What Is Olanzapine?
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Olanzapine - Uses, Dosage, Side Effects, Precautions, and Interactions

Published on Feb 07, 2023   -  16 min read


Olanzapine is an antipsychotic drug used to treat schizophrenia and bipolar disorders. Read the article to know more about it.


Olanzapine is an antipsychotic medication used to treat psychotic conditions such as schizophrenia and bipolar disorder in adults and children over the age of 13. It is a prescription drug and may also be used with Fluoxetine (an antidepressant used in major depressive disorder) to treat bipolar disorders. Olanzapine acts by regulating the number of certain substances, such as dopamine and serotonin, in the brain.

How Does Olanzapine Work?

Olanzapine belongs to a group of drugs called atypical antipsychotics that work by affecting the chemical messengers (neurotransmitters) such as dopamine and serotonin in the brain.

Olanzapine works by acting on the neurotransmitters such as dopamine and serotonin receptors. It works on dopamine D2 receptors in the mesolimbic pathways as an antagonist and inhibits its action at the postsynaptic receptor. Olanzapine augments the effect of serotonin reuptake inhibitors by suppressing GABA (gamma-aminobutyric acid) inhibition by antagonizing 5-HT6 receptors in the dorsal raphe nucleus.

Olanzapine is well absorbed and reaches its peak concentration six hours after oral administration. The drug is extensively metabolized by first-pass metabolism. The absorption of the drug is not affected by the presence of food. It may take several days or weeks to see visible improvement. Olanzapine has a half-life of 21 to 54 hours. It is mainly excreted in the urine (53 %) and feces (30 %).

Uses of Olanzapine:

Olanzapine treats symptoms of schizophrenia (a mental illness that causes unusual thinking and strong inappropriate emotions) and other mental conditions in adults and teenagers. The drug may be used in combination with other medications to treat depression.

Olanzapine treats bipolar disorder (a manic depressive disorder) that causes extreme mood swings with emotional highs and lows.

It helps to treat symptoms such as hallucinations and unusual thinking and enables more clarity and positivity. This helps the person to take part actively in daily activities. Olanzapine is used together with Fluoxetine to treat episodes of depression in adults and children of at least ten years.


  • Injectable Olanzapine carries the risk of post-injection syndrome. The signs and symptoms may include sedation and delirium that are consistent with Olanzapine overdose.

  • Olanzapine is not FDA-approved for patients under the age of 13.

  • Prolonged use of Olanzapine can cause tardive dyskinesia that is characterized by symptoms such as grimacing, sucking, and smacking of the lips.

Route of Administration

  • Oral

  • Injection.

Dosage Strengths


  • 2.5 milligrams.

  • 5 milligrams.

  • 7.5 milligrams.

  • 10 milligrams.

  • 15 milligrams.

  • 20 milligrams.

Orally Disintegrating Tablets

  • 5 milligrams.

  • 10 milligrams.

  • 15 milligrams.

  • 20 milligrams.

Short-Acting Injection - 10 milligrams.

Extended-Release Suspension -

  • 210 milligrams per vial.

  • 300 milligrams per vial.

  • 405 milligrams per vial.

Dosage Forms

  • Tablets

  • Orally Disintegrating Tablets.

  • Injection.

Typical Dosage

The starting oral dose for

  • Adults 64 and younger - 10 milligrams once a day.

  • Adults 65 and over - 5 milligrams once a day.

The starting dose of injection usually ranges from 150 milligrams to 405 milligrams.


Special Considerations:

Warnings and Contraindications


  • Hypersensitivity - Olanzapine should not be given to people who have had an allergic reaction to the active ingredients of the drug. A severe allergic reaction called hypersensitivity syndrome may occur in some people. It is a fatal reaction that involves several body organs if not treated immediately.

  • Diabetes - Olanzapine can cause fatal outcomes, such as diabetic ketoacidosis (a diabetes complication where the body produces excess blood acids) that may lead to death. Therapy with Olanzapine is contraindicated in patients with diabetes.

