Treatment of

Patients With
Schizophrenia

Introduction

  Assessment

Treatment

The printing and distribution of this educational resource was

supported by Janssen Pharmaceuticals, Inc. It is intended for
reference only and healthcare providers must make clinical
judgments based on their independent assessment of each
patient. Janssen Pharmaceuticals, Inc. was not involved in
the development of this publication or the underlying
guidelines on which this publication is based.
cp-173636v1
 Introduction

➤ The lifetime prevalence of schizophrenia is estimated to be

approximately 0.7%. Worldwide, schizophrenia is one of the top
20 causes of disability.

➤ Schizophrenia is also associated with increased mortality, with a

shortened lifespan and standardized mortality ratios that are reported
to be twofold to fourfold those in the general population. Individuals
often have physical health comorbidities such as cardiovascular,
respiratory, and infectious diseases and malignancies, particularly lung
cancer.

➤ About 4%–10% of persons with schizophrenia die by suicide, with

rates that are highest among males in the early course of the disorder.
Additional causes of death also include other unnatural events such as
accidents and traumatic injuries.

➤ Harms from therapeutic interventions may include:

• adverse events that range from serious to less serious but affect tolerability
to minor
• negative effects of the intervention on quality of life
• barriers and inconveniences associated with treatment
• other negative aspects of treatment that may influence decision-making
by the patient, the clinician or both.
➤ The guideline statements should be implemented in the context of
a person-centered treatment plan that includes evidence-based
nonpharmacological and pharmacological treatments for schizophrenia.

➤ See full text guideline <https://psychiatryonline.org/doi/pdf/10.1176/

appi.books.9780890424841> for additional information.

2
 Assessment

Note: none of the subsequent statements are meant to stand alone.

➤ As outlined in APA’s Practice Guidelines for the Psychiatric Evaluation of

Adults (3rd edition), APA recommends (1C) that the initial assessment
of a patient with a possible psychotic disorder include:
• the reason the individual is presenting for evaluation
• the patient’s goals and preferences for treatment
• a review of psychiatric symptoms and trauma history
• an assessment of tobacco and other substance use
• a psychiatric treatment history
• an assessment of physical health
• an assessment of psychosocial and cultural factors
• a mental status examination, including cognitive assessment
• an assessment of risk of suicide and aggressive behaviors.
➤ APA recommends (1C) that the initial psychiatric evaluation of a patient
with a possible psychotic disorder include a quantitative measure to
identify and determine the severity of symptoms and impairments of
functioning that may be a focus of treatment.

➤ APA recommends (1C) that patients with schizophrenia have a

documented, comprehensive, and person-centered treatment plan that
includes evidence-based nonpharmacological and pharmacological
treatments.

Elements to consider as part of the treatment plan:

• pharmacological interventions
• psychotherapies and other psychosocial interventions
• engaging support
• adherence
• addressing risks for suicide/aggression
• addressing tobacco and SUDs
• addressing other comorbid psychiatric symptoms, diagnoses
• addressing other comorbid health conditions
• pregnancy/postpartum concerns
• treatment setting
• involuntary treatment issues
• needs of patients in correctional settings

3
 Assessment

Figure 1. Managing Schizophrenia

Assessment

Quantitative Measure

Treatment plan

Both Pharmacotherapy &

Psychosocial Interventions

Antipsychotic with monitoring

Improvement?

NO YES

Adherence issues?

NO YES

Another antipsychotic LAI

Treatment resistance, suicide Improvement? YES Side effects?

risk, or aggressive behavior? NO
NO YES
NO YES

See guideline Clozapine

for further
options
Improvement?

Continue medication
NO YES

4
 • the patient’s goals and preferences
for treatment
• a review of psychiatric symptoms
and trauma history
• an assessment of tobacco use and
other substance use
• a psychiatric treatment history
• an assessment of physical health
• an assessment of psychosocial and
cultural factors
• a mental status examination,
including cognitive assessment
• an assessment of risk of suicide and
aggressive behaviors

• engaging support • addressing other comorbid health

• adherence
• addressing risks for suicide/
aggression
• addressing tobacco and SUDs
• addressing other comorbid
psychiatric symptoms, diagnoses
conditions
• pregnancy/postpartum concerns
• treatment setting
• involuntary treatment issues
• needs of patients in correctional
settings

• coordinated specialty care program • family interventions

(for first episode of psychosis) • self-management skills and enhancing
• CBTp person-oriented recovery
• psychoeducation • cognitive remediation
• employment services • social skills
• assertive community treatment • supportive psychotherapy

Select based on: Monitor for:

• available formulations • side effects
• interactions and metabolism • symptom response including non or
• pharmacokinetic properties partial response
• side-effect profile • adherence

Acute dystonia anticholinergic

• lowering the dosage of the antipsychotic medication,

Parkinsonism • switching to another antipsychotic medication, or
• treating with an anticholinergic medication

• lowering the dosage of the antipsychotic medication

• switching to another antipsychotic medication
Akathisia
• adding a benzodiazepine medication, or
• adding a beta-adrenergic-blocking agent

Tardive dyskinesia reversible inhibitor of the vesicular monoamine

transporter 2 (VMAT2)

Other side effects*

* See guideline for management and information on other side effects.

