New Adverse Drug Reaction: Elevated Blood Sugar from New Antipsychotic Drugs in Adolescents

Medical officers from the Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research, along with a physician from the Duke University Medical Center, have reported a possible link between the use of the new antipsychotic drugs clozapine (CLOZARIL) and olanzapine (ZYPREXA) in adolescents and elevations in blood sugar levels (hyperglycemia) in 20 of these children. The report was published as a letter to the editor in the November 28, 2001 issue of the Journal of the American Medical Association.

Exactly how these drugs cause elevated blood sugar levels is unknown.

These drugs are referred to as “atypical antipsychotics.” All antipsychotic drugs usually improve symptoms such as agitation, delusions, hallucinations, and suspiciousness. Atypical antipsychotics additionally tend to improve negative symptoms such as apathy, disorientation, emotional withdrawal, and lack of pleasure, more than the older antipsychotics. However, there is no clear evidence that they are more effective or better tolerated than the conventional antipsychotics.

The authors of the letter searched the FDA’s adverse drug reaction data base to identify cases of hyperglycemia in patients younger than 19 years of age.

Between January 1996 and May 2001, the FDA received nine reports of hyperglycemia associated with the use of olanzapine in four males and five females aged 13 to 18. In seven of these cases, the hyperglycemia was newly diagnosed and in two instances there was worsening of preexisting diabetes. Elevated blood sugar levels appeared within one week after starting olanzapine in two cases and within six months in six other cases. Control of blood sugar levels improved in four patients after the drug was stopped or the dosage decreased. However, in one case, the hyperglycemia recurred after the patient was switched to other drugs. In this group of patients there was one death from inflammation of the pancreas (pancreatitis).

The FDA also received reports of hyperglycemia in seven males and four females, all between 13 and 18, associated with the use of clozapine between January 1993 and March 2001. Hyperglycemia was newly diagnosed in eight of these children and two experienced worsening of existing diabetes. Hyperglycemia occurred within six weeks of starting clozapine in five children and within six months for five others. The drug was discontinued or the dosage lowered in six, and blood sugar control improved in three of the children.

In these 20 children, two also experienced pancreatitis, though one was also taking a drug known to cause this condition. Again, because pancreatitis is uncommon in children, this suggests a causal association with the use of olanzapine and clozapine. In addition, the two cases of pancreatitis were found in the search for hyperglycemia and may not represent all cases of pancreatitis in the FDA’s database.

In general, the newer atypical antipsychotics should not be considered as first choices for the treatment of severe mental illness in children and adolescents.

What You Can Do

If your child is taking olanzapine or clozapine, since there are no approved guidelines for monitoring blood sugar with these drugs, you should discuss with your child’s physician the possibility of routine monitoring for hyperglycemia.