Ageing is associated with a series of physiological changes that significantly alter the fraction of an ingested drug available for a psychoactive effect. Drug absorption shows little variation with age, despite changes in gastrointestinal motility and acidity, reduced absorption surface and slowed gastric emptying. However, once absorbed, the volume of distribution in an elderly subject is likely to have changed.

Ageing results in an increase in percentage body fat and a fall in total body water. Hydrophilic drugs, such as alcohol, are distributed in body water, such that with increasing age the volume of distribution falls and the peak concentration for a given dose may rise by 20%⁷, resulting in lower levels of intake giving the same intoxicant effect. Conversely, lipophilic drugs, such as benzodiazepines and other psychotropics, that are stored in fatty tissue will remain in the body for longer but at lower peak concentrations. A fall in plasma albumin in old age results in increased bioavailability of protein-bound drugs, such as warfarin and diazepam.

Drug elimination occurs primarily through direct excretion or metabolism. Both routes are reduced in the elderly. Glomerular filtration rates fall steadily in old age, leading to the accumulation of renally excreted drugs. This may be compounded by renal damage due to drug misuse, e.g. analgesic abuse⁸. Hepatic metabolism is impaired due to a loss of liver mass and a reduced blood flow, which may also be compounded by toxic drug effects. The efficiency of microsomal oxidation also falls with age, leading to reduced drug excretion of hepatically metabolized drugs⁹. The combination of these effects may greatly alter pharmacokinetics in the elderly. For example the half-life of diazepam in the very elderly has been shown to be over 3 days, compared with 20 h in a younger subject¹⁰.

Multiple drug use complicates the pharmacokinetics of a substance, due to competition for binding sites and metabolic pathways. Polypharmacy may have different effects, depending on whether it is acute or chronic. Alcohol will inhibit microsomal enzyme activity in acute use, while prolonged administration will induce the same enzymes. Hence, alcohol will acutely raise concentrations of benzo-diazepines, while lowering them if used chronically¹¹.

Pharmacodynamics also alter in the elderly. Sensitivity to drugs, particularly those acting on the central nervous system, tends to increase, while drug receptor populations also change with increased age. The particular effects of age-related brain changes on the reward effects of abused substances is currently difficult to predict¹².

As a consequence of all these variables, the extrapolation of a drug’s effects in the elderly, based on observation in younger adults, is foolhardy.

The terms ‘old age’ and ‘substance misuse’ are both terms that have a wide range of meaning to different readers. The current literature is based primarily upon chronological age banding of individuals, as opposed to banding by overall health, possibly a more valid measure. Definitions of substance misuse are similarly varied. Often in transgenerational studies, definitions of caseness are set at a level to prevent false-positive reports for younger adults. In older age groups, where less of a substance may have a greater effect, there is the possibility of missing cases if such standards are applied.

The elderly may display harmful use of any psychoactive substance. However, access to a potential substance of abuse is key to determining what an individual may misuse. Alcohol is obtainable with ease in most industrialized nations and is a socially acceptable and accessible psychoactive drug. Sedatives, hypnotics and analgesics are easily accessible through prescription and consequently, along with alcohol, are responsible for the majority of cases of harmful use. Over-the-counter medication is also easily obtained and may be misused. Illicit drugs are usually only available in potentially dangerous environments from individuals who may pose a significant risk to vulnerable older adults. Illicit drug use is therefore not commonly observed in the elderly, but numbers are on the rise¹³. Shah and Fountain identified the following as factors associated with illicit drug use in the elderly: male gender, ‘young old’ age group, belonging to the post-war cohort, African American ethnicity, prior convictions, diagnosis of mental illness or alcohol misuse, serious medical illness and past history of substance misuse with onset before age of 30¹⁴.

Benzodiazepines replaced barbiturates as the mainstay of pharmacological interventions in both anxiety and sleep disturbance. Benzodiazepines accumulate more readily in the elderly due to changes in body composition, leading to a greater volume of distribution for lipophilic drugs¹⁰. Chronic use may contribute to toxic effects, including cognitive impairment, poor attention and anterograde amnesia, cerebellar signs such as ataxia, dysarthria, tremor, impaired coordination and drowsiness¹⁵. Increased falls and hip fractures are associated with benzodiazepine use in the elderly¹⁶ while withdrawal may be accompanied by rebound insomnia, agitation, convulsions and an acute confusional state. If benzodiazepines are required for the elderly then short-acting drugs (i.e. with half-life less than 24 hours) at the lowest effective dose may be used for a short duration¹⁷. There is no ‘safe’ period of use but tolerance and dependence levels increase with prolonged use¹⁸.

