Antipsychotic Treatments For The Elderly Efficacy and Safety of Aripiprazole

EXPERT OPINION: ANTIPSYCHOTIC
TREATMENTS FOR THE ELDERLY:

EFFICACY AND SAFETY OF ARIPIPRAZOLE
NEUROPSYCHIATRIC DISEASE AND TREATMENT 2010: 6; 47-58
AUTHOR :
KOHEN I, LESTER PE, LAM S
PEMBIMBING :
DR. SABAR P. SIREGAR, SP. KJ
ABSTRACT
 Delusions, hallucinations and other psychotic symptoms can accompany a

number of conditions in late life.
 As such, elderly patients are commonly prescribed antipsychotic medications for
the treatment of psychosis in both acute and chronic conditions.
 Elderly patients are at an increased risk of adverse events from antipsychotic
medications because of age-related pharmacodynamic and pharmacokinetic
changes as well as polypharmacy.
 This paper provides a review the pharmacokinetics and pharmacodynamics of
aripiprazole as well as dosing, diagnostic indications, efficacy studies, and
tolerability including its metabolic profile.
INTRODUCTION
 Antipsychotic medications are commonly prescribed for older adults for the acute
management of psychosis in brief psychotic disorders or in psychosis due to a
general medical condition or from substance use.
 Chronic antipsychotic therapy is commonly used in patients with psychosis,
schizophrenia, dementia related psychosis, bipolar disorder, and psychosis related
to Parkinson’s disease.
 Common side effects in the elderly from antipsychotics include orthostatic
hypotension, sedation, anticholingergic side effects, extrapyramidal symptoms
(tremor and rigidity), and tardive dyskinesia (lip smacking).
 This paper provides a review of aripiprazole, a newer atypical antipsychotic agent,
review the indications and adverse drug reactions of this drug in the elderly.
PHARMACOLOGY AND PHARMACOKINETICS /
DYNAMICS OF ARIPIPRAZOLE
 Aripiprazole is a second-generation (atypical) antipsychotic that is approved for

schizophrenia, manic or mixed episodes associated with biploar I disorder, and as an
adjunctive treatment of major depressive disorder.
 It exhibits high affinity for D2, D3, 2-HT1a and 5-HT2a receptors, moderate affinity
for D4, 5-HT2c, 5-HT7, alpha 1 adrenergic and H1 receptors, and no affinity for
muscarinic receptors.
 It has moderate affinity for the serotonin reuptake transporter.
 The proposed mechanism of action for its efficacy is a combination of partial agonistic
activity at D2 and 5-HT1A receptors and antagonistic activity at 5-HT2A receptors.
 It is available in several dosage forms: intramuscular injection solution, oral
solution, tablets, and orally disintegrating tablets
CONT’
 Aripripazol e has an active metabolite (dehydroaripiprazole) that has affinities

for D2 receptors and an elimination half-life of 94 hours.
 The drug reaches the peak plasma concentration (Tmax) between 3 to 5 hours,
and achieves a steady-state concentration within 14 days.
 It can be taken with or without food, but high-fat meal delays Tmax by 3 hours.
Aripiprazole has a high volume of distribution (4.9 L/kg) and is highly bound to
albumin (99%).
EFFECT OF ARIPIPRAZOLE IN ELDERLY
 Anticholinergic effects can be detrimental to those who may already have urinary
symptoms, cognitive impairment, dry mouth, blurred vision and cardiac
abnormalities.
 Orthostatic hypotension and sedation may contribute to falls in patients who have
trouble with balance and gait.
 Extrapyramidal symptoms can be associated with long term antipsychotic
therapy  Patients with the comorbidity of PD are especially at risk for tremor
and muscle rigidity.
ARIPIPRAZOLE EFFICACY STUDIES
 Aripiprazole demonstrated its efficacy in four short-term placebo controlled trials

that enrolled acutely relapsed inpatients with schizophrenia.
 Clinical trials of aripiprazole included few elderly patients and more data are
needed on the effects of aripiprazole in this population, especially those with
comorbid medical illnesses.
 In one study, aripiprazole was used to treat 10 elderly hospitalized patients
between 62 and 85 years of age who manifested signs of psychosis related to
schizophrenia or schizoaffective disorder.
ARIPIPRAZOLE : SAFETY IN ELDERLY
 The most common side effects reported with aripiprazole (> 10% incidence) were
headache, insomnia, agitation, and anxiety.
 Other common side effects were dyspepsia, nausea and vomiting, lightneadedness,
somnolence, constipation and akathisia. The most frequent adverse events leading
to discontinuation of aripiprazole included psychosis (3.6%), agitation (0.6%) and
akathisia (0.6%).
 The median increase in fasting total cholesterol from baseline observed with
aripiprazole treatment was low and did not differ significantly from placebo. Only
5.5% of patients on aripiprazole had abnormally elevated fasting glucose levels
and only 1.4% of the patients on aripiprazole had random levels of glucose above
200 mg/dL.71 There were no clinically important differences in the adverse event
profile when stratified by age, gender or race in patients receiving aripiprazole.
CRITICAL APPRAISAL
IS THE SOURCE OF THE OPINION CLEARLY
IDENTIFIED?
Yes
The source of the opinion is clearly identified. The authors are:
 Izchak Kohen from division of geriatric psychiatry, Zucker-Hillside Hospital,
Glen Oaks, NY, USA
 Paula E Lester from division of geriatric medicine, Winthrop University
Hospital, Mineola, NY, USA
 Sum Lam from division of pharmacy and geriatrics, St. John’s University
College of Pharmacy and Allied Health Professions, Queens, NY, USA
IS THE SOURCE OF THE OPINION CLEARLY
IDENTIFIED?
 This expert opinion paper is published in Neuropsychiatric Disease and Treatment

