Psychotropic Medication Use in the Elderly



Fig. 22.1
Features and problems encountered in old age



High levels of potentially inappropriate prescribing of psychotropic medicines, in particular antipsychotics and sedatives, continue to be highlighted in Australia, especially in the oldest patients [1115].

Older adults are especially vulnerable because they often have multiple disease states and require the use of more drugs, to which must be added factors such as the specific physiological changes of aging, genetic constitution, and diet, which can alter the response to drugs, increasing the predisposition to various adverse effects and drug interactions [16].

A study conducted in Italy shows that in nursing home residents, the high consumption of psychotropic drugs is of particular concern [17]. Meanwhile, another study in Sweden showed that the prevalence of medication use and polypharmacy among older adult women has increased dramatically; in particular, the use of analgesics increased significantly, whereas antipsychotics decreased [18].

Guidelines worldwide have cautioned against the use of antipsychotics as first-line agents to treat neuropsychiatric symptoms of dementia. Vasudev et al. [19] investigated the changes over time in the dispensing of antipsychotics and other psychotropic drugs among older adults with dementia living in long-term care facilities. They found that their use declined slightly over the study period, but atypical antipsychotics continued to be used at a high rate. The use of benzodiazepines declined, and the use of sedative and non-sedative antidepressants increased. Psychotropic polypharmacy continues to be highly prevalent in these patient samples.

Several clinical practice guidelines were published by French regulatory agencies between 2006 and 2009 to improve psychotropic drug use in older patients. Practice guidelines for psychotropic drug prescription were partially respected in older inpatients [20].

In Argentina, the most consumed psychoactive drugs are anxiolytics, antidepressants, and antipsychotics, which accounted for 75.3% of drugs for the central nervous system and 11.5% of all drugs dispensed in pharmacies in 2011; lorazepam, bromazepam, alprazolam, diazepam, clonazepam, and carbamazepine were the most dispensed [21]. On the other hand, in Buenos Aires City, 15.5% of the population currently consume some type of psychotropic drug, and 29.4% have consumed once in their life. The highest use is in women and the elderly population (12.2% of benzodiazepines and 3% of antidepressants). Finally, 25% of those who consume are considered to be highly dependent [22]. The reasons for increased consumption of psychotropic drugs are shown in Fig. 22.2.

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Fig. 22.2
The reason for increased consumption of psychotropic drugs

The drugs used in the elderly are very complex, especially for those who use different types of psychotropic drugs. For these reasons, our objective is to describe some aspects related to the use of psychotropic drugs in the elderly, and to suggest possible measures to improve the situation.



Psychotropic Drugs


A psychotropic medication is considered as one that has profound and beneficial effects on behavior, mood, and cognition, but often does not change the process of the underlying disease [23].

Psychotropic drugs are used therapeutically because they can affect the behavior and the subjective state of the person; however, there are other substances with a psychotropic action, such as alcohol, nicotine, cocaine, and heroin, which are characterized by social or addictive uses, and do not have any recognized therapeutic applications in Western medicine. Finally, painkillers and other drugs also have effects on subjective state and behavior, but are not considered as psychotropic drugs because their principal use is not related with their psychoactive effects [24].

Psychotropic is used to describe any natural or synthetic compound that is capable of influencing the psychic functions by its action on the central nervous system, and psychotropic drugs, as a pharmaceutical product composed of psychotropic substances, used with the objective of treating a mental or neurological condition [25, 21]. Psychoactive drugs are substances that are primarily used to treat three types of alterations: schizophrenia and other psychoses, depression and mania, and the conditions produced by anxiety or excessive anxiety.

The drugs for anxiety which are most known and used are benzodiazepines, which increase the actions of the neurotransmitter γ-aminobutyric acid (GABA) involved in anxiety and in the action of many anti-anxiety drugs [26].

Antidepressants can be selective inhibitors of serotonin reuptake, tricyclic or inhibitors of monoamine oxidase. Antidepressants temporarily increase neurotransmitters such as serotonin and norepinephrine, either by inhibiting their degradation, or by blocking their reuptake [27].

