What are the risks and contraindications of administering multiple antipsychotics, including Latuda (lurasidone), Zyprexa (olanzapine), Haldol (haloperidol), and Thorazine (chlorpromazine), to an adult patient with a genetically confirmed resistance to psychosis, suspected Attention Deficit Hyperactivity Disorder (ADHD), and intersex condition, who has reported sexual abuse and harassment by staff, and is being denied their right to fill out an Advanced Directive/Power of Attorney (PoA)?

From the Guidelines

The administration of multiple antipsychotics, including Latuda (lurasidone), Zyprexa (olanzapine), Haldol (haloperidol), and Thorazine (chlorpromazine), to an adult patient with a genetically confirmed resistance to psychosis, suspected Attention Deficit Hyperactivity Disorder (ADHD), and intersex condition, poses a significant risk of severe adverse effects, including extrapyramidal symptoms, sedation, and cognitive impairment 1.

Risks and Contraindications

• Cardiac risks: The use of multiple antipsychotics, particularly those with QT-prolonging properties such as Thorazine, increases the risk of torsades de pointes and sudden death 1.
• Neurological risks: The administration of multiple antipsychotics increases the risk of acute extrapyramidal syndromes, including acute dystonia, akathisia, and Parkinsonian syndrome 1.
• Metabolic risks: The use of multiple antipsychotics, particularly those with metabolic side effects such as Zyprexa, increases the risk of weight gain, hyperglycemia, and diabetes 1.
• Other risks: The administration of multiple antipsychotics may also increase the risk of seizures, respiratory depression, and neuroleptic malignant syndrome 1.

Considerations for Special Populations

• Intersex condition: The use of antipsychotics in patients with intersex conditions requires careful consideration of the potential impact on hormonal balance and reproductive health.
• ADHD: The use of antipsychotics in patients with ADHD requires careful consideration of the potential impact on cognitive function and behavioral symptoms.
• Genetically confirmed resistance to psychosis: The use of antipsychotics in patients with genetically confirmed resistance to psychosis requires careful consideration of the potential impact on treatment efficacy and side effect risk.

Recommendations

• Monitor patients closely: Patients receiving multiple antipsychotics should be monitored closely for signs of adverse effects, including extrapyramidal symptoms, sedation, and cognitive impairment 1.
• Use lowest effective dose: The lowest effective dose of each antipsychotic should be used to minimize the risk of adverse effects 1.
• Consider alternative treatments: Alternative treatments, such as behavioral therapies and non-pharmacological interventions, should be considered for patients with ADHD and intersex conditions 1.

From the FDA Drug Label

WARNINGS Increased Mortality in Elderly Patients with Dementia-Related Psychosis Tardive Dyskinesia: Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs Patients with a history of a clinically significant low WBC or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy Haloperidol decanoate injection, 50 mg/mL and haloperidol decanoate injection, 100 mg/mL should be administered cautiously to patients: with severe cardiovascular disorders, because of the possibility of transient hypotension and/or precipitation of anginal pain

The administration of multiple antipsychotics, including Latuda (lurasidone), Zyprexa (olanzapine), Haldol (haloperidol), and Thorazine (chlorpromazine), to an adult patient poses significant risks, including:

• Tardive dyskinesia: a potentially irreversible syndrome of involuntary movements
• Neuroleptic malignant syndrome (NMS): a potentially fatal symptom complex
• Cardiovascular effects: transient hypotension, precipitation of anginal pain, and QTc interval prolongation
• Hematologic effects: leukopenia, neutropenia, and agranulocytosis
• Other adverse effects: extrapyramidal symptoms, seizures, and increased risk of mortality in elderly patients with dementia-related psychosis

Given the patient's complex medical history, including a genetically confirmed resistance to psychosis, suspected ADHD, intersex condition, history of sexual abuse and harassment, and denial of their right to fill out an Advanced Directive/Power of Attorney (PoA), the use of multiple antipsychotics should be approached with extreme caution. The benefits of treatment should be carefully weighed against the potential risks, and alternative treatment options should be considered. Close monitoring of the patient's physical and mental health is essential to minimize the risk of adverse effects 2, 3.

From the Research

Risks of Administering Multiple Antipsychotics

• The administration of multiple antipsychotics, including Latuda (lurasidone), Zyprexa (olanzapine), Haldol (haloperidol), and Thorazine (chlorpromazine), to an adult patient can lead to increased adverse effects, such as extrapyramidal symptoms, sedation, weight gain, hypotension, neuroleptic malignant syndrome, and corrected QT-interval (QTc) prolongation 4.
• Antipsychotic polypharmacy, which refers to the co-prescription of more than one antipsychotic drug, is associated with an increased adverse effect burden and is not generally considered adequate to warrant a recommendation for its use in routine clinical practice in psychiatry 5.
• The use of high-dose antipsychotics, such as olanzapine, can lead to severe toxicity, including neuroleptic malignant syndrome, which can be potentially lethal 4, 6.

Contraindications and Precautions

• Patients with a history of neuroleptic malignant syndrome, seizures, or other adverse effects should be closely monitored when administered antipsychotics 6, 7.
• The use of antipsychotics in patients with cardiovascular disease, diabetes, or other comorbidities should be approached with caution, as they may be at increased risk of adverse effects 6, 7.
• The administration of antipsychotics to patients who have experienced sexual abuse or harassment should be done with sensitivity and caution, taking into account the potential for increased vulnerability and trauma 4, 5.

Dose-Dependent Effects

• The efficacy and adverse effects of antipsychotics can be dose-dependent, with higher doses associated with increased risk of adverse effects, such as parkinsonism, hyperprolactinemia, weight gain, and neurocognitive impairment 7.
• The dose-response relationship of antipsychotics can vary depending on the specific medication and individual patient factors, such as age, sex, and comorbidities 7.

Reducing High-Dose Multiple Antipsychotics

• Gradually reducing the dose of antipsychotics, such as by 25 mg or lower of a chlorpromazine-equivalent dose per week for low potency drugs, and 50 mg or lower of a chlorpromazine-equivalent dose per week for high potency drugs, can help minimize adverse effects and reduce the risk of polypharmacy 8.
• Switching between antipsychotics can also help avoid polypharmacy and reduce the risk of adverse effects 8.