13.2: Antipsychotics
By the end of this section, you should be able to:
- 13.2.1 Identify the characteristics of drugs used to treat psychosis.
- 13.2.2 Explain the indications, actions, adverse reactions, contraindications, and interactions of drugs used to treat psychosis.
- 13.2.3 Describe nursing implications for drugs used to treat psychosis.
- 13.2.4 Explain the client education related to drugs used to treat psychosis.
Psychosis is a collection of symptoms that include some level of disconnection with reality. These symptoms can include hallucinations, paranoid thoughts, and illogical thinking. Psychosis can be a symptom of a mental illness—most commonly schizophrenia. It can also be a symptom of bipolar disorder or severe depression. Psychotic disorders are generally known to have a strong genetic component. The onset of psychotic symptoms can begin either gradually or quickly. Initial symptoms are commonly seen during adolescence or young adulthood (National Institute of Mental Health [NIMH], 2023c). Psychosis can also develop later in life with neurological conditions such as dementia or be caused by sleep deprivation, certain medications, or alcohol/substance use.
Schizophrenia is a severe mental disorder characterized by disorganized thought processes, blunted or inappropriate emotional responses, and bizarre behavior. In addition, it may involve social withdrawal ( asociality ) by the affected person. Eventually individuals begin to deteriorate and demonstrate a lack of self-care and interpersonal skills. Symptoms of schizophrenia are classified as either positive, referring to an excess of distortion of normal function (e.g., hallucinations), or negative, meaning diminishing or absent behaviors related to motivation or expression (Correll & Schooler, 2020). Schizophrenia is diagnosed with at least two of the following symptoms present (American Psychiatric Association, 2022). At least one of the symptoms must be delusions, hallucinations, or disorganized speech. Other possible symptoms include disorganized or catatonic behavior ( catatonia ) or negative symptoms (diminished emotional expression or avolition ). Research suggests that clients with schizophrenia have abnormal neurotransmission systems—primarily the dopaminergic, serotonergic, and glutamatergic systems. It is believed that positive symptoms are associated with overactivity of dopamine 2 (D 2 ) receptors in the basal ganglia, hypothalamus, limbic system, brainstem, and medulla. It is theorized underactive dopamine 1 (D 1 ) receptors in the prefrontal cortex account for the negative symptoms.
Special Considerations
Schizophrenia in Children
- Schizophrenia in children often presents with more intense clinical manifestations and has a more chronic course.
- The American Academy of Child and Adolescent Psychiatry has established current practice guidelines that advocate for high-quality assessment of the child who is receiving antipsychotic s. The purpose of the guidelines is to promote the appropriate use of antipsychotics and to enhance safety. Today, multiple antipsychotics have specific dosing for children and adolescents . These parents’ medication guides may be helpful for client education.
- Regulating medication dosing for children is challenging. Children require lower doses to reach full therapeutic effects, yet they also metabolize medications more quickly.
This section of the chapter will focus on treating psychosis. Historically, first-generation or “typical” antipsychotic agents were more effective in managing the positive symptoms versus the negative symptoms; however, the newer second-generation “atypical” medications have shown effectiveness in treating both the positive and negative symptoms. Antipsychotics are targeted at thought processes rather than affective states. Although they are not a cure, they can help both adult and pediatric clients be able to adequately function in a healthier manner. In acute psychosis, the goal is to reduce symptoms in the first week and normalize clients’ eating and sleeping patterns. Subsequent goals are to increase the ability for self-care and increase socialization. Most of these drugs take 1–2 months to reach full therapeutic effects. With adequate drug treatment, clients can engage in individual or group psychotherapy sessions as well as return to their level of functioning prior to the illness.
Safety Alert
Beers Criteria ®
The Beers Criteria ® for Potentially Inappropriate Medication Use in Older Adults is a list published by the American Geriatrics Society describing medications that are potentially harmful if prescribed to clients older than 65 years. Antipsychotics are included on the list because they are linked to higher rates of cognitive decline and death in persons with dementia.
