Schizophrenia Flashcards
age of onset
late teens to early thirties
earlier in men
what does positive symptoms mean
abnormally PRESENT:
hallucination, paranoia, delusion, hostility, disorganized speech, ideas of reference
what does negative symptoms mean
abnormally ABSENT
affect, alogia, avolition, asociality, anhedonia
the five As
other symptoms of schizophrenia
attention and memory deficits, poor hygiene, poor psychosocial function
dopamine hypothesis
brain of a patient with schizophrenia produces more dopamine than a typical brain
mesolimbic pathway effects of D2 blockade
decrease in positive symptoms
mesocortical pathway effects of D2 blockade
increase in negative symptoms
nigrostriatal pathway effects of D2 blockade
increase in EPS
tuberoinfundibular pathway effects of D2 blockade
increase in prolactin
differential diagnosis: things to rule otu
meds (dopa agonists, steroids, overdose, withdrawal, hallucinogens)
medical conditions like thyroid, infectious, epilepsy, wilson’s disease, SLE
goals of therapy
reduce/eliminate symptoms
promote/maintain recovery
reduce medication adverse effects
improve QOL
APA recommendations
treat with an antipsychotic and monitor for effectiveness and side effects. no evidence that one antipsychotic is superior to another (except clozapine)
when do you qualify for clozapine
after 2 failed trials of a FGA or SGA
factors to consider when selecting treatment
side effect profile, past response, health conditions, med formulations, drug interactions
antipsychotic response seen in hours to days
agitation, aggression, motor activity
antipsychotic response seen in 2-6 weeks
hallucinations
disorganized thinking
antipsychotic response seen in months or longer
delusions
negative symptoms
receptor targets
D2, M1, H1, alpha1, serotonin
effects of D2 receptor antagonism
therapeutic
EPS
hyperprolactinemia
effects of M1 receptor antagonism
anticholinergic
effects of H1 receptor antagonism
weight gain, sedation
effects of alpha1 receptor antagonism
syncope, orthostatic hypotension, reflex tachycardia
effects of serotonin receptor antagonism
reduce EPS, improve cognition, antidepressant
what is the optimal occupancy of D2 receptors
60-80%
general adverse effects of FGAs
extrapyramidal: akathisia, parkinsonism, dystonia, tardive dyskinesia
general adverse effects of SGAs
metabolic
FGAs
haloperidol
fluphenazine
trifluoperazine
thiothixene
loxapine
perphenazine
thioridazine
chlorpromazine
FGAs are characterized by
strong D2 affinity
low potency FGAs
chlorpromazine, thioridazine
high potency FGAs
haloperidol
fluphenazine
thiothixene
trifluoperazine
loxapine
perphenazine
implications of low potency FGAs
need a higher dose to get the D2 blockade
anticholinergic, sedation, orthostasis
implications of high potency FGAs
stronger D2 antagonism so stronger EPS
haloperidol pearls
IM:PO 1:2
fluphenazine pearls
IM:PO 1:2, dilute oral liquid prior to use
chlorpromazine pearls
weight gain, sedation (less potent)
IM:PO 1:4
thiothixene and trifluoperazine pearls
smoking may reduce levels due to CYP1A2 induction from hydrocarbons in cigarette smoke
thioridazine pearls
highest Qt prolongation risk
which FGAs have long acting injection forms
haloperidol and fluphenazine
describe dystonia
happens within 24-96 hours, involuntary muscle contraction results in slow repetitive movements or abnormal postures
dystonia risk factors
high potency antipsychotics, high dose, young men
dystonia treatment
diphenhydramine, benztropine
consider dose reduction
describe akathisia
happens within days to weeks, inner motor restlessness
akathisia risk factors
fast titration, middle aged females
akathisia treatment
propranolol, anticholinergic, benzodiazepine, consider dose decrease/medication change
describe pseudoparkinsonism
happens within days to weeks, stooped posture, shuffling gait, rigid, tremors, pill rolling hand motion
pseudoparkinsonism risk factors
high potency antipsychotics, high dose, older age, females
pseudoparkinsonism treatment
benztropine, diphenhydramine, amantadine, consider dose decrease
describe dyskinesia
months to years, rapid, repetitive, involuntary movements such as rolling tongue, smacking lips, chewing
dyskinesia risk factors
older age, females, other EPS, chemical abuse, mood disorders
dyskinesia treatment
VMAT inhibitors
switch to clozapine
pyridoxine
weak: ginko, clonazepam, amantadine
SGAs
aripiprazoke, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lumateperone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone
which SGAs have long acting injection forms
aripiprazole, olanzapine, paliperidone, risperidone
quetiapine pearls
sedation: dose at bedtime
XL formation once daily, <300 calories
olanzapine pearls
high metabolic risk
smoking induces CYP1A2 metabolism
do not give IM olanzapine within 2 hours of IM lorazepam (cardiorespiratory depression, excessive sedation)
risperidone pearls
strong D2 affinity
renal dose adjustments
hyperprolactinemia risk
paliperidone pearls
active metabolite of risperidone
renal dose adjustments
hyperprolactinemia
increased bioavailability with food
ghost tablet (shell of tablet in poop)
aripiprazole pearls
activating at low dose
low risk weight gain
dose adjustments for CYP inhibitors/inducers
may assist in antipsychotic-induced hyperprolactinemia
