Adverse effects of medications that
occur at lowfrequency
or low severity are often not detectedin
the current framework of drug approval andmonitoring.
Of particular concern are potentialbehavioral
consequences such as depression or cog-nitive
dysfunction that may occur from commonlyprescribed
medications. This study explores the useof
measuring daily affect, both positive and nega-tive,
as a method for detecting clinically relevantaffective
toxicity from medications commonly pre-scribed
to older adults. Findings from this studysuggest
that metoclopramide may have the poten-tial
for causing significant changes in affect amonghealthy
elderly adults. This may suggest that morevulnerable
or disabled adults may be at evengreater risk for affective changes
related to thismedication.
he Institute
of Medicine has recentlycalled
for a greater emphasis on postmarketingresearch in order to improve the detection
of adverseeffects
of medications that occur at a low incidence oroccur
when medications are used for a longer dura-tion
or at a higher dose than intended.1 Morrison
andKatz have
previously suggested that the current pro-cedures
for recognizing adverse effects of new drugsare
designed to identify effects that are serious andcommon.2 However, these
procedures are conductedpredominantly
in young and middle-aged populationsof
adult subjects and may not be adequate to detectside
effects that are significant in the elderly. Of par-ticular concern are central nervous
system effects,such
as cognitive changes or affective disturbances,which, unless
explicitly examined, often go unnoticedor
ignored. As highlighted by a recent report fromthe
US General Accounting Office (GAO), the grow-ing
elderly population may be particularly vulnera-ble
to adverse drug reactions and is an issue that isimportant
to national health care policy as well asclinical
practice.3 Moreover, the GAO report
empha-sizes that, even
in the absence of serious injury, lesssevere
or persistent adverse reactions can decreasethe
general quality of life of patients. In this context,it is important to ask whether medications
prescribedcommonly
for older patients regularly cause impair-ments
in affect and/or cognitive functioning.Previous
research by Katz and colleagues has estab-lished
methodologies for the systematic examinationof
the cognitive effects of medications in healthynoncognitively impaired elderly adults.4 This
line ofinvestigation
has demonstrated reproducible cognitiveimpairment
from medications such as oxybutynin andhas
failed to demonstrate effects of other medicationssuch
as cimetidine.4,5 We have now begun to
extend thismethodology
to include the systematic evaluation ofaffective
or mood disturbances related to commonlyF r e e
p a p e r sExploring
the affective toxicity of commonlyprescribed
medications in the elderlyDavid
W. Oslin, MD; Thomas R. Ten Have, PhDDavid W. OSLINKeywords:
medication; elderly; affect; adverse effectAuthor affiliations: Section
of Geriatric Psychiatry, University of Pennsylvania, VA Medical Center, USA (David
W. Oslin, Assistant Professor); Department of Epidemiology and Biostatistics,
Universtity of Pennsylvania, Philadelphia, Pa, USA (Thomas R. Ten Have, Associate
Professor) Address
for correspondence: Prof David Oslin, University of Pennsylvania,
Ralston Penn Center, 3615 Chestnut Street, Philadelphia, PA 19104, USA (e-mail:
oslin@mail.med.upenn.edu) 1
2 5T
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