Benzodiazepine in the elderly

Shorr RI, Robin DW. Rational use of benzodiazepines in the elderly. Drugs Aging 1994 4 9-20. 

Saizman C, Shader Rl, Greenblatt DJ, et al. Long vs. short half-life benzodiazepines in the elderly. Arch Gen Psychiatry 1983 40 293-297. 

Greenblatt DJ, Shader Rl. Benzodiazepines in the elderly pharmacokinetics and drug sensitivity. In Saizman C, Lebowitz BD, eds. Anxiety in the eideriy. Treatment and research. New York Springer, 1991. 

Petrovic M, Mariman A Warie H, et al. Is there a rationale for prescription of benzodiazepines in the elderly Review of the literature. Acta Clin Belg. 2003 58 27-36. 

These differences may become particularly germane if co-prescribing with some antipsychotics is undertaken. For example, in certain individuals, combinations of clozapine with benzodiazepines may lead to unexpected adverse events, including delirium and augmented respiratory depression (Jackson, Markowitz Brewer-ton, 1995 Grohmann et al, 1989). Presumably if there are additive or synergistic effects of ethnicity on clearance of one or both substances, adverse events may be enhanced. Similar interactions are theoretically possible with olanzapine, as adverse interactions have been described between olanzapine and benzodiazepines, at least in the elderly (Kryzhanovskaya etal, 2006). 

Zolpidem, chemically unrelated to benzodiazepines or barbiturates, acts selectively at the y-aminobutyric acidA (GABAA)-receptor and has minimal anxiolytic and no muscle relaxant or anticonvulsant effects. It is comparable in effectiveness to benzodiazepine hypnotics, and it has little effect on sleep stages. Its duration is approximately 6 to 8 hours, and it is metabolized to inactive metabolites. Common side effects are drowsiness, amnesia, dizziness, headache, and GI complaints. Rebound effects when discontinued and tolerance with prolonged use are minimal, but theoretical concerns about abuse exist. It appears to have minimal effects on next-day psychomotor performance. The usual dose is 10 mg (5 mg in the elderly or those with liver impairment), which can be increased up to 20 mg nightly. Cases of psychotic reactions and sleep-eating have been reported. 

There is an association between falls and hip fractures and the use of long-elimination half-life benzodiazepines thus, flurazepam and quazepam should be avoided in the elderly. 

The consequences of benzodiazepine use in the elderly may be severe. Benzodiazepines are common in drug poisoning suicides in the elderly (Carlsten et al. 2003). This is especially apparent for the hypnotics flunitrazepam and nitrazepam. Benzodiazepines are also associated with an increased risk of motor vehicle crashes in the elderly (Hebert et al. 2007). 

Lechin et al. 1996, Gray et al. 1999), but also increases the risk of falls and hip fractures (Passaro et al. 2000, Ray et al. 2000, Wang et al. 2001). Daily dose and longer duration of benzodiazepine use is associated with higher risk of fracture (van der Hooft et al. 2008). These fractures lead to great hospitalisation costs. In a European study it was estimated that costs of accidental injuries related to benzodiazepine use in the EU are between Euro 1.5 and Euro 2.2 billion each year. More than 90% of these costs were in the elderly with fractures as the major contributor (Panneman et al. 2003). 

The use of benzodiazepines should be avoided. There are other safer pharmacological alternatives. Benzodiazepine withdrawal may play a role in the occurrence of delirium in the elderly. Other withdrawal symptoms include tremor, agitation, insomnia and seizures (Turnheim 2003). Thus, when there is long-term use of benzodiazepines abrupt discontinuation might be difficult. Discontinuation should however not be withheld but done slowly and step-wise. If benzodiazepines are used in the elderly, short-acting benzodiazepines such as oxazepam are preferred, because they do not accumulate in the elderly to the same extent (Kompoliti and Goetz 1998). If short-acting benzodiazepines are used they should be prescribed with caution, at low doses, and for short periods. As with all pharmacotherapy the effects should be evaluated. Benzodiazepines are sometimes used as a behavioural control. One should always ask if this use is for the benefit of staff or the benefit of the patient. The presence of staff may be sufficient for behavioural control. 

Wang PS, Bohn RL, Glynn RJ et al. (2001) Hazardous benzodiazepine regimens in the elderly effects of half-life, dosage, and duration on risk of hip fracture. Am J Psychiatry 158(6) 892-898... 

Contraindication are myasthenia gravis, chronic obstructive pulmonary disease and severe hepatic disease. Both in the elderly and in children paradoxical reactions were described. In the elderly the use of benzodiazepines is strongly correlated with falls and hip fractures. 

For those with a history of substance abuse or intolerance to benzodiazepines and the elderly, caution must be used in controlling anxiety. In these cases, benzodiazepines may exacerbate other conditions. Preliminary reports suggest that antipsychotics such as quetiapine may alleviate symptoms of anxiety. Other strategies include use of antihistamines such as hydroxyzine and diphenhydramine. 

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