Standard dosage	Varies by agent [35]. To minimize side effects, starting dose should be half of that prescribed for a younger adult. Increase dose over 1 to 2 week intervals, with plan to reach therapeutic dosing within 4 weeks. While average therapeutic dose is typically lower than that of a younger adult, there is a fair amount of inter-individual variability, and some older adults will require doses that meet or exceed the average therapeutic dose for younger adults [34].
Contraindications	For venlafaxine: uncontrolled hypertension, hyponatremia.
Main drug interactions	For all SNRIs: simultaneous treatment with linezolid or an MAO-inhibiting agent. For duloxetine: avoid thioridazine due to CYP2D6 interaction. For desvenlafaxine: avoid axitinib due to CYP3A4 interaction [35].
Main side effects	Venlafaxine may cause noradrenergic side effects that include dry mouth, constipation, and tachycardia, as well as treatment-emergent hypertension. Abrupt discontinuation of venlafaxine may lead to symptoms such as nausea, chills, insomnia, irritability, and parasthesias. Duloxetine has lower risk for treatment-emergent hypertension, and fewer discontinuation symptoms when treatment is terminated, but may be associated with greater risk for liver enzyme abnormalities.
Special points	For individuals with normal hepatic metabolism, venlafaxine is primarily metabolized to O-desmethylvenlafaxine (ODV) by the enzyme CYP4502D6, and ODV plasma levels are normally two to three times higher than those of the parent drug. As a result, with the exception of patients who are “poor metabolizers” through the CYP450 2D6 system, patients who have been treated with venlafaxine have been treated (primarily) with desvenlafaxine.
Cost-effectiveness	The extended-release formulation of venlafaxine is considerably more expensive than the standard-release formulation, and its relatively small efficacy advantage has not been viewed as sufficient justification to offset its higher cost. Desvenlafaxine and duloxetine are not available in generic formulation, and are more expensive than standard-release venlafaxine.