Aggression in Huntington's Disease: A Systematic Review of Rates of Aggression and Treatment Methods

Abstract

Aggression is commonly reported in individuals with Huntington's disease (HD). While correlating factors for aggression are often speculated about, features that are associated with, and contribute to, aggression in this population have not been clearly determined. This systematic review investigates rates of aggression and treatment options for aggression in HD. A number of key findings were revealed. Studies reporting on rates of aggression revealed that its prevalence is high, falling between 22 and 66 percent in the majority of studies. Aggression may be more common in males with HD, and is also found in higher rates in individuals who experience frequent falls, have obsessive-compulsive symptoms and suicidal ideation. There is little research investigating antecedents for aggression in HD. A wide variety of psychotropic medications have been reported in the literature to treat individuals with HD and aggressive behaviour. However, due to methodological limitations, no treatment recommendations can be made, based on the current literature. Two non-medication therapies have been investigated, behaviour support and sensory modulation intervention. However, again, due to methodological limitations with these studies, further research is needed before they can be recommended as frontline interventions. This review highlights the need for further methodologically rigorous studies investigating the treatment of aggression in HD.

Full text

Journal of Huntington’s Disease 3 (2014) 319–332
DOI 10.3233/JHD-140127
IOS Press
319
Review
Aggression in Huntington’s Disease:
A Systematic Review of Rates of Aggression
and Treatment Methods
Caroline A. Fishera,b,∗, Katherine Sewellb, Anahita Brownband Andrew Churchyardc,d
aChild and Youth Mental Health Service, Adolescent Inpatient Psychiatric Unit, Box Hill Hospital, Eastern Health,
Melbourne, Australia
bBrain Disorders Program, Royal Talbot Rehabilitation Centre, Austin Health, Melbourne, Australia
cHuntington’s Disease Service, Calvary Health Care Bethlehem, Melbourne, Australia
dSchool of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University,
Melbourne, Australia
Abstract. Aggression is commonly reported in individuals with Huntington’s disease (HD). While correlating factors for
aggression are often speculated about, features that are associated with, and contribute to, aggression in this population have
not been clearly determined. This systematic review investigates rates of aggression and treatment options for aggression in
HD. A number of key findings were revealed. Studies reporting on rates of aggression revealed that its prevalence is high,
falling between 22 and 66 percent in the majority of studies. Aggression may be more common in males with HD, and is also
found in higher rates in individuals who experience frequent falls, have obsessive-compulsive symptoms and suicidal ideation.
There is little research investigating antecedents for aggression in HD. A wide variety of psychotropic medications have been
reported in the literature to treat individuals with HD and aggressive behaviour. However, due to methodological limitations, no
treatment recommendations can be made, based on the current literature. Two non-medication therapies have been investigated,
behaviour support and sensory modulation intervention. However, again, due to methodological limitations with these studies,
further research is needed before they can be recommended as frontline interventions. This review highlights the need for further
methodologically rigorous studies investigating the treatment of aggression in HD.
Keywords: Aggression, Huntington’s disease, prevalence, treatment, therapy
INTRODUCTION
Huntington’s disease (HD) is a neurodegenerative
genetic disorder with autosomal dominant inheritance
[1, 2] that is characterised clinically by motor abnor-
malities (chorea, falls) [3], cognitive impairment [4, 5]
∗Correspondence to: Dr. Caroline Fisher, Child and Youth Men-
tal Health Service, Adolescent Inpatient Psychiatric Unit, Box Hill
Hospital, Eastern Health, 5 Arnold Street, Box Hill, Victoria 3128,
Australia. Tel.: +61 3 9092 6725; Fax: +61 3 9348 2766; E-mail:
Caroline.Fisher@easternhealth.org.au.
and psychiatric disturbance [6]. High rates of aggres-
sion have also been reported. Aggression is one of the
primary causes of hospitalisation in this population [7],
is associated with higher rates of nursing home place-
ment [8] and places family members, carers and other
clients at risk of assault. While a number of previous
texts have speculated on factors that may contribute to
aggressive behaviour in HD [9–11] correlating clini-
cal symptoms and antecedents for aggression remain
unclear. There are also presently no recommended
clinical guidelines on how to manage aggression
effectively in Huntington’s disease.
ISSN 1879-6397/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License.

320 C.A. Fisher et al. / Aggression in Huntington’s Disease
This paper has two aims. The first is to review the
published evidence on rates of aggression in Hunting-
ton’s disease and identify correlating factors as well as
behavioural, situational or environmental antecedents
for this behaviour. The second is to review the pub-
lished evidence on treatment strategies for aggression
in HD, including both pharmacological and non-
pharmacological interventions. It is anticipated that
these investigations will provide a clearer understand-
ing of aggression in Huntington’s disease and help to
inform future research into this distressing behavioural
sequelae.
Identification and classification of studies
Aggression is an externalised behaviour that can be
directly observed and measured via observation from
carers, family members and hospital staff. In their
seminal text Bushmann and Anderson define aggres-
sion as a noxious stimuli that is delivered with the
intent to harm, threaten or reject the recipient [12].
For the purposes of this paper, aggression is defined
as: any behaviour that attempts to inflict uninvited
force, harm or damage to a person or inanimate object,
or verbal behaviour that is delivered in a intimidat-
ing manner (swearing, yelling, shouting, insults or
threats). Irritability has also been investigated in a
number of studies of HD sufferers [e.g. 13, 14] and
is sometimes grouped together in symptoms clusters
with aggression [15]. Irritability, however, is gener-
ally conceptualised as an internalised mood state [16]
that requires client participation to rate [17, 18], and
is not necessarily possible to monitor via observations.
As such, it is difficult to accurately gauge irritability
across all stages of HD as persons with advanced HD
may not be able to provide ratings of their internal
mood state and irritability levels, due to cognitive and
communication impairments. Due to the heterogeneity
between these clinical variables the review has focused
specifically on aggression as an overt, observable
behaviour.
To identify original studies reporting on aggres-
sion in Huntington’s disease a database search of
PubMed, Medline and PsycInfo to September 20th
2014 was performed. The search term “Huntington’s”
was combined with the terms “aggression”, “assault”
and “violence”. This revealed a total of 52 studies,
after duplicates were removed. A further 13 studies
were identified following reference section searches of
the papers initially obtained, as well as a three further
studies known to the authors. These 68 papers were
then examined and studies were included if they meet
at least one of the two inclusion criteria: I) original
research studies examining rates of aggression, cor-
relates with aggression or antecedents for aggression
in individuals with Huntington’s disease, II) original
research studies outlining treatment approaches for
aggression in Huntington’s disease. Fourteen papers
meet inclusion criteria I. Nineteen studies meet inclu-
sion criteria II. Studies were excluded if they: involved
animal rather than human subjects, if the HD par-
ticipants were included in a group study with other
disorders and the HD data could not be separated out, if
the data on aggression could not be separated out from
other sequelae (e.g. irritability), if they were review
papers not containing original research, if they did not
contain any subjects with Huntington’s disease, and if
they were not investigating aggression or the treatment
of aggression.
Rates of aggression in HD
Characteristics of studies
Of the studies that meet inclusion criteria I, fourteen
papers from thirteen individual studies are summarised
in Table 1 [7, 19–31]. The results of one study were
spread across two papers, and thus were combined so
that the reporting was not duplicated [7, 21]. A fur-
ther study [32], which reported on aggression only
as a correlate of suicidal ideation, rather than as an
individual variable of interest, was not included in the
table, but is reported in the Associations/Correlations
with Aggression section, below. For eleven of the
studies the sample sizes ranged between 27 and 250
participants. Of these studies the most common type
were case records reviews, followed by comparison
studies with another group, (i.e. Alzheimer’s disease
[23] or a control group [26]), monitoring studies [25,
28], a behaviour scale development study [27] and a
longitudinal symptoms monitoring study [30]. There
were also a further two studies of data reviews from
Huntington’s registries containing very large samples
[29, 31].
Gender ratios varied across the studies. Five studies
[22, 24–26, 30] contained a high percentage of female
participants (60.4 % or higher), while the remaining
studies had ratios ranging between 60:40 (in either
direction) and even 50:50 distribution. The average age
of the participants for the studies in which this figure
was reported (or was calculable via a mean weighted
average), ranged between 45.6 years and 57.2 years.
Four studies contained at least one participant with
juvenile onset Huntington’s (JHD) [19, 20, 23, 27]
and in one study JHD participants were excluded [26].

