Olanzapine: Advanced Antipsychotic Therapy for Symptom Control
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Synonyms | |||
Olanzapine is an atypical antipsychotic medication indicated for the treatment of schizophrenia and bipolar I disorder. It functions primarily as a multi-receptor targeting agent, demonstrating high affinity for serotonin, dopamine, muscarinic, histaminic, and adrenergic receptors. This comprehensive receptor profile underpins its efficacy in managing both positive and negative symptoms of psychotic disorders, as well as acute manic or mixed episodes. Clinicians value olanzapine for its established therapeutic history and robust clinical evidence supporting its use in acute and maintenance phases of treatment.
Features
- Active ingredient: Olanzapine
- Pharmacologic class: Thienobenzodiazepine derivative; atypical antipsychotic
- Available formulations: Oral tablets (2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg), orally disintegrating tablets (Zydis), and intramuscular injection for acute agitation
- Receptor binding profile: High affinity for 5-HT2A/2C, D1-4, H1, α1-adrenergic, and muscarinic receptors
- Half-life: 21–54 hours (permits once-daily dosing)
- Metabolism: Hepatic, primarily via CYP1A2 and UGT1A4; minor pathways include CYP2D6
Benefits
- Effective reduction of positive symptoms (hallucinations, delusions) and negative symptoms (social withdrawal, apathy) in schizophrenia
- Rapid control of acute agitation in manic or mixed episodes of bipolar I disorder, with availability of intramuscular formulation for emergent use
- Lower incidence of extrapyramidal symptoms compared to typical antipsychotics
- Proven efficacy in maintenance therapy, reducing relapse rates in both schizophrenia and bipolar disorder
- Flexible dosing options, including orally disintegrating tablets for enhanced compliance in patients with dysphagia or adherence challenges
Common use
Olanzapine is FDA-approved for the treatment of schizophrenia in adults and adolescents aged 13–17 years, and for acute monotherapy or combination therapy (with lithium or valproate) in manic or mixed episodes associated with bipolar I disorder. It is also indicated for maintenance treatment in bipolar I disorder. Off-label uses may include treatment of agitation in dementia (though with black box warnings), Tourette syndrome, and as an adjunct in treatment-resistant depression. Clinical decision-making should always be guided by a thorough risk-benefit assessment and adherence to approved indications unless compelling evidence supports alternative use.
Dosage and direction
Dosage must be individualized based on clinical presentation, tolerability, and treatment response.
- Schizophrenia (adults): Initial dose 5–10 mg once daily; target dose 10 mg/day within several days; range 10–20 mg/day. Maximum recommended dose: 20 mg/day.
- Schizophrenia (adolescents 13–17 years): Start with 2.5–5 mg once daily; adjust to target 10 mg/day; maximum 20 mg/day.
- Bipolar I Mania (monotherapy): Initial dose 10–15 mg once daily; adjust by 5 mg/day at intervals ≥24 hours; recommended range 5–20 mg/day.
- Bipolar I Mania (adjunct to lithium/valproate): Start at 10 mg once daily; range 5–20 mg/day.
- Elderly or debilitated patients: Consider lower starting dose (2.5 mg/day).
- Hepatic impairment: Consider starting dose of 5 mg in moderate to severe cirrhosis.
- Administration: Can be taken with or without food. Orally disintegrating tablets should be placed on the tongue and allowed to dissolve; no water needed.
Precautions
- Metabolic effects: Monitor weight, blood glucose, and lipids at baseline and periodically. Significant weight gain, hyperglycemia (including diabetic ketoacidosis), and dyslipidemia have been reported.
- Neuroleptic Malignant Syndrome (NMS): Although rare, monitor for hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability. Discontinue immediately if suspected.
- Tardive Dyskinesia (TD): Risk may increase with duration of treatment and total cumulative dose. Periodically assess for involuntary movements.
- Orthostatic hypotension: Due to α1-adrenergic blockade. Use caution in patients with cardiovascular or cerebrovascular disease.
- Sedation: Common during initial treatment. Advise patients regarding activities requiring alertness.
- Elderly patients with dementia-related psychosis: Increased risk of mortality and cerebrovascular adverse events. Not approved for this use.
- Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics.
Contraindications
- Hypersensitivity to olanzapine or any component of the formulation.
- Patients with narrow-angle glaucoma (due to anticholinergic effects).
Possible side effect
Common (≥5%):
- Somnolence, dizziness, insomnia
- Weight gain
- Dry mouth, constipation
- Increased appetite
- Orthostatic hypotension
Less common:
- Elevated prolactin (galactorrhea, amenorrhea)
- Transient asymptomatic elevations in hepatic transaminases
- Akathisia, parkinsonism (though less frequent than with typical antipsychotics)
- Rash
Rare but serious:
- Diabetic ketoacidosis, hyperosmolar coma
- Seizures
- Venous thromboembolism
- Priapism
Drug interaction
- CNS depressants (e.g., alcohol, benzodiazepines, opioids): Additive sedation and respiratory depression.
- Antihypertensives: Potentiated hypotension.
- Strong CYP1A2 inhibitors (e.g., fluvoxamine): Increase olanzapine exposure; consider dose reduction.
- CYP1A2 inducers (e.g., carbamazepine, omeprazole): Decrease olanzapine levels; may require dose adjustment.
- Levodopa and dopamine agonists: Olanzapine may antagonize effects.
- Medications that prolong QTc (e.g., antiarrhythmics, certain antibiotics): Theoretical additive effect; use with caution.
Missed dose
If a dose is missed, it should be taken as soon as remembered unless it is close to the time of the next scheduled dose. In that case, skip the missed dose and resume the regular dosing schedule. Do not double the dose to make up for a missed one.
Overdose
Symptoms may include drowsiness, slurred speech, tachycardia, hypotension, and extrapyramidal symptoms. In large overdoses, delirium, coma, respiratory depression, and cardiac arrhythmias are possible. There is no specific antidote. Provide supportive care, including continuous ECG monitoring, and consider activated charcoal if presented early. Hemodialysis is unlikely to be beneficial due to high protein binding.
Storage
Store at controlled room temperature (20–25°C or 68–77°F). Protect from light and moisture. Keep orally disintegrating tablets in the original blister pack until use. Keep all medications out of reach of children and pets.
Disclaimer
This information is intended for educational and clinical reference purposes only and does not constitute medical advice. Always consult a qualified healthcare professional for diagnosis, treatment decisions, and personalized dosing. Safety and efficacy in pediatric patients under 13 years of age have not been established for all indications. Use during pregnancy or lactation should be carefully weighed against potential risks.
Reviews
Olanzapine has been extensively studied in randomized controlled trials and real-world settings. Clinical evidence supports its efficacy in reducing psychotic and manic symptoms, though metabolic side effects are a significant consideration. Many experts regard it as a first-line option in acute settings due to its rapid onset and tolerability profile compared to typical antipsychotics. Long-term studies confirm its utility in maintenance therapy, though regular monitoring is essential. Patient adherence is often facilitated by once-daily dosing and formulation options.