JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY

Volume 19, Number 2, 2009

ª Mary Ann Liebert, Inc.
Pp. 203–206
DOI: 10.1089=cap.2008.020

Effectiveness of Mirtazapine in the Treatment of Inappropriate

Sexual Behaviors in Individuals with Autistic Disorder

Murat Coskun, M.D., Sevcan Karakoc, M.D., Fuat Kircelli, M.D., and Nahit Motavalli Mukaddes, M.D.

Abstract
Objective: The aim of this study was to investigate the efficacy and safety of mirtazapine in the treatment of
excessive masturbation and other inappropriate sexual behaviors (ISB) in individuals with the diagnosis of autistic
disorder (AD).
Method: Subjects (n ¼ 10; 2 females, 8 males; age range: 5.2–16.4 years) who suffered from excessive masturbation
with or without other ISB were treated with mirtazapine for 8 weeks. Clinical Global Impressions–Severity (CGI-S)
and Clinical Global Impressions–Improvement (CGI-I) scales were used for the evaluation of symptoms severity
and effectiveness. Mirtazapine was started at 7.5–15 mg=day and titrated up to 15–30 mg=day (mean
21.6
7.9 mg=day). The data for this study were collected from reviewing medical records of all subjects that
suffered from ISB and treated with mirtazapine.
Results: CGI scores at baseline and end point ranged from 5 to 7 (mean 6.22
0.83) and 2 to 4 (mean 3
0.7),
respectively. A nonparametric t-test showed significant difference in CGI-S scores between baseline and end point
assessments (Z ¼ 2.725; p ¼ 0.006, p < 0.01). Five subjects showed very much, 3 showed much, and 1 showed
moderate improvement in excessive masturbation on the CGI-I scale. One subject dropped out from clinical follow
up. Mirtazapine was generally tolerated well. The most frequently reported side effects were increased appetite,
weight gain (n ¼ 3; mean 0.78
1.20 kg), and sedation.
Conclusions: Mirtazapine could be an effective treatment to ameliorate ISB in a young population with a diagnosis
of AD. Well-designed, placebo-controlled studies are needed regarding this topic.

Introduction family, and environment, there are few studies and case re-
ports regarding the treatment of ISB in individuals with AD.

A utistic disorder (AD) is a neurodevelopmental disor-

der characterized by marked impairment in language
development, social interaction, and communication, along
with restricted, repetitive, and stereotyped patterns of inter-
ests and behaviors (American Psychiatric Association 1994).
Although an increasing number of studies has focused on the
efficacy of different treatment approaches to manage behav-
ioral problems associated with AD, there is a shortage of
studies on the treatment of inappropriate sexual behaviors
(ISB) in this population.
Previous research has found that individuals with AD may
display ISB frequently, such as undressing and masturbating
in public (Haracopos and Pedersen 1992; Ruble and Dal-
rymple 1993; Stokes and Kaur 2005), kissing of strangers
(Clements and Zarowska 2000), touching others inappropri-
ately and touching their private body areas in public (Stokes
and Kaur 2005), and sexual fetishism (Ruble and Dalrymple
1993; Coskun and Mukaddes 2008).
Although ISB have been frequently reported in individuals
with AD and have been a source of distress for the patient,
Some researchers recommend educational–behavioral ap-
proaches (Koller 2000), and some single-case reports describe
the efficacy of mirtazapine (Nguyen and Murphy 2001;
Albertini et al. 2006) or leuprolide (Realmuto and Ruble 1999)
in the treatment of excessive masturbation and the efficacy of
mirtazapine in the treatment of sexual fetishism (Coskun and
Mukaddes 2008) in individuals with AD. The present study is
a case series that aims to provide clinical data on the effec-
tiveness of mirtazapine in the treatment of ISB in individuals
with AD.
Methods
Participants
This study was conducted in the autism clinic in the Child
and Adolescent Psychiatry Department, Istanbul Faculty of
Medicine, Istanbul University. The participants were regular
patients of the autism clinic who had been followed up in
daily practice. The study included 10 individuals (2 females
and 8 males; age range, 5.2–16.4 years old; mean: 12.4
3.58

