Psychopharmacological Issues in Geriatrics

This chapter divides the history of Psychopharmacology into three different eras. The first, Empiric Psychopharmacology, was that of the serendipitous discovery of diverse molecules in the 1950s, in which the main current classes of compounds were roughly created. A second era, Scientific Psychopharmacology, was defined by the purposeful design of agents based on pathophysiological hypothesis developed from the identified mechanisms of action of the first psychiatric drugs. A third, modern era, of disenchantment, is marked by a growing criticism of Psychopharmacology and its commercial dimension. Finally, some remarks are made on the possible future of Psychopharmacology.

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 steadily increasing. After their use, drugs are excreted in their original 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.

Demographic evolution will extensively increase the number of subjects aged 65 years and beyond in the upcoming years. This demographic trend becomes a relevant challenge for the professionals of health and a growing of medication demand, and also for deeper comprehension on how age affects the effect of drugs and their interactions. 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. It is well known that the pathophysiologic changes that occur in the transition from middle age to old age alter responsiveness to drugs, including psychotropic drugs. These Pharmacodynamic changes are especially important in the central nervous system (CNS), where an increasing of the sensitivity of the CNS to drug side-effects with age is observed. This chapter reviews extensively the age-related pharmacokinetic/pharmacodynamic changes in psychopharmacological drugs.

The elderly population suffers more drug-drug interactions (DDI), drugdisease interactions (DDE) and adverse drug reactions (ADR) than other age groups. The main risk factor is the high number of drugs administered. The use of psychotropic medications is very high in elderly individuals, especially in residents of nursing homes. A lot of the clinically relevant DDI involve a psychotropic drug. Besides, their medical care implies multiple professionals from different specialties and psychotropic drugs may interact with other prescribed medications used to treat concomitant medical illnesses. Moreover, the amount of time dedicated to their attention is usually insufficient. All these circumstances extremely complicate the possibility to detect DDI while prescribing. This is the reason why we consider electronic programs an indispensable help for this task. Anyway, physicians should have a basic knowledge of the main mechanisms implicated in DDI and of those DDI clinically relevant.

The number of elderly people is rapidly growing all over the world. The use of drugs in this age group is risky due to physiological changes associated to the aging process and the potential interactions. 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 and high risk drugs is an important, simple and effective strategy to reduce the problems associated with medication in the elderly. A compromise between the principles of evidence-based medicine and good gerontological practice is required. Different strategies have been developed to help reduce potentially inappropriate prescribing. Regular and systematic review of treatment, patient education, collaboration with the pharmacist, the use of electronic aids and tools like Beers or STOPP-START criteria are strategies to help reduce potentially inappropriate prescribing of our elders.

The overall consensus is that elderly psychiatric patients are more prone to develop adverse drug reactions than younger patients as a consequence of psychopharmacological medication. Elderly persons with psychiatric disorders frequently suffer from somatic diseases and may receive polypharmacy more than younger patients. Thus, they may tend to develop adverse drug reactions more frequently. In addition, 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 a) Identifying the adverse effects of medications.and b) Reporting them in order to always maintain a favourable risk-benefit balance.

Anxiolytics are a group of drugs which currently is comprised of benzodiazepine compounds, buspirone, antihistamines as hydroxyzine, some anticonvulsants and chlormethiazole. Hypnotics, in turn, include some benzodiazepines, the so-called “z-agents” and other compounds like melatonin and ramelteon and sedative antidepressants. Even though they are a relatively 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.

Mood stabilizers are those drugs used to treat and prevent acute episodes of bipolar disorder. The concept includes a host of agents: lithium, several anticonvulsants, and antipsychotics, notably, second-generation compounds. This chapter reviews the different drugs labelled 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. 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, a population characterized by pharmacokinetic and pharmacodynamic changes, and frailty. Clozapine, the gold standard antipsychotic, is probably the most difficult to use, but with a judicious use it can be safe and effective 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 tranquillizers” they once were meant to be. On the other hand, antipsychotics pose serious risks to elderly, fragile patients with dementia. As a result, treating dementia with antipsychotics could be a case in point of an irrational use of drugs. The chapter reviews untoward effects linked to antipsychotics when used in dementia and suggests some guidelines to make its use less irrational.

The prevailing psychotic symptoms in Parkinson’s Disease (PD) are hallucinations and delusions. Hallucinations are sensory phenomena that are not induced by physical stimuli, and occur in each sensory modality. Visual hallucinations are the most common psychotic symptoms in PD followed by auditory hallucinations. Before treating psychotic symptoms in PD, it is important to rule out an underlying medical illness as the cause of the symptoms, like urinary and pulmonary infections, metabolic and endocrine imbalances, cerebral hypoperfusion states and psychosocial stressors. Antipsychotics medications lower brain dopaminergic transmission and can cause or worsen parkinsonism by diminishing dopaminergic transmission in the nigrostriatal pathways. Prior to the introduction of clozapine there was no effective treatment, 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, etc.

Substance use disorders (SUD) are under-recognized in the elderly. This chapter will discuss the drugs currently used for the treatment of SUD. For the sake of simplicity, clinical descriptions will be avoided and the focus will be placed almost exclusively on the drugs used to treat these conditions. Those are a heterogeneous group of agents with products exclusively or mainly used to treat SUD and other compounds and agents used in other indications. 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 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 for 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.