Antipsychotics and Schizophrenia Flashcards
what are positive schizophrenia sx
delusions, hallucinations
what are negative schizophrenia sx
affective flattening, alogia, avolition, anhedonia
which AP are approved for children
aripiprazole, lurasidone, paliperidone
what gens are atypical AP
2nd and 3rd
1st gen AP MOA
dopamine antagonists
_________ acetate is considered
1. short acting
2. intermed acting
3. long acting
2
________ decanoate is considered
1. short acting
2. intermed acting
3. long acting
3
SEs of FGA
EPS, metabolic/ antihistamine/ anticholinergic, NMS
which FGA may be mixed for acute and LT control
zuclo acetate + decanoate
SGA MOA
serotonin dopamine antagonists
T or F: ODT olanzapine/ risperidone work faster
F- not actually absorbed in oral mucosa, must swallow fragments to be absorbed in stomach
name the 3 short acting SGA / TGA
olanzapine, ziprasidone, aripiprazole
name the 3 long acting SGA/TGA
risperidone, paliperidone, aripiprazole LAOI
SGA/TGA SEs
metabolic, lowered risk of NMS (appears as more agitation/ anxiety), lower movement issues
NMS results in
rhabdomyolysis, hyperkalemia, renal failure, seizures, death
SGA NMS presents as ______________ which often results in ____________
more like agitation/ anxiety = give more of drug = worsen NMS
sx of NMS
↑ body temp >38C, confused or altered consciousness, sweating, muscle rigidity, autonomic imbalance
NMS tx
stop med immediately, go to hospital, supportive care (cool, hydrate, electrolytes), meds (dantrolene, diazepam- not v effective but no other options)
what is the gold standard AP
clozapine
clozapine class
prototypical atypical
SGA
clozpine is indicated for
treatment refractory schizophrenia (failure of 2 APs)
clozapine SEs
metabolic, sedation, hypersalivation, myocarditis, cardiomyopathy, seizures, hematological (1% risk of agranulocytosis)
T or F: clozapine does not lower suicidal ideation
F- has antisuicide effect
clozapine monitoring
NC qwk blood tests f6mths, q2wk f6mths, then qmth for duration of Rx
all FGA-LAIs are _______ dissolved in _______
prodrugs
vegetable oil
FGA-LAI SEs
neurological, vehicle leakage, injection site induration
what are the 3 FGA-LAIs
haloperidol/ flupenthixol/ zuclopenthixol decanoate
why are SGA/TGA-LAIs more difficult to use
must mix/ refrigerate due to different vehicles
all have different PK = different titration/ loading protocol
list 3 circumstances of schizophrenia where the risk of suicide is higher
Hospitalization hx: first, recent, frequent, early in hospitalization
Pt characteristics: young, white, single, unemployed, male
Disease state: <5yrs of illness, paranoid schizophrenia, dpressive sx, hx substance abuse, hx suicide attempts (including FamHx)
Functioning: good premorbid function, higher cog fxn, greater insight, hopelessness, dissatisfaction in social relationships
Tends to go for methods with more lethality like jumping from heights
suicidality in schizophrenia tends to
1. be less predictable than mood disorders
2. have a plan
3. be in the worse functioning pts (ex- lower cog abilities, more + sx)
4. be longer in their course of illness (>5yrs)
5. 3, 4
1
schizophrenia is
1. more common in lower socioeconomic classes
2. seen earlier in women than in men
3. has higher prevalence in men
4. decreases life expectancy by 10yrs
1
RF for schizo with substance use
younger age, male, homelessness, incarceration, living in urban center
what is public stigma
beliefs people hold about the pt- can become institutionalized
what is internalization/ self stigma
person feels that something is wrong with them
what is institutionlized stigma
less access to care due to stigma
schizophrenia etiology
genetics (strong gene component)
external factors (OB complications, SU, smoking)
what external factors may contribute to schizophrenia
Obstetrical complications
Inflammation
Cannabis use (RF for development of psychosis)
Cigarette smoking
immigration
waht is the neurodevelopmental hypothesis of schizophrenia
schizophrenia is a neurodevelopmental disorder where there is increased vulnerability to insults (pre/ parinatal + external) + brain morphology and neuropathology sees lower gray matter in multiple brain regions
which NT play a part in schizophrenia pathophysiology
dopamine, glutamate, GABA, ACh
increased DA in the misolimbic system results in
+ sx
increased DA in the mesocortical system results in
- sx
______ of DA receptors in the _______ results in EPS
blocking
nigrostriatal
________ DA in ______ pathway results in increased prolactin
block
tuberoinfundibular
which hypothesis forms the basis of current antipsychotics
dopamine hypothesis
glutamate is a _____ NT
excitatory
what changes are seen in the schizophrenic brain based on the glutamate hypothesis
increased levels in certain areas
decreased function of NMDA receptors
________ agonists help with + and - sx (mixed evidence)
NMDA
what is psychosis