5
 Assessment

Suggested physical and laboratory assessments for

patients with schizophrenia
Assessment Initial or baselinea Follow-upb

Assessments to monitor physical status and detect concomitant physical

conditions
Vital signs Pulse, blood pressure Pulse, blood pressure,
temperature as clinically
indicated
Body weight and Body weight, height, BMIc every visit for 6 months
height BMIc and at least quarterly thereafter
Hematology CBC, including ANC CBC, including ANC if clinically
indicated (e.g., patients treated
with clozapine)
Blood chemistries Electrolytes, renal As clinically indicated
function tests, liver
function tests, TSH
Pregnancy Pregnancy test
for women of
childbearing potential
Toxicology Drug toxicology Drug toxicology screen, if
screen, if clinically clinically indicated
indicated
Electrophysiological EEG, if indicated
studies on the basis of
neurological exam or
history
Imaging Brain imaging (CT
or MRI, with MRI
being preferred), if
indicated on the basis
of neurological exam
or historyd
Genetic testing Chromosomal testing,
if indicated on the
basis of physical
examination or
history, including
developmental
historye

6
Suggested physical and laboratory assessments for
patients with schizophrenia (cont'd)
Assessment Initial or baselinea Follow-upb
Assessments related to other specific side effects of treatment
Diabetesf Screening for diabetes Fasting blood glucose or
risk factors,g fasting hemoglobin A1C at 4 months after
blood glucoseh initiating a new treatment and at
least annually thereafterh
Hyperlipidemia Lipid paneli Lipid paneli at 4 months after
initiating a new antipsychotic
medication and at least annually
thereafter
Metabolic syndrome Determine whether Determine whether metabolic
metabolic syndrome syndrome criteria are metj at 4
criteria are metj months after initiating a new
antipsychotic medication and at
least annually thereafterj
QTc prolongation ECG before treatment ECG with significant change
with chlorpromazine, in dose of chlorpromazine,
droperidol, iloperidone, droperidol, iloperidone, pimozide,
pimozide, thioridazine, thioridazine, or ziprasidone,k
or ziprasidonek or in or with the addition of other
the presence of cardiac medications that can affect QTc
risk factorsl interval in patients with cardiac
risk factorsl or elevated baseline
QTc intervals
Hyperprolactinemia Screening for Screening for symptoms of
symptoms of hyperprolactinemia at each visit
hyperprolactinemiam until stable, then yearly if treated
Prolactin level, if with an antipsychotic known to
indicated on the basis increase prolactinm
of clinical history Prolactin level, if indicated on the
basis of clinical history
Antipsychotic- Clinical assessment Clinical assessment of akathisia,
induced movement of akathisia, dystonia, dystonia, parkinsonism, and
disorders parkinsonism, and other abnormal involuntary
other abnormal movements, including tardive
involuntary dyskinesia, at each visitn
movements, including Assessment with a structured
tardive dyskinesian instrument (e.g., AIMS, DISCUS)
Assessment with a at a minimum of every 6 months
structured instrument in patients at high risk of tardive
(e.g., AIMS, DISCUS) if dyskinesiao and at least every 12
such movements are months in other patientsp as well
present as if a new onset or exacerbation
of preexisting movements is
detected at any visit
See full text guideline <https://psychiatryonline.org/doi/pdf/10.1176/appi.
books.9780890424841> for additional important information in footnotes.

7
 Treatment

Pharmacotherapy
➤ APA recommends (1A) that patients with schizophrenia be treated with an
antipsychotic medication and monitored for effectiveness and side effects.*

The choice of medication should consider:

• addressing patient's non- or partial response
• side-effect profile
• presence of other health conditions that may be affected by medication
side effects
• formulations
• interactions and metabolism
• pharmacokinetic properties
See full text guideline <https://psychiatryonline.org/doi/pdf/10.1176/appi.
books.9780890424841> for more information.

