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SchizophreniaDisease Review
And Treatment Update
Edward Moldenhauer, MS, RPh
LCDR, MSC, USN
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Schizophrenia
Goal:To familiarize the practitioner with
schizophrenia and current treatment
options for the disease
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Schizophrenia
Objectives:- Describe how schizophrenia is diagnosed
- Describe the symptoms of schizophrenia
- Identify the common side effects of schizophrenia medications
- Describe adjunct medication treatment
options for schizophrenia
- Compare schizophrenia medications
relating to dosing, special patient
populations, side effects, interactions and
precautions
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Schizophrenia
True stories:“I thought that I had been shot in the head to remove a
blood clot. Then, I actually felt my brain crack open,
masses of blood came out of one of my ears and a small
trickle from the other.
Later that night, I thought that the devil was after me, I
saw him come through one of the speakers of my stereo
system. I was also probably hearing voices, but they were
mixed in with the radio music and DJs.”
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Schizophrenia
True stories:“I had one particular friend. I called him the „Controller‟,
only I could see him and hear him, but no one else could.
He would punish me if I did something he didn't like.
He spent a lot of time yelling at me and making me feel
wicked. I didn't know how to stop him from screaming at
me and ruling my existence. It got to the point where I
couldn't decipher reality from what the „Controller‟ was
screaming.”
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Schizophrenia
True stories:“Louis Wain, a prominent British
artist of the early 1900's, was
diagnosed with schizophrenia. He
was under psychiatric care but
lived at home surrounded by his
cats. Over a period of years he
painted their portraits, which are
in a way self-portraits, revealing
the tragic odyssey of his feelings.”
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Schizophrenia
True stories:“John Nash, noble prize winning
mathematician, was virtually
incapacitated by paranoid
schizophrenia during the prime of his genius. Referred to as
Princeton‟s "Phantom of Fine Hall“,
he was a ghostly, silent figure
shuffling around wearing purple
sneakers and occasionally writingtreatises on blackboards. He was
immortalized in 2002 Academy
Award winning film, A Beautiful
Mind.”
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Schizophrenia
Description: - a psychotic disorder characterized by a
loss of contact with the environment, by
noticeable deterioration in the level of
functioning in everyday life, and by thedisintegration of personality expressed as
disorder of feeling, thought, and conduct
Merriam-Webster Dictionary
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Schizophrenia
Description: - chronic, severe, disabling
-- one of the most disabling and
emotionally devastating illnesses - first identified in 1911
- NOT split personality
- linked to anatomical abnormalities- a neurodevelopmental disorder of
excessive dopamine levels
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Schizophrenia
Demographics: - risk factors;
-- genetic
-- perinatal- gender/age distribution
-- men & women equally prone
-- males; late teens/early 20s
-- women; late 20s to early 30s- no known racial differentiation
- most patients are smokers
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Schizophrenia
Childhood Schizophrenia: - rare in US (0.01% or 1 in 10,000)
- recently separated from autism
- occurrence rates increase as child
approaches adulthood
- suicide mortality rate: 5-11%
- child may exhibit a failure to meet
expected life milestones rather thandeterioration in functioning
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Schizophrenia
DSM-IV Criteria: - at least 2 characteristic symptoms
present for most of a 1-month period
over a 6-month period: Delusions
Hallucinations
Disorganized speech Catatonia / disorganized behavior
Negative symptoms
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Schizophrenia
Symptoms: - insidious onset in 50% of patients
- characterized by a group of
distinctive & predictable symptoms
- positive symptoms(grossly abnormal behavior)-- behavior that is there that shouldn‟t be
- deficit or negative symptoms (absence of normal behavior)-- behavior that is not there that should
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Schizophrenia
Positive Symptoms: - thought disorder
-- diminished ability to think clearly
and logically-- manifested by disconnected and
nonsensical language
-- incapable of participating in
conversation
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Schizophrenia
Positive Symptoms (cont): - delusions
-- false yet strongly held belief
resulting from an inability toseparate the real from unreal
