Geriatric Psychopharmacology

An elderly person is likely to experience many socioeconomic, emotional and physiological changes which will have a major bearing on psychotropic drug treatment. Such a population is therefore more likely to be exposed to more types of drug treatment than younger age groups.

It is found that the vast majority of elderly patients being treated for a psychiatric disorder also have at least one physical disorder that requires medication; 80% of all elderly patients have at least one chronic physical illness. Thus the elderly are the most likely group to experience adverse drug reactions and interactions. Studies show that patients over the age of 70 years have approximately twice as many adverse drug reactions as those under 50 years. Another problem which particularly affects the elderly population concerns compliance with prescribed medication. Factors such as impaired vision, making it difficult for the patient to recognize the various medications, hearing, manual dexterity and cognition all contribute to the non-compliance. Perhaps one of the most important factors that governs non-compliance is the increased frequency and severity of the side effects that occur with most types of medication in the elderly. This may be illustrated by the tricyclic antidepressants and phenothiazine neuroleptics, both these classes of drugs having pronounced antimuscarinic activity even in the physically healthy young patient. In the elderly there is evidence of excessive sensitivity to the anticholinergic effects of drugs. This is compounded by the decline in cognitive function which accompanies ageing. Thus one must anticipate that patient compliance for any psychotropic drug with pronounced anticholinergic and sedative side effects will be low. Another problem which can compromise compliance concerns the hypotensive actions of many psychotropic drugs (e.g. tricyclic antidepressants, phenothiazine neuroleptics). Due to the alpha1 receptor antagonistic action of these drugs, they are likely to cause severe orthostatic hypotension in some elderly patients. This can cause patients to fall and damage themselves. The increased sensitivity of the elderly to the sedative effects of drugs is also well known. As hypnotics and anxiolytics are frequently administered to the elderly, the sedative effects of these drugs can be minimized by using drugs that have a short to medium half-life. There seems little justification for using the long half-life sedative hypnotics in the elderly patient.

Dementia
The pathological and clinical features of the various types of dementia. A variety of conditions that occur in the elderly must be differentiated from true dementia. Delirium, for example, is associated with an alteration in the level of consciousness, disordered thinking and fluctuating cognitive impairment. Such a delirious state can occur for a variety of reasons, including inadequately treated diabetes, hyperparathyroidism or hepatic encephalopathy. Dementia must also be distinguished from psychosis, in which the patient shows impairment of thinking but not impairment of memory. The term ‘‘pseudo-dementia’’ is often used to describe a depressive episode in which the patient presents with abnormalities of mood, appetite and sleep disturbance with cognitive dysfunction which is directly caused by the depression. The cognitive deficits usually resolve with treatment of the underlying condition. Finally cerebrovascular disease or carotid occlusion may be associated with episodic memory loss. It is therefore important to diagnose correctly the cause of the memory and cognitive impairment so that appropriate treatment may be given. Should the results of clinical and neurological investigation clearly establish the existence of Alzheimer’s disease, then the appropriate symptomatic therapy (e.g. a cholinesterase inhibitor) may be considered.

Pseudodementia
This is defined as any condition which mimics dementia. The commonest psychiatric disorder which mimics dementia is depression in which the retardation can be confused with the apathy of dementia. The guiding principle is careful clinical assessment and, if in doubt, a trial of an appropriate antidepressant.

Depression
A disturbance in the sleep pattern is a common symptom of depression but changes in the sleep pattern also occur as a consequence of ageing. Once depression has been diagnosed, there are several types of antidepressants which may be given. Because of their potent anticholinergic side effects, there seems little merit in prescribing the older tricyclic antidepressants (e.g. amitriptyline, imipramine) to such patients. There is now sufficient evidence to suggest that sedative antidepressants such as mianserin or trazodone given at night reduce the likelihood that the patient will require a sedative hypnotic. For the more retarded elderly patient, a non-sedative antidepressant such as lofepramine or one of the SSRIs (e.g. fluoxetine, fluvoxamine or sertraline) may be used. The side effects and cardiotoxicity of the tricyclic antidepressants have been discussed in detail elsewhere in this volume and, while there is ample evidence of their therapeutic efficacy, it seems difficult to justify their use, particularly in a group of patients who are most vulnerable to their detrimental side effects. Of the newer antidepressants, the reversible inhibitors of monoamine oxidase type A such as moclobemide may also be of value in the elderly depressed patient, particularly in those patients who fail to respond to the amine uptake inhibitor type of antidepressant. The safety of antidepressants should be the first priority for the elderly. For this reason, the second-generation antidepressants, or the atypical tricyclic antidepressant lofepramine, should be the drugs of choice. Undoubtedly the SSRI antidepressants have a major role to play and of these, citalopram and fluvoxamine have been extensively studied in the elderly depressed patient. It should also be remembered that electroconvulsive therapy (ECT) can be potentially life-saving in the elderly, particularly if the patient is suffering from delusions or is retarded and depressed. ECT should also be considered when antidepressant drug treatment has failed.