➤ APA recommends (1A) that patients with schizophrenia whose

symptoms have improved with an antipsychotic medication continue to
be treated with an antipsychotic medication.*

➤ APA suggests (2B) that patients with schizophrenia whose symptoms

have improved with an antipsychotic medication continue to be treated
with the same antipsychotic medication.*

➤ APA recommends (1B) that patients with treatment-resistant

schizophrenia be treated with clozapine.*

➤ APA recommends (1B) that patients with schizophrenia be treated with

clozapine if the risk for suicide attempts or suicide remains substantial
despite other treatments.*

➤ APA suggests (2C) that patients with schizophrenia be treated with

clozapine if the risk for aggressive behavior remains substantial despite
other treatments.*

➤ APA suggests (2B) that patients receive treatment with a long-acting

injectable antipsychotic medication if they prefer such treatment or if
they have a history of poor or uncertain adherence.*

➤ APA recommends (1C) that patients who have acute dystonia associated
with antipsychotic therapy be treated with an anticholinergic medication.

➤ APA suggests (2C) the following options for patients who have
parkinsonism associated with antipsychotic therapy: lowering the dosage
of the antipsychotic medication, switching to another antipsychotic
medication, or treating with an anticholinergic medication.
8
➤ APA suggests (2C) the following options for patients who have
akathisia associated with antipsychotic therapy: lowering the dosage
of the antipsychotic medication, switching to another antipsychotic
medication, adding a benzodiazepine medication, or adding a beta-
adrenergic-blocking agent.

➤ APA recommends (1B) that patients who have moderate to severe or

disabling tardive dyskinesia associated with antipsychotic therapy
be treated with a reversible inhibitor of the vesicular monoamine
transporter 2 (VMAT2).

Psychosocial Interventions
➤ APA recommends (1B) that patients with schizophrenia who are
experiencing a first episode of psychosis be treated in a coordinated
specialty care program.*

➤ APA recommends (1B) that patients with schizophrenia be treated with

cognitive-behavioral therapy for psychosis (CBTp).*

➤ APA recommends (1B) that patients with schizophrenia receive

psychoeducation.*

➤ APA recommends (1B) that patients with schizophrenia receive

supported employment services.*

➤ APA recommends (1B) that patients with schizophrenia receive

assertive community treatment if there is a history of poor engagement
with services leading to frequent relapse or social disruption (e.g.,
homelessness; legal difficulties, including imprisonment).*

➤ APA suggests (2B) that patients with schizophrenia who have ongoing
contact with family receive family interventions.*

➤ APA suggests (2C) that patients with schizophrenia receive

interventions aimed at developing self-management skills and
enhancing person-oriented recovery.*

➤ APA suggests (2C) that patients with schizophrenia receive cognitive

remediation.*

➤ APA suggests (2C) that patients with schizophrenia who have a therapeutic
goal of enhanced social functioning receive social skills training.*

➤ APA suggests (2C) that patients with schizophrenia be treated with

supportive psychotherapy.*

* This guideline statement should be implemented in the context of a person-centered treatment

plan that includes evidence-based nonpharmacological and pharmacological treatments for
schizophrenia.
9
 Treatment

Antipsychotic medications: available oral and short-acting

intramuscular formulations*
Genric name Available U.S.
Trade name formulations
(most common in Metabolic enzymes/ (mg, unless otherwise
U.S., may change) transporters noted)
First-generation antipsychotics
Chlorpromazine CYP2D6 (Major), CYP1A2 Tablet: 10, 25, 50, 100, 200
Thorazine (Minor), CYP3A4 (Minor) Short-acting injection (HCl):
substrate 25/mL (1 mL, 2 mL)
Fluphenazine CYP2D6 (Major) substrate Tablet: 1, 2.5, 5, 10
Prolixin Oral concentrate: 5/mL
(120 mL)
Elixir: 2.5/5 mL (60 mL)
Short-acting injection (HCl):
2.5/mL (10 mL)
Haloperidol CYP2D6 (Major), CYP3A4 Tablet: 0.5, 1, 2, 5, 10, 20
Haldol (Major), CYP1A2 (Minor) Oral concentrate: 2/mL
substrate; 50-60% (5 mL, 15 mL, 120 mL)
glucuronidation Short-acting injection
(lactate):
5/mL (1 mL, 10 mL)
Loxapine CYP1A2 (Minor), CYP2D6 Capsule: 5, 10, 25, 50
Loxitane (Minor), CYP3A4 (Minor) Aerosol powder breath-
substrate; P-glycoprotein activated inhalation: 10
inhibitor
Molindone CYP2D6 substrate Tablet: 5, 10, 25
Moban
Perphenazine CYP2D6 (Major), CYP1A2 Tablet: 2, 4, 8, 16
Trilafon (Minor), CYP2C19 (Minor),
CYP2C9 (Minor), CYP3A4
(Minor) substrate
Pimozide CYP1A2 (Major), CYP2D6 Tablet: 1, 2
Orap (Major), CYP3A4 (Major)
substrate
Thioridazine CYP2D6 (Major) substrate Tablet: 10, 25, 50, 100
Mellaril and moderate inhibitor,
CYP2C19 (Minor) substrate
Thiothixene CYP1A2 (Major) substrate Capsule: 1, 2, 5, 10
Navane
Trifluoperazine CYP1A2 (Major) substrate Tablet: 1, 2, 5, 10
Stelazine

