Quetiapine

Definition

Quetiapine is an atypical antipsychotic drug used to treat symptoms of schizophrenia . It is available with a prescription under the trade name Seroquel.

Purpose

Quetiapine is classified as an atypical antipsychotic. It is used to treat schizophrenia and bipolar disorders.

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

Recently, the effectiveness of quetiapine 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 quetiapine—in comparison to a conventional antipsychotic drug in the treatment of schizophrenia. Contrary to expectations, the study found that the conventional antipsychotic generally was equally effective and tolerated as well as the newer, more expensive, atypical antipsychotic medications.

Only 16% of participants taking quetiapine in the Phase 1 study were able to continue throughout the entire 18 months. The study results indicate that the choice of a different medication for patients who stop taking an antipsychotic medication depends on why they stopped taking the first medication. 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 rather than 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 showed 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 were not well controlled on clozapine, olanzapine and risperidone tended to be more effective than ziprasidone or quetiapine.

Quetiapine is available in 25-mg, 100-mg, and 200-mg tablets.

Recommended dosage

Initially, a dosage of 25 mg should be taken twice a day. Each dose should be increased by 25-50 mg

increments every three to four days until achieving a target dose of 300-400 mg per day, administered in two or three divided doses. It is not known whether doses higher than 800 mg per day are safe.

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 heartbeat, or fainting.

Quetiapine may cause liver damage. As a result, patients should notify their health care providers if they experience flu-like symptoms, notice yellowing of their skin or eyes, or experience abdominal pain. Liver function should be assessed periodically. The drug should be used cautiously in people with a history of liver disease or alcoholic cirrhosis.

Quetiapine may alter the function of the thyroid gland. Those taking supplements for low thyroid function may require dosage adjustments in their thyroid medication.

Quetiapine may increase cholesterol levels and contribute to the formation of cataracts. Because of this possibility, cholesterol levels should be checked periodically and yearly eye exams should be performed.

Quetiapine should be used carefully in those with a history of seizure disorders because it may increase the tendency to have seizures .

Quetiapine may cause extreme drowsiness and should be used carefully by people who need to be mentally alert.

Do not take quetiapine while pregnant or breastfeeding.

Side effects

Relatively common side effects that accompany quetiapine usage include drowsiness, dizziness, rash, dry mouth, insomnia , fatigue , muscular weakness, anorexia, blurred vision, some loss of muscular control, and amenorrhea (lack of menstruation) in women.

Dystonia (difficulty walking or moving) may occur with quetiapine use. This condition may subside in 24 to 48 hours even when the person continues taking the drug and usually disappears when quetiapine is discontinued.

Quetiapine use may lead to the development of symptoms that resemble Parkinson’s disease. These symptoms may include a tight or mask-like expression on the face, drooling, tremors, pill-rolling motions in the hands, cogwheel rigidity (abnormal rigidity in muscles characterized by jerky movements when the muscle is passively stretched), and a shuffling gait. Taking the anti-Parkinson’s drugs benztropine mesylate or trihexyphenidyl hydrochloride along with the quetiapine usually controls these symptoms.

Quetiapine 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, face, or other groups of skeletal muscles. The incidence of tardive dyskinesia increases with increasing age and with increasing dosage of quetiapine. 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 quetiapine use 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). People who think they may be experiencing any side effects from this or any other medication should talk to their physicians promptly.

Interactions

Quetiapine may be less effective when it is taken with drugs like carbamazepine (Tegretol), phenytoin (Dilantin), rifampin (Rifadin), barbiturates , thioridazine (Mellaril), or corticosteriods such as prednisolone, methylprednisolone, prednisone, and dexamethasone because these drugs increase the breakdown of quetiapine in the liver causing lower than normal levels of the drug.

Antifungal drugs such as fluconazole (Diflucan) or ketoconazole (Nizoral), antibiotics such as erythromycin or clarithromycin (Biaxin), and cimetidine (Tagamet) may decrease the breakdown of quetiapine in the liver causing higher than normal levels of the drug.

Any drug that causes drowsiness may lead to decreased mental alertness and impaired motor skills when taken with quetiapine. Some examples include alcohol, antidepressants such as imipramine (Tofra-nil) or paroxetine (Paxil ), antipsychotics such as thio-ridazine (Mellaril), and some antihistamines.

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 antipsychotics or second-generation antipsychotics.

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.

Parkinsonian —Related to symptoms associated with Parkinson’s disease, a nervous system disorder characterized by abnormal muscle movement of the tongue, face, and neck, inability to walk or move quickly, walking in a shuffling manner, restlessness, and/or tremors.

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.

Resources

BOOKS

AstraZeneca. Seroquel Package Insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP, 2001.

Facts and Comparisons staff. Drug Facts and Comparisons. 6th ed. St. Louis, MO: Facts and Comparisons, 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.

El-Mallakh, Rif, et al. “Bipolar II Disorder: Current and Future Treatment Options.” Annals of Clinical Psychiatry 18.4 (Oct-Dec. 2006): 259-66.

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, et al. “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.

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

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

McEvoy, Joseph P., et al. “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.

Meisenzahl, E. M., et al. “Effects of Treatment with the Atypical Neuroleptic Quetiapine on Working Memory Function: A Functional MRI Follow-Up Investigation.” European Archives of Psychiatry and Clinical Neuroscience 256.8 (Dec. 2006): 522-31.

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.

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

Nasrallah, Henry A., Martin Brecher, and Björn Paulsson. “Placebo-Level Incidence of Extrapyramidal Symptoms (EPS) with Quetiapine in Controlled Studies of Patients with Bipolar Mania.” Bipolar Disorders 8.5, part 1 (Oct. 2006): 467-74.

Pae, Chi-Un, et al. “Adjunctive Risperidone, Olanzapine and Quetiapine for the Treatment of Hospitalized Patients with Bipolar I Disorder: A Retrospective Study.” Progress in Neuro-Psychopharmacology & Biological Psychiatry 30.7 (Sept. 2006): 1322-25.

Savaskan, Egemen, et al. “Treatment of Behavioural, Cognitive and Circadian Rest-Activity Cycle Disturbances in Alzheimer’s Disease: Haloperidol vs. Quetiapine.” International Journal of Neuropsychopharmacology 9.5 (Oct. 2006): 507-16.

Schneider, Lon S., et al. “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, et al. “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.

Tariot, Pierre N., et al. “Quetiapine Treatment of Psychosis Associated With Dementia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.” American Journal of Geriatric Psychiatry 14.9 (Sept. 2006): 767-76.

Thase, Michael E., et al. “Efficacy of Quetiapine Monotherapy in Bipolar I and II Depression: A Double Blind, Placebo-Controlled Study (The BOLDER II Study).” Journal of Clinical Psychopharmacology 26.6 (Dec. 2006): 600-09.

Weiden, Peter J. “EPS Profiles: The Atypical Antipsychotics Are Not All the Same.” Journal of Psychiatric Practice 13.1 (Jan. 2007): 13-24.

Kelly Karpa, R.Ph., PhD
Ruth A. Wienclaw, PhD

Quetiapine

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