Antipsychotics

Psychotic Disorders

Disorders characterized by impaired perception of reality. Antipsychotics are used to reduce psychotic symptoms and prevent relapse.

Therapeutic Uses of Antipsychotics

Schizophrenia • Delusional disorders • Bipolar disorder • Depressive psychoses • Drug-induced psychoses • Tourette syndrome • Suppression of emesis (antiemetic).

Black Box Warning for Antipsychotics

Do NOT use to treat dementia in older adults due to increased mortality risk.

Primary Indication for Antipsychotics

Schizophrenia.

Schizophrenia

A chronic psychiatric disorder characterized by disordered thinking, impaired perception of reality, and difficulty interpreting surroundings.

Three Symptom Categories of Schizophrenia

Positive symptoms • Negative symptoms • Cognitive symptoms.

Positive Symptoms

Things that should NOT be present: hallucinations, delusions, agitation, tension, paranoia.

Negative Symptoms

Loss of normal function: lack of motivation, poverty of speech, blunted affect, poor self-care, social withdrawal.

Cognitive Symptoms

Disorganized thinking, poor concentration, reduced attention span, learning difficulties, and memory impairment.

Clinical Presentation of Schizophrenia

Acute episodes commonly involve hallucinations and delusions. Residual symptoms include suspiciousness, poor insight, decreased judgment, and reduced motivation.

Disease Course of Schizophrenia

Chronic disease with acute exacerbations, partial remissions, and recurrent episodes throughout life.

Possible Causes of Schizophrenia

Genetics, perinatal influences, neurodevelopmental abnormalities, neuroanatomic abnormalities, excess dopamine activity, and decreased glutamate activity.

First-Generation Antipsychotics (FGAs)

Older antipsychotics that are inexpensive and effective for positive symptoms but have a higher risk of extrapyramidal symptoms (EPS).

Low-Potency FGA

Prototype: Chlorpromazine (Thorazine). Higher risk of sedation, orthostatic hypotension, and anticholinergic effects. Lower risk of EPS.

High-Potency FGA

Prototype: Haloperidol (Haldol). Higher risk of EPS. Lower risk of sedation and anticholinergic effects.

Mechanism of Action of FGAs

Block dopamine, acetylcholine, histamine, and norepinephrine receptors. Therapeutic effect primarily results from D₂ receptor blockade in the mesolimbic pathway.

FGAs Are Most Effective For

Positive symptoms of schizophrenia.

Extrapyramidal Symptoms (EPS)

Caused by dopamine blockade and may occur early or after long-term therapy.

Acute Dystonia

Onset: Hours–5 days. Muscle spasms of the face, tongue, neck, back, or eyes. Laryngeal dystonia is a medical emergency. Treat with benztropine or diphenhydramine.

Parkinsonism

Onset: 5–30 days. Tremor, rigidity, bradykinesia, shuffling gait, drooling, stooped posture, cogwheel rigidity. Treat by switching to an SGA or using benztropine, diphenhydramine, or amantadine. Never use levodopa.

Akathisia

Onset: 5–60 days. Inability to sit still, pacing, squirming, internal restlessness. Treat by lowering the dose, switching drugs, beta blockers, benzodiazepines, or anticholinergics.

Tardive Dyskinesia

Onset: Months to years. Often irreversible. Lip smacking, tongue protrusion, twisting tongue movements, involuntary facial and limb movements. Treat by reducing dose or switching to an SGA.

Neuroleptic Malignant Syndrome (NMS)

Medical emergency characterized by lead-pipe rigidity, high fever, profuse sweating, dysrhythmias, and unstable blood pressure. Treat by stopping the medication and administering dantrolene.

Anticholinergic Effects of FGAs

Dry mouth, constipation, urinary retention, blurred vision ("Can't see, can't spit, can't pee, can't shit").

Orthostatic Hypotension

Caused by alpha-1 blockade. Most common with low-potency FGAs.

Sedation

Caused by histamine blockade.

Other Adverse Effects of FGAs

Lower seizure threshold, sexual dysfunction, elevated prolactin, galactorrhea, gynecomastia, prolonged QT interval.

Toxicity of Antipsychotics

Overdose deaths are uncommon. Symptoms include hypertension, CNS depression, and EPS. Treat with IV fluids, alpha-adrenergic agonists, and gastric lavage. Emetics are ineffective.

Second-Generation Antipsychotics (SGAs)

Block dopamine and serotonin receptors. Better tolerated with fewer EPS but greater metabolic side effects.

Examples of SGAs

Clozapine (Clozaril), Risperidone (Risperdal), Olanzapine (Zyprexa), Quetiapine (Seroquel), Aripiprazole (Abilify).

Advantages of SGAs

Fewer extrapyramidal symptoms and generally better tolerated than FGAs.

Major Adverse Effects of SGAs

Agranulocytosis, metabolic syndrome, weight gain, diabetes, dyslipidemia, seizures, and fewer—but possible—EPS.

Agranulocytosis

Life-threatening decrease in neutrophils. Watch for fever, sore throat, and infection. Notify provider immediately and obtain CBC.

Clozapine

Most effective antipsychotic but carries the highest risk for agranulocytosis, weight gain, diabetes, dyslipidemia, and seizures. Monitor CBC and ANC.

FGA vs SGA Comparison

FGAs: More EPS, fewer metabolic effects, less expensive, better for positive symptoms. SGAs: Less EPS, more metabolic syndrome, more expensive, better tolerated overall.

Nursing Considerations

Promote medication adherence, teach not to stop abruptly, explain that side effects are manageable and medications are not addictive, encourage family supervision, and consider long-acting IM depot injections.

Nonpharmacologic Therapy

Counseling, family therapy, behavioral therapy, and vocational rehabilitation.

⭐ NCLEX Must Know

Black Box:

No antipsychotics for dementia

Haldol = High-potency = High EPS

Thorazine = Low-potency = Low EPS but more sedation & anticholinergic effects

Acute dystonia = Benztropine/Diphenhydramine

Parkinsonism = Never use levodopa

Akathisia = Can't sit still

Tardive dyskinesia = Often irreversible

NMS = Stop drug + Dantrolene

Clozapine = Agranulocytosis → Monitor CBC/ANC.