Antipsychotics
Key Points
- Antipsychotics block dopamine (D2) receptors; first-generation agents are effective for positive symptoms, second-generation agents treat both positive and negative symptoms.
- First-generation (“typical”) antipsychotics carry the highest risk of extrapyramidal side effects (EPS) including tardive dyskinesia.
- Second-generation (“atypical”) antipsychotics have lower EPS risk but are associated with metabolic syndrome, weight gain, and hyperglycemia.
- Neuroleptic malignant syndrome (NMS) can occur with either generation and requires immediate medication discontinuation and emergency treatment.
- Agitation/hallucination improvement may appear within days, delusions usually improve over weeks, and full effect commonly requires about 1-2 months.
- Long-acting injectable antipsychotics can improve adherence with schedules ranging from twice monthly to every 6 months.
- In older adults with dementia-related psychosis, both first- and second-generation antipsychotics are linked to increased mortality risk.
Pathophysiology
Psychosis involves abnormal dopaminergic, serotonergic, and glutamatergic neurotransmission. Positive symptoms (hallucinations, delusions, disorganized speech) correlate with D2 receptor overactivity in the basal ganglia and limbic system. Negative symptoms (flat affect, avolition, social withdrawal) relate to dopamine underactivity in the prefrontal cortex.
Antipsychotics primarily act by blocking D2 receptors, reducing positive symptoms. Second-generation agents also block serotonin 5-HT2A receptors, contributing to improved negative symptom control and lower EPS risk. Early response timing varies: agitation and hallucinations may improve in days, while delusions often improve over weeks and full therapeutic effect may take up to 6 weeks.
Classification
| Generation | Examples | Key Features |
|---|---|---|
| First-generation (typical) | Haloperidol, chlorpromazine, fluphenazine | High D2 blockade; high EPS risk; effective for positive symptoms |
| Second-generation (atypical) | Risperidone, olanzapine, quetiapine, aripiprazole, clozapine | D2 + 5-HT2A blockade; lower EPS; metabolic risks |
Clinical selection often prioritizes second-generation options first for positive-symptom management (with clozapine usually reserved for treatment-resistant pathways due to neutropenia risk).
Nursing Assessment
NCLEX Focus
Monitor for extrapyramidal side effects, metabolic changes (weight, glucose, lipids), and QTc prolongation before and during therapy.
- Assess baseline vital signs, weight, BMI, fasting glucose, and lipid panel.
- Obtain baseline and ongoing monitoring data as ordered: ECG (PR/QTc context), CBC, electrolytes, liver/renal function, thyroid panel, and glucose/lipid trends.
- Assess current medications for QTc-prolonging drugs or anticholinergic burden.
- For haloperidol specifically, screen for Parkinson disease or Lewy-body dementia history before administration due to high sensitivity to dopamine blockade.
- Screen for personal or family history of diabetes, cardiac arrhythmias, or metabolic disease.
- Assess for hyperprolactinemia effects (for example galactorrhea, gynecomastia, sexual dysfunction, menstrual changes).
- Assess involuntary movements using the Abnormal Involuntary Movement Scale (AIMS) at baseline.
- Clozapine requires baseline ANC (absolute neutrophil count) and enrollment in REMS program.
Nursing Interventions
- Administer with food to reduce GI upset; monitor for orthostatic hypotension especially with initiation.
- Teach patients not to abruptly discontinue — taper under provider supervision.
- Monitor and report common class effects: dry mouth, constipation, blurred vision, urinary retention, drowsiness, dizziness, restlessness, weight gain, nausea/vomiting, and low blood pressure.
- For sedation burden, coordinate dose timing with provider and apply fall-risk precautions early.
- Teach clients to contact the prescriber promptly for involuntary or uncontrollable movements.
- Reinforce that abrupt discontinuation can trigger withdrawal symptoms, including dizziness, nausea/vomiting, and uncontrolled mouth/tongue/jaw movements.
- Teach clients to avoid alcohol and other CNS depressants unless specifically cleared, because combined sedation can worsen psychomotor impairment and safety risk.
- In inpatient clozapine pathways, monitor bowel status closely (including bowel sounds) because severe constipation can progress to intestinal ischemia/necrotizing colitis.
- For highly suspicious/paranoid clients, open medications in front of the client and explain each step to reduce mistrust and improve administration cooperation.
