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Predictor

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Adverse drug reactions among elderly patients pose a significant clinical problem. The authors used a serum radioreceptor assay IRRA] to quantify drug-induced muscarinic blockade in 34 randomly selected nursing home residents. A random intervention group and the nonintervention control subjects were then retested 4 weeks later. The reduction of serum antimuscarinic activity (as determined by RR.A) did relate to changes on several measures of cognitive function. A calculated “antimuscarinic index” lost significance with the RRA following intervention and may have overestimated the impact of a dosage reduction. of Neuropsychiatry

Neurosciences

1991;

Ballus

Biomedical

people

prescriptions populations medication

often

and

Clinical

3:314-319)

C,

over

the

and

over-the-counter

(e.g., even

prescribed

class

assay

with

that

more

certain

iatrogenic

medications, a variety

sub-

a

are

from sedation The spectrum

and of

to anticholinergic mediin clinical practice. described a radiorecep-

quantifies to

risk

often in a doseof peripheral and

latter range impairment.4

attributable underrecognized and Metcalfe6

attributable

receive

drugs,

of drugs

effects.3 The to cognitive

(RRA)

activity

of 65 generally

home residents) are prescribed frequently.’ Among the most

These induce

cognitive disorders cations is probably Tune and Coyle5 tor

age

nursing more

the anticholinergics.2 dependent fashion,

serum

collective

antimuscarinic parent:metabolite

1306-1311 Received 18, 1990.

July11, 1990; revised From the Department

St. Paul-Ramsey

Medical

chiatry, reprint

of Minnesota to Dr. Tollefson,

University requests

Research

Section,

St. Paul,

Minnesota

Copyright

314

M.D.,

P. Lancaster,

central side drowsiness

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psychiatric

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19:222-223

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Gary D. Tollefson, Jon Montague-Clouse,

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REPORTS

dysfunction in schizophrenia mapping. Biol Psychiatry W, Breitling D, Banquet

hemisphere 22.

Psychiatry

W, Breitling

sphere activity 21. Cuenther nia.

RESEARCH

Center,

St. Paul-Ramsey

@ 1991

September11, of Psychiatry, St. Paul;

1990; accepted September Clinical Research Section, and

Medical School, Department Medical

the

Department

Minneapolis. of Psychiatry,

Center,

640

of PsyAddress Clinical

Jackson

Street,

#{149} SUMMER

1991

55101. The

American

VOLUME

Psychiatric

3

#{149} NUMBER

Press,

3

Inc.

CLINICAL

drug

pooi.

This

can

equivalents.” This flected iatrogenic

be

expressed

peripheral problems

in terms

measure has reportedly rein several diverse patient

groups. The objectives in this study were mine if a quantitative relationship induced

antimuscarinic

Psychometric

of “atropine

activity

as follows: 1) to deterexists between drug-

as measured

by both

the

Several administered

vention

Cancellation

designed

to reduce

the

total

amount

and, in turn, to on the subjects’

Subjects

Thirty-four

residents,

similar

nursing

study.

illness

cognition, presence versely

with

were

three in this

screened

by computerized record at least one anticholinergic

for

review. drug

for the previous 2 weeks. The followcriteria: 1) acute medical or psychi-

potential

short-term

e.g., pneumonia; of nonanticholinergic affect

from

to participate

of the residents

potential had received

at a constant dosage ing were exclusionary

of age or older,

consented

The medications

anticholinergic All subjects

atric

65 years

homes

cognition,

reversible

effects

on

2) pm-scheduled drugs; 3) drugs that might also ade.g.,

digoxin,

opioids,

benzodia-

zepines, and centrally active adrenergic blockers; 4) dementia or delirium7 with a Global Deterioration Scale Score4 greater than 6 (the patients were excluded to facilitate demonstration of an intervention effect and to ensure ability to complete tests); 5) visual acuity, hearing, comprehension, the study

or motor problems subject from completing

6) inability Study

of patients

severe enough psychometric

to provide

informed

to prevent tests; or

consent.