loss of touch with reality + brain creates false reality to make sense of it
visual hallucinations usually look like
often unformed- glowing orbs, flashes of colour, less commonly fully formed human figures/ faces
what is the most common type of hallucination
auditory
what are delusions
Fixed, false beliefs + may have delusional explanations for hallucinations
what is the difference between bizarre and nonbizarre delusions
Bizarre: clearly implausible
Nonbizarre: not true but technically possible
what are persecutory delusions
most common- belief that one will be harmed by another party
what are referential delusions
belief that certain gestures, comments, environmental cues are directed at oneself
what are nihilistic delusions
thinks that major catastrophe will occur
what are somatic delusions
preoccupations about health/ organ function (ex- pregnant delusions)
describe tangential and circumstantial speech
Tangential speech: off topic from question, will not answer Q
Circumstantial speech: round about way to answer Q
what are neologisms
creating new words that don’t exist
what is word salad
putting together random words that don’t mean anything
4 clinical + sx of psychosis
hallucinations
delusions
disorganized thinking
changes in behaviour
what is anhedonia
decreased pleasure
what is alogia
decreased communication
what s avolition
decreased motivation
the clinical course of schizophrenia
1. is heterogenious in onset, sx presentation, and outcomes
2. first starts usually in the late teens/ early 20s
3. rarely include a prodromal phase
4. 1+2
4
what is the 4 step clinical course of schizophrenia
Premorbid → prodromal → onset/ deterioration → residual/ stable
what is schizophrenia prodrome
period of time before psychotic disorder presents, deterioration in personal functioning (memory/ attention, social withdrawal, unusual behavior, communication, affect, bizarre ideas, poor hygiene)
first episode psychosis
1. usually happens in late 20s
2. only sees 15-20% fully recover
3. may result in residual sx
4. 2,3
5. all of the above
2,3
residual sx may be similar to
1. baseline functioning
2. mild depression/ anxiety
3. occasional psychotic breaks
4. prodromal sx
4
goals for acute psychosis
initial management
goals in 2-3wks after acute psychosis
↑ socialization, improvement in self care and mood, ↓ severity of + sx
what are some nonpharm tx for schizophrenia
therapy
psychosocial rehab
multidiscp teams
ECT in treatment resistant cases
is ECT used in schizophrenia?
yes- in tx resistant cases
characteristics of 1st gen AP
↑ D2 receptor occupancy, varying lvls of potency of D2 antagonism
characteristics of atypical AD
lower/ transient D2 ant (more time off), 5HT2A receptor antagonism
in schizophrenia tx studies
1. olanzapine had the lowest rates of drop out
2. risperidone had longest time to d/c
3. ziprasidone had lowest d/c due to lack of efficacy
4. risperidone had lowest hospitalization rate for exacerbations
1
olanzapine SEs
assoc with ↑ weight gain, hyperlipidemia, hyperglycemia
ziprasidone AEs
assoc with weight loss + improvements in lipids and BG
which AP has the lowest rate of d/c and longest time to d/c
olanzapine
which AP had the lowest hospitalziation rate for exacerbations? which had the highest?
lowest = olanzapine
highest = quetiapine
which of the following is false
1. only minority of pts remain on assigned treatment
2. there is no AP that is statistically superior
3. FGA are statistically worse than SGA in preventing relapses
4. FGAs are tolerated just as well as newer gens
3
AP should be selected based on
medical comorbidities
psych comorbs
age
medication considerations
which AP should be avoided if pt has metabolic sx
olanzapine, quetiapine, risperidone
which AP should be avoided if pt has QT prolongation
ziprasidone, quetiapine, chlorpromazine
which AP should be used if pt has insomnia
more sedating ones like olanzapine, quetiapine, risperidone
which AP to use if mania
risperidone, aripiprazole, paliperidone, quetiapine
which AP to use if depression
risperidone, aripiprazole, quetiapine are 1st line, quetiapine = 2nd line monotx
in anxiety ____. ____. ____ can be used as augmenting agents, ____ can be used as monotx in some cases
risperidone, aripiprazole, quetiapine can be used as augmenting agents, quetiapine can be used as monotx in some cases
which AP may exacerbate OCD
2nd gen AP
how should APs be selected in older pts >70yrs old
Older adults (>70yrs) more sus to AP SEs (esp anti-ACh) + OH (falls) = select those with lower a-antagonist activity
first episode psychosis
1. has no placebo controlled trials on efficacy of AP
2. would wait to trial AP to see if mediated by something else
3. often starts in late 20s
4. TGA prefered, esp LAI
1
how should first episode psychosis be tx
In most cases = start tx with AP ASAP- shorter duration of untx psychosis = better outcomes
in the acute management of psychosis, which AP are first line
