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CAREMARK Clinical Update Pharmaceutical Issues and Prescribing Trends for Today’s Professional Working in Healthcare JULY 2003 Schizophrenia Background About two million Americans suffer from schizophrenia, a disease that causes hallucinations, delusions, and paranoia. It is estimated to cost about $65 billion a year in direct treatment, societal, and family costs. If left untreated, persons with schizophrenia can have poorer outcomes, leading to greater healthcare costs.1 This illness, which affects approximately 1% of the adult population, typically develops in the late teens or early twenties. Individuals with schizophrenia are usually in lower socioeconomic classes as they often experience markedly impaired work function.2,3 Causes The exact cause of schizophrenia is unknown, however it tends to be hereditary. An identical twin of a person with schizophrenia has a 40% to 50% chance of developing the disease, and a child whose parent has schizophrenia has a 10% chance, compared to the 1% risk seen in the general population. There has been evidence linking schizophrenia to an imbalance of neurotransmitters (chemical messengers) in the brain, such as dopamine and glutamine.4 Others believe that difficulties prior to birth (such as starvation while in the mother’s uterus or viral infections), complications around the time of birth, and various nonspecific conditions that cause stress, are involved in the developAuthors: ment of schizophrenia. Audrey Moyna, Abnormalities in brain strucPharmD, RPh ture have also been Chris Baek, PharmD, observed in many MAEd individuals with Editorial Contact: schizophrenia. Studies are Dana Udovich, ongoing to determine the PharmD exact cause(s) of this publications@ disorder.5 caremark.com For past issues, please visit us at www.caremark.com Symptoms Schizophrenia is a chronic and disabling mental illness characterized by a wide array of unusual internal experiences, socially inappropriate behavior, and reduced participation in normal social and occupational activities.4 People with schizophrenia may have altered perceptions of reality that are strikingly different from those around them. They often suffer terrifying symptoms such as imaginary voices and beliefs that other people are reading their minds, controlling their thoughts, or plotting to harm them. Clinical symptoms of the illness are generally categorized as positive symptoms or negative symptoms. Positive symptoms include delusions, hallucinations, agitation, disorganized speech or behavior, and paranoia. Negative symptoms consist of inability to show emotion, emotional or social withdrawal, and indifference. Less obvious symptoms, such as social isolation or withdrawal, or unusual speech, thinking, or behavior may also be present.4 Outcomes Individuals with schizophrenia can have poor social and occupational outcomes, and often have difficulty maintaining relationships and holding down steady jobs.5 However, their quality of life can improve if they are compliant and responsive to medications.4 Treatment Typical Antipsychotics The first drugs developed for schizophrenia, now called “typical antipsychotics”, changed the treatment of this disease in the 1950s. These medications have been effective in reducing positive symptoms associated with schizophrenia, but have limited effect on the negative symptoms. Typical antipsychotics also tend to cause many adverse effects, including sedation, involuntary movements, extrapyramidal side effects (e.g., tremor, slurred CAREMARK Clinical Update JULY 2003 speech, or anxiety), increased prolactin levels (a hormone made by the pituitary gland), and weight gain.4 Atypical Antipsychotics During the last decade, newer antipsychotic drugs (i.e., “atypical antipsychotics”) with different mechanisms of action, have been widely used in the treatment of schizophrenia. Examples include Risperdal® (risperidone), Seroquel® (quetiapine), and Zyprexa® (olanzapine). These drugs may also be used in other disorders, such as bipolar disorder, mania, or psychotic symptoms. Atypical antipsychotics provide effective treatment of both positive and negative symptoms without the side effects associated with the typical antipsychotics. A major advantage of these newer products is the reduction of extrapyramidal side effects. However, these atypical antipsychotics can be associated with different side effects, including: weight gain, changes in the way blood sugar is processed, increased blood cholesterol, a decrease of certain white blood cells (infection fighting cells), inflammation and disease of the heart muscle, increased prolactin levels, and abnormal rhythms of the heart. Increased prolactin may interfere with ovulation in women, decreased libido in men, and decreased fertility. Weight gain is an important consideration among doctors because it can increase the risk of diabetes or high blood sugar, heart attack, stroke, and may cause some appearance-conscious individuals to stop their medication. The goal of newer medications is to improve efficacy while decreasing the side effects of these medications.4 Benefits and Risks Associated with Antipsychotic Use Antipsychotic medications can reduce the intensity and frequency of psychotic relapses (return of signs and symptoms), enabling 60% to 70% of individuals to live within the normal community.2,6 However, as mentioned previously, they can cause side effects, such as weight gain, seizures, and certain blood disorders. They can also predispose individuals to certain complications, such as heart disease and ©2003 Caremark Inc. All rights reserved. diabetes. Despite the risks associated with antipsychotic use, these medications have enabled many people with schizophrenia to work and lead more productive lives.4 Clinical Initiatives Antipsychotic agents are unique drugs used in the treatment of quite a disabling condition. One Caremark clinical program, such as SecureCare, helps to ensure that antipsychotic drugs are appropriately dispensed and utilized. This is accomplished through monitoring of refills, drug-drug interactions, and verification of high-dose prescriptions. The Pharmaceutical Services division also sends information to physicians concerning the latest clinical findings on new antipsychotics. These initiatives are an important process in the overall management of participants living with this disorder, so that they lead more productive, self-sufficient lives. References 1. The Schizophrenia Homepage. Available at: http://www.schizophrenia.com. Accessed June 5, 2003. 2. National Institute of Mental Health. Schizophrenia Research. Available at: http://www.nimh.nih.gov. Accessed January 15, 2003. 3. Schultz SK, Andreasen NC. Schizophrenia. Lancet. 1999; 353:1425-30. 4. Meltzer HY, Fatemi SH. Schizophrenia. In: Current diagnosis & treatment in psychiatry. Ebert MH, Loosen PT, Nurcombe B, eds. New York: Lange Medical Books/McGraw-Hill; 2000:260-77. 5. National Institute of Mental Health. Schizophrenia. Available at: http://www.nimh.nih.gov. Accessed January 15, 2003. 6. Williamson JS, Wyandt CM. Treating schizophrenia. New strategies. Drug Topics. 2000; 21(144):64-84. The Caremark Clinical Update is provided as reference material and is based in part on information derived from third parties. Caremark does not assume any liability or responsibility for the accuracy or completeness of any third party material footnoted in this piece.