Psychosis
A variety of psychotic conditions occur in the elderly, but it is important to remember that an elderly person who develops agitation, paranoid ideation or delusions may be suffering from a drug-induced delirium. The most common causes of such a condition are drugs that have potent central muscarinic-blocking properties, such as the antiparkinsonian agents, antihistamines, tricyclic antidepressants and antipsychotics. Withholding all psychotropic drug medication for a few days may be the most judicious management for this type of toxic psychosis. Agitation and aggression are often symptoms of advanced Alzheimer’s disease and high potency atypical antipsychotics such as risperidone or olanzapine may be of value in demented patients. Drugs such as chlorpromazine and thioridazine are more likely to produce hypotension, cardiac abnormalities and excessive sedation in the elderly patient, and side effects are, of course, a problem with the high potency neuroleptics in the elderly; centrally acting anticholinergic agents that are used to reverse some of the symptoms of parkinsonism in such patients should be used as little as possible and in the lowest possible doses. Mania can occur in any age group. Acute manic episodes in the elderly may best be managed with high potency neuroleptics. The use of lithium is not contraindicated in the elderly provided renal clearance is reasonably normal. The dose administered should be carefully monitored, as the halflife of the drug is increased in the elderly to 36–48 hours in comparison to about 24 hours in the young adult. The serum lithium concentration in the elderly should be maintained at about 0.5mEq/litre. It is essential to ensure that the elderly patient is not on a salt-restricted diet before starting lithium therapy. The side effects and toxicity of lithium have been discussed in detail elsewhere (see p. 198 et seq.), and, apart from an increase in the frequency of confusional states in the elderly patient, the same adverse effects can be expected as in the younger patient.


Paranoid disorders
According to DSM–IV, it has abandoned the terms paranoia and paraphrenia and replaced them with the term delusional disorder to describe non-affective and nonbizarre delusional states. Neuroleptics have been the group of drugs most widely recommended for delusional states. Of the first-generation neuroleptics, the sedative, cognitive impairing and extrapyramidal side effects are likely to be particularly prominent in the elderly. The introduction of the atypical neuroleptics should improve the treatment of these disorders as they are generally better tolerated due to their improved side-effect profile. TCAs, together with neuroleptics should be avoided as they may aggravate psychotic symptoms and potentiate any anticholinergic side effects. In the case of the very aggressive patient, parenteral administration of lorazepam or diazepam will usually be sufficient to enable the patient to be managed.

Anxiety and insomnia
Anxiety states are often expressed somatically in the elderly and therefore it is important to exclude any physical disorder, such as cerebrovascular disease and thyroid dysfunction, which can be associated with apprehension and agitation.

Most psychotropic drugs are highly lipophilic, and the increased fat to lean body mass ratio and the decreased metabolism and excretion in the elderly patient mean that the half-lives of most psychotropic drugs are increased. The benzodiazepine anxiolytics and hypnotics are no exception. Following a single dose of chlordiazepoxide, diazepam or flurazepam, the time for elimination of the parent compounds and their active metabolites can be as long as 72 hours. For this reason, it is now general practice to administer a short-acting benzodiazepine (e.g. oxazepam, alprazolam or temazepam) only as needed and for as short a period as possible. Such drugs should only be used for a period not exceeding 6 weeks. Supportive psychotherapy, either as an adjunct to drug therapy or as an alternative, has an important role to play in treating mild anxiety states in the elderly. Insomnia is a common complaint in the elderly. As people age they require less sleep, and a variety of physical ailments to which the elderly are subject can cause a change in the sleep pattern (e.g. cerebral atherosclerosis, heart disease, decreased pulmonary function), as can depression. Providing sedative hypnotics are warranted, the judicious use of short half-life benzodiazepines such as temazepam, triazolam, oxazepam and alprazolam for a period not exceeding 1–2 months may be appropriate. Because of their side effects, there would appear to be little merit in using chloral hydrate or related drugs in the treatment of insomnia in the elderly. It should be noted that even benzodiazepines which have a relatively short half-life are likely to cause excessive day-time sedation.


