Antidepressant use in the elderly: the role of pharmacodynamics and pharmacokinetics in drug safety.
BACKGROUND
Antidepressants (ADs) are widely used among elderly persons, making AD-related safety an important issue.


METHODS
This review highlights safety considerations related to AD use including risks associated with inappropriate and off-label use. The age-related pharmacokinetic and pharmacodynamic changes underlying safety concerns connected to ADs are outlined. Drug-drug interactions as a cause of AD-related adverse drug reactions (ADRs) are also discussed. We reviewed scientific evidence concerning three important safety outcomes related to ADs in elderly persons: cardiac arrhythmias, hyponatraemia and falls/fractures.


CONCLUSIONS
Several AD-related ADRs in elderly people are likely to be preventable. Current evidence suggests that selective serotonin re-uptake inhibitors (SSRIs) are best avoided particularly in persons with kidney disease due to the risk of hyponatraemia. The use of tricyclic antidepressants (TCAs) should be limited in the elderly due to anticholinergic adverse effects. TCAs should also be avoided in elderly persons at high risk of cardiovascular events due to a risk of cardiac arrhythmia. Emerging evidence suggests that SSRIs also have arrhythmogenic potential. Both TCAs and SSRIs should be used cautiously in elderly persons at risk of falls. Future research in this area should aim to investigate the lowest effective dose of AD possible, the relationship between AD dose and adverse effects, and which elderly subgroups are most prone to develop severe ADRs.
University of Messina, Policlinico Universitario G. Martino, Department of Clinical and Experimental Medicine , Via Consolare Valeria, 98125 Messina , Italy.
Janet
J
Sultana
Edoardo
E
Spina
Gianluca
G
Trifirò
D000367:Age Factors; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D057970:Inappropriate Prescribing / Q000009:adverse effects*; D056687:Off-Label Use; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D017367:Selective Serotonin Reuptake Inhibitors
adverse drug reaction; antidepressants; drug safety; elderly