ANTIPSYCHOTICS FOR AGGRESSION UNRELATED TO A PSYCHIATRIC DIAGNOSIS, 2008

Abstract

The occurrence of challenging behavior is an important problem in the intellectual disability
population. Antipsychotic medication has been widely used to suppress these behaviors but the
efficacy of these treatments has been in question. A recent paper by Tyrer and his colleagues
provided evidence that aggression without psychosis does not respond to antipsychotic medication.
We discuss the importance of these findings for clinical practice and also address problems which
may result from premature withdrawal of drug therapy. Prior to initiating drug therapy, a
comprehensive assessment of challenging behavior must determine the causes and then initiate
appropriate treatments

Full text

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Mental Health A spects of Deve lopmental Disabilities April/May/June 200 8 Vol. 11, N o. 2
ANDREW S. LEVITAS, M.D., JEREMY TURK, M.D.,
12
ASK THE DOCTOR DAVID BRAMBLE, M.D. & ANNE D. HURLEY, PH.D.
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ANTIPSYCHOTICS FOR AGGRESSION UNRELATED
TO A PSYCHIATRIC DIAGNOSIS
University of Medicine & Dentistry of New Jersey/School of Osteopathic Medicine, Center for Mental Health
1
Treatment for Persons with Intellectual Disabilities, Stratford, NJ, USA
St. George’s, University of London; Trustwide Child & Adolescent Mental Health Services Clinical Lead,
2
South West London & St. George’s Mental Health NHS Trust, London, UK
Telford & Wrekin Primary Care Trust, Shropshire, UK
3
Harvard Vanguard Medical Associates and Tufts University School of Medicine, Boston, MA, USA
4
Q.Drs. Levitas, Turk and Bramble, the issue of
using antipsychotic medications for
aggression has surfaced again. Why?
A.In January 2008, the prestigious British
medical journal Lancet published a study by
Tyrer and his colleagues. In addition, Lancet
10
published an accompanying editorial. This
7
multicenter randomized study failed to
demonstrate the superiority of risperidone and
haloperidol to placebo. A potential pool of 180
subjects resulted in 86 individuals with
aggression without psychosis. Study subjects were
required to have a M odified Overt Aggression Scale
(MOAS) score of at least 4. Most subjects (83%)
9
had mild to moderate intellectual disability; 62%
were m ale. Subjects were randomized to
risperidone (maximum dose 2 mg./day, titrated
over four weeks; n=29), haloperidol (maximum
dose 5 mg./day titrated over four weeks; n=28) or
placebo (n=29). MOAS scores and Clinical Global
Impression (CGI) were assessed at baseline, 4, 12
and 26 weeks; Aberrant Behavior Checklist (ABC),
Quality of Life, Uplift and Burden Scores were all
scored, as were UBU (extra-pyramidal effects).
Thirty-six patients withdrew from the study for
various reasons, three because of severe adverse
drug reactions. The results found no statistically
significant difference between a first generation
antipsychotic (FGA), a second generation
antipsychotic (SGA) and placebo in reducing
aggression in these subjects with intellectual
disability.
Q.Do the results suggest that antipsychotics
are always ineffective in treating behavior
that is independent of psychosis?
A.As the authors pointed out, antipsychotics
cannot be considered as routine in the early
treatment of aggressive behavior. We only use
antipsychotic medications as a last resort after
other interventions have failed. In addition, first
line treatm ent should include alteration in
programming supports and the use of
psychological and behavioral therapies. In an
accompanying editorial to this article, Matson and
Wilkins strongly advocate the use of behavioral
7
techniques, which are proven to be very effective
for most challenging behavior. Unfortunately, as
they also point out, sophisticated Applied
Behavioral Analysis (ABA) is seldom available
outside university settings, and skilled
The occurrence of challenging behavior is an important problem in the intellectual disability
population. Antipsychotic medication has been widely used to suppress these behaviors but the
efficacy of these treatments has been in question. A recent paper by Tyrer and his colleagues
provided evidence that aggression without psychosis does not respond to antipsychotic medication.
We discuss the importance of these findings for clinical practice and also address problems which
may result from premature withdrawal of drug therapy. Prior to initiating drug therapy, a
comprehensive assessment of challenging behavior must determine the causes and then initiate
appropriate treatments.
Keywords: intellectual disability, behavior, antipsychotic, side-effects, psychosis

