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PHAR358 > Psychosis > Flashcards

Psychosis Flashcards

1
Q

What are the 1st generation antipsychotics?

A

haloperidol
flupenthixol
chlorpromazine
perphenazine
fluphenazine
methotrimeprazine
loxapine
pimozide
trifluoperazine
zuclopenthixol

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2
Q

What are the 2nd generation antipsychotics?

A

asenapine
olanzapine
risperidone
paliperidone
quetiapine
clozapine
lurasidone
ziprasidone

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3
Q

What are the 3rd generation antipsychotics?

A

aripiprazole
brexpiprazole
cariprazine

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4
Q

What are some anticholinergic drugs that are reviewed in the psychosis section?

A

benztropine
diphenhydramine
trihexyphenidyl

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5
Q

What is schizophrenia?

A

a complex syndrome of disorganized bizarre thoughts, hallucinations, delusions, inappropriate affect, and impaired social functioning

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6
Q

What is the criteria for schizophrenia according to the DSM-5?

A

> 6 months + > 1 month of > 2 sxs
-one must be delusion, hallucinations, disorganized speech
-other: disorganized/catatonic behavior, negative sx, decreased functioning

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7
Q

What is psychosis?

A

presence of gross impairment of reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behavior without apparent awareness on the part of the patient of the incomprehensibility of their behavior
-schizophrenia is one of MANY causes of psychosis

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8
Q

What is treatment resistant schizophrenia?

A

no significant improvement in sxs despite tx with > 2 APs from different AP classes at optimal dose for 6-8 wks

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9
Q

What is schizophreniform disorder?

A

1-6 months, same sxs as schizophrenia, social/occupation functional impairment not required

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10
Q

What is schizoaffective disorder?

A

> 2 wks of delusions or hallucinations without mood sxs + uninterrupted period of illness containing either major depressive or manic episode with concurrent sxs diagnostic of schizophrenia
social/occupation functional impairment not required

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11
Q

What is brief psychotic disorder?

A

1 day to 1 month of > 1 of delusions, hallucinations, disorganized speech
return to premorbid function

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12
Q

What is delusional disorder?

A

> 1 month of delusions
hallucinations not prominent
function only mildly impaired, behavior not blatantly bizarre

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13
Q

What is substance induced psychosis?

A

hallucinations or delusions development during or within 1 month of substance use/withdrawal

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14
Q

Describe the epidemiology of psychosis.

A

usual age of onset 16-30 yrs
equal distribution between sexes
genetic heritability 80% (risk increases 15-20x if parent had)
pts die 10-20 yrs earlier than avg population
medication non-adherence rates ~50-60%

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15
Q

What is the risk of death in a patient with schizophrenia if they are never treated with an antipsychotic?

A

risk doubles

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16
Q

What is the pathophysiology of schizophrenia?

A

dopamine dysregulation is the key theory underlying the pathophysiology of the disease
serotonin dysregulation contributes
-modulates dopamine
glutamate and GABA also have a role

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17
Q

What are the 4 key dopamine tracts?

A

nigrostriatal
mesolimbic
mesocortical
tuberoinfundibular

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18
Q

What is the origin of the 4 dopamine tracts?

A

nigrostriatal: substantia nigra
mesolimbic: midbrain
mesocorticial: midbrain
tuberoinfundibular: hypothalamus

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19
Q

What is the innervation of the 4 dopamine tracts?

A

nigrostriatal: basal ganglia
mesolimbic: limbic areas
mesocortical: prefrontal and frontal cortex
tuberoinfundibular: anterior pituitary gland

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20
Q

What is the function of the nigrostriatal tract?

A

motor coordination
posture control

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21
Q

What are the effects of DA blocking in the nigrostriatal tract?

A

movement disorders (EPS)

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22
Q

What is the function of the mesolimibic tract?

A

pleasure/reward/desire
response to stimuli
motivational behavior
DA excess increases positive sx

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23
Q

What are the effects of DA blocking in the mesolimbic tract?

A

relief of psychosis (positive sx)
issue: blocks motivation and other things

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24
Q

What is the function of the mesocortical tract?

A

cognition
motivation
communication
social function
emotional response
problem solving
(DA deficiency increases negative sx)

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25
Q

What are the effects of DA blocking in the mesocortical tract?

