Table 15.2 (continued)

Antidepressant

Clinical study

Clinical observations

impaired hepatic function or severely impaired renal

function warrant specific warnings or dose

recommendations. Specifically, following oral

administration in the presence of fluvoxamine, the area

under the plasma concentration-time curve and Cmax of

duloxetine significantly increased by 460% (90%: CI

359, 584) and 141% (90%: CI 93, 200), respectively. In

addition, smoking is associated with a 30% decrease in

duloxetine concentration.

Skinner et al.

(2003)

Elderly participants >65 years of age had a safety

profile of duloxetine comparable to their younger

counterparts. Specific dose recommendations for

duloxetine in the elderly are not warranted

Mirtazapine

Timmer et al.

(2000)

Mirtazapine binds to plasma proteins (85%) in a

nonspecific and reversible way. The absolute

bioavailability is approximately 50%, mainly because

of gut wall and hepatic first-pass metabolism.

Mirtazapine shows linear pharmacokinetics over a dose

range of 15–80 mg. The presence of food has a minor

effect on the rate, but does not affect the extent, of

absorption. The PK profiles of mirtazapine are

dependent on gender and age: Females and the elderly

show higher plasma concentrations than males and

young adults. The elimination half-life of mirtazapine

ranges from 20 to 40 h, which is in agreement with the

time to reach steady state (4 to 6 days). Total body

clearance as determined from intravenous

administration to young males amounts to 31 L/h. Liver

and moderate renal impairment cause an approx. 30%

decrease in oral mirtazapine clearance; severe renal

impairment causes a 50% decrease in clearance.

Biotransformation is mainly mediated by the CYP2D6

and CYP3A4 isoenzymes. Inhibitors of these

isoenzymes, such as paroxetine and fluoxetine, cause

modestly increased mirtazapine plasma concentrations

(17% and 32%, respectively) without leading to

clinically relevant consequences. Enzyme induction by

carbamazepine causes a considerable decrease (60%) in

mirtazapine plasma concentrations

Hilas and Avena-

Woods (2014)

Nearly 15–20% of older adults experience

unintentional weight loss and require intervention to

maintain quality of life. In recent years, mirtazapine has

gained attention not only for its antidepressant effects

but also for its potential benefits in underweight

patients. This agent has been found to increase appetite

and weight in adults compared with placebo and other

antidepressants

Begg et al. (1989)

All of 12 elderly patients enrolled (aged 60–86 years)

showed half-lives greater than or equal to 2.5 days with

a mean of 6  2.8 (SD) days. In six of the patients, the

(continued)

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M. Bhaskar et al.