Implications of dosing tricyclic antidepressants and benzodiazepines in geriatrics.
It is important to understand both the kinetic and the dynamic implications of dosing TCAs and BZs in the elderly, for whom these drugs are frequently prescribed. The TCAs are used to treat responsive signs and symptoms including such somatic complaints as chest pain, dizziness, and arthralgias, as well as the endogenous signs such as loss of appetite with associated weight loss, psychomotor retardation, loss of libido, and insomnia. The pharmacokinetic studies of TCAs such as desipramine and nortriptyline have shown few, if any, age-related changes. The dose required for responsivity is significantly reduced for both TCAs (desipramine and nortriptyline) in the elderly, which may suggest increased end-organ responsiveness. The major recommendations for treatment of depression with nortriptyline in the elderly are (1) to administer small doses in order to avoid side effects, and (2) to expect a longer response time for the antidepressant effect than in young and middle-aged depressed patients. Although the BZs are extensively prescribed in the elderly, primarily for insomnia and anxiety, the physiologic and biochemical changes of aging alter the kinetics and dynamics of these extensively metabolized and slowly eliminated drugs. Based on the kinetic data and information in Tables 1 and 2, the relatively sensitive elderly population should receive a reduced dosage. Careful evaluation of the patient and the kinetic profile of the agent employed will ensure safe use of these drugs. A clear understanding of anxiety and respect for the alterations in the pharmacokinetics and pharmacodynamics of these agents in the elderly will allow the physician to prescribe the BZs wisely. As with the TCAs, remember to administer doses of BZs that are reduced by 50 to 75 per cent of the usual recommended doses for young and middle-aged individuals and to increase dosage in small increments. Ultimately, sound, scientifically based, clinical judgment that considers the needs of the patient is the best guide for the selection of an appropriate BZ.
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging; D000639:Amitriptyline / Q000008:administration & dosage; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage* / Q000009:adverse effects; D001008:Anxiety Disorders / Q000188:drug therapy; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy; D003891:Desipramine / Q000008:administration & dosage / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006801:Humans; D007099:Imipramine / Q000378:metabolism; D007700:Kinetics; D008875:Middle Aged; D003708:Nordazepam / Q000378:metabolism; D009661:Nortriptyline / Q000008:administration & dosage / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D001569:Benzodiazepines; D000639:Amitriptyline; D003708:Nordazepam; D009661:Nortriptyline; D007099:Imipramine; D003891:Desipramine