Olanzapine represents a cornerstone in modern psychopharmacology as a second-generation (atypical) antipsychotic medication. It functions as a multi-receptor targeting agent with potent antagonistic activity at dopamine D2 and serotonin 5-HT2A receptors, alongside significant histaminic, adrenergic, and muscarinic receptor interactions. This comprehensive receptor profile underpins its established efficacy across multiple psychiatric domains, particularly in managing positive and negative symptoms of schizophrenia and acute manic or mixed episodes associated with bipolar I disorder. Clinicians value olanzapine for its predictable pharmacokinetics and well-documented response profile in both acute and maintenance phases of treatment.

Features

• Active Ingredient: Olanzapine
• Pharmacological Class: Thienobenzodiazepine derivative; atypical antipsychotic
• Available Formulations: Oral tablets (standard, orally disintegrating), intramuscular injection (short-acting and extended-release)
• Receptor Binding Profile: High affinity for dopamine D1–D4, serotonin 5-HT2A/2C/3/6, muscarinic M1–M5, α1-adrenergic, and H1 histaminergic receptors
• Bioavailability: Approximately 60% following oral administration, not significantly affected by food
• Half-life: 21–54 hours (permits once-daily dosing)
• Metabolism: Primarily hepatic via CYP1A2 and UGT1A4; minor pathways involve CYP2D6
• Elimination: ~57% excreted in urine, ~30% in feces

Benefits

• Rapid reduction of acute psychotic agitation and aggression through intramuscular formulation
• Comprehensive symptom control addressing both positive (hallucinations, delusions) and negative (avolition, blunted affect) features of schizophrenia
• Effective stabilization of manic and mixed episodes in bipolar I disorder, often within 1–2 weeks
• Lower incidence of extrapyramidal symptoms compared to first-generation antipsychotics
• Proven efficacy as an adjunct in treatment-resistant depression and chemotherapy-induced nausea/vomiting
• Flexible dosing regimens and formulations supporting individualized treatment plans

Common use

Olanzapine is primarily indicated for the treatment of schizophrenia in adults and adolescents aged 13–17 years. It is equally established for the acute management of manic or mixed episodes associated with bipolar I disorder—as monotherapy or combined with lithium or valproate—and for maintenance treatment in responders. Off-label applications include adjunctive therapy in major depressive disorder (inadequate response to antidepressants), behavioral disturbances in dementia (with caution), Tourette syndrome, and as an antiemetic in chemotherapy protocols. Its sedative properties make it occasionally useful in severe insomnia and agitation, though not as a first-line indication.

Dosage and direction

Schizophrenia: Initial dose 5–10 mg once daily, titrating to 10 mg/day within several days. Target range: 10–20 mg/day. Maximum: 20 mg/day.
Bipolar Mania: Starting dose 10–15 mg daily; adjust by 5 mg/day at intervals ≥24 hours. Maintenance: 5–20 mg/day.
Adolescents (13–17 years): Schizophrenia/bipolar mania: Start 2.5–5 mg daily; increase to 10 mg/day. Maximum: 20 mg/day.
Elderly/Debilitated: Begin with 2.5 mg daily.
Hepatic Impairment: Consider starting dose of 2.5 mg.
Administration: May be taken with or without food. Orally disintegrating tablets should be placed on the tongue immediately after opening the blister.

Precautions

• Metabolic Monitoring: Regularly assess weight, BMI, blood glucose, and lipid profile due to risk of hyperglycemia, dyslipidemia, and weight gain
• Orthostatic Hypotension: Risk increased during initial dose titration; monitor blood pressure
• Sedation: Caution when operating machinery; avoid alcohol and other CNS depressants
• Hyperprolactinemia: Monitor for galactorrhea, amenorrhea, gynecomastia
• Dysphagia: Use cautiously in patients at risk for aspiration pneumonia
• Temperature Regulation: Impaired body temperature reduction may occur in heat exposure
• Withdrawal: Neonatal abstinence syndrome reported following third-trimester exposure

Contraindications

• Known hypersensitivity to olanzapine or any component of the formulation
• Concurrent use with other drugs known to cause QT prolongation (e.g., class Ia/III antiarrhythmics)
• Patients with narrow-angle glaucoma
• Severe hepatic impairment (Child-Pugh C)
• Combination with fluvoxamine (strong CYP1A2 inhibitor)

Possible side effect

Very Common (>10%): Somnolence, weight gain, increased appetite, dizziness
Common (1–10%): Orthostatic hypotension, peripheral edema, hyperprolactinemia, elevated transaminases, dry mouth, constipation, akathisia, parkinsonism
Uncommon (0.1–1%): QT prolongation, bradycardia, neutropenia, rash, urinary incontinence
Rare (<0.1%): Pancreatitis, diabetic ketoacidosis, neuroleptic malignant syndrome, tardive dyskinesia, seizures
Postmarketing Reports: Venous thromboembolism, priapism, rhabdomyolysis

Drug interaction

• CYP1A2 Inhibitors (fluvoxamine, ciprofloxacin): Increase olanzapine exposure → reduce olanzapine dose by 50%
• CYP1A2 Inducers (carbamazepine, omeprazole): Decrease olanzapine exposure → may require dose increase
• Antihypertensives: Enhanced hypotensive effects
• Dopamine Agonists (levodopa): Olanzapine may antagonize effects
• CNS Depressants (alcohol, benzodiazepines): Additive sedation and respiratory depression
• QT-Prolonging Agents (amiodarone, moxifloxacin): Increased arrhythmia risk

Missed dose

Take the missed dose as soon as remembered unless it is nearly time for the next scheduled dose. Do not double the dose to catch up. Resume regular dosing schedule. If multiple doses are missed, contact a healthcare provider before restarting to evaluate need for re-titration.

Overdose

Symptoms: Drowsiness, slurred speech, tachycardia, hypotension, agitation, extrapyramidal symptoms, coma. Rarely: respiratory depression, seizures.
Management: Provide supportive care; ensure airway protection. Gastric lavage may be considered if presented early. Activated charcoal can be effective. No specific antidote exists. Cardiovascular monitoring essential. Avoid epinephrine in hypotension (may exacerbate via α-adrenergic blockade). Hemodialysis not effective.

Storage

Store at 20–25°C (68–77°F); excursions permitted to 15–30°C (59–86°F). Protect from light and moisture. Keep orally disintegrating tablets in original blister package until use. Keep all medications out of reach of children and pets.

Disclaimer

This information is intended for healthcare professionals and educated patients under medical supervision. It does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider regarding any medical condition or treatment decisions. Dosage and indications may vary based on individual patient factors and regional prescribing guidelines.

Reviews

“Olanzapine remains a first-line option in our inpatient unit due to its rapid onset and reliable efficacy in acute psychosis. The metabolic side effects require vigilant monitoring, but its clinical benefits often outweigh risks in severe cases.” – Dr. Elena Rostova, Board-Certified Psychiatrist
“While weight gain is a concern, the orally disintegrating formulation has improved compliance in our adolescent population. Dosing flexibility allows fine-tuning based on tolerance and response.” – Dr. Michael Thorne, Child & Adolescent Psychiatry
“As an emergency physician, I value the rapid tranquilization achieved with IM olanzapine in agitated patients. It has reduced our need for physical restraints and repeat dosing compared to haloperidol.” – Dr. Sarah J. Lim, Emergency Medicine