Schizophrenias und Jazz
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Jazz, Schizophrenia And Side Effects
Matthew Herper, 06.15.05, 1:10 PM ET
Tom Harrell
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NEW YORK - Side effects have taken center stage in the $14 billion market for schizophrenia drugs.
To understand why, take the case of Tom Harrell, a renowned jazz musician and composer. Harrell, dubbed "the greatest trumpeter of his generation" by Entertainment Weekly, is also schizophrenic. For years, he has fought not only his disease, but also the crippling side effects of the drugs used to treat it.
For decades, he took Stelazine, one of an old class of antipsychotics that controlled his paranoia and delusions but also left him with muscle spasms that contorted his body.
Then, ten years ago, the drug caused a deadly condition called neuroleptic malignant syndrome, in which the muscles become rigid, blood pressure rises and muscles can deteriorate. His doctors told him to wait two-and-a-half weeks before starting a new schizophrenia medicine.
Instead, Harrell stayed off antipsychotics for six months, refusing to see a psychiatrist. His wife, Angela, says she started to worry for his safety. He finally agreed to try medicines again and was put on Zyprexa, which is made by Eli Lilly (nyse: LLY - news - people ). He occasionally also took anxiety and epilepsy drugs on top of it. But his muscle spasms returned, though studies said they were uncommon with Zyprexa. He also gained 30 pounds.
In 2000, Harrell switched again--this time to AstraZeneca's (nyse: AZN - news - people ) Seroquel on the recommendation of a movement disorder clinic and a doctor who came to one of his jazz shows. This time, his exaggerated tremors eased, and he has lost 60 pounds while still keeping his schizophrenia in check.
He still cuts an otherworldly figure, a grey-shocked wraith who stands stooped until he puts his horn to his mouth to play. But many of his symptoms--at least the drug-related ones--have improved.
Harrell is not alone. Seroquel is the fastest-growing antipsychotic, although it, too, can cause symptoms like weight gain and fatigue; some use it for unapproved symptoms.
Meanwhile, Zyprexa, the top seller for giant Eli Lilly, has seen its annual sales drop slowly in recent years as competitors such as Pfizer's (nyse: PFE - news - people ) Geodon and Abilify, from Bristol-Myers Squibb (nyse: BMY - news - people ), have boasted that they cause less weight gain.
Last Thursday, Eli Lilly announced plans to spend $690 million to end lawsuits from about 8,000 patients who said the firm had not adequately warned them that Zyprexa might also cause diabetes. Lilly did not admit any guilt.
"The weight of the evidence clearly is consistent with the patients' claims," says Daniel Casey, a psychiatry professor at Oregon Health & Science University, who has long criticized Zyprexa for raising the cardiovascular risk of patients.
Norman Sussman, head of psychiatry at New York University, says that Zyprexa works fast but has been connected with weight gain in his experience. Seeing that Lilly settled the cases--and sealed all records relating to them--makes him curious to know more. "As a clinician, it kind of whets my appetite for more information," Sussman says.
More information is unlikely to come from Lilly, but it may come from another source--a 1,600 patient clinical trial comparing widely used antipsychotics that is expected to be available later this summer. The trial, known by the codename CATIE, is being funded by the National Institute of Mental Health and will compare Zyprexa, Seroquel, Geodon and Risperdal, from Johnson & Johnson (nyse: JNJ - news - people ), and an older antipsychotic. Results are expected by the end of the summer.
Already stock analysts are starting to speculate on what CATIE might show. Timothy Anderson of Prudential Equity Group wondered in a note to investors whether Lilly's decision to settle at the high price of $85,000 per patient might indicate the firm had some doubts about the coming results. But Catherine Arnold of Credit Suisse First Boston says the study seems designed to play to Zyprexa's strengths, as patients will be switched off before weight gain or diabetes can develop.
But doctors like Sussman and Casey hope data from the new study will make it easier to match patients like Harrell with the right drug for them.
At a recent performance at a New York jazz club, Harrell showed up looking trim in a leather jacket and sunglasses--even though it was a hot, dark summer night. Harrell never said a word, and spent much of his time at the edge of the stage. But once or twice in every song, he would put his horn to his lips, stand ramrod straight, and play sweet, fast notes that danced in the air.
Diabetes Risk And Antipsychotics
Drug Drugmaker Weight Gain Diabetes Risk Cholesterol
Clozaril Novartis (nyse: NVS - news - people ) Strong Effect Clear Increased Risk Clearly Worse
Zyprexa Eli Lilly (nyse: LLY - news - people ) Strong Effect Clear Increased Risk Clearly Worse
Risperdal Johnson & Johnson (nyse: JNJ - news - people ) Some Effect Conflicting Data Conflicting Data
Seroquel AstraZeneca (nyse: AZN - news - people ) Some Effect Conflicting Data Conflicting Data
Abilify* Bristol-Myers Squibb (nyse: BMY - news - people ) and Otsuka Little Or No Effect No Effect No Effect
Geodon* Pfizer (nyse: PFE - news - people ) Little Or No Effect No Effect No Effect
*New medicine; less data is available. Source: Diabetes Care, Volume 27, No. 2, February 2004.
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