C.A. Fisher et al. / Aggression in Huntington’s Disease 321
Table 1
Studies on rates of aggression
First Author, Year,
[Reference number]
HD Participants Methodology % M/F Mean
Age
Functional
Capacity
Aggression
Overall
Aggression
Scale
Rating on
scale
Additional findings
Rosenbaum, 1941
[19]
46 hospital
admissions
Case records
review
58.7/41.3 65.2% 10.9% “attempted
homicide”
Tamir, 1969 [20] 32 clinic patients Case records
review
40.6/59.4 48 34.4% More aggression in M
(61.5%) vs. F (15.8%)
(p< 0.05)
Dewhurst, 1969 [21]
& 1970 [7]
102 patients
known to
clinicians
Case records
review
53.9/46.1 48.7125.5% More aggression early
in illness. 17.6%
violent crime
conviction
Tyler, 1983 [22] 92 inpatients and
outpatients
Questionnaire
survey
38.0/62.0 26% not
disabled, 37%
partially
disabled, 37%
totally
disabled
42.4% More aggression in M
(60%) vs. F (31.6%)
Burns, 1990 [23] 26 HD research
clinic patients
Comparison study 60.0/40.0 48.3 22.3 MMSE
mean
59% YAS mean 3.3 No signif. correlation
betw. aggress. &
MMSE
Pflanz, 1991 [24] 86 health service
referrals
Case records
review
39.5/60.5 44.0% PSE 9th Ed. Even M vs. F
aggression rates
Shiwach, 1993 [25] 27 nursing home
residents
Behaviour
monitoring study
29.6/70.4 45.6136% RAGE 25% mildly
aggressive
11% mod.
aggressive
Even M vs. F
aggression rates.
Weak signif.
correlation of
aggression with FRS
Jensen, 1998 [26] 250 HD register
cases
Comparison study
with registry data
39.6/60.4 57.213.6%1,2Higher rates of
convictions in M not F
Craufurd, [2001] [27] 134 outpatients Behaviour rating
scale study
47.0/53.0 50 5 TFC mean PBA-HD 40% v.aggress
22%
ph.aggress.
Aggression most freq.
8-9 yrs. post onset
Grimbergen, 2008
[28]
45 participants in
a prospective falls
study
Falls monitoring
study
48.9/51.1 51.919.71TFC
mean
UHDRS aggression
freq. mean
2.01,
aggression
severity mean
1.61
Fallers had higher
aggression frequency
(p= 0.01) and severity
scores (p= 0.02)

322 C.A. Fisher et al. / Aggression in Huntington’s Disease
Table 1
(Continued)
First Author, Year,
[Reference number]
HD Participants Methodology % M/F Mean
Age
Functional
Capacity
Aggression
Overall
Aggression
Scale
Rating on
scale
Additional findings
Anderson, 2010 [29] 1642 HD study
group participants
Registry data
review
49.6/50.5 8.2 TFC mean UHDRS mean 4.91SS with OCD Sx had
higher aggression
scores, (p< 0.001)
Thompson, 2012 [30] 111 HD research
clinic participants
Longitudinal
study
38.7/61.3 48 7.8 TFC mean PBA-HD 40% v.aggress
18%
ph.aggress.
Longitudinal rates
higher than point
prevalence
Hubers, 2013 [31] 2095 HD registry
participants
Registry data
review
50.9/49.1 50.3 TFC stages
1:33.3%,
2:33.0%,
3:25.5%,
4:7.0%,
5:1.2%
22.6% UHDRS Aggression correlated
with suicidal ideation,
(p< 0.001).
1Mean weighted average, 2Convicted of a violent crime, FRS – Functional Rating Scale, TFC – Total Functional Capacity, MMSE – Mini Mental State Examination, RAGE – Rating scale for
aggressive behaviour in the elderly, YAS – Yudofsky Aggression Scale, PSE - Present State Examination, PBA-HD – The Problem Behaviours Assessment for Huntington’s disease, UHDRS -
Unified Huntington’s Disease Rating Scale.