10
Initial dose Typical dose range Maximum daily dose
(mg/day) (mg/day) (mg/day)

25–100 200–800 Oral: 1000–2000

2.5–10 6–20 Oral: 40

IM: 10

1–15 5–20 Oral: 100

IM: 20

20 60–100a Oral: 250

Aerosol: 10

50–75 30–100a 225

8–16 8–32 64

0.5–2 2–4 10

150–300 300–800a 800

6–10 15–30 60

4–10 15–20 50

11
 Treatment

Antipsychotic medications: available oral and short-acting

intramuscular formulations* (cont'd)
Genric name Available U.S.
Trade name formulations
(most common in Metabolic enzymes/ (mg, unless otherwise
U.S., may change) transporters noted)
Second-generation antipsychotics
Aripiprazole CYP2D6 (Major), CYP3A4 Tablet: 2, 5, 10, 15, 20, 30
Abilify (Major) substrate Tablet, disintegrating: 10, 15
Tablet with ingestible event
marker (Mycite): 2, 5, 10,
15, 20, 30
Solution: 1/mL (150 mL)
Asenapine CYP1A2 (Major), CYP2D6 Tablet, sublingual: 2.5, 5, 10
Saphris (Minor), CYP3A4 (Minor)
substrate; glucuronidation
by UGT1A4; CYP2D6 weak
inhibitor
Asenapine CYP1A2 (Major), CYP2D6 Transdermal system:
Secuado (Minor), CYP3A4 (Minor) 3.8 mg/24 hours,
substrate; glucuronidation 5.7 mg/24 hours,
by UGT1A4; CYP2D6 weak 7.6 mg/24 hours
inhibitor
Brexpiprazole CYP3A4 (Major), CYP2D6 Tablet: 0.25, 0.5, 1, 2, 3, 4
Rexulti (Major) substrate
Cariprazine CYP3A4 (Major), CYP2D6 Capsule: 1.5, 3, 4.5, 6
Vraylar (Minor) substrate
Clozapinec CYP1A2 (Major), CYP2A6 Tablet: 25, 50, 100, 200
Clozaril, FazaClo, (Minor), CYP2C19 (Minor), Tablet, disintegrating:
Versacloz CYP2C9 (Minor), CYP2D6 12.5, 25, 100, 150, 200
(Minor), CYP3A4 (Minor) Oral suspension: 50/mL
substrate (100 mL)
Iloperidone CYP2D6 (Major), CYP3A4 Tablet: 1, 2, 4, 6, 8, 10, 12
Fanapt (Minor) substrate, CYP3A4
weak inhibitor
Lurasidone CYP3A4 (Major) substrate, Tablet: 20, 40, 60, 80, 120
Latuda CYP3A4 weak inhibitor
Olanzapine CYP1A2 (Major), CYP2D6 Tablet: 2.5, 5, 7.5, 10, 15, 20
Zyprexa (Minor) substrate; Tablet, disintegrating:
metabolized via direct 5, 10, 15, 20
glucuronidation Short-acting IM powder for
solution: 10/2 mL

