Olanzapine – Uses and Effects

Background

Olanzapine is a thienobenzodiazepine classified as an atypical or second-generation antipsychotic agent. The second-generation antipsychotics were introduced in the 90s and quickly gained traction due to their impressive efficacy, reduced risk for extrapyramidal side effects and reduced susceptibility to drug-drug interactions. Olanzapine very closely resembles clozapine and only differs by two additional methyl groups and the absence of a chloride moiety. It was discovered by scientists at Eli Lilly and approved to be marketed in the US in 1996.

Properties and Characteristics of Olanzapine

Drug class	Antipsychotic drug
Brand Names	Zyprexa®, Lybalvi, Olazax, Symbyax, Zalasta, Zypadhera,
Synonyms	Olanzapin, Olanzapina, Olanzapine, Olanzapinum
Molecular Formula	C17H20N4S
Molecular Weight	312.4 g/mol
IUPAC Name	2-methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine
Structural formula of main components
Pure active ingredient	Olanzapine
Appearance	Yellow crystalline solid
Melting point	189-195 °C
Solubility	In water, 39.88 mg/L at 25 °C (est)
Excretion	Mainly excreted in the urine
Storage	Recommended storage temperature: 2 – 8 °C
Available Forms	Tablet, orally disintegrating, Tablet, film coated
Prescription	Doctor prescription

Uses of Olanzapine

Olanzapine is a medication with several medical uses, primarily in the treatment of mental health disorders. Some of its primary uses include:

1. Schizophrenia: Olanzapine is commonly prescribed to individuals with schizophrenia. It helps manage symptoms such as hallucinations (false perceptions), delusions (false beliefs), thought disorders, and agitation.
2. Bipolar Disorder: Olanzapine is used in the treatment of bipolar disorder, particularly in the manic or mixed episodes. It can help stabilize mood and reduce the severity and duration of manic episodes.
3. Major Depressive Disorder (MDD): Olanzapine is sometimes used in combination with other medications for the treatment of major depressive disorder, especially when other treatments have not been effective.
4. Agitation Associated with Schizophrenia and Bipolar Disorder: Olanzapine can help manage severe agitation in individuals with schizophrenia or bipolar disorder.
5. Agitation Associated with Autism: It is also used to treat severe agitation and aggression in children and adolescents (ages 13-17) with autism spectrum disorder.
6. Tourette’s Disorder: It may be prescribed to individuals with Tourette’s disorder to help manage tics and associated behavioral symptoms.
7. Prevention of Nausea and Vomiting: In some cases, olanzapine is used in combination with other medications to prevent nausea and vomiting caused by chemotherapy or radiation therapy.

Olanzapine side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: skin rash, fever, swollen glands, muscle aches, severe weakness, unusual bruising, or yellowing of your skin or eyes.

High doses or long-term use of it can cause a serious movement disorder that may not be reversible. The longer you use olanzapine, the more likely you are to develop this disorder, especially if you are a woman or an older adult.

Olanzapine may cause serious side effects. Call your doctor at once if you have:

• Uncontrolled muscle movements in your face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement);
• Trouble speaking or swallowing;
• Swelling in your hands or feet;
• Confusion, unusual thoughts or behavior, hallucinations, or thoughts about hurting yourself;
• Low white blood cell counts–fever, chills, mouth sores, skin sores, sore throat, cough, trouble breathing, feeling light-headed; or
• Signs of dehydration–feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin;
• Liver problems–upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• High blood sugar–increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss; or
• Severe nervous system reaction–very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out.

Common side effects of olanzapine may include:

• Weight gain (more likely in teenagers), increased appetite;
• Headache, dizziness, drowsiness, feeling tired or restless;
• Problems with speech or memory;
• Tremors or shaking, numbness or tingly feeling;
• Changes in personality;
• Dry mouth, or increased salivation;
• Stomach pain, constipation; or
• Pain in your arms or legs.

Mechanism of action

The activity of olanzapine is achieved by the antagonism of multiple neuronal receptors including the dopamine receptor D1, D2, D3 and D4 in the brain, the serotonin receptors 5HT2A, 5HT2C, 5HT3 and 5HT6, the alpha-1 adrenergic receptor, the histamine receptor H1 and multiple muscarinic receptors.

As abovementioned, it presents a wide profile of targets, however, its antagonistic effect towards the dopamine D2 receptor in the mesolimbic pathway is key as it blocks dopamine from having a potential action at the post-synaptic receptor. The binding of olanzapine to the dopamine D2 receptors is easily dissociable and hence, it allows for a certain degree of dopamine neurotransmission.

