Schizophrenia Dr.OTT Flashcards
Key features that define psychotic disorders
delusion, hallucination, disorganized thinking, disoragnized or abnormal motor behavior
negative symptoms - withdrawal from social life, anxiety, depression, not taking care of self
Disease course in schizophrenia
onset late adolescence to early adulthood
men - late teens, early 20s
women - late 20s, early 30s
Link to substance use
smoking is associated with induction of 1A2 due to the hydrocabons in inhalants which decrease serum concentration of 1a2 substrate antipsychotics
Marijuiana, cocaine, and amphetamine use can hasten the onset of schizophrenia, exacerbate symptoms, and reduce time to relapse
Substance use treatment can be succussfully achieved along with mental health treatment in patients with schizophrenia, should be undertaken at the same time
MUST CONSIDER for antipsychotic drug therapy
dose per day
side effects
previous drug therapy
cost of drug therapy
concomitant drug therapy
need for monitoring
Antipsychotic drug selection
Oral antipsychotic drug therapy is generally considered first line, unless the patient presents with reasons to consider IM depot drug therapy first
Older agents
Primarily D2 receptor antagonists
Haloperidol - most commonly used - routine and PRN
fluphenazine
chlorpromazine
perphenazine
loxapine
thioridazine
these agents are very effective in treating the positive symptoms but are likely to worsen negative and cognitive symptoms
Atypical antipsychotics
D2 antagonists + 5HT antagonists
less EPS than typicals; more metabolic side effects
aripiprazole
clozapine
olanzapine
ziprasidone
asenapine
iloperidone
paliperidone
brexpiprazole
lumateperone
quetiapine
cariprazine
lurasidone
risperidone
Asenapine transdermal patch
apply 1 patch every 24 hours rotate pate site to minimize application site reaction
Reduce dose of patch if given with 1A2 inhibitor (fluvoxamine)
warning for QTC prolongation
Clozapine REMS
Monitoring timelines weekly x 6 months, biweekly x 6 months, then every 4 weeks
Olanzapine/ samidorphan (lybalvi)
samidorphan is an opioid antagonist with preferential activity at the mu opioid receptor
Lumateperone (Caplyta)
-low risk for weight gain or metabolic side effects
low risk for EPS or akathisia
- 3A4 substrate
Pimavanserin (nuplazid) side effects and use
Treatment of hallucination or delusions in patients with parkinsons disease
inverse agonist and antagonist at the serotonin 2A
3A4 substrate
SE: peripheral edema, confusional states, nausea, rare angioedema
Warning for all antipsychotics
Black box warning: increased risk of death in elderly patients treated with antipsychotics for dementia with related behaviors
metabolic adverse effects
Haloperidol injection
given every 4 weeks
load: 20 times oral dose
maintenance: 10 times oral dose
oil based Z-track method (pull needle out in Z shape to increase surface area)
Risperdal Consta (risperidone) injection
Has to be refridgerated, and reconstituted
Must supplement with oral risperidone for the first few weeks of treatment - I tell providers until 3 injections
Perseris (resperidone) Injection
Every 4 weeks
Abdominal subcutaneous injection (avoid belt line) - 90mg and 120mg
3A4 inducers - use 120mg dose or may need oral supplementation
easy conversion from injection to oral
Rykindo (risperidone)
Every 2 weeks IM injection
oral dose overlap is shorter than risperidal consta (7 days vs 21)
Uzedy (risperidone)
Abdominal or upper arm subcutaneous injection (ADVANTAGE - can be given upper arm)
Given once monthly or every 2 months
Invega Sustenna (paliperidone)
Loading dose, then booster, then every 4 weeks (starting 5 weeks after loading injection)
initial loading dose and booster dose must be given in deltoid to improve absorption consistency
if loading strategy followed no need for oral overlap
may require dose adjustment in moderate to severe renal impairment
Invega Trinza (paliperidone q3mo)
May be initiated for patients who has been on stable monthly IM injections of Invega sustenna at least 4 stable invega sustenna doses
recommended to be given in deltoid; gluteal administration results in a lower Cmax
not recommended if CrCl < 50ml/min
Invega Hafyera (paliperidone q6mo)
may be initiated after stable invega sustenna for 4 months or stable invega trinza after one 3 month dose