The first antipsychotics, known as first generation or typical, act by blocking dopamine D2 receptors. The atypical antipsychotics present some cognitive benefits, probably derived from their action on the cortical prefrontal function mediated by receptors that are not dopaminergic [28].


Clasification of Psycothropic Drugs


Psychotropic drugs can be classified from the following points of view: pharmacological, clinical, clinical–chemical, legal, industrial, and chemical–structural. De Wet [29] classified them as psycholeptics, psychoanaleptics, and generators of psychotic disorders. Later, Velasco and Alvarez [30] classified them as psycholeptics or depressants, psychoanaleptics or stimulants of the psychic activity, and psychodysleptics or hallucinogens [21].

Psychotropic drugs belong to the N group of the Anatomical–Therapeutic–Chemical classification system [31], and are specifically included within the N05 and N06 groups, corresponding to the psycholeptics and psychoanaleptics respectively. In some countries, the opioid analgesics (N02a) are included, despite the fact that they are mainly used for pain treatment.

Psycholeptics have depressant effects on mental activity, and are commonly used to treat psychosis (antipsychotics) and anxiety disorders (anxiolytics). They include antipsychotics, anxiolytics, hypnotics, and sedatives.

In contrast, psychoanaleptics are stimulants of the central nervous system and mental activity, and are commonly used to treat depression and attention-deficit hyperactivity disorder. This group includes antidepressants, nootropics, drugs against dementia, and psychostimulants.


Medicalization, Conflicts of Interest, and Inappropiate Use of Psychodrugs


The way of understanding mental illness has changed. Now, some problems of adaptation to certain situations of everyday life, such as stress, insomnia, and depression, have become diseases to be treated with drugs. Drug use has been mainly extended to achieve personal well-being and social performance [32]. If psychotropic drugs are prescribed not for diseases, but for another kind of suffering, they are useless or act as placebos in most cases. This banal and excessive utilization is called medicalization of mental health, which is mainly caused by aggressive promotion by the pharmaceutical industry. The current globalization of health has transformed patients into real consumers of all types of health services. Of concern are the change of perception of health and disease, the increase in the misuse of the psychotropic drugs, and the adverse reactions that are produced by the inclusion of the elderly as target of medicalization [33].

A deeply rooted cultural problem in the West is to see old age as synonymous of illness, leading inevitably to the elderly becoming favorite targets of medicalization, particularly with psychotropic drugs. In this way, problems of everyday life such as sadness or anxiety have become diseases that can be treated with drugs such as anxiolytics or antidepressants.

The withdrawal reactions to second-generation antidepressant drugs (selective serotonin reuptake inhibitors, SSRIs) have started to be called discontinuation syndromes [34], a denomination that conveys a more harmless impression than the withdrawal reactions from other drugs such as benzodiazepines — despite the fact that discontinuation syndromes of SSRIs are nevertheless withdrawal reactions, and that benzodiazepines continue to be more effective and with fewer side-effects that the SSRIs [35]. Thus, SSRIs have replaced benzodiazepines in the treatment of anxiety disorders [36]. This change has probably been one of the more important successes of pharmaceutical promotion in psychiatry, with the full endorsement of guidelines and professional societies [37]. In this way, conflicts of interest have led us to “buy” the idea that SSRIs are better than anxiolytics for anxiety [38].


Aging and Comorbidities


Aging is associated with progressive decrease in the functions of multiple organs, presence of comorbidities, functional and social problems that lead to polypharmacy, and accidental or inappropriate use of drugs. Consequently, the elderly are very vulnerable to presenting adverse reactions, interactions, hospitalizations, mortality, and poor adherence to treatment.

At present, the elderly are the most rapidly growing population group in Western countries; and aging seldom comes alone, it is often accompanied by chronic diseases, comorbidities, disability, frailty, and social isolation. Multiple diseases inevitably lead to the use of multiple drugs, a condition known as polypharmacy [3941].

The process of aging involves a continuum of changes in biological, functional, psychological, and social parameters that vary depending on genetic factors, age-related vulnerability, and differences in organ function and reserves [4043].

