Olanzapine (Zyprexa®, Lybalvi®, Symbyax®)

This article provides an extensive overview of olanzapine, including how it works, its indications, side effects, interactions, precautions, and other important treatment information.

Key Takeaways:

• Olanzapine is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It works by affecting levels of serotonin and dopamine in the brain.

• Weight gain and metabolic disturbances (e.g. high blood sugar) are some of the most common olanzapine side effects. There are many other possible side effects, some of which may be severe.

• Olanzapine may interact with many other medications, including potentially dangerous or life-threatening interactions with benzodiazepines, alcohol, and other central nervous system depressants. Your doctor will determine if the benefits of olanzapine treatment outweigh the risks.

Understanding Olanzapine

Olanzapine is a second-generation antipsychotic (SGA) medication. SGAs are also known as atypical antipsychotics. Olanzapine was first approved for use in the United States in 1996. It is only available as a prescription and is taken under the guidance of a medical professional. ^[1]

Olanzapine is primarily used to help manage symptoms of schizophrenia and bipolar disorder. It is commonly considered one of the most effective SGAs for these conditions, but it also has a relatively high risk of side effects compared to other SGAs. ^{[1] [2]}

How it Works

Olanzapine primarily works by indirectly affecting levels of dopamine and serotonin, which are both important neurotransmitters. Specifically, olanzapine acts as an antagonist to dopamine and serotonin, which ultimately reduces their overall levels in the brain and nervous system. ^{[1] [2]}

The blocking effects on dopamine are thought to help control positive symptoms of schizophrenia, such as hallucinations and delusions. The blocking effects on serotonin are thought to help improve negative symptoms, such as anhedonia and decreased attention. ^[2]

Brand Names

The most common olanzapine brand name is Zyprexa®, which is an oral tablet. There are also other forms of Zyprexa®, including: ^[3]

• Zyprexa® Zydis (orally disintegrating tablet)

• Zyprexa® Relprevv (extended-release intramuscular injectable)

• Zyprexa® intramuscular (short-acting intramuscular injectable)

In addition, there are brand names for specific products that combine olanzapine with other medications. This includes:

• Symbyax®: The brand name for olanzapine combined with fluoxetine. ^[4]

• Lybalvi®: The brand name for olanzapine combined with samidorphan

What is Olanzapine Used For?

On its own, olanzapine has two primary FDA-approved indications: ^[2]

• Schizophrenia (in individuals aged 13 and older)

• Bipolar I disorder

• Treatment of manic or mixed episodes

Olanzapine combined with fluoxetine is also FDA-approved to treat depression within bipolar I disorder, as well as treatment-resistant depression. This combination is approved only for individuals aged 10 years and older. ^[2]

Olanzapine combined with samidorphan is also FDA-approved to help manage weight gain associated with olanzapine use for schizophrenia and bipolar I disorder. ^[2]

There are also several off-label olanzapine uses, including: ^[2]

• Acute agitation

• Delirium

• Anorexia nervosa

• Chemotherapy-induced nausea and vomiting

Olanzapine Side Effects

There are several possible side effects of olanzapine. Some side effects may go away as your body gets used to the medication, while others may persist over time.

The most common olanzapine side effects are: ^{[2] [5]}

• Weight gain

• Constipation

• Dizziness

• Increased appetite

• Stomach pain

• Tremor

• Fatigue

• Dry mouth

• Sedation

• Sleepiness

• Restlessness

• Pain in extremities

• Postural hypotension (drop in blood pressure when going from sitting or lying down to standing)

Other possible side effects of olanzapine include: ^{[3] [4] [5]}

• Unusual behaviors

• Depression

• Trouble falling or staying asleep

• Weakness

• Difficulty walking

• Breast enlargement or discharge

• Late or missed menstrual periods

• Bodily pain

• Apathy

• Confusion

This list may not contain all possible olanzapine side effects. Contact your doctor if you notice any side effects after starting olanzapine.

Dangerous and Rare Side Effects

Less commonly, olanzapine can have dangerous and potentially life-threatening side effects. Contact your doctor as soon as possible if you notice symptoms of any of these rare side effects of olanzapine: ^{[2] [5]}

• Neuroleptic malignant syndrome (NMS): Symptoms include:

• High fever

• Muscle rigidity

• Changes in blood pressure

• Sweating

• Metabolic abnormalities, such as:

• Reduced insulin sensitivity and decreased glucose tolerance

• Hyperglycemia (high blood sugar)

• Dyslipidemia (abnormal levels of fats in the blood)

• Seizures

• Edema

• Leukopenia, neutropenia, and agranulocytosis: These are all diseases involving low white blood cell counts

• Extrapyramidal symptoms, which involve various movement-related disorders, such as:

• Akathisia: Restlessness and inability to sit still

• Tardive dyskinesia: repetitive, uncontrollable movements (e.g. lip smacking, grimacing, jerking of arms or legs)

• Parkinsonism: tremors, slow movements, muscle rigidity, and other symptoms

Precautions

There are several important precautions to understand with olanzapine. First and foremost, the use of olanzapine in elderly individuals (aged 65 and over) with dementia-related psychosis is associated with an increased risk of stroke and death. ^[5]

Also, there is an inherent risk of suicide in individuals with schizophrenia and bipolar disorder. Careful monitoring and supervision is required in these situations, as well as when olanzapine is combined with fluoxetine. ^[5]

Olanzapine should not be used by anyone with a hypersensitivity or allergy to it or any of its ingredients.