C.A. Fisher et al. / Aggression in Huntington’s Disease 323
The diagnosis of HD for participants, where reported,
was based on clinical categorisation in the majority of
studies [19, 20, 23, 24, 29], or inclusion on an HD reg-
istry [26]. Three studies contained confirmed HD gene
mutation carriers [27, 30, 31]. In one of these stud-
ies [31] 98 percent were motor symptomatic (thus,
up to two percent of this sample may have had pre-
manifest HD). Average CAG repeat mutations in these
three studies ranged between 44 and 46 (calculated
via the mean weighted average for Hubers, et al.).
As a number of the studies were case records reviews
(incorporating the patient’s behaviour over a number
of years) mean disease duration was often not reported.
However, where this was available, average disease
durations were 5.5 years [30], 5.7 years [31], 7.0 years
[28, 29], 9 years [27] and an estimate of 10 years [22].
A number of differing measures were used to calculate
the participants’ functional capacity, including Mini
Mental State Examination [33] and Total Function-
ing Capacity (TFC) [34] means, TFC stages and study
developed classifications [e.g. 22].
Rates of aggressive behaviour
Rates of aggression (any type) overall were high in
the majority of studies, ranging between 22.6 percent
and 65.2 percent, across eight studies [7, 19–25, 31].
The highest rate was reported in a case records review
study, that analysed patient file information, potentially
spanning many years for each client [19), followed by a
group comparison study that analysed the responses of
family/caregivers on a questionnaire about both current
and past behaviour [23]. The lowest rate was found in a
large registry data review study utilising scores on the
behavioural subscale of the Unified Huntington’s Dis-
ease Rating Scale (UHDRS) [31]. A low rate was also
found in a case records review study reporting the pri-
mary reason for admission to hospital in the HD cohort
[7, 21]. This data may represent an underestimation of
aggression, in total, in this cohort as others in the study
may also have exhibited aggressive behaviour that did
not result in a hospital admission. In one further study
[26] that only reported on convicted crimes, rates of
conviction for violent crimes were 3.6 percent. This
result differs significantly from reported rates of over-
all aggression in the other studies. It may indicate that,
at least in recent years, aggression perpetrated by HD
sufferers is either not commonly reported to the police,
or infrequently prosecuted.
Characteristics of the aggressive behaviour
A number of studies did not utilise a recognised
scale, or scoring system to rate or evaluate aggres-
sion [7, 19–22], making it difficult to draw any further
conclusions about the nature, severity or frequency
of aggression in these studies. When a rating scale
was used, the UHDRS aggression items were the most
common [28, 29, 31, 32]. The Problem Behaviours
Assessment for Huntington’s Disease (PBA-HD) [27,
30], Rating Scale for Aggressive Behaviour in the
Elderly (RAGE) [25], Yudofsky Aggression Scale [23]
and Present State Examination, 9th Edition [24], were
also utilised. Despite the comprehensive nature of
some of these scales in assessing rates, types and sever-
ity of aggression, the full findings were not always
reported, with overall subscale means for aggression
the most common type of data provided.
The UHDRS Behaviour Assessment [34] has a
Disruptive and Aggressive Behaviour subscale, with
descriptors that all relate to aggression. These include:
threatening behaviour, physical violence, verbal out-
bursts, and threatening, foul or abusive language.
The UHDRS rates these behaviours according to
both severity and frequency, but does not provide
information separately on the different types of aggres-
sion (physical, verbal and towards furniture/property).
Three papers utilised this scale. In a falls monitoring
study with 45 HD participants [28] the mean weighted
average for severity was 1.6 (rates between slight,
questionable and mild), and the mean frequency was
2.0 (consistent with a classification of sometimes). In
a large sample registry data review [29] the aggres-
sion score was calculated by multiplying the frequency
score by the severity score, providing a mean weighted
average of 4.9. Little further information can, thus,
be drawn about the severity, frequency or nature of
the aggression in this sample. In a second large sam-
ple registry data review [31], the authors indicated
that aggression was also calculated by multiplying the
frequency total by the severity total to produce an over-
all rating. This score does not appear to have been
reported, however. Instead aggression was reported as
the number of participants who exhibited aggression
in any form, at any level of severity (i.e. cases with
aggression ≥1), at a rate of 22.6%.
Two studies employed the Problem Behaviours
Assessment for Huntington’s Disease (PBA-HD)
[27, 30] to rate aggressive behaviour. This is a semi-
structured behavioural interview, which rates both
the frequency and severity of a range of problem
behaviours. Information is provided from both patients
and caregivers about behaviour over the preceding four
weeks. In the original development of the scale [27] the
items with a clear relationship to aggression are Tem-
per, verbal outbursts (appearing in subsequent studies

324 C.A. Fisher et al. / Aggression in Huntington’s Disease
as Verbal outbursts) and Threatening behaviour, vio-
lence (appearing in subsequent studies as Physical
aggression). The first study reported rates of verbal
outbursts as 40 percent and physical aggression as 22
percent [27]. In the second study [30], exact numer-
ical figures were not provided, but careful inspection
of the provided bar graph figure revealed point preva-
lence rates that appear to correspond with 40 percent
for verbal outbursts and 18 percent for physical aggres-
sion. Longitudinal ratings (reports of the behaviour at
any time point during the study) appear to correspond
to 75 percent for verbal outbursts and 49 percent for
physical aggression. The actual duration of the longi-
tudinal follow-up in this study is unclear, but appears
to be around 6.5 years (mean of five assessments per
participant, mean time between assessments 1.3 years).
More specific information about aggression frequency
and severity ratings are not provided in either study,
despite these variables being collected by the PBA-HD.
The RAGE [35] was another measure of aggression
employed in one of the studies [25]. Authors indicated
that this scale rates behaviour over a three-day obser-
vation period. It consists of 23 items. Nineteen of these
gauge observable behaviour, with some of these items
directly classifiable as overt aggressive behaviour (e.g.
shouted, yelled or screamed; attempted to bite, scratch,
pinch or hit others, etc.). Three items gauge con-
sequences of the aggressive behaviour (termed as
the non-behavioural items) and one item determines
a global judgement for overall aggressiveness. The
authors reported the data for 17 of the items on this
scale, by frequency (occurred once in three days,
occurred everyday in the past three days, occurred
more than once everyday in the past three days) in
the 27 participants. By far the most common form
of aggressive behaviour was found to be: shouted,
yelled or screamed (33% with positive ratings), with
the majority (29.6%) exhibiting this just once in three
days and a smaller number (3.7%, i.e. 1 out of 27 par-
ticipants) exhibiting it more than once a day, over the
three days. Attempting to bite, scratch, pinch or hit oth-
ers, was the most common form of physical aggression
(11.1% exhibited this at least once, with 3.7% exhibit-
ing this more than once a day). Destroying property
or throwing things around angrily occurred in 7.4%
of participants, at a frequency of once in three days
for all. The number of participants attempting to kick
(3.7%) or hit others (3.7%) was low, but when dis-
played, this behaviour was frequent (more than once a
day for both). Importantly however, not all the items
from the RAGE were included in the results table.
The results for “Pushed or shoved others” were not
included in the results table, although this behaviour
was reported as occurring in one in five participants,
in the text (pg. 45). Overall, 25% of participants were
rated as mildly aggressive, and 11.1% as moderately
aggressive.
One group comparison study utilised the Yudofsky
Aggression Scale. Information provided by the authors
[23] indicated that it is comprised of four components:
verbal aggression against self, physical aggression
against self, aggression against objects and aggression
against other people. During the data collection addi-
tional questions were also asked of relatives about: the
most recent outburst, what outbursts were usually like,
the frequency of the outbursts and any precipitating
factors. Despite this, only information about the mean
score on the scale, the number of participants above
a “cut-off point” for the presence of aggression (any
type) and the percentage of participants with aggres-
sive periods lasting longer than 24 hours (31%), were
reported. No information was provided about the types
of aggression (despite data being collected for this
within the scale). Information on precipitating factors
was also not analysed empirically, with only a gen-
eral statement provided, which indicated “Aggressive
outbursts were usually prompted by some event.. .
Typical precipitants in the HD group included argu-
ments with the spouse over money” (pg. 23). This was
the only study in which reference was made to the col-
lection of empirical data on precipitating, antecedent
or triggering events for the aggressive outbursts.
Finally, the Present State Examination, 9th Edition
[36] was also used to rate aggression in one study [24].
The measure is a semi-structured interview that rates
participants on 140 items, which can then be used for
diagnostic classification. It is unclear how many items
relate to the classification of aggression. However, as
presented in this study, the rating for aggression was
considered a unitary item, with no further information
provided other than prevalence rates, by gender (45%
in males and 44% in females).
Associations/correlations with aggression
A number of studies reported aggression results by
gender. In three studies [24, 25, 27] relatively simi-
lar rates of aggression were reported across males and
females. However, in a further three studies higher rates
of aggression were observed in males [20, 22, 26]. In
one study [7, 21] aggression was found to be more
prevalent in the early, rather than later stages of the ill-
ness (57.8% prevalence in the early phases; 9.8% in the
middle phases and 2.0% in the terminal phase). In a sec-
ond study [27] verbal aggression was found to be most

