Zyprexa, also known as olanzapine, is a second-generation atypical antipsychotic that was patented in 1971 and approved by the Food and Drug Administration (FDA) in 1996. It is primarily used for the treatment of schizophrenia and has been subsequently approved for treating depression in combination with fluoxetine and for managing mania in bipolar disorder. The drug became available in its generic form in 2011.
Indications and Approvals
Schizophrenia:
- Approved for individuals aged 13 and up.
- Can be used as adjunctive therapy with valproate or lithium in treatment-resistant cases.
Bipolar Disorder:
- Approved for treating manic episodes in individuals aged 13 and up.
- Used as an add-on therapy when valproate or lithium alone is insufficient.
Off-Label Uses
Zyprexa is frequently used off-label for conditions where evidence of its benefit is not robust. These include eating disorders, panic attacks, generalized anxiety disorder, delusions of parasitosis, post-traumatic stress disorder, Tourette syndrome, stuttering, hyperactivity, aggressive behavior, repetitive behaviors associated with autism, insomnia, and nausea and vomiting associated with chemotherapy.
Dosage and Administration
Zyprexa is available in 5, 10, 15, and 20 mg oral tablets. It also comes in an intramuscular injection form for rapid onset of action in patients with uncontrolled schizophrenia or mania. Additionally, it is available as an orally disintegrating tablet and a long-acting intramuscular injection.
Schizophrenia:
- Starting dose: 5-10 mg
- Target dose: 10 mg
Bipolar Disorder:
- Mania: 10-15 mg
- If adjunctive with lithium or valproate: 10 mg
Pharmacokinetics and Pharmacodynamics
Absorption:
- Well absorbed orally with maximum concentration reached within six hours.
- Metabolized via first-pass metabolism, with approximately 40% metabolized before reaching systemic circulation.
Half-Life:
- Approximately 30 hours, reaching steady state after about one week.
Excretion:
- About 60% excreted in urine and 30% in feces.
Mechanism of Action:
- Zyprexa works by antagonizing receptors for dopamine and serotonin, and it also affects histamine, adrenergic, and muscarinic receptors. This receptor activity helps alleviate symptoms of schizophrenia and bipolar disorder but also contributes to the drug’s side effect profile.
Common and Serious Side Effects
Common Side Effects:
- Increased blood sugar and diabetes risk
- Elevated triglyceride and cholesterol levels
- Weight gain
- Postural hypotension
- Constipation, dizziness, dry mouth, fatigue, erectile dysfunction, restlessness, and headaches
- Tardive dyskinesia
- Parkinson-like symptoms
Serious Side Effects:
- Agranulocytosis (decrease in white blood cells)
- Myocarditis and cardiomyopathy
- Neuroleptic malignant syndrome (fever, muscle rigidity, potential kidney failure)
- Increased risk of suicidal thoughts and behaviors
Monitoring and Management
Patients on Zyprexa should have regular monitoring of blood counts, liver function, blood sugar, triglycerides, and cholesterol levels. For those receiving the long-acting injection, it is essential to stay under medical supervision for at least three hours post-injection due to the risk of rapid blood level increase and associated side effects.
Usage in Special Populations
Pregnancy:
- Use only if benefits outweigh risks due to potential withdrawal symptoms in newborns and other risks.
Nursing:
- Some presence in breast milk; not recommended unless necessary.
Geriatric Patients:
- Should receive about half the usual dose due to reduced clearance.
Smokers:
- Smoking increases clearance by about 40%, reducing the drug’s effectiveness.
Efficacy and Comparisons
Studies have shown that Zyprexa is effective in treating positive symptoms of schizophrenia, such as agitation, hallucinations, and delusions, better than negative symptoms like apathy or social withdrawal. However, the drug is associated with significant side effects, making it crucial to balance efficacy with tolerability.
Legal and Financial Considerations
Zyprexa has been a significant seller, with sales peaking at over $3 billion annually. However, it has also been the subject of numerous lawsuits related to undisclosed side effects, such as weight gain and diabetes, and off-label promotion. The drug has faced scrutiny and regulations, especially concerning its use in elderly patients with dementia.
Conclusion
Zyprexa is an effective treatment for schizophrenia, bipolar disorder, and treatment-resistant depression. However, due to its significant side effects and risks, it should be used cautiously, and patients should be closely monitored. For any condition outside the main approved uses, it is advisable to seek a second opinion to ensure the appropriateness of this medication.