Olanzapine may be able to be used by pregnant women, but there is an increased risk of birth defects, especially when used in the third trimester. This includes breathing problems, feeding problems, and withdrawal symptoms. Your doctor will carefully examine the risks and benefits in this situation. Caution is also advised for use in breastfeeding women. ^{[2] [3] [5]}

Due to the possible side effects of weight gain and metabolic disturbances, extra caution is advised when giving olanzapine to overweight or obese individuals, as well as those with diabetes or other metabolic disorders. ^[2]

In addition, it’s important to tell your doctor if you have any of the following conditions: ^{[4] [5]}

• Heart problems

• Seizures

• Breast cancer

• Trouble swallowing

• Trouble with balance

• High or low blood pressure

• High cholesterol or triglycerides

• Low white blood cell counts

• Glaucoma

• Alzheimer’s disease

• Phenylketonuria

• Suicidality

• Depression

You may require a modified dose or may not be able to take olanzapine if you have these or other medical conditions. Always consult your doctor to determine if olanzapine treatment is safe for you.

Lastly, olanzapine may cause drowsiness and affect your cognitive and/or motor abilities. Do not drive, operate machinery, or perform other complex mental or physical tasks until you know how olanzapine affects you and you receive your doctor’s approval. ^[3]

Drug Interactions

Olanzapine may interact with several drugs and medications. Combining olanzapine with diazepam, lorazepam, and other benzodiazepines increases the risk of sedation and orthostatic hypotension. This risk is greatest with intramuscular administration. ^{[1] [2]}

Furthermore, any medication that increases drowsiness or slows your breathing may cause dangerous or life-threatening side effects when used with olanzapine. Examples of these drugs include: ^[3]

• Opioids (e.g. hydrocodone, fentanyl)

• Sleeping pills (e.g. eszopiclone)

• Muscle relaxants (e.g. cyclobenzaprine)

• Anticonvulsants (e.g. carbamazepine)

Olanzapine may also interact with: ^[3]

• Other antipsychotics (e.g. risperidone, quetiapine)

• Anti-seizure medications (e.g. carbamazepine)

• Antidepressants (e.g. fluoxetine, fluvoxamine)

• Sedating antihistamines (e.g. chlorphenamine)

• Antihypertensives (e.g. losartan, amlodipine)

• Levodopa and other dopamine agonists

This list does not provide all possible drug interactions with olanzapine. Tell your doctor everything you take or have taken, including prescription and over-the-counter medicines, vitamins, and dietary supplements.

Other Interactions

Smoking tobacco or marijuana may also lower the overall effects of olanzapine. In addition, combining olanzapine with alcohol may increase the risk of orthostatic hypotension and sedation. ^[1]

Olanzapine may also interact with cannabidiol (CBD), as well as other herbs or supplements that cause drowsiness or dizziness. ^[6]

Olanzapine Dosage

The specific olanzapine dosage depends on the indication and form of administration. Olanzapine is available as oral tablets, oral disintegrating tablets, and intramuscular injectables (which are in short-acting and extended-release forms).

The tablets are available in 2.5 mg , 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg dosages. The typical dosages for olanzapine are detailed below: ^[5]

• Schizophrenia:

• Adults:

• Starting dose: 5 to 10 mg, once per day

• Target dose: 10 mg per day

• Adolescents:

• Starting dose: 2.5 to 5 mg, once per day

• Target dose: 10 mg per day

• Bipolar I disorder:

• Adults:

• Starting dose: 10 to 15 mg, once per day

• Target dose: Typically not more than 20 mg per day

• Adolescents:

• Starting dose: 2.5 to 5 mg, once per day

• Target dose: 10 mg per day

What to Do in the Event of an Overdose

Taking high doses of olanzapine can result in toxicity, especially when combined with other medications. In the event of an overdose, contact emergency medical services or your poison control center immediately. Prompt medical treatment is required to reduce the risk of severe side effects from overdose. ^[2]

Symptoms of olanzapine overdose include CNS depression, delirium, extrapyramidal symptoms, agitation, sedation, rapid heart rate, and low blood pressure. Severe cases can lead to seizures, coma, and death. ^{[4] [5]}

Alternatives to Olanzapine

Alternatives to olanzapine primarily consist of other atypical antipsychotics, since they will have similar effects. Examples of other atypical antipsychotics include:

• Aripiprazole

• Asenapine

• Cariprazine

• Iloperidone

• Quetiapine

This is not an exhaustive list. Your doctor will determine which atypical antipsychotic, if any, is right for your situation.

Olanzapine FAQs

Is olanzapine a controlled substance?

No. Olanzapine is not a controlled substance because it is not deemed to have significant potential for abuse or addiction.

Does olanzapine make you sleepy?

Olanzapine may make you sleepy or drowsy. It does not happen in everyone, but it is a relatively common side effect.

Does olanzapine cause weight gain?

Weight gain is one of the most common side effects of olanzapine. In part, this is because olanzapine may cause metabolic disturbances, increased cravings, and other factors that promote weight gain.