Olanzapine is used to treat schizophrenia , to control manic episodes of bipolar disorder (manic-depressive disorder), or to treat dementia related to Alzheimer’s disease .

Olanzapine is thought to modify the actions of several chemicals in the brain . Olanzapine is chemically related to another atypical antipsychotic agent, clozapine , but differs both chemically and pharmacologically from the earlier phenothiazine antipsychotics.

Olanzapine is available as 2.5-mg, 5-mg, 7.5-mg, 10-mg, 15-mg, and 20-mg tablets that can be swallowed (Zyprexa) and 5-mg, 10-mg, 15-mg, and 20-mg tablets that disintegrate when placed under the tongue (Zyprexa Zydis). Olanzapine is broken down by the liver.

Recommended dosage

Recently, the effectiveness of olanzapine was evaluated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Study. This study evaluated the effectiveness and side effects of newer antipsychotic drugs (sometimes referred to as atypical antipsychotics)—including olanzapine—in comparison to a conventional antipsychotic drug in the treatment of schizophrenia.

The study found that the conventional antipsychotic generally was equally effective and tolerated as well as the newer, more expensive, atypical antipsychotic medications. Of the atypical antipsychotics, olanzapine performed somewhat better than the other drugs being investigated, and patients taking this drug were less likely to be hospitalized for psychotic relapse and tended to stay on their medication longer than patients taking other antipsychotic drugs in the study. However, patients on olanzapine also tended to gain significant weight and experience other metabolic changes associated with diabetes than did patients taking the other drugs in the study.

The study also showed that olanzapine and ris-peridone tend to be better tolerated than the other atypical antipsychotics investigated, although only 35% of participants on olanzapine were able to continue taking it throughout the entire 18 months of the study. Participants who stopped taking their antipsychotic medication in Phase 1 because it was not adequately controlling their symptoms were more likely to stay on their medication if they were switched to olanzapine or risperidone than to quetiapine or ziprasidone . There was no difference between the four medications tested in Phase 2, however, for participants who had stopped taking their Phase 1 medication because they experienced adverse side effects.

The study results also show that clozapine is often a good choice of medication for patients who did not respond well to other antipsychotic medications. In Phase 2 of the study, clozapine was more effective in controlling symptoms than the other atypical antipsychotics under evaluation. For patients whose symptoms are not well-controlled on clozapine, olanzapine and risperidone tend to be more effective than ziprasidone or quetiapine.

The dosage of olanzapine varies depending upon the reason for its use. When used to treat schizophrenia, 5–10 mg is the typical starting dosage. If dosage adjustments are needed, increases are made in 5-mg increments once a week. When treating schizophrenia, a total daily dosage of 10–15 mg is usually effective. When olanzapine is used to treat acute manic episodes, initial doses of olanzapine are often 10–15 mg. And 20 mg per day may be needed for maximum effect. The safety of doses greater than 20 mg per day has not been determined.

Olanzapine is eliminated from the body more quickly in young people than in older (over age 60) individuals, in men than in women, and in smokers faster than in nonsmokers. Dosage adjustments may be needed based upon individual patient characteristics.

Precautions

Caution should be used in patients with heart disease because the drug may cause blood pressure to fall too low resulting in dizziness, rapid heartbeats, or fainting. Olanzapine should be used carefully in people with known seizure disorders since olanzapine may alter properties of the brain, making seizures occur more easily. People with liver disease should have their liver function monitored regularly while taking olanzapine. Women who are pregnant or breast-feeding should not take olanzapine. People with phenylketo-nuria, a disorder in which the body is unable to metabolize a protein called phenylalanine, should avoid olanzapine disintegrating tablets, because this form of the drug contains phenylalanine.

Side effects

Side effects that occur in more than 5% of patients taking olanzapine include involuntary movements, weakness, dizziness, extreme drowsiness, nonviolent objectionable behavior, constipation, weight gain, dry mouth, low blood pressure, stomach upset, increased appetite, cold-like symptoms, or fever.

Other side effects that are possible include rash, body aches and pains, elevated liver enzymes, vision abnormalities, chest pain, or rapid heartbeats.

Olanzapine has the potential to produce a serious side effect called tardive dyskinesia . This syndrome

KEY TERMS

Antipsychotic —A medication used to treat psychotic symptoms of schizophrenia such as hallucinations, delusions, and delirium. May be used to treat symptoms in other disorders, as well.

Atypical antipsychotic —A newer antipsychotic drug that is less likely to cause significant adverse side effects than conventional antipsychotic medications. Atypical antipsychotics are also called novel anti-psychotics or second-generation antipsychotics.

Bipolar disorder (formerly manic-depressive disorder) —A mental disorder characterized by dramatic and sometimes rapid mood swings, resulting in both manic and depressive episodes.

Mania —An elevated or euphoric mood or irritable state that is characteristic of bipolar I disorder. This state is characterized by mental and physical hyper-activity, disorganization of behavior, and inappropriate elevation of mood.

