JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
Volume 25, Number x, 2015
Mary Ann Liebert, Inc.
Pp. 12
DOI: 10.1089/cap.2015.0135
Nasal and Gingival Bleeding during
Aripiprazole but not Haloperidol Treatment
Esra Hosxoglu, Ozlem Bayram, and Sabri Herguner
To The Editor:
A ripiprazole is a partial agonist at dopamine D2 and sero-
tonin 5-HT1A receptors, and is an antagonist at serotonin 5-
HT2A receptors. Several studies have reported that it was effective
for treatment in children and adolescents with irritability associated
with autistic spectrum disorder, and that it was safe and well tol-
erated (Marcus et al. 2011). Fatigue, increased appetite, headache,
sedation, and somnolence were among the most reported adverse
effects of aripiprazole (Owen et al. 2009).
In this report, we will describe a pediatric patient who developed
nasal and gingival bleeding during aripiprazole treatment.
Case Report
A 12-year-old boy with diagnoses of autism spectrum disorder
and moderate intellectual disability was referred to our outpatient
clinic with complaints of self-injurious behaviors, aggression, and
irritability. According to his medical history, he had coagulation
disorder (factor VII deficiency) and was receiving daily factor VII
replacement treatment. Aripiprazole 2.5 mg/day was prescribed for
his self-injurious and disruptive behaviors, and the dose was in-
creased to 5 mg/day 5 days later. During their second visit to our
clinic 3 weeks later, his mother reported that on the 2nd day of
aripiprazole treatment he had experienced nasal and gingival
bleeding. His bleeding occurred every day, and its frequency and
severity increased when the dose of aripiprazole was increased to
5 mg/day. They were referred to the hematology clinic 10 days after
beginning the aripiprazole treatment because of the patients nasal
and gingival bleeding. This condition was considered by his phy-
sician to be a possible adverse effect of aripiprazole, and the
medication was discontinued. After the cessation of aripiprazole,
bleeding did not reoccur. However, because of the severity of the
patients behaviors, the patient and his mother were referred to our
clinic. We decided to initiate haloperidol, and titrated the dose up to
1.5 mg/day. He had no bleeding during this treatment and tolerated
the medication well.
We presented a case who experienced nasal and gingival
bleeding during aripiprazole treatment but did not during halo-
peridol treatment. To our knowledge, there is no report in the lit-
erature of bleeding associated with aripiprazole. The chronological
relationship between the time of aripiprazole administration and the
development of bleeding and the fact that there was no occurrence
Department of Child and Adolescent Psychiatry, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey.
1
Letter to the Editor
after aripiprazole discontinuation suggest aripiprazole to be the
probable causative agent.
Discussion
Bleeding is a rarely reported side effect of antipsychotics, in-
cluding risperidone. The bleeding side effect of risperidone was
suggested to be associated with 5-HT2A receptor antagonism
(Coskun and Mukaddes 2008). The 5-HT2A receptor has a role on
mediating platelet aggregation and vasoconstriction in human
coronary arteries (Przyklenk et al. 2010). Antagonism of the 5-
HT2A receptor was suggested to cause bleeding by increasing
blood flow in microcirculation, reducing the platelet aggregation,
and inhibiting the release of vasoconstrictors from platelets (Cos-
kun and Mukaddes 2008). Therefore, in this reported case, we may
speculate that aripiprazoles 5-HT2A antagonism might have
possibly caused bleeding by its antithrombotic effect on microcir-
culation. However, this potential explanation may not describe the
entire mechanism of this adverse reaction.
Another issue that needs to be discussed is development of
bleeding during aripiprazole treatment but not during haloperidol
treatment. Aripiprazole has a higher 5-HT2A antagonism than
haloperidol (Amato 2015). Haloperidols low affinity to 5-HT2A
receptors might be the reason for nonoccurrence of bleeding.
Although bleeding is a rare side effect, clinicians should be
aware that aripiprazole may cause bleeding, especially in suscep-
tible patients with coagulation disorders.
Disclosures
No competing financial interests exist.
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