Comparative Effects of Sertraline
and Nortriptyline on Body Sway
in Older Depressed Patients
Fouzia Laghrlssi-Thode, M.D.,
Bruce G. Pollock, M.D., Ph.D., Mark Miller, Ph.D.,
Linda Altieri, M. S.N., DavidJ. Kupfer, M.D.
This study examined effects of nortriptyline and sertraline on the balance and stability ofdepressedgeriatric
inpatients. Body sway was measured with a stableforceplatform at three timepointsi before starting antidepressant medication, 5-7 days after medication was
initiated, and 1 week later. A group of healthy, unmedicated older volunteers was evaluated under the same
conditions as patients. In sertraline-treatedpatients (n =
10), significant differences (P < 0.05) between baseline
and the first week of treatment were found in the forceplatform measurements of sway length (L) and area of
the center a/pressure (Ao), with patients' eyes both open
and closed. This change in postural stability occurred in
the absence of orthostatic bypotension. By the second
uieel« .01 treatment, neither variable was found to be
significantly different from baseline. In the nonmedicated volunteers (n = 20) and in the group ofpatients
receiving nortriptyline (n = 11), no significant changes
in postural stability were found. (American Journal of
Geriatric Psychiatry 1995; 3:217-228)

F

alls t because of their frequency and
their physical, psychological, and socioeconomic consequences, are a major
public health problem in older people. An
estimated 6%-10% offalls result in serious
complications, such as hip fracture or sub-

dural hematoma.Y' These injuries and
their fatal complications are the sixth leading cause ofdeath in persons over the age
of 65. 4 Even falls that do not result in
serious injury may bring about a loss of
confidence, with self-imposed activity re-

Received September 7, 1994; revised December 14, 1994; accepted January 10, 1995. From the Department
of Psychiatry. University of Pittsburgh School of Medicinc, Western Psychiatric Institute and Clinic, Pittsburgh,
PA. Address correspondence to Dr. F. Laghrissi.. hode, Western Psychiatric Institute and Clinic, 3811 O'Hara
T
Street, Pittsburgh, PA 15213.
Copyright © 1995 American Association for Geriatric Psychiatry
THE AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY

217

Sertraline and Nortriptyline
strictions leading to further debilitation. 5t6 Medications and psychotropic
drugs, in particular, contribute to instability and increase the risk of falls among
older people. 7- l O This risk is present even
after controlling for confounding factors,
such as confusion, dementia, and depression.'t 10
More specifically, antidepressants
have been related to the incidence of falling, even after age, fall history and use of
other psychotropic medication are controlled. l 1 Older patients treated with tricyclic antidepressants have been found to
be at greater risk of hip fracture than
unmedicated matched control subjects.i
The mechanism by which antidepressants
contribute to falls remains unclear. Possible contributing factors are orthostatic
hypotension, sedation, extrapyramidal
side effects, and impaired neurophysiologic ability to compensate for changes
in postural stability

METHODS
We undertook an open comparative study
to determine whether or not antidepressant drugs affect postural stability in older
depressed patients. The subjects were inpatients on the Geriatric Clinical Research
Unit of Western Psychiatric Institute and
TABLE1.

o

o

Clinic, in Pittsburgh, PAl Patients had
been diagnosed as suffering from a major
depressive episode and were starting antidepressant treatment with either nortriptyline or sertraline. Patients' inclusion
in this study did not affect or interfere
with any aspect of their care, including
choice of antidepressant drug, which remained the decision of patients' own physicians. Any patient who could not stand
alone for 5 minutes or could not keep his
or her eyes closed for 20 seconds was
excluded. In order to determine whether
the variability observed among patients
differs from nonpatlents, a group of 20
healthy, older volunteers was evaluated
once per week for 3 consecutive weeks
under the same conditions as the patients.
These healthy volunteers took no psychotropic or cardiovascular medication
during the entire study period. Each subject gave written informed consent for
participation in this study.
The most common method used to
quantify body sway is a balance platform. 12- 14 This noninvasive tool consists
of an array of sensors that are scanned by
a computer to obtain the position of the
center of force when the subject stands
on the platform. An AMTI (Advanced
Medical Technology; Inc.; Newton, MA)15
force-platform (Model OR6-5) was used
to measure two force components of

Demographic and clinical characteristics of untreated (control) subjects, sertrallne-, and
nortriptyline-treated patients
Control
20)

(n

Mean age, years
Gender, MIW
Race, white/other
Weight, pounds
Height, inches
Mean dose, Week 1
mglday
Week 2