Gluteal injection ONLY
Abilify Maintena (aripiprazole)
Must overlap with oral aripiprazole for at least 14 days after first injection
deltoid or gluteal injection
IF patient is taking 2D6 inhibitor or 3A4 inducers for more than 14 days as concomitant therapy a dose adjustment is needed
Abilify asimtufii (aripiprazole)
every 2 months dosing - 720mg, 960mg
gluteal injection
continue oral aripiprazole for 2 weeks after first injection
Ariistada (aripiprazole lauroxil)
PRODRUG
overlap with oral aripiprazole for 3 weeks after first injection
Aristada initio
developed to avoid for 21 day oral overlap of antipsychotic
avoid in patients who are 2D6 poor metabolizers or with strong 3A4 or 2d6 inhibitors
Immediate release antipsychotiv injections/ psychiatric emergencies
Haloperidol, chlorpromazine, fluphenazine are used, haloperidol most commonly
olanzapine immediate release IM - CANNOT be given at the same time as a benzodiazepine immediae release injection - box warning for respiratory depression
loxapine for inhalation (Adasuve)
Clinical treatment strategies for EPS
Acute dystonia - IM anticholinergic NOW dose (benztropine 2mg, diphenhydramine 50mg)
Drug induced parkinsons - oral anticholinergic (benztropine, diphenydramine, trihexyphenidyl)
Akathisia - beta blockers - propranolol preffered, benzodiasepine - usually lorazepam
Tardive dyskinesia - VMAT inhibitors
VMAT inhibitors
Used to treat tardive dyskinesia in these patients
Tetrabenazine (xenazine)
Valbenazine (ingrezza) - 2D6/3A4 substrate, Qtc prolongation
Deutetrabenazine (austedo) - 2D6 substrate, QTC prolongation
Neuroleptic malignant syndrome
Life threatening is a medical emergency
hyperpyrexia, tachycardia, labile blood pressure, msucle rigidty - elevated CK
treatment is supportive
future antipsychotic use is not contraindicated
Metabolic adverse effects
Hyperglycemia, hyperlipidemia, hypertension
Clozapine = olanzapine (the worst for atypical antipsychotic risk)
quetiapine = risperidone = paliperidone = asenapine = iloperidone = cariprazine = brexpiprazole (first in the middle)
ziprasidone = lurasidone = aripiprazole (least likely for atypical antipsychotic risk)
Baseline monitoring
Personal and family hx
weight
waist cirvumference
blood pressure
FPG
fating lipids
4 weeks and 8 weeks post therapy monitoring
weight
12 weeks post monitoring
weight, blood pressure, FPG, fasting lipid
yearly monitoring
personal family hx
waist circumference
blood pressure
FPG
Aripirazole
Partial agonist
Stabilize dopamine transmission
associated with more akathisia than other antipsychotics
approved for adjunct treatment in depression so all have box warning for suicidal thoughts/behavior
2D6 and 3A4 substrate, moderate akathisia, low weight gain
brexpiprazole
Partial agonist
Stabilize dopamine transmission
associated with more akathisia than other antipsychotics
approved for adjunct treatment in depression so all have box warning for suicidal thoughts/behavior
2D6 and 3A4 substrate, moderate akathisia, low-moderate weight gain
cariprazine
Partial agonist
Stabilize dopamine transmission
associated with more akathisia than other antipsychotics
approved for adjunct treatment in depression so all have box warning for suicidal thoughts/behavior
3A4 substrate, moderate akathisia, Low-moderate weight gain
Asenapine
sublingual and patch formulation, 1A2 substrate, QTC prolongation
Clozapine
1A2 substrate, box warning - neutropenia, orthostasis, bradycardia, syncope, seizure, myocarditis, cardiomyopathy
Olanzapine
1A2 substrate, significant weight gain and sedation, high metabolic syndrome, DRESS warning
Quetiapine
3A4 substrate, QTC prolongation, weight gain and sedation, box warning for suicidal ideation
iloperidone
high risk for orthostasis and syncope, QTC prolongation, 2D6 substrate
Lurasidone
3A4 substrate, high risk for akathisia, warning for suicidal thoughts, adjunct for bipolar depression, take with food
Ziprasidone
QTC prolongation, Dress warning, take with food to increase absorption, 3A4 substrate and aldehyde oxidase
risperidone
Highest D2 blockade
2D6 substrate, EPS, hyperprolactinemia, weight gain, sedation, orthostasis
paliperidone
renally eliminated - dose adjustments in renal impairment, similar side effects with resperidone, QTC prolongation
Highest D2 blockade