C.A. Fisher et al. / Aggression in Huntington’s Disease 325
prevalent in clients with 8-9 years illness duration,
with physical aggression also showing a small increase
at this illness stage compared to a relatively even
rate of prevalence for physical aggression at earlier
and later illness stages. Correlation analysis between
aggression and cognitive or functional status was con-
ducted in two studies [23, 25]. In one, no correlation
was found between Mini Mental State Examination
(MMSE) scores and aggression [23]. In the other [25],
a significant but weak correlation was found between
aggression and Functional Rating Scale scores (Pear-
son’s correlation coefficient of 0.45, p< 0.01). This
study does not explicitly state the direction of the cor-
relation, however, from the information contained in
the text it appears that poorer functional ratings were
correlated with higher rates of aggression. In regard to
physical variables, one study found significantly higher
rates of aggression frequency and severity in partici-
pants with a high rate of falls, versus those without
[28]. Psychiatric correlates of aggression were exam-
ined in three studies, all of which used the UHDRS
to rate aggression. One found that participants with
Obsessive Compulsive Disorder (OCD) symptoms had
higher aggression scores [29], while two others found
that rates of aggression were correlated with suicidal
ideation [31, 32].
Data was also provided about rates of criminal
behaviour that related to aggression in three studies. In
one study [19] it was reported that 10.9 percent of par-
ticipants had “attempted homicide” (pg. 95), indicating
a relatively high proportion of participants perpetrat-
ing physical aggression against others with force of
potentially lethal intensity. It was further stated in the
text that “In none was the homicidal attempt felt to be
due to paranoid ideas – rather was it (sic) attributed to
explosive irritability” (pg. 95). One study specifically
examined the rates of criminality in HD sufferers, first
degree relatives and the general population, by com-
paring HD and criminal registry data [26]. It found
that overall crime rates were significantly increased
in HD sufferers compared to first-degree relatives, but
only for males. The increased rate of violent offences
observed in male HD sufferers compared to both first-
degree relatives, and a matched control group, failed
to reach statistical significance (HD 6%; first degree
relatives 1.5%; matched controls 1%). This contrasts
somewhat with an earlier study [7] that reported high
rates of conviction for a range of offenses in their HD
sample (no control group), including assault (13%),
offenses against property (12.7%) cruelty to children
(8.8%), malicious damage (1.9%), blackmail (1%) and
arson (1%).
Summary
Of the 14 studies that met the criteria for inclusion in
this section of the review the majority were not specifi-
cally focused on examining aggression in HD. Rather,
rates of aggression were collected along with a wide
number of clinical variables, or measures of aggres-
sion were obtained as part of general Huntington’s
or psychiatric symptom scales and then analysed in
relation to the main variable of interest. The major-
ity of studies utilised clinical characterisation for the
diagnosis of HD, with only three including confirmed
gene positive cases, leaving the possibility open that
a proportion of included participants may not have
actually been afflicted with HD. The study method-
ologies ranged widely and the reporting of data from
the clinical variables was poor in a number of stud-
ies. Overall, only 64 percent of the studies utilised a
recognised HD, behavioural or psychiatric scale for
evaluating aggression.
Even with consideration given to these methodolog-
ical issues, the results do appear to indicate that rates
of aggression in HD are high, ranging between 22.6
percent and 65.2 percent in the majority of studies.
Little information is available regarding the nature of
the aggressive behaviour (e.g. verbal aggression, phys-
ical aggression, aggression to furniture/property). In
the three studies that did report on types of aggression
[25, 27, 30] both verbal and physical aggression were
found to occur, with verbal aggression having a higher
prevalence. Aggression to property was reported to
have been exhibited by just two participants in one
study [25]. Overall, no studies reported empirical data
on precipitating, antecedent or triggering events for the
aggressive behaviour. One study that did collect this
data (but did not report it empirically), indicated that
aggressive outbursts were often triggered by arguments
with spouses over money.
In the studies where gender differences were
observed aggression was more prevalent in males.
However, several studies reported even rates of aggres-
sion for both genders. Data on whether aggression
becomes more or less prevalent in HD sufferers as
the disease progresses is unclear. One study reported
considerably higher rates of aggression in the early
phases of the disease [7, 21], a second indicated higher
rates in the middle phase (8-9 years) [27], while
in another aggression was weakly, but significantly,
correlated with poorer ratings on a functional scale.
Psychiatrically, there is evidence that aggression is
more prevalent in clients with co-morbid OCD symp-
toms and also correlates with higher rates of suicidal
ideation. Physically, it may also be more prevalent in

