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.
- Therapeutic effects take 1–2 months; monitoring for EPS, metabolic changes, and QTc prolongation is essential.
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.
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 |
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.
- Assess current medications for QTc-prolonging drugs or anticholinergic burden.
- Screen for personal or family history of diabetes, cardiac arrhythmias, or metabolic disease.
- 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.
- 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.
- 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.
- Clozapine: monitor weekly ANC for first 6 months due to agranulocytosis risk (ANC <1500/mm³ → hold drug).
Extrapyramidal Side Effects (EPS)
- Akathisia: motor restlessness, inability to sit still — can be mistaken for agitation
- Dystonia: involuntary muscle contractions (neck, jaw, eyes) — acute, treatable with anticholinergics
- 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
Beers Criteria
Antipsychotics are potentially inappropriate in older adults with dementia — associated with increased risk of cognitive decline and death.
Pharmacology
| Drug Class | Examples | Key Nursing Considerations |
|---|---|---|
| First-gen antipsychotics | Haloperidol, fluphenazine, chlorpromazine | High EPS risk; monitor AIMS; treat acute dystonia with diphenhydramine or benztropine |
| Second-gen antipsychotics | Olanzapine, quetiapine, risperidone, aripiprazole | Monitor weight, fasting glucose, lipids quarterly; less EPS but more metabolic risk |
| clozapine | Clozapine | Reserved for treatment-resistant schizophrenia; weekly ANC monitoring; agranulocytosis risk |
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?