Pharmacokinetic And Pharmacodynamic Considerations

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The use of antidepressants in older patients can be complicated by several factors. Older individuals use multiple medications (two or more prescription drugs) three times more frequently than younger persons, increasing the potential for interactions. Age-related alterations in physiology can result in variable plasma drug concentrations, which may increase the number of adverse events, and the elderly may be more sensitive to adverse events (McDonald et al., 2002). Aging is associated with a number of neuroendocrine changes, including alterations in monoamine oxidases, noradrenergic neurons, dopaminergic neurons and concentrations, cholinergic neurons and receptors, adrenocorticotropic hormone (ACTH) concentration and function, and serotonin receptors and concentrations (Rehman et al.,

2001). There is early evidence that some older patients with deficits in executive skills may respond poorly to antidepressant treatment compared with those with intact executive functions (Mohlman, 2005).

Recommended initial doses are lower for the elderly for all antidepressants, and increases should be slow and individualized (De Vane et al., 1999). The pharmacoki-netics of some selective serotonin reuptake inhibitors (SSRIs) may be altered in older patients, and it is recommended that doses be adjusted in these patients (De Vane et al., 1999). Lower doses should be used for citalopram and for paroxetine (Muijsers et al.,

2002). Medical conditions can affect drug elimination, which is decreased in patients with hepatic (citalopram, fluoxetine, fluvoxamine, sertraline) or renal (paroxetine) impairment (Muijsers et al., 2002).

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