12
Initial dose Typical dose range Maximum daily dose
(mg/day) (mg/day) (mg/day)

10–15 10–15 30

10 20 20

3.8 3.8–7.6 7.6

1 2–4 4

1.5 1.5–6 6b

12.5–25 300–450d 900

2 12–24 24

40 40–120 160

5–10 10–20 20e

13
 Treatment

Antipsychotic medications: available oral and short-acting

intramuscular formulations* (cont'd)
Genric name Available U.S.
Trade name formulations
(most common in Metabolic enzymes/ (mg, unless otherwise
U.S., may change) transporters noted)
Paliperidone P-glycoprotein/ABCB1, Tablet, extended release:
Invega CYP2D6 (Minor), CYP3A4 1.5, 3, 6, 9
(Minor) substrate
Quetiapine CYP3A4 (Major), CYP2D6 Tablet, immediate release:
Seroquel (Minor) substrate 25, 50, 100, 200, 300, 400
Tablet, extended release:
50, 150, 200, 300, 400
Risperidone CYP2D6 (Major), CYP3A4 Tablet: 0.25, 0.5, 1, 2, 3, 4
Risperdal (Minor), P-glycoprotein/ Tablet, disintegrating:
ABCB1 substrate, 0.25, 0.5, 1, 2, 3, 4
N-dealkylation (minor), Oral solution: 1/mL (30 mL)
CYP2D6 weak inhibitor
Ziprasidone CYP1A2 (Minor), CYP3A4 Capsule: 20, 40, 60, 80
Geodon (Minor) substrate, Solution reconstituted,
glutathione, aldehyde IM: 20
oxidase
* This table includes information compiled from multiple sources. Detailed information on such
issues as dose regimen, dose adjustments, medication administration procedures, handling
precautions, and storage can be found in product labeling. It is recommended that readers
consult product labeling information for authoritative information on these medications.
a
Usually given in divided doses.
b
Up to 9 mg/day has been studied in clinical trials.
c
Clozapine levels should be drawn after at least 3 days on a stable dose and about 12 hours
after the last dose. Levels associated with efficacy show individual variation, but efficacy
typically begins at a level above 250 ng/mL, with the most efficacy seen at levels higher
than 350 ng/mL. U.S. prescribers must complete Clozapine REMS education (https://www.
clozapinerems.com/) and follow requirements for a baseline CBC and ANC, and for ANC
monitoring before and during treatment. Refer to clozapine labeling for detailed instructions
on dose titration and dose adjustments with CYP450 interactions.
d
May be taken without regard to food or other medications unless specifically noted.
e
Olanzapine has been used at higher dosages, typically up to 30 mg/day, although some case
series describe use of up to 60 mg/day.
f
Dosages of risperidone up to 16 mg/day have been studied in clinical trials. However, doses
>6 mg for twice-daily dosing do not appear to confer additional benefit and have a higher
incidence of extrapyramidal symptoms than do lower doses.

14
Initial dose Typical dose range Maximum daily dose
(mg/day) (mg/day) (mg/day)
6 3–12 12

Immediate release: 50 400–800 800

Extended release: 300

2 2–8 8f

40 80–160 320

15
 Treatment

Antipsychotic medications: relative side effects of

oral formulations

Generic name Akathisia Parkinsonism Dystonia

First-generation antipsychotics
Chlorpromazine ++ ++ ++
Fluphenazine +++ +++ +++
Haloperidol +++ +++ +++
Loxapine ++ ++ ++
Molindone ++ ++ ++
Perphenazine ++ ++ ++
Pimozide +++ +++ ++
Thioridazine + + +
Thiothixene +++ +++ +++
Trifluoperazine ++ ++ ++
Second-generation antipsychotics
Aripiprazole ++ + +
Asenapine ++ + ++
Brexpiprazole ++ + +
Cariprazine ++ + +
Clozapine + + +
Iloperidone + + +
Lurasidone ++ ++ ++
Olanzapine ++ ++ +
Paliperidone ++ ++ ++
Quetiapine + + +
Risperidone ++ ++ ++
Ziprasidone ++ + +

16
Tardive
dyskinesia Hyperprolactinemiaa Anticholinergic Sedation

+++ + +++ +++

+++ +++ + +
+++ +++ + +
++ ++ ++ ++
++ ++ + ++
++ ++ ++ ++
+++ +++ + +
+ ++ +++ +++
+++ +++ + +
++ ++ ++ +

+ + + +
++ ++ + ++
+ + + ++
+ + ++ ++
+ + +++ +++
+ ++ + ++
++ + + ++
+ ++ ++ +++
++ +++ + +
+ + ++ +++
++ +++ + ++
+ ++ + ++

17
 Treatment

Antipsychotic medications: relative side effects of

oral formulations

Generic name Seizures Orthostasis QT prolongation

First-generation antipsychotics
Chlorpromazine ++ +++ +++
Fluphenazine + + ++
Haloperidol + + ++
Loxapine + ++ ++
Molindone + + ++
Perphenazine + ++ ++
Pimozide +++ + +++
Thioridazine ++ +++ +++
Thiothixene +++ + ++
Trifluoperazine + + ++
Second-generation antipsychotics
Aripiprazole + + +
Asenapine + ++ ++
Brexpiprazole + + ++
Cariprazine + + ++
Clozapine +++ +++ ++
Iloperidone + +++ +++
Lurasidone + + +
Olanzapine ++ ++ ++
Paliperidone + ++ ++
Quetiapine ++ ++ ++
Risperidone + ++ ++
Ziprasidone + ++ +++

+=seldom; ++=sometimes; +++=often

a
In general, rates of sexual dysfunction parallel rates of hyperprolactinemia except where
noted in comments.
b
Pigmentary retinopathy; high rates of sexual dysfunction; avoid use if QTc interval is >450
msec or with concomitant use of drugs that prolong the QTc interval or inhibit CYP2D6
c
FDA safety alert for impulse control disorders (e.g., gambling, binge eating); may reduce
hyperprolactinemia with other antipsychotics
18
 Glucose
Weight gain Hyperlipidemia abnormalities Comments

