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Query:

Response:

Calculated Shard: 112 (from laksa143)

2. Crawled Status Check

Query:

curl -X POST \
  'http://laksa112.int.ahrefs:8124/' \
  -H 'Content-Type: text/plain' \
  -H 'X-ClickHouse-Database: crawler3' \
  -H 'Authorization: Basic YXBpOg==' \
  -d 'SELECT getAhrefsURLFromUnparsed(src_unparsed) AS found_url, ifNull(toUnixTimestamp(download_stamp), 0) AS crawl_time, ifNull(toUnixTimestamp(props_url_first_seen), 0) AS first_indexed_time, download_http_code AS http_code, src_unparsed AS src_unparsed, src_root_hash AS src_root_hash, history_drop_reason AS history_drop_reason, meta_title AS meta_title, meta_descriptions AS meta_descriptions, attrs_boilerpipe_text AS attrs_boilerpipe_text, attrs_markdown AS attrs_markdown, attrs_readable_markdown AS attrs_readable_markdown, meta_canonical AS meta_canonical FROM crawler3.page_info_local FINAL PREWHERE (src_root_hash, src_unparsed) IN ((getAhrefsRootHashFromUnparsed(getAhrefsUnparsedNoserviceFromURL(\'https://www.mypcnow.org/fast-fact/non-oral-pharmacotherapy-options-for-depression/\')), getAhrefsUnparsedNoserviceFromURL(\'https://www.mypcnow.org/fast-fact/non-oral-pharmacotherapy-options-for-depression/\'))) FORMAT JSONEachRow'

Response:

{"found_url":"https:\/\/www.mypcnow.org\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/","crawl_time":1776456380,"first_indexed_time":1575193160,"http_code":200,"src_unparsed":"org,mypcnow!www,\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/ s443","src_root_hash":"12651975913890157512","history_drop_reason":null,"meta_title":"Non-Oral Pharmacotherapy Options for Depression | Palliative Care Network of Wisconsin","meta_descriptions":["Background for Fast Fact #372: While psychological counseling remains the mainstay of depression management, treatment with pharmacotherapy can achieve better outcomes for many patients (1). Palliative care clinicians may encounter patients with depression who are nothing by mouth (NPO) for prolonged periods of time due to swallowing problems or who have GI abnormalities"],"attrs_boilerpipe_text":"Skip to content\nAbout\nAdvocacy\nBoard of Directors\nFast Facts\nFast Facts Directory\nAbout Fast Facts\nFast Facts Quiz\nGeriatric Fast Facts\nPublications\nGuidebooks\nEssential Fast Facts\nFor Chaplains\nFor Nurses\nFor Social Workers\nResources\nPalliative Care Teams & Program Development\nEducation\nCommunication\nTools for Clinicians\nLectures & Presentations\nSystems Change\nNews\nContact\nDonate\nSearch for:\nSearch for:\nNon-Oral Pharmacotherapy Options for Depression\nPrint this Page\nFast Fact Number:\n372\nBy:\nCorey Tapper MD, MS, Robert M Arnold MD, Jennifer Pruskowski PharmD\nCategories:\nAge Friendly Care: The 4 Ms of Geriatric Care\n,\nFast Facts By Specialty\n,\nMedications\n,\nNon-Opioid Medications\n,\nPharmacology\n,\nPsychology\/Psychiatry\nPublished On:\nSeptember 4, 2024\nBackground for\nFast Fact #372\n:\n  While psychological counseling remains the mainstay of depression management, treatment with pharmacotherapy can achieve better outcomes for many patients (1).  Palliative care clinicians may encounter patients with depression who are nothing by mouth (NPO) for prolonged periods of time due to swallowing problems or who have GI abnormalities (e.g. small bowel transplant, a complicated abdominal wound, or severe pancreatitis). This\nFast Fact\nreviews the best evidence to identify a care approach for the non-oral pharmacologic management of depression.\nIs non-oral anti-depressant treatment necessary? \nThe first question to consider is whether a seriously ill patient who lost the ability to tolerate oral medications requires non-oral antidepressant pharmacotherapy. For many patients with a new 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. Alternatively, patients who are not actively depressed but rather are on anti-depressants for a history of depression may do better if their antidepressant pharmacotherapy is held until they were able to tolerate medications by mouth.  Prognosis and co-morbidities are important considerations.  Most antidepressants require several weeks to exhibit therapeutic benefit. Hence, patients with a short life expectancy are unlikely to benefit from their initiation.  Initiating anti-depressants is not appropriate for acutely delirious patients.\nCan the anti-depressant be given via an enteric tube?\n  Most antidepressants and psychostimulants can be crushed or given as an elixir via an enteric tube. Citalopram, escitalopram, fluoxetine, paroxetine, sertraline, nortriptyline, doxepin, and methylphenidate are all available as solutions or concentrate.  In general, short-acting formulations are safe to crush and give via an enteric tube, while long-acting formulations are not. If an enteric tube is not available and the patient is on an anti-depressant with a short half-life (e.g. paroxetine or immediate release venlafaxine), then withdrawal phenomenon could ensue. Initiation of a less standard non-oral anti-depressant (see below) may be warranted. Clinical pharmacists and consult liaison psychiatrists can be vital resources in guiding these decisions.\nFDA-approved non-oral anti-depressants\n:\n \nMirtazapine\nis 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.  Therefore, it may not be appropriate for strict NPO patients, especially those with proximal GI abnormalities.  See\nFast Fact\n#314 for more information on mirtazapine.\nSelegiline\nis a monoamine oxidase inhibitor (MAOI). 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 (4).\nThis means there is a decreased risk of tyramine-induced adverse events such as a hypertensive crisis, as there is no significant inhibition of gastrointestinal monoamine oxidase activity (5). Regardless, a psychiatrist should be involved if one wants to use this medication given its numerous drug and food interactions via oral and non-oral administration (6,7). Non-oral formulations of selegiline are relatively costly: a 30-day supply of the selegiline TD patch costs about $2000 and a 30-day supply of the ODT formulation typically costs around $3000.\nEsketamine\nis the s-enantiomer of ketamine.  It is administered intranasally, and its use is subject to a Risk Evaluation and Management Strategy.\nNon-oral formulations that have NOT been FDA-approved for depression management\n:\n \nTricyclic antidepressants (TCAs)\n: \nDoxepin\nis available in a topical cream to treat pruritus.  While there have been case reports regarding its use topically and rectally to treat depression (4), it has not been evaluated in any controlled way nor has a reasonable dose been identified.\nAmitriptyline\nis available intravenously (IV) outside the United States and there are case reports of its compounded use as buccal, topical, and rectal formulations (4,5).\nSelective serotonin reuptake inhibitors\n:\nFluoxetine:\na case report describes its effective use when compounded into topical and rectal formulations (5).\nCitalopram\nIV is available outside of the US (8).\nPsychostimulants\n: While data on psychostimulants for depression have been mixed (see\nFast Fact\n#61\n&\nFast Fact #309\n) and their provision as a Schedule II medication limits who may prescribe them, they are often considered for depressed 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 anti-depressants.  Methylphenidate is available as a solution for patients who can swallow small amounts or for whom use of an enteric tube is feasible.  For patients with strict “nothing by the GI tract” orders, there is a commercially available transdermal methylphenidate patch (9). The patch should be applied 2 hours prior to desired effect (ideally near the patient’s hip where it is felt to have best absorption) and removed 9 hours after (10). The patch and elixir costs about 7 times more than a tablet.\nKetamine\nis an N-methyl-D-aspartate (NMDA) receptor antagonist which has been studied for use in depression (11-13). Response to 0.5 mg\/kg IV can be rapid (within 24 hours) but brief (lasting up to two weeks); investigation into recurrent dosing is ongoing. See\nFast Fact\n#132\nand\nFast Fact #384\n.\nReferences\n:\n \nCujpers, P., et al. Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis. Depress Anxiety. 2009;26:279-288.\nAnttila, S. A., et al. A Review of the Pharmacological and Clinical Profile of Mirtazapine. CNS Drug Reviews, 2001;7:249-264.\nCroom, K., et al. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009;23:427-452.\nTábi, T., et al. The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson’s disease. Expert Opinion on Drug Metabolism & Toxicology. 2013;9:5,629-636.\nLee, KC., et al. Transdermal selegiline for the treatment of major depressive disorder.  Neuropsychiatr Dis Treat. 2007;3:527-537.\nKaminsky B., et al. Alternative routes of administration of antidepressant and antipsychotic medications.\nAnnals of Pharmac\notherapy. 2015;49:808-17.\nAttard A., et al. Alternative routes to oral antidepressant therapy: case vignette and literature review. \nJ of Psychopharmacology\n.  2010;24:449-454.\nKoelle J., et al. Antidepressants for the viscerally eviscerated patient: options instead of oral dosing. \nPsychosomatic Medicine\n. 1998;60:723-5.\nAzran C, et al.  Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass.  Surg Obes Relat Dis 2017;13(7):1245-7.\nMedline Plus: methylphenidate transdermal patch.\nhttps:\/\/medlineplus.gov\/druginfo\/meds\/a606014.html\n. Accessed 11\/30\/18.\nMcGirr, A., et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. \nPsychological Medicine,\n \n2015;45\n:693-704.\nZarate C.A., et al. Ketamine for depression: evidence, challenges and promise. \nWorld Psychiatry\n. 2015;14(3):348-350.\nCoyle C., et al. The use of ketamine as an antidepressant: a systematic review and meta-analysis.\nHuman Psychopharmacol Clin Exp.\n2015;30:152-63.\nSanacora G., et al. A consensus statement on the Use of Ketamine in the Treatment of Mood Disorders.  \nJAMA Psychiatry\n.  2017;74:399-405.\nConflicts of Interest:\nNone\nAuthors’ Affiliations:\nUniversity of Pittsburgh Medical Center; Pittsburgh, PA.\nVersion History:\nFirst electronically published in January 2019; originally edited by Sean Marks MD; reviewed and updated by Dr. Kerry Case in September 2024.\n \nFast Facts and Concepts\nare edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School) with the generous support of a volunteer peer-review editorial board, and are made available online by the\nPalliative Care Network of Wisconsin\n(PCNOW). The authors of each individual\nFast Fact\nand the\nFast Fact\nand Concepts\neditors are solely responsible for that\nFast Fact’s\ncontent. The full set of\nFast Facts\nare available at\nPalliative Care Network of Wisconsin\nwith contact information, and how to reference\nFast Facts.\nCopyright:\n All\nFast Facts and Concepts\nare published under a Creative Commons Attribution-NonCommercial 4.0 International Copyright (\nhttp:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/\n). \nFast Facts\ncan only be copied and distributed for non-commercial, educational purposes. If you adapt or distribute a\nFast Fact\n, let us know!\nDisclaimer:\nFast Facts and Concepts\nprovide educational information for health care professionals. This information is not medical advice.\nFast Facts\nare not continually updated, and new safety information may emerge after a\nFast Fact\nis published. Health care providers should always exercise their own independent clinical judgment and consult other relevant and up-to-date experts and resources. Some\nFast Facts\ncite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.\nSearch Fast Facts\nSearch Resources\nBecome a Subscriber\nSubscriptions are free and you will receive a weekly Fast Fact email every Friday!\nSign Up Now\nJoin PCNOW\nEmail Address\n*\nFirst Name\n*\nLast Name\n*\nPhone Number\nAddress\nOrganization\nTell Us About Yourself\n*\nClinical Role if Applicable\nDo you work in Wisconsin?\n*\nAbout\nFast Facts\nPublications\nResources\nNews\nContact\nDonate\n© 2026 Palliative Care Network of Wisconsin |   Built by\nHoan Marketing\n|\nTerms of Service\n|\nPrivacy Policy\nPage load link\nGo to Top","attrs_markdown":"[Skip to content](https:\/\/www.mypcnow.org\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/#content)\n\n[![Palliative Care Network of Wisconsin Logo](https:\/\/www.mypcnow.org\/wp-content\/uploads\/2023\/11\/PCNOW-Logo-outlined-e1696340127581.png) ![Palliative Care Network of Wisconsin Logo](https:\/\/www.mypcnow.org\/wp-content\/uploads\/2024\/01\/PCNOW-Logo-outlined-1-e1705337763292.png)](https:\/\/www.mypcnow.org\/)\n\n- [About](https:\/\/www.mypcnow.org\/about\/)\n  - [Advocacy](https:\/\/www.mypcnow.org\/about\/advocacy\/)\n  - [Board of Directors](https:\/\/www.mypcnow.org\/about\/board-of-directors\/)\n- [Fast Facts](https:\/\/www.mypcnow.org\/fast-facts\/)\n  - [Fast Facts Directory](https:\/\/www.mypcnow.org\/fast-facts\/fast-facts-directory\/)\n  - [About Fast Facts](https:\/\/www.mypcnow.org\/fast-facts\/about\/)\n  - [Fast Facts Quiz](https:\/\/www.mypcnow.org\/fast-facts\/quiz\/)\n  - [Geriatric Fast Facts](http:\/\/www.geriatricfastfacts.com\/)\n- [Publications](https:\/\/www.mypcnow.org\/publications\/)\n  - [Guidebooks](https:\/\/www.mypcnow.org\/publications#guidebooks)\n  - [Essential Fast Facts](https:\/\/www.mypcnow.org\/publications\/essential-fast-facts\/)\n  - [For Chaplains](https:\/\/www.mypcnow.org\/publications\/top-fast-facts-resources-for-chaplains\/)\n  - [For Nurses](https:\/\/www.mypcnow.org\/publications\/top-fast-facts-resources-for-nurses\/)\n  - [For Social Workers](https:\/\/www.mypcnow.org\/publications\/top-fast-facts-resources-for-social-workers\/)\n- [Resources](https:\/\/www.mypcnow.org\/resources\/)\n  - [Palliative Care Teams & Program Development](https:\/\/www.mypcnow.org\/resources\/palliative-care-teams-program-development\/)\n  - [Education](https:\/\/www.mypcnow.org\/resources\/educator-tools\/)\n  - [Communication](https:\/\/www.mypcnow.org\/resources\/communication\/)\n  - [Tools for Clinicians](https:\/\/www.mypcnow.org\/resources\/tools-for-clinicians\/)\n  - [Lectures & Presentations](https:\/\/www.mypcnow.org\/resources\/lectures-presentations\/)\n  - [Systems Change](https:\/\/www.mypcnow.org\/resources\/quality-improvement-projects\/)\n- [News](https:\/\/www.mypcnow.org\/news\/)\n- [Contact](https:\/\/www.mypcnow.org\/contact\/)\n- [Donate](https:\/\/www.mypcnow.org\/donate\/)\n\n#### Non-Oral Pharmacotherapy Options for Depression\n[Print this Page](https:\/\/www.mypcnow.org\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/?print=print)\n\n**Fast Fact Number:** 372\n\n**By:** Corey Tapper MD, MS, Robert M Arnold MD, Jennifer Pruskowski PharmD\n\n**Categories:** [Age Friendly Care: The 4 Ms of Geriatric Care](https:\/\/www.mypcnow.org\/fast-fact-category\/age-friendly-care-the-4-ms-of-geriatric-care\/ \"Age Friendly Care: The 4 Ms of Geriatric Care\"), [Fast Facts By Specialty](https:\/\/www.mypcnow.org\/fast-fact-category\/fast-facts-by-specialty\/ \"Fast Facts By Specialty\"), [Medications](https:\/\/www.mypcnow.org\/fast-fact-category\/medications\/ \"Medications\"), [Non-Opioid Medications](https:\/\/www.mypcnow.org\/fast-fact-category\/non-opioid-medications\/ \"Non-Opioid Medications\"), [Pharmacology](https:\/\/www.mypcnow.org\/fast-fact-category\/pharmacology\/ \"Pharmacology\"), [Psychology\/Psychiatry](https:\/\/www.mypcnow.org\/fast-fact-category\/psychology-psychiatry\/ \"Psychology\/Psychiatry\")\n\n**Published On:** September 4, 2024\n\n**Background for *Fast Fact \\#372*:** While psychological counseling remains the mainstay of depression management, treatment with pharmacotherapy can achieve better outcomes for many patients (1). Palliative care clinicians may encounter patients with depression who are nothing by mouth (NPO) for prolonged periods of time due to swallowing problems or who have GI abnormalities (e.g. small bowel transplant, a complicated abdominal wound, or severe pancreatitis). This *Fast Fact* reviews the best evidence to identify a care approach for the non-oral pharmacologic management of depression.\n\n**Is non-oral anti-depressant treatment necessary?** The first question to consider is whether a seriously ill patient who lost the ability to tolerate oral medications requires non-oral antidepressant pharmacotherapy. For many patients with a new 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. Alternatively, patients who are not actively depressed but rather are on anti-depressants for a history of depression may do better if their antidepressant pharmacotherapy is held until they were able to tolerate medications by mouth. Prognosis and co-morbidities are important considerations. Most antidepressants require several weeks to exhibit therapeutic benefit. Hence, patients with a short life expectancy are unlikely to benefit from their initiation. Initiating anti-depressants is not appropriate for acutely delirious patients.\n\n**Can the anti-depressant be given via an enteric tube?** Most antidepressants and psychostimulants can be crushed or given as an elixir via an enteric tube. Citalopram, escitalopram, fluoxetine, paroxetine, sertraline, nortriptyline, doxepin, and methylphenidate are all available as solutions or concentrate. In general, short-acting formulations are safe to crush and give via an enteric tube, while long-acting formulations are not. If an enteric tube is not available and the patient is on an anti-depressant with a short half-life (e.g. paroxetine or immediate release venlafaxine), then withdrawal phenomenon could ensue. Initiation of a less standard non-oral anti-depressant (see below) may be warranted. Clinical pharmacists and consult liaison psychiatrists can be vital resources in guiding these decisions.\n\n**FDA-approved non-oral anti-depressants**:\n\n- 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. Therefore, it may not be appropriate for strict NPO patients, especially those with proximal GI abnormalities. See *Fast Fact* \\#314 for more information on mirtazapine.\n- Selegiline is a monoamine oxidase inhibitor (MAOI). 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 (4). This means there is a decreased risk of tyramine-induced adverse events such as a hypertensive crisis, as there is no significant inhibition of gastrointestinal monoamine oxidase activity (5). Regardless, a psychiatrist should be involved if one wants to use this medication given its numerous drug and food interactions via oral and non-oral administration (6,7). Non-oral formulations of selegiline are relatively costly: a 30-day supply of the selegiline TD patch costs about \\$2000 and a 30-day supply of the ODT formulation typically costs around \\$3000.