Clozapine and the Treatment of Schizophrenia

The treatment of serious mental illness was revolutionized in the 1950s with the introduction of the drug chlorpromazine (thorazine). The use of chlorpromazine and other classes of antipsychotic agents over the past 30 years has led to improvement in many people with serious mental illness and has significantly increased the number of people who can live outside of hospitals and custodial settings. Today, however, there remains a core group of people with persistent mental illness, labeled "treatment resistant," who do not respond to pharmacological interventions and a variety of psychological and social therapies. These people continue to need frequent and sometimes continuous hospitalization, and their quality of life and functioning is marginal. People with serious mental illness who do not readily respond to treatment consume a large proportion of public mental health resources; people with schizophrenia occupy about 25 percent of all hospital beds in the United States (Wallis & Willwerth, 1992). For about 30 percent of people with schizophrenia, the best treatments, programs, and therapies available do not significantly help their illnesses. For patients, families, and mental health practitioners there is frustration, disappointment, and a sense of helplessness in the treatment of serious mental illness. The process of securing approval of the U.S. Food and Drug Administration (FDA) to market promising new antipsychotic drugs in the United States is long and tedious. Advocacy groups argue that illnesses such as schizophrenia are life-threatening (with a 15 percent to 20 percent suicide rate); therefore, they argue, drugs to treat schizophrenia should be on the same "fast track" for FDA approval as are drugs to treat acquired immune deficiency syndrome and Alzheimer's disease (Boodman, 1993). Clozapine (available as Clozaril from Sandoz Pharmaceuticals), an atypical antipsychotic agent, has raised hopes for people with serious mental illness who have thus far not responded to the best treatment efforts. It is hoped that clozapine is the first of many new antipsychotic drugs that will provide relief to seriously mentally ill people. For three decades clozapine has been studied as a drug for the treatment of schizophrenia; however, its introduction to the U.S. market was delayed until 1990 because of a potentially lethal side effect - agranulocytosis (a severe decrease in white blood cells). Since its introduction clozapine has been of enormous interest to the mental health community, evoking passion, frustration, economic crisis, and intense ethical debate. Social workers need to be familiar with the clinical aspects of clozapine treatment and the economic, ethical, and psychosocial implications of its use. CLOZAPINE Features Clozapine has been found to be superior to traditional antipsychotic drugs such as chlorpromazine in the treatment of schizophrenia (Kane, Honigfeld, Singer, Meltzer, & Clozaril Collaborative Study Group, 1988). The uniqueness of clozapine is its effectiveness in treating the nearly 30 percent of people with schizophrenia who have not benefited from conventional therapies (Kane, Honigfeld, Singer, Meltzer, & Clozaril Collaborative Study Group, 1989; Lindstrom, 1989; Meltzer, Burnett, Bastani, & Ramirez, 1990; Naber & Hippius, 1990). Of those who do not respond to conventional drug treatment with such agents as chlorpromazine, haloperidol, and fluphenazine, as many as one-third (Kane, 1990) to one-half (Owen, Beake, Marby, Dessian, & Cole, 1989) may significantly improve with clozapine treatment. Clozapine has been found to reduce or alleviate positive symptoms associated with schizophrenia such as hallucinations, delusions, and thought disorder as well as negative symptoms such as social withdrawal, poverty of thought, and inability to care for basic activities of daily living. At least one retrospective study (Yesavage & Honigfeld, 1992) concluded that clozapine is much more effective than conventional treatments in helping patients move from hospitals to community-based settings. …