Table 15.2 Clinical features of antidepressant drugs: safety and efficacy assessment in young
adults versus elderly persons
Antidepressant
Clinical study
Clinical observations
Amitriptyline
Schulz et al. (1983)
The disposition of a single parenteral or single oral dose
of amitriptyline was followed in seven young (mean
age 22 years, range 21–23) and five elderly (mean age
71 years, range 62–81) healthy men. The mean
systemic clearance did not change with age
(10.8 2.1 mL/min/kg in elderly and 12.5 2.3 mL/
min/kg in young subjects). Mean t1/2 was longer in the
older (21.7 2.9 h) than in the younger group
(16.2 6.1 h) as a result of an increase in the volume of
distribution (17.1 2.4 and 14.1 2.0 L/kg). The
bioavailability and the fraction of the drug bound to
plasma proteins did not change with age
Ghose and Spragg
(1989)
Elimination half-life of amitriptyline was 31 h in
elderly subjects. PK parameters of amitriptyline were
comparable to other published studies involving elderly
people. Compared to placebo and lofepramine,
amitriptyline produced drowsiness and dry mouth,
reduced salivary volume and increased movement
reaction time. These effects correlated with the plasma
amitriptyline levels
Henry et al. (1981)
The PK of amitriptyline (AMI) was evaluated in six
healthy elderly volunteers (72–83 years of age) after a
single dose of 125 mg of AMI-HCl. AMI was absorbed
rather slowly (mean peak time 10.4 1.6 h) but very
efficiently (F: 0.59–0.75). The rate of formation of
nortriptyline (NT) and the appearance clearance values
(0.18–0.45 L/h/kg) of AMI were significantly lower
than those previously described for younger subjects.
Reversible alterations in ECG were observed in five
cases concomitantly with AMI peak plasma
concentrations. The results indicate the desirability of
reduced and/or divided daily doses of AMI in the
elderly
Imipramine
Gram et al. (1977)
CSS of imipramine in 76 patients (20–65 years) who
were given a range of dosages (150–225 mg/day) for 2–
5 weeks were recorded. Women aged 30–39 years had
lower concentrations than women 20–29, 40–49, and
50–59, or men 50–59 and 60–65 (all at the p < 0.05
level, or better). Men aged 30–39 years had lower
concentrations than men 60–65 years
Bjerre et al. (1981)
Six patients (64–78 years) received imipramine 50–
200 mg/day. Plasma concentrations were determined
by quantitative TLC and compared with six patients
(62–79 years) receiving nortriptyline 40–100 mg/day.
An increase in imipramine dosage generally resulted in
a corresponding increase in imipramine concentrations;
and a disproportionate rise in the metabolite
desipramine was observed, making imipramine a
(continued)
250
M. Bhaskar et al.