Important considerations.
- Since most antidepressants require several weeks to demonstrate therapeutic benefit, patients with a short life expectancy are unlikely to benefit from their initiation.
- Initiating antidepressants is not appropriate for acutely delirious patients.
- Psychostimulants are often considered for patients with a prognosis shorter than a few months since their onset of action is typically days compared with weeks to a month with more usually prescribed antidepressants

For many patients with a diagnosis of depression and a markedly decreased quality of life, prompt initiation of psychological counseling and pharmacotherapy is often necessary, even if that means a non-oral route. On the other hand, patients who are not actively depressed but rather are on antidepressants for a history of depression, may do better if their antidepressant pharmacotherapy is held until they were able to tolerate medications by mouth.

Most antidepressants and psychostimulants can be crushed or given as an elixir via an enteral tube. Citalopram, escitalopram, fluoxetine, paroxetine, sertraline, nortriptyline, doxepin, and methylphenidate are all available as solutions or concentrate. Short-acting formulations are safe to crush and give via an enteral tube, while long-acting formulations are not.
Mirtazapine is available as an oral dissolving tablet (ODT). The ODT is placed under the tongue and dissolves upon contact with a patient’s saliva. Still, much of the absorption occurs in the stomach and intestines.
Selegiline is a monoamine oxidase inhibitor. It is available as an ODT and as a transdermal (TD) patch. These formulations experience less first-pass metabolism compared with the regular oral tablet of selegiline
Doxepin is a tricyclic antidepressant. It is available in a topical cream to treat pruritus. There have been case reports regarding its use of topically and rectally to treat depression, although it has not been evaluated in any controlled way nor has a reasonable dose been identified.
Amitriptyline is a tricyclic antidepressant. It is available intravenously (IV) and there are case reports of its compounded use as buccal, topical, and rectal formulations.
Fluoxetine is selective serotonin reuptake inhibitor. A case report describes its effective use when compounded into topical and rectal formulations
Citalopram is selective serotonin reuptake inhibitor. It is available IV.
Methylphenidate is psychostimulant. It is available as a solution for patients who can swallow small amounts or for whom use of an enteric tube is feasible. There is a commercially available transdermal methylphenidate patch that should be applied 2 hours prior to desired effect and removed 9 hours after.
Ketamine is an N-methyl-D-aspartate receptor antagonist. While the most effective dosing and delivery strategy has not yet been determined for use in depression, many studies have assessed IV dosing of 0.5 mg/kg either using single doses or repeated doses every 1-2 weeks.

See reference for more information.

Adapted from Tapper C, Arnold R, Pruskowski. Non-oral pharmacotherapy options for depression. Palliative Care Network of Wisconsin. Fast facts and concepts #372. Internet. Accessed on December 20, 2018.