Saturday, January 30, 2010

FDA's new warning on atypical antipsychotics and adolescents

The Federal Drug Administration on Friday issued a warning to doctors that adolescents taking the drug olanzapine have an "increased potential" -- in comparison with adults taking the new-generation antipsychotic drug -- for weight gain and metabolic disturbances that could result in diabetes or elevated blood cholesterol levels.

"Clinicians should consider the potential long-term risks when prescribing to adolescents," the FDA said in a statement released Friday night. "In many cases, this may lead to prescribe other drugs first," the statement went on.

The agency has not approved the marketing of olanzapine -- sold under the commercial nameZyprexa by the drug maker Eli Lilly -- for use in children under 13 who are diagnosed withschizophrenia or bipolar disorder. But the medication, one of a class of psychiatric medications called the "atypical antipsychotics," is widely prescribed for young patients, despite growing evidence that call its safety profile into question for this population.

The warning comes in the wake of the October publication in the Journal of the American Medical Assn., in which a study showed that children and adolescents taking their first-ever course of Zyprexa gained, on average, more than 17 pounds over a 12-week period, as well as dramatic increases in triglycerides and cholesterol levels -- all factors that put them at higher risk of developing cardiovascular disease. While two other antipsychotic drugs -- Seroquel and Risperdal -- were implicated in significant weight gain and metabolic changes, Zyprexa was found to carry the highest risks of all three.

The FDA said that in cases where physicians opt to prescribe olanzapine, the drug should be part of a "comprehensive treatment program," which could include psychological, educational and social counseling as well as medication therapy.


Melissa Healy in LA Times

1 comment:

Anonymous said...

I believe this FDA warning is intentionally misleading. Neither weight gain nor diabetes are the main toxicities of concern.

Last year the FDA held an advisory committee on the use of these drugs in adolescents. Olanzapine (Zyprexa) was recommended as second line treatmennt however, the most common as well as potentially deadly toxicity was hepatotoxicity and liver failure.

In the 3 week study with Zyprexa in adolescents only 1 child had to discontinue treatment due to weight gain whereas 6 times as many had to discontinue treatment (at week 2) due to liver toxicity and over 8% of all children had liver toxicity at week 2. In addition on long term use there were 2 deaths due to hepatic steatosis after 2 years. Considering the relatively unique metabolism this type of toxicity would be expected. Yet in heavy alcholics the same type of toxicity takes a decade or more to develop.

In addition, there were seveal cases of death due to or toxicity consistent with pulmonary arterial hypertension (phen-fen like toxicity) with multiple antipsychotics used in children and the FDA indicated that they were concerned of this for 3 years at that point (yet never mentioned anything).

These findings were independently confirmed in the FDA review of asenapine (saphis) with a recommendation that it not be approved.

Now the question is why did the reviewer indicate at the FDA transparency meeting that he was appealing being fired for speaking to the US Congress.