=

75.3 ± 4.1
10/10
18/2
145 ± 16
64.8 ± 4.2
None
None

Sertraline
(n

= 10)

72.4 ± 6.9

3n
9/1
144 ± 18
67.2 ± 3.4

66.6 ± 33
102.7 ± 8

NortriptyUne
(n = 11)
73.0
3/8
7/4
147
63.0
52.2
57.7

Statistic

± 4.8

O.79'J.
0.22 3

± 28
± 5.5
± 20
± 16

O.7S b
O.06b

All statistical values arc nonsignificant.
a Fisher's exact test (one-tailed).
b r-test,

Note:

218

VOLUME 3 • NUMBER 3 • SUMMER 1995

0

Laghrlssi-Thode et all

body sway in the lateral and sagittal
planes concomitantly This force-platform
was connected to a personal computer
via an analog/digital converter. The mean
position of the center of pressure relative
to the platform coordinates was calculated by CAS (Computer-Automated Stability Analysis) software,15 and the sway
data were plotted relative to this mean
position. Hufschmidt et al. 16 examined
the relative value of 13 different indices
derived from platform recording for application in neurological diagnoses. They
found the most useful measures to be the
mean amplitude, the length of path of the
center of pressure (L), and the area included within the path of the center of
pressure (Ao).
TABLE2.

Psychiatric diagnosis (DSM-III-R),

current medical illnesses, and patients with history of faU in the sertraUne and nortriptyline groups, "
Sertraline
(II

Psychiatric
diagnosis (n)

=10)

Nortriptyllne
(II = 11)

M.RoD. a (6)

M.R.D. (4)

MoR.Do b (3)
M.D.Eo e (1)
1

M.RoD.b (6)
Bop.d (1)
2

Patients with
history of fall
2
Hypertension
Ischemic heart
0
disease
Arrhythmia
1
Hypothyroidism
1
Diabetes
1
Arthritis
,3
Emphysema
0
Chronic. constipation 2
Prostatic hypertrophy 1
1
Glaucoma
Cataract
2
1
Seizure

3

4
4
0

3
1

3
1
1

3

3
1
0

a Major recurrent depression, severe, without
gSfchotic features.
Major recurrent depression, severe, with
psychotic features.
C Malordepressrve episode, single, moderate.
d Bipolar disorder, depressed, moderate.

Vissier17 has reported that the sway
path is probably the most useful index of
sway The author argues that the parameter of length would offer a greater potential than that of area in describing sway
Length appears to more adequately take
account ofdynamic action than does area
because a large amount of sway may occur within a restricted area. 12 Other parameters, such as radial area, elliptical
area, and root mean-square displacement
of the center of pressure, are highly dependent on use ofa single-leg stance, and
it has been concluded that such measures
are not necessary in a protocol restricted
to double-leg stance." For the safety of
the patients, our study was restricted to
double-leg stance rather than single-leg
stance; therefore the length of path of the
center of pressure (L, in em) and the area
included within the path of the center of
pressure (Ao, in sq. cm) were selected to
quantify body sway
The patients were evaluated on 2
consecutive days at three timepoints: before starting antidepressant medication
(at baseline), 5-7 days after the medication was initiated (Week 1), and 1 week
later (Week 2). To avoid the issue of diurnal variation of body sway; the patients
were all evaluated at approximately the
same time ofday The dose of medication
was held constant from baseline to Week
1 and from Week 1 to Week 2. Balance
evaluation was performed before dose
adjustment at Week 1. Each patient was
measured in double-leg stance on the
force-platform, with feet together, looking straight ahead, focusing on an object
at a distance of 3· meters, and with arms
by their sides. Because body sway is
greater with eyes closed than with eyes
open, the subjects were evaluated with
their eyes open and then closed. Three
consecutive trials were made for each
stance, and the measures were averaged
for each subject. Each trial was recorded
for 20 seconds.
To determine whether or not the ef-

THE AMERICAN JOURNAL OF GERIATIUC PSYCHIATRY

219

Sertraline and Nortriptyline
FIGURE 1.

Increase in length of sway path (L, in em) of older, depressed patients during the f"trst
2 weeks of treatment with sertraline (mean ± SD)

fects of antidepressants on body sway occurred independently of blood pressure
changes, blood pressure and pulse were
measured before each evaluation, after 5
minutes supine, and for the first 3 mlnutes in the standing position. The following variables were recorded: age, gender,
race, height, weight, psychiatric diagnosis
(by DSM..III-R), active medical problems,
ambulatory condition, medical history;
and history of falls. All medications taken
by the patient during the study period
and in the preceding 2 weeks were recorded, as well as the type and daily dose
of antidepressant.
Data were analyzed using SAS software (version 6.06; SAS Institute Inc"
Cary; NC). A repeated-measures. analysis
ofvariance (ANOVA) model with planned
comparisons was used to examine the
220

pairwise differences between baseline,
Week 1, and Week 2 of treatment.

