactinemia
Sedation
Orthostasis
Medium metabolic risk
Priapism
25 26

Pandina et al. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:218.
INVEGA SUSTENNA: CLINICAL UTILITY SAPHRIS

(PALIPERIDONE PALMITATE) (ASENAPINE)
PROS CONS Sublingual tablet
5mg, 10mg
Helps with adherence Dose-related EPS Indications
Acute and maintenance treatment of schizophrenia
Administered monthly Two dose initiation
Acute treatment of bipolar I manic or mixed episodes
No oral overlap required Antagonist at 5-HT2c, 5-HT6, 5-HT7, and 2 receptors
Twice daily dosing
95% protein bound
Bioavailability: 35% sublingually, 2% orally
Peak plasma concentrations 0.5-1.5 hours post-dose
27 28
Metabolized by CYP1A2 and UGT1A4
Elimination half-life: 24 hours Saphris package insert.
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3/27/2013
SAPHRIS: DOSING SAPHRIS: ADMINISTRATION

(ASENAPINE) (ASENAPINE)
Regular flavor or black cherry Remove immediately before

administration with dry hands
Initial dose: 5mg SL BID
Peel back colored tab to remove
Maintenance: increase to 10mg SL BID after 7 days tablet
Maximum dose: 20mg/day in divided doses Place under tongue and allow to
dissolve fully
Avoid eating or drinking for 10 minutes after administration
Reduces bioavailability Do not eat or drink for 10 minutes
post-administration
Dosage adjustments
29 30
NOT recommended in severe hepatic impairment Slide tablet pack into case until it
Saphris package insert. clicks Saphris package insert.
SAPHRIS: ADVERSE EFFECTS SAPHRIS: EFFICACY

(ASENAPINE) (ASENAPINE)
Oral hypoesthesia All studies were randomized, double-blind, placebo-, active controlled
STUDY ASENAPINE ACTIVE PRIMARY AND SECONDARY OUTCOMES
Bitter taste DURATION REGIMEN COMPARATOR (BASELINE TO ENDPOINT)
Black cherry flavor developed 6 weeks 5mg BID Risperidone PANSS-T in asen vs plac (p<0.005)
3mg BID Asen superior for PANSS-P and PANSS-N
Asen > plac for improvement on cognition
Akathisia
6 weeks 5mg BID Haloperidol PANSS-T in asen 5mg and halo vs plac
10mg BID 4mg BID
Somnolence
6 weeks 5mg BID Olanzapine PANSS-T in olan vs plac
10mg BID 15mg daily PANSS-P in asen 5mg and olan vs plac
Low metabolic side risk
Asen = iloperidone, risp = risperidone, halo = haloperidol, olan = olanzapine, plac = placebo
PANSS-T = Positive and Negative Symptom Scale, Total
PANSS-P = Positive and Negative Symptom Scale, Positive subscale
31 PANSS-N = Positive and Negative Symptom Scale, Negative subscale 32
Saphris package insert. Saphris package insert. Minassian et al. Expert Opin Pharmacother 2010;11:2107.
Bishara et al. Neuropsychiatr Dis Treat 2009;5:483. Citrome et al. Neuropsychiatr Dis Treat 2011;7:325.
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SAPHRIS: CLINICAL UTILITY ZYPREXA RELPREVV

(ASENAPINE) (OLANZAPINE PAMOATE)
PROS CONS Long-acting formulation of olanzapine
210mg, 300mg, 405mg
Low metabolic risk Akathisia
Indication: schizophrenia
BID dosing
Once to twice monthly injection
Patients without insight 93% protein bound
may swallow it instead of Metabolized by glucoronidation and CYP1A2
use it sublingually Peak plasma concentrations within 7 days
Elimination half-life: 30 days
Eating and drinking
affects bioavailability
33 34
Zyprexa Relprevv package insert.
ZYPREXA RELPREVV: DOSING ZYPREXA RELPREVV: ADMINISTRATION

(OLANZAPINE PAMOATE) (OLANZAPINE PAMOATE)
Must establish efficacy/tolerability on oral olanzapine first Loosen powder in the vial by light tapping
TARGET IM (GLUTEAL) DOSE IM (GLUTEAL) DOSE Withdraw desired diluent volume and inject into powder vial
ORAL DOSE IN FIRST 8 WEEKS AFTER 8 WEEKS
210mg q2 weeks 150mg q2 weeks Pad a hard surface and tap vial firmly until no powder is visible
10mg/day OR OR
405mg q4 weeks 300mg q4 weeks Shake vigorously until suspension is homogenous
210mg q2 weeks Yellow and opaque
15mg/day 300mg q2wks OR
405mg q4 weeks Inject immediately after reconstitution
20mg/day 300mg q2wks 300mg q2wks Otherwise, shake vigorously to re-suspend; stable for 24 hours
Dose adjustments Using 19 gauge or larger needle, inject into gluteal muscle
Geriatric or debilitated patients, and those with hypotension risk
35 Aspirate for several seconds to ensure not in blood supply 36
Starting dose 150mg IM q4 weeks
Clearance may be impaired in severe hepatic dysfunction