(Source: American Geriatrics Society, 2023)
Clinical Tip
Antipsychotics
First-generation antipsychotics are frequently referred to as “neuroleptics” because of the increased risk of producing extrapyramidal neurologic effects, including pseudoparkinsonism , dystonia (spasms of the tongue, back, legs, and neck), akathisia (not being able to sit still), and tardive dyskinesia (abnormal muscle movements). Health care providers should monitor clients for extrapyramidal effects so they can be treated and the antipsychotic medication can be changed (Ameer & Saadabadi, 2023).
Antipsychotics fit into the classification of dopamine receptor antagonists (blockers). They are used to treat disorders that involve thought processes. They help clients with organizing their thoughts and responding appropriately to stimuli. The therapeutic effects are most likely due to blocking dopamine receptors. Unfortunately, these medications can also bind to a variety of receptors, which leads to many of the ADRs. Antipsychotics are categorized in two main classes: first-generation agents, also known as typical or conventional, and second-generation agents, also known as atypical. These categories are based on their mechanism of action (described in the following sections). Although their names may imply that psychosis is the only condition these drugs are used for, there are numerous psychiatric disorders for which these drugs can be useful.
Clients should be made aware they will usually need to remain on these drugs for years, if not for life, because there is a high rate of relapse when drug therapy is stopped. Most antipsychotics come in an oral form. Those clients who are unable or unwilling to take daily doses may receive periodic injections of a long-acting form (LAIs). The benefit of the LAIs is that they allow prescribers to tailor pharmacotherapy to each client’s needs. The LAIs are administered via depot injections . This refers to the way the drug is deposited and stored in the muscle before being absorbed. Because the drug takes a longer time to move out of the muscle and into the bloodstream, its action is prolonged.
First-Generation (Typical) Antipsychotics
First-generation antipsychotics are classified by their potency (strength). The level of potency (low, medium, or high) refers to the concentration of the drug needed to produce a given response. Keep in mind that this is different from efficacy. All first-generation agents have the same ability to relieve symptoms of psychosis (efficacy). In addition to blocking dopamine receptors, they also block muscarinic, histaminergic, and alpha-adrenergic receptors, leading to numerous adverse effects (discussed later in this chapter). The three most common first-generation antipsychotics are:
- Chlorpromazine: This is a low-potency agent and a phenothiazine. It is also used to decrease preoperative restlessness and apprehension, treat intermittent porphyria, as an adjunct in the treatment of tetanus, and to help control nausea, vomiting, and intractable hiccups.
- Fluphenazine: This is a high-potency agent and a phenothiazine. Compared to other antipsychotics, this drug has a low potential for causing anticholinergic effects. It is available in oral and intramuscular forms.
- Haloperidol: This is a high-potency nonphenothiazine. It is frequently used to treat acute psychiatric situations when it is given intramuscularly. Its mechanism of action, ADRs, and contraindications are the same as for chlorpromazine. An added contraindication is severe mental depression.
Table 13.12 lists common first-generation antipsychotics and typical routes and dosing for adult and pediatric clients .
| Drug | Routes and Dosage Ranges |
|---|---|
|
Chlorpromazine
( Thorazine ) |
Adults (mild to moderate symptoms):
Initial dose: 25 mg 3 times daily; increase gradually until effective dose is reached, usually 400 mg/day.
