Psychopharmacological Issues in Geriatrics


by

Unax Lertxundi, Juan Medrano, Rafael Hernández

DOI: 10.2174/97816810803451150101
eISBN: 978-1-68108-034-5, 2015
ISBN: 978-1-68108-035-2



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Demographic changes due to improved life expectancy and access to medical care has increased the number of people aged 65 years and be...[view complete introduction]

Table of Contents

Foreword

- Pp. i-ii (2)

Enrique Echevarria

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Preface

- Pp. iii-v (3)

Unax Lertxundi, Juan Medrano and Rafael Hernández

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List of Contributors

- Pp. vii

Unax Lertxundi, Juan Medrano and Rafael Hernández

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Historical Perspective of Psychotropic Drug Use

- Pp. 3-15 (13)

Juan Medrano

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Evolution of Psychotropic Drug Use in Elderly Patients: Pharmaceuticals Emerging as Environmental Contaminants

- Pp. 17-30 (14)

Unax Lertxundi and Beatriz Corcostegui

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Age-Related Pharmacokinetic/Pharmacodynamic Changes in Psychopharmacological Drugs

- Pp. 31-48 (18)

Arantxa Isla Ruiz, María Ángeles Solinís Aspiazu and Alicia Rodríguez- Gascón

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Clinically Relevant Psychopharmacological Interactions in the Elderly

- Pp. 49-64 (16)

Ainhoa Urrutia, Javier Peral and Jesús Ángel Padierna

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Potentially Inappropriate Medication in Elderly

- Pp. 65-109 (45)

Rafael Hernández, Ane Gómez de Segura, Juan Medrano, Beatriz Corcóstegui and Unax Lertxundi

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Pharmacovigilance in Geropsychiatry

- Pp. 111-132 (22)

Carmelo Aguirre and Montserrat García

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Anxiolytics and Hypnotics

- Pp. 133-153 (21)

Juan Medrano

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Mood Stabilizers

- Pp. 155-185 (31)

Juan Medrano

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Antidepressants

- Pp. 187-216 (30)

Juan Medrano

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Antipsychotics

- Pp. 217-240 (24)

Juan Medrano

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Antipsychotics in Dementia

- Pp. 241-271 (31)

Juan Medrano

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Antipsychotic Use in Parkinson`s Disease

- Pp. 273-286 (14)

Saioa Domingo-Echaburu

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Antipsychotic Polypharmacy in Elderly Patients

- Pp. 287-304 (18)

Amaia Lopez de Torre

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Drugs Used in Substance Use Disorders

- Pp. 305-324 (20)

Juan Medrano

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Drugs Used in the Treatment of Dementia and Neurocognitive Disorders

- Pp. 325-332 (8)

Juan Medrano

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Subject Index

- Pp. 333-336 (4)

Unax Lertxundi, Juan Medrano and Rafael Hernández

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Foreword

In a beautiful passage of "Alice in Wonderland”, Lewis Carroll wrote: "In a Wonderland they lie, dreaming as the days go by, dreaming as the summers die. Ever drifting down the stream, lingering in the golden gleam. Life, what is it but a dream?. May be that any of us could have dreamed to be for ever Alice, a lovely little girl living in a Wonderland. However, life is not a dream at all, and people, even Alice, usually become old and ailing with time.

Although biomedical research has prolonged human life, it is not possible to live forever, and we cannot avoid unpleasant feelings such as ache, anxiety, depression and fear, especially in aging. The latin sentence "Post iucundam iuventutem, post molestam senectutem, nos habebit humus” (we will become dust after a funny youth and an annoying elderly), that is a part of an old song of our students in the University, indicates that the real problem is what to do with elderly, in which those "thousand natural shocks that flesh is heir to”, as was well expressed by Shakespeare, are even more unpleasant.

After a long life, aged men and women will be suffering in many cases due to pain in osteoarthritis, sadness in depression, communication disability in Parkinson disease and other dyskinesias, as well as to social isolation and cognitive impairment in dementia. Moreover, anxiety caused by social exclusion, the loss of relatives and friends and the terrible fear of death, "the undiscovered country, from whose bourn no traveler returns” make difficult in the elderly "to take arms against a sea of troubles, and by opposing end them” as was said by prince Hamlet.