++ + ++
++ + +
++ + +
+ + +
+ + +
++ + +
+ + +
++ + + b

+ + +
++ + +

+ + + c

++ ++ ++ d

+ ++ +
++ + +
+++ +++ +++ e

++ + ++
+ ++ ++ f

+++ +++ +++

++ ++ +
++ +++ ++
++ + ++ g

+ + +
d
Oral hypoesthesia
e
Increased salivation common; high rate of sexual dysfunction; severe constipation and paralytic
ileus possible; fever can occur with initiation; myocarditis is infrequent; cardiomyopathy and
severe neutropenia are rare
f
Dose-related creatinine increase in some patients
g
Intraoperative floppy iris syndrome reported

19
 Treatment

Long-acting injectable antipsychotic medications: dosing*

Initial dose
Generic name Trade name Dose conversions (mg)
First-generation antipsychotics
Fluphenazine Prolixin For each 10 mg/day 6.25–25 every
Decanoate oral, give 12.5 mg 2 weeks
decanoate every 3
weeks

Haloperidol Haldol For each 5 mg/day Determined by oral

decanoate oral, give 50–75 mg dose and/or risk
decanoate every 4 of relapse up to a
weeks maximum of 100 mg
Second-generation antipsychotics
Aripiprazole Abilify Not applicable 400
monohydrate Maintena

Aripiprazole Aristada Not applicable 675

lauroxil Initio

Aripiprazole Aristada 10 mg/day orally, give Monthly:

lauroxil 441 mg IM/month 441, 662, 882
15 mg/day orally, give Every 6 weeks:
662 mg/month IM, 882
882 mg IM every 6 Every 2 months:
weeks, or 1,064 mg 1,064
IM every 2 months
20 mg/day or greater
orally, give 882 mg/
month IM

20
Typical dose Maximum Dosing Need for initial oral
(mg) dose (mg) frequency supplementation

6.25–25 every 100 2–4 weeks Decrease oral dose

2–4 weeks by half after first
injection, then
discontinue with
second injection
50–200 (10–15 450/month 4 weeks Taper and discontinue
times previous after two to three
oral dose) injections

400 400/month Monthly Continue oral for

14 days after initial
injection
675 675 Single dose to Must be administered
initiate Aristada in conjunction with
treatment one 30 mg dose of
or reinitiate oral aripiprazole.
treatment after a
missed Aristada
dose. Not for
repeated dosing.
Monthly: 882/month Monthly: There are two ways to
441, 662, 882 441, 662, 882 initiate treatment:
Every 6 weeks: Every 6 weeks: 1. Give one IM injection
882 882 of Aristada Initio
Every 2 months: Every 2 months: 675 mg and
1,064 1,064 one dose of oral
aripiprazole 30
mg, or
2. Give 21 days of
oral aripiprazole in
conjunction with
the first Aristada
injection

21
 Treatment

Long-acting injectable antipsychotic medications: dosing*

(cont'd)
Olanzapine Zyprexa 10 mg/day orally, Determined by oral
Relprevv 210 mg every 2 dose
weeks for four
doses, or 405 mg
every 4 weeks
15 mg/day orally, 300
mg every 2 weeks
for four doses
20 mg/day orally, 300
mg every 2 weeks
Paliperidone Invega 3 mg oral 234 mg IM on day 1
palmitate Sustenna paliperidone, and 156 mg IM
give 39–78 mg IM 1 week later, both
6 mg oral, administered in the
give 117 mg IM deltoid muscle
9 mg oral,
give 156 mg IM
12 mg oral,
give 234 mg IM
Paliperidone Invega Trinza Conversion from Dependent on last
palmitate monthly Invega dose of monthly
Sustenna to every paliperidone
3-month injections of
Invega Trinza:
78 mg, give 273 mg
117 mg, give 410 mg
156 mg, give 546 mg
234 mg, give 819 mg
Risperidone Risperdal Oral risperidone to 25 every 2 weeks
Consta Risperidone Consta IM:
≤3 mg/day, give
25 mg/2 weeks
>3 to ≤5 mg/day, give
37.5 mg/2 weeks
>5 mg/day, give
50 mg/2 weeks
Risperidone Perseris Oral risperidone Determined by oral
to subcutaneous dose
risperidone
extended release:
3 mg/day, give
90 mg/monthly
4 mg/day, give
120 mg/monthly
* This table includes information compiled from multiple sources. Detailed information on such
issues as dose regimen, dose adjustments, medication administration procedures, handling
precautions, and storage can be found in product labeling. It is recommended that readers
consult product labeling information for authoritative information on these medications.
22
150 mg, 210 mg, 300 mg 2–4 weeks Not required
or 300 mg every every 2
2 weeks or 300 weeks or
mg or 405 mg 405 mg
every 4 weeks every 4
weeks