Department of Child and Adolescent Psychiatry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

203
204 COSKUN ET AL.

years old) with a primary diagnosis of AD who developed and side effects of mirtazapine treatment. A structured side-
ISB. Seven of subjects developed ISB during follow up and the effects checklist was used to query the subjects’ caregivers
other 3 were referred by their schools because of the emer- about side effects that occurred during treatment with mir-
gence of ISB. tazapine.
The severity of symptoms and the efficacy of treatment
were assessed using Clinical Global Impressions–Severity
Assessment
(CGI-S) and CGI-I scales. These scales were administered at
All subjects were diagnosed with AD according to Diag- baseline and end point. The diagnostic evaluation and the
nostic and Statistical Manual of Mental Disorders, 4th edition baseline and end point assessments were made by the first
(DSM-IV) criteria (American Psychiatric Association 1994). author (M.C.) and senior author (N.M.M.), who is the founder
In addition to the patients’ life-long problems in social- and director of the autism clinic.
communicative areas, ISB was one of the major concerns for
all of their parents that had been present for a long period Results
(6–36 months; mean 20.67
9.06 months).
Nine out of 10 subjects were included (completed the
ISB was defined as all sexual behaviors that are socially or
follow-up period) study. One subject dropped out of clinical
physically distressful for the family and environment and=or
follow up after first visit. CGI-S scores of ISB at baseline and
disturbing the social adaptation and=or educational program
end point ranged from 5 to 7 (mean 6.22
0.83) and 2 to 4
of the subject. The characteristics, severity, frequency, dura-
(mean 3
0.7), respectively. A Wilcoxon nonparametric t-test
tion, and impact of each ISB on subjects’ adaptive functioning
showed a significant difference in CGI-S scores between
and daily lives were assessed through detailed clinical inter-
baseline and end point assessments (Z ¼ 2.725; p ¼ 0.006,
views with families and, whenever possible, by observing the
p < 0.01). Five subjects showed very much improvement,
videos of these behaviors. The ISB in this group were mas-
3 subjects showed much improvement, and 1 subject showed
turbation at home and=or in public (100%), touching people
moderate improvement in excessive masturbation on the
inappropriately (50%), disrobing in public (20%), sexual in-
CGI-I scale. Six subjects also showed different levels of im-
terest in or arousal by some particular body parts or nonhu-
provement in other ISB (such as touching women inappropri-
man objects (20%), and observing people bathing or
ately, disrobing in public, fetishistic behaviors, etc.) (Table 1).
undressed (10%). The total time spent pursuing these ISB in a
According to parents’ statements, all subjects spent much less
day for each of the subjects ranged from 1 hour to almost the
time with ISB after treatment than before treatment; ISB almost
entire day.
disappeared in 3 subjects and decreased from the entire day to
As a part of regular assessment in our autism clinic, addi-
a few hours in 2 subjects. Four subjects were able to restart their
tional psychiatric disorders were assessed during a stan-
educational program. In addition, according to the parents’
dard psychiatric interview according to DSM-IV criteria.
reports, 2 subjects showed moderate improvement in ADHD,
Psychiatric examination of the subjects revealed attention-
2 subjects showed mild or moderate improvement in
deficit=hyperactivity disorder (ADHD) in 2 subjects; hyper-
hyperactivity=irritability, 2 subjects showed mild or much
activity (that did not meet criteria for ADHD) and irritability
improvement in irritability and aggressive behaviors, and 1
in 3 subjects; episodes of aggressive behaviors and irritability
subject showed moderate improvement in irritability, self-
in 2 subjects; and major depression in 2 subjects. Clinical
biting, and headache. In addition to improvement in these
manifestations of depression in these individuals included
behaviors, 2 subjects showed moderate or much improve-
increased social withdrawal, anhedonia, sad affect, crying,
ment in depression.
irritability, sleep problems, and an increase in stereotyped
All subjects reported at least one side effect possibly related
behaviors. The improvement in depression, hyperactivity,
to mirtazapine treatment. The most frequently reported side
irritability, and aggressive behaviors was rated with the
effects were increased appetite (n ¼ 5), weight gain (n ¼ 3;
Clinical Global Impressions–Improvement (CGI-I) scale, de-
0–3 kg; mean 0.78
1.20 kg), and sedation (n ¼ 5). Other re-
pending on clinical observation and parents’ reports. None of
ported side effects included tremor in hands and pain in legs
the participants had additional diagnosis of bipolar, obsessive
(n ¼ 1), worsening of previously existing constipation (n ¼ 1),
compulsive, or tic disorders. There was no report of sexual or
and increased water consumption and urinary frequency
physical maltreatments or known medical conditions except
(n ¼ 1). None of the subjects discontinued mirtazapine due to
for seizure disorder in 1 subject.
the side effects. The final mean dose of mirtazapine was
Before mirtazapine treatment began, 7 out of 10 subjects
21.6
7.9 mg=day. Marked improvement was reported in 4
had already taken other medications such as risperidone
subjects after 2 weeks of treatment, and the treatment con-
(n ¼ 6) and olanzapine (n ¼ 1) for behavioral problems (i.e.,
tinued in the same dosage in these subjects. Due to the lack of
hyperactivity, irritability, and aggression) and valproate
significant response, the dosage was increased in 5 subjects
(n ¼ 1) for epilepsy. All parents gave verbal informed consent
after 2 weeks. Three of them showed remarkable improve-
before mirtazapine treatment. The data for this study were
ment, but 2 displayed moderate improvement. Table 1 shows
collected by reviewing medical records of all subjects that
the characteristics of the subjects, the dosage range, and their
suffered from ISB and were treated with mirtazapine for their
response to treatment.
ISB. Mirtazapine was started at the dosage of 7.5–15 mg=day
and, according to clinical response and=or adverse effects,
Discussion
titrated up to maximum dosage of 30 mg=day. Parents were
encouraged to monitor the frequency and duration of each ISB We have presented here a study demonstrating the effec-
as well as insistence on and distractibility from having ISB. All tiveness of mirtazapine in the treatment of ISB in 9 subjects
subjects were evaluated every 2 weeks to monitor the efficacy with the diagnosis of AD. The majority of subjects showed
 Table 1. Characteristics of the Subjects and Their Response to Treatment