Design

The study was a randomized, repeated measures design using “intervention” and “control” groups. A Structured

Clinical Interview for Diagnosis (SCID),8 psychometric testing, and serum RRA for anticholinergic activity5 were performed on all subjects at study entrance. The “intervention”

group

subjects

tion

change made primary physician)

ergic

index9

baseline.

and

the RRA

JOURNAL

by at least

Where

discontinued; was substituted.

OF

were

25%

possible, if not

required

to have

(in cooperation to reduce their

the

feasible,

a less-anticholinergic

later,

psychometric

during

were

the afternoon

used.

All

tests

at the

same

time

were in an

tion

(MMSE),”

Wechsler Rating

Test,’#{176}Mini-Mental

Brief

Memory Test

Scale

Cognitive (WMS)’2

(LCT),’3

State

Rating

Scale

(BCRS),4

(Forms

I and

II), Letter

Psychogeriatric

(PGDRS),’4 Global Deterioration Delirium Checklist (SDC),’5 and

Dependency

Scale

katoon Sign, Side

Effect Checklist Collaborative

(SSSE) Research

Examina-

(NIMH Protocol).

the

Scale,4 SasSymptom,

Treatment

of

In addition to the psychometric and serum RRA data, the following information was collected from the patients’ nursing home records to better characterize and control the subject population: 1) subject demographics, 2) educational level, 3) medication proffle, 4) estimated anticholinergic index, 5) concomitant medical diagnoses, 6) psychiatric diagnoses, 7) estimated number of hours per week/month subject received visitors, and 8) duration of residence in an extended care facility. Serum Antimuscannic Analysis Procedure The serum antimuscarinic RRA was performed (according to Tune and Coyle,5 Tune et al.,’6 and Rovner et al.’7) immediately upon completion of the psychometric test battery. The RRA employed the muscarinic antagonist (3H)-quinucidinyl benzylate. Because samples are stable over time, they were batched, frozen, and run at a later date. Serum levels were corrected for dilution and expressed in atropine equivalents (pmol/ml serum). Statistical Analysis Procedure two-way repeated measure analysis of variance (ANOVA) was performed. Trends over time, as well as intervention effects and an interaction effect, were assessed in each group by a repeated measures design. This analysis was performed for various dependent variables, including the RRA, the calculated anticholinergic index, and the cognitive battery. All measures of variance given refer to standard deviations. A

a medicapatient’s

calculated anticholin(atropine equivalents) from

the anticholinergic

One month were repeated.

NEUROPSYCHIATRY

with

scales

Reminding

Depression

METHODS

REPORTS

effort to control for diurnal variation in mental performance and for medication administration sequencing (i.e., 4-8 hours after last dosage). The testing utilized in this study included the Buschke Selective

procedure

RESEARCH

Procedures psychometric

calculated anticholinergic index or RRA (atropine equivalents) and mental status in a group of nursing home patients, and 2) to determine the effectiveness of an interof anticholinergic medication prescribed determine the effect of the reduction cognitive and behavioral performance.

AND

agent(s)

was drug

testing

RESULTS A total

of 34 subjects completed the protocol (26 females, 8 males). Their mean age was 79±9.7 years. There were no significant differences in education or other demographics between the two study groups. The intervention recommendation was successfully carried out on 15 subjects

315

CLINICAL

(two

AND

patients’

RESEARCH

physicians

REPORTS

declined

participation

because

of patient deterioration after initial drug change). Nineteen control subjects (including one originally assigned for intervention) had their drug dosage(s) held constant during the investigation. Psychiatric diagnoses by SCID8 were as follows: schizophrenia, n=13; major affective, n=10; no psychiatric diagnosis, n=9; substance abuse (inactive), n=1; and generalized anxiety, n=1. Four-week retest results are in Table 1. The preintervention/postintervention RRA values are presented in Table 2. The calculated anticholinergic index values are summarized in Table 3. An ANOVA was highly significant in differentiating the two groups’ anticholinergic postintervention activity (F=34.63, p