Weight gain induced with olanzapine in adolescent

Abstract

Children and adolescents are being treated with antipsychotics more often than before, although the risk of adverse events in this age group still remains unclear. Because of increased use of antipsychotics in children and adolescents, their endocrine and metabolic side-effects (weight gain, obesity, and related metabolic deviations) are of particular worrying, especially within pediatric and adolescent population that appears to be at greater risk comparing with adults for antipsychotic-induced metabolic adverse events. In this work we will present the course of treatment of an adolescent girl with psychotic symptoms, within the clinical diagnosis of Organic delusional disorder, who had a considerable weight gain after one year of olanzapine treatment.

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Psychiatria Danubina, 2011; Vol. 23, No. 1, pp 101–104 Conference case report
© Medicinska naklada - Zagreb, Croatia
WEIGHT GAIN INDUCED WITH OLANZAPINE IN ADOLESCENT
Mirjana Graovac
1,2
, Klementina Ružić
1,2
, Jelena Rebić
1
, Elizabeta Dadić-Hero
3,4
,
Ana Kaštelan
1,2
& Tanja Frančišković
1,2
1
University Psychiatric Clinic Rijeka, Clinical Hospital Centre Rijeka, Rijeka, Croatia
2
Department of Psychiatry and psychological medicine, School of Medicine, Rijeka, Croatia
3
Department of Social Medicine and Epidemiology, School of Medicine, Rijeka, Croatia
4
Community Primary Health Centre, Primorsko-goranska country, Croatia
SUMMARY
Children and adolescents are being treated with antipsychotics more often than before, although the risk of adverse events in this
age group still remains unclear.
Because of increased use of antipsychotics in children and adolescents, their endocrine and metabolic side-effects (weight gain,
obesity, and related metabolic deviations) are of particular worrying, especially within pediatric and adolescent population that
appears to be at greater risk comparing with adults for antipsychotic-induced metabolic adverse events.
In this work we will present the course of treatment of an adolescent girl with psychotic symptoms, within the clinical diagnosis
of Organic delusional disorder, who had a considerable weight gain after one year of olanzapine treatment.
Key words: olanzapine - weight gain - adolescence
* * * * *
INTRODUCTION
Children and adolescents are being treated more and
more with antipsychotics. The risk of side effects and
metabolic abnormalities in this age group remains
unclear (Overbeek et al. 2010).
Despite increasing use of psychotropic medication in
children and adolescents, their endocrine and metabolic
side-effects (weight gain, obesity, and related metabolic
abnormalities such as hyperglycaemia and dyslipi-
demia) are of particular concern, especially within this
pediatric population that appears to be at greater risk as
compared with adults for antipsychotic-induced
metabolic side-effects. In addition to medication, many
factors contribute to weigh gain in psychiatric patients,
including sedentary lifestyle and poor diet. Excessive
weight gain has several deleterious effects in psychiatric
patients, including stigmatization and further social
withdrawal, and non compliance with medication.
Furthermore, excessive corpulence may evolve to a
metabolic syndrome with a high-risk state for future
cardiovascular morbidity and mortality in adult age.
Because youths are still developing at the time of
psychotropic drug exposure, in a context of physio-
logical changes in hormonal and endocrine levels and
body composition, most reference values need to be
adjusted for gender, age and growth charts. Hence, sex-
and age-adjusted body mass index (BMI) percentiles are
crucial to assess weight gain in children and adolescents
(Goeb et al. 2010).
Olanzapine is an atypical antipsychotic that belongs
to the thienobenzodiazepine class. Olanzapine binds to a
large number of neurotransmitter receptors, including
the dopamine D
1
, D
2
, and D
4
receptors, serotonin 5-
HT
2A
, 5-HT
2C
, 5-HT
6
, and 5-HT
3
receptors, histamine
H
1
receptor, muscarinic receptors, α- and β-adrenergic
receptors, γ-amino butyrate (GABA)
a1
receptor, and the
benzodiazepine binding sites (Bymaster et al. 1996).