A

akathisia ?
treatment of negative sx and depression ?

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26
Q

What is the function of the tuberoinfundibular tract?

A

regulates prolactin release

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27
Q

What are the effects of DA blocking in the tuberoinfundibular tract?

A

hyperprolactinemia
-gynecomastia
-galactorrhea
-amenorrhea
-weight gain
-osteoporosis
-hirsutism
-sexual dysfunction
-erectile dysfunction

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28
Q

What kind of features might be seen before schizophrenia is “full blown”?

A

prodromal features
-often recognized retrospectively after the diagnosis has been made
-reclusive adolescence without close friends
-not functioning well in occupational, social, and personal activities
-markedly peculiar behavior, abnormal affect, unusual speech, bizarre ideas
-perceptual experiences

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29
Q

What are the signs and symptoms specific to schizophrenia?

A

no sign or symptom is specific to schizophrenia
-complex, heterogenous disorder

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30
Q

What are the 4 symptom clusters in schizophrenia?

A

positive symptoms:
-hallucinations
-paranoia
-delusions
-disturbed thought content
-bizarre or disorganized speech
-thought disorder
negative symptoms:
-apathy, social indifference
-avolition
-alogia
-flat affect
-poor self care
-psychomotor retardation
cognitive symptoms:
-memory impairment
-poor concentration
-impaired executive function
mood symptoms:
-dysphoria, depression
-excitement, mania

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31
Q

What are delusions?

A

fixed beliefs that are not amendable to change in light of conflicting evidence

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32
Q

What are hallucinations?

A

perception-like experiences that occur without an external stimuli
-vivid and clear with the full force and impact of normal perceptions and not under voluntary control
-may occur in any sensory modality but auditory most common in schizophrenia

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33
Q

How do we typically infer that a patient has disorganized thinking?

A

through their speech

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34
Q

How does disorganized/abnormal motor behavior manifest in patients with schizophrenia?

A

variety of ways
-unpredictable agitation to childlike silliness
-difficulties in performing activities of daily living

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35
Q

What is catatonia?

A

marked decrease in reactivity to the environment
-ranges from resistance to instruction to a rigid posture to a complete lack of verbal and motor response
-can also include purposelessness and excessive motor activity without obvious causes

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36
Q

What are some commonly associated clinical features of schizophrenia?

A

substance use
-common, 45% of pts
smoking:
-50-75% of pts
-induces 1A2 which affects metabolism of clozapine & olanzapine
-may decrease AEs of AP through nicotine-dept activation of DA neurons
suicidality:
-leading cause of premature death
-40-50% of pts with schizophrenia attempt atleast once

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37
Q

What are some examples of drug induced psychosis?

A

bupropion
amphetamines and cocaine
caffeine
cannabis
steroids
efavirenz
chloroquine
ketamine
mechanism: increased DA = + symptoms

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38
Q

What is an example of measurement based care for schizophrenia?

A

PANSS (positive and negative syndrome scale)
-study response defined as > 20% decrease in score

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39
Q

What are the goals of therapy for schizophrenia?

A

prevent harm to self and others
improve patient functioning
decrease intensity and duration of active psychotic sx
optimize medications to obtain clinical response
minimize AE of therapy
promote adherence and compliance to therapy
prevent relapse
patient/family education

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40
Q

What are some non-pharm treatments for schizophrenia?

A

exercise, healthy diet, adequate sleep
decrease substance use/nicotine/caffeine/alcohol
support service interventions for med adherence
establish trusting relationship (shared decision making)
CBT, occupational rehabilitation techniques

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41
Q

What are the major receptor targets of antipsychotics?

A

D2
5HT2A
muscarinic
H1
a1

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42
Q

What are the effects of antipsychotics on D2 antagonism?

A

therapeutic effect: antipsychotic, improve + sx
-mesolimbic blockade
adverse effects:
-EPS (nigostriatal blockade)
-sexual dysfx, increased prolactin (tuberoinfundibular blockade)
-worsening of - sx (mesocortical blockade)

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43
Q

What are the effects of antipsychotics on 5HT?

A

therapeutic: antipsychotic (2A/2C antag), anxiolytic (1A agon)
adverse effects: sedation, hypotension, sexual dysfx

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44
Q

What are the effects of antipsychotics on a1/2?