In addition to the benzodiazepines, there may be a role for the nonbenzodiazepine drugs such as zalaplon, zolpidem or zopiclone in the treatment of anxiety and insomnia in the elderly. These drugs appear to be well tolerated in younger populations of patients, but it is essential to await the outcome of properly conducted trials of these drugs on a substantial number of elderly patients before any conclusions may be drawn regarding their value as alternatives to the benzodiazepines.

Depression ,Bipolar Illness,Schizophrenia,Dementia

Depression
· severe illness may lead to homicide
· the depressed person is usually acting on delusions
· family member is usually the victim in altruistic homicides
· the killer often commits suicide afterwards
· sometimes associated with shoplifting
Bipolar Illness
· offending is more common than in depression
· manic patients may spend excessively, hire cars and fail to return them, or steal cars
· may be charged with fraud or false pretences
· prone to irritability and aggression, though any resulting violence is seldom severe
Schizophrenia
· more likely to commit non-violent as well as violent crimes
· minor offences more likely than serious offences
· most criminal behaviour followed the onset of schizophrenia, although crime is
frequently a result of personality difficulties and social incompetence
· risk of homicide is moderately increased in schizophrenia compared to the general
population
· violence in schizophrenics may be associated with any of:
· great fear and loss of self control associated with non-systematized
delusions
· systematized paranoid delusions of persecution
· irresistible urges
· instructions from hallucinatory voices
· unaccountable frenzy
· risk of violence is greatest where delusions are accompanied by strong affect, and
when the person has made efforts to try to confirm the truth of the delusions
Dementia
· 44% are mildly aggressive
· 10% severely aggressive
· association between offending and dyspraxia
Episodic dyscontrol syndrome (Bach-y-Rita et al. 1971)
· repeated unprovoked episodes of violence
· excluded epilepsy, schizophrenia, pathological intoxication, drug intoxication
· unexplained violence preceded by a sequence of aura, headache, and drowsiness
· 50 % reported amnesia for the episode
· 50 % have EEG abnormalities, usually in the temporal lobes

MOOD DISORDERS – DEPRESSION

MOOD DISORDERS – DEPRESSION
Although mood disorders have some symptoms in common, they are very different in terms of their prevalence and causes. Major depressive disorder, also called Unipolar depression, is one of the most common of these disorders, whereas bipolar disorder (also known as manic-depression), like schizophrenia, is less prevalent.
Both disorders often result in severe impairment. Symptoms of major depressive disorder The primary symptom of major depressive disorder is, not surprisingly,
a depressed or sad mood. Almost everyone experiences a sad mood some time in their life, but major depressive disorder goes much further than simply feeling sad. Other symptoms include:
Losing interest or pleasure in things that you usually enjoy
- an experience called anhedonia. psychosocial factors psychological, environmental and social factors that may play a role in psychopathology expressed emotion (EE) specific set of feelings and behaviours directed at people with schizophrenia by their family members % relapsing in 9–12 months High EE Low EE
100
90
80
70
60
50
40
30
20
10
0
Bipolar disorder
Alcoholism
Depression
Schizophrenia