2010: 6; 47-58 and licensed by Dove Medical Press Ltd which is open access.
 The article is indexed in:
 PMCID: PMC2846120
 PMID: 20361061
DOES THE SOURCE OF OPINION HAVE
STANDING IN THE FIELD OF EXPERTISE?
Yes
 This paper’s topic is about geriatric psychiatry which explain and review about
antipsychotic treatments for the elderly with focused topic, efficacy and safety of
aripiprazole.
 The authors’ expertise are appropriate to the topic of the article, which are
geriatric psychiatry; geriatric medicine; pharmacy and geriatrics.
ARE THE INTERESTS OF THE RELEVANT POPULATION
THE CENTRAL FOCUS OF THE OPINION?
Yes
 The purpose of the paper is to provide a review of aripirazole, a newer second
generation antipsychotic agent, for its use in a variety of psychiatric disorders in
elderly including schizophrenia, bipolar disorder, dementia, Parkinson’s disease and
depression.
 The paper reviews about pharmacokinetics and pharmacodynamics, dosing, diagnostic
indications, efficacy studies, tolerability and the metabolic profile of aripiprazole.
 This paper also presents about the quality of life, patient satisfication and adherence
due to aripiprazole treatment as antipsychotic agent in elderly patients.
IS THE STATED POSITION THE RESULT OF AN
ANALYTICAL PROCESS, AND IS THERE LOGIC IN THE
OPINION EXPRESSED?
Yes
 The antipsychotic profile including efficacy and safety of aripiprazole to elderly
patient stated in the paper are evidence based. The data are based on some
clinical trials; meta-analysis; RCT; and studies from phase II and III trials.
 This paper also stated about patient-focused perspective including:
 Quality of life based on STAR study, double-blind study, systemic review.
 Patient satisfication/acceptability based on Randomized Control Trials and other
controlled studies.
 Adherence based on meta analysis, and other controlled studies.
IS THERE REFERENCE TO THE EXTANT
LITERATURE?
Yes
 The main points of this paper is to present about antipsychotic treatment, by
aripiprazole in elderly patient.
 Elderly patients are at risk of adverse drug events because of age-related
pharmacokinetics and pharmacodynamics changes and polypharmacy.
 The arguments and data stated in the paper are evidence based.
 The arguments in the paper support the main points based on the valid data and
literatures.
IS THERE ANY INCONGRUENCE WITH THE
LITERATURE/SOURCES LOGICALLY DEFENDED?
Yes
 In this paper, the authors present some studies related to the efficacy, safety,
pharmacokinetics, pharmacodynamics of aripipprazole and patient-focused
perspective which are compared in the paper.
 The data are evidence based.
OVERALL APPRAISAL AND CONCLUSION
 The expert opinion paper titled Antipsychotic treatments for the elderly: efficacy
and safety of aripiprazole by Kohen I, Lester PE, Lam S present
comprehensively about the elderly patients who needs antipsychotic treatment
(population targeted); pharmacodynamics, pharmacokinetics, efficacy and safety
of aripiprazole; and patient-focused perspective.
 The data and arguments that support the main points are evidence based with
various comparison between studies and trials.
 This paper could give insight to study about the other antipsychotic agents
treatment in elderly patients; the efficacy and safety of antipsychotic agents in
more specific elderly population such as polypharmacy patients, patients with
complicated disease; the efficacy and safety of antipsychotic agent related to the
period of the treatments; or other related studies and trials.
THANKYOU

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EXPERT OPINION: ANTIPSYCHOTIC

TREATMENTS FOR THE ELDERLY:

 Delusions, hallucinations and other psychotic symptoms can accompany a

 Aripiprazole is a second-generation (atypical) antipsychotic that is approved for

 Aripripazol e has an active metabolite (dehydroaripiprazole) that has affinities

 Aripiprazole demonstrated its efficacy in four short-term placebo controlled trials

 This expert opinion paper is published in Neuropsychiatric Disease and Treatment

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