Ch. 64 Schizophrenia/Psychosis

Stabinsky

EPS

a group of side effects related to irregular movements

dystonias

prolonged contraction of muscles during drug initiation, including painful muscle spasms

life threatening if airway is compromised

higher risk with younger males

centrally-acting anticholinergics can be used for prophylaxis or treatment

akathisia

restlessness with anxiety and an inability to remain still

treated with benzos and propranolol

parkinsonism

looks similar to parkinson disease, with tremors, abnormal gait, and bradykinesia

treat with anticholinergics or propranolol if tremor is the main symptom

tardive dyskinesia

abnormal facial movements, primarily in the tongue or mouth

higher risk with elderly females

TD can be irreversible

must stop the drug and replace with a second gen antipsychotic with low EPS risk

dyskinesias

abnormal movements

more common with dopamine replacement for parkinsons

background

thought disorder

common symptoms include --> hallucinations, delusions, and disorganized thinking/behavior

treatment adherence is often difficult to achieve

diagnosis includes both positive and negative symptoms --> DSM-5

patho

involves dopamine, serotonin, and glutamine

DSM-5 diagnostic criteria for schizo

** delusions, hallucinations, or disorganized speech MUST be present

negative s/s --> lack of emotion (apathy), social withdrawal, loss of motivation (avolition), lack of speech (alogia)

positive s/s --> hallucinations, delusions, disorganized thinking/behavior

meds that can cause psychotic symptoms

anticholinergics (centrally-acting, high-doses)

dextromethorphan

dopamine or dopamine agonists

interferons

stimulants

systemic steroids

cannabis

cocaine

LSD

meth

PCP

synthetic cathinones

drug treatment

antipsychotics block dopamine receptors --> newer ones also block serotonin

SGAs are first line due to a lower incidence of EPS

FGAs have higher incidence of EPS, including dystonias, dyskinesias, TD, and akathisia

TD can be irreversible and the drug should be DC

formulations

**adherence is poor

long-acting injections

ODTs are useful to prevent cheeking

oral solutions/suspensions

acute IM injections provide "stat" relief --> IM APs are often mixed with other drugs (in cocktails) such as benzos and anticholinergics to reduce dystonias

** olanzapine and benzos should not be given together

BBW

APs are not indicated for agitation control in elderly patients with dementia-related psychosis --> increased risk of mortality

several APs also carry a warning for increased stroke risk in patients with dementia

all carry a warnings for falls

FGAs

work mainly by blocking dopamine 2 receptors

many are in the phenothiazine class

FGA drgus

low potency --> chlorpromazine, thioridazine

mid potency --> loxapine (adasuve - inhalation), perphenazine

high potency --> haloperidol (haldol), pluphenazine, thiothixene, trifluoperazine

**haldol is in the butyrophenone class

FGA BBW

increased risk of death in elderly patients with dementia related psychosis

thioridazine --> QT prolongation

FGA warnings

QT prolongation --> especially with thioridazine, haloperidol, chlorpromazine

orthostasis/falls

anticholinergic effects

CNS depression

EPS

hyperprolactinemia

NMS

FGA SEs

sedation

dizziness

anticholinergic effects

EPS --> can give anticholinergic to limit/avoid painful dystonias

FGA notes

lower potency drugs have increased sedation and less EPS

higher potency drugs have less sedation and increased EPS

** all cause both though

SGAs

block dopamine 2 and 5-HT2A receptors

SGA drugs

aripiprazole (abilify)

clozapine (clozaril)

lurasidone (latuda)

olanzapine (zyprexa)

paliperidone (invega)

quetiapine (seroquel)

risperidone (risperdal)

ziprasidone (geodon)

asenapine (saphris)

cariprazine

brexpiprazole

iloperidone

lumaterperone

aripiprazole

SEs --> akathisia, activating or sedating

clozapine

used no sooner than 3rd line due to more severe SE potential

clozapine BBW

neutropenia/agranulocytosis

myocarditis and cardiomyopathy

seizures

clozapine SEs

agranulocytosis

seizures

constipation

increased weight

hypersalivation

clozapine monitoring

REMS --> pharmacies must be certified

ANC must be 1,500 or higher

stop therapy if ANC < 1000

lurasidone

SEs -->

somnolence

EPS (dystonias)