Across many disorders, people who have family members who are high on EE are more likely to relapse than are people who have family members who are low on EE. Source: Adapted from Butzlaff & Hooley (1998); O’Farrell et al. (1998).n Changes in ppetite – some find nothing appealing and have to force themselves to eat, resulting in significant weight loss, while others want to eat more and gain a lot of weight.
n Changes in sleep habits – depressed people may be unable to sleep or want to sleep all the time. n A very low level of energy, extreme fatigue and poor concentration.
Depressed people have no motivation to do anything, often find themselves unable to get out of bed and unable to complete school or work assignments. They may move through their lives very slowly, feeling that even simple activities require too much energy. n Feeling very badly about themselves – low self-esteem, feeling worthless and blaming themselves for all that has gone wrong in their lives and the world. Depressed people tend to feel hopeless about the future and don’t believe they will ever feel better.
Major depressive disorder has negative consequences not only for how people feel about themselves and their future, but also for their relationships. During a depressive episode people tend to withdraw socially, feel insecure in relationships, elicit rejection from others and experience high levels of interpersonal conflict
and stress. Romantic, family and peer relationships all suffer.
Given their level of suffering, impairment and hopelessness, it is hardly surprising that depression is one of the biggest risk factors for suicide, with around 15 per cent of depressed people committing suicide (Clark & Goebel-Fabbri, 1999).
The course of the disorder Major depressive disorder follows a recurrent course. Although some people have isolated episodes, most experience multiple episodes of depression that may become more severe over time (e.g. Lewinsohn, Zeiss & Duncan, 1989). Mild forms of depressionwith just a few symptoms rather than full-blown major
depressive disorder can predict the onset of more serious depression later on (e.g. Pine et al., 1999). Although depression was once thought to be a disorder of adulthood, we now know that it affects people of all ages, including children (figure 15.9). In fact, the age of onset of majordepressive disorder is decreasing, and the rates of major depressive disorder in childhood and adolescence are ncreasing rapidly.
Early onset predicts a worse course of depression over time (e.g. Lewinsohn et al., 1994), so depression in childhood and adolescence is a serious problem that can lead to ongoing difficulties throughout life.
Causes of major depressive disorder and factors affecting its course 1 Genetic and biological factors Like schizophrenia, major depressive disorder can be genetically transmitted (e.g. McGuffin et al., 1996). As for biological factors, the current view is that no single neurotransmitter is associated with major depressive disorder.
Instead, it most likely involves dysregulation of the entire neurotransmitter system (Siever & Davis, 1991). Indeed, it may be the balance of various neurotransmitters that regulate mood. Major depressive disorder may also involve neuroendocrine dysfunction. Depressed people tend to have elevated cortisol levels (e.g. Halbreich, Asnis & Shindledecker, 1985). Cortisol is involved in regulating the body’s reaction to stress and becomes elevated under stress. This suggests that, physiologically, depressed people may be in a state of chronic stress and they are perhaps more reactive to stress than are non-depressed people (e.g. Gold, Goodwin & Chrousos, 1988). As we see in the next section, stress plays an important role in ulnerability to major depressive disorder.
2 Psychosocial factors Unlike schizophrenia, which almost certainly has a genetic and/or biological trigger, major depressive disorder can be caused by either genetic/biological or psychosocial factors.
One of the primary psychosocial factors is life stress, including significant negative life events and chronically stressful circumstances (e.g. Brown & Harris, 1989). Of course, many people experience stressful situations, but they don’t all become depressed, suggesting that a diathesis–stress process might be occurring.
Specifically, it may be the particular way we perceive and think about life tressors that leads to depression. Consistent with a cognitive model of sychopathology, people who think about life events in a pessimistic, dysfunctional way are more likely to get depressed than people who think about life events in an
optimistic way (e.g. Metalsky, Halberstadt & Abramson, 1987). Beck (1967; Beck et al., 1979) describes pessimistic ways of thinking about ourselves, the world and the future as cognitive distortions. Examples are viewing things in a black and white manner, focusing on and exaggerating negative aspects and minimizing our positive qualities. When people engage in cognitive distortions, like those below, to explain their life circumstances, they put themselves at risk for experiencing negative moods like depression:
All or nothing thinking – ‘I’m a total loser!’
Overgeneralization – ‘I’m always going to be a total loser!’
Catastrophizing – ‘I’m so bad at my job that I’m sure to fail, then I’ll get fired, I’ll be totally humiliated, nobody will ever hire me again, and I’ll be depressed forever!’
Personalization – ‘It’s all my fault that my sister’s boyfriend broke up with her – if I hadn’t been so needy of her attention, she would have spent more time with him and they would have stayed together!’
Emotional reasoning – ‘I feel like an incompetent fool, therefore I must be one!’
Similarly, Seligman and colleagues (e.g. Abramson, Seligman & Teasdale, 1978) suggest that people who are vulnerable to depression tend to offer internal, global and stable causal explanations for negative events (see also chapter 14). For example, if a date goes badly, reactions might include:
It’s all because of me (internal);
I always do the wrong thing (global); and
I’ll never have a proper boyfriend (stable).
Negative interpersonal circumstances are particularly likely to play a role in epression. Marital, family and peer relations are often troubled, and interpersonal forms of stress – such as relationships ending, conflicts and lack of supportive relationships – are consistently associated with depression (see Beach & Fincham, 1998; Davila, 2000; Hammen, 1991).