Warnings and Precautions

  • Dementia - Therapy with Olanzapine in patients, especially the elderly, can increase the risk of cerebrovascular adverse effects such as stroke and transient ischemic attacks. The use of atypical antipsychotic agents is not approved for treating patients with dementia-related psychosis.

  • Acute Alcohol Intoxication - Therapy with Olanzapine is contraindicated in patients with acute alcohol intoxication, as it may aggravate central nervous system depressant effects. This can result in severe respiratory depression and respiratory arrest.

  • Central Nervous System Depressants - Olanzapine is contraindicated in patients with severe central nervous system depression. The drug can potentially depress the nervous and respiratory systems and aggravate the condition.

  • Neuroleptic Malignant Syndrome - Treatment with Olanzapine may precipitate or aggravate a fatal symptom complex known as a neuroleptic malignant syndrome (NMS) with symptoms including hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability.

  • Tardive Dyskinesia - Therapy with Olanzapine may precipitate symptoms of tardive dyskinesia, a syndrome that causes involuntary rhythmic movements of the tongue, face, mouth, lips, jaw, and extremities. There may be a risk of irreversible conditions with the duration and dose of the drug.

  • Aspiration - Olanzapine should be cautiously administered in patients at risk for aspiration pneumonia.

  • Lipid Alterations - The use of Olanzapine is associated with alterations in lipid levels. It is important to obtain a fasting lipid profile before initiation of the therapy.

  • Obesity - Olanzapine can increase the risk of weight gain and should be monitored at baseline. Patients with diabetes should be monitored for blood glucose when treated with Olanzapine.

  • Liver Disease - The liver extensively metabolizes Olanzapine. Therapy with neuroleptics should be administered with caution in patients with liver disease and may be initiated with lower dosages.

  • Diabetes - Olanzapine can increase blood sugar levels. It is important to check the blood sugar levels before and during the treatment with Olanzapine.

For Patients

What Is Schizophrenia?

Schizophrenia is a serious mental disorder affecting a person's thinking. Chronic conditions impact a person's speech, thinking, and emotions, which may affect their social interactions and daily activities. Schizophrenia is a life-long condition, but the patient can be treated for the symptoms. Research shows that schizophrenia affects men and women equally and is usually diagnosed in people between 16 and 30.

Symptoms of schizophrenia are characterized by significant impairment in how reality is perceived and behavioral changes related to

  • Persistent delusions (false reality).

  • Hallucinations (seeing or hearing things that are not there).

  • Disorganized thinking.

  • Extreme agitation.

  • Trouble concentrating.

  • Movement disorders.

What Is Bipolar Disorder?

It is a mental illness, formerly known as a manic-depressive illness, that affects the brain. A person with bipolar disorder experiences intense mood, energy levels, and behavior variations. There are maniac (feeling high) episodes and depressive episodes (feeling low).

Some symptoms of bipolar disorder include

  • Feeling sad or hopeless most of the time.

  • Lacking energy.

  • Feeling of worthlessness.

  • Difficulty in concentrating.

  • Self-doubt.

  • Distractibility.

  • Increased or fast speech.

Bipolar disorder can be treated with medications and psychotherapy.

Why Is Olanzapine Prescribed For Schizophrenia?

Olanzapine helps to improve thinking, mood, and behavior. It is also associated with low extrapyramidal symptoms in people taking antipsychotic drugs, such as the inability to sit still, involuntary muscle contractions, or involuntary facial movements. These symptoms often cause discontinuation of the treatment and poor patient compliance.

Facts One Should Know About Olanzapine:

  • Olanzapine does not work immediately. It may take several days or weeks to show improvement in the symptoms.

  • Common side effects of Olanzapine are dizziness, constipation, or sleepiness.

  • Do not stop taking Olanzapine without informing the doctor, even if one starts to feel better. Adults and people over 18 can take Olanzapine.