A

therapeutic effect: nil
adverse effects:
-a1: postural hypotension, dizziness, sedation, reflex tachy
-a2: sexual dysfx

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45
Q

What are the effects of antipsychotics on H1?

A

therapeutic effects: nil
adverse effects:
-sedation, weight gain, postural hypotension

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46
Q

What are the effects of antipsychotics on muscarinic receptors?

A

therapeutic effects: nil
adverse effects:
-dry mouth, constipation, sedation, blurred vision, confusion

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47
Q

Provide a summary of receptor activity for the different generations of antipsychotics.

A

1st gen:
-D2 antagonism
-dirty pharmacology
2nd gen:
-D2 antagonism
-5HT2A/2C antagonism
-dirty pharmacology
3rd gen:
-D2 partial agonism
-5HT2A antagonism
-5HT1A & 2C partial agonism

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48
Q

What is the main side effect of the different generations of antipsychotics?

A

1st gen: movement disorders
2nd gen: metabolic AE
3rd gen: akathisia

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49
Q

True or false: despite groupings and being very different from eachother, the overall efficacy amongst antipsychotics is similar

A

true
except clozapine

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50
Q

What is the principle property of high potency FGAs?

A

increased risk of movement disorders
-weaker anticholingergic effects

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51
Q

What are some examples of high potency FGAs?

A

haloperidol
flupenthixol
perphenazine
fluphenazine

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52
Q

What is the principle property of low potency FGAs?

A

lower risk of movement disorders
-strong anticholinergic effects
-highly sedating

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53
Q

What are some examples of low potency FGAs?

A

chlorpromazine
methotrimeprazine

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54
Q

What makes an antipsychotic “atypical”?

A

different receptor activity (2A/C) in addition to D2 blockade
decreased risk of movement disorders, increased risk of metabolic AEs

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55
Q

Describe the pharmacology of risperidone.

A

high affinity for D2, 5HT2, alpha-adrenergic receptors
binds with lower affinity to a2 and H1
no muscarinic affinity (no anticholinergic side effects)

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56
Q

What is a dose-related risk of risperidone?

A

EPS (>8mg acts like an FGA)

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57
Q

What are the adverse effects of risperidone?

A

sexual dysx/increased prolactin more vs other SGAs
EPS more vs SGAs, less than haloperidol
weight gain
anxiety
headache
rhinitis
orthostasis
possible QT risk

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58
Q

What are the interactions to be aware of with risperidone?

A

pharmacodynamic such as CNS depression
3A4/2D6 (fluoxetine!)

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59
Q

Describe the pharmacology of paliperidone.

A

primary active metabolite of risperidone

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60
Q

What is special about the formulation of paliperidone?

A

OROS (like Concerta)
-sustained levels over 24h
-shell will be passed in stool

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61
Q

What are the adverse effects of paliperidone?

A

insomnia (more vs risperidone)
weight gain (less vs risperidone)
sexual dysx/increased prolactin (similar to risperidone)
orthostasis (less vs risperidone)
EPS
headache
anxiety
rhinitis
possible QT risk

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62
Q

What are the drug interactions to keep in mind for paliperidone?

A

minimal risk of DIs

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63
Q

What limits the initial use of olanzapine?

A

metabolic AEs

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64
Q

What are the adverse effects of olanzapine?

A

WEIGHT GAIN (>10 lbs or > 7% baseline)
increased T2DM, dyslipidemia risk vs others
orthostasis
anticholinergic
sedation
dizziness
increased liver enzymes
EPS (dose dependent)
possible QT risk

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65
Q

What are the drug interactions to keep in mind with olanzapine?

A

smoking (CYP1A2) = decreased olanzapine levels
pharmacodynamic interactions
1A2 inhibitors/inducers

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66
Q

What is the effectiveness of quetiapine in psychosis?

A

even though its thought to be equally effective (except clozapine), clinically it doesnt seem that effective
-not used as much for psychosis

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67
Q

What is the dosing of quetiapine for psychosis?

A

bigger doses when compared to use for insomnia, bipolar, depression or anxiety

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68
Q

What are the adverse effects of quetiapine?

