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In children and adolescents, the so-called atypical antipsychotic agents lead to a marked and rapid weight gain, researchers said.

In a 12-week observational study of four of the newer drugs, the average weight gain was between 4.4 and 8.5 kilograms (9.7 and 18.7 lbs), depending on the agent, according to Christoph Correll, MD, of Zucker Hillside Hospital in Glen Oaks, N.Y., and Albert Einstein College of Medicine, and colleagues.

On the other hand, metabolic changes were less uniform, Correll and colleagues wrote in the Oct. 28 issue of the Journal of the American Medical Association.

The atypical agents -- also called second-generation antipsychotics -- are thought to be more effective than older drugs, but in a pediatric population, their cardiometabolic effects have not been well studied, the researchers said.

To help fill the gap, they studied 272 patients ages 4 through 18, who had not been previously treated with an antipsychotic drug. The Second-Generation Antipsychotic Treatment Indications, Effectiveness, and Tolerability in Youth (SATIETY) study took place between December 2001 and September 2007 at institutions in the borough of Queens, N.Y.

Patients were treated with aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), or risperidone (Risperdal) for 12 weeks. The 15 patients who refused to take part or did not adhere to the protocol served as a comparison group.

After a median of 10.8 weeks of treatment, the researchers found that weight increased by:

• 8.5 kg (18.7 lb) on average among the 45 patients taking olanzapine
• 6.1 kg (13.4 lb) among the 36 patients on quetiapine
• 5.3 kg (11.7 lb) among the 135 patients on risperidone
• 4.4 kg (9.7 lb) among the 41 patients on aripiprazole
• 0.2 kg (0.4 lb) in the untreated comparison group

All the weight gains were significant, compared with baseline weight, at P<0.001.

The researchers also found that fat mass, body mass index, and waist circumference increased significantly for those taking the drugs, compared with baseline, while those in the untreated group saw no significant changes.

On the other hand, metabolic effects were much more varied, Correll and colleagues said.

Specifically, olanzapine and quetiapine were associated with significant average increases in total cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol and the ratio of triglycerides to HDL cholesterol.

Risperidone was associated only with a significant increase in the average triglyceride level.

And there were no significant changes seen in the aripiprazole or in the untreated comparison groups, the researchers said.

The study is limited by several factors, they acknowledged, including its nonrandomized, observational design, baseline differences that precluded rigorous group comparisons, flexible dosing, allowance of co-medications, a relatively short treatment period, and a small comparison group.

Despite limitations, the "results challenge the widespread use of atypical antipsychotic medications in youth," said Christopher Varley, MD, and Jon McClellan, MD, both of Seattle Children's Hospital.

In an accompanying editorial, they argued that the growing use of the medications in young patients is based mainly on adult literature.

While the drugs can be life-saving, they said, the long-term consequences of weight gain and metabolic effects mean "the widespread and increasing use of atypical antipsychotic medications in children and adolescents should be reconsidered."

They concluded that "consideration of less risky treatment interventions and scrupulous attention to metabolic parameters in children and adolescents who receive atypical antipsychotic medications are essential."