5.8 Antipsychotics V2
Antipsychotic drugs are used to treat drug-induced psychosis, schizophrenia, extreme mania, depression that is resistant to other therapy, and other CNS conditions. Antipsychotics used to be called tranquilizers because they produce a state of tranquility. First-generation antipsychotics, also called conventional antipsychotics, have similar mechanisms of action. An example of a conventional antipsychotic is haloperidol. Conventional antipsychotics have several potential adverse effects, and the selection of a medication is based on the client’s ability to tolerate the adverse effects.
Second-generation antipsychotics, also referred to as atypical antipsychotics, have the benefit of fewer adverse effects and are used for many neurological conditions such as depression, anxiety, and psychosis. There are many atypical antipsychotics used in Canada, including risperidone, clozapine, olanzapine, quetiapine and aripiprazole (McCuistion et al, 2018). Due to the limitations of this unit, we will focus only on three medications, haloperidol and two atypical meds, quetiapine and clozapine. Links to some useful resources are available at the end of this unit.
1st and 2nd Generation Antipsychotics
Mechanism of Action
All antipsychotics block dopamine receptors in the brain. First generation or conventional antipsychotics, such as haloperidol, are dopamine-2 receptor antagonists in certain areas of the CNS, such as the limbic system and the basal ganglia. These areas are associated with emotions, cognitive function, and motor function, and blockage thus produces a tranquilizing effect. They also have noradrenergic, cholinergic, and histaminergic blocking action. This class includes many meds including phenothiazines (prochlorperazine) and butyrophenones (haloperidol), among others (Chokhawala & Stevens,2023).
Second-generation, or atypical antipsychotics are serotonin-dopamine antagonists. They block specific dopamine 2 receptors and specific serotonin 2 receptors. There are 12 different medications in this class and they all work very similar. We will focus mostly on clozapine and aripirazole as our prototype meds, with a brief overview of quetiapine.
To learn more about the mechanism of action of antipsychotics, click on the link:
Neuroscientifically Challenged (2025). 2-minute Neuroscience: Antipsychotics.
Youtube: https://www.youtube.com/watch?v=RSJlCdOba7w
Indications for Use
Antipsychotics are primarily used to manage psychosis and to also treat acute agitation, bipolar mania, and other psychiatric conditions.
Conventional Antipsychotics
Conventional antipsychotics (first generation), such as haloperidol or chlorpromazine, both work similarly with the same antipsychotic effects. They are used to treat the positive symptoms of schizophrenia or other psychotic disorders (mania, agitation, acute psychosis).
The difference between both meds is potency (size of dose to produce a given response). Chlorpromazine is a low-potency drug whereas haloperidol is high-potency drug (small dose needed to produce desired effect). Where they differ mostly is in the side effects, which is based on the anticholinergic effects.
Low potency (Chlorpromazine) = high sedation + high Ach + low extrapyramidal effects.
High potency (haloperidol) = low sedation + low Ach + high extrapyramidal effects.
Atypical antipsychotics
Atypical antipsychotics (second generation or SGA) treat both the positive and negative symptoms of schizophrenia or other psychotic disorders. They are often used first as they treat a wider range of symptoms. Some atypical antipsychotics are also used as an adjunct therapy for depression or nausea. Due to the sedative effects, Quetiapine (Seroquel) is used for insomnia.
The benefit of SGAs is they have less extrapyramidal symptoms, leading to better adherence, but have other adverse effects that may be less desirable. These will be discussed in the adverse effects section (Burchum Rosenjack & Rosenthal, 2019; Halter, Pollard & Jacubec, 2019).
Positive Symptoms of Schizophrenia: hallucinations (auditory such as hearing voices, or command hallucinations such as telling them to hurt themselves) and delusions.
Negative Symptoms of Schizophrenia: withdrawn, guilty feelings, low energy, lack of motivation for activities or ADLs.
Nursing Considerations for Antipsychotics
Older adult: anticholinergic effects is a concern, due to risk of falls for dizziness or confusion. On Beers List for potentially inappropriate drugs for the older adult. If required, start at the lowest possible dose and titrate.
Elderly clients with dementia-related psychosis treated with antipsychotic drugs should be closely monitored for signs and symptoms of cardiovascular events or infections such as pneumonia.
Caution with concurrent use with other CNS medications. Avoid with other CNS depressants such as barbiturates, benzothiazines or opioids.