Olanzapine is associated with weight gain, dyslipi-
demia, and transaminase elevations in youth. Extrapyra-
midal symptoms, neuroleptic malignant syndrome, and
blood dyscrasias have also been reported, but appear
rare (Maloney
& Sikich 2010). In addition, olanzapine-
associated weight gain has been linked to genetic
variations in the 5-HT
2A
, 5-HT
2C
, and β
3
-adrenergic
receptor, leptin, and the G-protein β
3
subunit genes
(Templeman et al. 2005, Ujike et al. 2008).
Jerrell et al. (2008) in their research on side effects
in children and adolescents treated with antipsychotics
conclude that exposure to multiple antipsychotics and
serotonin-specific reuptake inhibitors consistently con-
fers a higher risk of developing a range of neurological
adverse events in young patients, especially those with
preexisting central nervous system, mental retardation,
or cardiovascular disorder (Jerell et al. 2008).
The experts disagree in their opinions on particular
issues, such as clustering risk factors, importance of
particular diagnostic procedures for the early detection
and monitoring of metabolic syndrome and the role of
antipsychotics in occurrence of metabolic syndrome.
There is, however, unique attitude about importance of
early detection and treatment of metabolic syndrome as
well as necessity of further investigations (Kozumplik et
al. 2010).
The use of antipsychotics in treatment of children
and adolescents requires good knowledge of psycho-
pathology, psychofarmacotherapy, developmental pro-
cesses and family relations (Graovac et al. 2010).
In our country olanzapine is registered for adoles-
cents over the age of 18.

Mirjana Graovac, Klementina Ružić, Jelena Rebić, Elizabeta Dadić-Hero, Ana Kaštelan & Tanja Frančišković: WEIGHT GAIN
INDUCED WITH OLANZAPINE IN ADOLESCENT Psychiatria Danubina, 2011; Vol. 23, No. 1, pp 101–104
102
CASE REPORT
The adolescent girl that we are presenting comes to
first psychiatric examination in summer of 2007, at the
age of 15. She was referred from a neuropediatrician
who suspected a psychotic state. From her mother we
found out that her daughter began to change at the time
of some awkward and unfortunate circumstances during
neurological treatment she was submitted to (the
retirement of her neuropediatrician, small number of
available neuropediatricians, a large number of children
in need of a neuropediatrician), she could not influence
to change. When she became agitated, started to have
hallucinations, with incoherent talk and refusal of food,
she was hospitalized on Clinic of pediatry, for
correction of antiepileptic medications.
Her mother shows us medical documentation of
convulsions on the day the girl was born. Regular
course of pregnancy was interrupted with premature
labour and complications (umbilical cord wrapped
around the neck of the baby, she was not breathing and
had to be resuscitated), that required two weeks of
treatment in intensive care unit. The recommended
therapy was phenobarbital, and she was regularly
examined by a neuropediatrician. When she was 9, she
had to be hospitalized again on the Ward of nero-
pediatry for epileptic seizures (diagnosis: Epilepsy,
secondarily generalized seizures). Carbamazepine was
introduced in therapy, and the girl had taken it until a
few months ago. In the period between 9 and 15 years
of age, she did not have crisis of loss of consciousness.
During the first consiliar psychiatric examination,
the psychic state of the patient was evaluated as
psychotic and low doses of risperidone (1 mg in the
evening) and alprazolame (1 mg per day) were
prescribed. The patient continued treatment on Clinic of
pediatry, along with regular psychiatric controls, during
and after hospitalization.
Routine laboratory blood parameters were in the
range of referent values.
A range of neurologic tests was performed: EEG -
border result; brain CT - mostly regular; brain MR -
signs of bilateral demielinization along occipital horns
of lateral ventricles (possibly due to ischemia).
Psychological evaluation shows border degree of
intellectual capacities (verbal quotient on the lower end
of average scores, nonverbal quotient on level of mental
retardation).