A

increased risk of T2DM and dyslipidemia
weight gain
sedation
headache, dizziness
increased liver enzymes
orthostasis
may reduce thyroid hormone levels
QT risk

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69
Q

What are the drug interactions to keep in mind with quetiapine?

A

pharmacodynamic
3A4

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70
Q

What are the adverse effects of ziprasidone?

A

weight neutral
decreased risk of hyperglycemia/lipidemia vs other SGAs
dizziness
sedation or insomnia
dyspepsia/constipation/nausea
orthostasis
EPS
conditional QT risk
-?higher risk vs others
-CI: QT prolongation, concurrent QT prolonging drug, recent MI, HF

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71
Q

What are the drug interactions to keep in mind with ziprasidone?

A

pharmacodynamic
3A4 inducers/inhibitors

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72
Q

What is special about the formulation of asenapine?

A

SL

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73
Q

What is the evidence for asenapine for schizophrenia?

A

superiority not demonstrated vs placebo
not clinically used

74
Q

What are the adverse effects of asenapine?

A

minimal effect on weight, glucose, lipids
increased prolactin
possible QT risk
sedation or insomnia
HA, dizziness
EPS
akathisia
suicidal ideation
orthostasis

75
Q

What are the drug interactions to keep in mind with asenapine?

A

1A2 inhibitors/inducers
pharmacodynamic
QT

76
Q

What is the evidence for lurasidone in schizophrenia?

A

efficacy established in studies up to 6 weeks
rarely used for schizophrenia in clinical practice

77
Q

What are the side effects of lurasidone?

A

little to no metabolic effects
still some EPS, sedation, etc

78
Q

What are the drug interactions to keep in mind with lurasidone?

A

3A4

79
Q

How should lurasidone be taken?

A

with food (350kcal) to increase F

80
Q

What is the hallmark of 3rd generation antipsychotics?

A

reduced risk of metabolic and movement adverse drug effects
high rate of akathisia
-aripriazole > > brexipiprazole

81
Q

What is the pharmacology of aripiprazole?

A

acts as a partial agonist at the 5HT1A and D2 and antagonist at 5HT2A
referred to as a “dopamine system stabilizer”
-“Goldilocks Principle”
-in high levels of DA production (+ sx) it acts as an antagonist
-in low levels of DA production (- sx) it acts an agonist

82
Q

What are the adverse effects of aripiprazole?

A

headache
GI complaints
insomnia or sedation (more often activating vs sedating)
akathisia
some anxiety
minimal weight gain
EPS
orthostasis
suicidal behavior
possible risk of QT prolongation

83
Q

What are the drug interactions of aripiprazole?

A

2D6
3A4

84
Q

What are the indications for brexipiprazole?

A

schizophrenia
MDD add-on therapy

85
Q

What is the pharmacology of brexipiprazole?

A

partial agonist at the 5HT1A and D2 and antagonist at 5HT2A

86
Q

What are the adverse effects of brexipiprazole?

A

similar to aripiprazole but less akthsia

87
Q

What is the newest third generation antipsychotic?

A

cariprazine
-limited clinical experience

88
Q

What is the pharmacology of cariprazine?

A

high affinity partial agonist at D3 + D2 receptors
at low doses –> higher affinity for D3 than D2
lower affinity for D2 than aripiprazole and brexipiprazole
high affinity partial agonist at 5HT1A
antagonist at 5HT2A, 5HT2B

89
Q

What is the function of the D3 receptor?

A

has been associated with mood, cognition, addictive behaviors, and reward behaviors in animal models
partial agonism is thought to have implications in improving negative sx of schizophrenia

90
Q

How is cariprazine metabolized?

A

extensively metabolized by 3A4

91
Q

What are some important kinetic parameters of cariprazine?

A

91-97%
t1/2: 2-4 days, longer for active metabolites
time to SS: 1-3 wks, longer for active metabolites

92
Q

Provide a summary of the evidence for cariprazine for schizophrenia.

A

may be effective for the treatment of acute exacerbations and prevention of relapse after acute exacerbations
-more direct comparative evidence is needed
may have implications for negative sx of schizophrenia due to D3 partial agonism
safety
-limited by short duration of trials
-long term withdrawal design included enriched population

93
Q

What are some key points to consider when selecting an antipsychotic?