Clients who are concurrently taking lithium and antipsychotics should be monitored closely for neurotoxicity (weakness, lethargy, fever, tremulousness, confusion, and extrapyramidal symptoms) and symptoms should be immediately reported.
Specific nursing considerations for conventional: haloperidol and Atypical: clozapine:
Haloperidol
- Highly lipophilic, wide distribution, metabolized in the liver. Partially excreted in the kidney. Dosage reductions are not required if renal or hepatic disease.
- Oral, IM, IV, nasal spray. IM either short acting immediate release or depot preparation. Depending on the reason, can be given in different dosages and routes. For example, acute psychosis give 0.5-2 mg orally TID or 2-5 mg IM q 4-8 hours. 20mg /day is the maximum dosage.
- Oral (PO): Give with food, milk, or a full glass of water to minimize GI upset. Do not mix the concentrate with coffee or tea.
- Haloperidol is contraindicated in clients with Parkinson’s disease, Lewy Body dementia, or comatose clients due to the dopaminergic effects.
- Pretreatment:
- Assess mental health status prior to and throughout treatment
- ECG due to risk of QT prolongation
- Most common side effects: anticholinergic effects (dry mouth, weight gain, erectile dysfunction in males, oligomenorrhea or amenorrhea in females.
- Less common adverse effects: photosensitivity, pruritus, diarrhea, orthostatic hypotension
- Extrapyramidal adverse effects due to blockade of dopamine in the brain.
- Acute dystonia, akathisia, neuroleptic malignant syndrome, parkinsonism, tardive dyskinesia
- Monitoring:
-
- Monitor for orthostatic hypotension (dizziness, falls); advise slow position changes, adequate hydration, and leg exercises. Monitor HR and BP with change in positions.
- CV: Monitor for change in ECG such as prolongation of QT. Ensure electrolytes within normal range.
- Monitor for Extrapyramidal Symptoms (EPS): Watch for tremors, rigidity, restlessness (akathisia), or involuntary movements (dystonia, tardive dyskinesia)
- Watch for Neuroleptic Malignant Syndrome (NMS): assess for fever, muscle rigidity, altered mental status, and autonomic instability (tachycardia, labile blood pressure).
(Burchum Rosenjack & Rosenthal, 2019; Halter, Pollard & Jacubec, 2019; Rahman & Marwaha, 2023)
Clozapine
- oral administration, can be taken with or without food. Dose reductions if significant hepatic or renal disease.
- Pretreatment:
- Assess mental health status prior to and throughout treatment
- Labs include complete blood count (CBC), absolute neutrophil count (due to risk of agranulocytosis, electrolytes, A1C, lipid panel
- Baseline weight, waist circumference and BMI. Monitor q 6 months.
- ECG due to risk of QT prolongation
- Most common side effects: sedation and weight gain. Adrenergic effects include orthostatic hypotension. Anticholinergic effects: dry mouth, constipation, tachycardia
- Rare adverse effects include: seizures (dose dependent) and myocarditis, agranulocytosis, cardiomyopathy, neutropenia, paralytic ileus and pneumonia. Close monitoring required especially early in treatment.
- There is less of a risk for extrapyramidal effects than with conventional antipsychotics.
- Monitoring
- Monitor for improved mental health status, including therapeutic drug monitoring early in treatment with dosage adjustments expected.
- Risk of agranulocytosis (severe form of neutropenia), so mandatory neutrophil count. Risk appears greater in first 6 months of therapy. Assess for fever, sore throat or signs of infection. Can be fatal if not detected early and treated.
- Risk of metabolic syndrome: diabetes, obesity and dyslipidemia all a risk with atypical antipsychotics. Weight gain can be substantial. Monitor q 6 months.
- Monitor for orthostatic hypotension (dizziness, falls); advise slow position changes, adequate hydration, and leg exercises.
- Seizure Prevention & Management: Be alert for new or increased seizure activity. Document and report, and ensure safety. Lowers seizure threshold in clients with epilepsy.
- Enquire about constipation: common side effect. Risk of paralytic ileus. Ask regarding bowel habits and diet. Assess for any nausea/vomiting, abdominal pain or distension.
