NAPLEX 2026 - Schizophrenia/Psychosis

What are the hallmark symptoms of schizophrenia?

Hallucinations

Delusions

Disorganized speech/behavior

What's included in the DSM-5 diagnostic criteria for schizophrenia?

Note: delusions, hallucinations, or disorganized speech must be present

Negative S/Sx:

- loss of interest in everyday activities

- lack of emotion (apathy)

- inability to plan or carry out activities

- poor hygiene

- social withdrawal

- loss of motivation (avolition)

- lack of speech (alogia)

Positive S/Sx:

- hallucinations

- delusions

- disorganized speech/behavior

- difficulty paying attention

What neurotransmitters are primary involved in schizophrenia?

Dopamine

5-HT

Glutamine

What medications/substances can cause psychotic symptoms?

Anticholinergics (centrally-acting, increased doses)

Dextromethorphan

DA or DA agonists (ropinirole, pramipexole, Sinemet)

Efavirenz

Interferons

Ketamine

Levetiracetam

Quinolones

Stimulants

Systemic steroids

Illicit substances: cannabis, cocaine, LSD, PCP, bath salts

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• Angry = Anticholinergics

• Dragon = Dextromethorphan

• Dancing = Dopamine agonists

• Every = Efavirenz

• Inch = Interferons

• Kicking = Ketamine

• Little = Levetiracetam

• Quiet = Quinolones

• Students = Stimulants

• Silly = Steroids

What are the EPS and when do they occur?

EPS - a group of side effects related to irregular movements that can be caused by antipsychotic

Akathisia - occurs within days to weeks

- restlessness with anxiety and inability to remain still

- treated with benzos or propranolol

Dystonia - occurs within 24-96 hours

- prolonged contraction of muscles, including painful muscle spasms; life threatening if airway is compromised; higher risk in young males

- centrally-acting anticholinergics (benztropine, diphenhydramine) can be used for prophylaxis or treatment

Parkinsonism - occurs within days to weeks

- looks similar to Parkinson Disease, with tremors, abnormal gait, and bradykinesia

- treated with anticholinergics; amantadine can be used as an alternative

Tardive dyskinesia (TD) - occurs within months to years

Formulations

Long-acting injections

ODT

Oral Solutions/Suspensions

Acute IM injections

• IM antipsychotics can be mixed with other drugs such as a benzodiazepine for anxiolytic/sedative effects and an antipsychotic to reduce dystonia (haloperidol, lorazepam, diphenhydramine)

• IM Olanzapine and a parenteral benzodiazepine should not be given together due to risk of excessive sedation and difficulty breathing.

Boxed warnings associated with all antipsychotics

Increased risk of mortality in older adults with dementia-related psychosis

• due to cardiovascular conditions (HF, sudden death) and infection

Other warnings for antipsychotic

Several antipsych also carry warning for an increased risk of stroke in patients with dementia

All antipsych carry a warning for falls

FGAs: MOA

Block dopamine-2 (D2) receptors, with little serotonin receptor blockade

Many are in the phenothiazine class and names end with -azine (i.e thioridazine, fluphenthiazine)

- except haloperidol: class: butryophenone

• and thiothixene

• and loxapine

FGAs: drugs

Low potency:

- chlorpromazine

- thioridazine

Mid potency:

- loxapine

- perphenazine

High potency:

- haloperidol

- fluphenazine

- thiothixene

- trifluoperazine

FGAs: boxed warnings and warnings

BWs:

- elderly with dementia-related psychosis: increased risk of death

- thioridazine (low potency): QT prolongation

• Loxapine (mid potency): bronchospasm (REMS)

Warnings:

- CV effects: QT prolongation (increased risk with parenteral administration and with thiodazine, haloperidol, and chlorpromazine), orthostasis/falls

- anticholinergic effects (constipation, xerostomia, blurry vision, urinary retention)

