21 antidepressants showed that in order to derive better clinical benefits, the dose

adjustment of antidepressants should be based on both age and dose combined

covariates than age or dose separately (Holper 2020). Presently, there are four

major categories of antidepressants, viz., selective serotonin reuptake-inhibitors

(SSRIs), monoamine oxidase-inhibitors (MAOI), the presynaptic noradrenalin-

receptor antagonists, and others. Due to limitations of space, we are not able to

discuss every member of the antidepressants, but some typical examples of the main

representatives of the groups involved are described in detail.

Tricyclic antidepressants (TCAs) such as amitriptyline, imipramine, desipramine,

nortriptyline, and tetracyclic maprotiline constitute old and traditional agents used in

the pharmacological treatment of depression in elderly patients. These molecules are

characterized by incomplete absorption, varying systemic availability secondary to

hepatic first-pass extraction, lipid solubility, and high degree of tissue and protein

binding (Ereshefsky et al. 1988). The use of these drugs is of highest concern in

elderly as a result of increased drug sensitivity or because of increased plasma

concentrations secondary to altered drug disposition. CNS toxicity, orthostatic

hypotension leading to dizziness or falls, and direct electrophysiological cardiac

effects (QT prolongation) that may trigger cardiac arrhythmia are the major concerns

with these agents (Taylor 2015). CNS-induced toxicity by TCAs is generally under-

reported, because it may be difficult to diagnose in the early stages when it may be

mistaken for increasing depression or emerging psychosis. In severe form, it may

appear as overt delirium or seizures. Several clinical studies have concluded that

both TCA plasma concentrations and age are risk factors for TCA-induced delirium;

however, all antidepressants can contribute to delirium (Alagiakrishnan and Wiens

2004).

At present, selective serotonin reuptake inhibitors (SSRIs) are the most prescribed

class of antidepressants, and newer molecules often have more selective benefits

(MacQueen et al. 2016). The main members of SSRIs are fluoxetine, paroxetine,

sertraline, citalopram, and escitalopram, which are frequently used in clinical prac-

tice. Due to the weak receptor affinity, they have better tolerability than TCAs.

However, fluoxetine due to its longer half-life and subsequent higher side effects and

paroxetine due to the high anticholinergic effects are not recommended for elderly

patients. SSRIs are usually well absorbed from the GI tract and represent high

protein binding in the blood stream. Venlafaxine, duloxetine, and reboxetine pro-

duce dual effect s (serotonin and norepinephrine), and are selectively norepinephrine

reuptake inhibitors (SNRIs) with similar efficacy to TCAs, but have weaker auto-

nomic side effects. Venlafaxine may increase blood pressure. Fluoxetine and parox-

etine are also strong inhibitors of CYP450 coenzymes; therefore, they have high

potential to cause pharmacokinetic drug-drug interactions. Less potent inhibitors of

this class are citalopram and escitalopram. The abovementioned representatives of

SNRIs exert weak interaction activity with other drugs.

Because of the high rates of side effects and drug-drug interactions (DDIs), the

monoamine oxidase inhibitors (MAO) are not considered the first- or even the

second-line of treatment for depression in the elderly. Thus, we do not intend to

go into many details about this group of drugs. Owing to their synergistic effect with

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