Although death is denied by modern culture, our passing "through nature to eternity” should be helped by biomedical research in order to soften unpleasant feelings and moods that are linked in many cases to aging. The issues in psychopharmacology focused on the elderly, which are clearly exposed in the present work, can contribute to an improvement in life quality, especially in the case of aged people.

Oblivion in institutions with elevated costs that we can hardly afford is not a social lasting solution for aged people, and soon the elevated economic and social cost of assistance to elderly will be unbearable. Then, the "land full of wonder, mystery, and danger”, as it is said in the famous novel by Lewis Carroll, could become a terrible place, even if "some say, to survive it”.

Aggressive behavior, amnesia, cognitive and sensory deficits, paralysis, hallucinations, delirium and seizures in older people, as well as neurologic damage following to ictus and cerebrovascular pathology, and neurodegenerative diseases, can be deleterious for the health of those youngers charged with the responsibility towards older parents and relatives, leading to sadness, frustration and even desperation in caregivers, many of them women, that will be deprived to enjoy there own life.

This is very well described by William Makepeace Thackeray in his novel "Vanity Fair”, when he tells about the character of Amelia nursing her dying mother:

"Ceaseless slavery meeting with no reward; constant gentleness and kindness met by cruelty as constant; love, labour, patience, watchfulness, without even so much as the acknowledgement of a good word; all this, how many of them have to bear in quiet, and appear abroad with cheerful faces as if they felt nothing".

The present work comes to describe a partial solution to the suffering of older people and their caregivers, as a useful clinical tool in order to improve the pharmacological management of central nervous system pathology in the elderly.

Enrique Echevarria
Phisyology Department
University of the Basque Country
Victoria-Gasteiz
Spain


Preface

Demographic evolution will extensively increase the number of subjects aged 65 years and beyond in the upcoming years. This demographic trend raises an important new challenge for healthcare professionals. Changes in organ functions, homeostatic mechanisms and receptor responsiveness impair drug distribution, metabolism and excretion, and reduce the effectiveness of medicines. Good clinical trial data in this age group are often lacking, under-treatment is common, and increasingly fragility can make drug administration difficult. As a consequence, medication management is much more challenging in the elderly than in younger adult patients. Pathophysiologic alterations occurring in the passing to middle age to old age are known to modify the response to drugs, including phycotropic drugs.

The use of drugs in the general population and especially in the elderly has dramatically increased over the last decades, with older people aged 65 consuming about four times as many drugs as the rest of the population. Psychotropic drugs prescription in particular is becoming a major public health issue as its use is continuously increasing. One (frequently inadverted) risk of such use is the envionmental impact of pharmaceuticals. After their use, drugs are excreted in their native form or as metabolites and enter aquatic systems via different ways. Although there is some information about the environmental impact of certain drugs, knowledge about what happens with the vast majority of them is simply lacking.

Other deleterious consequences are drug interactions and inappropriate drug prescription. In this sense, the elderly population suffers more drug-drug interactions, drug-disease interactions and adverse drug reactions than other age groups derived from the high number of drugs administered. Polypharmacy and potentially inappropriate medication is a common finding in the elderly and it is considered a public health issue related to morbidity, mortality and health care resource use. Avoiding the use of inappropriate drugs and high risk drugs is an important, simple and effective strategy to reduce the problems associated with medication in the elderly.

Specific considerations about pharmacovigilance in elderly patients are widely described. In this sense, medications are brought to market with limited experience regarding their adverse effects, given the small number of people who have taken them during pre-marketing clinical tests. This is particularly true with elderly patients. As a result of this conditioning factor, in particular during the years leading up to the appearance of a new medication, health professionals (basically the physician) should pay special attention to: both identifying adverse effects of medications and reporting them in order to maintain a favorable risk-benefit balance always.

In the second part of the book, a comprehensive and actualized review of the main specific classes of psychopharmacological agents used in geriatric patients is provided, including antipsychotics, anxiolytics & hypnotics, mood stabilizers and antidepressants.