- EPS: increase risk with injectables

- CNS depression

- hyperprolactine mia

- Neuroleptic malignant syndrome (NMS)

FGAs: side effects

Sedation

Dizziness

Anticholinergic effects

Increased prolactin

EPS

All FGAs cause sedation and EPS but LOWER POTENCY have _____sedation and _____ EPS while HIGHER Potency have ____ sedation and ____ EPS

Lower Potency: inc, dec

Higher Potency: dec, inc

SGAs: MOA

AKA atypical antipsychotics

Block dopamine (D2) and serotonin (5-HT2A) receptors

(ABC) Aripiprazole, brexipiprazole and cariprazine are D2 and 5-HT1A partial agonists

Brexipiprazole also a 5-HT2A antagonist

SGAs: drugs

Aripiprazole (Abilify)

Clozapine (Clozaril)

Lurasidone (Latuda)

Olanzapine (Zyprexa)

Paliperidone (Invega)

Quetiapine (Seroquel)

Risperidone (Risperdal)

Ziprasidone (Geodon)

Asenapine

Cariprazine (Vraylar)

Brexipiprazole (Rexulti)

Iloperidone (Fanapt)

Lumateperone (Caplyta)

Aripiprazole: side effects

Akathisia

Activating

Clozapine: boxed warnings, side effects, monitoring

Use reserved for treatment-resistant schizophrenia (resistance to >/= 2 other antipsychotics

BWs:

- significant risk of potentially life-threatening neutropenia/agranulocytosis

- myocarditis and cardiomyopathy

- seizures

SEs:

- agranulocytosis, seizures, constipation, metabolic syndrome (increased weight), QT prolongation sialorrhea (increased salivation)

Monitoring:

- to start, baseline ANC must be >/= 1500/mm3 → Checked weekly x 6 months then every 2 weeks for 6 months, then monthly

- stop if ANC < 1000

- REMS no longer required

NOTES:

Titrate slowly to decrease the risk of seizures and cardiovascular effects

Lurasidone CI

Use with strong CYP3A4 inhibitors and inducers

Lurasidone: side effects

Somnolence

EPS (dystonia)

Nausea

Decreased risk of metabolic syndrome

NOTE: Take with food ≥ 350 kcal - helps with absorption

Think LURA needs light meal, ZIP needs heavy meal

Olanzapine: boxed warnings and side effects

BW:

- Zyprexa Relprevv: sedation and delirium following injection, must be administered in healthcare facility and monitored for 3 hours post injection (REMS) and monitor for 3 hours post-infection (REMS program requirements)

SEs:

- somnolence

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

Paliperidone: side effects

Increased prolactin (sexual dysfunction, galactorrhea, oligomenorrhea/amenorrhea)

EPS, especially at higher doses

Metabolic syndrome (increased weight, BG, lipids)

Quetiapine: side effects

Somnolence

Metabolic syndrome (increased weight, BG, lipids)

Low EPS risk - often used for psychosis in Parkinson’s Disease

Take XR at night, without food or with a light meal ≤ 300 kcal

Risperidone: side effects

Increased prolactin

EPS, especially at higher doses

Metabolic syndrome (increased weight, BG, lipids)

Ziprasidone: contraindications

QT prolongation - do not use with QT risk

Note: taken with food

Asenapine: side effects

Tongue numbness (SL tabs)

Note: no food/drink for 10 minutes after dose

What drugs should be avoided if cardiac risk/QT prolongation risk?

Ziprasidone

Haloperidol

Thioridazine

Chlorpromazine

What drugs should be avoided if history of a movement disorder (e.g., PD)? What's preferred?

Avoid drugs with high risk of EPS

- FGAs

- Risperidone, Paliperidone (at higher doses)

Preferred: quetiapine

What drugs should be avoided if overweight/metabolic risk (e.g., high TG)? Which have lower risk?