  • Olanzapine is not approved for dementia-related psychosis, especially in the elderly, as it can increase the risk of cardiovascular events, including death. The drug has a “Black Box warning” and is available only through a restricted distribution program.

  • Missing a dose of Olanzapine can increase the risk of relapse of the condition's symptoms.

How Should One Take Olanzapine?

  • Olanzapine is available in tablet form and may be taken daily. It is also available as orally disintegrating tablets that dissolve in the mouth.

  • The drug may be taken with or without meals.

  • Olanzapine tablets must be taken at the same time each day. This helps to avoid missing the dose.

  • Taking Olanzapine tablets more than the prescribed dose can cause adverse effects and should be avoided.

  • Avoid touching the orally disintegrating tablets with wet hands, as it can damage the medicine. The medicine should be taken with dry hands and immediately administered with or without liquid.

  • Olanzapine may take several weeks to show full benefits and results and should not be stopped even if one starts to feel well.

  • Do not increase or decrease the dosage of Olanzapine without consent from the doctor. The doctor will change it according to how well the medicine is working.

  • If you miss a dose of Olanzapine, it should be taken as soon as possible. Do not take two doses at once, as it may cause adverse events.

  • Typically, the medication is started on a low dose and increases slowly over several weeks.

Information Be Given to the Doctor Before Taking Olanzapine:

  • Allergies - Therapy with Olanzapine can cause a rare but severe skin reaction known as Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) that can cause fever, swollen lymph nodes, or swelling in the face.

  • Medical History - Inform the doctor of any concurrent illnesses one may be suffering from, especially brain-related damages such as head injury, cancer, seizures, prolonged breathing problems such as asthma, sleep apnea, obstructive pulmonary disease, kidney disease, liver disease, mental disorders such as confusion, depression, suicidal thoughts, or history of substance abuse.

  • Drug History - Give the doctor a complete list of the prescription and non-prescription medications one may be taking, including any herbal supplements, nutritional supplements, and vitamins. Ensure to inform the doctor if one is already taking antidepressants or antipsychotic medications.

  • Pregnancy- Olanzapine can be taken during pregnancy. The patient must inform the doctor about their medication. If the person becomes pregnant during medication, do not stop the medication without telling the doctor.

  • Lactation - Olanzapine passes into the breast milk. The doctor may allow the patient to continue taking the medication if the baby is born healthy. However, If the baby is unusually irritated or sleepy, one may consult the doctor.

  • Geriatrics - Elderly patients are likelier to have dementia or age-related liver and kidney problems. These patients may require an adjustment in the dosage while receiving Olanzapine.

  • Children - Olanzapine is not approved for use in children.

Safety of Olanzapine:

The second-generation antipsychotic is better tolerated than the first-generation antipsychotic but is associated with clinically significant metabolic disturbances, such as diabetes, dyslipidemia, and weight gain. However, Olanzapine has the highest risk for metabolic syndrome among second-generation atypical antipsychotics, especially when taken for an extended period.

Olanzapine therapy is associated with a lower incidence of extrapyramidal symptoms (drug-induced movement disorder) than typical and some atypical antipsychotics.

Effectiveness of Olanzapine:

Olanzapine is more effective than other second-generation drugs. The antipsychotic may not cure the condition, but it improves the symptoms of mental health conditions, such as schizophrenia and bipolar disorder. The drug has been shown to help address a range of anxiety and depressive symptoms in individuals with schizophrenia.

Side Effects Expected With Olanzapine:

Olanzapine may cause common side effects that may include

  • Weakness.

  • Restlessness.

  • Dizziness.

  • Unusual behavior.

  • Difficulty falling asleep.

  • Constipation.

  • Weight gain.

  • Dry mouth.

  • Breast enlargement.

  • Fast or slow heartbeat.

  • Decreased sexual ability.

  • Pain in the arms, legs, back, or joints.

Serious side effects may include

  • Seizures.

  • Muscle stiffness.

  • Fast and irregular heartbeat.

