Study questions use of newer antipsychotic drugs in children

Sep 16 2008

A new study has found that older antipsychotic drugs are as effective as newer ones for some children.

The researchers from Chapel Hill School of Medicine in North Carolina say currently most children with schizophrenia or a schizoaffective disorder are commonly prescribed one of the second-generation, or “atypical” drugs, such as olanzapine and risperidone.

However the researchers say there has never been evidence that these drugs are more effective than the older, first-generation medications.

A study by the team has in fact revealed that the older drug molindone is as effective as the newer ones and they say it should be used as a first line of therapy for some children with such disorders.

Dr. Lin Marie Sikich, an associate professor in the department of psychiatry, says the study's findings indicate that guidelines will need to be rewritten so that some of the milder, traditional or older medications are considered first-line treatments in some cases.

Dr. Sikich says it was always thought that the second-generation drugs were superior because they had no side effects but in fact it was found that molindone works as well as the newer drugs, and in some cases is safer.

The study the 'Treatment of Early-Onset Schizophrenia Spectrum Disorders' (TEOSS) is the largest head-to-head trial which has compared the newer drugs, which became available in the 1990s, to the older ones, which have been around since the 1950s.

The study conducted from 2002 to 2006, involved 119 people aged 8 to 19 years who were randomly assigned to receive molindone, olanzapine or risperidone over an eight-week period.

The study took place at four sites - UNC; McLean Hospital and Cambridge Health Alliance at Harvard Medical School; Seattle Children’s Hospital and the University of Washington; and Case Western Reserve University.

Dr. Sikich says the decline in symptoms was similar across the three medications but the drugs caused very different types of side effects.

Both olanzapine and risperidone were associated with significant weight gain and could put young patients at risk of developing heart disease and diabetes and the evidence was so strong that the National Institute of Mental Health, which sponsored the study, halted recruitment into the olanzapine arm of the study because of the weight gain problem and the resulting increase in cholesterol and glucose levels.

Dr. Sikich says olanzapine should not be a first-line therapy in adolescents.

Both the older “typical” antipsychotics and newer “atypical” ones block dopamine receptors in the brain, but the newer drugs also interact with serotonin receptors and cause fewer muscle side effects, including stiffness, muscle cramps, restlessness and involuntary movements - the involuntary movements with some of the older drugs can lead to permanent physical disabilities.

The researchers found there were more reported cases of restlessness with molindone treatment than with either of the two newer treatments and those treated with molindone also needed another drug, benztropine, to decrease muscle cramps and stiffness.

One participant enrolled in the study about four years ago was initially prescribed olanzapine but quickly began gaining weight, ultimately adding more than 45 pounds over 36 weeks.

When he was switched to molindone he only gained about 8 pounds over the next 31 weeks and saw improvements similar to those with olanzapine.

However Dr. Sikich says as a result of being on olanzapine, the boy developed fatty liver disease and was ultimately prescribed two other medications.

The boy had been treated at age 3 for ADHD but medications and other therapies failed to help and he became violent.

Dr. Sikich saw the boy when he was 14, is now doing well on an even newer drug, ziprasidone.

Dr. Sikich says the study highlights two other points - the benefits of proper diagnosis and the need for more effective medications - as none of the medications were as well tolerated as had been hoped and better alternatives need to be found.

Dr. Sikich says a late diagnosis is a common problem with many children who develop early onset schizophrenia or schizoaffective disorder, and the diseases usually develop more severely when they begin in childhood.

In the TEOSS trial only half of all of the participants responded to any medication and the researchers say medications can make a vast difference in peoples’ lives, but better treatment options are needed.

The trial will next compare outcomes after a one-year course of treatment.

Use of Zyprexa and Risperdal have increased more than fivefold in the last 15 years and are all too often used in children with a wide variety of diagnoses, despite serious side effects - drug makers say the medications are not approved for use in children.

According to experts the results of the landmark study are likely to affect treatments for an estimated one million children and intensify the controversy over new medications.