\n- Esketamine is the s-enantiomer of ketamine. It is administered intranasally, and its use is subject to a Risk Evaluation and Management Strategy.\n\n**Non-oral formulations that have NOT been FDA-approved for depression management**:\n\n- Tricyclic antidepressants (TCAs): *Doxepin* is available in a topical cream to treat pruritus. While there have been case reports regarding its use topically and rectally to treat depression (4), it has not been evaluated in any controlled way nor has a reasonable dose been identified. *Amitriptyline* is available intravenously (IV) outside the United States and there are case reports of its compounded use as buccal, topical, and rectal formulations (4,5).\n- Selective serotonin reuptake inhibitors: *Fluoxetine:* a case report describes its effective use when compounded into topical and rectal formulations (5). *Citalopram* IV is available outside of the US (8).\n- Psychostimulants: While data on psychostimulants for depression have been mixed (see [*Fast Fact*](https:\/\/www.mypcnow.org\/fast-fact\/use-of-psycho-stimulants-in-palliative-care\/) \\#61 & [*Fast Fact \\#309*](https:\/\/www.mypcnow.org\/fast-fact\/pharmacologic-management-of-depression-in-advanced-illness\/)) and their provision as a Schedule II medication limits who may prescribe them, they are often considered for depressed 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 anti-depressants. Methylphenidate is available as a solution for patients who can swallow small amounts or for whom use of an enteric tube is feasible. For patients with strict “nothing by the GI tract” orders, there is a commercially available transdermal methylphenidate patch (9). The patch should be applied 2 hours prior to desired effect (ideally near the patient’s hip where it is felt to have best absorption) and removed 9 hours after (10). The patch and elixir costs about 7 times more than a tablet.\n- Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist which has been studied for use in depression (11-13). Response to 0.5 mg\/kg IV can be rapid (within 24 hours) but brief (lasting up to two weeks); investigation into recurrent dosing is ongoing. See [*Fast Fact*](https:\/\/www.mypcnow.org\/fast-fact\/ketamine-in-palliative-care\/) *\\#132* and [*Fast Fact \\#384*](https:\/\/www.mypcnow.org\/fast-fact\/the-role-of-ketamine-in-depression\/).\n\n**References**:\n\n1. Cujpers, P., et al. Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis. Depress Anxiety. 2009;26:279-288.\n2. Anttila, S. A., et al. A Review of the Pharmacological and Clinical Profile of Mirtazapine. CNS Drug Reviews, 2001;7:249-264.\n3. Croom, K., et al. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009;23:427-452.\n4. Tábi, T., et al. The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson’s disease. Expert Opinion on Drug Metabolism & Toxicology. 2013;9:5,629-636.\n5. Lee, KC., et al. Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2007;3:527-537.\n6. Kaminsky B., et al. Alternative routes of administration of antidepressant and antipsychotic medications. *Annals of Pharmac*otherapy. 2015;49:808-17.\n7. Attard A., et al. Alternative routes to oral antidepressant therapy: case vignette and literature review. *J of Psychopharmacology*. 2010;24:449-454.\n8. Koelle J., et al. Antidepressants for the viscerally eviscerated patient: options instead of oral dosing. *Psychosomatic Medicine*. 1998;60:723-5.\n9. Azran C, et al. Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass. Surg Obes Relat Dis 2017;13(7):1245-7.\n10. Medline Plus: methylphenidate transdermal patch. <https:\/\/medlineplus.gov\/druginfo\/meds\/a606014.html>. Accessed 11\/30\/18.\n11. McGirr, A., et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. *Psychological Medicine,* *2015;45*:693-704.\n12. Zarate C.A., et al. Ketamine for depression: evidence, challenges and promise. *World Psychiatry*. 2015;14(3):348-350.\n13. Coyle C., et al. The use of ketamine as an antidepressant: a systematic review and meta-analysis. *Human Psychopharmacol Clin Exp.* 2015;30:152-63.\n14. Sanacora G., et al. A consensus statement on the Use of Ketamine in the Treatment of Mood Disorders. *JAMA Psychiatry*. 2017;74:399-405.\n\n**Conflicts of Interest:** None  \n **Authors’ Affiliations:** University of Pittsburgh Medical Center; Pittsburgh, PA.  \n **Version History:** First electronically published in January 2019; originally edited by Sean Marks MD; reviewed and updated by Dr. Kerry Case in September 2024.\n\n***Fast Facts and Concepts*** are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School) with the generous support of a volunteer peer-review editorial board, and are made available online by the [Palliative Care Network of Wisconsin](http:\/\/www.mypcnow.org\/) (PCNOW). The authors of each individual *Fast Fact* and the *Fast Fact* *and Concepts* editors are solely responsible for that *Fast Fact’s* content. The full set of *Fast Facts* are available at [Palliative Care Network of Wisconsin](http:\/\/www.mypcnow.org\/) with contact information, and how to reference *Fast Facts.*\n\n**Copyright:**  All *Fast Facts and Concepts* are published under a Creative Commons Attribution-NonCommercial 4.0 International Copyright (<http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/>). *Fast Facts* can only be copied and distributed for non-commercial, educational purposes. If you adapt or distribute a *Fast Fact*, let us know\\!\n\n**Disclaimer:** *Fast Facts and Concepts* provide educational information for health care professionals. This information is not medical advice. *Fast Facts* are not continually updated, and new safety information may emerge after a *Fast Fact* is published. Health care providers should always exercise their own independent clinical judgment and consult other relevant and up-to-date experts and resources. Some *Fast Facts* cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.\n\n## Search Fast Facts\n## Search Resources\n\n## Become a Subscriber\nSubscriptions are free and you will receive a weekly Fast Fact email every Friday\\!\n\n[Sign Up Now](https:\/\/www.mypcnow.org\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/)\n\n×\n\n### Join PCNOW\n\n![Palliative Care Network of Wisconsin Logo](https:\/\/www.mypcnow.org\/wp-content\/uploads\/2023\/11\/PCNOW-Logo-outlined-e1696340127581.png)![Palliative Care Network of Wisconsin Logo](https:\/\/www.mypcnow.org\/wp-content\/uploads\/2024\/01\/PCNOW-Logo-outlined-1-e1705337763292.png)\n\nToggle Navigation\n\n- [About](https:\/\/www.mypcnow.org\/about\/)\n- [Fast Facts](https:\/\/www.mypcnow.org\/fast-facts\/)\n- [Publications](https:\/\/www.mypcnow.org\/publications\/)\n- [Resources](https:\/\/www.mypcnow.org\/resources\/)\n- [News](https:\/\/www.mypcnow.org\/news\/)\n- [Contact](https:\/\/www.mypcnow.org\/contact\/)\n- [Donate](https:\/\/www.mypcnow.org\/donate\/)\n\n© 2026 Palliative Care Network of Wisconsin \\| Built by [Hoan Marketing](https:\/\/hoanmarketing.com\/) \\| [Terms of Service](https:\/\/www.mypcnow.org\/terms) \\| [Privacy Policy](https:\/\/www.mypcnow.org\/privacy-policy\/)\n\n[Page load link](https:\/\/www.mypcnow.org\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/)\n\n[Go to Top](https:\/\/www.mypcnow.org\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/)","attrs_readable_markdown":"[Skip to content](https:\/\/www.mypcnow.org\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/#content)\n\n[![Palliative Care Network of Wisconsin Logo](https:\/\/www.mypcnow.org\/wp-content\/uploads\/2023\/11\/PCNOW-Logo-outlined-e1696340127581.png) ![Palliative Care Network of Wisconsin Logo](https:\/\/www.mypcnow.org\/wp-content\/uploads\/2024\/01\/PCNOW-Logo-outlined-1-e1705337763292.png)](https:\/\/www.mypcnow.org\/)\n\n- [About](https:\/\/www.mypcnow.org\/about\/)\n  - [Advocacy](https:\/\/www.mypcnow.org\/about\/advocacy\/)\n  - [Board of Directors](https:\/\/www.mypcnow.org\/about\/board-of-directors\/)\n- [Fast Facts](https:\/\/www.mypcnow.org\/fast-facts\/)\n  - [Fast Facts Directory](https:\/\/www.mypcnow.org\/fast-facts\/fast-facts-directory\/)\n  - [About Fast Facts](https:\/\/www.mypcnow.org\/fast-facts\/about\/)\n  - [Fast Facts Quiz](https:\/\/www.mypcnow.org\/fast-facts\/quiz\/)\n  - [Geriatric Fast Facts](http:\/\/www.geriatricfastfacts.com\/)\n- [Publications](https:\/\/www.mypcnow.org\/publications\/)\n  - [Guidebooks](https:\/\/www.mypcnow.org\/publications#guidebooks)\n  - [Essential Fast Facts](https:\/\/www.mypcnow.org\/publications\/essential-fast-facts\/)\n  - [For Chaplains](https:\/\/www.mypcnow.org\/publications\/top-fast-facts-resources-for-chaplains\/)\n  - [For Nurses](https:\/\/www.mypcnow.org\/publications\/top-fast-facts-resources-for-nurses\/)\n  - [For Social Workers](https:\/\/www.mypcnow.org\/publications\/top-fast-facts-resources-for-social-workers\/)\n- [Resources](https:\/\/www.mypcnow.org\/resources\/)\n  - [Palliative Care Teams & Program Development](https:\/\/www.mypcnow.org\/resources\/palliative-care-teams-program-development\/)\n  - [Education](https:\/\/www.mypcnow.org\/resources\/educator-tools\/)\n  - [Communication](https:\/\/www.mypcnow.org\/resources\/communication\/)\n  - [Tools for Clinicians](https:\/\/www.mypcnow.org\/resources\/tools-for-clinicians\/)\n  - [Lectures & Presentations](https:\/\/www.mypcnow.org\/resources\/lectures-presentations\/)\n  - [Systems Change](https:\/\/www.mypcnow.org\/resources\/quality-improvement-projects\/)\n- [News](https:\/\/www.mypcnow.org\/news\/)\n- [Contact](https:\/\/www.mypcnow.org\/contact\/)\n- [Donate](https:\/\/www.mypcnow.org\/donate\/)\n\n#### Non-Oral Pharmacotherapy Options for Depression\n[Print this Page](https:\/\/www.mypcnow.org\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/?print=print)\n\n**Fast Fact Number:** 372\n\n**By:** Corey Tapper MD, MS, Robert M Arnold MD, Jennifer Pruskowski PharmD\n\n**Categories:** [Age Friendly Care: The 4 Ms of Geriatric Care](https:\/\/www.mypcnow.org\/fast-fact-category\/age-friendly-care-the-4-ms-of-geriatric-care\/ \"Age Friendly Care: The 4 Ms of Geriatric Care\"), [Fast Facts By Specialty](https:\/\/www.mypcnow.org\/fast-fact-category\/fast-facts-by-specialty\/ \"Fast Facts By Specialty\"), [Medications](https:\/\/www.mypcnow.org\/fast-fact-category\/medications\/ \"Medications\"), [Non-Opioid Medications](https:\/\/www.mypcnow.org\/fast-fact-category\/non-opioid-medications\/ \"Non-Opioid Medications\"), [Pharmacology](https:\/\/www.mypcnow.org\/fast-fact-category\/pharmacology\/ \"Pharmacology\"), [Psychology\/Psychiatry](https:\/\/www.mypcnow.org\/fast-fact-category\/psychology-psychiatry\/ \"Psychology\/Psychiatry\")\n\n**Published On:** September 4, 2024\n\n**Background for *Fast Fact \\#372*:** While psychological counseling remains the mainstay of depression management, treatment with pharmacotherapy can achieve better outcomes for many patients (1). Palliative care clinicians may encounter patients with depression who are nothing by mouth (NPO) for prolonged periods of time due to swallowing problems or who have GI abnormalities (e.g. small bowel transplant, a complicated abdominal wound, or severe pancreatitis). This *Fast Fact* reviews the best evidence to identify a care approach for the non-oral pharmacologic management of depression.\n\n**Is non-oral anti-depressant treatment necessary?** The first question to consider is whether a seriously ill patient who lost the ability to tolerate oral medications requires non-oral antidepressant pharmacotherapy. For many patients with a new 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. Alternatively, patients who are not actively depressed but rather are on anti-depressants for a history of depression may do better if their antidepressant pharmacotherapy is held until they were able to tolerate medications by mouth. Prognosis and co-morbidities are important considerations. Most antidepressants require several weeks to exhibit therapeutic benefit. Hence, patients with a short life expectancy are unlikely to benefit from their initiation. Initiating anti-depressants is not appropriate for acutely delirious patients.\n\n**Can the anti-depressant be given via an enteric tube?** Most antidepressants and psychostimulants can be crushed or given as an elixir via an enteric tube. Citalopram, escitalopram, fluoxetine, paroxetine, sertraline, nortriptyline, doxepin, and methylphenidate are all available as solutions or concentrate. In general, short-acting formulations are safe to crush and give via an enteric tube, while long-acting formulations are not. If an enteric tube is not available and the patient is on an anti-depressant with a short half-life (e.g. paroxetine or immediate release venlafaxine), then withdrawal phenomenon could ensue. Initiation of a less standard non-oral anti-depressant (see below) may be warranted. Clinical pharmacists and consult liaison psychiatrists can be vital resources in guiding these decisions.\n\n**FDA-approved non-oral anti-depressants**:\n\n- 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. Therefore, it may not be appropriate for strict NPO patients, especially those with proximal GI abnormalities. See *Fast Fact* \\#314 for more information on mirtazapine.\n- Selegiline is a monoamine oxidase inhibitor (MAOI). 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 (4). This means there is a decreased risk of tyramine-induced adverse events such as a hypertensive crisis, as there is no significant inhibition of gastrointestinal monoamine oxidase activity (5). Regardless, a psychiatrist should be involved if one wants to use this medication given its numerous drug and food interactions via oral and non-oral administration (6,7). Non-oral formulations of selegiline are relatively costly: a 30-day supply of the selegiline TD patch costs about \\$2000 and a 30-day supply of the ODT formulation typically costs around \\$3000.\n- Esketamine is the s-enantiomer of ketamine. It is administered intranasally, and its use is subject to a Risk Evaluation and Management Strategy.\n\n**Non-oral formulations that have NOT been FDA-approved for depression management**:\n\n- Tricyclic antidepressants (TCAs): *Doxepin* is available in a topical cream to treat pruritus. While there have been case reports regarding its use topically and rectally to treat depression (4), it has not been evaluated in any controlled way nor has a reasonable dose been identified. *Amitriptyline* is available intravenously (IV) outside the United States and there are case reports of its compounded use as buccal, topical, and rectal formulations (4,5).\n- Selective serotonin reuptake inhibitors: *Fluoxetine:* a case report describes its effective use when compounded into topical and rectal formulations (5). *Citalopram* IV is available outside of the US (8).\n- Psychostimulants: While data on psychostimulants for depression have been mixed (see [*Fast Fact*](https:\/\/www.mypcnow.org\/fast-fact\/use-of-psycho-stimulants-in-palliative-care\/) \\#61 & [*Fast Fact \\#309*](https:\/\/www.mypcnow.org\/fast-fact\/pharmacologic-management-of-depression-in-advanced-illness\/)) and their provision as a Schedule II medication limits who may prescribe them, they are often considered for depressed 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 anti-depressants. Methylphenidate is available as a solution for patients who can swallow small amounts or for whom use of an enteric tube is feasible. For patients with strict “nothing by the GI tract” orders, there is a commercially available transdermal methylphenidate patch (9). The patch should be applied 2 hours prior to desired effect (ideally near the patient’s hip where it is felt to have best absorption) and removed 9 hours after (10). The patch and elixir costs about 7 times more than a tablet.\n- Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist which has been studied for use in depression (11-13). Response to 0.5 mg\/kg IV can be rapid (within 24 hours) but brief (lasting up to two weeks); investigation into recurrent dosing is ongoing. See [*Fast Fact*](https:\/\/www.mypcnow.org\/fast-fact\/ketamine-in-palliative-care\/) *\\#132* and [*Fast Fact \\#384*](https:\/\/www.mypcnow.org\/fast-fact\/the-role-of-ketamine-in-depression\/).\n\n**References**:\n\n1. Cujpers, P., et al. Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis. Depress Anxiety. 2009;26:279-288.\n2. Anttila, S. A., et al. A Review of the Pharmacological and Clinical Profile of Mirtazapine. CNS Drug Reviews, 2001;7:249-264.\n3. Croom, K., et al. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009;23:427-452.\n4. Tábi, T., et al. The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson’s disease. Expert Opinion on Drug Metabolism & Toxicology. 2013;9:5,629-636.\n5. Lee, KC., et al. Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2007;3:527-537.\n6. Kaminsky B., et al. Alternative routes of administration of antidepressant and antipsychotic medications. *Annals of Pharmac*otherapy. 2015;49:808-17.\n7. Attard A., et al. Alternative routes to oral antidepressant therapy: case vignette and literature review. *J of Psychopharmacology*. 2010;24:449-454.\n8. Koelle J., et al. Antidepressants for the viscerally eviscerated patient: options instead of oral dosing. *Psychosomatic Medicine*. 1998;60:723-5.\n9. Azran C, et al. Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass. Surg Obes Relat Dis 2017;13(7):1245-7.\n10. Medline Plus: methylphenidate transdermal patch. <https:\/\/medlineplus.gov\/druginfo\/meds\/a606014.html>. Accessed 11\/30\/18.\n11. McGirr, A., et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. *Psychological Medicine,* *2015;45*:693-704.\n12. Zarate C.A., et al. Ketamine for depression: evidence, challenges and promise. *World Psychiatry*. 2015;14(3):348-350.\n13. Coyle C., et al. The use of ketamine as an antidepressant: a systematic review and meta-analysis. *Human Psychopharmacol Clin Exp.* 2015;30:152-63.\n14. Sanacora G., et al. A consensus statement on the Use of Ketamine in the Treatment of Mood Disorders. *JAMA Psychiatry*. 2017;74:399-405.\n\n**Conflicts of Interest:** None  \n **Authors’ Affiliations:** University of Pittsburgh Medical Center; Pittsburgh, PA.  \n **Version History:** First electronically published in January 2019; originally edited by Sean Marks MD; reviewed and updated by Dr. Kerry Case in September 2024.\n\n***Fast Facts and Concepts*** are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School) with the generous support of a volunteer peer-review editorial board, and are made available online by the [Palliative Care Network of Wisconsin](http:\/\/www.mypcnow.org\/) (PCNOW). The authors of each individual *Fast Fact* and the *Fast Fact* *and Concepts* editors are solely responsible for that *Fast Fact’s* content. The full set of *Fast Facts* are available at [Palliative Care Network of Wisconsin](http:\/\/www.mypcnow.org\/) with contact information, and how to reference *Fast Facts.*\n\n**Copyright:**  All *Fast Facts and Concepts* are published under a Creative Commons Attribution-NonCommercial 4.0 International Copyright (<http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/>). *Fast Facts* can only be copied and distributed for non-commercial, educational purposes. If you adapt or distribute a *Fast Fact*, let us know\\!\n\n**Disclaimer:** *Fast Facts and Concepts* provide educational information for health care professionals. This information is not medical advice. *Fast Facts* are not continually updated, and new safety information may emerge after a *Fast Fact* is published. Health care providers should always exercise their own independent clinical judgment and consult other relevant and up-to-date experts and resources. Some *Fast Facts* cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.\n\n## Search Fast Facts\n## Search Resources\n\n## Become a Subscriber\nSubscriptions are free and you will receive a weekly Fast Fact email every Friday\\!\n\n[Sign Up Now](https:\/\/www.mypcnow.org\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/)\n\n### Join PCNOW\n\n![Palliative Care Network of Wisconsin Logo](https:\/\/www.mypcnow.org\/wp-content\/uploads\/2023\/11\/PCNOW-Logo-outlined-e1696340127581.png)![Palliative Care Network of Wisconsin Logo](https:\/\/www.mypcnow.org\/wp-content\/uploads\/2024\/01\/PCNOW-Logo-outlined-1-e1705337763292.png)\n\n- [About](https:\/\/www.mypcnow.org\/about\/)\n- [Fast Facts](https:\/\/www.mypcnow.org\/fast-facts\/)\n- [Publications](https:\/\/www.mypcnow.org\/publications\/)\n- [Resources](https:\/\/www.mypcnow.org\/resources\/)\n- [News](https:\/\/www.mypcnow.org\/news\/)\n- [Contact](https:\/\/www.mypcnow.org\/contact\/)\n- [Donate](https:\/\/www.mypcnow.org\/donate\/)\n\n© 2026 Palliative Care Network of Wisconsin \\| Built by [Hoan Marketing](https:\/\/hoanmarketing.com\/) \\| [Terms of Service](https:\/\/www.mypcnow.org\/terms) \\| [Privacy Policy](https:\/\/www.mypcnow.org\/privacy-policy\/)\n\n[Page load link](https:\/\/www.mypcnow.org\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/)\n\n[Go to Top](https:\/\/www.mypcnow.org\/fast-fact\/non-oral-pharmacotherapy-options-for-depression\/)","meta_canonical":null}

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Meta Description	Background for Fast Fact #372: While psychological counseling remains the mainstay of depression management, treatment with pharmacotherapy can achieve better outcomes for many patients (1). Palliative care clinicians may encounter patients with depression who are nothing by mouth (NPO) for prolonged periods of time due to swallowing problems or who have GI abnormalities
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Boilerpipe Text	Skip to content About Advocacy Board of Directors Fast Facts Fast Facts Directory About Fast Facts Fast Facts Quiz Geriatric Fast Facts Publications Guidebooks Essential Fast Facts For Chaplains For Nurses For Social Workers Resources Palliative Care Teams & Program Development Education Communication Tools for Clinicians Lectures & Presentations Systems Change News Contact Donate Search for: Search for: Non-Oral Pharmacotherapy Options for Depression Print this Page Fast Fact Number: 372 By: Corey Tapper MD, MS, Robert M Arnold MD, Jennifer Pruskowski PharmD Categories: Age Friendly Care: The 4 Ms of Geriatric Care , Fast Facts By Specialty , Medications , Non-Opioid Medications , Pharmacology , Psychology/Psychiatry Published On: September 4, 2024 Background for Fast Fact #372 : While psychological counseling remains the mainstay of depression management, treatment with pharmacotherapy can achieve better outcomes for many patients (1). Palliative care clinicians may encounter patients with depression who are nothing by mouth (NPO) for prolonged periods of time due to swallowing problems or who have GI abnormalities (e.g. small bowel transplant, a complicated abdominal wound, or severe pancreatitis). This Fast Fact reviews the best evidence to identify a care approach for the non-oral pharmacologic management of depression. Is non-oral anti-depressant treatment necessary? The first question to consider is whether a seriously ill patient who lost the ability to tolerate oral medications requires non-oral antidepressant pharmacotherapy. For many patients with a new 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. Alternatively, patients who are not actively depressed but rather are on anti-depressants for a history of depression may do better if their antidepressant pharmacotherapy is held until they were able to tolerate medications by mouth. Prognosis and co-morbidities are important considerations. Most antidepressants require several weeks to exhibit therapeutic benefit. Hence, patients with a short life expectancy are unlikely to benefit from their initiation. Initiating anti-depressants is not appropriate for acutely delirious patients. Can the anti-depressant be given via an enteric tube? Most antidepressants and psychostimulants can be crushed or given as an elixir via an enteric tube. Citalopram, escitalopram, fluoxetine, paroxetine, sertraline, nortriptyline, doxepin, and methylphenidate are all available as solutions or concentrate. In general, short-acting formulations are safe to crush and give via an enteric tube, while long-acting formulations are not. If an enteric tube is not available and the patient is on an anti-depressant with a short half-life (e.g. paroxetine or immediate release venlafaxine), then withdrawal phenomenon could ensue. Initiation of a less standard non-oral anti-depressant (see below) may be warranted. Clinical pharmacists and consult liaison psychiatrists can be vital resources in guiding these decisions. FDA-approved non-oral anti-depressants : 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. Therefore, it may not be appropriate for strict NPO patients, especially those with proximal GI abnormalities. See Fast Fact #314 for more information on mirtazapine. Selegiline is a monoamine oxidase inhibitor (MAOI). 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 (4). This means there is a decreased risk of tyramine-induced adverse events such as a hypertensive crisis, as there is no significant inhibition of gastrointestinal monoamine oxidase activity (5). Regardless, a psychiatrist should be involved if one wants to use this medication given its numerous drug and food interactions via oral and non-oral administration (6,7). Non-oral formulations of selegiline are relatively costly: a 30-day supply of the selegiline TD patch costs about $2000 and a 30-day supply of the ODT formulation typically costs around $3000. Esketamine is the s-enantiomer of ketamine. It is administered intranasally, and its use is subject to a Risk Evaluation and Management Strategy. Non-oral formulations that have NOT been FDA-approved for depression management : Tricyclic antidepressants (TCAs) : Doxepin is available in a topical cream to treat pruritus. While there have been case reports regarding its use topically and rectally to treat depression (4), it has not been evaluated in any controlled way nor has a reasonable dose been identified. Amitriptyline is available intravenously (IV) outside the United States and there are case reports of its compounded use as buccal, topical, and rectal formulations (4,5). Selective serotonin reuptake inhibitors : Fluoxetine: a case report describes its effective use when compounded into topical and rectal formulations (5). Citalopram IV is available outside of the US (8). Psychostimulants : While data on psychostimulants for depression have been mixed (see Fast Fact #61 & Fast Fact #309 ) and their provision as a Schedule II medication limits who may prescribe them, they are often considered for depressed 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 anti-depressants. Methylphenidate is available as a solution for patients who can swallow small amounts or for whom use of an enteric tube is feasible. For patients with strict “nothing by the GI tract” orders, there is a commercially available transdermal methylphenidate patch (9). The patch should be applied 2 hours prior to desired effect (ideally near the patient’s hip where it is felt to have best absorption) and removed 9 hours after (10). The patch and elixir costs about 7 times more than a tablet. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist which has been studied for use in depression (11-13). Response to 0.5 mg/kg IV can be rapid (within 24 hours) but brief (lasting up to two weeks); investigation into recurrent dosing is ongoing. See Fast Fact #132 and Fast Fact #384 . References : Cujpers, P., et al. Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis. Depress Anxiety. 2009;26:279-288. Anttila, S. A., et al. A Review of the Pharmacological and Clinical Profile of Mirtazapine. CNS Drug Reviews, 2001;7:249-264. Croom, K., et al. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009;23:427-452. Tábi, T., et al. The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson’s disease. Expert Opinion on Drug Metabolism & Toxicology. 2013;9:5,629-636. Lee, KC., et al. Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2007;3:527-537. Kaminsky B., et al. Alternative routes of administration of antidepressant and antipsychotic medications. Annals of Pharmac otherapy. 2015;49:808-17. Attard A., et al. Alternative routes to oral antidepressant therapy: case vignette and literature review. J of Psychopharmacology . 2010;24:449-454. Koelle J., et al. Antidepressants for the viscerally eviscerated patient: options instead of oral dosing. Psychosomatic Medicine . 1998;60:723-5. Azran C, et al.  Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass.  Surg Obes Relat Dis 2017;13(7):1245-7. Medline Plus: methylphenidate transdermal patch. https://medlineplus.gov/druginfo/meds/a606014.html . Accessed 11/30/18. McGirr, A., et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes.  Psychological Medicine,   2015;45 :693-704. Zarate C.A., et al. Ketamine for depression: evidence, challenges and promise.  World Psychiatry . 2015;14(3):348-350. Coyle C., et al. The use of ketamine as an antidepressant: a systematic review and meta-analysis. Human Psychopharmacol Clin Exp. 2015;30:152-63. Sanacora G., et al. A consensus statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry . 2017;74:399-405. Conflicts of Interest: None Authors’ Affiliations: University of Pittsburgh Medical Center; Pittsburgh, PA. Version History: First electronically published in January 2019; originally edited by Sean Marks MD; reviewed and updated by Dr. Kerry Case in September 2024. Fast Facts and Concepts are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School) with the generous support of a volunteer peer-review editorial board, and are made available online by the Palliative Care Network of Wisconsin (PCNOW). The authors of each individual Fast Fact and the Fast Fact and Concepts editors are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at Palliative Care Network of Wisconsin with contact information, and how to reference Fast Facts. Copyright: All Fast Facts and Concepts are published under a Creative Commons Attribution-NonCommercial 4.0 International Copyright ( http://creativecommons.org/licenses/by-nc/4.0/ ). Fast Facts can only be copied and distributed for non-commercial, educational purposes. If you adapt or distribute a Fast Fact , let us know! Disclaimer: Fast Facts and Concepts provide educational information for health care professionals. This information is not medical advice. Fast Facts are not continually updated, and new safety information may emerge after a Fast Fact is published. Health care providers should always exercise their own independent clinical judgment and consult other relevant and up-to-date experts and resources. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used. Search Fast Facts Search Resources Become a Subscriber Subscriptions are free and you will receive a weekly Fast Fact email every Friday! 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Markdown	[Skip to content](https://www.mypcnow.org/fast-fact/non-oral-pharmacotherapy-options-for-depression/#content) [![Palliative Care Network of Wisconsin Logo](https://www.mypcnow.org/wp-content/uploads/2023/11/PCNOW-Logo-outlined-e1696340127581.png) ![Palliative Care Network of Wisconsin Logo](https://www.mypcnow.org/wp-content/uploads/2024/01/PCNOW-Logo-outlined-1-e1705337763292.png)](https://www.mypcnow.org/) - [About](https://www.mypcnow.org/about/) - [Advocacy](https://www.mypcnow.org/about/advocacy/) - [Board of Directors](https://www.mypcnow.org/about/board-of-directors/) - [Fast Facts](https://www.mypcnow.org/fast-facts/) - [Fast Facts Directory](https://www.mypcnow.org/fast-facts/fast-facts-directory/) - [About Fast Facts](https://www.mypcnow.org/fast-facts/about/) - [Fast Facts Quiz](https://www.mypcnow.org/fast-facts/quiz/) - [Geriatric Fast Facts](http://www.geriatricfastfacts.com/) - [Publications](https://www.mypcnow.org/publications/) - [Guidebooks](https://www.mypcnow.org/publications#guidebooks) - [Essential Fast Facts](https://www.mypcnow.org/publications/essential-fast-facts/) - [For Chaplains](https://www.mypcnow.org/publications/top-fast-facts-resources-for-chaplains/) - [For Nurses](https://www.mypcnow.org/publications/top-fast-facts-resources-for-nurses/) - [For Social Workers](https://www.mypcnow.org/publications/top-fast-facts-resources-for-social-workers/) - [Resources](https://www.mypcnow.org/resources/) - [Palliative Care Teams & Program Development](https://www.mypcnow.org/resources/palliative-care-teams-program-development/) - [Education](https://www.mypcnow.org/resources/educator-tools/) - [Communication](https://www.mypcnow.org/resources/communication/) - [Tools for Clinicians](https://www.mypcnow.org/resources/tools-for-clinicians/) - [Lectures & Presentations](https://www.mypcnow.org/resources/lectures-presentations/) - [Systems Change](https://www.mypcnow.org/resources/quality-improvement-projects/) - [News](https://www.mypcnow.org/news/) - [Contact](https://www.mypcnow.org/contact/) - [Donate](https://www.mypcnow.org/donate/) #### Non-Oral Pharmacotherapy Options for Depression [Print this Page](https://www.mypcnow.org/fast-fact/non-oral-pharmacotherapy-options-for-depression/?print=print) Fast Fact Number: 372 By: Corey Tapper MD, MS, Robert M Arnold MD, Jennifer Pruskowski PharmD Categories: [Age Friendly Care: The 4 Ms of Geriatric Care](https://www.mypcnow.org/fast-fact-category/age-friendly-care-the-4-ms-of-geriatric-care/ "Age Friendly Care: The 4 Ms of Geriatric Care"), [Fast Facts By Specialty](https://www.mypcnow.org/fast-fact-category/fast-facts-by-specialty/ "Fast Facts By Specialty"), [Medications](https://www.mypcnow.org/fast-fact-category/medications/ "Medications"), [Non-Opioid Medications](https://www.mypcnow.org/fast-fact-category/non-opioid-medications/ "Non-Opioid Medications"), [Pharmacology](https://www.mypcnow.org/fast-fact-category/pharmacology/ "Pharmacology"), [Psychology/Psychiatry](https://www.mypcnow.org/fast-fact-category/psychology-psychiatry/ "Psychology/Psychiatry") Published On: September 4, 2024 *Background for Fast Fact \#372:* While psychological counseling remains the mainstay of depression management, treatment with pharmacotherapy can achieve better outcomes for many patients (1). Palliative care clinicians may encounter patients with depression who are nothing by mouth (NPO) for prolonged periods of time due to swallowing problems or who have GI abnormalities (e.g. small bowel transplant, a complicated abdominal wound, or severe pancreatitis). This Fast Fact reviews the best evidence to identify a care approach for the non-oral pharmacologic management of depression. Is non-oral anti-depressant treatment necessary? The first question to consider is whether a seriously ill patient who lost the ability to tolerate oral medications requires non-oral antidepressant pharmacotherapy. For many patients with a new 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. Alternatively, patients who are not actively depressed but rather are on anti-depressants for a history of depression may do better if their antidepressant pharmacotherapy is held until they were able to tolerate medications by mouth. Prognosis and co-morbidities are important considerations. Most antidepressants require several weeks to exhibit therapeutic benefit. Hence, patients with a short life expectancy are unlikely to benefit from their initiation. Initiating anti-depressants is not appropriate for acutely delirious patients. Can the anti-depressant be given via an enteric tube? Most antidepressants and psychostimulants can be crushed or given as an elixir via an enteric tube. Citalopram, escitalopram, fluoxetine, paroxetine, sertraline, nortriptyline, doxepin, and methylphenidate are all available as solutions or concentrate. In general, short-acting formulations are safe to crush and give via an enteric tube, while long-acting formulations are not. If an enteric tube is not available and the patient is on an anti-depressant with a short half-life (e.g. paroxetine or immediate release venlafaxine), then withdrawal phenomenon could ensue. Initiation of a less standard non-oral anti-depressant (see below) may be warranted. Clinical pharmacists and consult liaison psychiatrists can be vital resources in guiding these decisions. FDA-approved non-oral anti-depressants: - 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. Therefore, it may not be appropriate for strict NPO patients, especially those with proximal GI abnormalities. See Fast Fact \#314 for more information on mirtazapine. - Selegiline is a monoamine oxidase inhibitor (MAOI). 