Adults (severe symptoms): Initial dose: 25 mg 3 times daily; after 1–2 days, daily dosage may be increased by 20–50 mg until client becomes calm. Older adults: Initial dose: 1/4 to 1/3 of the level for younger adults. Children (6 months to 12 years for severe behavioral problems): Outpatient dose: 0.25 mg/lb orally every 4–6 hours as needed. Inpatient dose: 50–200 mg/day orally until symptoms improve. |
|
Fluphenazine
( Prolixin , Modecate ) |
Adults: Initial dose: 2.5–10 mg orally divided into intervals of 6–8 hours. Maximum dose: 40 mg/day; maintenance dose: 1–5 mg/day as a single dose. |
|
Haloperidol
( Haldol ) |
Oral:
Adults: 0.5–5 mg orally 2 or 3 times daily. Children (3–12 years): Initial dose: 0.5 mg/day orally. Increase dose by 0.5 mg increments at intervals of 5–7 days until desired effect is achieved. Intramuscular: Adults: Long-acting: Starting dose form should be based on 10–20 times the previous daily dose in oral haloperidol equivalents and adjusted as needed. Short-acting: 2–5 mg as often as every hour up to a maximum dose of 20 mg/day. |
Adverse Effects and Contraindications
Most of the ADRs are related to these drugs’ anticholinergic properties, including blurred vision, dry mouth, constipation, urine retention, nasal congestion, and photophobia. Arrhythmias can be caused by the dopamine-blocking effects or prolongation of the QTc interval, which could lead to fatal arrhythmias. Prolactin levels will increase, causing gynecomastia and changes in libido. First-generation antipsychotics are known to cause extrapyramidal symptoms (EPS), which are involuntary, uncontrollable movements. These include pseudoparkinsonism (muscle tremors, cogwheel rigidity, stiff facial muscles, drooling due to difficulty swallowing, shuffling gait, and slow movements), dystonia, akathisia, and tardive dyskinesia. Extrapyramidal symptoms may be more problematic with depot injections.
Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal condition that can develop with antipsychotic use. The clinical manifestations include a sudden high-grade fever, fluctuations in blood pressure, dysrhythmias, extreme muscle rigidity, and significant tachycardia. Immediate supportive management must be instituted if this develops, which might include cooling blankets/fluids and administering antipyretics (drugs to reduce fever), antiarrhythmics, and dantrolene to treat muscle rigidity.
The manifestations of Parkinson's disease can be exacerbated by antipsychotics due to their effect on dopamine receptors. This can happen with any antipsychotic that causes EPS. In addition, these drugs can cause urinary retention and constipation. Individuals who have a mechanical or neurological obstruction of the renal or GI system should avoid these drugs, including those with benign prostatic hyperplasia (BPH).
Due to their anticholinergic properties, these drugs can increase intraocular pressure, worsening glaucoma and possibly causing vision loss. Furthermore, those with a seizure disorder may need an increase in their antiseizure medications because the antipsychotics tend to lower the seizure threshold.
Alcohol intake and taking medications that cause CNS depression will amplify the depressant effect.
Safety Alert
Similarly Named Drugs Associated with First-Generation Antipsychotics
Do not confuse chlorpromazine (antipsychotic) with chlordiazepoxide ( sedative ) or chlorpropamide ( sulfonylurea antidiabetic ).
(Source: ISMP, 2023)
Table 13.13 is a drug prototype table for first-generation antipsychotics featuring haloperidol. It lists drug class, mechanism of action, adult and pediatric dosage , indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
First-generation antipsychotic (typical antipsychotic) Mechanism of Action Blocks dopamine-2 receptors, which prevents the stimulation of the postsynaptic neurons by dopamine Exact mechanism of action for schizophrenia is unclear |
Drug Dosage
Oral: Adults: 0.5–5 mg orally 2 or 3 times daily. Children (3–12 years): Initial dose: 0.5 mg/day orally. Increase dose by 0.5 mg increments at intervals of 5–7 days until desired effect is achieved. Intramuscular: Adults: Long-acting: Starting dose form should be based on 10–20 times the previous daily dose in oral haloperidol equivalents and adjusted as needed. Short-acting: 2–5 mg as often as every hour up to a maximum dose of 20 mg/day. |
|
Indications
Schizophrenia Treatment of psychotic symptoms associated with brain impairment (head trauma, tumor, stroke, alcohol withdrawal, and overdoses of CNS stimulants) Therapeutic Effects Blocks dopamine receptors in the brain Limits the stimuli coming into the brain |
Drug Interactions
CNS depressants, such as opioids or sedatives Antiarrhythmic medications that prolong the QTc interval Food Interactions Kava kava Alcohol |
