Table 15.2 (continued)
Antidepressant
Clinical study
Clinical observations
“difficult drug to use in the elderly,” when compared
with nortriptyline
Glassman et al.
(1979)
A group of 44 inpatients (34–76 years, mean
58.5 years) received imipramine to achieve a
therapeutic imipramine plus desipramine concentration
of at least 200 μg/L. An orthostatic change of 26 mmHg
was seen during treatment, compared with a
pretreatment drop of 10.9 mmHg
Benetello et al.
(1990)
26 patients received a single 25 mg dose of imipramine
by intramuscular injection. 14 patients were between
the ages of 66 and 77 years. A significant age difference
in total body CL was observed only in males. The six
younger men had a mean CL of 0.851 L/h/kg compared
with 0.396 L/h/kg for the seven older men. The extent
of formation of desipramine was also significantly
reduced in the elderly regardless of gender
Desipramine
Antal et al. (1982)
Calculated CL after a single desipramine 75 mg oral
dose in 12 non-institutionalized elderly patients (55 to
86 years, mean age 72 years). Based on calculated oral
CL values, maintenance doses were chosen to produce
CSS at the low end of the presumed therapeutic range
(30–50 μg/L). Mean oral CL was 1.78 L/h/kg (range
0.60–8.36), and mean t1/2 was 21 h (range 9.4–36.5 h).
Predicted CSs correlated with observed CSs (r ¼ 0.967,
p < 0.0005)
Abernethy et al.
(1985)
35 healthy volunteers aged 21–85 years received 50 mg
orally. The t1/2 was somewhat prolonged in elderly men
compared with younger men (31 vs 21 h, p < 0.05),
with oral CL slightly and not significantly reduced. For
women, t1/2 and CL did not change significantly with
age. There were no changes in protein binding. Thus,
little change in desipramine dose is required to obtain
similar desipramine plasma concentrations during long-
term administration for both young and elderly patients
Kutcher et al.
(1986)
ECG or EKG changes in 10 elderly patients 60–
85 years of age (no younger control group) who were
undergoing treatment with desipramine was analyzed.
Significant changes in EKG parameters were
prolongation in PR interval and QRS complexes, QTc
was decreased, and a further observation that a
significant correlation existed between PR and QTc
changes and 2-hydroxy-desipramine concentrations.
These investigators suggest the necessity of regular
ECG monitoring for elderly patients
Nortriptyline
Rubin et al. (1985)
Kragh-Sorensen
and Larsen (1980)
The relationship between dose and CSS in 33 patients
(24–86 years) as well as the relation between age and
CSs in 116 hospitalized patients (18–86 years) was
evaluated. Groups were comprised of participants in
different studies and concentrations were determined
(continued)
15
The Importance of Drug Dose Adjustment in Elderly Patients with Special. . .
251