Schizophrenia

Faria Chaudhry PharmD

August 12, 2020
 Describe Describe the pathophysiology of schizophrenia and its symptoms

Summarize Summarize how to diagnose schizophrenia according to DMS-5

Objectives Recommend Recommend appropriate pharmacotherapy for patients

Identify Identify major side effects and monitoring of antipsychotic drugs

Demonstrate ability to recommend alternative treatment agents for specific

Demonstrate patient populations
 3 truths and one lie

A. The life expectancy for people with schizophrenia is less than the
general population
B. Cardiovascular disease is the leading cause of death
C. Schizophrenia typically appears in patient’s teens to 20ies
D. Schizophrenia comes from the greek word hallucination
  Prevalence: ~ 1% of population is
diagnosed with schizophrenia
 Age of onset: during adolescence
 Males: early to mid 20s
 Females: 20s-30s, second peak
Epidemiology during menopause
 Male to female ratio: 1.4:1
 Co-occurring conditions:
psychiatric and chronic diseases
Etiology

 Exact cause unknown

 Genetic correlation
 First degree relative, 10 fold increase of risk
 Both parents with schizophrenia, 40% chance
 Risk favors
 Obstetrical factor complications
 Late winter to early spring birth
 Living in an urban area
 Advanced paternal age at conception
Economic Impact

 2.5% of total healthcare cost

 Cost in United States $63 billion dollars
 Top 25 leading cause of disability in the world
 Diagnosis
DSM-5 Criteria
At least 2 or more symptoms must be present for at least one month
• Hallucinations
• Delusions
• Disorganized speech
• Grossly organized behavior
• Negative symptoms

Continuous disturbance for 6 months

Social or occupational dysfunction
Does not meet criteria for other mood disorders or substance use disorders
 Serotonin

Pathophysiology Dopamine

Glutamate
Which dopamine pathway is responsible for
extrapyramidal motor system symptoms?

A. Mesocortical pathway
B. Tuberoinfundibular pathway
C. Nigrostriatal pathway
D.Mesolimbic pathway
 Dopamine hypothesis
Nigrostriatal
Mesocortical
Dopamine hypoactivity Part of extrapyramidal motor
negative symptoms, system
cognitive impairment

Tuberoinfundibular Mesolimbic

Inhibits prolactin Dopamine hyperactivity,

release positive symptoms
 symptoms

Positive
• Delusions Negative
• Hallucinations • Anhedonia
• Disorganized • Avolition
speech • Alogia
• Disorganized • Blunted affect
behavior
 Reduce or
Psychotic eliminate
episode
Treatment Treatment phases symptoms

Phases Stabilization Maximize quality

of life
And Goals
Maintenance Promote
recovery
 Treatment

Non- Typical Atypical

pharmacologic antipsychotics antipsychotics
 Generic Name Brand Name Potency

Chlorpromazine Thorazine Low

First generation Thioridazine Mellaril Low

antipsychotics Loxapine Loxitane Medium

Molindone Moban Medium

Perphenazine Trilafon Medium

Prochlorperazine Compazine Medium

Thiothixene Navane High

Fluphenazine Prolixin High

Haloperidol Haldol High

Typical antipsychotic receptor potencies
Typical antipsychotics D2 5-HT2A 5-HT2A/D2 H1 M A1 A2

Fluphenazine .8 3.2 3.9 14 1,1oo 6.5 310

Haloperidol 1.2 57 47 1700 >10,000 12 1,130

Chlorpromazine 3.6 3.6 1 3.1 32 0.3 250

Perphenazine 0.8 5.6 7.4 8 1500 10 810

Thioridazine 8 28 3.5 16 13 3,2 130

thiothixene 0.7 50 72 8 >10,000 12 80

First Generation Side effects

 Drug Name Drug Name

Aripiprazole (Abilify) Asenapine (Saphris)

Second
generation Brexipiprazole (Rexulti) Clozapine (Clozaril)
antipsychotics
Lurasidone (Latuda) Olanzapine (Zyprexa)

Paliperidone (Caplyta) Quetiapine (Seroquel)

Risperidone (Risperidal) Ziprasidone (Geodon)

Second Generation Side Effects and
Affinities
What this translates to
 TYPE ONSET SYMPTOMS TREATMENT
DYSTONIA 24-96 HRS facial grimacing, Benzotropine,
involuntary eye Diphenhydramine.
movement, May use prophylaxis
muscle spasms of
tongue and face

AKATHESIA 2-3 weeks Motor Propranolol, BZD

restlessness
PSEUDOPARKINISM Within 3 months stooped posture, benztropine,
rigidity, trihexyphenidyl,
bradykinesia diphenhydramine

EPS TARDIVE
DYSKINESIA
Months-years abnormal
involuntary
movements,
irreversible
VMAT2 inhibitors
(Deutetrabenazine,
Valbenazine)

NEUROLEPTIC < 2 weeks after muscle rigidity, Supportive care,

MALIGNANT initiation hyperthermia, bromocriptine,
SYNDROME autonomic amantadine, BZD
dysfunction
Drugs with unique
side effects or
monitoring
Which of these A. Myocarditis
is a black box B. Pancreatitis
warning for C. Hyperlipidemia
clozapine? D. Hirsutism
Clozapine (Clozaril)

