6.6 Antipsychotics

Antipsychotic medicines are primarily used to manage 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). Antipsychotic medications may also be used in combination with other medications to treat the symptoms of other mental health conditions, including attention deficit hyperactivity disorder (ADHD), eating disorders, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and generalized anxiety disorder.^[1]

One rare but life-threatening adverse reaction to antipsychotic medications is neuroleptic malignant syndrome (NMS). NMS is most commonly associated with first-generation (typical) antipsychotics but can also occur with second-generation (atypical) antipsychotics. This condition is characterized by high fever, muscle rigidity, altered mental status, and autonomic instability (e.g., fluctuations in blood pressure or heart rate). NMS is a medical emergency, and early recognition is critical. Nurses should be alert to signs of NMS and ensure immediate discontinuation of the antipsychotic medication, followed by supportive care and possible pharmacologic treatment (e.g., dantrolene or bromocriptine).^[2]

First-generation antipsychotics (also called typical antipsychotics) have several potential adverse effects, and medication is prescribed based on the client’s ability to tolerate the adverse effects. Second-generation antipsychotics (also referred to as atypical antipsychotics) have fewer adverse effects and are generally better tolerated. 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.^[3]

First-Generation (Typical) Antipsychotics

Common first-generation antipsychotic medications (also called “typical” antipsychotics) include chlorpromazine, haloperidol, perphenazine, and fluphenazine.^[4]

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).

Second-Generation (Atypical) Antipsychotics

Second-generation antipsychotics (also called atypical antipsychotics) work by blocking specific D2 dopamine receptors and serotonin receptors. Second-generation medications include risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, and lurasidone. Several atypical antipsychotics have a “broader spectrum” of action than the older medications and are used for treating bipolar depression or depression that has not responded to an antidepressant medication alone. They 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.

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, patients 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.^[6]