Administer injection at steady, continuous pressure
9
3/27/2013
POST-INJECTION DELIRIUM/SEDATION ZYPREXA RELPREVV REGULATIONS

(PDSS) BLACK BOX WARNING (OLANZAPINE PAMOATE)
Incidence <0.1% per injection, 2% per patient Must be given in registered healthcare facility with ready access
to emergency response services
Related to excessive olanzapine plasma concentrations
Must observe patient for at least 3 hours once administered
Prior to releasing patient, healthcare professional must confirm

alertness, orientation, and lack of signs/symptoms of PDSS
DO NOT administer if patient will not be accompanied on release
REMS medication distributed through Zyprexa Relprevv Patient

Care Program, which requires registration of:
37 38
Prescriber, healthcare facility, patient, and pharmacy
Zyprexa Relprevv package insert. Zyprexa Relprevv package insert.
ZYPREXA RELPREVV ADVERSE EFFECTS ZYPREXA RELPREVV: EFFICACY

(OLANZAPINE PAMOATE) (OLANZAPINE PAMOATE)
Injection site reaction Similar to oral olanzapine and haloperidol in symptom reduction
PDSS Similar to Risperdal Consta in 1 year treatment-completion rates
Sedation Dose-related rate of discontinuation due to lack of efficacy
Orthostasis
Anticholinergic
High metabolic risk

39 40
Zyprexa Relprevv package insert. Detke et al. BMC Psychiatry 2012;12:51.

Hill et al. BMC Psychiatry 2011;11:28. Ascher-Svanum et al. Int J Gen Med 2012;5:391.
10
3/27/2013
ZYPREXA RELPREVV: CLINICAL UTILITY LATUDA

(OLANZAPINE PAMOATE) (LURASIDONE)
PROS CONS Oral tablet
20mg, 40mg, 80mg, 120mg
Helps with adherence Registration requirements
Up to once monthly Long observation period
dosing Partial agonist at 5-HT1A and antagonist at 5-HT7 and 2c
High metabolic risk receptors
No oral overlap required
Unclear guidance for doses Once daily dosing
greater 20mg orally 99% protein bound
Poor absorption: 9-19%, peak plasma concentrations 1-3 hours
Metabolized by CYP3A4 into ID-14283 and ID-14326
41 42
Elimination half-life: 18 hours
Latuda package insert.
LATUDA: DOSING LATUDA: ADVERSE EFFECTS

(LURASIDONE) (LURASIDONE)
Initial dose: 40mg PO daily Akathisia
Target dose: 40-160mg PO daily
Parkinsonism
Maximum dose: 160mg/day
Somnolence
Take with food (at least 350 calories)
Dizziness
Dosage adjustments Low metabolic risk
CrCl 49ml/min - reduce 50%
Moderate hepatic impairment reduce 50% Nausea
Severe hepatic impairment initiate 20mg, max 40mg/day
Moderate CYP3A4 inhibitor reduce 50% 43
Dizziness 44
CONTRAINDICATED with strong CYP3A4 inhibitors or inducers

Latuda package insert. Latuda package insert.
11
3/27/2013
LATUDA: EFFICACY LATUDA: CLINICAL UTILITY

(LURASIDONE) (LURASIDONE)
Comparable to olanzapine, quetiapine XR, and ziprasidone in PROS CONS
decreasing PANSS-T from baseline to endpoint at 6 weeks
Once daily dosing Must take with food
STUDY LURASIDONE ACTIVE OUTCOME
DURATION REGIMEN COMPARATOR (BASELINE TO ENDPOINT)
6 weeks 80mg/day Quetiapine XR Sign. improv in MADRS for all groups vs plac Low metabolic risk
160mg/day 600mg/day (p<0.001)
6 months 80mg/day Quetiapine XR Luras 160mg superior to plac and QXR on
160mg/day 600mg/day composite cognitive functioning measure
UPSA-B scores superior to plac for all groups
21 days 120mg/day Ziprasidone Statistical trend for luras to improve SCoRS
80mg BID (p=0.058)
Luras = lurasidone, QXR = quetiapine XR, plac = placebo, sign. improv = significant improvement
MADRS = Montgomery-Asberg Depression Rating Scale 45 46
UPSA-B = UCSD Performance-based Skills Assessment, Brief
SCoRS = Schizophrenia Cognition Rating Scale
Latuda package insert.
Caccia et al. Neuropsychiatr Dis Treat 2012;8:155. Yasui-Furukori et al. Drug Des Devel Ther 2012;6:107.
ABILIFY MAINTENA ABILIFY MAINTENA: DOSING

