Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also sometimes used off-label in cancer patients for treatment of chemotherapy-induced nausea and vomiting and as an appetite stimulant. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.
Common side effects include feeling tired, dizziness, constipation, dry mouth, and restlessness. Other side effects include low blood pressure with standing, allergic reactions, neuroleptic malignant syndrome, diabetes mellitus, seizures, and tardive dyskinesia. In older people with dementia, its use increases the risk of death. Use in the later part of pregnancy may result in a movement disorder in the baby for some time after birth. Although its mechanism of action is not entirely clear, it is known to block dopamine and serotonin receptors.
Olanzapine was patented in 1991 and approved for medical use in the United States in 1996. It is available as a generic medication. In 2023, it was the 167th most commonly prescribed medication in the United States, with more than 3million prescriptions. It is on the World Health Organization's List of Essential Medicines.
Medical uses It is approved by the FDA for the following indications:
schizophrenia. acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder. adjunct to lithium or valproate in the treatment of manic or mixed episodes associated with bipolar I disorder. combination olanzapine/fluoxetine (Symbyax) for the treatment of depressive episodes of bipolar I disorder and for treatment-resistant depression. combination olanzapine/samidorphan (Lybalvi) for the treatment of schizophrenia and bipolar I disorder. Lybalvi suppresses the metabolic side effect of olanzapine. More precisely, olanzapine produces weight gain of about 9 kg (20 pounds) in the short-term, which typically increases to around 23–45 kg (50–100 pounds) following long-term use. In contrast, Lybalvi only triggers roughly 5 kg (11 pounds) before subsiding.
In the United Kingdom and Australia, it is approved for schizophrenia, moderate to severe manic episodes, alone, or in combination with lithium or valproate and the short-term treatment of acute manic episodes associated with bipolar I disorder.
Olanzapine is also used off-label for the treatment of chemotherapy-induced nausea and vomiting.
Schizophrenia The first-line psychiatric treatment for schizophrenia is antipsychotic medication. Olanzapine appears to be effective in reducing symptoms of schizophrenia, treating acute exacerbations, and treating early-onset schizophrenia. The usefulness of maintenance therapy, however, is difficult to determine, as more than half of people in trials quit before the 6-week completion date. Treatment with olanzapine (like clozapine) may result in increased weight gain and increased glucose and cholesterol levels when compared to most other second-generation antipsychotic drugs used to treat schizophrenia.
Bipolar disorder Olanzapine is recommended by the National Institute for Health and Care Excellence as a first-line therapy for the treatment of acute mania in bipolar disorder. Other recommended first-line treatments are aripiprazole, haloperidol, quetiapine, and risperidone. It is recommended in combination with fluoxetine as a first-line therapy for acute bipolar depression, and as a second-line treatment by itself for the maintenance treatment of bipolar disorder.
The Network for Mood and Anxiety Treatments recommends olanzapine as a first-line maintenance treatment for bipolar disorder and the combination of olanzapine with fluoxetine as a second-line treatment for bipolar depression.
A review on the efficacy of olanzapine as maintenance therapy in people with bipolar disorder was published in 2006. A 2014 meta-analysis concluded that olanzapine with fluoxetine was the most effective among nine treatments for bipolar depression included in the analysis.
Specific populations
Pregnancy and lactation Olanzapine is associated with the highest placental exposure of any atypical antipsychotic. Despite this, the available evidence suggests it is safe during pregnancy, although the evidence is insufficiently strong to say anything with a high degree of confidence. Olanzapine is associated with weight gain, which according to recent studies, may put olanzapine-treated patients' offspring at a heightened risk for neural tube defects (e.g. spina bifida). Breastfeeding in women taking olanzapine is advised against because olanzapine is secreted in breast milk, with one study finding that the exposure to the infant is about 1.8% that of the mother.
Elderly Citing an increased risk of stroke, in 2004, the Committee on the Safety of Medicines in the UK issued a warning that olanzapine and risperidone, both atypical antipsychotic medications, should not be given to elderly patients with dementia. In the U.S., olanzapine comes with a black box warning for increased risk of death in elderly patients. It is not approved for use in patients with dementia-related psychosis. A BBC investigation in June 2008 found that this advice was being widely ignored by British doctors. Evidence suggested that the elderly are more likely to experience weight gain on olanzapine compared to aripiprazole and risperidone.
Adverse effects
The principal side effect of olanzapine is weight gain, which may be profound in some cases and/or associated with derangement in blood-lipid and blood-sugar profiles (see section metabolic effects). A 2013 meta-analysis of the efficacy and tolerance of 15 antipsychotic drugs (APDs) found that it had the highest propensity for causing weight gain out of the 15 APDs compared with an SMD of 0.74. Extrapyramidal side effects, although potentially serious, are infrequent to rare from olanzapine, but may include tremors and muscle rigidity.
