Mohammed T. Abou-Saleh

566 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYfatigue, drowsiness, sedation, muscle weakness, blurred vision,nystagmus, dysarthria, ataxia and impaired psychomotor andcognitive performance 12,25,26 . The impairment of motor coordinationcauses drivers taking benzodiazepines to be five times morelikely of being involved in a serious road accident 27 . Cognitiveimpairment can be severe enough to present as a pseudodementiain susceptible elderly patients.Benzodiazepines may also cause a paradoxical reaction ofrestlessness, confusion, irritability and even aggression. Outburstsof anger in elderly patients receiving benzodiazepines mayindicate the need to consider an alternative medicine. There arealso published case reports of benzodiazepines inducing asecondary mania 28,29 . Benzodiazepines may cause mild respiratorydepression in patients with chronic obstructive lung disease.Mixing benzodiazepines with other CNS depressants such asalcohol can lead to severe intoxication or (potentially lethal)respiratory depression.SelectionIn general, benzodiazepines are equivalent in terms of overallefficacy 30 . The selection of a particular benzodiazepine is primarilybased upon the patient’s particular problem and the medicationproperties (route of metabolism, length of half-life, onset ofaction, and presence of active metabolites) 31 . In general, thefollowing guidelines should be considered when using a benzodiazepine:1. Benzodiazepines that undergo conjugation to water-solubleglucuronides prior to excretion in the urine (e.g. temazepam,lorazepam, oxazepam) have no active metabolites and theirpharmacokinetics are not significantly changed by the agingprocess 32 . They are probably the wisest choice for elderlypatients with severely impaired hepatic function.2. Short (but not ultrashort) half-life drugs are preferable to longhalf-life medications, since they appear less likely to increasethe risk for hip fractures 21 .3. Accumulation of benzodiazepines is directly related to theamount of fat. Therefore, the obese or severely medically frailpatients may be at increased risk.4. Avoid benzodiazepine use in patients dependent on alcohol orother drugs.5. Begin with lower doses and titrate upwards gradually (‘‘startlow and go slow’’).6. Try to limit the length of use to 3–4 months. Taperbenzodiazepines over a 4–8 week period.BuspironeBuspirone (Buspar) is a novel anti-anxiety agent unrelated to thebenzodiazepines in chemical structure or pharmacologic characteristics.Its mechanism of action is probably related to its highaffinity for the serotonin type 5-HT 1A receptor, which causesreduced serotoninergic activity. In addition, it enhances braindopaminergic and noradrenergic activity 33,34 .EfficacyBuspirone is effective in the treatment of generalized anxietydisorder in the elderly. It is well tolerated and as effective as thebenzodiazepines 35–38 . However, buspirone does not appear to beeffective in the treatment of panic disorder 39 . Some researcherssuggest that buspirone may be helpful in mixed anxiety/depressionsymptoms. It may also be effective as an adjunct treatment forOCD. Its use in PTSD and social phobia appears to be limited.AdministrationTherapeutic doses are in the range 20–60 mg daily; however,buspirone’s short half-life (averaging 2–3 h) requires that it begiven three times a day (usually with meals). Studies havedemonstrated that buspirone may remain effective for at least 6weeks, although longer efficacy is presumed.Two major disadvantages of buspirone are the requirement formultiple daily dosing and the lack of immediate effect. Buspironemay take 1–3 weeks at therapeutic dosing before the anxiolyticeffect begins. Some researchers have also suggested that theefficacy of buspirone may be reduced in patients who havepreviously been treated with benzodiazepines 40 . Others suggestusing a benzodiazepine for the first 1–2 weeks when initiatingtreatment with buspirone until it becomes effective.Side EffectsBuspirone side effects include nausea, headache, nervousness,dizziness, lightheadedness and fatigue. Unlike the benzodiazepines,buspirone does not appear to cause psychomotorimpairment, dependence, withdrawal or abuse 41 . Further, it doesnot interact with alcohol and other sedative drugs. Buspironelacks hypnotic, anticonvulsant and muscle relaxant properties.Therefore, it may be of particular value in the treatment ofpatients unable to tolerate the sedative effects of benzodiazepines42 , or patients with a history of substance abuse.AntidepressantsTricyclic AntidepressantsEfficacy. Tricyclic antidepressants (TCAs) have been shown tobe effective in treating mixed anxiety–depression states, panicdisorder and generalized anxiety disorder in the elderly 43–46 . In thegeneral adult population, TCAs are frequently used in PTSD andclomipramine has been approved by the FDA to treat OCD.However, the overall use of TCAs has decreased as other options(especially the SSRIs) have become available. This is primarilydue to the significant side effects TCAs have at therapeutic dosesthat also increase the risk to physically ill patients and potentiatestoxicity in overdose. Further, like all other medications used forthe treatment of anxiety (except the benzodiazepines), TCAsusually require several weeks to show maximal benefit. Despitetheir shortcomings, tricyclic antidepressants remain an alternativetreatment for GAD 47 .Side Effects. Common side effects may be mediated by a-adrenergic blockade, anticholinergic effects and antihistaminergiceffects. The a-adrenergic blockade of TCAs may cause significantorthostatic hypotension or cardiac conduction irregularities. Theelderly are particularly susceptible to injury from orthostatic falls.Patients with complete heart block should not be given TCAsbecause these medications can cause a prolonged QRS complex.Trazodone, a heterocyclic antidepressant, is sometimes used as asedative or in the treatment of agitation for demented patients,but the side effects of postural hypotension may limit its use 20 .Anticholinergic side effects of TCAs are dry mouth, blurredvision, constipation, urinary retention and confusion or evenpsychosis. This may be particularly significant in patients with