Our website uses cookies. We use cookies to remember settings and to help provide you with the best experience we can. We also use cookies to continuously improve our website by compiling visitor statistics. Read more about cookies

Fewer side effects of dexamethasone in children with leukemia

Children with acute lymphocytic leukemia (ALL) often receive the drug dexamethasone, and some children may suffer side effects. Physician-researcher Annelienke van Hulst investigated how behavioral changes caused by dexamethasone can be reduced. The results were different than expected: hydrocortisone works no better than placebo, but both seem effective. (van Hulst et al., 2023)

Dexamethasone is an important part of the treatment of ALL. In some children, this drug can also cause side effects, such as bone problems or weight gain, as well as sleep or behavioral changes. Parents and children especially find the behavioral changes a challenging side effect. Annelienke van Hulst, PhD-student in the Van den Heuvel-Eibrink and Grootenhuis research groups, investigated in the DexaDagen-2 study how this side effect could be reduced.


Reduced side effect

Previous research showed that behavioral changes may be reduced when hydrocortisone is given alongside dexamethasone treatment. Annelienke van Hulst: 'In the DexaDagen-2 study, we investigated in 52 children with many side effects of dexamethasone whether hydrocortisone could really reduce them.’ This study was prospectively randomized (randomized beforehand) and blinded to give the most reliable results.

‘If you want to investigate whether a drug works well, you always have to compare the drug (in this case hydrocortisone) with a placebo: a drug that looks the same but does not contain the active ingredient. Our study showed that hydrocortisone did not work better than placebo. We observed that the behavioral changes caused by dexamethasone decreased with both hydrocortisone and placebo.’


Placebo-effect

The results of the study were different than expected. One explanation for the results found may be the placebo effect. Placebo-effects are based on positive expectations: apparently it helps to actively do something we expect to help. Therefore, both hydrocortisone and placebo can have a positive effect in supporting children who experience many symptoms.

Annelienke explains: 'Based on our research, we will give parents of children who suffer a lot from the side effects of dexamethasone the choice to use hydrocortisone or a placebo. This will be done after proper explanation of how a placebo works. People often think a placebo only works if you don’t know it's a placebo, but previous research has shown that it doesn't! Even if you know it, a placebo can be very effective. This is because the body is capable of automatically responding to the intake of a medication, even if there is no active ingredient in it. A positive expectation about its effectiveness enhances this automatic response.’


Take the edge off

The study also showed that twice as many children have many side effects from dexamethasone compared to our earlier similar study. Annelienke: ‘We suspect that more side effects are reported because there is more awareness and attention being paid to the potential side effects of dexamethasone. Expectations, information and previous experiences of parents and children can contribute enormously to the occurrence of side effects of a drug. This is also known as a nocebo-effect. By adjusting and streamlining information and communication about dexamethasone, we are trying to minimize the nocebo effect.’

At the Princess Máxima Center, professionals respond to both the placebo- and nocebo-effect. In this way, we hope to provide appropriate support to children who experience many symptoms during dexamethasone treatment. Annelienke van Hulst summarizes the effect of her DexaDagen-2 study: 'We don't expect all the side effects of dexamethasone to suddenly disappear, but if the edges are taken off, a lot has already been gained for children and their parents.'


The scientific publication can be found here: van Hulst AM, van den Akker ELT, Verwaaijen EJ, Fiocco M, Rensen N, van Litsenburg RRL, Pluijm SMF, Zwaan CM, van Santen HM, Pieters R, Evers AWM, Grootenhuis MA, van den Heuvel-Eibrink MM. Hydrocortisone to reduce dexamethasone-induced neurobehavioral side-effects in children with acute lymphoblastic leukaemia-results of a double-blind, randomised controlled trial with cross-over design. Eur J Cancer. 2023 Jul;187:124-133.