Interpersonal models of depression highlight how the disorder can be both a cause and a consequence of interpersonal problems.
For example, Coyne (1976) suggested that depressed people engage in behaviours that elicit rejection from others, and this rejection leads to further depression. Similarly, Hammen (1991) proposed that depressed people generate interpersonal stress
in their lives, which then makes them more depressed. It’s possible that, for some people, depression has its roots in childhood experiences (Cicchetti et al., 1994). An insecure attachment in childhood may set the stage for depression by putting children at a disadvantage in four important areas:
1. Low self-esteem puts them at risk for a pessimistic way of viewing themselves and the world.
2. Inability to successfully regulate their negative emotions leaves them unable to fend off feelings of depression.
3. Never having learned to cope well with stress, they may employ inappropriate strategies (such as keeping problems hidden or ruminating on them).
4. Negative views of others and learned dysfunctional ways of interacting with others (e.g. excessive dependence on, or complete avoidance, of others) puts them at risk for depression through the negative effect it has on their interpersonal relationships.

Symptoms of bipolar disorder
In bipolar disorder, depression alternates with periods of mania, which is virtually the polar opposite of depression. During amanic period, people feel euphoric or elated. And just as major depression isn’t the same as simply feeling sad, mania is not the same as simply feeling happy. Mania is characterized by these symptoms:
An excessively euphoric mood typically associated with a sense of grandiosity. Manic people feel unbelievably good about themselves, to the extent that they often believe they can do anything. And they frequently try to!
Engaging in many more activities than usual. This increase in activity often becomes excessive to the point of being dangerous. For example, manic people may go on shopping sprees, spend amounts of money that go well beyond their means, and incur enormous levels of debt. They may takeoff on a trip in their car, driving recklessly and leaving responsibilities behind. They may engage in frequent sexual indiscretions, putting themselves at risk for sexually transmitted diseases, pregnancy and relationship conflict.
A decreased need for sleep – even staying awake for days at a time.
High distractibility and poor concentration as the mind races with a million thoughts.
Speaking very quickly – others can barely get a word in during conversations.
The course of the disorder The most common onset for bipolar disorder is in early adulthood, but, like major depressive disorder, it can occur earlier. Bipolar disorder is a lifelong, recurrent disorder that can take a variable course. Although some people regularly alternate between mania and depression, the number of pisodes, their timing and their order can vary widely.
Bipolar disorder can be seriously debilitating, but with appropriate medication many sufferers live highly productive, normal lives between episodes.
Causes of bipolar disorder and factors affecting its course
1 Genetic and biological factors There is even more evidence of genetic transmission for bipolar disorder than for major depressive disorder (Gershon, 1995).
There is also evidence of dysfunction of various neurotransmitters, including serotonin, dopamine and norepinephrine, although it may not be the levels of eurotransmitters themselves that are problematic, but the pattern of neuronal firing. Sodium ions are critical in proper neuronal firing (see chapter 1), and lithium, which is used to treat bipolar disorder, is chemically similar to sodium, so lithium may work by regulating dysfunctional neuronal firing (e.g. Goodwin & Jamison, 1990).
2 Psychosocial factors Like schizophrenia, there is no evidence that psychosocial factors are the initial cause of bipolar disorder.
But they do influence the course of the disorder. Stressful life events, articularly those that disrupt social and biological regularities (e.g. birth of a child, change in work hours, travel), may lead to relapse (see Johnson & Roberts, 1995). Negative social relations may also lead to relapse. In particular, sufferers with high EE families are more likely to relapse (Miklowitz et al., 1988)