(ARIPIPRAZOLE) (ARIPIPRAZOLE)
Long-acting formulation of aripiprazole Must establish efficacy/tolerability on oral aripiprazole first
300mg, 400mg
300-400mg IM (gluteal) q4 weeks
Oral aripiprazole overlap x2 weeks
Partial agonist at D2 and 5-HT1A receptors Upon initiation or if missed dose occurs
Potential to lower prolactin levels and improve mood
Dose adjustments
Once monthly injection CYP2D6 poor metabolizers
99% protein bound Strong CYP2D6 or CYP3A4 inhibitor >14 days
Metabolized by CYP2D6 and CYP3A4 to dehydro-aripiprazole Combination of CYP2D6 or CYP3A4 inhibitor >14 days
Peak plasma concentrations at 5-7 days AVOID use with CYP3A4 inducers >14 days
47 48
Elimination half-life: 29.9 days (300mg), 46.5 days (400mg)
Abilify Maintena package insert. Abilify Maintena package insert.
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ABILIFY MAINTENA: ADMINISTRATION ABILIFY MAINTENA: ADVERSE EFFECTS

Suspend Abilify Maintena with appropriate amount of sterile Injection site reaction
water for injection
Akathisia
Shake vigorously for 30 seconds until suspension is uniform
Visually inspect for particles/discoloration Low metabolic risk
Opaque and milky white
Inject immediately after reconstitution

Otherwise, keep at room temperature and shake at least 60 seconds
to re-suspend
Attach vial adapter to syringe and draw up recommend volume

49 50
Attach 21 gauge needle and slowly administer into gluteal
muscle Abilify Maintena package insert. Abilify Maintena package insert.
ABILIFY MAINTENA: EFFICACY ABILIFY MAINTENA: CLINICAL UTILITY

52-week randomized, double-blind, placebo-controlled trial PROS CONS
Terminated early
Helps with adherence More akathisia compared
Time to impending relapse significantly delayed (p<0.0001) to other antipsychotics
Administered monthly
Relapse rates significantly lower (10.0% arip. vs 39.6% placebo) Oral overlap required
Depot formulation with
lowest metabolic risks
May improve mood
Reduces prolactin levels

51 52
Kane et al. J Clin Psychiatry 2012;73:617.
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VERSACLOZ VERSACLOZ: CLINICAL UTILITY

(CLOZAPINE) (CLOZAPINE)
Oral suspension formulation PROS CONS
50mg/ml
Effective for treatment- Registration requirements
Indications: resistant schizophrenia
Treatment-resistant schizophrenia Frequent blood monitoring
Recurrent suicidal behavior in schizophrenia & schizoaffective disorder
Multiple black box
Slow dose titration similar to other clozapine formulations warnings
Side effects similar to other clozapine formulations Slow dose titration
REMS program due to agranulocytosis risk High metabolic risk

53 54
Prescribers, patients, and dispensing pharmacies must be registered
Versacloz package insert.
ATYPICAL FORMULATIONS RELATIVE METABOLIC RISK

PO ODT ORAL LIQUID SHORT- LONG-
ACTING IM ACTING IM Clozapine
Clozapine Fazaclo Versacloz Olanzapine
Risperidone M-tab Consta Quetiapine
Olanzapine Zydis Relprevv High risk
Medium risk Risperidone
Quetiapine IR, XL Paliperidone*
Low risk
Ziprasidone Iloperidone*
Aripiprazole Discmelt Maintena Aripiprazole*
Paliperidone XR Sustenna Ziprasidone*
Iloperidone Asenapine*
Asenapine SL Lurasidone*
Lurasidone
55 56
ODT = orally disintegrating tablet; IM = intramuscular * Limited long-term data exists
IR = immediate release; XR/XL = extended release; SL = sublingual Product package inserts. American Diabetes Association. Diabetes Care 2004;27:596.
Product package inserts.
14
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CONCLUSIONS POST-TEST: QUESTION 1

Place in therapy of newer agents largely limited by lack of Blockade of which receptor makes lurasidone a novel
head-to-head trials antipsychotic, due to the belief that it improves cognition?
Fanapt, Saphris, and Latuda appear to be me-too agents A. 5-HT7
Dosing and administration restrictions B. 5-HT2A
More data needed for efficacy of negative and cognitive symptoms C. 5-HT1A
D. D2
Sustenna, Relprevv, and Maintena have provided for longer
dosing interval of q4 weeks compared to previous IMs
Relprevv use limited due to need for registration and monitoring
Maintena has low metabolic risk, but still requires oral overlap
Versacloz provides another formulation option for patients 57 58
with treatment-resistant schizophrenia
POST-TEST: QUESTION 2 POST-TEST: QUESTION 3