  • Swelling in the arms, hands, feet, or lower legs.

  • Hives.

  • Vision changes.

  • Difficulty in breathing and swallowing.

  • Excessive sweating.

  • Sore throat, associated with fever and chills.

  • Redness in the skin.

Can One Stop Taking Olanzapine Suddenly Without the Doctor's Approval?

  • Never stop taking medicines without talking to the doctor. The doctor will decrease the dose gradually.

  • Do not take the drug more than advised by the doctor.

  • Abruptly stopping Olanzapine causes withdrawal symptoms or relapse of the illness. The doctor tells us that the drug dose should be gradually tapered down.

Dietary Restrictions to Consider When Taking Olanzapine:

  • Grapefruit - Avoid grapefruit or juice with Olanzapine, as it can cause fatal side effects.

  • Tobacco Products - Avoid consumption of tobacco or smoking, as it may alter the drug's effectiveness.

  • Caffeinated Foods - Consuming caffeine-containing foods and beverages should be avoided, as it can interact with the liver enzymes P$%)-CYP1A2, the enzyme that metabolizes Olanzapine. Caffeine can increase the drug levels in the blood and increase the risk of adverse effects.

Storage of Olanzapine:

  • Keep Olanzapine medicine in their original packing.

  • Store at room temperature between 15 to 30 degrees. The injections before reconstitution may be stored at 20 to 25 degrees centigrade.

  • Store the orally disintegrating tablets in their sealed package. Once opened, immediately use the medicine.

  • Direct contact with heat, air, and light may damage the medicines. Therefore, keep the medicines away from direct light and heat.

  • Keep all medicines out of reach of children and pets. Always lock the safety caps of the medication to protect small children from poisoning themselves.

Disposal of Olanzapine Medicines:

  • Do not keep outdated medicines or medicines that are no longer needed. Discard any unused portion of the reconstituted vial.

  • Likewise, unneeded Olanzapine tablets should not be disposed of by flushing or throwing them out with regular garbage.

  • Dispose of the medicine through the local medicine take-back program, which can be accessed or learned more about through the local pharmacist.

  • Some people may not have access to a drug take-back program. Ask the local pharmacist about any other drug disposal options available.


  • In case of an overdose, call the poison control helpline.

  • Call the emergency services if the person has collapsed or has trouble breathing.

  • Overdose symptoms include nausea, vomiting, dizziness, confusion, Extreme thirst, fainting, headache, flushing, or loss of consciousness.

  • Symptoms of overdose may include drowsiness, fast heartbeat, slurred speech, agitation, sudden loss of movement (standing and walking), and loss of consciousness.

  • Supportive treatment is initiated following the patient's clinical signs and symptoms.

For Doctors


  • Olanzapine is a second-generation atypical antipsychotic medication used to treat schizophrenia and certain bipolar disorders. It is approved for use with antidepressants, Fluoxetine, to treat episodes of depression associated with bipolar disorder type 1 and treatment-resistant depression.

  • It is also indicated in combination with Lithium or Valproate for short-term treatment of acute manic or mixed episodes associated with bipolar disorder in adults.

  • Olanzapine has been recently approved to be used with Samidorphan to attenuate Olanzapine-induced weight gain for schizophrenia and bipolar disorder.

  • Olanzapine can be used off-label for acute agitation, delirium, anorexia nervosa, and chemotherapy-induced nausea and vomiting.

Pharmacology of Olanzapine:


Olanzapine is a thienobenzodiazepine drug classified as an atypical or second-generation antipsychotic drug.


Active Ingredients - Olanzapine.

Inactive Ingredients -

  • Crospovidone.

  • FD and C blue no. 2 aluminum lakes.

  • Hydroxypropyl cellulose.

  • Hypromellose.

  • Lactose.

  • Magnesium stearate.

  • Microcrystalline cellulose.

  • Polyethylene glycol.

  • Titanium dioxide.