Prevalence of Benzodiazepine Use

Establishing levels of benzodiazepine among the elderly is problematic. National prescription audits can reflect trends in use but are unhelpful when considering particular population subgroups.

Following the publication of guidance for the appropriate use of benzodiazepines by the UK Committee on Safety of Medicines (CSM) in 1988¹⁹, prescribing of benzodiazepines has fallen dramatically. In England and Wales prescriptions have fallen by 32% from 1987 to 1996²⁰, while prescribing of benzodiazepines by general practitioners in England has fallen from 15.8 million prescriptions in 1992 to 12.7 million in 2002²¹. Of concern, however, is that 30% of prescriptions were for long-term treatment and 56% of prescriptions for the three most commonly prescribed benzodiazepines were issued to patients over the age of 65²¹. More recent trends for England show a relatively stable annual prescription rate of 10 million items for hypnotics; however, Z drugs (zopiclone, zolpidem, zaleplon) appear to be responsible for a larger proportion of prescriptions, rising from 33% in 2001 to 44% in 2004²².

A community follow-up study of 5 000 over-65s in Liverpool²³ revealed that 10% were using benzodiazepines on first assessment and that of these some 70% were taking a benzodiazepine two years later. A further four-year follow-up revealed that 69% of these were still on benzodiazepines. Women were twice as likely to be taking a benzodiazepine as men at any stage in the study. In the USA, a study found 6.3% of a large sample of over-65s used a hypnotic, one third of these daily and nine tenths for at least a year²⁴. Five-year follow-up found 46.6% still using hypnotics, but with a switch away from barbiturates and longer-acting benzodiazepines towards short-acting ones²⁵.

Use of benzodiazepines in institutional samples has traditionally been higher and associated with female gender, greater age, bereavement and poor health²⁶. Chronic benzodiazepine use in older adults’ nursing homes has been associated with depression, sleep disturbances and demand for medication²⁷. In the USA a study found that one quarter of nursing home residents were prescribed a benzodi-azepine and nearly 10% of all residents had chronic benzodiazepine use²⁷. Studies from other countries reveal similarly high levels of benzodiazepine use among institutionalized older adults²⁸.

The level of morbidity among institutional residents is likely to be higher than community-dwelling elders. While chronic pain may require treatment with dependence-inducing medication, there are few indications for long-term benzodiazepine use. It has been argued that the regular use of benzodiazepines in institutions is a form of behavioural control, used more for the benefit of staff and others than these users. In many cases, the individual may be incapable of giving valid consent to taking such medication. The use of medication in such circumstances may be considered benzodiazepine misuse by some and as elder abuse by others²⁹.

Correlates

Psychiatric morbidity

Significantly high rates of psychiatric disorder have been described among elderly benzodiazepine users³⁰. Among elders using short-acting benzodiazepines as hypnotics, one third reach caseness for depression, while a further third have a diagnosable anxiety disorder. Among users of anxiolytic benzodiazepines, half are depressed and one fifth are anxious in spite of treatment. As with alcohol misusers, one third of elders requiring inpatient treatment for benzodiazepine misuse are of late onset, while two thirds have graduated from misusing benzodiazepines or other drugs while younger³¹. The incidence of co-morbid alcohol abuse has not been consistently shown to be significantly greater among benzodiazepine misusers³¹. However, more recent research suggests that a prior history of alcoholism may predispose to later benzodiazepine misuse in the elderly³². An all-age study found that DSM-III-R Axis I co-morbidity existed in all cases of a sample of benzodiazepine-dependent users in Spain³³. The commonest diagnoses were insomnia, anxiety disorders and affective disorders. Obsessive–compulsive, histrionic and dependent personality disorders were found in half of the cases and physical problems in one third of the cases.

Gender and age

Benzodiazepine use is over-represented among women of all ages. The likelihood of use of a benzodiazepine increases with age. There is little evidence that this gender divide narrows on reaching old age. Legislative approaches and prescribing guidelines have made some inroads into the over-representation of prescribing to the elderly³⁴. Increasing public awareness of the side effects of benzodiazepines and an increase in advocacy services for the elderly are likely to have a similar effect.

The elderly routinely receive a wide variety of medications, the majority of which may be misused. One quarter of prescription drugs sold in the United States are used by the elderly often for conditions such as chronic pain, insomnia and anxiety³⁵. Ten per cent of over-64s are on prescribed analgesics at any one time, with at least an equal number using over-the-counter medication. Edwards and Salib³⁶