Neuroleptic malignant syndrome (NMS) —An unusual but potentially serious complication that develops in some patients who have been treated with antipsychotic medications. NMS is characterized by changes in blood pressure, altered states of consciousness, rigid muscles, and fever. Untreated NMS can result in coma and death.

Psychosis (plural: psychoses) —A severe state that is characterized by loss of contact with reality and deterioration in normal social functioning; examples are schizophrenia and paranoia. Psychosis is usually one feature of an overarching disorder, not a disorder in itself.

Schizophrenia —A severe mental illness in which a person has difficulty distinguishing what is real from what is not real. It is often characterized by hallucinations, delusions, language and communication disturbances, and withdrawal from people and social activities.

Tardive dyskinesia —A condition that involves involuntary movements of the tongue, jaw, mouth, face, or other groups of skeletal muscles that usually occurs either late in antipsychotic therapy or even after the therapy is discontinued. It may be irreversible.

consists of involuntary, uncoordinated movements that may appear late in therapy and that may not disappear even after the drug is stopped. Tardive dyskinesia involves involuntary movements of the tongue, jaw, mouth, face, or other groups of skeletal muscles. The incidence of tardive dyskinesia increases with increasing age and with increasing dosage of olanza-pine. Women are at greater risk than men for developing tardive dyskinesia. There is no known effective treatment for tardive dyskinesia, although gradual (but rarely complete) improvement may occur over a long period.

An occasionally reported side effect of olanzapine is neuroleptic malignant syndrome. This is a complicated and potentially fatal condition characterized by muscle rigidity, high fever, alterations in mental status, and cardiac symptoms such as irregular pulse or blood pressure, sweating, tachycardia (fast heartbeat), and arrhythmias (irregular heartbeat).

Interactions

Any drug that causes drowsiness may lead to decreased mental alertness and impaired motor skills when taken with olanzapine. Some examples include alcohol, antidepressants such as imipramine (Tofranil) or paroxetine (Paxil ), antipsychotics such as thioridazine (Mellaril), and some antihistamines. Because olanzapine may lower blood pressure, it may reduce blood pressure to dangerously low levels if taken with drugs that are used to treat high blood pressure. Carbamazepine (Tegretol), a drug commonly used to treat seizures, may decrease the effectiveness of olanzapine.

Resources

BOOKS

Facts and Comparisons staff. Drug Facts and Comparisons. 6th ed. St. Louis, MO: A Wolter Kluwer Company, 2002.

Medical Economics Co. staff. Physician’s Desk Reference. 56th ed. Montvale, NJ: Medical Economics Company, 2002.

Preston, John D., John H. O’Neal, and Mary C. Talaga. Handbook of Clinical Psychopharmacology for Therapists%, 4th ed. Oakland, CA: New Harbinger Publications, 2004.

PERIODICALS

Casey, Daniel E. “Implications of the CATIE Trial on Treatment: Extrapyramidal Symptoms.” CNS Spectrums 11.7, Supp. 7 (July 2006): 25–31.

Gentile, Salvatore. “Extrapyramidal Adverse Events Associated with Atypical Antipsychotic Treatment of Bipolar Disorder.” Journal of Clinical Psychopharmacology 27.1 (Feb. 2007): 35–45.

Glick, Ira D. “Understanding the Results of CATIE in the Context of the Field.” CNS Spectrums 11.7, Supp. 7 (July 2006): 40–47.

Haro, Josep Maria, and others. “Remission and Relapse in the Outpatient Care of Schizophrenia: Three-Year Results from the Schizophrenia Outpatient Health Outcomes Study.” Journal of Clinical Psychopharmacology 26.6 (Dec. 2006): 571–78.

Harvey, Philip D., Christopher R. Bowie, and Antony Loe-bel. “Neuropsychological Normalization with Long-Term Atypical Antipsychotic Treatment: Results of a Six-Month Randomized, Double-Blind Comparison of Ziprasidone vs. Olanzapine.” Journal of Neuropsychiatry & Clinical Neurosciences 18.1 (Winter 2006): 54–63.

Jarema, Marek. “Atypical Antipsychotics in the Treatment of Mood Disorders.” Current Opinion in Psychiatry 20.1 (Jan. 2007): 23–29.

Kinon, Bruce J., and others. “Randomized, Double-Blind 6-Month Comparison of Olanzapine and Quetiapine in Patients with Schizophrenia or Schizoaffective Disorder with Prominent Negative Symptoms and Poor Functioning.” Journal of Clinical Psychopharmacology 26.5 (Oct. 2006): 453–61.

Lieberman, Jeffrey A., and others. “Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia.” New England Journal of Medicine 353.12 (Sept. 2005): 1209–23.

Lipkovich, I., and others. “Predictors of Risk for Relapse in Patients with Schizophrenia or Schizoaffective Disorder During Olanzapine Drug Therapy.” Journal of Psychiatric Research 41.3–4 (Apr.–June 2007): 305–10.