78–234 mg 234 mg/ Monthly Not required

monthly month
beginning at
week 5

273–819 819/3 Every 3 months Not applicable

months

25–50 every 2 50 every 2 2 weeks Continue oral for 3

weeks weeks weeks (21 days)

90–120 monthly 120/month Monthly Neither a loading dose

nor oral overlap is
needed

23
 Treatment

Reversible inhibitors of human vesicular monoamine

transporter type 2a
Genric name Deutetrabenazine Tetrabenazine Valbenazine
Trade name Austedo Xenazine Ingrezza
Available Tablet: 6, 9, 12 Tablet: 12.5, 25 Capsule: 40, 80
formulations
(mg)
Typical dose 12–48 25–75 40–80
range (mg/day)
Bioavailability 80% 75% 49%
Time to peak 3–4 1–2 0.5–1
level (hours)
Protein binding 60% to 68% 82% to 85% >99%
(alpha-HTBZ) 60% to 68% 64% alpha-HTBZ
59% to 63% (alpha-HTBZ)
(beta-HTBZ) 59% to 63%
(beta-HTBZ)
Metabolism Hepatic Hepatic Hepatic
Metabolic Major substrate Major substrate Major substrate
enzymes/ of CYP2D6, of CYP2D6 of CYP3A4,
transporters minor substrate minor substrate
of CYP1A2 and of CYP2D6
CYP3A4
Metabolites Deuterated alpha Alpha, beta and alpha- HTBZ:
and beta HTBZ: O-dealkylated Active
Active HTBZ: Active
Elimination half- Deuterated alpha Alpha-HTBZ: 4–8 15-22
life (hours) and beta HTBZ: Beta-HTBZ: 2–4
9–10
Excretion Urine (~75%-85% Urine (~75% Urine: 60%;
changed); changed); feces: 30%
feces (~8%–11%) feces (~7%–16%)

24
Reversible inhibitors of human vesicular monoamine
transporter type 2a (cont'd)
Genric name Deutetrabenazine Tetrabenazine Valbenazine
Trade name Austedo Xenazine Ingrezza
Hepatic Contraindicated Contraindicated Maximum dose
impairment of 40mg daily
with moderate
to severe
impairment
(Child-Pugh
score 7–15)
Renal impairment No information No information Use not
available available recommended
in severe renal
impairment (CrCl
<30 mL/min)
Common adverse Sedation Sedation, Sedation
effect depression,
extrapyramidal
effects, insomnia,
akathisia,
anxiety, nausea,
falls
Effect of food on Food effects Unaffected by Can be taken
bioavailability maximal food with or without
concentration. food. High fat
Administer with meals decreased
food. Swallow the Cmax and AUC
tablets whole for valbenazine
and do not chew, but values
crush, or break. for the active
metabolite
(alpha-HTBZ) are
unchanged
a
This table includes information compiled from multiple sources. Detailed information on
issues such as dose regimen, dose adjustments, medication administration procedures,
handling precautions, and storage can be found in product labeling. It is recommended
that readers consult product labeling information for authoritative information on these
medications.

25
 Treatment

Medications for treatment of medication-induced

parkinsonisma
Genric name Amantadine Benztropine mesylate
Trade name Symmetrel Cogentin
Typical use Parkinsonism Acute dystonia,
parkinsonism
Mechanism of action Uncompetitive NMDA Muscarinic antagonist
receptor antagonist
(weak)
Available formulations Tablet: 100 Tablet: 0.5, 1, 2
(mg, unless otherwise Tablet, extended release: Solution, injection: 1/mL
noted) 129, 193, 258 (2 mL)
Capsule: 100
Capsule, liquid filled:
100
Capsule, extended
release: 68.5, 137
Oral syrup: 50/5 mL
Typical dose range Immediate release Tablet: 0.5–6.0
(mg/day) tablet or capsule: Solution, injection: 1–2
100–300
Extended release tablet:
129–322
Bioavailability 86%–94% 29%

Time to peak level Immediate release: 2–4 Oral: 7

(hours) Extended release: 7.5–12 IM: minutes
Protein binding 67% 95%

Metabolism Primarily renal Hepatic

Metabolic enzymes/ Substrate of organic Substrate of CYP2D6

transporters cation transporter 2 (minor)

Metabolites Multiple; unknown Not known

activity
Elimination half-life 16–17 7
(hours)
Excretion Urine 85% unchanged; Urine
0.6% fecal
Hepatic impairment No dose adjustments No dose adjustments
noted in labeling noted in labeling

26
Diphenhydramine Trihexyphenidyl hydrochloride
Benadryl Artane
Acute dystonia, parkinsonism Acute dystonia, parkinsonism