|
Adverse Effects
Prolongation of the PR and QTc interval Anticholinergic effects (blurred vision, xerostomia , constipation, urine retention, nasal congestion, photophobia) Sexual dysfunction Hypotension/arrhythmias Pseudoparkinsonism Akathisia Tardive dyskinesia Sedation/drowsiness Impaired mobility Impaired speech and mental processes |
Contraindications
Parkinson’s disease Older adults with dementia Cardiac arrhythmias/prolonged QTc interval Liver damage Coronary artery disease (CAD) Cerebrovascular disease Caution: Glaucoma Seizures Active alcohol use disorder |
Second-Generation (Atypical) Antipsychotics
The second-generation antipsychotics , also known as atypical antipsychotics , are the drugs of choice. This is especially true for clients who are newly diagnosed. The atypical antipsychotics block both dopamine and serotonin receptors. This class of antipsychotics has a broader range of action than the first-generation agents because of their effects on the serotonergic, noradrenergic, and dopaminergic systems. They seem to be more effective in relieving some symptoms and usually produce milder adverse effects (Ameer & Sadabadi, 2023). The most common second-generation antipsychotics are:
- Aripiprazole: This is the first of a new class of atypical antipsychotic medications called the dopamine system stabilizers . This class is sometimes referred to as a third-generation antipsychotic. In its oral form, aripiprazole can be used in the management of schizophrenia, major depressive disorder, bipolar disorder, irritability related to autism spectrum disorder, and Tourette syndrome. In its injectable, immediate-release form, it is used to treat agitation associated with schizophrenia or bipolar mania. This drug does not prolong the QTc interval; however, the FDA has issued a safety alert, confirming that compulsive or uncontrollable urges to gamble, binge eat, shop, and have sex with multiple partners have been reported.
- Cariprazine: Used to treat schizophrenia or mania and depression related to bipolar disorder. It is also used to treat MDD.
- Clozapine: This medication was one of the first atypical antipsychotic medications used to treat schizophrenia, but because of its side effects, is only used when other treatments have failed. Clozapine is available only through to the FDA’s Approved Risk Evaluation and Mitigation Strategies (REMS) program to ensure monitoring of WBC count and absolute neutrophil count.
- Lurasidone: Used to treat schizophrenia and bipolar depression in clients age 13 and older. Administering this drug with food can greatly increase its absorption. This drug does not prolong the QTc interval, cause orthostatic hypotension, or have any cholinergic effects.
- Olanzapine: In addition to treating schizophrenia, this drug is used for manic or mixed episodes of bipolar disorder and can be given parenterally to treat acute agitation.
- Paliperidone: Used in clients age 12 and over to treat schizoaffective disorders. This is a major active metabolite of risperidone; therefore, it has the same therapeutic and adverse effect profiles. Paliperidone is available in three forms: one short-acting oral and two long-acting injectables (one administered monthly and the other every 3 months).
- Quetiapine: Used to treat schizophrenia and depressive disorder as well as for short-term treatment of acute manic episodes associated with bipolar disorder. The extended-release form is for use only in adults.
- Risperidone: Used to treat schizophrenia and acute bipolar mania. It is also frequently used to manage irritability and aggression associated with autism spectrum disorder in children and adolescents. In schizophrenia, relief of positive and negative symptoms can occur in as little as 1 week.
- Ziprasidone: Indicated for schizophrenia and bipolar disorder.
Table 13.14 lists common second-generation antipsychotics and typical routes and dosing for adult and pediatric clients .
| Drug | Routes and Dosage Ranges |
|---|---|
|
Aripiprazole
( Abilify ) |
Adults:
10–15 mg/day orally initial dose; effective dose range: 10–30 mg/day.
Adolescents (13–17 years): Initial dose: 2 mg/day orally; target dose: 10 mg /day. |
|
Cariprazine
( Vraylar ) |
Adults:
1.5 mg orally daily; recommended dose: 1.5–6 mg/day.
Pediatric safety, effectiveness, and dose have not been established. |
|
Clozapine
( Clozaril ) |
Adults: Initial dose: 12.5 mg/day orally; total daily dose can be increased in increments of 25–50 mg/day; target dose: 300–450 mg/day in divided doses. |
|
Lurasidone
( Latuda ) |
Adults and adolescents (13–17 years): Initial dose: 20 mg/day orally. Maximum dose for adults: 120 mg/day. Maximum dose for adolescents: 80 mg/day. |
|
Olanzapine
( Zyprexa ) |
Adults:
5–10 mg/day orally; target dose: 10 mg/day.