- Monitor for signs of neuroleptic malignant syndrome (NMS): hyperthermia, severe rigidity, confusion/agitation, and autonomic instability. Watch for associated lab abnormalities (elevated WBC, creatine phosphokinase, liver enzymes, and myoglobinuria with possible acute kidney injury). Stop antipsychotic therapy and escalate immediately if suspected.
- In suspected NMS, anticipate treatment plans including dantrolene and bromocriptine plus hydration, cooling, and electrolyte monitoring.
- If lithium is co-administered, monitor closely for neurotoxicity cues (weakness, lethargy, fever, tremor, confusion, worsening EPS) and escalate immediately.
- Clozapine: monitor weekly ANC for first 6 months due to agranulocytosis risk (ANC <1500/mm³ → hold drug).
- Consider long-acting injectable options for adherence barriers (for example twice-monthly, monthly, every 3 months, or every 6 months formulations by agent).
- In clozapine pathways, coordinate ANC monitoring under REMS requirements and escalate fever/infection signs immediately.
- Reinforce class-specific teaching such as sun protection/photosensitivity precautions and annual eye follow-up when glaucoma risk or anticholinergic burden is present.
Extrapyramidal Side Effects (EPS)
- Akathisia: motor restlessness, inability to sit still — can be mistaken for agitation
- Dystonia: involuntary muscle contractions (neck, jaw, eyes, or larynx) — acute laryngeal dystonia is an airway emergency
- Pseudoparkinsonism: tremor, rigidity, bradykinesia — requires dose reduction or anticholinergic
- Tardive dyskinesia: repetitive involuntary movements (tongue, face, limbs) — may be irreversible; more common with first-generation agents and long-term use
- Acute dystonia often improves within 10-30 minutes after parenteral diphenhydramine or benztropine.
Beers Criteria
Antipsychotics are potentially inappropriate in older adults with dementia — associated with increased risk of cognitive decline and death.
Anticholinergic Burden Risk
First-generation pathways can worsen urinary and bowel retention and increase intraocular pressure; use extra caution in BPH, mechanical or neurologic GI/GU obstruction, and angle-closure glaucoma contexts.
Boxed Warning
Older adults with dementia-related psychosis treated with antipsychotics have increased mortality risk. Monitor closely for cardiovascular events and infections (including pneumonia) in this population.
Pharmacology
| Drug Class | Examples | Key Nursing Considerations |
|---|---|---|
| First-gen antipsychotics | Haloperidol, fluphenazine, chlorpromazine | High EPS/TD risk; monitor AIMS; treat acute dystonia with diphenhydramine or benztropine |
| Second-gen antipsychotics | Olanzapine, quetiapine, risperidone, aripiprazole, lurasidone | Monitor weight, fasting glucose, lipids quarterly; less EPS but more metabolic risk; lurasidone absorption increases with food. |
| clozapine | Clozapine | Reserved for treatment-resistant schizophrenia; weekly ANC monitoring; agranulocytosis risk |
| VMAT2 inhibitors for TD | Deutetrabenazine, valbenazine | First-line pharmacologic options for persistent tardive dyskinesia after antipsychotic reassessment |
Aripiprazole-specific safety context includes rare compulsive-behavior patterns (for example gambling, binge eating, compulsive shopping, or hypersexual behavior), which should be screened and escalated promptly.
Clinical Judgment Application
Clinical Scenario
A patient on haloperidol for schizophrenia develops neck stiffness, upward deviation of the eyes, and jaw rigidity.
- Recognize Cues: Acute dystonia — a first-generation antipsychotic EPS.
- Analyze Cues: Sudden-onset EPS following antipsychotic administration.
- Prioritize Hypotheses: Acute dystonia requiring immediate treatment.
- Generate Solutions: Administer IM diphenhydramine or benztropine as ordered; notify provider.
- Take Action: Implement PRN order; reassess in 20–30 minutes.
- Evaluate Outcomes: Muscle spasm resolves; consider switching to lower EPS-risk agent.
Related Concepts
- psychopharmacology - Psychiatric medication overview across drug classes.
- psychotropic-medications - Broad psychiatric drug class framework.
- antidepressants - Concurrent use for schizoaffective disorder.
- metabolic-syndrome-and-adult-chronic-disease-risk - Major long-term risk with second-generation antipsychotics.
- sedatives - Additive CNS depression risk with concurrent use.
Self-Check
- What is the difference between first-generation and second-generation antipsychotics in terms of receptor action and side effect profiles?
- What are the four types of extrapyramidal side effects, and which is potentially irreversible?
- What baseline and ongoing monitoring parameters are required for patients taking antipsychotics?