A

FGA appear to have comparable efficacy to SGA
-except for clozapine
individual studies have shown higher dc rates due to AE and lack of treatment effect with SGA
major issue with FGA is EPS
-particularly in younger pts
pts with early psychosis have been shown to be more at risk for EPS and develop it at lower doses than those with a long history of psychosis/AP treatment
conflicting evidence for whether risk of relapses is higher wit FGA compared to SGA
SGA preferred for pts with early psychosis due to EPS risk with FGA

94
Q

What is the use of LAIAs?

A

if oral medications are effective and tolerated, may continue with oral therapy or switch to long-acting injectable depot to improve adherence (given q2-4 wks)
may be considered if a patient relapses due to non-adherence or if patient prefers injection

95
Q

What are the benefits of LAIA?

A

decreased risk of relapse
decreased hospitalization
decreased patient/caregiver burden
increased interactions with healthcare team/rapport
increased adherence

96
Q

What should be established before starting an LAIA?

A

tolerability with oral

97
Q

What should always be double checked before switching from oral to LAIA?

A

how long to overlap with oral
-may not show up on last 4 months of PIP but may still be pharmacologically active in the patients body, always double check date of last dose
-consult product monograph or SwitchRx

98
Q

What are some general monitoring guidelines for all antipsychotics?

A

vitals (including postural BP and HR)
behaviors
-improved psychosis & signs of toxicity
-CNS changes
-anticholinergic effects
-EPS
-sexual dysfx
CBC at baseline and then as clinically needed
LFTs at baseline, 1 mo, then q6-12 mo
ECG if baseline risk factors

99
Q

What does the 2017 Canadian Schizophrenia Guidline stress the importance of?

A

earlier treatment of symptoms
need for greater attention to the physical care of people with schizophrenia due to reduce lifespan
greater emphasis on recovery and the need to provide personalized care rather than focusing primarily on symptomatic management

100
Q

What is critical with the treatment of a first episode of psychosis?

A

early treatment
-early detection & tx can decrease depression, increase mood/cognitive, increase overall function at 10 yrs
-first 2 to 5 yrs of illness are critical to offset future disability and improve outcomes; longer duration of untreated psychosis results in decreased response to tx

101
Q

What is the treatment of a first episode of psychosis?

A

no particular AP or class found to be clinically superior in 1st episode
usually SGA (compared to FGA: decreased AE, decreased dc, equal efficacy)
choose agent based on AE profile & use lowest effective dose
using LAIA may decrease relapse vs oral

102
Q

What is the treatment duration for a first episode of psychosis?

A

controversial; minimum 18 months
-indefinite therapy reasonable

103
Q

How should antipsychotics be titrated for a first episode of psychosis?

A

further titrated based on efficacy and tolerability with a target dose on the lower end of dose range

104
Q

What is an adequate trial of an antipsychotic for a first episode of psychosis?

A

4-6 @ optimally tolerated dose

105
Q

How is an acute exacerbation of psychosis treated?

A

1st screen for nonadherence, substance use, drug interactions
-neither constitute treatment failure
2nd: increase or change AP, trial x 6-8 wks to determine effect
-use SwitchRx (usually cross taper to prevent AP withdrawal)

106
Q

What is the benefit of maintenance therapy for psychosis?

A

contributes to relapse prevention and decrease hospitalization rates

107
Q

What is the duration of therapy for maintenance of schizophrenia?

A

guidelines suggest for 2 yrs (up to 5 yrs longer)

108
Q

What should all patients with psychosis be screened for?

A

SUD
-SUD found in up to 45% of schizophrenia patients
-stimulant use and cannabis use associated with psychosis
-substance use results in worse outcomes
often difficult to determine whether psychosis came first and substances used for self-treatment or whether substances have caused psychosis

109
Q

What is the treatment of psychosis + SUD?

A

no evidence of benefit for one AP over another for psychosis and SUD
-clozapine preferred but limited data

110
Q

What is treatment resistant schizophrenia/psychosis?

A

> 2 positive sx of moderate severity or 1 positive sx of severe severity after > 2 adequate AP trials
-adequate trial: orally minimum 6 wks at > midpoint dose or LAIA at SS x 6 wks

111
Q

What is the first step in assessing treatment resistant schizophrenia?

