Table 15.2 (continued)

Antidepressant

Clinical study

Clinical observations

comparable decreases in AUC0-24 and Cmax. In the

elderly volunteers, the t1/2 for fluoxetine was 25%

longer (5.0 vs. 4.0 days) and for norfluoxetine was 33%

longer (20 vs. 15 days), although variability and sample

size precluded statistical significance. Fluoxetine

dosing inhibited CYP2C19 activity in both age groups,

increasing the (S)- to (R)-mephenytoin ratio three- to

four-fold ( p < 0.01). The half-lives of fluoxetine and

norfluoxetine at 40 mg/day were longer than commonly

reported in the literature and may be longer in elderly

subjects. Fluoxetine substantially inhibited the

metabolism of the CYP2C19 substrate (S)-

mephenytoin

Gibbons et al.

(2012)

Response and remission rates at 6 weeks were analyzed

for 2635 adults. The antidepressant fluoxetine and

venlafaxine are efficacious for major depressive

disorder in all age groups, although more so in young

and adults compared with geriatric patients

Goldstein et al.

(1997)

The high BMI group, but not the low/normal BMI

group, had a statistically greater proportion of

fluoxetine-treated patients who lost at least 5% of their

baseline weight

Paroxetine

Bourin et al. (2001)

Paroxetine is well absorbed orally and undergoes

extensive first pass metabolism that is partially

saturable. Its metabolites are pharmacologically

inactive. Steady-state levels are achieved after 4–

14 days and an elimination half-life of 21 h is consistent

with once-daily dosing. There is a wide inter-individual

variation in the PK of paroxetine in adults as well as in

the young and the elderly with higher plasma

concentrations and slower elimination noted in the

latter. Serious adverse events are, however, extremely

rare even in overdose.

Feng et al. (2006)

A two-compartment nonlinear PK model with additive

and proportional error provided the best base model for

description of the data of 171 subjects with mean age of

77 years. Weight and CYP2D6 polymorphisms were

found to have a significant effect on maximal velocity

(Vm), whereas sex had an effect on volume of

distribution of the central compartment. The Vm

estimates in each of the CYP2D6 phenotypic groups

were 125 μg h^1 in poor metabolizer (n ¼ 1),

182 μg h^1 in intermediate metabolizers (n ¼ 28),

454 μg h^1 in extensive metabolizers (n ¼ 36) and

3670 μg h^1 in ultra-rapid metabolizers (n ¼ 5)

Kaye et al. (1989)

In elderly subjects, there is wide inter-individual

variation in steady-state PK parameters, with

statistically significantly higher plasma concentrations

and slower elimination than in younger subjects,

(continued)

15

The Importance of Drug Dose Adjustment in Elderly Patients with Special. . .

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