Schizophrenia/Psychosis

Common symptoms

hallucinations, delusions, disorganized thinking/behaviour

Hallucinations

Sensing something not present

Delusions

Belief about something real that is not true

Disorganized thinking/behaviour

Inability to focus attention and communicate organized thoughts

Onset of symptoms

Young adulthood

Neurotransmitters involved

Dopamine, serotonin, glutamine

Medications causing psychosis

Anticholinergics, dextromethorphan, dopamine/dopamine agonists, interferons, stimulants, systemic steroids

Illicit substances causing psychosis

Cannabis, cocaine, LSD, methamphetamine, PCP, synthetic cathinones (bath salts, MDPV)

Negative symptoms

Loss of interest, lack of emotion, inability to carry out/plan activites, poor hygeine, social withdrawal, loss of motivation, lack of speech

Avolition

Lack of motivation

Alogia

Lack of speech

Positive signs and symptoms

Hallucinations (auditory or visual or somatic), delusions, disorganized thinking/behavior, difficulty paying attention

What symptoms (positive vs negative) do drugs typically treat

positiveS

Typical first-line treatment (general)

SGA

EPS symptoms

dystonias, dyskinesias, tardive dyskinesias, akathisia, parkinsonism

Dystonias

prolonged contraction of muscles; painful muscle spasms; higher risk in young males. Can be life threatening (airway)

Dystonia prophylaxis/treatment

Centrally acting anticholinergics; benztropine, diphenhydramine

Akathisia

restlessness with anxiety; inability to sit still

Akathisia treatment

BZDs or propranolol

Parkinsonism

Similar to parkinsons disease; tremors, abnormal gait and bradykinesia

Parkinsonism treatment

Anticholinergics (propranolol if tremor is main symptom)

Tardive dyskinesias

abnormal facial movements; primarily tongue or mouth; higher riks elderly females

Irreverisble EPS symptoms

TD

Tardive dyskinesia treatment

stop drug; replace with SGA with low EPS risk (quietiapine, clozapine)

Dyskinesias

Abnromal movments, more common with dopamine replacement for parkinson disease

Olanzapine + BZD = ?

excessive sedation and breathing difficulty; avoid

Black Box Warnings; General

Not indicated for agitation control in elderly with dementia related psychosis; increased risk of mortality (CV).

Increased risk for stroke

Warning of falls

FGA; MOA

Blocking D2 receptors, minimal 5HT2a blockage.

-azine ending

Phenothiazines

High potency FGAs

Haloperidol, fluphenazine, thiotixen, trifluoperazine

Mid potency FGAs

loxapine, pherphenazine

Low potency FGAs

Chlopromazine, thioridazine

Loxapine (inhalation brand)

Adasuve

Haloperidol class

Butryophenone

Boxed warning; thioridazine

QT prolongation

Boxed warning; adasuve

Bronchospasm (REMS)

FGA warnings (general)

CV, anticholinergic, CNS depression, EPS, hyperprolactinemia, NMS, Blood dyscrasias

FGA- CV

Qt prolongation, orthostatic/falls, tachycardia

FGA- highest QT prolongations

Thioridazine, haloperidol, chlorpromazine

FGA- anticholinergic

constipation, xerostomia, blurred vision, urinary retention

FGA- hyperprolactinemeia

infertility, oligomenorrhea/amenorrhea, glactorrhea, erectile dysfunction, decreased libido

FGA- NMS (neuroleptic malignant syndrome)

mental status changes, fever, muscle rigitidy, autonomic instability

FGA- blood dyscrasias

leukonpenia, nuetropenia, agranulocytosis, ocular effects

FGA sides effects

Sedation dizziness, anticholinergic effects, increased prolactin

EPS

Adasuve side effects

dysgeusia

Lower potency drug effect on EPS and sedation

lower EPS; higher sedation

Higher potency drug effect on EPS and sedation

higher EPS; lower sedation

SGA MOA; general

block D2 and 5HT2A

D2 and 5HT1a partial agonist

aripiprazole, cariprazine

D2 and 5HT1a partial agonist; 5HT2a antagonist

brexpiprazole

Aripiprazole (abilify) side effects

akathisia, activing or sedating, headache, anxiety, constipation; lower risk weight gain, some QT prolongation; EPS in children

Aripiprazole- Aristada initio

one time IM LD dose with oral aripiprazole

Ability MyCite

aripiprazole tablets wtih ingestible sensor

Clozapine (generic)

Clozaril, Versaclox susp (brand)

Clozapine; use when?