Which of the following antipsychotics is NOT available as a Which of the following is a black box warning for Zyprexa
long-acting injectable? Relprevv (olanzapine), requiring that a patient be observed
A. Olanzapine for at least 3 hours after administration?
B. Aripiprazole A. Acute dystonia
C. Paliperidone B. Post-injection delirium/sedation syndrome
D. Quetiapine C. Hyperglycemia
D. Increased mortality in elderly patients with
dementia-related psychosis
59 60
15

N I "M T ?": Ewer Typical Ntipsychotics

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N I "M T ?": Ewer Typical Ntipsychotics

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3/27/2013

ANTIPSYCHOTICS: Review new formulations of previously approved

PRE-TEST: QUESTION 1 PRE-TEST: QUESTION 2

PRE-TEST: QUESTION 3 BACKGROUND

AVAILABLE ATYPICALS SCHIZOPHRENIA PATHOPHYSIOLOGY

DOPAMINE BRAIN PATHWAYS SCHIZOPHRENIA CORE SYMPTOMS

ATYPICAL ANTIPSYCHOTICS COMMON ADVERSE SIDE EFFECTS

Cause blockade of 1, H1, and mACh receptors Anticholinergic side effects

RARE ADVERSE SIDE EFFECTS BLACK BOX WARNINGS

Seizures Thermoregulation Suicidality in children and young adults due to depression

FANAPT: DOSING FANAPT: ADVERSE EFFECTS

Initial dose: 1mg PO BID, titrating by 1-2mg BID daily Orthostasis

Target dose: 6-12mg PO BID Medium metabolic risk

Maximum dose: 24mg/day in divided doses QTc prolongation (~11.4 msec)

Dosage adjustments reduce by 50% Priapism

Fanapt package insert. Fanapt package insert.

FANAPT: EFFICACY FANAPT: CLINICAL UTILITY

INVEGA SUSTENNA INVEGA SUSTENNA: DOSING

Once monthly injection Then, 117mg IM (deltoid or gluteal) q4 weeks

SWITCHING TO INVEGA SUSTENNA INVEGA SUSTENNA: ADMINISTRATION

PO QDAY IM Q4 WEEKS Attach appropriate needle based on injection site

INVEGA SUSTENNA: ADVERSE EFFECTS INVEGA SUSTENNA: EFFICACY

Invega Sustenna package insert. Invega Sustenna package insert.

INVEGA SUSTENNA: CLINICAL UTILITY SAPHRIS

SAPHRIS: DOSING SAPHRIS: ADMINISTRATION

Regular flavor or black cherry Remove immediately before

SAPHRIS: ADVERSE EFFECTS SAPHRIS: EFFICACY

SAPHRIS: CLINICAL UTILITY ZYPREXA RELPREVV

Zyprexa Relprevv package insert.

ZYPREXA RELPREVV: DOSING ZYPREXA RELPREVV: ADMINISTRATION

Clearance may be impaired in severe hepatic dysfunction

POST-INJECTION DELIRIUM/SEDATION ZYPREXA RELPREVV REGULATIONS

Prior to releasing patient, healthcare professional must confirm

DO NOT administer if patient will not be accompanied on release

REMS medication distributed through Zyprexa Relprevv Patient

ZYPREXA RELPREVV ADVERSE EFFECTS ZYPREXA RELPREVV: EFFICACY

PDSS Similar to Risperdal Consta in 1 year treatment-completion rates

Sedation Dose-related rate of discontinuation due to lack of efficacy

High metabolic risk

Zyprexa Relprevv package insert. Detke et al. BMC Psychiatry 2012;12:51.

ZYPREXA RELPREVV: CLINICAL UTILITY LATUDA

LATUDA: DOSING LATUDA: ADVERSE EFFECTS

CONTRAINDICATED with strong CYP3A4 inhibitors or inducers

LATUDA: EFFICACY LATUDA: CLINICAL UTILITY

ABILIFY MAINTENA ABILIFY MAINTENA: DOSING

ABILIFY MAINTENA: ADMINISTRATION ABILIFY MAINTENA: ADVERSE EFFECTS

Inject immediately after reconstitution

Attach vial adapter to syringe and draw up recommend volume

ABILIFY MAINTENA: EFFICACY ABILIFY MAINTENA: CLINICAL UTILITY

May improve mood

Reduces prolactin levels

Kane et al. J Clin Psychiatry 2012;73:617.

VERSACLOZ VERSACLOZ: CLINICAL UTILITY

Side effects similar to other clozapine formulations Slow dose titration

REMS program due to agranulocytosis risk High metabolic risk

ATYPICAL FORMULATIONS RELATIVE METABOLIC RISK

CONCLUSIONS POST-TEST: QUESTION 1

Versacloz provides another formulation option for patients 57 58

with treatment-resistant schizophrenia

POST-TEST: QUESTION 2 POST-TEST: QUESTION 3

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