Antipsychotic Drug Olanzapine (Zyprexa)

By | January 14, 2015

Information About Antipsychotic Drug Olanzapine (Zyprexa) for Patients and Families

Olanzapine (Zyprexa) was first marketed in the United States in 1996, primarily for treatment of schizophrenia and schizoaffective disorder. However, olanzapine was also shown to be effective for treating mood disorders, such as bipolar disorder, and received an indication from the U.S. Food and Drug Administration (FDA) for the treatment of acute mania and in maintenance therapy for bipolar disorder. Recent studies suggest that olanzapine may be effective for the treatment of psychotic depression as well.

Olanzapine is a second-generation antipsychotic, a newer class of antipsychotics that have actions different from those of the older, first-generation antipsychotics. Olanzapine, like the other second-generation antipsychotics, is more effective than the older antipsychotics, such as haloperidol, for treating “negative symptoms” of schizophrenia, such as apathy, lack of motivation, flat emotional expression, withdrawal, and depression. Furthermore, second-generation antipsychotics at standard doses rarely cause side effects associated with movement disorders, such as extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). This is a very important distinction between the newer and older antipsychotics.

Olanzapine is available only as the brand Zyprexa, in 2.5-, 5-, 7.5-, 10-, 15-, and 20-mg strength tablets and in rapidly dissolving wafers (Zyprexa-Zydis) that do not need swallowing. Zyprexa is also available in an injectable for for intramuscular administration in acute treatment.

How Olanzapine Is Prescribed

The usual starting daily dose is 5 mg, and the dosage is increased to a target of 10 mg/day within several days. In acute treatment, a dosage range of 15 to 20 mg/day is usually needed for antipsychotic treatment, although some patients require dosages higher than 20 mg/day. Olanzapine may be taken in divided doses twice a day, but it is preferably taken as a single bedtime dose.

Proper Use Of Your Drug

Storing Your Drug

  • • Keep your drug in a tamper-resistant vial and out of reach of children.
  • • Store your drug so that it is kept from excessive heat, moisture, and direct light.
  • • Keep your drug in its original prescription vial with the label intact to prevent others from taking the drug inadvertently.

Taking Your Drug

  • • Take your drug as instructed by your physician. Do not abruptly stop taking your drug without consulting your physician.
  • • If you miss a dose, take it as soon as possible. However, if it is near the time of your next dose, skip the dose you missed and go back to your regular dosing schedule, but do not double-up the dose.
  • • Olanzapine may be taken with food or at mealtime without affecting its absorption.

Use of Alcohol and Other Drugs

Individuals should refrain from alcohol consumption while taking olanzapine. When the two are combined, sedation and drowsiness may be significantly enhanced. Some medications, including over-the-counter medicines, may interact with olanzapine. The drug interaction may lower the blood level of the affected drug and decrease the drug’s effectiveness; or, it may elevate the blood level of the affected drug and induce toxicity. A number of drugs when combined with olanzapine may make certain side effects worse. Inform your doctor of all the prescription and over-the-counter drugs you are taking. If you have any questions or concerns about your drugs, consult your physician or pharmacist.

Possible Side Effects

Sedation. Olanzapine often produces significant sedation and drowsiness at the start of therapy, but these side effects eventually subside as the patient develops greater tolerance to the drug. Frequently, taking olanzapine in a single bedtime dose can mitigate the patient’s daytime drowsiness.

Orthostatic hypotension. Olanzapine may oppose the body’s ability to elevate blood pressure in response to a change in position. Orthostatic hypotension occurs when blood pressure cannot be raised in time as the person stands up. As a result, the individual feels light-headed and dizzy and may faint and fall. By learning to rise slowly and allowing the blood pressure to adjust gradually, the individual can minimize orthostatic hypotension. This practice is important when standing up after sitting for long periods or when rising from bed. Usually the individual adapts to postural hypotension. If the problem is severe, lowering the dose or switching to another drug may correct it.

Dry mouth. This side effect may be bothersome in the beginning. Often it subsides when the patient develops greater tolerance to the drug. Chewing sugarless gum or sucking on sugarless candy may provide some relief for the patient.

Constipation. Olanzapine may slow gastrointestinal movement and cause constipation. To prevent constipation, the patient should increase fluid intake, increase fiber content in the diet, and exercise regularly. Bulk laxatives or a stool softener, such as docusate, may be needed at times to relieve constipation.