The model used three main effects:
week, 'da}', and trial. Two analyses were
run for each group: one for the data recorded when subjects had their eyes
open, and one for data recorded when
subjects had their eyes closed.
The data from the three groups were
not normally distributed; therefore, sta..
tistical analyses were performed on the
square-root transformation of the length
of path of the center of pressure (L) and
the area included within the path of the
center of pressure (Ao).
A one-way, repeated-measures
ANOYA model was used to determine the
interindividual variability among the
three trials with eyes open and the three
trials with eyes closed.
VOLUME

3 • NUMBER 3 • SUMMER 1995

Lagbrissi-Tbode et ale

FIGURE 2.

Length of sway path (L, in em) with eyes open for individual subjects treated wtth sertraUne

L (em)
200

180

-f-

Patient #4

-IE-

160

Patient #1

Patient #13

--- Patient #14

140

-No-

Patient #15

-+-

Patient #19

-.- Patient #20

100

-I-

-

80

Patient #22
Patient #25

-.- Patient #34
60
40

0

1

Week

RESULTS
In all, 20 healthy, older volunteers, 11
older, depressed patients treated with
nortriptyline, and 10 older, depressed patients treated with sertraline completed
this study. There were no statistical differences among the three groups regarding
their demographic and clinical characteristics (Table 1). The psychiatric diagnoses (DSM-III-R), intercurrent illnesses,
THE AMBRICAN JOURNAL OF GEIUATRIC PSYCHIATRY

2

and prior fall. history of the antidepressant-treated patients are presented in Table 2. All medication taken by the patients
during the study period and in the preceding 2 weeks are reported in Table 3.
In sertraline-treated patients, postural sway increased whether subjects
had their eyes open or closed. This increase was statistically significant, and the
planned comparison indicates that the
significant difference for the variable L
was between baseline and Week 1 (eyes
221

Sertraline and Nortriptyline
TABLE 3.

Concomitant treatment ofsertrallneand nortriptyUne-treated patients
during the study period and in the
preceding 2 weeks, 71
Sertraline
(II
10)

Norbiptyline

0

4

1
1

3

=

Calcium channel
blockers
Diuretics
Angiotensin
converting
enzyme inhibitors
Nitroglycerin
Insulin
Levothyroxine
sodium
Atropine eye drops
Cholinesterase
inhibitor eye drops
Vitamin 812. C. or E

0
1

(II

= 11)

1

1

0

0
3

2

1

1
1

2
2

=

open, P 0.004; eyes closed, P = 0.005;
Figure 1). By the second week of treatment, sertraline tended to increase L,but
this increase failed to achieve statistical
significance between baseline and Week 2
(eyes open, P 0.202; eyes closed, P =
0.205). Figures 2 and 3 display individual
changes in L with eyes open and closed
over the 2 weeks of treatment with sertraIine. The Ao of the sertraline group
(Figure 4) was comparable to the Ao of
the untreated group (Figure 5) at baseline. After 1 week of treatment, sertraline
significantly increased the variable Ao
(eyes open, P = 0.014j eyes closed, P =
0.006). After 2 weeks of treatment,
however, the increase inAo was not statistically different from baseline (eyes open,
P = 0.222; eyes closed, P = 0.219).
Changes in postural stability occurred in
the absence of orthostatic hypotension
and were clinically noticeable in five patients (#1, #4, #13, #22, and #34).
Three patients (#1, #13, and #22) spontaneously complained of dizziness after
the first week of treatment. Two other
patients (#4 and #34) were not aware of
their body sway changes with eyes open

=

222

and reported unsteadiness only during
the Romberg test with their eyes closed.
No falls were observed during the study
period.
In the group of patients receiving
nortriptyline, no significant changes in
any of the two variables were found (P <
0.3; Figure 6). The body sway of these
patients remained comparable to the
sway of the untreated subjects (Figure 7).
Individual measures of Land Ao did not
differ from each other. No significant variation was found among the three trials
with eyes open (P ~ 0.7) as well as among
the three trials with eyes closed (P ~ 0.5).

