Table 15.2 (continued)

Antidepressant

Clinical study

Clinical observations

by different analytical methods. The results indicated

that nortriptyline C^SS were proportional to dosage.

Furthermore, dose normalized C^SS appeared to increase

with age, suggestive of altered disposition of

nortriptyline in older patients

Dawling et al.

(1980)

Patients received a single dose of nortriptyline before

starting long-term therapy; plasma nortriptyline

concentrations were determined by GC with nitrogen-

phosphorus detection

CL of the initial dose was used to predict the regimen

needed to bring C^SS into the 50–150 μg/L range.

Predicted and actual mean C^SS were significantly

correlated (r ¼ 0.71, p < 0.002), suggesting this as a

possible method for avoiding toxicity in the elderly

Doxepin

Ereshefsky et al.

(1988)

A group of 61 patients (mean 57 years) undergoing

plasma concentration were monitored from facilities

throughout the state of Texas. Over 80% of the plasma

concentrations were generated from inpatients. Based

on C^SS of doxepin and dimethyl-doxepin, the

investigators reported a weak but significant reduction

in oral CL vs age, with r ¼ 0.16 ( p < 0.002). A

comparison of mean oral CL values in patients less than

55 years vs those >55 years suggested that lower doses

would be needed to achieve a targeted C^SS in elderly

patients. In their database, doxepin was frequently

prescribed for the elderly. Of the 211 patients treated

with either imipramine (n ¼ 151) or doxepin (n ¼ 61),

the mean age for doxepin recipients was 57 years

compared with 28 years for imipramine

Fluoxetine

Altamura et al.

(1994)

Fluoxetine has a nonlinear PK profile. Therefore, the

drug should be used with caution in patients with

reduced metabolic capability (i.e., hepatic dysfunction).

In contrast, the PK values of other antidepressants are

not affected by age. This finding together with the

better tolerability profile of fluoxetine (compared with

tricyclic antidepressants) makes this drug particularly

suitable for use in elderly patients with depression.

Furthermore, the PK parameters of fluoxetine are

neither affected by obesity nor renal impairment

Ferguson and Hill

(2006)

Plasma concentration of fluoxetine and norfluoxetine in

geriatric patients was higher than previously reported in

the literature. Elderly women had a significantly higher

serum level of norfluoxetine than men. The terminal

half-life of norfluoxetine was longer in patients over the

age 75; elderly women had a significantly slower rate of

norfluoxetine elimination than similarly aged men

Harvey and

Preskorn (2001)

Fluoxetine AUC0-24, C0, and Cmax did not differ in

young and elderly subjects. The norfluoxetine C0 was

22% lower in elderly subjects ( p < 0.05), with

(continued)

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M. Bhaskar et al.