Depression & Anxiety:
Aphorisms by Nascher
by James W. Jefferson, M.D.| Geriatric Times |  |
May/June 2000 | |
Vol. I | |
Issue 1 |
I.L. Nascher, a New York City physician, made a number of astute observations in his 1914 article "Some Geriatric Aphorisms." Try this one: "Some are aged before they are old, some are old but are not aged." Nascher also suggests that geriatrics deals with what he refers to as the senile state, rather than years of life.
Perhaps he was aware of progeria, a genetic disorder involving accelerated aging in children. This was first described in 1886 by Hutchinson and Gilford and is now referred to as Hutchinson-Gilford progeria syndrome (Progeria Research Foundation, 2000). Without question, progeria is the extreme example of being aged without being old, with victims often dying in their teens from advanced cardiovascular disease.
Whether one can truly get old, especially very old, without aging is unknown. Some researchers currently view aging as a genetic disease, possibly with a genetic cure, rather than as an evolutionary process that is part of nature's grand design.
Nascher's first rule of therapeutics was, "Increase dose of stimulants and decrease dose of sedatives." He must have foreseen the present-day geriatric use of amphetamines and other stimulants and of sedatives such as benzodiazepines. While stimulants have never fared well in rigorous trials of major depression, they are probably underutilized as a relatively safe, rapid-acting, short-term treatment for apathy and minor depression in the elderly, particularly in the hospitalized medically ill (Murray and Cassem, 1998).
Benzodiazepines, particularly those with longer half-lifes, have been implicated in causing motor vehicle accidents (Hemmelgarn et al., 1997) and hip fractures (Ray et al., 1989) in the elderly. While a long half-life may well be a risk factor with benzodiazepines, one study found that falls and fractures were strongly related to dose rather than to half-life (Herings et al., 1995). In a case-control study in Germany, no association was found between an increase in hip fractures and a history of current benzodiazepine use. While only 18% of the hip fracture group gave a history of benzodiazepine use, 41% tested positive for benzodiazepines in their blood. Benzodiazepine use correlated strongly with an increased risk of hip fracture (Schwab et al., 1999).
Before getting excited about the prospects of stamping out hip fracture in the elderly by depriving them of benzodiazepines, be aware that the New York State triplicate prescription policy, which reduced benzodiazepine prescribing by nearly half, had no significant impact on the rate of hip fracture.
A clinical crossroads conference published in JAMA focused on an 87-year-old woman who had taken alprazolam (Xanax) regularly for 15 years. Her current physician wanted this medication stopped (Salzman, 1999). In addition to the risk of falls, fractures and motor vehicle accidents, the discussant, Carl Salzman, M.D., acknowledged that benzodiazepines may impair cognition by affecting memory, attention, visuospatial function and word recall. He also noted, however, that patients have told him that they would rather take a drug that calms them than have sharp memory function. Likewise, Salzman also stressed the risk of drug interactions in the elderly, who are likely to co-medicate (alprazolam is metabolized by CYP 3A4, an enzyme induced or inhibited by a great number of drugs). He noted, even in the very old, benzodiazepines should neither be condoned nor condemned just because they are benzodiazepines, but they should be judged by their effects on individual patients.
Nascher was also attuned to the sensitivity of the elderly to medication side effects, observing, "Secondary effects of drugs may act more powerfully upon the senile organism than the primary or desired effect." Even today, our search continues for drugs that will benefit the ever-growing number of "senile organisms" in our population without causing them harm. We are certainly fortunate to be blessed with the newer, nontricyclic antidepressants (the selective serotonin reuptake inhibitors and others) for use in geriatric depression, although some have suggested, "The evidence that newer drugs are much better than the old is thin" (Livingston and Livingston, 1999). The newer drugs have not been shown to be more efficacious than the tricyclics, and many comparative studies failed to find substantially different drop-out rates (the exclusion of patients with major medical illnesses from most clinical trials may have minimized newer drug/tricyclic differences in tolerability). A meta-analysis of comparative studies did find a 10% lower overall drop-out rate and a 25% lower drop-out rate due to side effects with SSRIs compared to tricyclics, although the authors concluded the overall difference is comparatively small and may not be clinically relevant (Anderson and Tomenson, 1995).
A case-control study of hip fracture in the elderly found a significantly increased risk of fracture with SSRIs, secondary-amine tricyclics and tertiary-amine tricyclics (adjusted odd ratios of 2.4, 2.2 and 1.5, respectively) (Liu et al., 1998). This surprisingly high risk of fracture with SSRIs may have been due, in part, to their preferential use in higher risk, more fragile patients. The finding of a lower increased risk with tertiary-amine tricyclics such as amitriptyline (Elavil) and imipramine (Tofranil) may have been an artifact of lower doses and differences in the underlying disorder. This finding should not suggest that drugs such as amitriptyline and imipramine are the preferred medications for geriatric depression (the new nontricyclics have earned that distinction).
Accordingly, here is another relevant Nascher aphorism:
Drugs act differently upon senile degenerating tissue than they do upon the
normal tissues in maturity. They should be given singly if possible, and the
action of each determined in each individual case.
Nascher was aware of the risk of drug interactions, but he could not have anticipated the recent explosion in knowledge about cytochrome P450 and other drug metabolizing systems. In his era, as well as today, the elderly consumed a wide array of medications: prescription, over-the-counter, herbal (Ernst, 1999) and whatever else might be supplied by well-intentioned friends and relatives. Not only do multiple medications increase the risk of adverse drug interactions (Rosholm et al., 1998), but they also increase the risk of treatment noncompliance. With the elderly in particular, less is often more.
Dwell upon this one final Nascher aphorism: "Flattery is a more powerful mental stimulus than drugs." Could he have been referring to the power of the placebo?
Dr. Jefferson is distinguished senior scientist at the Madison Institute of Medicine and clinical professor of psychiatry at the University of Wisconsin Medical School.
References
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Ernst E (1999), Herbal medications for common ailments in the elderly. Drugs Aging 15(6):423-428.
Hemmelgarn B, Suissa S, Huang A et al. (1997), Benzodiazepine use and the risk of motor vehicle crash in the elderly. JAMA 278(1):27-31 [see comments].
Herings RM, Stricker BH, de Boer A et al. (1995), Benzodiazepines and the risk of falling leading to femur fractures. Dosage more important than elimination half-life. Arch Intern Med 155(16):1801-1807.
Liu B, Anderson G, Mittmann N et al. (1998), Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and risk of hip fractures in elderly people. Lancet 351(9112):1303-1307 [see comments].
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Progeria Research Foundation Inc. (2000), Progeria Research Foundation Inc. Available at: www.progeriaresearch.org. Accessed March 5.
Ray WA, Griffin MR, Downey W (1989), Benzodiazepines of long and short elimination half-life and the risk of hip fracture. JAMA 262(23):3303-3307 [see comments].
Rosholm JU, Bjerrum L, Hallas J et al. (1998), Polypharmacy and the risk of drug-drug interactions among Danish elderly. A prescription database study. Dan Med Bull 45(2):210-213.
Salzman C (1999), An 87-year-old woman taking a benzodiazepine. JAMA 281(12):1121-1125 [clinical conference].
Schwab M, Roder F, Ammon S et al. (1999), Increased number of hip fractures. Lancet 353(9170):2160 [letter].