nausea

decreased risk of metabolic syndrome

olanzapine

BBW --> zyprexa relprevv --> monitor for 3 hours post injection

SEs --> somnolence, metabolic syndrome (increased weight, BG, and lipids)

paliperidone

SEs -->

increased prolactin --> sexual dysfunction, galactorrhea, irregular periods

EPS, especially at higher doses

metabolic syndrome (increased weight, increased BG, increased lipids)

quetiapine

SEs --> somnolence, metabolic syndrome, low EPS risk (often used for psychosis in PD)

notes --> take without food or with a light meal (300kcal or less)

risperidone

SEs --> increased prolactin, EPS (especially at high doses), and metabolic syndrome

ziprasidone

take with food

acute injection --> geodon IM

CI --> QT prolongation; do not use with QT risk

asenapine

no food/drink for 10 min after dose

SEs --> tongue numbness

selecting an AP

SGAs cause increased weight, cholesterol, TGs, and BG --> avoided in DM or CVD

some SGAs can cause dose-related EPS

prolactin levels can increase

clozapine has the highest efficacy, but the worst SE (agranulocytosis, seizures)

treatment considerations

when assessing treatment resistance or evaluating the best option for a partial response, it is important to evaluate whether the patient has had an adequate trial (at least 6 weeks) of an AP, including whether the dose is inadequate and whether the patient has been taking the medication as prescribed

did it work and was it tolerated? --> if the drug was being taken and did not work well, dont use it again; do not choose a treatment that was poorly tolerated in the past

cardiac risk/QT prolongation risk --> do not choose a QT-prolonging drug like ziprasidone, haloperidol, thioridazine, or chlorpromazine

history of movement disorders --> do not choose a drug with high risk of EPS

overweight/metabolic risk --> do not choose a drug that worsens metabolic issues like with olanzapine or quetiapine. there is a lower metabolic risk with aripiprazole, ziprasidone, lurasidone, and asenapine

nonadherence or unhoused patients --> choose a long-acting injection

STAT

acute psychosis and refusing PO meds

1st --> haloperidol IV/IM +/- diphenhydramine and lorazepam

alternatives --> ziprasidone IM or olanzapine IM

chronic treatment and adherent to daily PO treatment

FGA or SGA oral tablets or other formulations

failure with 2 or more APs --> clozapine tablet or versacloz suspension

chronic treatment and not adherent to daily PO treatment or swallowing difficulties

long acting injectable IM or SC

ODTs --> aripiprazole, olanzapine, risperidone

SL --> asenapine

oral liquids --> aripiprazole, fluphenazine, haloperidol, risperidone

patch --> asenapine

failure with 2 or more APs --> clozapine tablet or versacloz suspension

meds that last 6 months

IM paliperidone (invega hafyera)

meds that last 3 months

IM paliperidone (invega trinza)

meds that last 2 months

IM aripiprazole (abilify asimtufii)

meds that last 1-2 months

IM aripiprazole (aristada)

SC risperidone (uzedy)

meds that last 1 month

IM aripiprazole (abilify maintena)

IM haloperidol (haldol deconoate)

IM paliperidone (invega sustenna)

SC risperidone (perseris)

meds that last 2-4 weeks

IM olanzapine (relprevv)

meds that last 2 weeks

IM fluphenazine decanoate

IM risperidone (risperdal consta, rykindo)

psychosis in PD

pimavanserin (nuplazid) is approved

AP drug interactions

all can prolong the QT interval --> thioridazine has the highest risk

all AP counseling

medguides required

can cause drowsiness, orthostasis, unusual body movements, fever, sweating, and severe muscle stiffness

olanzapine, risperidone, paliperidone, and quetiapine counseling

can cause hyperglycemia and weight gain

clozapine counseling

can cause low WBC count

requires monitoring via REMS

risperidone counseling

risperdal oral solution --> administered directly from the calibrated pipette, or mixed with water, coffee, orange juice, or low-fat milk

it cannot be mixed with cola or tea

asenapine SL counselng

can cause tongue numbness

TD

valbenazine and deutrabenazine reversibly inhibit VMAT2, which regulates monoamine uptake

both are approved for treatment of TD

valbenazine (ingrezza) --> somnolence

deutrabenzine (austedo) --> hepatic impairment, somnolence

NMS

rare but is highly lethal --> medical emergency

due to D2 blockade

signs --> hyperthermia, muscle rigidity

treatment --> stop the AP and relax the muscles with dantrolene