An antiepileptic drug, oxcarbazepine 900 mg per
day, divided in two daily doses, was introduced in
therapy. Diagnoses at discharge: Epilepsy (G 40),
Organic delusional disorder (F 06.2), Mild mental
retardation (F 70).
During the following year, our patient came to
regular psychiatric control examinations, accompanied
by her mother. Risperidone was titrated to 6 mg per day,
enough for satisfactory control of the symptoms. She
continued her education, and had relatively good school
marks at the end of her second grade. She also had
regular neurologic control examinations and took
antiepileptic drugs that were prescribed to her. She had
no epileptic seizures.
The deterioration of her psychic state occurred in
fall of 2008, when she became distant, introvert, seemed
to be deep in her thoughts, staring at one point, laughing
with herself. She would leave house to go to school,
where she would not come. Mother had to watch over
her all the time. To our recommendation for hospita-
lization of the patient, we did not get mother's approval,
and she decided to take her daughter for a second
opinion, psychiatric evaluation at another psychiatrist,
who removed risperidone from therapy, and introduced
sulpyride (100 mg), lamotrigine (100 mg), as well as
alprazolame (0,75 mg), promazine (100 mg) and
diazepam (5 mg).
On the following control, one year after, we come to
know that our patient's psychic condition deteriorated,
with periods of psychomotor agitation, aggressiveness
and irritability, which were interrupted by periods when
she was distant, staring at one point, having hallu-
cinations and listening at sounds. At that time her
mother agreed to hospital treatment of the girl. The
patient was hospitalized at two occasions, in spring
(April) and summer (August) of 2009. During
hospitalization in April, a correction of medications was
conducted; olanzapine 15 mg per day and lamotrigine
150 mg per day, were prescribed. EEG result was
regular, as well as were laboratory blood parameters.
With prescribed medication, the patient became calmer,
and her sleep was also improved. Despite occasional
episodes of agitation, according to mother's information,
girl's condition was notably better compared to the
period before hospital treatment.
8 to 9 months after olanzapine was introduced to
therapy, an abrupt weight gain was observed. We
measured and found that the patient's weight was 68 kg
(BMI=28), which was a weight gain of 16 kg.
Laboratory blood parameters at this point were changed,
and revealed increased levels of glucose in blood,
cholesterol and thyroid-stimulating hormone.
Weight gain was a valid indication for correction of
antipsychotic, switching from olanzapine to quetiapine
500 mg.
Since this medication correction, body weight and
BMI were monitored.
After two months, body weight was 62 kg
(BMI=25,5), and four months after medication
correction body weight was 56 kg (BMI=23).
Laboratory blood parameters were completely stabilized
six month after correction.
One year after our patient regained her "normal
weight" - 52 kg (BMI=21,5).
During the change of therapy her psychic condition
was not deteriorated, beside periods of somnolence and
psychomotor retardation in the first three weeks after
medication change. She did not have epileptic seizures.

Mirjana Graovac, Klementina Ružić, Jelena Rebić, Elizabeta Dadić-Hero, Ana Kaštelan & Tanja Frančišković: WEIGHT GAIN
INDUCED WITH OLANZAPINE IN ADOLESCENT Psychiatria Danubina, 2011; Vol. 23, No. 1, pp 101–104
103
At this point, the patient's therapy consists of
quetiapine with prolonged action, in the dose of 600 mg,
with lamotrigine 300 mg and diazepam 15 mg per day.
Her psychic condition is now in partial remission, with
occasional hallucinatory experiences of pleasant nature.
DISCUSSION
In this clinical case report our aim was to present the
course of treatment of a girl adolescent with olanzapine
and the occurrence of a side-effect - weight gain.