326 C.A. Fisher et al. / Aggression in Huntington’s Disease
sufferers that are also frequent fallers. In contrast to
previous speculation [10, 11] there is presently lit-
tle evidence that aggression in HD is associated with
cognitive deterioration, irritability, personality factors,
depression, psychosis or mania. Such associations may
exist, but have yet to be thoroughly examined in the
literature. Future research that focuses on investigat-
ing these factors carefully, using systematic evaluation
of psychiatric symptoms and thorough cognitive and
functional evaluation would be useful, as the methods
employed thus far (e.g. MMSE, disease stage, FRS)
may lack sufficient sensitivity to detect important asso-
ciations. Finally, despite the high rates of aggression
reported in most samples, the reported conviction rates
for violent offenses in HD in the one recent study that
examined this [26] were relatively low. This may reflect
lower levels of reporting such episodes to police and/or
infrequent prosecution of HD individuals.
Treatment of aggression
Characteristics of studies
Nineteen studies met inclusion criteria II, and are
summarised in Table 2 [37–55]. All of the included
studies had small samples sizes (1 to 6 participants),
with eleven case studies [39, 41, 42, 44, 46, 48, 49,
51–54], seven case series [38, 40, 43, 45, 47, 50, 55]
and one very small group study [37]. The majority of
the studies were medication trials, with just two stud-
ies reporting non-medication interventions. Blass et
al. [48] included a structured behaviour support plan,
in addition to a poly medication trial, while Brown
and Fisher [55] utilised sensory modulation interven-
tion. Fifteen of the participants across the studies were
female and twenty were male. The majority of partici-
pants were aged in their 30 s to 50 s, with three younger
participants, aged 16, 19 and 22 years, and three older
participants, aged 60, 67 and 74 years, respectively.
Where reported, the duration of HD from the onset
of symptoms was variable. Participants who had been
symptomatic for 10+ years were reported in five stud-
ies [38, 43, 47, 50, 55] while the remaining timelines
reported were between 1 and 9 years. The functional
or cognitive capacity of participants was reported in
seven studies. In two studies intellectual capacity was
reported, with IQ scores at the time of the intervention
of 65 [51] and 89 [41]. Reported MMSE scores var-
ied considerably, from participants who were unable
to complete any MMSE tasks, scoring 0/30 [45, 48],
moderately impaired participants, scoring 20/30 [54],
to those who exhibited no difficulties on this measure,
scoring 30/30 [42]. One study utilised the Shoulson’s
Huntington’s disease rating scale [46], with the partic-
ipant in this study being classified as Stage V.
Characteristics of the aggressive behaviour
Only one study used a recognised behaviour scale,
the Cohen-Mansfield Agitation Inventory (CMAI),
to quantify the participant’s behaviour [53]. For all
remaining studies behaviour was categorised via the
authors’ descriptions. Nevertheless, there was suffi-
cient information provided in most studies, to allow
for the classification of the aggressive behaviour into
three major types (physical, verbal or against furni-
ture/objects), see Table 2. Physical aggression was the
most common type, with a high prevalence of verbal
aggression also reported. In only one study was aggres-
sion against property/furniture clearly described. The
majority of studies made no mention of antecedents
to the aggressive behaviour, with just three studies
providing specific information about this. One study
[55] outlined precursors for aggression individually for
each of the participants. This study reported that for
the female participant pacing, voicing hunger, verbal
aggression and intrusiveness, where signs that often
lead to behavioural escalation, whilst for the male par-
ticipant loud noise from the television or co-residents
was a precursor to verbal and physical aggression.
The second study [42] stated that the participant self
reported that her aggression was triggered by inter-
nal feelings of anger and irritability, which developed
rapidly following minor irritants or changes in her rou-
tine. In the third study [48] the authors reported that
the participant’s behaviour was initially believed to
be related to psychotic sequelae and delirium. How-
ever, following the implementation of a systematic
behaviour evaluation period, it was then identified
that the participant’s behaviour escalated when he was
asked to take medication or to interrupt a pleasant
activity, such as walking or watching television. Prob-
lematic touching of female staff members was also
found to occur during bathing or dressing activities.
Treatment efficacy
The quantification, measurement and evaluation of
the effect of the therapeutic agents on aggression were
generally poor. In just one study was an empirical mea-
sure of baseline behaviour provided [53] via a singular
pre-treatment rating on the CMAI of 78. This study
was also the only study to provide empirical outcome
measures, via two further CMAI ratings during the
medication treatment period with zuclopenthixole and
medroxyprogresterone (CMAI of 56 at six weeks, and
57 at ten weeks). However, the statistical significance

C.A. Fisher et al. / Aggression in Huntington’s Disease 327
Table 2
Treatment of aggression
First Author, Year
[Reference number]
N M/F Age (s) in years Aggression Type: Treatment type Medication Treatment
duration
Reduction in
Aggression
Adverse Effects
reported
Leonard, 1975 [37] 6 0/6 Physical Medication Lithium
carbonate+
Haloperidol
12 weeks Yess, physical
aggression only
Stewart, 1987a [38] 2 2/0 43, 41 Physical, Verbal Medication Amantadine 1) 4 mths No
2) 6 days
Stewart, 1987b [39] 1 1/0 67 Medication Propranolol+
Haloperidol
2 mths approx. No
Stewart, 1987c [40] 3 3/0 48, 44, 50 Physical, Verbal Medication Propranolol 3–12 mnths Yes◦
von Hafften, 1989
[41]
1 1/0 48 Physical, Verbal Medication Pindolol 10 days
approx.
No
Findling, 1993 [42] 1 0/1 16 Physical, Verbal Medication Buspirone not reported Yes◦
Byrne, 1994 [43] 2 2/0 58, 60 Medication Buspirone 1 mnth
approx.
Yes◦
Patel, 1996 [44] 1 0/1 19 Physical Medication Fluoxetine+
L-deprenyl
12 mths Yes◦
Ranen, 1996 [45] 2 1/1 52, 42 Physical, Verbal,
Furniture/ Objects
Medication Sertraline 1) 5 mnths Yes◦
2) not reported
Bhandary, 1997 [46] 1 1/0 74 Physical Medication Buspirone unclear Yes◦
Grove, 2000 [47] 2 1/1 39, 52 Medication Olanzapine+
Valproate
7–8 weeks Yes◦
Blass, 2001 [48] 1 1/0 32 Physical Medication+
Behaviour
Support Plan
Admiss. 1:
Clonazepam,
Carbamazepine
and Thioridazine,
Medroxyproges-
terone acetate
Admiss 2:
Haloperidol also
introduced
Admiss1:42
days, Admiss
2:13 days
Yes◦
Fogliani, 2003 [49] 1 0/1 51 Medication Trifluoperazine,
then Fluoxetine+
Olanzapine
4 mths approx. Yes◦, slight
improve-ment
with fluox.