Age=gender and Concomitant

Case DSM-IV diagnosis Mirtazapine dosage medications Target symptoms CGI-I

I 5.2 years=female, autism (V), plus ADHD 7.5–15 mg=day None Masturbation Very much improved
Hyperactivity Moderately improved
II 12 years=male, autism (NV), plus major depression 15 mg=day Risperidone, 1 mg=day Masturbation Very much improved
Foot fetishism Very much improved
Major depression Much improved
III 14.4 years=male, autism (V), plus ADHD 15 mg=day Risperidone, 2 mg=day Masturbation Much improved
Hyperactivity Moderately improved
IV 12.5 years=male, autism (NV) 15–30 mg=day Risperidone 1 mg=day; Masturbation Very much improved
Valproate 500 mg=day Touching and rubbing women Moderately improved
Hyperactivity, irritability Mildly improved
V 7 years=female, autism (NV) 7.5 mg=day None Masturbation Not assessed due to
being dropped out
VI 13.8 years=male, autism (NV) 15–30 mg=day Risperidone, 1 mg=day Masturbation Much improved
Touching womens’ breasts Moderately improved
Disrobing Very much improved
Hyperactivity, irritability Moderately improved
VII 15 years=male, autism (NV) 15 mg=day Risperidone, 1 mg=day Masturbation Very much improved
Disrobing Very much improved
Irritability and aggression Much improved
VIII 16.4 years=male, autism (NV) 15–30 mg=day Risperidone, 1 mg=day Masturbation Moderately improved
Irritability=self- biting=headache Moderately improved
IX 14.6 years=male, autism (V) 15–30 mg=day Olanzapine 10 mg=day Masturbation Much improved
Socks fetishism Mildly improved
Irritability, aggression Mildly improved
X 13.2 years=male, autism (NV), plus major depression 15 mg=day None Masturbation Very much improved
Touching and rubbing women Moderately improved
Major depression Moderately improved

