UWORLD Chapter 63: Schizophrenia/Psychosis

What is schizophrenia?

A chronic, severe, and disabling thought disorder that affects all societies.

What are the hallmark symptoms of schizophrenia?

Hallucinations, delusions, and disorganized speech/behavior.

What is a hallucination?

Sensing something that is not present, such as imaginary voices.

What is a delusion?

A belief about something real that is not true, such as believing one's family wishes to harm them.

What is disorganized speech or behavior in schizophrenia?

inability to focus attention and communicate organized thoughts

What are negative symptoms of schizophrenia?

Loss of interest in activities, lack of emotion, inability to plan or carry out activities, poor hygiene, social withdrawal, loss of motivation (avolition), and lack of speech (alogia).

What are positive symptoms of schizophrenia?

Hallucinations (auditory, visual, or somatic), delusions, disorganized speech/behavior (incoherent speech, often on unrelated topics, purposeless behavior, or difficulty speaking and organizing thoughts, such as stopping in mid-sentence or jumbling together meaningless words), and difficulty paying attention.

What is the typical age of onset for schizophrenia symptoms?

Young adulthood.

What is the DSM-5?

The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, which sets the diagnostic criteria for psychiatric conditions.

What factors contribute to the pathophysiology of schizophrenia?

Altered brain structure and chemistry, particularly involving dopamine, serotonin, and glutamine, along with genetics and environmental factors.

What medications can cause psychotic symptoms?

Anticholinergics, dopamine agonists, stimulants, efavirenz, Interferons, Ketamine, Levetiracetam, Quinolones, Systemic steroids (especially with high doses)

What recreational drugs can cause psychotic symptoms?

Cannabis, Cocaine, LSD, Methamphetamine, Phencyclidine (PCP), Synthetic cathinones (bath salts, MDPV)

What is the first-line treatment for schizophrenia?

Antipsychotics, which primarily block dopamine receptors.

What are extrapyramidal side effects (EPS)?

A group of side effects related to irregular movements caused by antipsychotics.

What is akathisia? When does it occur in relation to antipsychotic initiation?

Restlessness with anxiety and an inability to remain still, occurs within days to weeks of initiation

How is akathisia treated?

treated with benzodiazepines or propranolol.

What is dystonia?

Prolonged contraction of muscles, including painful muscle spasms; which can be life-threatening if it compromises the airway.

Who is at most risk for dystonias? When do they occur after initiation of antipsychotics?

young males; 24-96 hours

What are the treatments for dystonias?

Centrally acting anticholinergics (diphenhydramine, benztropine) can be used for prophylaxis and treatment

What is pseudoparkinsonism with antipsychotics? What are treatments for it?

- Looks similar to parkinson disease, with tremors, abnormal gait and bradykinesia which occurs within days to weeks of starting an antipsychotic

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

What is tardive dyskinesia (TD)?

A movement disorder that occurs months to years after starting antipsychotic treatment.

What are long-acting injections in schizophrenia treatment?

Injections that eliminate daily oral dosing to improve adherence.

What is the risk associated with antipsychotics in elderly patients with dementia-related psychosis?

Increased risk of mortality due to cardiovascular conditions and infections.

What are first-generation antipsychotics (FGAs)?

Antipsychotics that primarily block dopamine-2 (D2) receptors with little serotonin receptor blockade.

Name a low potency first-generation antipsychotic.

Chlorpromazine.

What is the mechanism of action for second-generation antipsychotics (SGAs)?

They block both serotonin and dopamine receptors.

What is the significance of adherence to antipsychotic treatment?

Poor adherence is primarily due to a lack of insight into the illness.

What are orally disintegrating tablets (ODTs) used for?

They are useful for patients with dysphagia and help prevent cheeking.

Why should IM olanzapine and a parenteral benzodiazepine not be given together?

due to risk of excessive sedation and difficulty breathing

What is the role of acute IM injections in schizophrenia?

They provide immediate relief for agitated, psychotic patients.

What should be done if extrapyramidal side effects occur?

Adjust the antipsychotic regimen, such as lowering the dose or switching medications.

What is a significant risk associated with Thioridazine?

QT prolongation

What serious condition can Adasuve cause?

Bronchospasm (REMS program)

List some cardiovascular effects of antipsychotics.

QT prolongation, orthostasis/falls, tachycardia

What are common anticholinergic effects of first generation antipsychotics?

Constipation, xerostomia, blurred vision, urinary retention

What are extrapyramidal symptoms (EPS)?

Movement disorders caused by antipsychotics, risk increases with injectable formulations.

What is hyperprolactinemia and its effects?

Increased prolactin levels causing infertility, oligomenorrhea/amenorrhea, galactorrhea, erectile dysfunction.

What is Neuroleptic Malignant Syndrome (NMS)?

A life-threatening reaction to antipsychotics characterized by muscle rigidity, fever, and autonomic instability.

What are common side effects of first generation antipsychotics?

Sedation, dizziness, anticholinergic effects, increased prolactin, EPS, CNS depression

What FGAs have an increased risk of QT prolongation?

increased risk with parenteral administration and thioridazine, haloperidol, and chlorpromazine

What is the difference in side effect profiles of low potency FGAs vs high potency FGAs?

- lower potency: increased sedation but lower risk of EPS

- Higher potency: decreased sedation and higher risk of EPS

What are the low potency FGAs?

Chlorpromazine, thioridazine

What are the mid potency FGAs?

loxapine, perphenazine

What are the high potency FGAs?

haloperidol, fluphenazine, trifluoperazine, thiothixene

What drug class is haloperidol in besides FGAs?

butyrophenone

What is the brand name of aripiprazole and what dosage forms does it come in?