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Mental Health A spects of Deve lopmental Disabilities April/May/June 200 8 Vol. 11, N o. 2
outside university settings, and skilled
implementation of behavioral interventions
requires a level of caregiver train ing rarely
encountered in community settings.
When a person with intellectual disability has a
diagnosed psychiatric disorder, the correct
treatment is the treatment specific to the disorder.
Antipsychotic medications remain the mainstay for
treatment of hallucinations and delusions, and
have a place as adjunctives in the treatment of
bipolar disorder. Tyrer et al. demonstrate
10
convincingly, if not conclusively, that
antipsychotics do not treat non-specific
aggression.
Q.Is there any countervailing data?
A.Tyrer et al. cite two other studies with adults
showing greater improvement with
risperidon e, the m ost recent of which is
essentially an extension of the RUPP and RDBSG
studies of risperidone in children with intellectual
disability, autism spectrum disorders, and
disruptive behavior disorders. These studies
2,3
showed reductions in disruptive behaviors w ith
low-dose risperidone. This may, however, be a
different population. All subjects had a diagnosis
of one of the DSM-IV disruptive behavior
disorders, antisocial personality disorder or
intermittent explosive disorder; target behaviors
included not only aggression but also other
disruptive behaviors (e.g., self-injury). Tyrer et al.
excluded patients with psychosis but not subjects
who might have m et DSM -IV criteria for a
disruptive behavior disorder, antisocial
personality disorder or intermittent explosive
disorder, all of which feature a pattern of
aggressive (or other disruptive) behavior.
Therefore, it is not en tirely clear how comparable
the two subject populations are.
Q.Are the antipsychotics harmful?
A.Potentially yes. The side-effects of FGAs such
as haloperidol include sedation, motor
restlessness (akathisia), muscle tone changes
(dystonia) and over time, Parkinson’s disease-like
tremor (“Drug-Induced Parkinsonism,” tardive
dyskinesia), withdrawal emergent phenomena
when attempts are made to stop medication, and
an array of less common side-effects. SGAs such
5,6
as risperidone are less prone to cause movement
disorders (but still can) and sedation, but can
cause weight gain, hyperlipidemia and insulin
insensitivity (“Metabolic Syndrome”), as well as
changes in cardiac conduction. None of these are
6
trivial. One of the m ovement disorders, akathisia
(unpleasant motor restlessness, often with a
subjective irritability), seen with both FGAs and
SGAs, could in fact contribute to aggression,
whatever therapeutic effects the drugs are
assumed to have; this might in part account for
the greater numeric drop in MOAS score in the
placebo group (although UBU scores in all groups
were com parable).
Q.Why would all the subjects get better, even
those on placebo?
A.For one thing, all the subjects were being
observed and assessed; they were all getting
more than routine caregiver contact and
encouragement, and (this is the point) the
addition of a drug in the two treatment groups
added nothing to the outcome.
Q.What do you think are the potential effects of
this study on clinical practice?
A.We are hopeful that the routine use of
antipsychotics for challenging behavior will
decrease. On the other hand, this study may be
misinterpreted. Some may get the impression that
psychiatrists always overuse antipsychotics, and
this is not true. Psychiatrists do, however,
experience extreme pressure from families and
caregivers to prescribe medicine for challenging
behavior. As M atson and W ilkins pointed out, this
is often a reaction to less than adequate supports
and the lack of available professionally trained
behavior therapists.
We are concerned that some m ay misinterpret
this paper. Because it is difficult to diagnose
psychoses in people with intellectual disability, it
may not be recognized and psychiatrists may feel
reticent to prescribe without a firm diagnosis.
Secondly, it is difficult to withdraw patients from
long-term treatment to antipsychotic medicines.
Side-effects of withdrawal can occur in addition to
an increase in ch allen ging behavior. W e saw this
when a “black box” warning was published on
thioridazine. Thus, the psychiatrist must have a
slow and careful schedule of tapering with very
close monitoring. Further, withdrawal-emergent
movement disorders can occur, and may be
irreversible.1,4,5,8,11
Q.Are we asking the right questions here? In
what way is aggression related to psychiatric
disorders, or it is purely a “behavioral” problem?
Is the provision of ABA skilled behavior

