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 combination of antipsychotics may lead to acute extrapyramidal syndromes, including acute dystonia, akathisia, and Parkinsonian syndrome 1.
• Metabolic risks: The use of antipsychotics, particularly atypical antipsychotics such as Zyprexa and Latuda, may lead to weight gain, hyperglycemia, and metabolic syndrome 1.
• Interactions with other medications: The concurrent use of other medications, such as benzodiazepines, may increase the risk of sedation, respiratory depression, and cognitive impairment 1.

Considerations for Treatment

• Monotherapy: Antipsychotic monotherapy should be strived for, as it generally incurs less health service costs and gives a lower overall risk for adverse effects 1.
• Pharmacogenetics: Pharmacogenetic testing may be useful in determining the optimal treatment approach, particularly for patients who are slow or fast metabolizers of certain antipsychotics 1.
• Dose adjustment: Dose adjustment may be necessary based on the patient's metabolic status, smoking status, caffeine consumption, and recreational drug use 1.

Patient-Specific Considerations

• Genetically confirmed resistance to psychosis: The patient's genetically confirmed resistance to psychosis may affect the treatment approach, and clozapine monotherapy may be considered 1.
• Suspected ADHD: The patient's suspected ADHD may require additional treatment considerations, such as the use of stimulants or non-stimulants.
• Intersex condition: The patient's intersex condition may require additional treatment considerations, such as hormone therapy or gender-affirming care.
• History of sexual abuse and harassment: The patient's history of sexual abuse and harassment may require additional treatment considerations, such as trauma-informed care or psychotherapy.
• Denial of right to fill out Advanced Directive/Power of Attorney (PoA): The patient's denial of right to fill out an Advanced Directive/Power of Attorney (PoA) may require additional treatment considerations, such as patient advocacy or legal intervention.

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. The patient's condition should be closely monitored, and the treatment plan should be regularly reassessed 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.