Olanzapine: Effective Atypical Antipsychotic for Symptom Control
Olanzapine
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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 antagonist, with high affinity for serotonin, dopamine, muscarinic, histamine, and adrenergic receptors. Its pharmacodynamic profile contributes to efficacy in managing both positive and negative symptoms of psychotic disorders, as well as acute manic or mixed episodes. Approved by regulatory bodies including the FDA, olanzapine represents a cornerstone in modern psychopharmacology due to its well-established efficacy and tolerability profile in appropriate patient populations.
Features
- Active Ingredient: Olanzapine
- Pharmacologic Class: Thienobenzodiazepine derivative; atypical antipsychotic
- Available Formulations: Oral tablets, orally disintegrating tablets (ODT), and intramuscular injection
- Receptor Binding Profile: High affinity for 5-HT2A/2C, D1-4, H1, α1-adrenergic, and muscarinic receptors
- Bioavailability: Approximately 60% following oral administration, not significantly affected by food
- Half-life: 21–54 hours (mean 30 hours), permitting once-daily dosing
- Metabolism: Primarily hepatic via glucuronidation and CYP1A2-mediated oxidation
- Elimination: Urine (57%) and feces (30%)
Benefits
- Demonstrates robust efficacy in reducing positive symptoms (hallucinations, delusions) and negative symptoms (avolition, blunted affect) in schizophrenia
- Effective in acute manic or mixed episodes associated with bipolar I disorder, both as monotherapy and adjunctive treatment
- Lower incidence of extrapyramidal symptoms (EPS) compared to typical antipsychotics
- Proven efficacy in maintenance treatment, reducing relapse rates in both schizophrenia and bipolar disorder
- Available in multiple formulations allowing for individualized treatment approaches across clinical settings
- Orally disintegrating tablet formulation enhances compliance in patients with swallowing difficulties or acute agitation
Common use
Olanzapine is FDA-approved for the treatment of schizophrenia in adults and adolescents aged 13–17 years. It is also indicated for acute monotherapy or combination therapy of manic or mixed episodes in bipolar I disorder in adults and pediatric patients aged 13–17 years, and as maintenance treatment in bipolar I disorder. Off-label uses include treatment of behavioral disturbances in dementia (with caution due to mortality risk), treatment-resistant depression (as an adjunct), and prevention of chemotherapy-induced nausea and vomiting. Clinical use should always be guided by comprehensive diagnostic assessment and risk-benefit evaluation.
Dosage and direction
Schizophrenia (Adults): Initial dose 5–10 mg once daily; target dose 10 mg/day within several days; maximum 20 mg/day.
Schizophrenia (Adolescents 13–17 years): Initial dose 2.5–5 mg once daily; target dose 10 mg/day; maximum 20 mg/day.
Bipolar I Mania (Adults): Initial dose 10–15 mg once daily; adjust by 5 mg/day at intervals ≥24 hours; maximum 20 mg/day.
Bipolar I Mania (Adolescents 13–17 years): Initial dose 2.5–5 mg once daily; target dose 10 mg/day; maximum 20 mg/day.
Administration: May be taken without regard to meals. Orally disintegrating tablets should be placed on tongue immediately after opening blister; administer with or without liquid. Intramuscular formulation is reserved for acute agitation in schizophrenia and bipolar mania (dose 10 mg; maximum 30 mg/24 hours). Dosage adjustments required in elderly, debilitated patients, those with predisposition to hypotensive reactions, or with concomitant potent CYP1A2 inhibitors (e.g., fluvoxamine). Avoid use in patients with moderate to severe hepatic impairment.
Precautions
- Metabolic Effects: Monitor weight, waist circumference, blood glucose, and lipids at baseline and periodically during treatment. Significant weight gain, hyperglycemia, and dyslipidemia may occur.
- Neurological: Risk of tardive dyskinesia (potentially irreversible) and neuroleptic malignant syndrome (NMS). Observe for extrapyramidal symptoms, particularly at higher doses.
- Cardiovascular: Orthostatic hypotension may occur, especially during initial dose titration. Use with caution in patients with cardiovascular disease, cerebrovascular disease, or conditions predisposing to hypotension.
- Hematological: Transient, asymptomatic elevations in prolactin possible. Rare reports of leukopenia/neutropenia and thrombocytopenia.
- Cognitive Impairment: May impair judgment, thinking, or motor skills; caution patients about operating machinery or driving.
