A new study published in the October 19, 2005, edition of the Journal of the American Medical Association found that Zyprexa, Risperdal, Seroquel and Abilify, drugs used to treat schizophrenia, may raise the death rates in elderly patients treated with the drugs for dementia. These drugs are produced by some of the biggest drug companies in the world, including Eli Lilly and Company (Zyprexa), Janssen Pharmaceutical (Risperdal), AstraZeneca Pharmaceuticals (Seroquel), and Bristol-Myers Squibb and Otsuka America Pharmaceuticals (Abilify).

An analysis of 15 separate drug studies and more than 5,000 patients found that 3.5% of those getting these drugs for eight to twelve weeks died, compared with 2.3% of patients on placebos. The findings come on the heels of risks first disclosed by the FDA in April concerning these drugs.

Lead researcher Lon Schneider, professor of psychiatry at the University of Southern California’s Keck School of Medicine, said that doctors may want to take elderly patients off of these drugs more quickly if they fail to immediately benefit from these drugs, given these findings.

Source: Michelle Fay Cortez, “Lilly, J&J, AstraZeneca Dementia Drugs Boost Deaths in Study,” Bloomberg.com, October 18, 2005.

The results of a large clinical trial of schizophrenia drugs were published in the New England Journal of Medicine this week. The study found that Seroquel, the dominant drug on the market, and other newer treatments were no better than the older generic drug perphenazine at controlling schizophrenic symptoms despite their higher cost. The study also found that Seroquel had the highest dropout rate among users, with 82% of users discontinuing treatment within 18 months of their first dose.

Similar results were seen for Eli Lilly and Co.’s Zyprexa, Johnson & Johnson’s Risperdal, and Pfizer, Inc.’s Gedeon.

Source: Ben Hirschler, “Critical drug study tarnishes Astra star Seroquel,” Reuters, September 20, 2005.

Researchers reported that three drugs commonly used to calm agitation and aggression in Alzheimer’s patients are not more effective than placebos and put patients at risk for serious side effects, including Parkinson’s disease-like symptoms. This is the third report in the last year to conclude that atypical antipsychotics are not as effective or as safe as originally thought.

The three drugs tested in the study - Zyprexa, marketed by Eli Lilly; Seroquel, marketed by AstraZeneca; and Risperdal, marketed by Janssen Pharmaceutical - are known as atypical antipsychotics and are primarily used to treat schizophrenia. They are often prescribed for elderly patients in long-term care facilities.

Overall, the report found the adverse effects of the three drugs outweighed the benefits, with up to a quarter of the patients in the study dropping out because of the effects.

Some of the side effects observed include:

• Parkinson’s disease-like symptoms, including tremors (12 percent)
• Sedation (15-24 percent of the patients)
• Confusion (6 percent of the patients)

Risperdal, Zyprexa and Seroquel were not approved by the Food and Drug Administration (FDA) for use in Alzheimer’s patients. About 4.5 million Americans suffer from the progressive dementia of Alzheimer’s disease, with most exhibiting agitation or delusions at some point. Almost one-third of the 2.5 million Medicare beneficiaries in nursing homes in the US have taken the medications, accounting for an estimated $2 billion in the annual sales of the drugs.

“The question is whether these drugs have a place in the treatment of Alzheimer’s patients at all,” Dr. Jason Karlawish, an associate professor of medicine at the University of Pennsylvania, said. “I think the answer is yes, but only for a subgroup of patients who can tolerate them, and in facilities that have the expertise to manage the side effects.”

The drugs are required by the FDA to have a black-box warning on the prescription drug insert that states, “elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo.”

Researchers in the study followed 421 Alzheimer’s patients who suffer from agitation, delusions or hallucinations. After 12 weeks, there were no signs of significant improvement. About 80 percent stopped taking the drugs and the placebos alike before the end of the study, and those on the drugs were found more likely to quit because of side effects.

“What this study shows is that these drugs are clearly not the answer; they may be helpful for a minority of patients but we need to come up with better medications,” Dr. Thomas R. Insel, director of the National Institute of Mental Health, which financed the study, said.

Sources: Benedict Carey, “Alzheimer’s drugs offer no help, study finds,” New York Times, October 12, 2006; Neil Osterweil, “Atypical Antipsychotics Get Poor Grade for Alzheimer’s Psychoses,” MedPageToday, October 11, 2006.

Billy Robbins filed suit in East St. Louis on April 28, 2006 alleging the anti-psychotic drug Seroquel caused him to develop pancreatitis, an inflammatory disease that can cause serious and life-threatening gastrointestinal disorders in patients. In severe cases, internal bleeding, tissue damage, and infections can occur. Some patients may develop pseudocysts, which are accumulations of fluid and tissue debris that can become toxic and begin to break up and flood the bloodstream with dangerous infectious organisms.

According to Mr. Robbins’ complaint, the maker of Seroquel, AstraZeneca, failed to warn consumers regarding the significant risks of serious or even fatal injuries to the liver, kidney and pancreas of patients. The warning label on Seroquel may not have included adequate information about the significant risks being alleged by Mr. Robbins, including:

• Ketoacidosis, a serious condition of dangerously high levels of acidic ketones which can lead to diabetic coma
• Diabetes mellitus
• Heart disease
• Blindness
• Seizures
• Coma & Death

Mr. Robbins is seeking damages in excess of $750,000 in his personal injury lawsuit.

Source: Steve Gonzalez, “Plaintiff claims Seroquel caused pancreatitis in federal suit,” Madison-St. Clair Record, May 1, 2006, accessed May 2, 2006.

Health Canada, the Canadian regulatory agency similar to the Food and Drug Administration in the United States, has issued a request to manufacturers of certain atypical anti-psychotic medications to include a warning in certain medication labeling for elderly patients with dementia. Recent studies of these types of drugs, which are second-generation anti-psychotic medications usually prescribed for schizophrenia, have shown that elderly patients with dementia had a 1.6 time higher death rate that other elderly patients when taking the drugs Seroquel, Zyprexa, and Risperdal. While no studies were done with the anti-psychotic drug Clozaril, a similar drug, Health Canada has requested that Clozaril labeling also contain a warning.

Seroquel, Zyprexa and Clozaril are not approved in Canada for treating patients with dementia but are approved for use with schizophrenic patients. Prescribing a drug for uses other than its approved indication, a practice known as “off-label” prescribing in the U.S., may cause harm to patients.

Sources: Anne Winstanley, Toronto 680 News, June 15, 2005; Canadian Press, June 16, 2005.