 Major SE:QT prolongation, metabolic syndrome, anticholinergic side effects

 BBW: agranulocytosis, seizures, myocarditis, respiratory and cardiovascular
effects, mortality in dementia related psychosis
 Indication: Shows superiority to other antipsych drugs in treatment resistant
schizophrenia. DO NOT use as initial treatment
 Major drug interactions: metabolized CYP1A2, CYP3A4
 Inducers: carbamazepine, phenytoin, primidone
 Inhibitors: fluvoxamine, fluoxetine, clarithromycin, protease inhibitors, cimetidine
 WM is a 35 year old WM with resistant schizophrenia. His
past history is positive for pneumocystis pneumonia. He has
treatment-resistant schizophrenia but is currently controlled
on clozapine. He is getting his blood work done as part of
the REMS program. What is the best action to take?
WBC 1.4

Polyps 48
A. Continue treatment
B. Interrupt treatment and recommend a
hematology consultation
Bands 5 C. Continue treatment but prophylactically treat
patient with Bactrim
D. Discontinue treatment
Work out
ANC = [(% neutrophils + % bands) x WBC]/ 100

ANC= [(48+5) x 1400]/100 = 742

Clozaril ANC
Monitoring
  CATIE trial, superiority over other
antipsychotics
 Major SE: metabolic adverse effects,
Olanzapine high weight gain, moderate EPS,
(Zyprexa)  Dosage forms: IM, ODT, tablet
 BBW: PDSS (post-injection
delirium/sedation syndrome)
CATIE
trial
Zyprexa Relprevv
LM is a patient diagnosed with
schizophrenia. He is currently taking Abilify
and has given power of attorney to his
parents. His parents have doubts that LM is
taking his medication. What can be done to
ensure that the patient is taking his
medication? Note, the patient’s family has a
lot of money they are willing to spend 
 First Generation
Putting it all • More EPS
• Within generation, the higher the potency
together the higher the chance of EPS
• Within class, anticholinergic SE and
sedation higher with lower potency
First
generation

Second generation
• Less EPS, but more metabolic side
effects
Second
generation • All drugs have varying degrees of
cholinergic SE and sedation based
on MOA
Side
Effects
FDA Black Box Warning
  BMP  AIMS
 CBC  Toxicology
 BMI  Pregnancy
How do you  BP, HR, temperature  Infectious diseases
manage all the  A1C  EKG
side effects?  Lipids  Prolactin
 Match the drug to the Side effect It’s most likely to
cause

A.Clozapine 1. QTC prolongation

B. Aripiprazole 2. Agranulocytosis
C. Paliperidone 3. Hyperprolactinemia
D.Ziprasidone 4. Akathesia
E. Fluphenazine 5. Most likely to cause all
EPS SE
LM and his family are back to see you.
Thanks to Abilify Mycite, the family has
identified that the LM is not taking his
medication. Everyday is a struggle to get
him to take his medication. The family is
looking for another solution. What do you
recommend?
Long Acting
Decanoates

This Photo by Unknown Author is licensed under CC BY-NC

 Long acting decanoates
Long Acting Decanoate injections
ALL PATIENTS MUST BE STABLE ON PO DOSE BEFORE TRANSITIONING
Drug Frequency Transition Notes
Fluphenazine decanoate (Prolixin Decanoate) 2-4 weeks PO dose x 1.25 = IM
Continue using oral dose for 2-4 days with IM
Haloperidol decanoate (Haldol Decanoate) 4 weeks PO dose x 10-15 = IM
Continue oral dose with IM for one month
Aripiprazole (Abilify Maintena) monthly Continue PO dose for 3 weeks with IM. Must
be reconstituted.
Aripiprazole lauroxil (Aristada) 1-2 months Continue PO dose for 2 weeks with IM

Olanzapine pamoate (Zyprexxa Relprevv) 2-4 weeks PO x 15-20 = IM dose

Paliperidone palmitate (Invega Sustenna) monthly Recommended dose is 117 mg. No oral overlap
necessary
Paliperidone palmitate (Invegga Trinza) 3 months Recommended dose is 117 mg. No oral overlap
necessary

Risperidone (Risperdal Consta) 2 weeks Overlap with oral meds for 3 weeks. Do not
taper dose for at least 4 day increments
 Drug Risk DM Worsening Lipid Weight gain
profile

Clozapine + + +++

Olanzapine + + +++
ADA
Consensus on Risperidone Discrepant
results
Discrepant
results
++

Antipsychotic
Quetiapine Discrepant Discrepant ++
Drugs results results

Aripiprazole No effect No effect +/-

Ziprasidone No effect No effect +/-

Diabetes Care. 2004:27:596-601. J Clin Psychiatry. 2004;65:267-272

  Patient specific (SE, family history)
 Make sure on adequate trial (4-6 weeks)
Factors to  Maximize to tolerable dose (EPS threshold)
consider when  Monitor patient side effects and patient response
treating a  After trying 2-3 medications, made try clozapine or olanzapine
patient  Patient population has high discontinuation rate (>70%). For
specific patients who are at risk of discontinuation or adherence,
consider injections
 Treat schizophrenia
patients with a more Monitor side effects
holistic approach and have regular lab
tests
Summary High co-morbidities
Utilize LAI only
Find appropriate after establishing
treatment option for rapport on PO
patients
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2013.
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2014, 198-219.
 Davis, J. The use of depot medications in the treatment of schizophrenia. Am J
Psychiatry 2010. 167:125-126
 Diabetes Care. 2004:27:596-601. J Clin Psychiatry. 2004;65:267-272.
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