Abilify

Tablet, ODT, oral film, oral solution, IM prefilled syringe

What are the main side effects of aripiprazole?

Akathisia, activating, lower risk of weight gain

What is Clozapine used for?

Treatment-resistant schizophrenia (resistance to 2 or more other antipsychotics)

What is the brand name of clozapine?

Clozaril

What are the boxed warnings for clozapine?

severe neutropenia/agranulocytosis; orthostatic hypotension, syncope, bradycardia; cardiac arrest; myocarditis, cardiomyopathy; Seizures

What are side effects of clozapine?

Weight gain, hyper salivation, myocarditis, QT prolongation, agranulocytosis, constipation

What are the unique instructions of administration for Lurasidone?

take with at least 350 calories of food

What are side effects of lurasidone?

somnolence, EPS (dystonias), nausea, decreased risk of metabolic syndrome compared to other SGAs

What is the brand name of lurasidone?

Latuda

What is the brand name of olanzapine?

Zyprexa

What is the REMS program for Zyprexa Relprevv?

for sedation and delirium, must be administered in a healthcare facility and monitored for 3 hours post injection

What is the brand name of paliperidone?

Invega

How often is invega trinza given?

every 3 months

How often is invega hafyera given?

every 6 months

What are the main side effects of paliperidone?

- increased prolactin

- EPS, especially at higher doses

- Metabolic syndrome (increased weight, BG, and lipid levels)

What is the brand name of quetiapine?

Seroquel, Seroquel XR

What are unique administration instructions for Seroquel XR?

take at night, without food or with a light meal (300 cals max)

What are common side effects with quetiapine?

somnolence, metabolic syndrome, low risk of EPS (used often for psychosis in Parkinson's disease

What is the brand name of risperidone?

Risperdal, Risperdal Consta

What are the side effects of risperidone?

- increased prolactin

- EPS, especially with higher doses

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

What is the risk associated with Ziprasidone?

QT prolongation; don't use with QT risk

What is the brand name of ziprasidone?

Geodon, Geodon IM

What is unique about Asenapine's administration?

It is a sublingual tablet; no food/drink for 10 min after dose.

What is the main side effects with asenapine?

tongue numbness

What should be monitored when prescribing Clozapine? What is the frequency?

Absolute Neutrophil Count (ANC) due to risk of agranulocytosis.

- baseline ANC must be 1500 or more

- check ANC weekly for 6 months, then every 2 weeks for 6 months, then monthly thereafter

At what ANC should you stop clozapine?

less than 1000

What are the generic names of all the SGAs?

aripiprazole, clozapine, lurasidone, olanzapine, paliperidone, risperidone, quetiapine, ziprasidone, asenapine, cariprazine, brexpiprazole, iloperidone, lumateperone

What is the mechanism of SGAs?

AKA atypical antipsychotics; block dopamine (D2) and serotonin (5HT2A) receptors

What is the significance of the REMS program for Clozapine?

It was required due to the risk of agranulocytosis but is no longer necessary.

What is the effect of smoking on Clozapine levels?

Smoking reduces drug levels.

What are the side effects of Iloperidone?

EPS, dystonia, headache, insomnia.

What is the risk of metabolic syndrome associated with antipsychotics?

Increased weight, blood glucose, cholesterol, and triglycerides.

What is the dosing for Aripiprazole Maintena?

Monthly intramuscular injection.

What are the side effects of Olanzapine?

Somnolence, metabolic syndrome (increased weight, BG, and lipids), orthostasis, QT prolongation.

What are the common side effects of elevated prolactin levels?

Gynecomastia, galactorrhea, sexual dysfunction, oligomenorrhea/amenorrhea

Which antipsychotic has the highest efficacy but multiple boxed warnings?

Clozapine

What is the minimum duration for an adequate trial of an antipsychotic?

At least 6 weeks

What should be avoided in patients with a history of painful dystonia?

Drugs that caused poor tolerance in the past, such as haloperidol, other FGAs, risperidone, and paliperidone (at higher doses)

Which antipsychotics are associated with high cardiac risk/QT prolongation?

Ziprasidone, haloperidol, thioridazine, chlorpromazine

What is the preferred antipsychotic for patients with a history of movement disorders?

Quetiapine

Which drugs have a lower risk of metabolic side effects?

aripiprazole, ziprasidone, lurasidone, and asenapine

What should be considered for patients with metabolic risk when using certain antipsychotics?

Initiation of metformin

Which dosage forms of antipsychotics are preferred for nonadherent or unhoused patients?

long acting injectables

What are the medications given for acute psychosis patients that are refusing oral medications?

haloperidol or olanzapine (IV/IM) +/- diphenhydramine and lorazepam. alternative is ziprasidone IM

How often is abilify asimtufii IM given?

every 2 months

What long acting injectable antipsychotics are given every 1-2 months?

aripiprazole (Aristada) and risperidone (Uzedy)

What LAI antipsychotics are given monthly?

abilify maintena, haloperidol decoanate, paliperidone (invega sustenna, erzofri), risperidone (perseris)

How often is olanzapine Relprevv given?

every 2-4 weeks

What LAI antipsychotic are given every 2 weeks?

fluphenazine decoanate and risperidone (risperdal consta)

What antipsychotics come as ODTs?

aripiprazole, olanzapine, and risperidone

What antipsychotics come as sublingual?

Asenapine

What antipsychotics come as oral liquids?

aripiprazole, fluphenazine, haloperidol, risperidone

Which antipsychotics come as patches?

asenapine

Which antipsychotic is specifically approved for psychosis in Parkinson's disease?

Pimavanserin

What are the side effects of clozapine and olanzapine?

Hyperglycemia and weight gain