1. Use of Clozapine to Treat Behavioral Disturbance in a Patient with Early Onset Dementia
Michelle Graf, PA-S
Brenda Swanson-Biearman DNP, MPH, RN
Duquesne University
Department of Physician Assistant Studies
REFERENCES
1.Lin Tan LT, Wang HF, Tan CC, Tan MS, Meng XF,
Wang C, Yu JT. Efficacy and safety of atypical
antipsychotic drug treatment for dementia: a systematic
review and meta-analysis. Alzheimers Res Ther.
2015:7(20). doi:10.1186/s13195-015-0102-9.
2.Sampson EL, White N, Leurent B, Scott S, Lord K,
Round J, Jones L. Behavioral and psychiatric symptoms in
people with dementia admitted to the acute hospital: a
prospective cohort study. BJPysch. 2014;205(3):189-196.
doi: 10.1192/bjp.bp.113.130948.
3.Clozapine. Lexi-Drugs. Lexi-Comp Online. Hudson, OH:
Lexi-Comp; 2016. Accessed January 16, 2016.
4.Frogley C, Taylor D, Dickens G, Picchioni M. A
systematic review of the evidence of clozapine's anti-
aggressive effects. Int J Neuropsychopharmacol. 2012
Oct;15(9):1351-71. doi: 10.1017/S146114571100201X.
5.Lee HB, Hanner JA, Yokley JL, Appelby B, Hurowitz L,
Lyketsos CG. Clozapine for treatment-resistant agitation in
dementia. Geriatr Psychiatry Neurol. 2007;20:178.182.
CONCLUSION
Clozapine is an atypical antipsychotic
medication. Studies have indicated that
atypical antipsychotic medications can be
used for the treatment of behavioral
disturbance in patients with psychiatric
conditions. Due to severe possible adverse
effects, fewer studies have been conducted on
the use of clozapine in patients with
dementia. Our patient had a positive response
to the clozapine therapy. This off-label use of
clozapine should be further explored to
determine if this medication is an appropriate
treatment option.
INTRODUCTION
Dementia is the decline in mental functioning
that interferes with daily life, affecting 24
million people worldwide. It has been
suggested that the neuropsychiatric
symptoms, rather than the cognitive
impairment of dementia patients, inflict the
greatest hardship on family members.1
The
most common behavioral and psychiatric
symptom is aggression.2
Clozapine is an
atypical antipsychotic that is conventionally
used in the treatment of schizophrenia. One
off-label use of this drug is the treatment of
behavioral and psychiatric symptoms in
patients with dementia.3
We describe a case
of a patient with early onset dementia
exhibiting behavioral disturbance. The use of
clozapine in the treatment will be examined.
ABSTRACT
Dementia is a mentally debilitating condition
that can cause behavioral disturbance.
Behavioral issues are often not well
controlled with non-pharmacologic therapies.
Clozapine is an atypical antipsychotic drug
that is not commonly used due to the
possibility of severe adverse effects. An off-
label use of this medication is to treat
behavioral disturbance and psychiatric
symptoms in patients with dementia. We
present a 58-year-old white female with early
onset dementia presenting with aggressive
behavior, which included yelling, throwing
objects, and hitting the staff members at the
personal care unit where she was living. With
an unremarkable medical workup, the
patient’s behavior only began to improve
after she was switched to clozapine therapy
from risperidone.
CASE SYNOPSIS
A 58-year-old white female with early onset
dementia was committed on a 302 to the
inpatient psychiatric unit for aggressive
behavior that she displayed at her personal
care home. Her inappropriate behavior
included yelling and throwing objects. The
patient had been physically aggressive and
repeatedly threatened her peers for several
days. Patient history was obtained from the
personal care home and her brother. Her past
medical history included hypertension,
hyperlipidemia, and COPD. Her past
psychiatric history was significant for anxiety
and depression. Her medications included
donepezil, memantine, and escitalopram.
Upon arrival, her vital signs were stable.
CBC, CMP, TSH, UA, CXR, and EKG were
all unremarkable and her toxicology screen
was negative. Upon examination, her attitude
was guarded and uncooperative, her mood
was irritable, and her affect was restricted.
She had disorganized thoughts and
psychomotor retardation. She was alert and
oriented to self only. Quetiapine therapy was
initiated. The patient continued to be agitated
and combative to the unit staff. After several
weeks of no improvement in her behavior, the
patient was placed on clozapine 12.5 mg PO
daily. The quetiapine was discontinued. The
clozapine was slowly titrated up over the
course of several days to 100 mg daily. The
use of this medication improved the behavior
of the patient considerably as she no longer
shouted inappropriate words and attempted to
hit other patients and staff members.
DISCUSSION/LITERATURE
REVIEW
Clozapine is an FDA approved atypical
antipsychotic used for treatment resistant
schizophrenia.3
A study by Lin Tan et al
presented the effects of atypical antipsychotic
drugs for treatment of neuropsychiatric
symptoms in patients with dementia. Atypical
antipsychotics such as risperidone and
aripiprazole have been successful in improving
psychotic and behavioral symptoms in
dementia patients. Few studies have been
conducted on clozapine as significant adverse
effects exist such as severe neutropenia,
anticholinergic effects, cardiac risks, and
increased morbidity and mortality.1
Therefore,
atypical antipsychotic drugs used to treat
behavioral problems associated with dementia
should not be used until alternative non-
pharmacologic therapies have failed or patients
are at risk for harming themselves or others.3
A 2012 systematic review by Frogley et al
demonstrated favorable outcomes from using
clozapine in managing aggressive behavior in
patients with schizophrenia and other
psychiatric conditions. Clozapine was effective
in cases in which other treatments have failed.4
A study by Lee et al is one of the few studies
that examined the use of clozapine to treat
behavioral problems in patients with treatment
resistant dementia. Clozapine was successful in
calming the patients in addition to reducing
agitation and aggressive behavior.5
Our patient
improved significantly on the clozapine
therapy. It is noted that our patient was younger
than most patients with dementia, which may
have decreased her risk to adverse effects.