brexpiprazole pearls
renal dose adjust, hepatic dose adjust, CYP dose adjust
cariprazine pearls
avoid CrCL<30
lurasidone pearls
take with 350 calories
renal/hepatic dose adjust
low weight gain risk
ziprasidone pearls
take with 500 calories
QT prolongation (especially IM)
low weight gain risk
iloperidone pearls
significant orthostasis– titrate by no more than 4 mg/day
pimavanserin pearls
no D2 activity
only used in Parkinson Disease Psychosis
asenapine pearls
SL tablet: no food/drink for 10 mins
contraindicated in severe hepatic impairment
lumateperone
take with food
dose adjust in hepatic impairment
metabolic syndrome criteria
must meet at least 3 criteria:
waist circumference >40 inches male, 35 female
triglycerides >150
HDL <40 male, 50 female
fasting blood glucose >110
BP>130/85
SGAs with highest risk of EPS, hyperprolactinemia
risperidone, paliperidone
SGAs with highest risk of seizures, anticholinergic
clozapine, olanzapine
SGA with highest risk of orthostatic hypotension, sedation, weight gain, increased blood glucose, lipid abnormalities
clozapine
5 black box warnings for clozapine
severe neutropenia
seizure
myocarditis
orthostatic hypotension, bradycardia, syncope
increased mortality in elderly patients with dementia related psychosis
what is the black box warning on ALL antipsychotics
increased mortality in elderly patients with dementia related psychosis
what is REMS monitoring requirement for clozapine
severe neutropenia, agranulocytosis
how is clozapine dosed (starting and titration)
start at 12.5 mg once or twice daily
increase by 25-50 mg/day inpatient or per week outpatient
what do do if you missed a dose of clozapine for >48 hours
re-initiate with 12.5-25 mg/day
what is the risk with missing clozapine doses
hypotension, bradycardia, syncope
associated with the alpha antagonism & building a tolerance to it
therapeutic drug monitoring for clozapine: what is the target trough level
350-500 ng/mL
but really we are targeting how they respond, not an exact level
what must the ANC count be before initiating clozapine
> 1500
what is the ANC monitoring schedule for clozapine
weekly x 6 months
biweekly x 6 months
then monthly
what is the recommendation for clozapine if ANC 1000-1499 (mild neutropenia)
monitor 3x/week and resume normal schedule once ANC >1500
what is the recommendation for clozapine if ANC 500-999 (moderate neutropenia)
interrupt therapy and monitor daily ANC until >1000 (may resume at this point)
then monitor 3x/week until ANC>1500
what is the recommendation for clozapine if ANC <500 (severe neutropenia)
interrupt therapy & do not rechallenge unless prescriber determines benefit outweighs risk
daily ANC until >1000 then 3x/week until >1500
what are TITRATION-DEPENDENT adverse effects of clozapine
orthostasis
tachycardia
sedation
myocarditis
what are DOSE-DEPENDENT adverse effects of clozapine
seizures
what are DOSE-INDEPENDENT adverse effects of clozapine
sialorrhea (drooling), constipation, urinary incontinence
how can you treat sialorrhea with clozapine?
atropine eye drops SL or ipratropium nasal spray SL
glycopyrrolate, benztropine, clonidine
how can you treat constipation with clozapine?
osmotic laxatives (miralax), stimulant laxatives (senna(, stool softeners (colace)
how can you treat seizures with clozapine?
seizure prophylaxis when levels reach >1000 mcg/L
what is neuroleptic malignant syndrome?
rare life-threatening syndrome that involves fever, lead-pipe rigidity, mental status changes, leukocytosis, elevated creatinine kinase, AST/ALT
how is neuroleptic malignant syndrome managed?
-straight to the hospital
-discontinue antipsychotic for at least 2 weeks
-no other psychotropic (except benzos) for 2 weeks
-bromocriptine and dantrolene
when to use caution with antipsychotics for QT prolongation
pre-existing abnormalities, other QT prolonging agents, patients with baseline QT ~500
monitoring for QT prolongation?
baseline & annual EKG, K+, Mg2+
which antipsychotics cause the most QT prolongation
thioridazine, ziprasidone
which antipsychotics are used for acute psychotic agitation
haloperidol
fluphenazine
clorpromazine
olanzapine
ziprasidone
risperidone, aripiprazole
what agents are used for anxiety-related agitation
benzos like lorazepam*, diazepam
non-benzo hydroxyzine
* note separate IM olanzapine and IM lorazepam by at least 2 hours
which agents are used for extrapyramidal symptoms and sedation for acute agitation?
benztropine, diphenhydramine
what are the key principles to initiation of LAIAs
establish oral tolerability first
screen for dose adjustments/contraindications to LAIA
identify if loading dose or oral overlap needed
determine maintenance dose & frequency
which FGAs are available as injectables
haloperidol decanoate and fluphenazine decanoate
which SGAs are available as injectables
aripiprazole
olanzapine
paliperidone
risperidone
are there any allergy considerations for LAIAs
fluphenazine decanoate and haloperidol decanoate are suspended in sesame oil– check for sesame allergy
which LAIA has a rems program?
olanzapine pamoate: for post-injection delirium/sedation syndrome, increased mortality in elderly patients with dementia-related psychosis
MUST OBSERVE FOR AT LEAST 3 HOURS AFTER INJECTION, BE ACCOMPANIED UPON LEAVING FACILITY
aka a lot of paperwork