(Correll et al, 2022; Halter, Pollard & Jacubec, 2019)
Aripiprazole
Aripiprazole is an atypical antipsychotic that is used to treat schizophrenia, bipolar disorder and as a secondary medication for major depression. It has similar effects as other SGAs with headache, drowsiness, nausea, insomnia and dizziness as common side effects. It is administered orally, with or without food. Pretreatment assessment is the same as clonidine. Monitoring also includes blood glucose levels due to the risk of hyperglycemia, weight due to risk of weight gain and impulse control (Gettu & Saadabadi, 2023).
Adverse/Side Effects
Adverse effects and common side effects are identified above in the nursing considerations for each medication but are also summarized below. You might notice that the conventional medications have more adverse effects that can be undesirable and even life-threatening.
Potential Adverse Effects of Antipsychotic Medications (Halter, Pollard & Jacubec, 2019; McCuistion et al, 2018)
| Adverse Effects | Conventional Antipsychotics (Haloperidol) | Atypical Antipsychotics (Clozapine, Risperidone, Aripiprazole) |
| Most common effects: | Anticholinergic effects (dry mouth, dry eyes etc)
Weight gain, orthostatic hypotension, diarrhea |
Sedation
Weight gain can be substantial. Adrenergic effects include orthostatic hypotension. Anticholinergic effects: dry mouth, constipation, tachycardia
|
|
Less common effects: |
photosensitivity, pruritus, Prolongation of QT interval
Erectile dysfunction in males, oligomenorrhea or amenorrhea in females. |
metabolic changes: diabetes and hyperlipidemia. Monitor blood glucose levels and lipid panel. |
|
Adverse Effects |
Extrapyramidal Symptoms*:
Parkinsonism, tardive dyskinesia, Neuroleptic Malignant Syndrome (NMS) (rare) |
Rare, but can be life-threatening:
Seizures (dose dependent) myocarditis, agranulocytosis, cardiomyopathy, neutropenia, paralytic ileus pneumonia. |
* These adverse effects are due to the blockage of alpha-adrenergic, dopamine, endocrine, histamine, and muscarinic receptors. For additional details about these types of receptors, see the Autonomic Nervous System chapter.
| Adverse Effect | Definition |
|---|---|
| Tardive Dyskinesia | Involuntary contraction of the oral and facial muscles (such as tongue thrusting) and wavelike movements of the extremities. |
| Neuroleptic Malignant Syndrome (NMS) | Potentially life-threatening adverse effects, including reduced consciousness, muscle rigidity, and autonomic symptoms (high fever, unstable BP, tachycardia, diaphoresis) and myoglobinemia. Immediate emergency care required. |
| Extrapyramidal Symptoms | Involuntary motor symptoms, similar to those associated with Parkinson’s disease. Includes symptoms such as akathisia (distressing motor restlessness) and acute dystonia (painful muscle spasms.). Also includes tardive dyskinesia. Often treated with anticholinergic medications such as benztropine and trihexyphenidyl. EPS is due to blockage of certain receptor in the brain. Higher risk with conventional meds. |
Client Teaching
- Advise client to take medication as directed. Medication doses should be evenly spaced throughout the day.
- This drug may take several weeks to manifest desired effects.
- Clients should be advised regarding the possibility of extrapyramidal symptoms and that abrupt withdrawal may cause dizziness, nausea and vomiting, or uncontrolled movements of mouth, tongue, or jaw.
- The client should be careful to avoid alcohol or other CNS depressants while using the medication.
- There is a fall risk due to sedative, motor instability or dizziness.
Additional Client Teaching for clozapine
Inform client of potential adverse effects and symptoms. They should report any physical or mental health concerns to their prescriber (Correll et al, 2022).
- Encourage them to weigh themselves regularly due to the potential for weight gain. Encourage diet, exercise and a healthy lifestyle. May start on metformin as a treatment option.
- Inform client of the potential for constipation. Encourage adequate fluid and fiber intake. Report any abdominal pain or nausea & vomiting.
- Inform client of rare risk of myocarditis. Report any shortness of breath, fatigue, fever or rapid heart rate immediately.
- Inform client that blood work will be ordered periodically to check their white blood cell count.
Quetiapine
Quetiapine (Seroquel) is an atypical antipsychotic that is widely used. Like most meds in this class, it is used to treat schizophrenia, acute manic episodes, and adjunctive treatment for major depressive disorder. It is used off label for insomnia due to its sedating properties. Although it is sometimes used for insomnia on a prn basis, there is safety concerns.