Psychotic decompensation in the adolescent patient
occurred at the time of inadequately controlled neuro-
logic disorder - epilepsy, coincided with the develop-
mental period of middle adolescence. An increased risk
for occurrence of psychic symptoms in our patient is
due to verified organic base (anoxia at birth,
convulsions, epilepsy), decreased intellectual capacities,
as well as interrupted antiepileptic therapy.
Comorbidity is an extremely important issue in
comprehensive, individual and personalized patient
menagement (Jakovljević 2009).
During one year use of olanzapine (15 mg per day)
we achieved relatively good control of psychotic
symptoms. In first 8 to 9 months of therapy with
olanzapine, body weight was not changed significantly,
but the following 2 to 3 months showed notable weight
gain.
Comparative studies of olanzapine use in adoles-
cents of Kryzhanovskaya et al., revealed significance of
a side-effect - weight gain in adolescents treated with
olanzapine in comparison to placebo. Average weight
gain in adolescents treated with olanzapine was 3,9 kg.
Authors emphasize that the increase in body mass index
(BMI) is a more appropriate measure of increased size
in youth. In examining the time course of weight gain,
there appears a marked reduction in the slope of weight
gain after 4 weeks of treatment (Kryzhanovskaya et al.
2009).
We find the fact of abrupt weight gain (16 kg) in an
adolescent treated with a stabile dose of olanzapine,
during the last 2 to 3 months of one-year treatment,
rather interesting.
The literature shows contradictory results, for
example, similar findings of rapid weight gain followed
by slower weight gain have been observed in other trials
(Ratzoni et al. 2002, Fleischhaker et al. 2008, Findling
et al. 2010).
The researches of Gebhardt et al. show that female
gender and younger age when treated were associated
with the magnitude of antipsychotic-associated weight
gain independent of medication. Further, individuals
with low pretreatment BMI initially show more rapid
weight gain than their heavier peers even though total
weight gain with treatment is less (Gebhardt et al.
2009).
A more gentle body constitution (156 cm, 52 kg) of
our patient, as well as the dose of antipsychotic used,
according to findings of Gebhardt, can be taken under
consideration in finding an explanation for such abrupt
weight gain in a short period of time.
Certainly, weight gain with increased BMI and
changed laboratory blood parameters in our patient,
showed the seriousness of this side-effect and the
potential risk of the development of metabolic
syndrome. According to psychopharmacotherapy
recommendations we monitored these parameters, along
with medication correction and observation of psychic
condition of the patient.
With the change of antipsychotic, increased
laboratory blood parameters gradually stabilized, and
body weight was reduced to previous values. In the
contrary, the "window for some new disorders would be
still open".
CONCLUSION
In everyday clinical practice we rather often
encounter adolescents that, beside psychic disorders,
have comorbidities. The specificities of "other"
disorders instruct us to the need of interdisciplinary
approach and cooperation. It is extremely important to
know very well all possible side-effects of the
medications we prescribe, so we could promptly
intervene, according to achievements and professional
rules.
Our clinical presentation of the course of treatment
of an adolescent girl with psychotic symptoms, who was
diagnosed with Organic delusional disorder and
Epilepsy, shows that, beside positive effects
antipsychotics have on psychotic symptoms, we also
have to take care of possible side-effects of medication.
Measurement of body weight and calculation of
BMI are very simple and easily applicable methods, as
well as laboratory blood parameters, give a very good
insight to some side-effects of antipsychotic therapy.
Olanzapine has played a critical role in alerting
scientists to the metabolic consequences of most
antipsychotics, particularly within children and
adolescents. Weight and metabolic changes observed in
olanzapine-treated youth stimulated investigations of
such effects among youth treated with other
antipsychotics and provided a need for further long-term
studies of antipsychotic tolerability in youth.
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Correspondence:
Mirjana Graovac
University Psychiatric Clinic Rijeka, Clinical Hospital Centre Rijeka
Department of Psychiatry and psychological medicine, School of Medicine
Cambierieva 17/7, 51000 Rijeka, Croatia
E-mail: mirjana.graovac@ri.t-com.hr