Histamine H1 antagonist Muscarinic antagonist

Capsule: 25, 50 Oral elixir: 0.4/mL (473 mL)

Oral elixir: 12.5/5 mL Tablet: 2, 5
Oral solution: 12.5/5 mL, 6.25/1 mL
Tablet: 25, 50
Solution, injection: 50/1 mL
Other brand name formulations are
available for allergy relief

Oral: 75–200 Oral: 5–15

Solution, injection: 10–50

40%–70% 100%

1–4 1.3

76%–85% Not known

Hepatic Not known

Extensively hepatic N-demethylation None known

via CYP2D6; minor demethylation
via CYP1A2, CYP2C9 and CYP2C19;
inhibits CYP2D6 (weak)
Inactive Not known

4–8 4

Urine (as metabolites and unchanged Urine and bile

drug)
No dose adjustments noted in No dose adjustments noted in
labeling labeling

27
 Treatment

Medications for treatment of medication-induced

parkinsonisma (cont'd)
Genric name Amantadine Benztropine mesylate
Trade name Symmetrel Cogentin
Renal impairment Elimination half-life No dose adjustments
increases with renal noted in labeling
impairment

Comments Negligible removal by Onset of action with

dialysis; do not crush or IV dose is comparable
divide extended release to IM
products

a
This table includes information compiled from multiple sources. Detailed information on such
issues as dose regimen, dose adjustments, medication administration procedures, handling
precautions, and storage can be found in product labeling. It is recommended that readers
consult product labeling information for authoritative information on these medications.

28
Diphenhydramine Trihexyphenidyl hydrochloride
Benadryl Artane
No dose adjustments noted in No dose adjustments noted in
labeling. However, dosing interval labeling
may need to be increased or dosage
reduced in older individuals and
those with renal impairments.
Total daily dose typically divided into
3–4 doses per day.
Maximum daily dose 300 mg for oral
and 400 mg for IM/IV, with 100 mg
maximum dose for IV/IM.
Give IV dose at a rate of 25 mg/minute.
Give IM dose by deep intramuscular
injection because subcutaneous
or intradermal injection can cause
local necrosis.

29
 Grading Recommendations
Grade Description
1 Recommendation: indicates confidence that the benefits of the
intervention clearly outweigh harms.
2 Suggestion: indicates greater uncertainty: although the benefits of the
statement are still viewed as outweighing the harms, balance of benefits
and harms is more difficult to judge, or the benefits or the harms may
be less clear. With a suggestion, patient values and preferences may
be more variable, and this can influence the clinical decision that is
ultimately made.

Grade Strength of Evidence

A High: high confidence that the evidence reflects the true effect. Further
research is very unlikely to change our confidence in the estimate of effect.
B Moderate: moderate confidence that the evidence reflects the true effect.
Further research may change our confidence in the estimate of effect
and may change the estimate.
C Low: low confidence that the evidence reflects the true effect. Further
research is likely to change our confidence in the estimate of effect and is
likely to change the estimate.

Abbreviations
AIMS, Abnormal Involuntary Movement Scale; ANC, absolute neutrophil count; AUC,
area under the curve; BMI, body mass index; CBC, complete blood count; CBTp,
cognitive-behavioral therapy for psychosis; Cmax, maximum plasma concentration; CrCl,
creatinine clearance; CT, computed tomography; CYP, cytochrome P450; DISCUS,
Dyskinesia Identification System-Condensed User Scale; EEG, electroencephalogram;
HCl, hydrochloride; HTBZ, dihydrotetrabenazine; IM, intramuscular; IV, intravenous; LAI,
long-acting injectable; MRI, magnetic resonance imaging; NMDA, N-methyl-D-aspartate;
QTc, corrected QT interval; REMS, risk evaluation and mitigation strategy; TSH, thyroid
stimulating hormone; VMAT2, vesicular monoamine transporter 2

Source
American Psychiatric Association: Practice Guideline for the Treatment of Patients With
Schizophrenia, 3rd Edition. Washington, DC, American Psychiatric Publishing, 2021

Disclaimer
This pocket guide attempts to define principles of practice that should produce high-quality
patient care. It is applicable to specialists, primary care, and providers at all levels. This pocket
guide should not be considered exclusive of other methods of care reasonably directed at
obtaining the same results. The ultimate judgment concerning the propriety of any course of
conduct must be made by the clinician after consideration of each individual patient situation.
Neither IGC, the medical association, nor the authors endorse any product or service associated
with the distributor of this clinical reference tool.
The most common U.S. trade names are included for reference only. At the time of publication,
some of these products may be manufactured only as generic products. Other medications or
other formulations of the listed medications may be available in Canada.
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