Clinical Pharmacology

Mechanism of Action: Olanzapine affects the brain's chemical messengers (neurotransmitters), such as dopamine and serotonin. Olanzapine works by acting on the neurotransmitters such as dopamine and serotonin receptors. It works on dopamine D2 receptors in the mesolimbic pathways as an antagonist and inhibits its action at the postsynaptic receptor. Olanzapine augments the effect of serotonin reuptake inhibitors by suppressing GABA (gamma-aminobutyric acid) inhibition by antagonizing 5-HT6 receptors in the dorsal raphe nucleus.


The effect of Olanzapine on the D2 receptors produces positive effects, such as a decrease in hallucination, delusion, disorganized speech, thoughts, and behaviors. However, the effect on serotonin 5HT2A receptors prevents the onset of anhedonia (lack of pleasure), poor speech, lack of motivation, and poor attention.

The drug has a high affinity for dopamine D2 receptors compared to other dopamine receptor isotypes.


  • The Mean Cmax- 29.4 L per hour.

  • Median Tmax- Within five to eight hours.

[Cmax- Maximum concentration achieved by a drug in the blood, cerebrospinal fluid, or target organ after administration of a dose]

[Tmax- Time taken for a drug to reach maximum concentration after administration of a dose]

The absorption of the drug is not affected by the presence of food.

Pharmacokinetic Changes

A. Distribution

  • Steady-state Plasma Levels - 150 ng/ml with an AUC (area under the curve) of 333 ng/ ml.

  • Protein Bound - 93 %.

  • Time to Approach Steady-state Levels - Six hours.

  • Mean Volume of Distribution - 1000 liters.

B. Metabolism

  • Metabolic Processes- The drug is extensively metabolized through direct glucuronidation and CYP450 oxidation. The primary circulating metabolites of Olanzapine are 10-N-glucuronide and 4-N-desmethyl Olanzapine which is clinically inactive and formed by the activity of CYP1A2. The CYP2D6 catalyzes the formation of 2-OH Olanzapine, and the flavin-containing monooxygenase (FMO3) is responsible for N-oxide Olanzapine. UST1A4 plays a crucial role in generating direct conjugation forms of Olanzapine.

C. Elimination

The mean terminal elimination half-life of Olanzapine in healthy individuals varies based on age and gender. Olanzapine presents a half-life ranging between 21 to 54 hours, with an average half-life of 30 hours.

  • Urine - 57 percent.

  • Feces - 30 percent.

Special Considerations:

  • Pregnancy - Olanzapine should be taken during pregnancy only if the potential benefits justify the risk to the mother and the fetus.

  • Renal Impairment - Studies have linked Olanzapine with an increased risk of acute kidney injury and chronic kidney disease.

  • Hepatic Impairment - Therapy with Olanzapine has been associated with severe liver toxicity and should not be used in patients with preexisting liver dysfunction.

  • Alcohol - Alcohol can increase the nervous system side effects of Olanzapine, such as dizziness, drowsiness, and difficulty concentrating. Avoid or limit the use of alcohol while being treated with Olanzapine.

Drug Interactions:

Certain medications may interact with Olanzapine and affect its effectiveness. These include

  • Clozapine - Avoid using Olanzapine with other atypical antipsychotic drugs, as it can cause serious cardiovascular side effects, such as low blood pressure. There may be an increase in other side effects, including dizziness, blurred vision, constipation, or irregular heart rhythm.

  • Carbamazepine - The use of benzodiazepines, such as Carbamazepine, Lorazepam, Midazolam, or Triazolam, is not recommended due to the potential for excessive sedation and cardiorespiratory depression. It is more likely to occur in older adults or those in a debilitating condition.

  • Fluvoxamine - Fluvoxamine (a selective serotonin reuptake inhibitor used for obsessive-compulsive disorder) increases the level of Olanzapine in the blood. It may cause side effects, such as dizziness, drowsiness, dry mouth, or constipation.