A

review for substance use, adherence, drug interactions, assess dose

112
Q

What is first line for treatment resistant schizophrenia/psychosis?

A

clozapine
-response rate 30-60% but underprescribed due to fear of AE and lack of familiarity

113
Q

How does clozapine work?

A

dont fully know, proposed mechanisms:
-noradrenergic
-serotonergic
-mesolimbic dopaminergic
-dopamine subtypes
most distinctive activity:
-D4
-5HT2A
-a1
-M1

114
Q

What is the most effective antipsychotic for treatment resistant schizophrenia?

A

30% response rate

115
Q

What are the common side effects of clozapine?

A

drooling
drowsiness
dizziness
blurred vision
constipation
increased cholesterol and/or blood sugar
tachycardia and orthostatic hypotension

116
Q

What are the serious side effects of clozapine?

A

agranulocytosis
myocarditis
cardiomyopathy
constipation
seizures
neuroleptic malignant syndrome

117
Q

What is clozapine-induced agranulocytosis?

A

dangerously low neutrophil count
- < 1.5 x 10/L
-increased infection risk

118
Q

True or false: clozapine-induced agranulocytosis is reversible upon discontinuation

A

true

119
Q

What does Health Canada required be done for clozapine-induced agranulocytosis?

A

Health Canada mandates registration of each patient into a monitoring database to detect potentially reversible agranulocytosis

120
Q

What is clozapine-induced myocarditis?

A

allergic-like reaction causing inflammation of the heart muscle

121
Q

How can we monitor for clozapine-induced myocarditis?

A

CRP and troponin

122
Q

What is the risk associated with constipation induced from clozapine?

A

can be severe
-can lead to adynamic ileus
requires bowel function monitoring

123
Q

When is clozapine-induced agranulocytosis most likely to occur?

A

in first 6 months of treatment

124
Q

When is clozapine-induced myocarditis most likely to occur?

A

in first 4-8 weeks of treatment

125
Q

When is clozapine-induced cardiomyopathy most likely to occur?

A

after months to years of treatment

126
Q

What is the main takeaway regarding the onset of clozapine-induced agranulocytosis/myocarditis/cardiomyopathy?

A

although they have high risk timeframes, they can still occur at anytime during treatment

127
Q

What is clozapine-induced cardiomyopathy?

A

disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body

128
Q

What might be some symptoms of clozapine-induced cardiomyopathy and myocarditis?

A

orthostatic blood pressure changes
fatigue and decreased exercise tolerance
chest pain
palpitations
SOB
peripheral edema
fever

129
Q

What is the lab marker we are looking for with clozapine-induced agranulocytosis?

A

absolute neutrophil count
-this is why it is important to order a CBC differential vs just a CBC

130
Q

As per Health Canada, what is required for clozapine to be used?

A

if hematological monitoring can be guaranteed AND patient is actively registered with a clozapine registry (has a clozapine pin #)

131
Q

What is the SHA preferred brand of clozapine?

A

AA-clozapine

132
Q

What do clozapine registries ensure?

A

registration of patient, physician, lab, and pharmacy
maintenance of a national database that monitors the hematologic results and provides timely feedback
identification of non-rechallengeable status

133
Q

Describe appropriate clozapine monitoring.

A

weekly blood tests for the first 6 months
-high risk period
change to once every 2 weeks if “green light” has been maintained during the first 6 months of therapy and clinically stable
change to once every 4 weeks if “green light” for another 6 months
monitoring must continue for as long as the patient is on clozapine and even for 4 weeks after stopping

134
Q

Describe the protocol for missed doses of clozapine.

A

monitoring frequency does not have to be modified if therapy is interrupted for 3 days or less but dosing needs to be re-titrated if miss > 48 hours
hematological testing should be resumed weekly for an additional 6 weeks if therapy is disrupted for more than 3 days

135
Q

Differentiate green light, yellow light, and red light for clozapine lab monitoring.

A

green: ANC > 2.0
yellow: ANC 1.5-2.0
red: ANC < 1.5

136
Q

When does clozapine become non-rechallengeable?

A

must stop and cannot ever restart therapy if total WBC < 2 or ANC < 1.5 from clozapine therapy
-must be communicated with clozapine registry
-will require weekly CBC x 4 wks then stopped

137
Q

What is the quantity of clozapine you should dispense?

