Mohammed T. Abou-Saleh

PHARMACOKINETIC AND PHARMACODYNAMIC CONSIDERATION IN OLD AGE PSYCHOPHARMACOLOGY 63PRACTICAL ISSUESBearing in mind the above-described pharmacokinetic andpharmacodynamic changes of psychotropic drugs in the elderly,a few principles could be recommended as prescribing guidelines38 : one should become familiar with a number of preparationsand preferably administer them; use as few drugs as possible(including drugs for non-psychiatric conditions); ‘keep it as simpleas possible’: give written instructions; avoid depot-forms, thetreatment should be started in low dosages (1/5 to 1/4 of averageadult dosage) and slowly increased (no sooner than every 5–7days 39 ); the maintenance dosage is about 1/3–1/2 40 of averageadult dosage (‘start low and go slow’), but some elderly patientsmight need and can tolerate full doses 8 . The times required toreach steady-state therapeutic levels are longer.Moreover, it ought to be emphasized that some psychotropicsare more suitable for the elderly than others. For the treatment ofaffective disorders, tricyclic antidepressants are efficacious andinexpensive, but SSRIs and newer antidepressants are bettertolerated and safer in overdose 41 . With respect to the putativediminished 5-HT responsivity in this population, the ability toidentify SSRI non-responders via 5-HT challenge in combinationwith neuroimaging measures may have important clinical utility 33 .Among the SSRIs, preference is possibly given to sertraline 12 . Theselective MAO-A inhibitors have not been extensively studied inthe elderly, but they have definitely overcome the use of theclassical MAO inhibitors. Lithium is still the mainstay for thetreatment of bipolar disorders, but careful dosage and monitoringof plasma concentration are necessarily required. On the otherhand, bipolar elderly patient responders to valproate ought toachieve higher serum concentrations of valproate itself 42 .The age-related changes in the pharmacokinetics and pharmacodynamicsof the benzodiazepines (still the most frequentlyprescribed drugs for anxiety in the elderly) recommend preferentialuse of those agents that are metabolized via conjugation(oxazepam); risperidone (which is better tolerated in the elderly)may be used as an alternative. However, together with the sedationincrease, with a sedative/hypnotic prescription a cognitivefunction decrease is observed in the elderly, with consequent risksof falls and injury (especially if the diazepam-equivalent dosage ishigher and if the patient is prescribed with more different drugs) 43 .According to some suggestions 44 , because of the high level of comorbiditybetween generalized anxiety disorder and majordepression in late life and the observation that anxiety is usuallysecondary to depression, antidepressants constitute the primarypharmacological treatment for many older people. For thetreatment of insomnia, both zopiclone and temazepam are to beconsidered as effective hypnotics, but the first shows a superiorityon sleep architecture 45 . New promising agents, such as cholecystokinin-Breceptor antagonists, seem to be specific, in agedanimals, for an improvement of sleep quality 46 . For the treatmentof psychotic syndromes, due to the elderly extreme sensitivity toparkinsonian side effects and to the anticholinergic properties ofthe classical antipsychotics, attention is given to the newerantipsychotics, but there is still a paucity of data. Clozapine maybe a useful drug but adverse effects can occur 47 .Notwithstanding the aforementioned I am in agreement withJovic 38 , who stated that ‘‘psychotropic drugs cannot compensatefor the lack of human contacts, devotion and intensive relationships,but complement them’’.REFERENCES1. Roberts J, Tumer N. Pharmacodynamic basis for altered drug actionin the elderly. Clin Geriat Med 1998; 4: 127–49.2. Banerjee S, Dickinson E. Evidence-based health care in old agepsychiatry. Int J Psychiat 1997; 27: 283–92.3. Zubenko GS, Sunderland T. Geriatric psychopharmacology: whydoes age matter? Harvard Rev Psychiat 2000; 7: 311–33.4. Tourigny-Rivard MF. Treating depression in old age: is it worth theeffort? 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