Failure to 2 AP treatments or significant ADRs

Clozapine BBW

Neutropenia/agranulocytosis

Bradycardia, orthostatic HoTn, syncope and cardiac arrest (highest during titration period- titrate slowly)

Mycoarditis and cardiomyopathy

Siezures (start no higher than 12.5mg QD/BID)

Clozapine REMS

neutropneia/agranulocytosis

Start; ANC must be >1500

ANC weekly x 6 mo; then q2week x 6mo; then monthly

D/C if ANC <1000

Clozapine; side effects

agranulocytosis, seizures, contsipation, somnolence, metabolic syndrome, sialorrhea, hypotension

Metabolic syndrome

Increased weight, BG, lipids

Sialorrhea

hypersalivation

Clozapine and smoking

Smoking reduces drug levels

Lurasidone (generic)

Latuda (brand)

Lurasidone CI

Use wtih a strong CYP450 3A4 inducer/inhibitor

Lurasidone side effects

somnolence, EPS (dystonia), N

Decreased risk of Metabolic syndrome vs other SGAs

Zyprexa Relprevv BBW

sedation (coma) and delirium (agitation, anziety, confusion, disorientation); monitor for 3 hours post injection; REMS

Olanzapine side effects

Smonolence, metabolic syndrome, orthostasis

Olanzapine and smoking

Smoking reduces drug levels

Olanzapine and lybalvi (samidrophan) use

Mitigate weight gain; opioid reeptor antagonist; cannot use in those using opioids/opioid withdrawal

Paliperidone (generic)

Invega (brand)

Paliperidone, risperidone side effects

incrased prolactin, eps (esp at higher doses), metabolic syndrome, somnolence, tachycardia, qt prolongation

Quetiapine (generic)

seroquel (brand)

Quetiapine side effects

Somnolence, metabolic syndome, orthostasis, possible occular effects/cataracts

Low EPS risk

Agent commonly used for psychosis in parkinsons disease

quetiapine/seroquel

Ziprasidone (generic)

Geodon (brand)

Ziprasidone CI

QT prolongation; do NOT use wtih QT risk

Ziprasidone; side effects

QT prolongation

somnolence, EPS, dizziness, nausea

Asenapine (generic)

Spahris, secuado (brand)

Asenapine CI

severe hepatic impairment

Asenapine side effects

somnolence, tongue numbness, EPS (slight), QT prolongation

Cariprazine (generic)

Vraylar (brand)

Cariprazine side effects

eps, dystonias, headache, insomnia

Brexpiprazole (generic)

Rexulti (brand)

Brexpiprazole side effects

weight gain, dyspepsia, diarrhea, akathisia

Iloperidone (generic)

Fanapt (brand)

iloperidone side effects

dizziness, somnolence, orthostasis, tachycardia, QT prolongation

lumateperone (generic)

caplyta (brand)

Lumateperone side effects

somnolence, eps

Questions to ask for treatment (5)

Did it work/well tolerated (with adequate adherence)

CV risk/QT prolongation

Hx of movement disorder (parkinsons)

Overweight/metabolic risk

Nonadherence/unhoused patients

Stat; acute psychosis / NPO

haloperidone, diphenhydramine, lorazepam

ziprasidone or olanzapine IM

Pimavanserin (generic)

nuplazid (brand)

pimavanserin moa

inverse agnoist and antagonist at 5HT2a receptors; less extent at 5HT2c receptors. No effect on dopamine

Where do you use pimavanserin?

Parkinsons disease psychosis

Pimavanserin warnings

not approved for dementia related psychosis

Qt prolonging.

Pimavanserin side effects

QT prolongation, peripheral edema, confusion

Risperidone caution with WHAT cyp?

cyp 2d6 inhibitors (paroxetine, fluoxetine)

valbenazine and deutrabenazine moa

reversibly inhibitor VMAT2 (receptor regualting monoamine uptake from cytopalsm to synaptic vesicle)

Valbenazine (generic)

ingrezza (brand)

Valbenazine warnings

qt prolongation, smonolence. Pgp inhibitor; increase digoxin concentrations. avoid with MAOi

Deutrabenazine (generic)

austedo (brand)

Deutrabenazine ci

hepatic impairement; co adminstration with tetravenazine or valbenazine; MAOi within 14 days