SGA
4 common AP if severely agitated/ psychotic
olanzapine, loxapine, haloperidol, lorazepam
what AP may be given in acute psychosis if there is severe agitation
zuclo acetate
after initial agitation is managed in acute psychosis, ____ are preferred as first line tx
SGA/ TGAs (less EPS)
+ sx should respond within ____, with full response in ____
4wks
12wks
how long is an adequate trial of AP
min 4-6wks
at 4 wks of AP, what should we do if there is
no response
partial response
No response: consider changing meds
Partial response: optimize dose, reassess at 8wks
LAIs have a delayed ____ and ___
therapeutic effect and SS = later peak plasma levels
T or F: in a patient who has been on an LI for 2 mths, but plasma levels are not yet at target (trending up), we should increase the dose
F- plasma lvls ↑ over wks-mths without ↑ in dose due to accumulation
what is an absolute sx change
treatment response defined as having no more than mild dx
how is sx change used to evaluated treatment efficacy
evaluation of tx response relative to baseline
Better form of measurement
A change of 20% = min that can be routinely detected clinically
what is the minimum sx change that can be routinely detected clinically
20%
what is considered an adequate treatment response to AP
Absolute or relative response to treatment
Functional impairment should be no more than mild
Resp sustained for min 12wks
what is considered remission in a schizophrenic pt
Pt has no/min sx
Sx do not interfere with behaviour
Sustained for min 6mths
remission must see no/min sx for ____
6mths
3 times to switch AP
Insuff tx response
AEs (risk psych destabilization if pt stable)- can it be managed?
if pt/ fam wants to switch - Engage pt/ fam with decision
in regards to AP polypharmacy
1. it may be used after failure of one AP
2. it has insig increased efficacy
3. it has a much higher risk of AEs
4. usually only used in treatment resistant schizophrenia
5. all
6, 2, 3
7. 1, 2, 3
6
switching AP is usually done through ________
crosstapering/ titration
when would we not crosstaper AP to switch
if there is severe EPS/ NMS with AP = must do complete washout
how should LAIs be cross tapered?
don’t need to be- they are self tapering and you just need to admin the new LAI on the day the previous one was due
____% pts do not respond adequately to P
30%
TRS is defined as
persistent psychotic sx of at least mod severity + mod functional impairment
min 2 failed AP trials
what is considered 2 failed AP trials
=>6 wks adequate duration trial at therapeutic dose with adequate adherence (=>80% doses taken)
what is considered adequate AP adherence
=>80% doses taken
what is the tx of choice for TRS
clozapine
clozapine has _____ D2 binding, which results in lowered risk of ____ and _____
lower binding
EPS and hyperprolactinemia
clozapine has increased risk of
weight gain + metabolic SEs (H1)
Sedation (H1)
OH (a1, a2)
Tachycardia (a1, a2)
Anticholinergic SEs (M1): constipation (+++), blurred vision, dry mouth, etc
what are some concerns specific to clozapine that are severe
neutropenia, myocarditis, cardiomyopathy, seizure risk
how should you monitor for hematological changes with clozapine
monitor ANC baseline, qwk f26wks, then q4wks after
how would you monitor for cardiomyopathy and myocarditis with clozapine
CRP and troponin q4wks
watch for flu like sx, respiratory sx, persistent tachy, chest pain, syncope
which of the following is not a MAJOR/ severe clozapine SE
1. constipation
2. seizures
3. orthostatic hypotension
4. increased blood glucose
5. hyperprolactinemia
6. cardiomyopathy
5- lowered risk due to decreased D2 binding
clozapine is a substrate of CYP ___
1A2
what induces clozapine metabolism
smoking increases CYP 1A2 = higher metabolism
what is the issue with transfering to hospital/ out to community with clozapine and smoking
Admission to hospital → abrupt d/c smoking → ↑ clozapine conc = ↑ risk toxicity
Discharge from hospital → abrupt resumption = ↓ clozapine conc = ↑ risk psych decompensation
what is ultraresistant schizophrenia
clozapine resistant schizophrenia
Pts that meet criteria for TRS + inadequate tx response to adequate tx with clozapine
___% respond adequately to clozapine
30-60%
which treatment for URS has the most robust effects?
1. higher dose clozapine
2. mood stabilizers
3. additional AP
4. ECT
5. none of the above
5
which strategy is the most promising for URS
1. higher dose clozapine
2. mood stabilizers
3. additional AP
4. ECT
5. none of the above
4
which AP combination has better evidence in URS
clozapine + aripiprazole or amisulpride
EPS with AP are _____ related, more common with _____
dose related
more common with high dose FGA
EPS is less common with these 4 AP
clozapine, olanzapine, quetiapine, aripiprazole
EPS can
1. occur early or later as tardive after AP start
2. may present as akathisias
3. is more common with high dose SGAs than FGAs
4. 1+2
4