McCue, Robert E., and others. “Comparative Effectiveness of Second-Generation Antipsychotics and Haloperidol in Acute Schizophrenia.” British Journal of Psychiatry 189 (Nov. 2006): 433–40.

McEvoy, Joseph P., and others. “Effectiveness of Clozapine Versus Olanzapine, Quetiapine, and Risperidone in Patients with Chronic Schizophrenia Who Did Not Respond to Prior Atypical Antipsychotic Treatment.” American Journal of Psychiatry 163.4 (Apr. 2006): 600–10.

Meltzer, Herbert Y., and William V. Bobo. “Interpreting the Efficacy Findings in the CATIE Study: What Clinicians Should Know.” CNS Spectrums 11.7, Supp. 7 (July 2006): 14–24.

Morrens, Manuel, and others. “Psychomotor and Memory Effects of Haloperidol, Olanzapine, and Paroxetine in Healthy Subjects After Short-Term Administration.” Journal of Clinical Psychopharmacology 27.1 (Feb. 2007): 15–21.

Nasrallah, Henry A. “Metabolic Findings From the CATIE Trial and Their Relation to Tolerability.” CNS Spectrums 11.7, Supp. 7 (July 2006): 32–39.

Schneider, Lon S., and others. “Effectiveness of Atypical Antipsychotic Drugs in Patients with Alzheimer’s Disease.” New England Journal of Medicine 355.15 (Oct. 2006): 1525–38.

Stroup, T. Scott, and others. “Effectiveness of Olanzapine, Quetiapine, Risperidone, and Ziprasidone in Patients with Chronic Schizophrenia Following Discontinuation of a Previous Atypical Antipsychotic.” American Journal of Psychiatry 163.4 (Apr. 2006): 611–22.

Kelly Karpa, R.Ph., PhD

Ruth A. Wienclaw, PhD

The Gale Encyclopedia of Mental Health

Olanzapine

views updated May 23 2018

Olanzapine

Definition

Olanzapine is classified as an atypical antipsychotic drug. It is available in the United States under the brand names Zyprexa and Zyprexa Zydis.

Purpose

Olanzapine is used to treat schizophrenia , to control manic episodes of bipolar disorder (manic-depressive disorder), or to treat dementia related to Alzheimer's disease .

Description

Olanzapine is thought to modify the actions of several chemicals in the brain . Onlanzapine is chemically related to another atypical antipsychotic agent, clozapine , but differs both chemically and pharmacologically from the earlier phenothiazine antipsychotics.

Recommended dosage

The dosage of olanzapine varies depending upon the reason for its use. When used to treat schizophrenia, 5–10 mg is the typical starting dosage. If dosage adjustments are needed, increases are made in 5-mg increments once a week. When treating schizophrenia, a total daily dosage of 10–15 mg is usually effective. When olanzapine is used to treat acute manic episodes, initial doses of olanzapine are often 10–15 mg; 20 mg per day may be needed for maximum effect. The safety of doses greater than 20 mg per day has not been determined.

Olanzapine is eliminated from the body more quickly in young people than in older (over age 60) individuals, in men than in women, and in smokers faster than in non-smokers. Dosage adjustments may be needed based upon individual patient characteristics.

Precautions

Caution should be used in patients with heart disease because the drug may cause blood pressure to fall too low resulting in dizziness, rapid heartbeats, or fainting. Olanzapine should be used carefully in people with known seizure disorders since olanzapine may alter properties of the brain making seizures occur more easily. People with liver disease should have their liver function monitored regularly while taking olanzapine. Women who are pregnant or breast-feeding should not take olanzapine. People with phenylketonuria, a disorder in which the body is unable to metabolize a protein called phenylalanine, should avoid olanzapine disintegrating tablets, because this form of the drug contains phenylalanine.

Side effects

Other side effects that are possible include rash, body aches and pains, elevated liver enzymes, vision abnormalities, chest pain, or rapid heartbeats.

Olanzapine has the potential to produce a serious side effect called tardive dyskinesia . This syndrome consists of involuntary, uncoordinated movements that may appear late in therapy and not disappear even after the drug is stopped. Tardive dyskinesia involves involuntary movements of the tongue, jaw, mouth or face or other groups of skeletal muscles. The incidence of tardive dyskinesia increases with increasing age and with increasing dosage of olanzapine. Women are at greater risk than men for developing tardive dyskinesia. There is no known effective treatment for tardive dyskinesia, although gradual (but rarely complete) improvement may occur over a long period.

Interactions

Any drug that causes drowsiness may lead to decreased mental alertness and impaired motor skills when taken with olanzapine. Some examples include alcohol, antidepressants such as imipramine (Tofranil) or paroxetine (Paxil), antipsychotics such as thioridazine (Mellaril), and some antihistamines. Because olanzapine may lower blood pressure, it may reduce blood pressure to dangerously low levels if taken with drugs that are used to treat high blood pressure. Carbamazepine (Tegretol), a drug commonly used to treat seizures, may decrease the effectiveness of olanzapine.