- Elderly Patients with Dementia-Related Psychosis: Not approved for use; increased risk of cerebrovascular adverse events and mortality.
- Withdrawal: Avoid abrupt discontinuation; taper gradually to prevent potential withdrawal symptoms or rebound psychosis.
Contraindications
- Known hypersensitivity to olanzapine or any component of the formulation
- Patients with narrow-angle glaucoma due to anticholinergic effects
- Concurrent use with other drugs known to cause QT prolongation in patients with known QT prolongation or history of cardiac arrhythmias
- Severe hepatic impairment (Child-Pugh Class C)
- Combination with other central nervous system depressants where additive effects may be dangerous
Possible side effect
Very Common (≥10%): Somnolence, weight gain, increased appetite, dizziness, asthenia
Common (1–10%): Orthostatic hypotension, dry mouth, constipation, dyspepsia, akathisia, parkinsonism, elevated prolactin, peripheral edema, elevated liver enzymes
Uncommon (0.1–1%): Rash, bradycardia, QT prolongation, syncope, leukopenia, neutropenia
Rare (<0.1%): Neuroleptic malignant syndrome, tardive dyskinesia, seizures, allergic reactions, pancreatitis
Post-marketing Reports: Diabetic ketoacidosis, hyperosmolar coma, venous thromboembolism, priapism
Drug interaction
- CNS Depressants: Additive sedation with alcohol, benzodiazepines, opioids, or other sedating agents
- Antihypertensives: Enhanced hypotensive effects
- CYP1A2 Inhibitors: Fluvoxamine significantly increases olanzapine exposure (reduce olanzapine dose by 50%)
- CYP1A2 Inducers: Carbamazepine decreases olanzapine exposure (consider dose increase)
- QT-Prolonging Agents: Avoid concomitant use with Class IA/III antiarrhythmics, certain antibiotics, and other QT-prolonging drugs
- Levodopa/Dopamine Agonists: Olanzapine may antagonize effects
- Anticholinergics: Additive anticholinergic effects
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, the missed dose should be skipped and the regular dosing schedule resumed. Do not double the dose to make up for a missed one. Consistent daily administration is important for maintaining therapeutic levels; consider setting reminders or using pill organizers to improve adherence.
Overdose
Symptoms: Drowsiness, slurred speech, tachycardia, hypotension, extrapyramidal symptoms, agitation, coma. Rarely, respiratory depression, seizures, or cardiac arrhythmias.
Management: Provide supportive care including continuous cardiac monitoring. Activated charcoal may be considered if presented early. Hypotension should be managed with IV fluids and vasopressors if necessary. Avoid epinephrine and dopamine due to potential paradoxical hypotension. There is no specific antidote; hemodialysis is not likely to be effective due to high protein binding.
Storage
Store at controlled room temperature 20–25°C (68–77°F); excursions permitted to 15–30°C (59–86°F). Protect from light and moisture. Keep in original container; orally disintegrating tablets must remain in blister package until immediately before use. Keep out of reach of children and pets. Do not use after expiration date printed on packaging.
Disclaimer
This information is for educational purposes and does not constitute medical advice. Olanzapine is a prescription medication that should be used only under the supervision of a qualified healthcare professional. Individual response to therapy may vary. Healthcare providers should review full prescribing information including boxed warnings before initiating treatment. Patients should report any adverse effects or concerns to their prescribing physician promptly.
Reviews
“Olanzapine has been transformative in managing treatment-resistant schizophrenia in my practice. Its efficacy in addressing both positive and negative symptoms, coupled with a relatively favorable neurological side effect profile, makes it a first-line option. However, vigilant metabolic monitoring is non-negotiable.” – Dr. Eleanor Vance, Board-Certified Psychiatrist
“In adolescent bipolar disorder, olanzapine demonstrates rapid antimanic effects that are particularly valuable in acute settings. The availability of an orally disintegrating formulation has been crucial for compliance in younger populations. Weight management strategies must be implemented proactively.” – Dr. Marcus Thorne, Child and Adolescent Psychiatrist
“While effective, olanzapine’s metabolic consequences require careful long-term management. I reserve it for cases where other antipsychotics have failed or where sedation is clinically desirable. Regular metabolic panels and lifestyle counseling are essential components of therapy.” – Dr. Isabel Cortez, Clinical Pharmacologist