Even though anxiolytics & hypnotics are relatively a safe group that can provide rapid symptomatic amelioration, most of them are associated to the development of addiction and pose specific problems in old age. Therefore, the peculiars of these compounds and the characteristics of the elderly make especially accurate the classical recommendation to prescribe these drugs for short periods of time only.

The following chapter reviews the different drugs labeled as mood stabilizers and where available introduces some considerations on their use in old age. Given the lack of controlled trials enrolling elderly bipolar patients, most information derives from application to geriatric patients’ characteristics of those data obtained in studies with other age groups, and also from decades of clinical experience, especially with lithium.

Antidepressants are drugs used for the treatment of depression and many other psychiatric conditions. Albeit belonging to different chemical families and with a number of mechanisms of action, all of them enhance neurotransmitters at the synaptic cleft. They have a range of adverse effects and effectiveness compared with placebo, according to meta-analysis, is poor. However, they have shown to be efficacious in the elderly. Second-generation antidepressants are safer and better tolerated, but not devoid of side effects, something not to be forgotten when treating a population in which frailty and polypharmacy are common.

Antipsychotics are those psychiatric drugs primarily used for the treatment of psychosis, mainly schizophrenia. Since their introduction, they have been used in a host of indications, but apart from mood disorders and somatoform disorders or insomnia in some European countries, most non-psychosis uses are off-label. Antipsychotics are associated to serious adverse effects, which call for a careful use, especially in the elderly. Dementia is a common off-label use of antipsychotics. However, there are neither controlled studies, nor theoretical grounds supporting their use, especially in the treatment of behavioral disorder, where antipsychotics behave mainly as the "major traqnuillizers” they once were meant to be. As a result, treating dementia with antipsychotics could be a case in point of an irrational use of drugs. Untoward effects linked to antipsychotics when used in dementia are extensively reviewed. Some guidelines to make its use less irrational is also provided.

One disease were antipsychotic use can be problematic is Parkinson’s Disease (PD), can because they can worsen parkinsonism by diminishing dopaminergic transmission in the nigrostriatal pathways. Prior to the introduction of clozapine there was no effective treatment for PD psychosis, and by the time being, is the only antipsychotic that has level I evidence to support its use in PD patients. Several open label studies on quetiapine for the treatment of psychosis in PD have been reported. Some of them showed quetiapine to be effective without worsening motor function while in others it was reported as ineffective although well tolerated.

The simultaneous use of more than one antipsychotic in the management of psychiatric diseases has become a common practice worldwide. Although some theoretical bases have been suggested supporting this practice known as antipsychotic polypharmacy (APP), there is more personal experience than evidence-based behind it. APP is more frequent among young men. Nevertheless, some authors have estimated an APP prevalence in patients aged 65 or more up to 25% or even higher in the outpatient setting. Antipsychotics in the elderly are mainly used in the management of dementia-related behavioural alterations and schizophrenia but, as guidelines recommend, they should be used for short-term treatments. This limitation of duration of treatment has been associated with a wide range of potential risks like cerebrovascular events, hip fracture, pneumonia, QT prolongation, metabolic disorders or even death. These risks are boosted when geriatric population and high dosage derived from polypharmacy are considered. In this concern, some special considerations should be taken into account: optimal antipsychotic election according to patient´s morbidities and other medications in order to avoid interactions, maximal daily dosage, optimal follow-up intervals and recommendations, among others.

Another chapter will discuss the currently used drugs in of proposed for the treatment of substance use disorders, which are under-recognized in the elderly. The lack of studies focused on elderly populations call for a cautious, careful use of pharmacological agents, which must always be accompanied by psychosocial approaches.

Dementia is a devastating illness for which currently there is no curative treatment. In the last twenty years, acetylcholinesterase inhibitors have been approved in the mild to moderate stages of the illness to delay the progression of Alzheimer’s disease, the most prevalent form of dementia, while memantine has been approved in later stages. Clinical experience shows that drug treatment of cognitive symptoms is of little benefit, but there is evidence that both acetylcholinesterase inhibitors and memantine could be helpful to alleviate the behavioral and psychological symptoms of dementia, especially in variants where other alternatives, such as antipsychotics, can be detrimental.

