Older antipsychotic drugs get new respect

A comparison of medications for severe mental illness shows that an old drug works just as well as new ones for teenagers, plus it doesn't cause the weight gain that has worried patients, parents and doctors, researchers at the University of North Carolina at Chapel Hill report today.

The study, the first to compare the two generations of schizophrenia drugs, could change the way doctors prescribe treatments for teens. The powerful new medications are increasingly prescribed for a variety of disorders, including aggression, hyperactivity, depression and autism.

A national study published in 2006 found that between 1993 and 2002, there was a sixfold increase in the number of doctor visits that resulted in young people getting prescriptions for antipsychotic medications.

And overwhelmingly, teenagers are prescribed the new drugs, which include Risperdal, Zyprexa, Seroquel, Geodon and Abilify.

Few of the drugs have been specifically approved by the Food and Drug Administration for children. But they are widely prescribed because doctors have perceived them as generally safe.

Unlike old medicines that came out in the 1950s, the new drugs are less prone to causing stiffness and debilitating muscle spasms.

But the new drugs have other side affects, and one of them is weight gain -- sometimes alarmingly fast and excessive.

Brandon Constantineau, 18, of Wilmington, took Zyprexa for about eight months while participating in the trial at UNC-CH. He gained 34 pounds before he was shifted to another drug.

"It seemed like I gained more and more," Constantineau said in an interview. "It was real depressing, and kids picked on me."

A large weight gain is more than a vanity issue. It raises the likelihood of diabetes, high blood pressure, elevated cholesterol and heart disease -- ailments typically associated with older adults.

"Those cut down on life expectancy and have an impact on long-term health and well-being," said Dr. Lin Sikich, an associate professor in the Department of Psychiatry at UNC-CH. Sikich was lead author of the drug study, published today in the American Journal of Psychiatry.

"We want people to think carefully about the risk-benefit profile of these medicines when they choose what to use."

In the study, Sikich and doctors at three other medical centers enlisted 119 youngsters between the ages of 8 and 19 who had been diagnosed with either schizophrenia, or schizo-effective disorder, a condition that includes hallucinations plus radical mood swings.

The patients were randomly assigned to take one of three drugs: olanzapine, which goes by the brand name Zyprexa; risperidone, sold as Risperdal; and molindone, an old-line medicine known as Moban.

All three drugs eased schizophrenic symptoms similarly. But the youngsters on the two newer drugs tended to gain weight, prompting the National Institute of Mental Health, which paid for the study, to stop researchers from recruiting patients to the olanzapine arm of the study.

Sikich said olanzapine should not be prescribed to young people as a first choice. Instead, she said, older drugs should be given a new look.

"Many people are still pretty uncomfortable about using the older drugs," she said. But she said the comparative study will enable doctors to consider the data and make more-informed choices for their patients, especially for young people who are already overweight.

'It worked wonders'

Donna Whitaker said the choice of the old drug saved her son, Shane, from compounding problems. He entered the trial at UNC-CH in 2006, driving to Chapel Hill weekly from the family's home in Williamston, in Martin County. Shane was randomly assigned to take risperidone.

"He gained 15 pounds in a very short period of time," Whitaker said. "His face was real swollen and his hands were real puffy. He was just zombied out, like in a fog all the time."

As part of the trial, neither the doctors nor the participants knew which drugs were prescribed for which patients; a computer made the choices to keep everyone from developing biases.

After about four months, however, the Whitakers asked to switch to one of the other drugs in the trial, and the computer picked molindone for Shane, who is now 18.

"It worked wonders," Whitaker said. "We did not have the weight gain, nor the puffiness. He just did extremely well."

UNC-Chapel Hill researchers said they are now working on a clinical trial to help teenagers lose weight, or not gain weight, when they are prescribed the newer antipsychotic drugs.