A

quantity must be limited to the frequency of clozapine bloodwork

138
Q

Can you interchange between brand/generic of clozapine?

A

no

139
Q

What are the impacts of smoking on clozapine?

A

induces 1A2 = induces metabolism of clozapine

140
Q

What is the evidence for clozapine and suicide?

A

InterSePT trial showed clozapine reduces the risk of suicide in patients with schizophrenia or schizoaffective disorder
NNT = 13
retrospective studies suggest clozapine may reduce suicidal behavior in schizophrenia

141
Q

What is clozapine-resistant (ultra-resistant) schizophrenia?

A

8-12 wks at dose > 400mg/day and trough level > 350ng/ml for once daily dosing or > 250ng/ml for equal divided BID dosing

142
Q

What is the treatment for clozapine-resistant (ultra-resistant) schizophrenia?

A

no consistent evidence to support use of high dose AP, switching APs or AP polypharmacy
-recent cohort data found clozapine + aripiprazole LAIA found decrease psychiatric hospitalization vs clozapine mono tx due to synergy and adherence but more AEs

143
Q

Differentiate the onset of acute EPS and tardive symptoms.

A

acute EPS: within 30 days
tardive: after months or years of tx, tends to perist for yrs/decades

144
Q

Differentiate the proposed mechanisms of acute EPS and tardive symptoms.

A

acute EPS: D2 blockade
tardive: precise pathophys not clear

145
Q

Differentiate the treatments of acute EPS and tardive symptoms.

A

acute EPS: antiparkinsonian drugs
tardive: valbenazine and deutetrabenazine only proven drugs

146
Q

What is key with the treatment of tardive symptoms?

A

prevention
-early recognition and dc of AP may improve chance of remission
-dose decrease or use of LED is another alt but increases chance of relapse
-if dc or dose decrease, taper to avoid worsening TD sx

147
Q

What are the symptoms of acute dystonia?

A

physical:
-torsions and spams of muscle groups
-usually affects muscles of head and neck
psychological:
-anxiety, fear, panic, dysphoria, repetitive meaningless thoughts

148
Q

What are the proposed risk factors for acute dystonia?

A

young males, AP naive, high potency FGA
rapid dose increase
recent cocaine use
dehydration
prior dystonic rxn
hypocalcemia, hyperthroid

149
Q

What is the onset of acute dystonia?

A

acute
-usually within 24-48h of first dose
-90% occur within 1 week

150
Q

Describe the clinical course of acute dystonia.

A

acute, spasmodic, painful
oculogyria may be recurrent
if laryngeal/pharyngeal can be life threatening

151
Q

What is the treatment for acute dystonia?

A

1st line: IM benztropine
IM DPH, SL lorazepam

152
Q

What are the symptoms of akathisia?

A

physical symptoms:
-motor restlessness, fidgeting, pacing, rocking, inability to lie still
-respiratory: dyspnea or breathing discomfort
psychological symptoms:
-restlessness, intense urge to move, irritability, agitation, violent outbursts, feeling wound up/antsyW

153
Q

What is the onset of akathisia?

A

acute to insidious (hours to days)
90% occur within first 6 weeks of treatment

154
Q

What are the proposed risk factos for akathisia?

A

elderly female, young adults
high caffeine intake
high potency FGAs
lower risk with SGA
genetic predisposition
anxiety
mood disorder
microcytic anemia, low ferritin
concurrent SSRI use

155
Q

Describe the clinical course of akathisia.

A

may continue throughout entire treatment
increases risk of tardive dyskinesia
may contribute to suicide and violence

156
Q

What are the treatment options for akathisia?

A

reduce or change antipsychotics
benzos, beta-blockers (propranolol), mirtazapine

157
Q

What are the symptoms of acute pseudoparkinsonism?

A

physical symptoms:
-tremor, cogwheel rigidity, bradykinesia, shuffled gait, stooped posture
psychological symptoms:
-slowed thinking, fatigue, cognitive impairment, drowsiness

158
Q

What is the onset of acute pseudoparkinsonism?

A

acute to insidious
90% occur within first 6 weeks of treatment

159
Q

What are the proposed risk factors for acute pseudoparkinsonism?