Adolescents (13-17 years): Initial dose: 2.5–5 mg/day; target dose: 10 mg/day. |
|
Paliperidone
( Invega ) |
Adults:
Initial dose: 6 mg/day orally; maximum dose: 12 mg/day.
Adolescents (12 –17 years): 3 mg orally once daily. Maximum dose: 6 mg for clients weighing less than 51 kg; 12 mg for clients weighing 51 kg or greater. |
|
Quetiapine
( Seroquel ) |
Adults:
Initial dose: 300 mg/day orally titrated to effect; maximum dose 800 mg/day.
Adolescents: Initial dose: 50 mg/day orally; titrated to effect: maximum 800 mg/day. |
|
Risperidone
( Risperdal ) |
Adults:
2 mg/day orally; effective dose: 4–16 mg/day.
Adolescents: Initial dose: 0.5 mg/day; effective dose: 1–6 mg/day. |
|
Ziprasidone
( Geodon ) |
Adults: 20 mg orally twice daily; maximum dose: 80 mg twice daily for schizophrenia; 40 mg orally twice daily; 80 mg twice daily for bipolar disorder. |
Adverse Effects and Contraindications
For second-generation antipsychotics, the risk of seizures is higher as the drug dose increases. Hematologic effects include agranulocytosis, neutropenia, and fatal agranulocytosis. Clozapine is subject to additional monitoring through the FDA’s REMS program to decrease the risk of severe neutropenia. Metabolic effects are more common with these medications and include hyperglycemia and weight gain. Concerning ADRs for quetiapine include increased systolic and diastolic readings, decreased high-density cholesterol, and increased total cholesterol, low-density cholesterol, and triglycerides.
Drugs with anticholinergic properties will potentiate these effects of clozapine. Alcohol can increase the sedative effect. Cimetidine and caffeine can increase the risk of toxicity for clozapine.
Safety Alert
Similarly Named Drugs Associated with Second-Generation Antipsychotics
Do not confuse:
- Aripiprazole (antipsychotic) with pantoprazole ( proton pump inhibitor )
- Clozaril (antipsychotic) with Colazal ( anti-inflammatory for inflammatory bowel disorder)
- Olanzapine (antipsychotic) with quetiapine (antipsychotic)
- Zyprexa (antipsychotic) with Zestril ( ACE inhibitor ) or Zyrtec ( histamine-1 receptor antagonist )
- Risperdal (antipsychotic) with Restoril ( benzodiazepine sedative-hypnotic ) or Ropinirole ( dopamine agonist )
(Source: ISMP, 2023)
Table 13.15 is a drug prototype table for second-generation antipsychotics featuring risperidone. It lists drug class, mechanism of action, adult and pediatric dosage , indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Second-generation antipsychotic (atypical antipsychotic) Mechanism of Action Blocks dopamine and serotonin receptors in the brain |
Drug Dosage
Adults: 2 mg/day orally; effective dose: 4–16 mg/day. Adolescents: Initial dose: 0.5 mg/day; effective dose: 1–6 mg/day. |
|
Indications
Schizophrenia Bipolar mania Therapeutic Effects Decreases hallucinations and disordered thoughts in clients with schizophrenia Decreases symptoms of mania including irritability, aggressive thoughts, elevated mood and activity, and sexual interest |
Drug Interactions
Carbamazepine Cimetidine Ranitidine Fluoxetine Paroxetine Erythromycin Amitriptyline Food Interactions Alcohol |
|
Adverse Effects
Orthostatic hypotension Increased risk of seizures Hematologic effects (leukopenia, neutropenia, and agranulocytosis) Hyperglycemia Dyslipidemia Neuroleptic malignant syndrome Development of diabetes mellitus Weight gain |
Contraindications
Known hypersensitivity to risperidone, paliperidone, or any derivatives Dementia-related psychosis Caution: Severe renal impairment Hepatic impairment Cardiovascular disease Diabetes mellitus Pulmonary disease |
Nursing Implications
The nurse should do the following for clients who are taking antipsychotics:
- Watch carefully for developmental progress in children.