Although olanzapine causes an early dose-related rise in prolactin, this is less frequent and less marked than that seen with haloperidol, and is usually transient. A rise in prolactin is seen in about half of patients on olanzapine compared to over 90% of those taking risperidone, and enduring increases were less frequent in those taking olanzapine.
It is not recommended to be used by IM injection in acute myocardial infarction, bradycardia, recent heart surgery, severe low blood pressure, sick sinus syndrome, and unstable angina.
Several patient groups are at a heightened risk of side effects from olanzapine and antipsychotics in general. Olanzapine may produce nontrivial high blood sugar in people with diabetes mellitus. Likewise, the elderly are at a greater risk of falls and accidental injury. Young males appear to be at heightened risk of dystonic reactions, although these are relatively rare with olanzapine. Most antipsychotics, including olanzapine, may disrupt the body's natural thermoregulatory systems, thus permitting excursions to dangerous levels when certain situations (exposure to heat, strenuous exercise) occur.
Other side effects possibly include galactorrhea, amenorrhea, gynecomastia, and erectile dysfunction (impotence).
Metabolic effects The US Food and Drug Administration (FDA) requires atypical antipsychotics to include a warning about the risk of developing hyperglycemia and diabetes, both of which are factors in the metabolic syndrome. These effects may be related to the drugs' ability to induce weight gain, although some reports have been made of metabolic changes in the absence of weight gain. Studies have indicated that olanzapine carries a greater risk of causing and exacerbating diabetes than another commonly prescribed atypical antipsychotic, risperidone. Of all the atypical antipsychotics, olanzapine is the most likely to induce significant weight gain based on various measures. The effect is dose dependent in humans and animal models of olanzapine-induced metabolic side effects. There are some case reports of olanzapine-induced diabetic ketoacidosis. Olanzapine may decrease insulin sensitivity, though one 3-week study seems to refute this. It may also increase triglyceride levels.
Despite weight gain, a large multicenter, randomized National Institute of Mental Health study found that olanzapine was better at controlling symptoms because patients were more likely to remain on olanzapine than the other drugs. One small, open-label, nonrandomized study suggests that taking olanzapine by orally dissolving tablets may induce less weight gain, but this has not been substantiated in a blinded experimental setting.
Post-injection delirium/sedation syndrome Postinjection delirium/sedation syndrome (PDSS) is a rare syndrome that is specific to the long-acting injectable formulation of olanzapine, olanzapine pamoate. The incidence of PDSS with olanzapine pamoate is estimated to be 0.07% of administrations, and is unique among other second-generation, long-acting antipsychotics (e.g. paliperidone palmitate), which do not appear to carry the same risk. PDSS is characterized by symptoms of delirium (e.g. confusion, difficulty speaking, and uncoordinated movements) and sedation. Most people with PDSS exhibit both delirium and sedation (83%). Although less specific to PDSS, a majority of cases (67%) involved a feeling of general discomfort. PDSS may occur due to accidental injection and absorption of olanzapine pamoate into the bloodstream, where it can act more rapidly, as opposed to slowly distributing out from muscle tissue. Using the proper, intramuscular-injection technique for olanzapine pamoate helps to decrease the risk of PDSS, though it does not eliminate it entirely. This is why the FDA advises that people who are injected with olanzapine pamoate be watched for 3 hours after administration, in the event that PDSS occurs.
Animal toxicology Olanzapine has demonstrated carcinogenic effects in multiple studies when exposed chronically to female mice and rats, but not male mice and rats. The tumors found were in either the liver or mammary glands of the animals.
Discontinuation The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly, vertigo, numbness, or muscle pains may occur. Symptoms generally resolve after a short time.
Tentative evidence indicates that discontinuation of antipsychotics can result in psychosis, as a temporary withdrawal symptom. It may also result in reoccurrence of the condition that is being treated. Rarely, tardive dyskinesia can occur when the medication is stopped.
Overdose Symptoms of an overdose include tachycardia, agitation, dysarthria, decreased consciousness, and coma. Death has been reported after an acute overdose of 450 mg, but also survival after an acute overdose of 2000 mg. Fatalities generally have occurred with olanzapine plasma concentrations greater than 1000 ng/mL post mortem, with concentrations up to 5200 ng/mL recorded (though this might represent confounding by dead tissue, which may release olanzapine into the blood upon death). No specific antidote for olanzapine overdose is known, and even physicians are recommended to call a certified poison control center for information on the treatment of such a case. Olanzapine is considered moderately toxic in overdose, more toxic than quetiapine, aripiprazole, and the SSRIs, and less toxic than the monoamine oxidase inhibitors and tricyclic antidepressants.
Interactions