Abbreviations: DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th edition; CGI-I, Clinical Global Impressions–Improvement; ADHD, attention-deficit=hyperactivity disorder; V, verbal;
NV, nonverbal.
206
significant improvement in these symptoms. The first point
that needs to be clarified is whether mirtazapine or any other
medication could be considered as the first-line treatment for
ISB in this group of patients. According to some studies,
management of these behaviors should begin with educational
and behavioral interventions (Koller 2000). However, in our
study, most subjects were attending an educational program,
and their parents claimed that behavioral approaches and
parent training programs (including contingency manage-
ment, distraction, and modifying the environment) had not
been effective in reducing these behaviors. In addition, edu-
cational programs were discontinued in some cases due to the
presence of these problems. Therefore, because of the disturb-
ing effects of these problems on the subjects’ social and edu-
cational lives and their distressing influence on their families,
pharmacological treatment of these problems was necessary.
The second point that needs to be discussed is our rationale
for choosing mirtazapine. Mirtazapine is a second-generation
antidepressant that has both noradrenergic and serotonergic
properties. Our rationale for selecting mirtazapine was its
previously reported antilibidinal effect (Nyugen and Murphy
2001; Albertini et al. 2006; Coskun and Mukaddes 2008) and
its efficacy on associated symptoms of AD (Posey et al. 2001).
Also, given the compulsive nature of ISB in most cases, mir-
tazapine may also have an anticompulsive effect (Koran et al.
2005). Selective serotonin reuptake inhibitors (SSRIs) could be
another choice for these subjects. However, due to possible
side effects, such as behavioral activation and the fact that
most of these subjects suffered from hyperactivity, irritability,
and aggression, these agents were avoided.
Mirtazapine was also effective in a variety of other related
symptoms of AD (such as hyperactivity, aggression, irrita-
bility, self-injury, sleep disturbances, and depression). It is
important to note that improvement in these symptoms
is consistent with the report of Posey et al. (2001), and, ac-
cording to the results of this study, mirtazapine seems to be
more effective in treating ISB than other related symptoms.
One subject showed moderate improvement in possible mi-
graine headache; the role of mirtazapine in the treatment and
prophylaxis of the migraine headache was previously re-
ported (Lévy and Margolese 2003). Although social commu-
nication, responsiveness, and adaptation were not initially
included as target symptoms, parents reported a significant
improvement in these parameters in 3 cases. Posey et al. (2001)
reported that mirtazapine did not affect the core autistic
symptoms of social impairment. However, improvement in
social communication in these cases could be the result of a
decrease in time-consuming and socially dysfunctioning ISB
and=or due to the improvement in depressive symptoms in
these subjects rather than a direct effect of medication.
To sum up, mirtazapine treatment could be favorable in the
management of ISB in individuals with AD. However, this
study suffers from several methodological limitations, and
thus we prefer to interpret the results of this study with cau-
tion. The small sample size, uncontrolled and retrospective
nature of the study, and a possible hawthorne effect are the
COSKUN ET AL.
most important limitations of this study. Further systematic,
placebo-controlled, double-blind studies are needed regard-
ing this topic.
Disclosures
Drs. Coskun, Karakoc, Kircelli, and Mukaddes have no
conflicts of interest or financial ties to disclose.
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Address reprint requests to:
Dr. Nahit Motavalli Mukaddes
Istanbul Tip Fakultesi
Cocuk-Ergen Psikiyatrisi Anabilim Dali
34093 – Capa, Istanbul, Turkey
E-mail: nmotavalli@yahoo.com