Antipsychotics (Schizophrenia & Psychosis) 3/13

Do men and women have the same prevalence of schizophrenia, and how does the onset differ?

equally affected

women late 20s

men early 20s

What theory explains the later onset of schizophrenia in women?

The neuroprotective effect of estrogen.

What is the minimum duration of symptoms required for a schizophrenia diagnosis, and how much of that must be active symptoms?

6 months sx, 1 month active

hallucinations, delusions, or disorganized speech.

What must be ruled out before diagnosing schizophrenia?

Drug abuse → psychotic symptoms.

Which neurotransmitter is primarily associated with drug-induced psychosis in the mesolimbic area?

Dopamine

How do typical antipsychotics help with positive symptoms of schizophrenia?

By blocking D2 receptors.

What is a common downside of D2 blockade in the mesocortical region?

It can worsen negative sx alogia, avolition, and social withdrawal.

What dual receptor blockade characterizes atypical antipsychotics?

Blockade of both 5-HT2A and D2 receptors.

How do atypical antipsychotics differ in treating symptoms compared to typical antipsychotics?

less effective solely for positive symptoms but help alleviate both positive and negative symptoms while reducing EPSE and hyperprolactinemia.

What are the four dopamine pathways in the brain?

Nigrostriatal, Mesolimbic, Mesocortical, and Tuberoinfundibular.

What side effects can result from D2 blockade in the nigrostriatal pathway?

EPSE = dystonia, akathisia, and pseudo-Parkinsonism.

What is the desired effect of D2 blockade in the mesolimbic pathway?

lower dopamine, diminishing positive symptoms like hallucinations and delusions.

What effect does D2 blockade in the mesocortical pathway have?

cognitive impairment and worsen negative symptoms.

What is the role of the tuberoinfundibular pathway, and what happens if dopamine is blocked here?

prolactin release;

blockade dop →hyperprolactinemia.

How does blocking 5-HT2A receptors affect dopamine activity?

It increases dopamine levels in the mesocortical, nigrostriatal, and tuberoinfundibular regions, which helps reduce EPSE, negative symptoms, and hyperprolactinemia.

Which two atypical antipsychotics are most associated with EPSE and hyperprolactinemia?

Risperidone and Paliperidone.

Which three atypical antipsychotics have the highest risk for metabolic syndrome?

Clozapine, Olanzapine, and Quetiapine.

Give an example of an atypical antipsychotic with a long-acting injectable (LAI) formulation and its dosing interval.

Invega Sustenna is administered monthly.

Name a long-acting injectable formulation for typical antipsychotics.

Haldol Decanoate is given monthly

Prolixin Decanoate is administered every 2 weeks.

Why can antiemetic agents like promethazine cause EPSE?

They act as D2 blockers, which can lead to extrapyramidal side effects

What is the most dangerous dystonic reaction from long-term antipsychotic use, and what is the recommended immediate treatment?

Laryngospasm; treatment IV Benztropine or Diphenhydramine

What characterizes antipsychotic-induced akathisia?

An inner restlessness

uncontrollable urge to move

What is the treatment of choice for akathisia?

Propranolol

What are the main symptoms of antipsychotic-induced pseudoparkinsonism?

Akinesia (slowed movement),

mask-like face, resting tremor, stooped posture, drooling, and rigidity.

How is pseudoparkinsonism commonly managed?

Amantadine.

What is tardive dyskinesia (TD)?

repetitive, involuntary movements of the face, jaw, or extremities

due to long-term D2 receptor blockade.

What is the proposed mechanism behind tardive dyskinesia?

Hypersensitivity of D2 receptors following long-term antipsychotic use.

What are the FDA-approved treatments for tardive dyskinesia?

Ingrezza (Valbenazine)

Austedo (Deutetrabenazine)

What are the key clinical features of Neuroleptic Malignant Syndrome (NMS)?

Body rigidity, altered consciousness, unstable blood pressure and heart rate, fever, and diaphoresis.

How should Neuroleptic Malignant Syndrome be managed?

Stop dopamine antagonists ,

(cooling, fluids), dopamine agonists (e.g., bromocriptine) and muscle relaxants (e.g., dantrolene).

How does cigarette smoking affect the pharmacokinetics of Clozapine and Olanzapine?

induces CYP1A2 metabolism, reducing plasma levels and potentially necessitating higher doses.

What is included in the boxed warning (BBW) for Clozapine?

Agranulocytosis, severe hypotension, syncope, seizures, myocarditis, cardiomyopathy, and increased risk of death in elderly patients with dementia-related psychosis.

What is agranulocytosis, and how should ANC be monitored in patients on Clozapine?

A severe reduction in white blood cells (granulocytes); monitor weekly for the first 6 months, every other week for months 6–12, then monthly.

Which antibiotics should be used with caution in patients taking Clozapine or Olanzapine, and why?

Fluoroquinolones (e.g., Ciprofloxacin)

inhibition of CYP1A2, which can increase antipsychotic levels.

Which atypical antipsychotics should be taken with food to increase bioavailability?

Ziprasidone (Geodon) and Lurasidone (Latuda)

What is incorrect about administering Saphris 5 mg BID, and what is the proper method?

Saphris is meant to be taken sublingually, not orally.

Why might a patient experience severe dizziness when started on Seroquel 100 mg BID?

Seroquel is a potent alpha-1 blocker;

high dose can lead to significant orthostatic hypotension and dizziness.

What is the boxed warning for antipsychotic use in elderly patients with dementia-related psychosis?

There is a 1.6–1.7× increased risk of death, mainly from cardiovascular events such as stroke and myocardial infarction.

What is the FDA-approved treatment for Parkinson’s psychosis?

Pimavanserin (Nuplazid); clozapine and quetiapine are used off-label.

How do typical and atypical antipsychotics compare regarding efficacy and side effects?

Typical more effective for psychosis but have higher rates of EPSE

atypical reduce EPSE risk but may increase the risk for metabolic syndrome.

Which long-acting injectable atypical antipsychotic is associated with post-injection delirium/sedation syndrome?

Zyprexa Relprevv (Olanzapine)

What is the term for the side effect of hyperprolactinemia that causes breast enlargement in males?

Gynecomastia.

What is the most common extrapyramidal side effect seen with Aripiprazole, and how common is it?

Akathisia, occurring in approximately 10% of patients.

How does valproic acid interact with paliperidone?

Valproic acid inhibits glucuronidation, increasing paliperidone concentrations by about 50%.

Which two antipsychotics are FDA-approved for monotherapy in bipolar depression?

Latuda (Lurasidone) and Seroquel (Quetiapine).

Which antipsychotic is used off-label at low doses for insomnia?

Quetiapine (Seroquel).

What are the dosing ranges for Vraylar (Cariprazine) in schizophrenia and bipolar disorders?

For schizophrenia: 1.5–6 mg; for bipolar depression: 1.5–3 mg; for bipolar mania: 3–6 mg.

What role does samidorphan play when combined with olanzapine?

It acts as a mu-opioid antagonist to help reduce olanzapine-associated weight gain.