-- “paranoid delusions”: belief that
they are being conspired against
-- “broadcasting”: belief thatthoughts can be heard by others
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Schizophrenia
Positive Symptoms (cont): - hallucinations
-- heard, seen, or even felt
-- most often they take the formof voices heard only by the patient
-- may describe the person's actions,
warn of danger or direct actions
-- at times, several voices may becarrying on a conversation
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Schizophrenia
Deficit or Negative Symptoms: - the absence of normal behavior
- flat or blunted affect
(i.e. lack of emotional expression)- apathy
- social withdrawal
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Schizophrenia
Diagnostic Parameters: - Cross-sectional
-- current clinical status
- Longitudinal -- frequency
-- severity
-- treatments
-- consequences of past episodes
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Schizophrenia
Diagnostic Tools: - Structured Clinical Interview for
DSM-IV (SCID)
-- gold standard
-- admin by psych professional
-- takes 1-2 hours to administer
- Teaching Interview for Psychiatric
Students (TIPS)-- shorter than the SCID
-- guide for routine, brief clinical evals
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Schizophrenia
Diagnostic Tools: - Positive and Negative Syndrome
Scale (PANSS)
-- structured clinical interview tool
-- 30-40 minute formalized interview
-- 30 questions on a 7-point scale
-- separates out nine different clinical
dimensions- Brief Psychiatric Rating Scale (BPRS)
-- evaluates psychotic symptoms
-- numerically scales symptoms
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Schizophrenia
Differential Diagnosis: - other psychological disorders
-- bipolar affective disorder
-- delusional disorder
-- schizotypal personality disorder
- other medical illnesses
-- brain tumor, intracranial bleeding
-- head trauma-- systemic lupus erythematosus
-- Huntington disease
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Schizophrenia
Differential Diagnosis: - metabolic disorders
-- Wilson‟s disease
-- porphyria
-- hypoxemia
-- electrolyte / vitamin imbalances
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Schizophrenia
Differential Diagnosis: - endocrine disorders
-- hypo- or hyperthyroid
-- hypo- or hyperadrenalism
-- hypo- or hyperparathyroidism
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Schizophrenia
Differential Diagnosis: - infectious diseases
-- neurosyphilis
-- HIV-1
-- cerebral abscesses
-- Creutzfeldt-Jakob disease
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Schizophrenia
Differential Diagnosis: - miscellaneous
-- multiple sclerosis
-- heavy metal poisoning
-- seizure disorder
-- substance abuse
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Schizophrenia
Differential Diagnosis: - medications
• corticosteroids (psychosis/mania)
• levodopa (hallucinations/insomnia)
• antidepressants (mania)
• interferon-alpha (depression)
• beta-blockers (depression)
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Schizophrenia
Disease Course: - initial signs may appear as weird
changes in normal behavior
- “acute”
-- onset of severe psychotic sx
- “psychosis”
-- state of mental impairment
marked by hallucinations and/or delusions
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Schizophrenia
Disease Severity: - “single”
-- only one episode
- “mild/moderate”
-- many episodes over lifetime with
relatively normal during interims
- “chronic”
-- continuous or recurring-- often do not fully recover
-- typically require long-term tx
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Schizophrenia
Chronic Disease Treatment: - some patients completely recover
- many must be institutionalized
- medication treatment
-- 70% of patients respond well
-- 15% moderately improve but
still require support
-- 15% have no response
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Schizophrenia
Disease Treatment: - supportive therapy
-- social work, family counseling
-- vocational rehabilitation
- hospitalization
-- brief in-patient to stabilize
- out-patient care
-- alcohol and drug abuse-- depression
-- medication non-compliance
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Schizophrenia
Disease Treatment Phases: - acute phase
-- alleviate/reduce acute symptoms
-- assessment
-- treatment setting
-- psychiatric management
-- initiate medication
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Schizophrenia
Disease Treatment Phases: - stabilization phase
-- minimize stress and relapse
- stable/maintenance phase
-- assessment
-- psychiatric management and specific
psychosocial treatments
-- monitoring medications-- early intervention
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Schizophrenia
Medication Adherence/Relapse: - up to 75% of patients don't take
their medication regularly or stop
treatment altogether
- ~80% relapse within one year if
