Table 15.2 (continued)

Antidepressant

Clinical study

Clinical observations

profile of elimination was suggestive of saturable

elimination. There was a marked variability in the

elimination of mirtazapine in elderly patients

Reboxetine

Poggesi et al.

(2000)

Reboxetine displayed linear PK, with dose-

proportional changes, in elderly depressed patients.

Mean total urinary recovery ranged from 4.06% to

6.17%. The mean area under the plasma concentration-

time curve (AUCtau) and the maximum plasma drug

concentration (Cmax) showed considerable variation

between patients given a dose of 4 mg/day, AUCtau

was 1466–6866 ng h/mL, and Cmax ranged from 169 to

663 ng/mL. It means Cmax and AUCtau values are

higher (and more variable) than in young adults. These

observations support the use of a lower starting dose

(4 mg/day) of reboxetine in the elderly

Bergmann et al.

(2000)

Cmax in the healthy elderly was 271  86 ng/mL,

compared with 111  28 ng/mL in the young subjects

after a single 4 mg dose, although in both groups Cmax

was observed after 2 h. the AUC infinity was nearly

four times that in the younger subjects

(8345  3107 ng h/mL vs. 2106  881 ng h/mL) and

the t1/2 was twice as long (24  6 h vs. 12  3 h). Renal

clearance was also reduced

Hajós et al. (2004)

Unlike conventional tricyclic antidepressants (TCAs),

reboxetine had only minimal sedative and

cardiovascular liabilities, probably due to increased

pharmacological specificity of reboxetine as compared

with TCAs. Unlike serotonin reuptake inhibitors, this

selective and specific norepinephrine reuptake inhibitor

demonstrated a distinct side-effect profile with

diminishing sexual dysfunction and GI tract side

effects. The starting dose of reboxetine should be

reduced by 50% in the elderly patients with renal or

hepatic impairment or in patients receiving potent

CYP3A4 inhibitors

Agomelatine

Fornaro et al.

(2010)

Melatonin and its receptor agonists (e.g., agomelatine)

help to correct age-related changes in circadian rhythm

response to environmental stimuli in rodents and could

prove to be useful in treating/preventing or delaying

disturbances of circadian rhythmicity and/or sleep

disorders in older people. In humans, agomelatine is

well absorbed following oral administration, but

absolute bioavailability is about 5–10% due to its high

first-pass effect, which may be considered in special

populations such as the elderly or hepatic disordered

patients. Volume of distribution of approx. 35 L, and is

85–95% bound to plasma proteins. Extensively

metabolized by the CYP450 isoforms 1A1, 1A2, and

2C9. The mean terminal elimination half-life is 2.3 h

(continued)

15

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

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