On the other hand, olanzapine acts in the serotonin 5HT2A receptors in the frontal cortex in a similar manner than the reported-on dopamine D2 receptors. This determined effect allows for a decrease in adverse effects.

Olanzapine interaction with other drugs

Olanzapine, like many medications, can interact with other drugs, potentially affecting their effectiveness or causing adverse effects. It’s crucial to inform your healthcare provider about all the medications, supplements, and herbal products you are taking to avoid potential interactions. Here are some notable drug interactions with olanzapine:

1. Anticholinergic Drugs: Olanzapine may enhance the anticholinergic effects of drugs such as tricyclic antidepressants, antihistamines, and antiparkinsonian medications. This can lead to increased side effects like dry mouth, blurred vision, constipation, and urinary retention.
2. Central Nervous System (CNS) Depressants: Combining olanzapine with other CNS depressants, such as alcohol, sedatives, opioids, and tranquilizers, can result in excessive sedation, drowsiness, and impaired coordination.
3. Antihypertensive Medications: Olanzapine may increase the blood pressure-lowering effects of drugs used to treat hypertension (high blood pressure). Close monitoring of blood pressure is advisable when using these medications together.
4. Diazepam: It may increase the blood levels of diazepam, potentially leading to enhanced sedation and drowsiness. Dose adjustments may be needed.
5. Fluvoxamine: Co-administration of olanzapine with fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), can lead to increased olanzapine levels in the blood. Your healthcare provider may need to adjust the olanzapine dosage.
6. Ciprofloxacin and Fluvoxamine: These drugs can increase olanzapine levels in the blood, potentially leading to increased side effects. Dose adjustments may be necessary.
7. Carbamazepine: Carbamazepine can decrease the effectiveness of olanzapine by increasing its metabolism. Higher olanzapine doses may be needed when taking it with carbamazepine.
8. Rifampin: Rifampin, an antibiotic, can also reduce the levels of olanzapine in the blood, potentially decreasing its effectiveness. Your healthcare provider may need to adjust the olanzapine dosage.
9. Lithium: It may increase the blood levels of lithium, which can increase the risk of lithium toxicity. Close monitoring is essential when using these medications together.
10. Phenytoin: Phenytoin can increase the metabolism of olanzapine, potentially reducing its effectiveness. Your healthcare provider may need to adjust the olanzapine dosage.

These are some of the common drug interactions associated with olanzapine, but there may be others depending on your specific medications and medical history. Always consult your healthcare provider before starting, stopping, or changing the dosage of any medications while taking olanzapine to ensure safe and effective treatment.

How and when to take olanzapine?

Olanzapine is a prescription medicine. It’s important to take it as your doctor tells you.

Dosage and strength

Olanzapine tablets come in different strengths: 2.5mg, 5mg, 7.5mg, 10mg, 15mg and 20mg.

How much you take will depend on what you’re taking it for. Your doctor may ask you to adjust your dose depending on how well olanzapine works for you.

If you have problems with your kidneys or liver, your doctor may ask you to take a lower dose and increase your dose very slowly.

Dosage for schizophrenia

The usual starting dose for:

• adults aged 64 and younger is 10mg, taken once a day
• adults aged 65 or over is 5mg, taken once a day

Dosage for mania symptoms of bipolar disorder

You’ll usually start on 15mg, taken once a day. If you’re taking other medicines to help your symptoms, you may start on 10mg.

Dosage to prevent mania symptoms coming back

You’ll usually start on a dose of 10mg, taken once a day. If you have been taking olanzapine to treat your mania symptoms, you may stay on the same dose.

In case of emergency/overdose

In case of overdose, call the poison control helpline. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services.

Symptoms of overdose may include:

• Drowsiness
• Slurred speech
• Agitation
• Fast heartbeat
• Sudden movements that you cannot control
• Coma (loss of consciousness for a period of time)

Warnings

• Allergy: May cause severe allergic reactions, including trouble breathing, swelling, itching, and hives. Seek immediate medical help if experienced.
• Alcohol Interaction: Avoid alcohol as it increases the risk of low blood pressure and drowsiness when taking olanzapine.
• Health Conditions: Caution for those with Alzheimer’s, seizures, diabetes, heart problems, high cholesterol, blood problems, liver issues, enlarged prostate, narrow-angle glaucoma, or bowel problems.
• Pregnancy and Breastfeeding: Olanzapine is a category C pregnancy drug, meaning potential risks to the fetus. Discuss with a doctor if pregnant or breastfeeding.
• Seniors: Seniors may experience slower drug processing, increasing the risk of side effects.
• Children: Olanzapine’s safety and effectiveness vary by condition and age group in children. Consult a healthcare provider for appropriate use.

Always consult with a healthcare provider for personalized guidance on olanzapine use and potential risks.