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 (4). This means there is a decreased risk of tyramine-induced adverse events such as a hypertensive crisis, as there is no significant inhibition of gastrointestinal monoamine oxidase activity (5). Regardless, a psychiatrist should be involved if one wants to use this medication given its numerous drug and food interactions via oral and non-oral administration (6,7). Non-oral formulations of selegiline are relatively costly: a 30-day supply of the selegiline TD patch costs about \$2000 and a 30-day supply of the ODT formulation typically costs around \$3000. - Esketamine is the s-enantiomer of ketamine. It is administered intranasally, and its use is subject to a Risk Evaluation and Management Strategy. Non-oral formulations that have NOT been FDA-approved for depression management: - Tricyclic antidepressants (TCAs): Doxepin is available in a topical cream to treat pruritus. While there have been case reports regarding its use topically and rectally to treat depression (4), it has not been evaluated in any controlled way nor has a reasonable dose been identified. Amitriptyline is available intravenously (IV) outside the United States and there are case reports of its compounded use as buccal, topical, and rectal formulations (4,5). - Selective serotonin reuptake inhibitors: Fluoxetine: a case report describes its effective use when compounded into topical and rectal formulations (5). Citalopram IV is available outside of the US (8). - Psychostimulants: While data on psychostimulants for depression have been mixed (see [Fast Fact](https://www.mypcnow.org/fast-fact/use-of-psycho-stimulants-in-palliative-care/) \#61 & [Fast Fact \#309](https://www.mypcnow.org/fast-fact/pharmacologic-management-of-depression-in-advanced-illness/)) and their provision as a Schedule II medication limits who may prescribe them, they are often considered for depressed 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 anti-depressants. Methylphenidate is available as a solution for patients who can swallow small amounts or for whom use of an enteric tube is feasible. For patients with strict “nothing by the GI tract” orders, there is a commercially available transdermal methylphenidate patch (9). The patch should be applied 2 hours prior to desired effect (ideally near the patient’s hip where it is felt to have best absorption) and removed 9 hours after (10). The patch and elixir costs about 7 times more than a tablet. - Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist which has been studied for use in depression (11-13). Response to 0.5 mg/kg IV can be rapid (within 24 hours) but brief (lasting up to two weeks); investigation into recurrent dosing is ongoing. See [Fast Fact](https://www.mypcnow.org/fast-fact/ketamine-in-palliative-care/) \#132 and [Fast Fact \#384](https://www.mypcnow.org/fast-fact/the-role-of-ketamine-in-depression/). References: 1. Cujpers, P., et al. Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis. Depress Anxiety. 2009;26:279-288. 2. Anttila, S. A., et al. A Review of the Pharmacological and Clinical Profile of Mirtazapine. CNS Drug Reviews, 2001;7:249-264. 3. Croom, K., et al. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009;23:427-452. 4. Tábi, T., et al. The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson’s disease. Expert Opinion on Drug Metabolism & Toxicology. 2013;9:5,629-636. 5. Lee, KC., et al. Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2007;3:527-537. 6. Kaminsky B., et al. Alternative routes of administration of antidepressant and antipsychotic medications. Annals of Pharmacotherapy. 2015;49:808-17. 7. Attard A., et al. Alternative routes to oral antidepressant therapy: case vignette and literature review. J of Psychopharmacology. 2010;24:449-454. 8. Koelle J., et al. Antidepressants for the viscerally eviscerated patient: options instead of oral dosing. Psychosomatic Medicine. 1998;60:723-5. 9. Azran C, et al. Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass. Surg Obes Relat Dis 2017;13(7):1245-7. 10. Medline Plus: methylphenidate transdermal patch. <https://medlineplus.gov/druginfo/meds/a606014.html>. Accessed 11/30/18. 11. McGirr, A., et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychological Medicine, 2015;45:693-704. 12. Zarate C.A., et al. Ketamine for depression: evidence, challenges and promise. World Psychiatry. 2015;14(3):348-350. 13. Coyle C., et al. The use of ketamine as an antidepressant: a systematic review and meta-analysis. Human Psychopharmacol Clin Exp. 2015;30:152-63. 14. Sanacora G., et al. A consensus statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry. 2017;74:399-405. Conflicts of Interest: None Authors’ Affiliations: University of Pittsburgh Medical Center; Pittsburgh, PA. Version History: First electronically published in January 2019; originally edited by Sean Marks MD; reviewed and updated by Dr. Kerry Case in September 2024. *Fast Facts and Concepts* are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School) with the generous support of a volunteer peer-review editorial board, and are made available online by the [Palliative Care Network of Wisconsin](http://www.mypcnow.org/) (PCNOW). The authors of each individual Fast Fact and the Fast Fact and Concepts editors are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at [Palliative Care Network of Wisconsin](http://www.mypcnow.org/) with contact information, and how to reference Fast Facts. Copyright: All Fast Facts and Concepts are published under a Creative Commons Attribution-NonCommercial 4.0 International Copyright (<http://creativecommons.org/licenses/by-nc/4.0/>). Fast Facts can only be copied and distributed for non-commercial, educational purposes. If you adapt or distribute a Fast Fact, let us know\! Disclaimer: Fast Facts and Concepts provide educational information for health care professionals. This information is not medical advice. Fast Facts are not continually updated, and new safety information may emerge after a Fast Fact is published. Health care providers should always exercise their own independent clinical judgment and consult other relevant and up-to-date experts and resources. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used. ## Search Fast Facts ## Search Resources ## Become a Subscriber Subscriptions are free and you will receive a weekly Fast Fact email every Friday\! 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Readable Markdown	[Skip to content](https://www.mypcnow.org/fast-fact/non-oral-pharmacotherapy-options-for-depression/#content) [![Palliative Care Network of Wisconsin Logo](https://www.mypcnow.org/wp-content/uploads/2023/11/PCNOW-Logo-outlined-e1696340127581.png) ![Palliative Care Network of Wisconsin Logo](https://www.mypcnow.org/wp-content/uploads/2024/01/PCNOW-Logo-outlined-1-e1705337763292.png)](https://www.mypcnow.org/) - [About](https://www.mypcnow.org/about/) - [Advocacy](https://www.mypcnow.org/about/advocacy/) - [Board of Directors](https://www.mypcnow.org/about/board-of-directors/) - [Fast Facts](https://www.mypcnow.org/fast-facts/) - [Fast Facts Directory](https://www.mypcnow.org/fast-facts/fast-facts-directory/) - [About Fast Facts](https://www.mypcnow.org/fast-facts/about/) - [Fast Facts Quiz](https://www.mypcnow.org/fast-facts/quiz/) - [Geriatric Fast Facts](http://www.geriatricfastfacts.com/) - [Publications](https://www.mypcnow.org/publications/) - [Guidebooks](https://www.mypcnow.org/publications#guidebooks) - [Essential Fast Facts](https://www.mypcnow.org/publications/essential-fast-facts/) - [For Chaplains](https://www.mypcnow.org/publications/top-fast-facts-resources-for-chaplains/) - [For Nurses](https://www.mypcnow.org/publications/top-fast-facts-resources-for-nurses/) - [For Social Workers](https://www.mypcnow.org/publications/top-fast-facts-resources-for-social-workers/) - [Resources](https://www.mypcnow.org/resources/) - [Palliative Care Teams & Program Development](https://www.mypcnow.org/resources/palliative-care-teams-program-development/) - [Education](https://www.mypcnow.org/resources/educator-tools/) - [Communication](https://www.mypcnow.org/resources/communication/) - [Tools for Clinicians](https://www.mypcnow.org/resources/tools-for-clinicians/) - [Lectures & Presentations](https://www.mypcnow.org/resources/lectures-presentations/) - [Systems Change](https://www.mypcnow.org/resources/quality-improvement-projects/) - [News](https://www.mypcnow.org/news/) - [Contact](https://www.mypcnow.org/contact/) - [Donate](https://www.mypcnow.org/donate/) #### Non-Oral Pharmacotherapy Options for Depression [Print this Page](https://www.mypcnow.org/fast-fact/non-oral-pharmacotherapy-options-for-depression/?print=print) Fast Fact Number: 372 By: Corey Tapper MD, MS, Robert M Arnold MD, Jennifer Pruskowski PharmD Categories: [Age Friendly Care: The 4 Ms of Geriatric Care](https://www.mypcnow.org/fast-fact-category/age-friendly-care-the-4-ms-of-geriatric-care/ "Age Friendly Care: The 4 Ms of Geriatric Care"), [Fast Facts By Specialty](https://www.mypcnow.org/fast-fact-category/fast-facts-by-specialty/ "Fast Facts By Specialty"), [Medications](https://www.mypcnow.org/fast-fact-category/medications/ "Medications"), [Non-Opioid Medications](https://www.mypcnow.org/fast-fact-category/non-opioid-medications/ "Non-Opioid