DISCUSSION
The prevalence of drug-induced falls in
older people and the association between
falling and impaired balance has led to the
development of the concept of body sway
as a measure of drug effects. Increased
body sway is associated with an increased
risk of falling. I 9-22 This falling may result
from impaired postural control and impaired corrective responses once balance
is lost. Previous studies23- 26 have examined the effects of psychotropic medications on body sway and have pointed out
that benzodiazepines (diazepam,
lorazepam), potent HI antihistaminic
compounds (chlorpheniramine, diphenhydramine), and anticonvulsant medications (phenytoin, meprobamate,
amylbarbitone) consistently increase
body sway. In contrast, psychostimulant
compounds (caffeine, dexamphetamine,
hydergine) showed no significant effect
on sway.27 However, most ofthese studies
have been conducted on healthy, young
subjects after a single, oral dose.
Dizziness and vertigo are common
side effects ofantidepressant drugs. How..
ever, instability is rarely quantified, and
objective measurement of body sway remains primarily research based. Use of
tricyclic antidepressants (TCAs) is comVOLUME 3 • NUMBER 3 • SUMMER 1995

Lagbrhs~7bodeetal

monly recognized to increase the risk of
falls and hip fractures in older patients. In
contrast, little is known about the use of
selective serotonin reuptake inhibitors
(58RIs) in older patients despite their increased use in this group. Unlike the
TeAs, 55RIs are not associated with seda..
tion, significant anticholinergic effects,
cardiac conduction changes, or orthostatic hypotension. Therefore, they
may be considered to be a safer treatment, particularly for the medically compromised geriatric patient. However, a
recent study (Ruthazer and Lipsitz 1 !)

noted that among elderly; institutionalized women receiving antidepressant
treatment, a larger percentage of those
taking SSRIs fell, compared with those
taking TeAs (53% vs, 14%; ratio 9/17 vs.
5/35; P = 0.003). These authors did not
specify which 55RIs were studied and did
not find a relationship between SSRIsand
falls in men. According to our findings,
one way by which SSRIs might increase
the risk of falling in older patients is balance impairment. The underlying mechanism of such impairment is unclear. The
main sensory systems involved in control-

FIGURE 3. length of 8'vay path (L t in em) with eyes closed for individual subjects treated with sertraUne

L (em)

200
180

-

Patient#1

-f- Patient#4

160

-- Patient #13
--- Patient #14

140

-H-

-+-

120

Patient #15

Patient #19

........ Patient #20

100

--- Patient #22
..... Patient #25

80

-.- Patient#34

60
40

0

1

Week

THE AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY

2

223

Sertraline and Nortriptyline
FIGURE 4. Increase of the area included within the path of the center of pressure (Ao, in sq. em)
of older, depressed patients during the first 2 weeks oCtreatment with scrtraUne
(mean ±SD)

ling the body's center of gravity are proprioception, enteroception, vision, and
the vestibular system. The afferent pathways involve the spinal cord, brain stem,
cerebellum, midbrain, and sensory areas
of the cortex. Interference with any of
these pathways may therefore result in an
increase in body sway SSRIs could affect
these pathways at three levels: basal ganglia, vertebrobasilar blood flow; and cerebellum. 24
Bouchard et al. 28 reported an increased risk of extrapyramidal symptoms
during treatment with fluoxetine, They
suggested that this effect might arise
through SSRI-mediated inhibition of
dopamine production or through release
by neurons of the basal ganglia. Older
patients with age-related dopamine
neuronal degeneration are probably
more sensitive to this decrease of
dopamine availability and may not be
able to compensate as rapidly for this
224

impairment. Baldessarini and Marsh 29
tested this hypothesis in a laboratory
model and concluded that fluoxetine
moderately, but significantly; inhibited
acute synthesis of dopamine in several
areas of the mammalian forebrain. These
effects appeared to persist or even to increase in the hippocampus and striatum.
Recent data30 suggest the possibility that
serotonergic projections from the raphe
nuclei to the midbrain and basal ganglia
can inhibit dopamine neurons, thus de..
creasing dopamine availability at their terminals by a 5-HTz-mediated synaptic
mechanism. Sertraline does not block
dopamine receptors but is unique among
antidepressants at blocking uptake of
dopamine into rat brain synaptosomes. 3 1,32 It is not known whether sertraline's potency is sufficient to affect
dopamine uptake in vivo.
Recent studies33t34 point out that diz ..
ziness in older patients is often provoked
VOLUME 3 • NUMBER 3 • SUMMER 1995