328 C.A. Fisher et al. / Aggression in Huntington’s Disease
Table 2
(Continued)
First Author, Year
[Reference number]
N M/F Age (s) in years Aggression Type: Treatment type Medication Treatment
duration
Reduction in
Aggression
Adverse Effects
reported
Alpay, 2006 [50] 5 3/2 40, 40, 42, 34, 38 Medication Quetiapine 1-2 mths Yes◦
Soliman, 2007 [51] 1 0/1 48 Physical, Verbal Medication Risperidone+
fluvoxamine
4 mths Yes◦
Edlinger, 2013 [52] 1 1/0 39 Medication Olanzapine,
risperidone,
amisulpride+
aripiprazole, then
clozapine+
reboxetine
6 mths Yes◦, only with
aripip. intro.
Clozapine:
“sedation and
confusion”
Rej, 2013 [53] 1 1/0 58 Physical, Verbal Medication Zuclopenthixol+
medroxyproges-
terone
10 weeks Yessc Medroxyprogrest:
“fluid retention”
Ding, 2014 [54] 1 1/0 60 Physical, Verbal Medication Risperidone+
citalopram
1 month Yes◦
Brown, In press [55] 2 1/1 22, 31 Physical, Verbal Sensory
Modulation
not reported Yes◦
Yess= statistically significant reduction, Yes◦= reduction based on observational opinion only, Yessc = reduction in behaviour rating scale, significance level not reported.

C.A. Fisher et al. / Aggression in Huntington’s Disease 329
of the rate of change on this measure was not provided.
Multiple baseline data for aggression were not reported
in any studies. In one study [37] a placebo control
condition was used, as well as blinded nursing staff
who rated aggressive behaviour. However, the study
reports that ratings were made only once at the end
of each three week medication period, with no infor-
mation provided about whether episodes of aggressive
behaviour were recorded during the period (leaving the
ratings open to potential confounds of the raters’ mem-
ories over the entire three week period). This study
reported a statistically significant positive effect of
a combined pharmacotherapy approach [lithium car-
bonate and haloperidol) over placebo. This was the
only study in which statistical analysis was applied to
the behavioural data to determine the efficacy of the
intervention. For all remaining studies the information
provided about the efficacy of the treatment was based
on the observational opinion of the authors.
Within the context of these methodological issues
the majority of the studies reported positive effects
of the therapeutic agents at reducing aggression (see
Table 2). Antipsychotic medications were the most
commonly reported pharmacotherapies. Haloperidol,
a butyrophenone neuroleptic, was utilised with eight
subjects, across three studies [37, 39, 48]. In one study
it was reported to be effective at reducing aggres-
sion in six participants, when combined with lithium
carbonate. However, in a single subject case study
[39] no efficacious effect was reported on aggressive
symptoms when haloperidol was combined with pro-
pranolol, a nonselective beta-blocker. Haloperidol was
also introduced to a poly medication regime during a
second admission in a further case study [48]. Queti-
apine, an atypical antipsychotic, was also utilised in
one study [50] containing five HD participants and
was reported to have been affective at reducing aggres-
sion. Olanzapine, another atypical antipsychotic, was
utilised in three participants across three studies [47,
49, 52]. In all of these studies it was used as part of a
poly medication regime. It was reported as efficacious
when combined with valproate [48], an anticonvulsant
also with antipsychotic properties, and with fluoxe-
tine [49], an antidepressant, although the authors in the
later study attributed the small improvement in aggres-
sion primarily to the fluoxetine. Finally, olanzapine
was also used as one of five psychotropic medica-
tions in another case study [52]. However, in this study
the authors primarily attributed the improvement in
aggression to the introduction of aripiprazole, another
of the three antipsychotic agents employed in this case
study. Thioridazine, a peperidine typical antipsychotic
(now withdrawn in many countries due to cardiotoxi-
city and retinopathy at high does) was used in a poly
medication regime in combination with behaviour sup-
port modifications [48], making its effect on aggression
difficult to determine. Trifluoperazine, a phenothiazine
neuroleptic, had little effect on aggression in one single
case study [49], whilst zuclopenthixole, a thioxanthene
neuroleptic, was reported to be efficacious in combi-
nation with, medroxyprogesterone, a progestogen, in
another single case study [53]. However, the medrox-
yprogesterone is reported to have resulted in fluid
retention and abdominal bloating. Side effects from
the antipsychotic agent clozapine, were also reported
in one study [52] and were described as sedation and
confusion.
Two reported case studies combined the antipsy-
chotic agent risperidone with selective serotonergic
reuptake inhibitor antidepressants (SSRIs), specifi-
cally fluvoxamine [51] and citalopram [54]. In both
of these studies aggression was reported to have
decreased, following the introduction of the duo med-
ication regimes. SSRIs were also used in several other
studies. Sertraline was reported to improve aggres-
sive symptoms in two HD clients in one case series
study [45]. Fluoxetine was reported as the medication
primarily responsible for reduction in aggression in
one poly medication single case study [49], and was
also reported to be effective when combined with L-
deprenyl in another [44]. The anxiolytic buspirone has
also been utilised in four participants, across three stud-
ies with improvements reported in aggression in all
cases [42, 43, 46].
Beta-adrenergic blocking agents were mixed in their
effectiveness on aggressive symptoms in HD. Pin-
dolol was reported to be ineffective in one single case
study [41], as was propranolol, when combined with
haloperidol, in another [39]. However, in a second
study investigating the effect of propranolol alone,
improvement in aggression was reported in three
HD clients [40]. Finally, two medications generally
employed for the treatment of movement disorders
were also utilised. Amantadine alone did not improve
aggressive behaviour in two participants in one study
[38], whilst L-deprenyl when combined with fluoxe-
tine (as indicated above) was reported to be effective
in another [44].
In two studies, non-medication treatments were
investigated. In one of these a behaviour support plan
was instigated in conjunction with a poly medica-
tion trial over two separate inpatient admissions in
a single case study [48]. This involved a systematic
behaviour monitoring period, from which antecedents