Medications"), [Pharmacology](https://www.mypcnow.org/fast-fact-category/pharmacology/ "Pharmacology"), [Psychology/Psychiatry](https://www.mypcnow.org/fast-fact-category/psychology-psychiatry/ "Psychology/Psychiatry") Published On: September 4, 2024 *Background for Fast Fact \#372:* While psychological counseling remains the mainstay of depression management, treatment with pharmacotherapy can achieve better outcomes for many patients (1). Palliative care clinicians may encounter patients with depression who are nothing by mouth (NPO) for prolonged periods of time due to swallowing problems or who have GI abnormalities (e.g. small bowel transplant, a complicated abdominal wound, or severe pancreatitis). This Fast Fact reviews the best evidence to identify a care approach for the non-oral pharmacologic management of depression. Is non-oral anti-depressant treatment necessary? The first question to consider is whether a seriously ill patient who lost the ability to tolerate oral medications requires non-oral antidepressant pharmacotherapy. For many patients with a new 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. Alternatively, patients who are not actively depressed but rather are on anti-depressants for a history of depression may do better if their antidepressant pharmacotherapy is held until they were able to tolerate medications by mouth. Prognosis and co-morbidities are important considerations. Most antidepressants require several weeks to exhibit therapeutic benefit. Hence, patients with a short life expectancy are unlikely to benefit from their initiation. Initiating anti-depressants is not appropriate for acutely delirious patients. Can the anti-depressant be given via an enteric tube? Most antidepressants and psychostimulants can be crushed or given as an elixir via an enteric tube. Citalopram, escitalopram, fluoxetine, paroxetine, sertraline, nortriptyline, doxepin, and methylphenidate are all available as solutions or concentrate. In general, short-acting formulations are safe to crush and give via an enteric tube, while long-acting formulations are not. If an enteric tube is not available and the patient is on an anti-depressant with a short half-life (e.g. paroxetine or immediate release venlafaxine), then withdrawal phenomenon could ensue. Initiation of a less standard non-oral anti-depressant (see below) may be warranted. Clinical pharmacists and consult liaison psychiatrists can be vital resources in guiding these decisions. FDA-approved non-oral anti-depressants: - 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. Therefore, it may not be appropriate for strict NPO patients, especially those with proximal GI abnormalities. See Fast Fact \#314 for more information on mirtazapine. - Selegiline is a monoamine oxidase inhibitor (MAOI). 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 (4). This means there is a decreased risk of tyramine-induced adverse events such as a hypertensive crisis, as there is no significant inhibition of gastrointestinal monoamine oxidase activity (5). Regardless, a psychiatrist should be involved if one wants to use this medication given its numerous drug and food interactions via oral and non-oral administration (6,7). Non-oral formulations of selegiline are relatively costly: a 30-day supply of the selegiline TD patch costs about \$2000 and a 30-day supply of the ODT formulation typically costs around \$3000. - Esketamine is the s-enantiomer of ketamine. It is administered intranasally, and its use is subject to a Risk Evaluation and Management Strategy. Non-oral formulations that have NOT been FDA-approved for depression management: - Tricyclic antidepressants (TCAs): Doxepin is available in a topical cream to treat pruritus. While there have been case reports regarding its use topically and rectally to treat depression (4), it has not been evaluated in any controlled way nor has a reasonable dose been identified. Amitriptyline is available intravenously (IV) outside the United States and there are case reports of its compounded use as buccal, topical, and rectal formulations (4,5). - Selective serotonin reuptake inhibitors: Fluoxetine: a case report describes its effective use when compounded into topical and rectal formulations (5). Citalopram IV is available outside of the US (8). - Psychostimulants: While data on psychostimulants for depression have been mixed (see [Fast Fact](https://www.mypcnow.org/fast-fact/use-of-psycho-stimulants-in-palliative-care/) \#61 & [Fast Fact \#309](https://www.mypcnow.org/fast-fact/pharmacologic-management-of-depression-in-advanced-illness/)) and their provision as a Schedule II medication limits who may prescribe them, they are often considered for depressed 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 anti-depressants. Methylphenidate is available as a solution for patients who can swallow small amounts or for whom use of an enteric tube is feasible. For patients with strict “nothing by the GI tract” orders, there is a commercially available transdermal methylphenidate patch (9). The patch should be applied 2 hours prior to desired effect (ideally near the patient’s hip where it is felt to have best absorption) and removed 9 hours after (10). The patch and elixir costs about 7 times more than a tablet. - Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist which has been studied for use in depression (11-13). Response to 0.5 mg/kg IV can be rapid (within 24 hours) but brief (lasting up to two weeks); investigation into recurrent dosing is ongoing. See [Fast Fact](https://www.mypcnow.org/fast-fact/ketamine-in-palliative-care/) \#132 and [Fast Fact \#384](https://www.mypcnow.org/fast-fact/the-role-of-ketamine-in-depression/). References: 1. Cujpers, P., et al. Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis. Depress Anxiety. 2009;26:279-288. 2. Anttila, S. A., et al. A Review of the Pharmacological and Clinical Profile of Mirtazapine. CNS Drug Reviews, 2001;7:249-264. 3. Croom, K., et al. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009;23:427-452. 4. Tábi, T., et al. The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson’s disease. Expert Opinion on Drug Metabolism & Toxicology. 2013;9:5,629-636. 5. Lee, KC., et al. Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2007;3:527-537. 6. Kaminsky B., et al. Alternative routes of administration of antidepressant and antipsychotic medications. Annals of Pharmacotherapy. 2015;49:808-17. 7. Attard A., et al. Alternative routes to oral antidepressant therapy: case vignette and literature review. J of Psychopharmacology. 2010;24:449-454. 8. Koelle J., et al. Antidepressants for the viscerally eviscerated patient: options instead of oral dosing. Psychosomatic Medicine. 1998;60:723-5. 9. Azran C, et al. Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass. Surg Obes Relat Dis 2017;13(7):1245-7. 10. Medline Plus: methylphenidate transdermal patch. <https://medlineplus.gov/druginfo/meds/a606014.html>. Accessed 11/30/18. 11. McGirr, A., et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychological Medicine, 2015;45:693-704. 12. Zarate C.A., et al. Ketamine for depression: evidence, challenges and promise. World Psychiatry. 2015;14(3):348-350. 13. Coyle C., et al. The use of ketamine as an antidepressant: a systematic review and meta-analysis. Human Psychopharmacol Clin Exp. 2015;30:152-63. 14. Sanacora G., et al. A consensus statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry. 2017;74:399-405. Conflicts of Interest: None Authors’ Affiliations: University of Pittsburgh Medical Center; Pittsburgh, PA. Version History: First electronically published in January 2019; originally edited by Sean Marks MD; reviewed and updated by Dr. Kerry Case in September 2024. *Fast Facts and Concepts* are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School) with the generous support of a volunteer peer-review editorial board, and are made available online by the [Palliative Care Network of Wisconsin](http://www.mypcnow.org/) (PCNOW). The authors of each individual Fast Fact and the Fast Fact and Concepts editors are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at [Palliative Care Network of Wisconsin](http://www.mypcnow.org/) with contact information, and how to reference Fast Facts. Copyright: All Fast Facts and Concepts are published under a Creative Commons Attribution-NonCommercial 4.0 International Copyright (<http://creativecommons.org/licenses/by-nc/4.0/>). Fast Facts can only be copied and distributed for non-commercial, educational purposes. If you adapt or distribute a Fast Fact, let us know\! Disclaimer: Fast Facts and Concepts provide educational information for health care professionals. This information is not medical advice. Fast Facts are not continually updated, and new safety information may emerge after a Fast Fact is published. Health care providers should always exercise their own independent clinical judgment and consult other relevant and up-to-date experts and resources. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used. ## Search Fast Facts ## Search Resources ## Become a Subscriber Subscriptions are free and you will receive a weekly Fast Fact email every Friday\! 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