Zyprexa was approved for the treatment of schizophrenia--a mental illness characterized by hallucinations, delusions, withdrawal and inability to feel pleasure--in the U.S. in October 1996. In March 2000 it was approved for short-term treatment of acute manic episodes associated with bipolar disorder. Some physicians prescribe it off-label for other psychiatric disorders.

Approximately three million Americans suffer from bipolar disorder, while some 2.5 million have schizophrenia. Approximately one percent of the population develops schizophrenia during their lifetime.

New Class of Antipsychotic Drugs

Zyprexa is one of a new class (thienobenzodiazepine) of antipsychotic drugs called atypical antipsychotics. Other drugs in this class are clozapine (approved in 1989; sold by Novartis as Clozaril, and by IVAX Pharmaceuticals as a generic), risperidone (approved in 1994; sold by Janssen Pharmaceutica Products as Risperdal), quetiapine (approved in September 1997; sold by AstraZeneca Pharmaceuticals as Seroquel), ziprasidone (approved in February 2001; sold by Pfizer Inc. as Geodon), and aripiprazole (approved in December 2002; sold as Abilify by Bristol-Myers Squibb). These drugs are believed to work by blocking specific dopamine and serotonin receptors linked to schizophrenia and other psychotic disorders, although the exact mechanism is unclear.

Zyprexa is available as a standard tablet and under the Zyprexa Zydis name as an orally disintegrating tablet. Zyprexa is the most-prescribed antipsychotic with sales of $3.7 billion last year.

The chief advantage of atypical antipsychotics over older antipsychotic drugs is that the newer medications are less likely to cause movement disorders such as akathisia (restlessness), dystonia (muscular spasms of the neck, eyes, tongue, or jaw), Drug-Induced Parkinsonian Syndrome (muscle stiffness, shuffling gait, drooling, and tremor), and tardive dyskinesia.

Zyprexa Linked to Blood Sugar Disorders

Zyprexa has its own dangers, however: blood chemistry changes leading to diabetes, hyperglycemia, and other blood sugar disorders. On September 15, 2003, the federal Food and Drug Administration ordered Lilly to add warning language concerning these risks to the Zyprexa product label. This language was also added to the product labels for the other atypical antipsychotics.

Several studies have indicated that Zyprexa use is linked to an increased risk of diabetes:

A study published in the July 2003 issue of the Journal of Clinical Psychiatry concluded that patients receiving Zyprexa had a significantly greater risk of diabetes than untreated patients, while Zyprexa also showed significantly higher odds of diabetes with an increasing dose.

A study published in the August 3, 2002, issue of the British Medical Journal concluded that patients taking Zyprexa have a "clinically important and significant increased" risk of diabetes.

A study published in the July 2, 2002, issue of Pharmacotherapy found 289 cases of diabetes in patients who had been prescribed Zyprexa. Of the 289 cases, 225 were newly diagnosed cases. One hundred patients developed ketosis (presence in the bloodstream of chemicals that the body makes when there is not enough insulin and it must break down fat for its energy), and 22 people developed pancreatitis (inflammation of the pancreas), which is a life-threatening condition. There were 23 deaths, including a 15-year-old adolescent who died of necrotizing pancreatitis, a condition where the pancreas breaks down and dies. Most cases (71 percent) occurred within six months of starting the drug and many cases were associated with moderate weight gain.

In April 2002 the Medicines Control Agency in the U.K., which is now known as the Medicines and Healthcare Products Regulatory Agency, published an analysis finding that, among patients prescribed Zyprexa, "forty reports of hyperglycemia, diabetes mellitus, or exacerbation of diabetes have been received in the UK. Four were associated with ketoacidosis and/or coma including 1 with a fatal outcome."

Also in April 2002 the Japanese Ministry of Health, Labour and Welfare Ministry warned Eli Lilly Japan concerning side effects of Zyprexa after the deaths of two diabetic users of the drug. The ministry said seven other patients had lost consciousness or become comatose after taking the drug in the previous 10 months. The ministry said no new diabetes patients should be treated with the drug and ordered Eli Lilly to warn doctors to closely monitor diabetics already on the medication.