A

elderly females
high potency FGA (low risk with SGA and TGA)
increased dose of antipsychotic
multiple antipsychotic concurrently
discontinuation of anticholinergics
concurrent neurological disorder
HIV infection
family hx of Parkinsons disease

160
Q

Describe the clinical course of acute pseudoparkinsonism.

A

may continue throughout entire treatment

161
Q

What are the treatment options for acute pseudoparkinsonism?

A

reduce dose or change antipsychotic
antiparkinsonian drugs (benztropine, DPH, procyclidine, trehexiphenidyl

162
Q

What are the symptoms of Pisa Syndrome?

A

leaning to one side

163
Q

What is the onset of Pisa Syndrome?

A

can be acute or tardive

164
Q

What are the proposed risk factors for Pisa Syndrome?

A

elderly patients
compromised brain function
dementia

165
Q

Describe the clinical course of Pisa Syndrome.

A

often ignored by patients

166
Q

What are the treatment options for Pisa Syndrome?

A

antiparkinsonian drugs (benztropine, procyclidine, trihexyphenidyl)

167
Q

What are symptoms of Rabbit Syndrome?

A

fine tremor of lower lip

168
Q

What is the onset of Rabbit Syndrome?

A

after months of therapy

169
Q

What are the proposed risk factors for Rabbit Syndrome?

A

elderly patients

170
Q

Describe the clinical course of Rabbit Syndrome.

A

often ignored by patients

171
Q

What are the treatment options for Rabbit Syndrome?

A

antiparkinsonian drugs (benztropine, procyclidine, trihexyphenidyl)

172
Q

What are the symptoms of tardive dyskinesia?

A

physical symptoms:
-involuntary abnormal movements of face (tics, framing, grimacing), jaw (chewing, clenching), tongue (fly-catching tongue, rolling), eyelids (blinking, blepharospasms), limbs (tapping, piano-playing fingers), trunk (rocking, twisting), neck (nodding)
-can co-exist with Parkinsonism and akathisia
psychological symptoms:
-cognitive impairment, distress, and embarrassment

173
Q

What is the onset of tardive dyskinesia?

A

after 3 or months of therapy in adults (earlier in elderly)
common early sign is rapid flicking movement of tongue

174
Q

What are the proposed risk factors for tardive dyskinesia?

A

over 40 yrs old
female
history of severe EPS early in treatment
chronic use of AP (FGA more than SGA/TGA), metoclopramide
chronic use of high doses of dopamine agonists in treatment of Parkinsons
presence of mood component
diabetes
cognitive impairment
alcohol and drug abuse

175
Q

Describe the clinical course of tardive dyskinesia.

A

persistent
discontinuation of AP early increases chance of remission
spontaneous remission in 15-24% after 5 yrs

176
Q

What are the treatment options for tardive dyskinesia?

A

valbenazine and deutetrabenazine
switch to SGA or TGA (? clozapine or quetiapine)
? pyridoxine, clonazepam, tetrabenazine, vitamin E, levetiracetam
nothing is curative, need to prevent it

177
Q

How should ziprasidone be taken?

A

with 500 kcal of food

178
Q

What is neuroleptic malignant syndrome?

A

acute, life-threatening EPS that can occur with any AP
-rare, idiosyncratic rxn
-fever, severe muscle rigidity, altered mental status, autonomic instability, elevated WBC and CK

179
Q

What is the typical time frame from starting an AP where neuroleptic malignant syndrome can occur?

A

anytime
-often early in treatment

180
Q

What is the treatment for neuroleptic malignant syndrome?

A

stop antipsychotic immediately
supportive care
consider bromocriptine
dantrolene sometimes used for malignant hyperthermia

181
Q

Summarize the key drug interactions for antipsychotics.

A

clozapine:
-substrate: 1A2, 3A4, 2D6
olanzapine:
-substrate: 1A2
risperidone:
-substrate: 2D6, 3A4
quetiapine:
-substrate: 3A4
ziprasidone:
-substrate: 3A4
aripiprazole:
-substrate: 2D6, 3A4
haloperidol:
-substrate: 3A4
-inhibitor: 2D6
chlorpromazine:
-substrate: 2D6
-inhibitor: 2D6
zuclopenthixol:
-substrate: 2D6

PHAR358 (20 decks)

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