330 C.A. Fisher et al. / Aggression in Huntington’s Disease
and precursors to problem behaviours were identified.
A clear behaviour support plan was then developed
involving a highly structured daily timetable routine,
the minimisation of behaviour triggers where possi-
ble, positive verbal reinforcement of desired behaviour
and rewards. The behaviour support plan was intro-
duced two weeks after the new medication regime
was commenced, and was reported to have resulted
in dramatically improved behaviour within five days
(in conjunction with the continued pharmacotherapy).
The behaviour plan was reportedly successfully trans-
ferred to the patients’ nursing home environment after
discharge. It was also reinstituted on the inpatient unit
when the patient was readmitted four months later,
after a second period of suspected medication induced
delirium.
In another study sensory modulation intervention
was administered in a two case series [55]. This
study reported on individual triggers for aggressive
behaviour in both of the patients, as well as their indi-
vidual sensory profiles. Sensory modulation treatment
plans were developed for each client, utilising vari-
ous sensory equipment (e.g. weighted blankets, puff
massagers, click-clack balls), which were provided to
clients to prevent the escalation of problem behaviour.
The duration of the intervention was not specified, but
was also reported to have resulted in a reduction in
aggressive behaviour in both clients.
Summary
A wide variety of psychotropic medications have
been reported in the literature to treat individuals with
HD and aggressive behaviour. However, the published
studies have very small sample sizes and poor mea-
surement and evaluation of the effect of the therapeutic
agents on aggression. No randomised controlled trials
were revealed by the search, and none of the case stud-
ies or case series reports employed multiple baseline
measures of aggression by frequency, type or sever-
ity. Two studies attempted to empirically quantify the
effect of the medication on behaviour, however, each
of these studies still contained methodological prob-
lems. Only two studies reported non-pharmacological
measures to treat aggression in HD. Sensory modu-
lation intervention was utilised in one study, whist
behaviour support intervention was used in another,
in conjunction with poly medication therapy. Overall,
no recommendations for specific treatments for aggres-
sion in HD can be made based on the currently available
literature. However, the information contained in this
review can be used as a starting reference point for
treating clinicians to help determine which medica-
tion and non-medication treatments may be suitable
for their clients. It can also be used to direct future
research with stronger methodological properties.
CONCLUSION
Aggression is a commonly occurring behavioural
sequelae in HD. Further research into the antecedents
and precursor “triggers” for this behaviour in HD is
required. Given the rarity of the disorder, it is not
surprising that treatment studies seeking to reduce
aggression in individuals with HD contain small
sample sizes. A large randomised controlled trial eval-
uating the efficacy of treatment for aggression in
HD may be difficult to conduct. However, case stud-
ies, case series and smaller group studies should be
conducted utilising scientifically rigorous methodol-
ogy. This should include the use of multiple baseline
measures of pre-treatment behaviour, quantification
of aggressive behaviour using a recognised scale or
clearly defined parameters, post treatment evaluation
of significance levels and follow-up data to determine
the efficacy of the treatment over longer time periods.
CONFLICT OF INTEREST
The authors do not declare any conflict of interest.
REFERENCES
[1] Gusella G, Wexler N, Conneally P, Naylor S, Anderson M,
Tanzi R, et al. A polymorphic DNA marker genetically linked
to Huntington’s disease. Nature. 1983;306:234-38.
[2] The Huntington’s Disease Collaborative Research Group. A
novel gene containing a trinucleotide repeat that is expanded
and unstable on Huntington’s disease chromosomes. Cell.
1993;72:971-83.
[3] WalkerF. Huntington’sdisease. Lancet. 2007;369(9557):218-
28.
[4] Brandt J, Butters N. The neuropsychology of Huntington’s
disease. Trends Neurosci. 1986;9:118-20.
[5] Lemiere J, Decruyenaere M, Evers-Kiebooms G, Vanden-
bussche E, Dom R. Cognitive changes in patients with
Huntington’s disease (HD) and asymptomatic carriers of the
HD mutation. J Neurol. 2004;251(8):935-42.
[6] Paulsen J, Ready R, Hamilton J, Mega M, Cummings J.
Neuropsychiatric aspects of Huntington’s disease. J Neurol
Neurosurg Psychiatry. 2001;71(3):310-4.
[7] Dewhurst K, Oliver J, McKnight A. Socio-Psychiatric
Consequences of Huntington’s Disease. Br J Psychiatry.
1970;116(532):255-8.
[8] Wheelock V, TempkinT, Marder K, Nance M, Myers R, Zhao
H, et al. Predictors of nursing home placement in Huntington
disease. Neurology. 2003;60(6):998–1001.
[9] Rosenblatt A, Leroi I. Neuropsychiatry of Huntington’s dis-
ease and other basal ganglia disorders. Psychosomatics.
2000;41(1):24-30.