Unax Lertxundi
Pharmacy Service
Araba´s Mental Health Network
C/Alava 43 01006 Vitoria-Gasteiz
Araba/Álava
Spain

Juan Medrano
Ezkerraldea - Enkarterri Mental Health Community Services
Bizkaia´s Mental Health Network
Portugalete
Bizkaia/Vizcaya
Spain

&

Rafael Hernández
Internal Medicine
Araba´s Mental Health Network
C/Alava 43 01006 Vitoria-Gasteiz
Araba/Álava
Spain

List of Contributors

Editor(s):
Unax Lertxundi
Pharmacy Service
Araba´s Mental Health Network
C/Alava 43 01006 Vitoria-Gasteiz
Araba/Álava
Spain


Juan Medrano
Ezkerraldea - Enkarterri Mental Health Community Services
Bizkaia´s Mental Health Network
C/Alava 43 01006 Vitoria-Gasteiz
Bizkaia/Vizcaya
Spain


Rafael Hernández
Internal Medicine
Araba´s Mental Health Network
C/Alava 43 01006 Vitoria-Gasteiz
Araba/Álava
Spain




Contributor(s):
Ainhoa Urrutia
Pharmacy Service
Galdakao-Usánsolo Hospital
Barrio Labeaga s/n, 48960 Galdakao
Bizkaia/Vizcaya
Spain


Alicia Rodríguez-Gascón
Pharmacokinetics, Nanotechnology and Gene Therapy Group, Pharmananogene Faculty of Pharmacy
Vitoria-Gasteiz
Spain


Amaia López de Torre
Pharmacy Service
Galdakao-Usánsolo Hospital
Barrio Labeaga s/n, 48960 Galdakao
Bizkaia/Vizcaya
Spain


Ane Gómez de Segura
Pharmacy Service
Araba´s Mental Health Network,Vitoria-Gasteiz
Araba/Álava
Spain


Arantxa Isla Ruiz
Pharmacokinetics, Nanotechnology and Gene Therapy Group, Pharmananogene Faculty of Pharmacy
University of the Basque Country UPV/EHU
Vitoria-Gasteiz
Spain


Beatriz Corcóstegui
Pharmacy Service
Bizkaia´s Mental Health Network
Bizkaia
Spain


Carmelo Aguirre
Basque Country Pharmacovigilance Unit
Galdakao-Usansolo Hospital
BarrioLabeaga s/n, 48960 Galdakao
Bizkaia/Vizcaya
Spain


Javier Peral
Pharmacy Service
Galdakao-Usánsolo Hospital
Barrio Labeaga s/n, 48960 Galdakao
Bizkaia/Vizcaya
Spain


Jesús Ángel Padierna
Psychiatry Service
Galdakao-Usansolo Hospital
Barrio Labeaga s/n, 48960 Galdakao
Bizkaia/Vizcaya
Spain


Juan Medrano
Ezkerraldea - Enkarterri Mental Health Community Services
Bizkaia´s Mental Health Network, Portugalete
Bizkaia
Spain


Maria Ángeles Solinís Aspiazu
Pharmacokinetics, Nanotechnology and Gene Therapy Group, Pharmananogene Faculty of Pharmacy
University of the Basque Country UPV/EHU
Vitoria-Gasteiz
Spain


Monserrat García
Basque Country Pharmacovigilance Unit
Galdakao-Usansolo Hospital
Barrio labeaga s/n, 48960 Galdakao
Bizkaia/Vizcaya
Spain


Rafael Hernández
Internal Medicine
Araba´s Mental Health Network
C/Alava 43 01006, Vitoria-Gasteiz
Araba/Álava
Spain


Saioa Domingo-Echaburu
Pharmacy Service
Alto Deba Integrated Health Organization, Avda, Nafarroa, 16
20500 Arrasate Gipuzkoa/Guipuzcoa
Spain


Unax Lertxundi
Pharmacy Service
Araba´s Mental Health Network, Vitoria-Gasteiz
Araba
Spain




Reviews

“ …very well documented, written in a clear language… …comes to meet the need to expand the small number of works aimed at drug treatment of the elderly…” Reviewed by Luis F. Agüera Ortiz, President, Spanish Society of Psychogeriatrics, August 2015

Full text book review

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