medications are stopped
- only 20% relapse if continually treated
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Schizophrenia
Medication Classes: - classic antipsychotics
-- haloperidol (Haldol)
-- droperidol (Inapsine)
-- fluphenazine (Prolixin)
-- thioridazine (Mellaril)
-- chlorpromazine (Thorazine)
- a.k.a.; "neuroleptics“, due to potential
for inducing neurological side effects
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Schizophrenia
Medication Classes: - atypical antipsychotics
-- Clozapine (Clozaril)
-- Risperidone (Risperdal)
-- Olanzapine (Zyprexa)
-- Quetiapine (Seroquel)
-- Ziprasidone (Geodon)
-- Aripiprazole (Abilify)- a.k.a.; SDAs
-- serotonin-dopamine antagonists -- pleiotropic pharmacology
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Schizophrenia
Medication Classes: - therapy adjuncts
-- pimozide (Orap)
-- divalproex (Depakote)
-- carbamazepine (Tegretol)
-- lithium
-- anticholinergics
-- benzodiazepines (BZDs)-- antidepressants
-- ECT
S
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Schizophrenia
Classical Antipsychotic Side Effects:(a.k.a.; EPS: Extrapyramidal Side Effect) - akathisia (restless leg)
- dystonia
- hyperprolactinemia
- akinesia & Parkinsonism-like sx
- weight gain
- anticholinergic adverse effects
S hi h i
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Schizophrenia
Classical Antipsychotic Side Effects:(a.k.a.; EPS: Extrapyramidal Side Effect) - Neuroleptic Malignant Syndrome (NMS)
-- hyperthermia
-- muscular rigidity
-- altered mental state
-- autonomic instability
S hi h i
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Schizophrenia
Classical Antipsychotic Side Effects:(a.k.a.; EPS: Extrapyramidal Side Effect) - Tardive Dyskinesia (TD)
-- high incidence in elderly (~70%)
-- involuntary and repetitive (not
rhythmic) mvt of mouth and face
-- rocking back & forth or tap feet
-- diaphragmatic dyskinesia exists,-- risk factors:
age, female, lower IQ,
negative symptoms
S hi h i
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Schizophrenia
haloperidol (Haldol): - DOC for acute psychosis(when no contraindications exist)
- dopamine (D2) antagonist
- high potential for EPS/dystonia- precautions
-- monitor development of TD
-- if IV/IM, monitor for hypotension-- caution in diagnosed CNS depression,
cardiac disease, history of seizures
-- significant in body temp may indicate
intolerance
S hi h i
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Schizophrenia
clozapine (Clozaril): - adrenergic, cholinergic, histaminic and
serotonin receptor antagonist
- precautions-- do not D/C aburptly
-- requirement to perform WBC count
-- hypotension, myoclonic jerks, seizures
-- urinary incontinence, constipation- requires National Registry registration
S hi h i
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Schizophrenia
clozapine (Clozaril):
www. clozapineregistry.com
S hi h i
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Schizophrenia
risperidone (Risperdal):- dopamine & serotonin receptor
antagonist
- precautions-- EPS, NMS, hyperprolactinemia,
hypotension, tachycardia, arrhythmias
-- cerebrovascular warning of stroke in
elderly patients with dementia-- can lengthen QT interval
- availability-- oral tablets, soln, &
distinegrating tabs
S hi h i
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Schizophrenia
olanzapine (Zyprexa): - dopamine, serotonin and
muscarinic receptor antagonist
- precautions-- glaucoma, vascular disease, BPH,
seizures, hypovolemia, dehydration
-- may lead to weight gain
- availability-- oral tablets, disintegrating tablets
S hi h i
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Schizophrenia
quetiapine (Seroquel):- dopamine and serotonin receptor
antagonist
- precautions-- may induce orthostatic hypotension
associated with dizziness, tachycardia,
and syncope
-- NMS
- availability-- oral tablets
S hi h i
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Schizophrenia
ziprasidone (Geodon): - dopamine and serotonin receptor
antagonist
- injectable used for acutely agitated pt
- precautions-- prolongs QT/QTc (caution in patients
with known risk factors)
-- caution in seizure disorders-- may cause hypotension, EPS,
somnolence
- availability
-- oral capsules and injection
S hi h i
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Schizophrenia
aripiprazole (Abilify): - MOA is unknown, hypothesized to
work differently meds
- antagonizes serotonin (5HT2A)
- partial dopamine (D2) and
serotonin (5HT1A) agonist
- precautions:
-- headache, anxiety, somnolence, andinsomnia
- availability-- oral tablets
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Schizophrenia- Debilitating to patient, family, society
- Severe personality changes
- Linked to neurochemical abnormalities- Positive and Negative Symptoms
- Differential diagnosis
- Treatment options- classic and atypical antipsychotics
- side effects and precautions
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Schizophrenia