Blurred vision. Olanzapine may cause blurred vision and affect accommodation (ability of the eye to adjust when looking at close objects). If this occurs, the patient should inform his or her physician. Lowering the dose may eliminate this problem.

Weight gain. Weight gain is a common side effect of olanzapine, and some patients may experience significant weight gain from the drug. Weight gain may be due to increased appetite or some underlying metabolic change. The major concern from excessive weight gain is the health consequences to the patient, including the potential for developing diabetes and cardiovascular disease. Furthermore, patients may stop taking their drug when they become self-conscious about excessive weight. If this becomes problematic, the patient should consult with his or her physician. Both the physician and patient can agree on a supervised program to include diet and exercise to reduce and control weight. The alternative is switching to another second-generation antipsychotic drug that may be more weight-neutral.

Altered glucose metabolism and diabetes. Atypical antipsychotics may affect the way the body handles glucose, perhaps by decreasing the body’s sensitivity to insulin. As a result, glucose levels in the blood may be elevated (hyperglycemia). Cases of drug-induced diabetes have been reported with olanzapine and clozapine.

Extrapyramidal side effects. Neurologic side effects from antipsychotic drugs resulting in movement disorders are commonly known as extrapyramidal symptoms (EPS). EPS include akathisia, Parkinson-like symptoms, and dystonia. Conventional antipsychotic drugs such as haloperidol frequently induce EPS, whereas olanzapine, at standard doses, rarely produces EPS.

At higher doses, some patients may experience akathisia, which is described as an inner feeling of restlessness, expressed by constant pacing, inability to sit still, nervousness, and even agitation. Reducing the dose of olanzapine is usually the most effective treatment of akathisia. Also, at higher doses, olanzapine may induce Parkinson-like symptoms, which are manifested in movement disorders very similar to Parkinson’s disease. Patients with Parkinson-like symptoms may have a tremor of the fingers and hands, muscle stiffness, a shuffle when walking, stooped posture, drooling, and a masklike face. These side effects can be effectively treated with an anticholinergic agent like benztropine (Cogentin), diphenhydramine (Benadryl), or trihexyphenidyl (Artane).

Patients should be aware of an EPS that may occur with any antipsychotic medication, although it occurs rarely with olanzapine. This reaction, called dystonia, is a sudden spasm of the muscles of the tongue, jaw, or neck. Although it can be very frightening, it is not an allergic reaction. The patient should immediately seek medical attention, because a dystonic reaction can be rapidly reversed with an intramuscular injection of an anticholinergic drug (benztropine or diphenhydramine).

Organs and Systems


• A 66-year-old woman taking chlorpromazine and que-tiapine had QTC interval prolongation, which improved when these drugs were withdrawn. However, prolongation later recurred while she was taking high-dosage olanzapine (60 mg/day), which had not occurred with a smaller dosage (40 mg/day).

• QTC prolongation occurred in a 28-year-old woman while she was taking olanzapine 40 mg/day; after olanzapine withdrawal, the QTC interval returned to normal.

• A 61-year-old woman with Wolff-Parkinson-White syndrome, who had previously had QTC interval prolongation with both sulpiride 1200 mg/day and clozapine 50 mg/day, had a QTC interval of 390 ms, which increased to 466 ms when she took olanzapine 5 mg/day and returned to 395 ms in 2 days when olanzapine was withdrawn. When she was given olanzapine again in the same dose, the QTC interval increased to 473 ms in 2 weeks and returned to baseline when olanzapine was withdrawn. She was also taking daily valproate 1500 mg/day, lithium 300 mg/ day, lorazepam 2 mg/day, and propranolol 40 mg/day.

Nervous system

• A 29-year-old woman with paranoid schizophrenia took olanzapine 20 mg/day for 3 months, stopped taking it, restarted it within 2 months, and 2.5 months later developed involuntary intermittent choreoathetoid knee movements and foot squirming in both legs; the movements persisted for more than 4 weeks. She denied any subjective sense of restlessness; other reasons for symptoms were excluded and tardive dyskinesia was diagnosed. The movements ceased after 4 months of treatment with quetiapine 300 mg/day later increasing to 600 mg/day. Some months later, her psychotic symptoms increased and she was given additional risperidone 1 mg/day. This resulted in writhing lower limb movements, which disappeared with risperidone withdrawal.

• A 16-year-old boy developed fever, generalized rigidity, leukocytosis, and increased serum transaminase and creatine kinase activities while taking olanzapine and lithium; when both drugs were withdrawn, his fever and rigidity subsided and the biochemical tests returned to normal, without any complications.

