6.6 Antipsychotics

Antipsychotic medicines are primarily used to treat psychosis (i.e., a loss of contact with reality that may include delusions or hallucinations). Psychosis can be a symptom of a physical condition (such as a high fever, head injury, or substance intoxication) or a mental disorder (such as schizophrenia, bipolar disorder, or severe depression).^[1]

Antipsychotic medications reduce the intensity and frequency of psychotic symptoms by inhibiting dopamine receptors. Certain symptoms of psychosis, such as feeling agitated and having hallucinations, resolve within days of starting an antipsychotic medication. Symptoms like delusions usually resolve within a few weeks, but the full effects of the medication may not be seen for up to six weeks.^[2]

First-Generation (Typical) Antipsychotics

Common first-generation antipsychotic medications (also called “typical” antipsychotics) treat positive symptoms of schizophrenia. Examples include chlorpromazine, haloperidol, perphenazine, and fluphenazine.^[3]

First-generation antipsychotics work by blocking dopamine receptors 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. As a result, blockage produces a tranquilizing effect in psychotic clients. However, several adverse effects are caused by this dopamine blockade, such extrapyramidal side effects (e.g., involuntary or uncontrollable movements, tremors, and muscle contractions) and tardive dyskinesia (a syndrome of movement disorders that persists for at least one month and can last up to several years despite discontinuation of the medications).^[4]

Second-Generation (Atypical) Antipsychotics

Newer, second-generation antipsychotics (also called atypical antipsychotics) work by blocking specific D2 dopamine receptors and serotonin receptors. Examples of second-generation medications include risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, and lurasidone. Second generation antipsychotics treat both positive and negative symptoms of schizophrenia, and several are also used for treating bipolar depression or depression that has not responded to an antidepressant medication alone. Second generation antipsychotics have a significantly decreased risk of extrapyramidal side effects but are associated with weight gain and the development of metabolic syndrome.^[5] Metabolic syndrome increases the risk of heart disease, stroke, and type 2 diabetes. Clinical symptoms of metabolic syndrome include high blood glucose, symptoms of diabetes (i.e., increased thirst and urination, fatigue, and blurred vision), obesity with a large abdominal girth, hypertension, elevated triglyceride, and lower levels of HDL.

See Table 6.6 for a list of common antipsychotic medications. Some are taken daily in pill or liquid form. Others can be administered as injections twice a month, monthly, every three months, or every six months, which can be more convenient and improve medication adherence.

Table 6.6 Common Antipsychotic Medications^[6],[7],[8]

Clients respond differently to antipsychotic medications, so it may take several trials of different medications to find the one that works best for their symptoms.^[9]

Clozapine

Clients with treatment-resistant schizophrenia may be prescribed clozapine, a specific atypical antipsychotic medication that binds to both serotonin and dopamine receptors. Clozapine is often effective when other antipsychotics have failed, but it carries a complex side effect profile, including strong anticholinergic, sedative, cardiac, and hypotensive properties, as well as frequent drug-drug interactions. One of the most important risks to note is agranulocytosis, a rare but potentially life-threatening drop in white blood cells that significantly increases infection risk. For this reason, clients must be enrolled in a REMS (Risk Evaluation and Mitigation Strategy) program, with regular monitoring of their absolute neutrophil count (ANC)—typically weekly during the initial months of treatment. Nurses play a critical role in educating clients about the importance of lab work and recognizing early signs of infection such as fever or sore throat, which must be reported immediately.^[10]

Side Effects

Common side effects of both first- and second-generation antipsychotics include the following:

• Anticholinergic symptoms: dry mouth, constipation, blurred vision, or urinary retention
• Drowsiness
• Dizziness
• Restlessness
• Weight gain
• Nausea or vomiting
• Low blood pressure
• Falls related to sedation, motor instability, and postural hypotension

Neuroleptic malignant syndrome (NMS) is a rare but fatal adverse effect that can occur at any time during treatment with antipsychotics. It typically develops over a period of days to weeks and resolves in approximately nine days with treatment. Signs include increased temperature, severe muscular rigidity, confusion, agitation, hyperreflexia, elevation in white blood cell count, elevated creatinine phosphokinase, elevated liver enzymes, myoglobinuria, and acute renal failure. The antipsychotic should be immediately discontinued when signs occur. Dantrolene and bromocriptine are typically prescribed for treatment. Nursing interventions include adequate hydration, cooling, and close monitoring of vital signs and serum electrolytes.^[11]

Black Box Warning

A Black Box Warning states that elderly clients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.^[12]

Side Effects of First-Generation Antipsychotics

First-generation antipsychotics have significant potential to cause extrapyramidal side effects and tardive dyskinesia due to their tight binding to dopamine receptors. ^[13]

Extrapyramidal (EPS) side effects refer to akathisia (psychomotor restlessness), rigidity, bradykinesia (slowed movement), tremor, and dystonia (involuntary contractions of muscles of the extremities, face, neck, abdomen, pelvis, or larynx in either sustained or intermittent patterns that lead to abnormal movements or postures). Acute dystonic reactions affecting the larynx can be a medical emergency requiring intubation and mechanical ventilation. EPS symptoms usually resolve dramatically within 10 to 30 minutes of administration of parenteral anticholinergics such as diphenhydramine and benztropine.^[14]

Tardive dyskinesia (TD) is a syndrome of movement disorders that can occur in clients taking first-generation antipsychotics. Hallmark symptoms are smacking and puckering lips, eye blinking, grimacing, and twitching. TD persists for at least one month and can last up to several years despite discontinuation of the medications. Primary treatment of TD includes discontinuation of first-generation antipsychotics and may include the addition of another medication. Second-generation VMAT2 inhibitors such as deutetrabenazine and valbenazine are considered first-line treatment for TD. Clonazepam and ginkgo biloba have also shown good effectiveness for improving symptoms of TD.^[15],[16]

Side Effects of Second-Generation Antipsychotics

Second-generation antipsychotics have a significantly decreased risk of extrapyramidal side effects but are associated with weight gain and the development of metabolic syndrome.^[17] Metabolic syndrome is a cluster of conditions that occur together, increasing the risk of heart disease, stroke, and type 2 diabetes. Symptoms include increased blood pressure; high blood sugar; excess body fat around the waist (also referred to as having an “apple waistline”); and abnormal cholesterol, triglyceride levels, and high-density lipoprotein (HDL) levels. Weight, glucose levels, and lipid levels should be monitored before treatment is initiated then annually.

Client Education

Clients should be advised to contact their provider if and side effects occur.  This includes the development of any involuntary or uncontrollable movements. They should be warned to not suddenly stop taking the medication because abrupt withdrawal can cause dizziness; nausea and vomiting; and uncontrolled movements of the mouth, tongue, or jaw. Clients should be warned to not consume alcohol or other CNS depressants because their ability to operate machinery or drive may be impaired.

Some people may experience relapse, meaning their psychosis symptoms come back or get worse. Relapses typically occur when people stop taking their prescribed antipsychotic medication or when they take it sporadically. Some people stop taking prescribed medications because they feel better or they feel that they don’t need it anymore, but medication should never be stopped suddenly. After talking with a prescriber, clients can gradually taper their medications in some situations. However, most people with schizophrenia must stay on an antipsychotic continuously for mental wellness.^[19]