  • Ciprofloxacin - Use of Ciprofloxacin (a quinolone antibiotic) or Enoxacin may significantly increase the levels of Olanzapine in the blood and may result in side effects, such as dizziness, dry mouth, constipation, and increased appetite, and increased blood sugar.

  • Buprenorphine - Combining narcotic analgesics, such as Buprenorphine, can cause central nervous system depression leading to respiratory distress or coma.

  • Alfentanil - Taking Alfentanil, Butorphanol, Codeine, or other cough medications can cause central nervous system depression with side effects like respiratory distress, coma, or even death. These medications and Olanzapine can exacerbate symptoms, such as dizziness, difficulty concentrating, and impaired judgment.

  • Bupropion - Combining Olanzapine with antidepressants, such as Bupropion, can increase the risk of seizures. It is more likely to occur in susceptible people, such as the elderly, those undergoing alcohol withdrawal, or having a history of seizures.

  • Lohexol - Injection of Iohexol used in imaging procedures can cause seizures.

  • Omeprazole - Taking Olanzapine with Omeprazole can reduce the effectiveness of the antipsychotic drug or may worsen the condition.

What Have Clinical Trials Shown About Olanzapine?

Trial 1:

Objective - Does continuing antipsychotic medicines reduce the risk of relapse among patients with psychotic depression in remission?

  • A 36-week randomized clinical trial was conducted at four academic medical centers.

  • Eighteen years and older patients with psychotic depression were acutely treated with Sertraline and Olanzapine for 12 weeks. These patients met the criteria for remission of psychosis and depressive symptoms for eight weeks before entering the trial.

  • Participants were randomized to continue Olanzapine or switch to placebo while continuing with Sertraline.

Primary Outcome - Risk of relapse.

Secondary Outcome - Changes in weight, waist circumference, lipids, serum glucose, and hemoglobin (HbA1C).


Among 126 participants, 114 completed the trial. The median dosage of Sertraline was 150 milligrams, and the dosage of Olanzapine was 15 milligrams.

  • Thirteen participants were randomized to Olanzapine, and 34 of the placebo experienced a relapse.

  • The effect of Olanzapine on the daily rate of anthropometric and metabolic measures is significantly different from the placebo.


Among the patients with psychotic depression remission, continuing with Sertraline and Olanzapine compared with Sertraline plus placebo reduced the risk of relapse over 36 weeks.

Trial 2:

Objective - To compare Olanzapine with Risperidone to treat schizophrenia.

  • A meta-analysis was carried out to compare the safety and efficacy of Olanzapine with Risperidone in the treatment of schizophrenia.

  • Data from randomized, double-blinded studies were analyzed according to short and longer-term treatment.

  • It included all dose analyses and sensitivity analyses of clinically relevant doses.

  • A range of efficacy and safety parameters was measured.


Olanzapine produced statistically significant improvements in efficacy and safety parameters compared with Risperidone over the short and longer term. All The scores and scale changes were significantly in favor of Olanzapine. Also, results from the sensitivity analysis of only clinically relevant doses further favored Olanzapine compared with the all-doses analysis.


Small changes in the presence or severity of psychotic symptoms and side effects can affect a patient's prognosis and quality of life. The study conveys the clinical relevance and safety advantages of Olanzapine.

Complications or Side Effects:

Drowsiness - Consuming alcohol with Olanzapine should be avoided, as it can tire one. Avoid driving and operating heavy machinery, as Olanzapine can make you drowsy or sleepy.

Dizziness - Initial doses of Olanzapine may make one feel dizzy. The problem wears off when one gets used to the medicine. Avoid standing up suddenly after a long-time sitting or lying position. Wait until the dizziness subsides.

Rash - Olanzapine can cause rashes and allergic reactions, which may require the person to take antihistamines.

Constipation - One of the common side effects of Olanzapine is constipation. Eat more high-fiber foods, such as leafy vegetables and cereals. Drinking several glasses of water can help reduce constipation.

Article Resources

Last reviewed at:
07 Feb 2023  -  16 min read




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