Many of the side effects are the same, such as metabolic issues with weight gain, dyslipidemia and elevated blood sugars. There is also concern with clients with a history of cardiac issues such as arrythmias as it has a risk of prolonging the QT interval. The most common side effects are somnolence, orthostatic hypotension, and dizziness. The assessment and monitoring of quetiapine is the same as with other anti-psychotic medications (Maan, et al, 2023).
To learn more about these and other medications to treat mental health disorders, a helpful resource is the eMentalHealth.ca. Click on the links:
Quetiapine (Seroquel) https://www.ementalhealth.ca/Canada/Quetiapine/index.php?m=article&ID=20700
Risperidone https://www.ementalhealth.ca/Canada/Risperidone/index.php?m=article&ID=20509
Medication Table: Antipsychotic Medications https://www.ementalhealth.ca/Canada/Medication-Table-Antipsychotic-Medications/index.php?m=article&ID=71688
Comparing Antipsychotics
Now let’s take a closer look at the medication grid for haloperidol and risperidone (McCuistion et al, 2018). This table is intended to assist students to learn key points about each medication. Because information about medication is constantly changing, nurses should always consult evidence-based resources to review current recommendations before administering specific medication. Basic information related to each class of medication is outlined below.
Downloadable file (.docx): Comparing Types of Antipsychotics
To support your learning, you can access the Chapter 5 CNS Mood and Cogniton Medication Cards. This is a downloadable and editable document to allow you to update and add content.
Interactive Activities
Critical Thinking and Decision Making Activities
1.A community health nurse is working with a patient who was started on clozapine while in the hospital. When the patient asks why frequent lab work is necessary, the nurse explains:
a. One uncommon but serious side effect of clozapine is a decrease in neutrophils, which are white blood cells that help fight infection. Regular blood tests allow us to detect this early and intervene if needed to keep you safe.
b. We need to monitor the medication to ensure the level of the medication in the blood is within safe parameters.
c. A side effect of clozapine is electrolyte changes, and it is important for us to know if this is happening to avoid issues with your heart and muscles.
d. The blood test can help us to understand if the medication is helpful by looking at impacts on neurotransmitters.
2. One month later, the patient calls to cancel their appointment, stating that they have developed fever and chills. What is the most appropriate next step?
a. Counsel the patient on managing flu-like symptoms and agree to reschedule the appointment for next week.
b. Advise the patient to seek immediate medical attention to rule out agranulocytosis.
c. Advise the patient to have blood work done tomorrow to assess for neutropenia.
d. Advise the patient to stop taking clozapine and reschedule the appointment for next week.
Note: Answers to the Clinical Reasoning Activities and Critical Thinking questions can be found in the “Answer Key” sections at the end of the book.
References
Chokhawala, K. & Stevens, L. (2023). Antipsychotic Medications. National Library of Medicine. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK519503/
Correll, C. Agid, O., Crespo-Facorro, B., de Bartolomeis, A., Fagiolini, A., Seppälä, N., Howes, O. (2022). A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia. CNS Drugs, 36(7):659-679. doi: 10.1007/s40263-022-00932-2. PMID: 35759211; PMCID: PMC9243911.
Gettu, N. & Saadabadi, A. (2023). Aripiprazole. National Library of Medicine. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK547739/#:~:text=Aripiprazole%20is%20a%20medication%20used%20to%20manage,syndrome.%20It%20is%20a%20third%2Dgeneration%20antipsychotic%20medication
Haidary, H.& Padhy, R. (2023). Clozapine. National Library of Medicine. StatPearls[ Internet]. Clozapine – StatPearls – NCBI Bookshelf
Halter, M., Pollard, C. & Jacubec, S. (2019). Varcarolis’s Canadian Psychiatric Mental Health Nursing. A clinical approach (2nd ed.). Elsevier: Canada.
Maan, J., Ershadi, M.,Khan, I. & Saadabadi, A. (2023). Quetiapine. National Library of Medicine. StatPearls [internet]. Quetiapine – StatPearls – NCBI Bookshelf
McCuistion, L., Vuljoin-DiMaggio, K., Winton, M, & Yeager, J. (2018). Pharmacology: A patient-centered nursing process approach. pp. 227-305. Elsevier. ↵
Rosenjack Burchum, J., & Rosenthal, L. (2019). Lehne’s pharmacology for nursing care (10th ed.). Elsevier: Canada
