Systemic antihistamines in the treatment of attention-deficit/hyperactivity disorder (ADHD): a pilot study.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral
disorder which emerges before the age of 7 years. Epidemiological studies
showed that ADHD has an estimated prevalence rate of 5% among school-aged
children, with a 3 to 4-fold higher rate for boys than girls. [1] ADHD is
characterized by behavioral symptoms like inattention, impulsivity,
hyperactivity and social disabilities. The diagnostic and statistical manual
for mental disorders (DSM IV) is the standard used for ADHD diagnosis; it is
based particularly on these characteristics of ADHD. For what is known at this
moment, ADHD does not have one overall cause, it is more likely that various
factors influence the occurrence of the disorder. Factors such as environment,
nutrition and genetics have been mentioned in former research based on their
association with ADHD.
Like ADHD, atopic diseases are also very common among children. In the
Netherlands approximately 115,000 children are diagnosed with asthma and it has
been indicated that about 20% of the children has a type of atopic disease in
general. In many children these diseases co-occur. As an example, children with
asthma have a higher chance on development of atopic rhinitis, and the other
way around, than children without atopic diseases. As ADHD and atopic diseases
are both most common diseases among children, this finding raised the question
whether there is a common causal pathway. Research data on this subject show
conflicting results, but all mention a possible raise of risk. Recently, we
confirmed the association in the General Practitioner Research Database a large
British database and found an increased risk for atopic diseases in boys with
ADHD. [4]
The possibility that both allergic diseases and ADHD have a common
pathophysiology has been posed before. Pelsser et al discussed this and studied
the influence of a diet, low in allergens, in children with ADH. She found a
significant and relevant decrease of ADHD symptoms. The diet, however, was
difficult to keep. [6]
Another way to influence a possible common pathophysiology could be to use
antihistamines. Histamine plays a key role in the development of allergic
symptoms by blocking histamine-receptor. To date, at least three types of
histamine-receptors have been identified. Type I is important in allergy, type
II is necessary in the production of gastric acid and type III is recognized as
a cerebral transmitter. As far as we know, there is only one study started to a
pharmacological intervention of allergy and ADHD, results of this study are not
published. Other studies on this subject are low in quality, due to low number
of participants or design, such as blinding.

Primary objective

To assess whether the use of alimemazine improves symptoms of allergic diseases
and ADHD, as scored by the parents using standardized questionnaires (Sample
Snap IV rating scales)

This is a cross-over study. After inclusion the patients will use the
alimemazine/placebo for 4 weeks and then the symptoms will be assessed. After
one week for wash-out, the patients will use placebo/alimemazine for 4 weeks
and then the symptoms will be assessed again.

The intervention will be the use of 5 mg alimemazine, an antihistaminic drug,
once daily for 4 weeks.

ADHD is a relatively common disorder, affecting 5% of school chidren. At this
moment, methylphenidate is the drug of choice. We will study whether the
addition of alimemazine will influence ADHD symptoms. In an earlier study we
found that in the group of children with ADHD more children have an allergic
disease and this could mean that there is a common pathway in pathofysiology.

We consider the burden of using one tablet of 5 mg alimemazine once daily
relatively low. These children use tablets of methylphenidate for a prolonged
period. The risk of alimemazine is drowsiness and sleepiness. Therefore we will
advice the children to take the medication for bed-time. so that this side
effect is minimalised.
If we find that adding alimemazine is beneficial for these children with a
mimimun of side-effects, this will give another treatment option for this
group. Some children have side effects during the use methylphenidate and
therefore do not use more despite the fact sometimes they still have symptoms.
When we find that alimemazine is beneficial we can diminish the symptoms
without increasing side effects.