Avoid clozapine or olanzapine — if these must be used, consider initiation of metformin

- also risk with risperidone, Paliperidone, and quetiapine

Lower risk: aripiprazole, ziprasidone, lurasidone, and asenapine

What treatment should be considered for patients with nonadherence or unhoused patients?

Long-acting injections

What are the long acting injections and their dosing intervals?

IM: Paliperidone (Invega Hafyera)

- 6 months

IM: paliperiodone (Invega Trinza)

- 3 months

IM: aripiprazole (Abilify Asimtufii)

- 2 months

IM: aripiprazole (Aristada) & SC: Risperidone (Uzedy)

- 1 to 2 months

IM: aripiprazole (Abilify Maintena), haloperidol (Haldol Decanoate), paliperiodone (Invega Sustenna, Erzofri)

& SC: risperidone (Perseris)

- monthly

IM: olanzapine (Relprevv)

- 2 to 4 weeks

IM: fluphenazine decanoate, risperidone (Risperdal Consta, Rykindo)

- 2 weeks

What meds/formulations are used for STAT! treatment (acute psychosis and refusing PO meds)?

Haloperidol or olanzapine (IV/IM) +/- diphenhydramine and lorazepam

Alternative: Ziprasidone IM

What meds/formulations are used for chronic treatment if adherent to daily PO treatment?

FGA or SGA oral tablets or other formulations

Failure with 2 or more antipsychotics:

- clozapine tablet

- Versacloz suspension

What meds/formulations are used for chronic treatment if not adherent to daily PO treatment or swallowing difficulties?

Long-acting injectables

ODT:

- aripiprazole (Abilify)

- olanzapine (Zyprexa Zydis)

- risperidone

Sublingual:

- asenapine (Saphris)

Oral liquids:

- aripiprazole (Abilify)

- fluphenazine

- haloperidol

- risperidone (Risperdal)

Patch:

- asenapine (Secuado)

Failure with 2 or more antipsychotics:

- clozapine (Clozaril) tablet

- Versacloz suspension

What drugs are used for psychosis in Parkinson Disease?

Quetiapine

Pimavanserin (atypical antipsychotic approved only for psychosis in PDh

- antagonist only at serotonin receptors (5-HT2A and 5-HT2C)

- no effect in dopamine receptors and does not worsen motor symptoms of PD

What is tardive dyskinesia (TD)?

Complication that can occur with dopamine blockade

Can cause irreversible symptoms that include uncontrollable movements in the tongue, face, trunk, and extremities

- can interfere with walking, talking, and breathing

What drugs are used for treatment of TD? MOA? Warnings? CIs?

Valbenazine (Ingrezza)

- warning: somnolence'

• P-gp inhibitor and can increase digoxin

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Deutetrabenazine (Austedo)

- warning: somnolence

- CI: hepatic impairment

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MOA: reversibly inhibits VMAT2, a transporter that regulates monoamine uptake from the cytoplasm

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Will require Dose reduction with CYP2D6 inhibitors or CYP2D6 poor metabolizers

Avoid with MAOI

What is neuroleptic malignant syndrome (NMS)?

Rare but highly lethal - medical emergency

Most commonly occurs with FGAs and is due to D2 blockade

Intense muscle contractions can lead to acute renal injury (due to rhabdo), suffocation, and death

What are the signs, lab values, and treatment for NMS?

Signs:

- hyperthermia (high fever, profuse sweating)

- extreme muscle rigidity (can lead to respiratory failure aka “lead pipe” rigidity

- mental status changes

- tachycardia, tachypnea, and BP changes

Lab values:

- increased creatine phosphokinase

- increased WBCs

Treatment:

- stop the antipsychotic and provide supportive care

- control patients temperature: cooling bed, antipyretics, cooled IV fluids

- relax the muscles: benzodiazepines, dantrolene

- after resolution of symptoms, consider a different antipsychotic (i.e. quetiapine, clozapine)