Multimorbidity in the elderly has been estimated to range from 55 to 98% [44], and is highest in the very old, in women, and in individuals belonging to low socioeconomic classes [44, 45]. Nobili et al. considered that over the last 20–30 years, problems related to aging, multimorbidity, and polypharmacy have become a prominent issue in global healthcare [43].


Adverse Drug Reactions


The most serious side-effects in the older age group are caused by antiplatelet agents, diuretics, non-steroidal anti-inflammatory drugs, and anticoagulants, among others. The prevalence of adverse reactions to drugs has risen over recent decades in older people [4649].

Impaired physical functioning, delirium, and the increased risk of falls, cardiovascular events, and hospital admissions have been reported [5055].

The 84% of war veterans hospitalized for hip fracture had been taking at least one medicine that could increase the risk of falls or fracture, such as antihypertensive drugs (63%), antidepressants (29%), benzodiazepines (26%), and opioids (19%) [3, 56].

Among the side-effects of benzodiazepines, we can mention sedation and the impairments in attention, memory, and psychomotricity. In addition, with the continued use that is still being observed, side-effects such as confusion, irritation, and agitation have increased significantly due to lower tolerance in the elderly. There is also the possibility of occurrence of depressive states induced by benzodiazepines. It is very important to note that although benzodiazepines are very safe and effective in the treatment of anxiety in the short term, if their use is extended by more than 6 months can lead to tolerance and dependence [57].

The oral atypical neuroleptics, such as risperidone, quetiapine or olanzapine bring an increased risk of hospitalization with acute kidney injury within the 90 days after they were prescribed in older patients. Likewise, hypotension, acute urinary retention, pneumonia, myocardial infarction, and ventricular arrhythmia are adverse effects that can lead to kidney injury and increase the risk of mortality [58].

The high usage rate of anxiolytics that has been found in patients with hip fractures may indicate that this is a risk factor for hip fractures related to falls in elderly patients [59].

Jacquin-Piques et al. [60] compared the type and number of psychotropic drugs prescribed in elderly nursing home residents with dementia with those in community-living patients. A significant association between living in a nursing home and the more frequent prescription of anxiolytics, hypnotics, and antipsychotics, with a greater number of psychotropic drug classes prescribed was found, whatever the severity of the dementia. Psychotropic drugs are frequently prescribed in nursing homes, despite the contrary was expected, because nursing home residents may have more and better psychosocial interventions than patients living at home.

An association between the incidence of diabetes mellitus and the use of antipsychotic therapy has been proven. The use of atypical antipsychotics has a stronger association than the use of typical antipsychotics. From all the antipsychotics, clozapine followed by olanzapine appear to be the atypical neuroleptics most closely related to metabolic syndrome and diabetes. This metabolic dysregulation appears to be multifactorial in origin, and the result of pharmacological, environmental, and genetic interactions [61].

Typical antipsychotics are associated with a higher incidence of extra-pyramidal dysfunctions such as tremor, parkinsonism, akathisia, neuroleptic malignant syndrome and tardive dyskinesia. They produce also a higher incidence of central anticholinergic effects such as poor attention, impaired memory, and behavioral problems. Furthermore, they can induce urinary retention, nausea, constipation, diarrhea, cholestasis, increase of transaminase enzyme activity, weight gain, and diabetes mellitus. In the case of patients suffering epilepsy, these drugs may facilitate convulsions. The main cardiovascular effects are the orthostatic hypotension that can increase the risk of falls, and possible arrhythmias.

Among the atypical antipsychotics, clozapine is associated with sedation, confusion, and agranulocytosis, with resultant requirement of regular monitoring of blood counts. Risperidone induce extrapyramidal symptoms at low doses in older patients, particularly those with pre-existing dementia. The most frequent adverse effects of olanzapine are weight gain, hypotension, constipation, somnolence, and dizziness. The common side-effects of quetiapine include sedation, headache, and orthostatic hypotension [62].