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Mental Health A spects of Deve lopmental Disabilities April/May/June 200 8 Vol. 11, N o. 2
intervention programs a sufficient answer to the
problem of non-specific aggression?
A.Aggression occurs in many psychiatric
disorders and may be an atypical feature of
mood disorders and anxiety disorders, for
example, in the intellectually disabled population.
However, aggression and challenging behavior
occur independently of psychiatric conditions in
this population for many reasons. For exam ple,
people with intellectual disability may respond to
a change in residence or loss of a parent w ith
aggression. The proper course of action for
challenging behavior is to conduct a
comprehensive analysis and determine the cause.
Behavioral therapies are effective and often the
treatment of choice. Beyond behavioral analysis,
which still defines the problem as that of the
individual patient, lies Systems Analysis. We
place individuals in living situations and
vocational programs according to w hat is
available, not necessarily what is best, or what is
clinically indicated. Individuals are expected to
make problem-free relationships with roommates,
housemates and caregivers, and are assumed to be
in need of mental health intervention when these
fail, in spite of obvious system deficiencies such as
caregiver turnover, lack of caregiver training,
inappropriate vocational placement, little real
community involvement, and, most frequently,
poverty. Further, environments may be adverse for
reasons not encompassed by our ideologies.
One of us (AL) was a consultant at a large
congregate living facility that was reorganized into
smaller living situations. Many residents m oved to
small community homes of five individuals. After
living in a 40-bed dormitory, five residents now
lived in a comfortable and spacious home. We
quickly saw decreases in problem behaviors in the
smaller, more “normalized” setting. But the same
improvement was seen in residents left behind
when the 40 bed dormitory decreased to a
population of 20. Life was very different: less
noise, increased staff attention, less wait time for
eating, toileting, and bathing.
Q.Are antipsychotics used frequently for
children with intellectual disability, most of
whom are living at home with families?
A.Families are much more sensitive to the
overuse of medicines than paid caregivers.
However, with severe challenging behaviors,
families may become desperate for any solution
because we have very few supports available to
families an d ob taining residential placement is
extrem ely difficult.
Q.Does the financing of health care have an
impact on prescribing?
A.This is certainly a problem in the US because
of poor contact between helping systems,
resulting in use of drugs for lack of other easily
available alternatives. In the UK, the focus on
acute physical health targets, with consequent
reciprocal declines in resourcing for services like
respite care and other desperately needed help for
our more vulnerable clients, places more pressure
on health professionals to undertake cheaper
“solutions.” Ironically, as our local authority
colleagues become more cash-strapped, they are,
in our experience, at risk of becoming m ore likely
to “medicalise” their clients’ problems. Th is
represents quite a turn around from the past
when they were often driven ideologically to do
exactly th e opposite.
As this column is written, the US, and perhaps
the w orld, econom y is slowing. M edication is
cheaper than any changes in the care system for
persons with intellectual disability. We believe
there is a real danger of history repeating itself
with many individuals being commenced
unnecessarily on antipsychotics, often to be
continued long term, without recourse to other
more evidence-based non-pharmacological
approaches to managing their presenting
challenging behaviors.
Q.
Do you have any final comments?
A.Yes we do. Practitioners should prescribe
antipsychotics when they are needed in the
treatment of psychosis or mood disorders. In
addition, if a practitioner decides to withdraw a
patient from an antipsychotic, this should not be
done without team involvement, analysis of the
possible causes of challenging behavior, altered
environmental supports, and therapies. Further,
withdrawal of antipsychotics can result in many
unpleasant side-effects and tapers must be
handled carefully.
We believe there is a need to improve the
education of all mental health professionals in the
diagnosis of psychiatric disorder and functional
analysis of behavioral issues in persons with
intellectual disability. The message needs to be
stated explicitly: no more ongoing prescriptions of
antipsychotic with discharge back to community
housing or family.

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Mental Health A spects of Deve lopmental Disabilities April/May/June 200 8 Vol. 11, N o. 2
REFERENCES
1. Aman MG, Singh NN . Dyskinetic symptoms in
profoundly retarded reside nts following neuroleptic
withdrawal and during methylphenidate treatment.
J Ment Defic Res 1985;29:187-195.
2. Findling RL, Aman MG, Eerdekens M, et al. Long-
term, open-label study of risperidone in children with
severe disruptive behaviors and below-average IQ.
Am J Psychiatry 2004;161:677-684.
3. Gagiano C, Read S, Thorpe L, et al. Short- and long-
term efficacy and safety of risperidone in adults with
disruptive behavior disorders. Psychopharmacol
2005;179:629-636.
4. Gilbert PL, Harris MJ, McAdams LA, Jeste DV.
Neuroleptic withdrawal in schizophrenic patients. A
review of the literature. Arch Gen Psychiatry
1995;52:173-188.
5. Levitas A, Hurley A. The history behind the use of
antipsychotic medications in persons with
intellectual disability. Ment Health Aspects Dev
Disabil 2006;9:26-32.
6. Levitas A, Hurley A. The history behind the use of
antipsychotic medications in persons with
intellectual disability, Part II. Ment Health Aspects
Dev Disabil 2006;9:93-101.
7. Matson JL, Wilkins J. Antipsychotic drugs for
aggression in intellectual disability. Lancet
2008;371:9-10.
8. Smith RC. Lower-dose therapy with traditional
neurolep tics in chronically hospitalized schizophrenic
patients. Arch Gen Psychiatry 1994;51:427-429.
9. Sorgi P, Ratey J, Knoedler DW, et al. Rating
aggression in the clinical setting. A retrospective
adaptation of the Overt Aggression Scale: Preliminary
results. J Neuropsychiatry Clin Neurosci
1991;3:S52–S56.
10. Tyrer P, Oliver-Afric ano PC, Ahmed Z, et al.
Risperidone, haloperidol, and placebo in the
treatment of aggressive challenging behaviour in
patients with intellectual disability: A randomised
controlled trial. Lancet 2008;371:57-63.
11. Witschy JK, Malone GL, Holden LD. Psychosis after
neuroleptic withdrawal in a manic-depressive
patient. Am J Psychiatry 1984;141:105-106.
CORRESPONDENCE: Andrew S. Levitas, M .D.,
Dept. of Psychiatry, UMDNJ/SOM, 40 East Laurel
Road, Suite 200, Stratford, NJ 07084-1504; em ail:
levitaan@umdnj.edu.