• A 75-year-old man developed typical neuroleptic malignant syndrome while taking olanzapine; he had previously had haloperidol-associated neuroleptic malignant syndrome.

• A 31-year-old woman with multiple psychiatric and medical disorders, including a generalized seizure disorder (a probable confounding factor in this case), developed seizures when she switched from haloperidol to olanzapine.

• A 27-year-old woman had a seizure while taking a stable dosage of olanzapine 15 mg/day 1 day after the introduction of quetiapine 100 mg in the evening. She suddenly fell to the ground and had generalized shaking and inarticulate vocalization for about 30-60 seconds.

Sensory systems

• A 37-year-old man who had taken olanzapine 10 mg/ day at bedtime for 1 week developed an excessive whitish discharge from the eyes.

• A 36-year-old woman taking olanzapine 5 mg tds had new-onset panic attacks, with feelings of severe anxiety, shortness of breath, trembling, palpitation, and sweating, and felt that she was going to die. She had no previous history of panic attacks, which responded to the addition of alprazolam. The authors hypothesized that the 5-HT2 antagonist action of olanzapine had triggered the onset of this condition.


• A 35-year-old woman developed hyperprolactinemia after 2 months of risperidone treatment; the effects persisted after she switched to olanzapine, mean dose 2.5 mg/day.

• A 34-year-old woman, who developed amenorrhea while taking risperidone, regained her normal menstrual pattern along with a marked fall in serum prolactin concentration 8 weeks after being switched to olanzapine, whereas amantadine had failed to normalize the menses and had apparently reactivated the psychotic symptoms.


• A 32-year-old African-American man with no prior history of diabetes mellitus or glucose intolerance had a raised blood glucose concentration after 6 weeks of olanzapine therapy, and required insulin. Olanzapine was withdrawn and blood glucose concentrations returned to normal about 2 weeks later. At rechallenge hyperglycemia occurred again.

• A 50-year-old man developed acute ketoacidosis with de novo diabetes mellitus after 8 months of adjunctive olanzapine. His dosage was then gradually titrated to 30 mg/day over 6 months, and after withdrawal of olanzapine his diabetes mellitus disappeared completely.

Warning: Olanzapine may cause drowsiness and sedation and impair physical coordination and mental alertness. Until you are sure that these side effects will not impair your ability to perform daily tasks, it is important to avoid potentially dangerous activities, such as driving a car or operating machinery.

Possible Adverse Reactions

Tardive dyskinesia. TD is by definition a late-onset abnormal, involuntary movement disorder that commonly includes “pill-rolling” movements of the fingers, darting and writhing movements of the tongue, lip puckering, facial grimacing, and other irregular movements. Experience to date suggests that olanzapine rarely produces TD, but there may be a risk from chronic exposure to antipsychotics. With olanzapine, as with all antipsychotics, routine monitoring for TD is important.

Seizures. Olanzapine may lower the seizure threshold and precipitate seizures in susceptible individuals, particularly those with a history of seizure disorders. The risk of seizures is very low. Olanzapine, however, should be used cautiously in patients with a history of seizures.

Neuroleptic malignant syndrome (NMS). NMS is a rare, toxic reaction to antipsychotics, including olanzapine. The symptoms are severe muscle stiffness, rigidity, elevated body temperature, increased heart rate and blood pressure, irregular pulse, and sweating. NMS can lead to delirium and coma. It may be fatal if medical intervention is not immediately provided. There are no tests that can predict if an individual may be susceptible to developing NMS when treated with an antipsychotic. Hence, NMS must be recognized early because it is a medical emergency that requires immediate discontinuation of the antipsychotic, timely hospitalization, and intensive medical treatment.

Heatstroke. Patients taking antipsychotics may be susceptible to heatstroke when they are exposed to very hot weather and become dehydrated. To prevent heatstroke, the patient should drink plenty of fluids and avoid prolonged exposure in hot weather.

Use In Pregnancy And Breast Feeding

Olanzapine is classified in Category C of the FDA Pregnancy Risk Categories. There are no clinical studies or available information to use in determining the risk of olanzapine use during pregnancy; therefore, the extent of risk is not known. Women who are pregnant, or who are planning to become pregnant, should not take olanzapine. However, if the risk of not treating poses a greater danger for the mother and child, the benefits from olanzapine may outweigh any unknown risks.

It is not known if olanzapine passes into breast milk. However, it is recommended that women taking olanzapine not breastfeed.

If you have any questions about this handout, please consult your physician.