Falls cause significant morbidity and mortality in old age, but happen at all stages of life. For this reason, two meta-analyses were performed to determine the relationship between psychopharmacological treatments and the risk of falls in people over 60 years. In both studies, the existence of an increased risk of falls associated with the use of antipsychotics, antidepressants, anxiolytics, sedatives, and benzodiazepines was found [63, 64]. Also, in this latest study, new associations between non-steroidal anti-inflammatory drugs, opioids, and risk of falls were identified. Among these psychotropic drugs, short- and long-acting benzodiazepines, analogues Z (zolpidem, zoplicone), antipsychotics, and antidepressants, alone or in combination with antihypertensive, anti-arrhythmic, and other cardiovascular medicines, have also been shown to facilitate falls [6567].

A longitudinal study examined the dispensing of psychotropic medications in Australia from 2000 to 2011. A 58.2% increase in the dispensing of psychotropic drugs was found. The major increases were in antidepressants (95.3%), atypical antipsychotics (217.7%), and ADHD medications (72.9%). Valproate and lamotrigine also increased markedly. The anxiolytics and lithium remained unchanged, while sedatives and typical antipsychotics decreased by 26.4% and 61.2% respectively. Antidepressants accounted for 66.9% of total psychotropics, far greater than anxiolytics (11.4%), antipsychotics (7.3%), mood stabilizers (5.8%), sedatives (5.5%), or ADHD medications (3.0%) [68].

Psychotropic drugs, benzodiazepines, tricyclic antidepressants, and antipsychotic medications are frequently prescribed and are of high risk in older adults. Anxiolytics produce excessive sedation, decreased alertness, confusion, ataxia, falls, and hip fractures. Some symptoms of dementia, such as memory problems, may be worsened. Additionally, an inappropriate use of these drugs may increase mortality. Lack of response to treatment and anticholinergic effects are manifested with the antidepressants. Antipsychotics produce limited benefit, and risk of mortality and stroke.


Polypharmacy and Interactions


The prescription and use of multiple drugs to deal with multiple concomitant diseases is known as polypharmacy [6971]. Moreover, the high prevalence of polypharmacy with aging may lead to an increased risk of inappropriate use of drugs, under-use of effective treatments, medication errors, poor adherence, different interactions, and adverse drug reactions [7277]. The latter is related to the fact that elderly people are frailer and highly sensitive to pharmacotherapy, as a consequence of their changes in pharmacokinetic and pharmacodynamic parameters [78, 79]. Polypharmacy is an important risk factor for inappropriate medication prescribing, which is very frequent among elderly people [73, 80].

Moreover, polypharmacy is often the consequence of a prescribing cascade, which is caused by failure to recognize a new medical event as an adverse drug reaction [81, 82]. In this case, another drug is unnecessarily prescribed to treat the adverse event instead of withdrawing the responsible drug, creating a vicious circle and adding further risks [43].

In elderly people, polypharmacy has been associated with many adverse clinical outcomes, such as drug interactions and adverse drug reactions, disability and cognitive impairment, falls and fractures, malnutrition, hospitalization and institutionalization, mortality, and rising healthcare costs [73, 75, 8394].

Polypharmacy in psychopharmacology is very important, although clinical guidelines advise otherwise. This is a result of increase of the primary drug, prevention of adverse reactions from the main medication, and treatment of comorbidities [95].

Drug–drug interactions may or may not be clinically significant. Clinically significant drug–drug interactions are events in which the pharmacodynamic or pharmacokinetic characteristics of a drug are modified by the aggregate of another drug, which can often increase serious adverse reactions or attenuate the efficacy of the first drug [96, 97].

Pharmacodynamic drug–drug interactions occur when concomitantly administered medications share similar target sites of action, producing either an additive or an antagonistic effect that can respectively enhance or weaken the physiologic effect of the primary drug [96, 98]. Clinically significant pharmacodynamic interactions can produce extrapyramidal symptoms, central nervous system depression, seizures, serotonin syndrome, and QT-interval prolongation [98, 99].

