Concerns about the growing medicalisation of children and adolescents with psychiatric and related illnesses will gain further credence following the publication of a new US study in which use of second-generation antipsychotics in a cohort aged four to 19 years resulted in rapid and dramatic weight gain.

With some of the drugs used, noted the research team led by Dr Christoph Correll from the Zucker Hillside Hospital and the Feinstein Institute for Medical Research in New York, there were also substantial adverse metabolic effects, such as increased blood levels of cholesterol or triglycerides.

In an accompanying editorial published in the Journal of the American Medical Association (JAMA), Drs Christopher Varley and Jon McClellan of Seattle Children’s Hospital suggested that “given the risk for weight gain and long-term risk for cardiovascular and metabolic problems, the widespread and increasing use of atypical antipsychotic medications in children and adolescents should be reconsidered”.

The Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) study, conducted between December 2001 and September 2007 in Queens, New York, enrolled 338 children and adolescents aged four to 19 years with mood spectrum, schizophrenia spectrum, and disruptive or aggressive behaviour spectrum disorders who had been taking antipsychotics for one week or less.

Of these patients, 272 had at least one post-baseline assessment. Fifteen patients who refused participation or were non-compliant with treatment were used as a comparison group. The active group were prescribed one of four second-generation antipsychotics and were followed over the first 12 weeks of treatment to assess changes in weight, blood glucose and lipids.

After a median of 10.8 weeks, patients had gained an average of 8.5 kg on olanzapine (Zyprexa, Eli Lilly), 6.1 kg on quetiapine (Seroquel, AstraZeneca), 5.3 kg on risperidone (Risperdal, Johnson & Johnson) and 4.4 kg on aripiprazole (Abilify, Otsuka/Bristol-Myers Squibb. In the untreated comparison group, the average weight gain was 0.2 kg.

With the patients prescribed Zyprexa and Seroquel, there were significant increases in mean levels of total cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol and the ratio of triglycerides to HDL cholesterol, Correll et al reported. Triglyceride levels were also raised significantly in patients given Risperdal. Metabolic baseline-to-endpoint changes in the Abilify and the comparison groups were not significant.

“Our results, together with data from first-episode studies, suggest that guidelines for antipsychotic medication exposure for vulnerable paediatric and adolescent patients naive to antipsychotic medication should consider more frequent (e.g., biannual) cardiometabolic monitoring after the first three months of treatment,” the researchers wrote.

“Finally, in view of poor physical health outcomes and sub-optimal metabolic monitoring in the severely mentally ill, the benefits of second-generation antipsychotic medications must be balanced against their cardiometabolic risks through a careful assessment of the indications for their use, consideration of lower-risk alternatives, and proactive adverse effect monitoring and management.”