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, exhibiting high affinity for serotonin, dopamine, muscarinic, histamine, and adrenergic receptors. Its pharmacodynamic profile underpins its efficacy in managing both positive and negative symptoms of psychotic disorders, as well as acute manic or mixed episodes. This comprehensive profile details its clinical use, mechanisms, and essential safety information for healthcare professionals.

Features

• Active Ingredient: Olanzapine
• Pharmacologic Class: Second-generation (atypical) antipsychotic
• Mechanism of Action: Antagonist activity at serotonin 5-HT2A, dopamine D2, muscarinic M1-5, histamine H1, and adrenergic α1 receptors
• Available Formulations: Oral tablets, orally disintegrating tablets (ODT), and short-acting intramuscular (IM) injection
• 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 cytochrome P450 (CYP1A2 and CYP2D6)
• Excretion: Approximately 57% in urine, 30% in feces

Benefits

• Demonstrates high efficacy in reducing positive symptoms of schizophrenia, such as hallucinations and delusions
• Shows significant activity against negative symptoms, including social withdrawal and affective flattening
• Effective in the acute treatment of manic or mixed episodes associated with bipolar I disorder
• Provides rapid tranquilization in agitated patients via intramuscular formulation
• May be used as maintenance therapy to prevent relapse in both schizophrenia and bipolar disorder
• Lower incidence of extrapyramidal symptoms compared to typical antipsychotics

Common use

Olanzapine is FDA-approved for the treatment of schizophrenia and acute manic or mixed episodes associated with bipolar I disorder. It is also used as maintenance treatment in bipolar disorder to prevent recurrence. Off-label uses may include treatment of agitation associated with dementia (with caution due to black box warning), Tourette’s syndrome, and as an adjunct in treatment-resistant depression. Its broad receptor activity profile makes it particularly useful in cases where both psychotic and mood symptoms are present.

Dosage and direction

Initial dose for schizophrenia: 5–10 mg once daily, with a target dose of 10 mg/day within several days. Bipolar mania: 10–15 mg once daily. Dosage adjustments should occur at intervals not less than 24 hours. The maximum recommended daily dose is 20 mg. For geriatric patients or those with predisposition to hypotensive reactions, consider initial dose of 5 mg. IM administration: 10 mg (5 mg in vulnerable populations), may repeat every 2–4 hours; maximum daily IM dose 30 mg. Administration with or without food is acceptable. Orally disintegrating tablets should be placed on tongue immediately after opening blister.

Precautions

Monitor patients for neuroleptic malignant syndrome (NMS), characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability. Use with caution in patients with cardiovascular disease, cerebrovascular disease, or conditions that predispose to hypotension. May cause transaminase elevations; periodic liver function testing recommended. Can prolong QT interval; assess baseline and periodic ECGs in at-risk patients. May alter thermoregulation; caution advised when exposed to extreme heat. Antiemetic effect may mask signs of intestinal obstruction or brain tumor.

Contraindications

Known hypersensitivity to olanzapine or any component of the formulation. Concurrent use with other drugs known to cause agranulocytosis or neutropenia. Severe central nervous system depression or comatose states. Patients with narrow-angle glaucoma due to anticholinergic effects.

Possible side effect

Very common (>10%): Somnolence, weight gain, increased appetite, dizziness, orthostatic hypotension.
Common (1-10%): Peripheral edema, elevated prolactin, extrapyramidal symptoms, dry mouth, constipation, dyspepsia, akathisia, tremor.
Uncommon (0.1-1%): Rash, bradycardia, syncope, elevated liver enzymes, leukopenia.
Rare (<0.1%): Neutropenia, agranulocytosis, seizures, priapism, allergic reactions.
Metabolic effects: May cause hyperglycemia, dyslipidemia, and weight gain requiring ongoing monitoring.

Drug interaction

Strong CYP1A2 inhibitors (e.g., fluvoxamine) increase olanzapine exposure; reduce olanzapine dose by 50%.
CYP1A2 inducers (e.g., carbamazepine) decrease olanzapine levels; may require dose adjustment.
Potentiates effects of antihypertensives and CNS depressants (alcohol, benzodiazepines, opioids).
May antagonize effects of dopamine agonists (e.g., levodopa).
Fluvoxamine, ciprofloxacin: Increase olanzapine concentrations.
Omeprazole: May slightly decrease olanzapine absorption.

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 dose.

Overdose

Symptoms may include drowsiness, slurred speech, tachycardia, hypotension, extrapyramidal symptoms, and agitation. Delirium, coma, convulsions, and respiratory depression may occur in severe cases. No specific antidote exists; provide symptomatic and supportive treatment. Cardiovascular monitoring essential. Consider activated charcoal if presented early. Hemodialysis unlikely to be beneficial due to high protein binding.

Storage

Store at controlled room temperature 20–25°C (68–77°F). Protect from light and moisture. Keep in original container with lid tightly closed. Orally disintegrating tablets must remain in blister package until time of use. Keep out of reach of children and pets.

Disclaimer

This information is intended for healthcare professionals and should not replace clinical judgment. Prescribers should consult full prescribing information before initiating therapy. Dosage must be individualized based on clinical assessment. Patients should be monitored regularly for therapeutic response and adverse effects, particularly metabolic parameters.

Reviews

Clinical trials demonstrate olanzapine’s superiority over placebo in acute schizophrenia (PANSS reduction ≥30% in 55.1% vs 26.1% placebo) and bipolar mania (YMRS response rates 64.8% vs 42.8% placebo). Maintenance studies show significant relapse prevention with number needed to treat (NNT) of 5 for schizophrenia. Real-world evidence supports its efficacy in treatment-resistant cases, though metabolic side effects require careful management. Systematic reviews position it among most effective antipsychotics for overall symptom control but with higher metabolic liability than some alternatives.