Pharmacokinetic drug–drug interactions are modifications of absorption, distribution, metabolism, and elimination of a drug by the addition of a second drug, increasing or decreasing the serum concentration of the primary drug; these interactions are often difficult to predict [100]. In these interactions, the drug absorption often changes as result of psysico-chemical changes in the primary drug, leading to decreased absorption [99, 101]. Additionally, transport of a large number of drugs across the intestinal wall are regulated by transporter proteins; principal among these is P-glycoprotein, which may play a significant role in determining blood concentrations and bioavailability of many drugs [99, 102]. Inhibition of P-glycoprotein by drugs such as verapamil result in decreased translocation of the drug back into the intestinal lumen, and a subsequent increase in systemic exposure of the drug, leading to a potential increase risk in adverse effects or enhanced efficacy [103].

Drug–drug interactions involving changes in drug distribution process a theoretical risk due to differences in protein affinity and displacement from the drug of its binding proteins [96]. While interactions involving drug displacement of their plasma-binding protein can result in elevation in plasma concentrations of the displaced drug, the clinical significance of these interactions is limited, since displacement from binding proteins results in an increase in unbound plasma concentrations, facilitating increased metabolism and clearance of the displaced drug [104].

Of the many interactions with psychotropic drugs, a minority are potentially hazardous. Most interactions are pharmacodynamic, resulting in augmented or antagonistic action at a receptor for different mechanisms in the same tissue. The most important pharmacokinetic interactions are due to effects on metabolism or renal excretion. The major enzymes involved belong to the cytochrome P450 system. Genetic variations in the CYP system produce poor, extensive or ultra-rapid metabolisers. The most frequent hazardous interaction results from enzyme inhibition, but the probability of interaction depends on the initial levels of the enzyme activity and the availability of an alternative metabolic route of elimination of the drug. The most serious interactions with psychotropic drugs result in profound sedation, central nervous system toxicity, large changes in blood pressure, ventricular arrhythmias, an increased risk of dangerous side-effects, or a decrease in therapeutic effects of one of the interacting drugs [105].

The number of psychotropic drugs has expanded tremendously over the past few decades, with a proportional increase in drug–drug interactions. The majority of psychotropic agents are biotransformed by hepatic enzymes, which can lead to significant drug–drug interactions. Most drug–drug interactions of psychotropics occur at the metabolic level, involving the hepatic cytochrome P450 enzyme system [106].

Moreover, among the elderly population interaction between some SSRI antidepressants, especially fluvoxamine, and medication for the prevention of cardiovascular or cerebrovascular accidents, such as statins (atorvastatin, simvastatin or lovastatin), can produce effects adverse such as myopathy [107]. Antipsychotic drugs are used mostly for the treatment of behavioral and psychological symptoms in delirium cases. The increased mortality in elderly patients with dementia who receive antipsychotics suggests exercising caution before prescribing antipsychotics to treat delirium [10, 108].


Conclusions

Taking into account the findings exposed previously, some reflections and proposals to achieve an adequate use of psychotropic drugs in older people are presented in conclusion. The proposals are summarized in Table 22.1.


  1. 1.


    The risks associated with the inadequate use of groups of psychotropic drugs in this population group should be taken into account before prescribing. For this reason, it is necessary to improve the competence of physicians with regard to use and misuse of psychoactive drugs.

     

  2. 2.


    Health professionals should contribute to the reduction of prescription and excessive and unnecessary consumption of psychotropic drugs in older patients, promote de-prescription, encourage patients to face their difficulties without the help of medication, and search for other solutions, such as the adoption of hygienic–sanitary measures, reducing both health costs and risks to patient health.

     

  3. 3.


    The continuing and high use of benzodiazepines and the rapid increase in the consumption of serotonin/noradrenaline reuptake inhibitors, despite their side-effect profile, and the dramatic increase in antidepressant prescriptions, despite doubts about their efficacy in mild to moderate depression, are very worrying and require the attention of all members of the health system.

     

  4. 4.
Oct 20, 2017 | Posted by in PSYCHIATRY | Comments Off on Psychotropic Medication Use in the Elderly

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