C.A. Fisher et al. / Aggression in Huntington’s Disease 331
[10] Cummings J. Behavioral and psychiatric symptoms associ-
ated with Huntington’s disease. Adv Neurol. 1995;65:179-86.
[11] Folstein S, Folstein M. Psychiatric features of Hunting-
ton’s disease: Recent approaches and findings. Psychiatr Dev.
1983;1(2):193-205.
[12] Bushman B, Anderson C. Methodology in the Study of
Aggression: Integrating Experimental and Nonexperimen-
tal Findings. In: Geen, RG, Donnerstein E, editor. Human
Aggression: Theories, Research, and Implications for Social
Policy. San Diego: Academic Press; 1998. pp. 23-48.
[13] Groves M, van Duijn E, Anderson K, Craufurd D, Edmond-
son MC, Goodman N, et al. An international survey-based
algorithm for the pharmacologic treatment of irritability in
Huntington’s disease. PLoS Curr. 2011;3.
[14] Reedeker N, Bouwens JA, Giltay EJ, Le Mair SE, Roos RAC,
van der Mast RC, et al. Irritability in Huntington’s disease.
Psychiatry Res. 2012;200(2-3):813-8.
[15] Van Duijn E, Craufurd D, Hubers A, Giltay E, Bonelli R,
Rickards H, et al. Neuropsychiatric symptoms in a European
Huntington’s disease cohort (REGISTRY). J Neurol Neuro-
surg Psychiatry. 2014;85(12):1411-8.
[16] Snaith RP, Taylor CM. Irritability: Definition, assessment and
associated factors. Br J Psychiatry. 1985;147(2):127-36.
[17] Holtzman S, O’Connor BP, Barata PC, Stewart DE.
The Brief Irritability Test (BITe) A Measure of Irri-
tability for Use Among Men and Women. Assessment.
2014;1073191114533814.
[18] Chatterjee A, Anderson K, Moskowitz C, Hauser W, KS
M. A comparison of self-report and caregiver assess-
ment of depression, apathy, and irritability in Huntington’s
disease. J Neuropsychiatry Clin Neurosci. 2005;17(3):
378-83.
[19] Rosenbaum D. Psychosis with Huntington’s chorea. Psychiat
Quart. 1941;15:93-9.
[20] Tamir A, Whittier J, Korenyi C. Huntington’s chorea: A sex
difference in psychopathological symptoms. Dis Nerv Syst.
1969;30(2):103.
[21] Dewhurst K, Oliver J, Trick K, McKnight A. Neuro-
psychiatric aspects of Huntington’s disease. Confin Neurol.
1969;31(4):258-68.
[22] Tyler A, Harper P, Davies K, Newcome R. Family Break-
Down and Stress in Huntington’s Chorea. J Biosoc Sci.
2008;15(02):127-38.
[23] Burns A, Folstein S, Brandt J, Folstein M. Clinical assess-
ment of irritability, aggression, and apathy in Huntington and
Alzheimer disease. J Nerv Ment Dis. 1990;178(1):20-6.
[24] Pflanz S, Beeson J, Ebmeier K, Simpson S. The clinical
manifestation of mental disorder in Huntington’s disease: A
retrospective case record study of disease progression. Acta
Psychiatr Scandanavia. 1991;83:53-60.
[25] Shiwach R, Patel V. Aggressive behaviour in Huntington’s
disease: A cross-sectional study in a nursing home population.
Behav Neurol. 1993;6:43-7.
[26] Jensen P, Fenger K, Bolwig T, Sørensen S. Crime in Hunt-
ington’s disease: A study of registered offences among
patients, relatives and controls. J Neurol Neurosurg Psychia-
try. 1998;65(4):467-71.
[27] Craufurd D, Thompson J, Snowden J. Behavioral Changes in
Huntington Disease. Neuropsychiatry Neuropsychol Behav
Neurol. 2001;14(4):219-26.
[28] Grimbergen Y, Knol M, Bloem B, Kremer B, Roos R,
Munneke M. Falls and gait disturbances in Huntington’s dis-
ease. Mov Disord. 2008 May 15;23(7):970-6.
[29] Anderson KE, Gehl CR, Marder KS, Begliner LJ, Paulsen,
JS, Huntington’s Study Group. Comorbidities of obsessive
and compulsive symptoms in Huntington’s disease. J Nerv
Ment Dis. 2010;198(5):334-8.
[30] Thompson JC, Harris J, Sollom AC, Stopford CL, Howard E,
Snowden JS, et al. Longitudinal Evaluation of Neuropsychi-
atric Symptoms in Huntington’s Disease. J Neuropsychiatry
Clin Neurosci. 2012;24(1):53-60.
[31] Hubers A, van Duijn E, Roos R, Craufurd D, Rickards H,
Bernhard Landwehrmeyer G, et al. Suicidal ideation in a
European Huntington’s disease population. J Affect Disord.
Elsevier; 2013;151(1):248-58.
[32] Wetzel H, Gehl C, Dellefave-Castillo L, Schiffman J, Shan-
non K, Paulsen J. Suicidal ideation in Huntington disease:
The role of comorbidity. Psychiatry Res. Elsevier Ltd;
2011;188(3):372-6.
[33] Folstein M, Folstein S, McHugh P. Mini-mental state: A prac-
tical method of grading the cognitive state of patients for the
clinician. J Psychiatr Res. 1975;12:189-98.
[34] Huntington’s Study Group. Unified Huntington’s disease
rating scale: Reliability and consistency. Mov Disord.
1996;11:136-42.
[35] Patel V, Hope R. A rating scale for assessment of aggres-
sion in the elderly—the RAGE. Psychol Med. 1992;22(1):
211-21.
[36] Wing J, Cooper J, Sartorius N. Measurement and classification
of psychiatric symptoms. Cambridge: Cambridge Univeristy
Press; 1974.
[37] Leonard D, Kidson M, Brown J, Shannon P, Taryan S. A
double blind trial of lithium carbonate and haloperidol in
Huntington’s chorea. Aust NZ J Psychiat. 1975;9(2):115-8.
[38] Stewart J. Adverse behavioral effects of amantadine therapy
in Huntington’s disease. South Med J. 1987;80(10):1324.
[39] Stewart J. Paradoxical aggressive effect of propranolol in
a patient with Huntington’s disease. J Clin Psychiatry.
1987;48(3):106-8.
[40] Stewart J, Mounts M, Clark R. Aggressive behavior in
Huntington’s disease: Treatmentwith propranolol. J Clin Psy-
chiatry. 1987;48(3):106-8.
[41] Von Hafften A, Jensen C. Paradoxical response to pindolol
treatment for aggression in a patient with Huntington’s dis-
ease. J Clin Psychiatry. 1989;50(6):203-31.
[42] Findling R. Treatment of aggression in juvenile-onset
Huntington’s disease with buspirone. Psychosomatics.
1993;34(5):460-1.
[43] Byrne A, Martin W, Hnatko G. Beneficial effects of bus-
pirone therapy in Huntington’s disease. Am J Psychiatry.
1994;151(7):1994.
[44] Patel S, Tariot P, Asnis J. L-Deprenyl augmentation of flu-
oxetine in a patient with Huntington’s disease. Ann Clin
Psychiatry. 1996;8(1):23-6.
[45] Ranen N, Lipsey J, Treisman G, Ross C. Sertraline in the
Treatment of Severe Aggressiveness Huntington ’ s Disease
in. 1996;(3).
[46] Bhandary A, Masand P. Buspirone in the management of
disruptive behaviors due to Huntington’s disease and other
neurological disorders. Psychosomatics. 1997;38(4):389-91.
[47] Grove V, Quintanilla J, DeVaney G. Improvement of Hunt-
ington’s disease with olanzapine and valproate. New Engl J
Med. 2000;343(13):973-4.
[48] Blass D, Steinberg M, Leroi I, Lyketsos C. Successful Mul-
timodal Treatment of Severe Behavioral Disturbance in a
Patient With Advanced Huntington’s Disease. Am J Psychi-
atry. 2001;158(12):1966-72.
[49] Fogliani A, Giorgio A, Di Bonomo V. Awareness of invol-
untary movements in Huntington disease with olanzapine: A
case report. Minerva Psychiatr. 2003;44(3):189-90.

332 C.A. Fisher et al. / Aggression in Huntington’s Disease
[50] Alpay M, Koroshetz WJ. Quetiapine in the Treatment of
Behavioral Disturbances in Patients With Huntington’s Dis-
ease. Psychosomatics. 2006;47(1):70-2.
[51] Soliman S, Haque S, George E. Stalking and Hunting-
ton’s Disease: A Neurobiological Link? J Forensic Sci.
2007;52(5):1202-4.
[52] Edlinger M, Seppi K, Fleischhacker W, Hofer A. Treatment of
psychotic and behavioral symptoms with clozapine, aripipra-
zole, and reboxetine in a patient with Huntington’s disease.
Int Clin Psychopharmacol. 2013;28(4):214-6.
[53] Rej S, Desautels R. Experience with intramuscular
zuclopenthixol and medroxyprogesterone acetate in the
treatment of agitation and aggression in Huntington’s
disease. J Neuropsychiatry Clin Neurosci. 2013;25(3):
E33-4.
[54] Ding J, Gadit A. Psychosis with Huntington’s disease: Role
of antipsychotic medications. BMJ Case Rep. 2014;2014:
2013-5.
[55] Brown A, Fisher C. Optimising Occupational Performance
through Sensory Modulation: Case reports of two young
adults diagnosed with Juvenile Huntington’s Disease. Br J
Occup Ther. In press.