- Monitor for symptoms of schizophrenia.
- Obtain baseline physical assessment and relevant tests including an electrocardiogram, CBC, electrolytes, liver and renal function tests, lipid panel, blood glucose levels, and thyroid function. Continue to monitor these on an ongoing basis to identify potential adverse effects.
- Obtain baseline vital signs and urinary output.
- Monitor weight for weight gain, agitation, and/or sleep disturbances.
- Evaluate for the potential effects of hyperprolactinemia (high levels of the hormone prolactin in the blood).
- Assess for any anticholinergic effects. Promote comfort measures if necessary, such as laxatives or catheterization.
- Measure the PR and QTc interval at baseline and during the use of thioridazine or ziprasidone.
- Obtain a detailed history for any cardiovascular conditions, glaucoma, diabetes, obstructions, seizure disorder, pregnancy (or thinking about getting pregnant), and breastfeeding.
- Ensure the client is not a danger to themselves or others.
- Auscultate bowel sounds every 4 hours if client is an inpatient. The constipation caused by clozapine is significant and can progress to intestinal ischemia and necrotizing colitis.
- To prevent any unnecessary stress, explain gynecomastia and the reason it occurs.
- Assess CNS alertness and orientation and provide safety precautions when necessary.
- Assess for any extrapyramidal effects and provide safety measures.
- Ensure client receives an annual eye exam to monitor for glaucoma or worsening of glaucoma.
- Care for the client in a holistic manner, such as proper nutrition, adequate hygiene, activity level, and social interactions.
- With acute psychotic episodes, observe for decreased agitation, combativeness, and psychomotor activity to evaluate therapeutic effectiveness.
- Observe for decreased psychotic behaviors, such as decreased hallucinations and delusions.
- Ensure clozapine does not get stopped abruptly because it will cause acute psychosis. This drug should be tapered over a 2-week period.
- For clients taking clozapine, perform a thorough assessment of their cardiovascular and cardiopulmonary status.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking an antipsychotic should:
- Drink adequate amounts of water (at least 64 ounces/day or other prescribed amount), especially during hot weather.
- Have a total understanding that full therapeutic effects will not occur immediately; it may take several weeks to be able to experience effects.
- Obtain weekly blood tests to determine safe and effective dosage.
- Lie down for 30–60 minutes after an IM injection to prevent hypotension.
- Take the oral form 1–2 hours prior to bedtime because the drug peaks in 2 hours.
- Wear protective clothing when out in the sun.
- Report dark urine, right upper quadrant pain, clay-colored stools, and yellowing of the eyes or skin to the provider.
- Notify the health care provider if sore throat, fever, or flu-like symptoms arise.
- If needed, take the drug with food to decrease gastric upset.
- Increase fluid intake, dietary fiber, and exercise to prevent constipation.
- Be aware that only 1 week of medicine will be dispensed at a time (clozapine).
- Immediately notify the provider if having difficulty moving their bowels. The provider may need to prescribe a stool softener.
- Practice frequent hand hygiene and wear a mask in public if white blood cell count is low to decrease risk of infection.
- Practice good oral care and rinse mouth frequently or chew on sugarless gum to manage symptoms of dry mouth.
- Monitor for extrapyramidal symptoms and notify the provider if they occur.
The client taking an antipsychotic should not:
- Allow the liquid concentrations to touch the skin because it can cause contact dermatitis.
- Quickly change positions due to orthostatic hypotension.
- Drive a vehicle or operate heavy machinery due to dizziness and sedation.
FDA Black Box Warning
Antipsychotics
First- and second-generation antipsychotics: Increasing mortality occurs in the older adult with dementia-related psychosis.
Aripiprazole: Use places the client at risk for developing compulsive or uncontrollable urges to gamble, shop, binge eat, or be promiscuous.