Lagbrlss~7bodeetaL

by disorders of the autoregulatory mechanism of the cerebellar blood flow This
suggests an important contribution of
vertebrobasilar ischemia to dizziness. Serotonin is a potent vasoconstrictor that
may reduce the vertebrobasilar flow The
consequence of such reduction may not
be clinically relevant in younger patients
with adequate vascular autoregulation
and compensatory mechanisms. Further
research is needed to elucidate SSRIs' effects on cerebellar blood flow
In the molecular layer of the cerebellum, 5-HTI-B serotonin receptors have
been found, and 5-HT2 serotonin receptors have been described in the inferior
olive. 35 In thiamine-deprived animals, a
specific serotonergic cerebellar syndrome includes a selective degeneration
of the serotonergic cerebellar systems
and an exaggerated serotonergic tumover. 35 In human cerebellar cortical
atrophy; comparable serotonergic disturbance has been observed in the cerebro-

spinal fluid. 36 The effects of SSRIs on the
serotonergic cerebellar systems are unknown. Therapeutic results have been
obtained with L-5-HTP in patients with
cerebellar cortical atrophy; therefore it is
possible that 55RIs may also improve
these patients. Alternatively SSRIs may
deplete the serotonergic cerebellar neurons by blocking serotonin reuptake and
result in a cerebellar syndrome analogous
to thiamine deprivation in animals.

CONCLUSION
Sertraline caused an acute significant
change in body sway in older, depressed
patients with their eyes both open and
closed. This change in balance happened
after 1 week of treatment and did not
appear to be dose dependent. By the second week of treatment, the increase in
body sway failed to achieve significance.
Apparently the patients compensated for

FIGURE 5. Area Included within the path of the center of pressure (Ao, in sq. em) of healthy, untreated (control) subjects

THE AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY

225

Sertraline and Nortriptyline
the drug-induced impairment of their
body sway during the second week of
treatment despite sertraline dose increase. The increase of body sway may
have failed to achieve significance at Week
2 because of the limited number of patients. Perhaps more sensitive measures,
such as single-leg stance, would have
yielded greater statistical significance. Despite the absence of clinical .and demographic differences between the sertraline
and nortriptyline groups, the interpretation of the current data should be tempered by the fact that patients were not
strictly randomized. In. order to confirm
the results and determine whether other
SSRIsaffect body sway, we are continuing
to evaluate patients during double-blind
therapy with nortriptyline vs, SSRIs. Further prospective controlled studies looking at the association between the use of
SSRIs and risk of falls are also needed. In
FIGURE 6.

226

the current study, nortriptyline did not
increase instability in older patients despite its greater tendency to induce sedation and its anticholinergic and
orthostatic-hypotensive effects. Miller et
al.37 reported a decrease in subjective
complaints of dizziness in older, depressed patients after nortriptyline treatment of underlying depression. Like
other somatic complaints in depressed
patients, dizziness may be erroneously
attributed to medication side effects. Objective measurement with the force-platform quantifies the body sway and may
clarify the relationship between the subjective complaint ofdizziness and the use
of antidepressants. Our unexpected finding, that sertraline acutely impairs the balance of older patients, highlights the fact
that medications are frequently introduced in older populations on the assumption that their side-effect profiles

Length of sway path (L, in em) of older, depressed patients during the rust 2 weeks of
treatment with nortriptyUne

VOLUME 3 • NUMBER 3

•

SUMMER 1995

"Lagbrissi-Tbode et ale

FIGURE 7.

Length of sway path (L, in em) ofhealtlty, untreated (control) subjects

match those obtained in younger patients. Using newly introduced medications without first identifying those that
have the potential to induce gait instability and falls in older patients may be particularly injudicious. Because of the high
risk of falling identified in epidemiologic
studies, it would seem prudent for geriatric psychiatrists to examine the postural
stability of patients by means of a simple
clinical procedure such as a Romberg test
before starting such patients on SSRI
medications.
Note: Data in this article were presented in part at the New Investigator
Awardee Poster Session, 34th Annual
Meeting of the New Clinical Drug Evalu-

ation Unit of the National Institute of
Mental Health, Marco Island, PL, May 31,
1994.
The authors thank the medical and nursing staffofthe Geriatric Clinical Unit; in
particular, Benoit H. Mutsant, M.D.,
Robert Sweet, M.D., Jules Rosen, M.D.,
Rona E. Pasternak, M.D., and Robert D.
Nebes, Ph.D.
This study was supported in part by
a Merck/AFAR Fellowship in Geriatric
Clinical Pharmacology (Dr. LaghrissiThode) and USPHS grants MH..OI040 (Dr.
Po/lock) and 30915 (Dr. Kupferf from the
National Institute "ofMental Health, Bethesda, MD.

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VOLUME 3 • NUMBER 3

• SUMMER 1995