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"The duloxetine + [[mirtazapine]] combination is a particularly effective tool in the antidepressant arsenal. Duloxetine is a very high affinity blocker of both the serotonin and norepinephrine transporters, at 0.8 for the SERT and 7.5 for the NET respectively, resulting in increased serotonergic and noradrenergic neurotransmission, which results in improvements in mood, cognition, desire to work, motivation, greater skill at performing tasks effectively, memory, alertness, and keenness, while also alleviating depression, anxiety, and obsessive-compulsive ideation. Mirtazapine’s antagonism of the α<sub>2</sub> receptors further preserves and enhances serotonergic and noradrenergic neurotransmission and its very high antagonism of the 5-HT<sub>2</sub> receptors also alleviates depression and anxiety. Importantly, duloxetine is a moderate affinity inhibitor of the [[CYP2D6]] enzyme, thereby increasing the plasma concentration of the substrate, mirtazapine, to between 2-5 times the normal levels. After beginning use of this regimen, symptoms such as prolonged headache, fatigue, and even a worsening of psychological symptoms tend to predominate for 3 weeks before going away. Therapeutic effects set in 3-4 weeks after beginning use, even if one has just discontinued a previous antidepressant.<ref name="Nassa + SNRI for TR depression">{{cite journal|title=SNRI-NaSSA combination therapy for treatment-resistant depression.|journal=Opinion/Wiley|doi=10.1002/pnp.153/pdf|url=http://onlinelibrary.wiley.com/doi/10.1002/pnp.153/pdf}}</ref><ref name="SR Explained">{{cite web|last1=Stahl|first1=Steven|title=Serotonin Receptors Explained.|website=http://www.universitypsychiatry.com/clientuploads/stahl/Stahl_3rd_ch12_Part2.pdf.|publisher=University Psychiatry|accessdate=December 6, 2017}}</ref>"
"The duloxetine + [[mirtazapine]] combination is a particularly effective tool in the antidepressant arsenal. Duloxetine is a very high affinity blocker of both the serotonin and norepinephrine transporters, at 0.8 for the SERT and 7.5 for the NET respectively, resulting in increased serotonergic and noradrenergic neurotransmission, which results in improvements in mood, cognition, desire to work, motivation, greater skill at performing tasks effectively, memory, alertness, and keenness, while also alleviating depression, anxiety, and obsessive-compulsive ideation. Mirtazapine’s antagonism of the α<sub>2</sub> receptors further preserves and enhances serotonergic and noradrenergic neurotransmission and its very high antagonism of the 5-HT<sub>2</sub> receptors also alleviates depression and anxiety. Importantly, duloxetine is a moderate affinity inhibitor of the [[CYP2D6]] enzyme, thereby increasing the plasma concentration of the substrate, mirtazapine, to between 2-5 times the normal levels. After beginning use of this regimen, symptoms such as prolonged headache, fatigue, and even a worsening of psychological symptoms tend to predominate for 3 weeks before going away. Therapeutic effects set in 3-4 weeks after beginning use, even if one has just discontinued a previous antidepressant.<ref name="Nassa + SNRI for TR depression">{{cite journal|title=SNRI-NaSSA combination therapy for treatment-resistant depression.|journal=Opinion/Wiley|doi=10.1002/pnp.153/pdf|url=http://onlinelibrary.wiley.com/doi/10.1002/pnp.153/pdf}}</ref><ref name="SR Explained">{{cite web|last1=Stahl|first1=Steven|title=Serotonin Receptors Explained.|website=http://www.universitypsychiatry.com/clientuploads/stahl/Stahl_3rd_ch12_Part2.pdf.|publisher=University Psychiatry|accessdate=December 6, 2017}}</ref>"

===Another version===
"The duloxetine + [[mirtazapine]] combination is a particularly effective tool in the antidepressant arsenal.<ref name="Case for LRF">{{cite web|last1=Meagher|first1=David J|last2=Hannan|first2=Noel|last3=Leonard|first3=Maeve|title=Duloxetine-mirtazapine combination in depressive illness: The case for Limerick 'rocket fuel'.|url=https://www.researchgate.net/publication/265047831_Duloxetine-mirtazapine_combination_in_depressive_illness_The_case_for_Limerick_%27rocket_fuel%27|website=Research Gate|accessdate=Dec 12, 2017}}</ref><ref>{{cite journal|title=SNRI-NaSSA combination therapy for treatment-resistant depression.|journal=Opinion/Wiley|doi=10.1002/pnp.153/pdf|url=http://onlinelibrary.wiley.com/doi/10.1002/pnp.153/pdf}}</ref> Duloxetine is a very high affinity blocker of both the serotonin and norepinephrine transporters, at 0.8 for the SERT and 7.5 for the NET respectively,<ref name="pmid11750180"/> resulting in increased serotonergic and noradrenergic neurotransmission, which results in improvements in mood, cognition, desire to work, motivation, energy, greater skill at performing tasks effectively, memory, alertness, and keenness, while also alleviating depression, anxiety, and obsessive-compulsive ideation.<ref name="Role of NE and 5-HT in cognition, emotion, energy">{{cite journal|last1=Moret, Briley|first1=Chantal, Mike|title=The importance of norepinephrine in depression.|journal=Pub Med Center|date=May 31, 2011|doi=10.2147/NDT.S19619| pmc=3131098 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131098/}}</ref><ref name="All About Serotonin">{{cite journal|last1=Jenkins|first1=Trisha A.|last2=Nguyen|first2=Jason C.D.|last3=Polglaze|first3=Kate E.|last4=Bertrand|first4=Paul P.|title=Influence of Tryptophan and Serotonin on Mood and Cognition.|journal=Nutrients|date=January 20, 2016|doi=10.3390/nu8010056| pmc=4728667 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728667/|accessdate=December 14, 2017}}</ref><ref name="NE for Motivation, Cognition, Intellectual Skills">{{cite web|title=Low Norepinephrine and Depression: Is there a link?|url=http://mentalhealthdaily.com/2014/05/08/low-norepinephrine-and-depression-is-there-a-link/.|website=Mental Health Daily.}}</ref> Mirtazapine’s antagonism of the α<sub>2</sub> receptors further preserves and enhances serotonergic and noradrenergic neurotransmission and its very high antagonism of the 5-HT<sub>2</sub> receptors also alleviates depression and anxiety.<ref name="pmid11607047">{{cite journal | vauthors = Anttila SA, Leinonen EV | title = A review of the pharmacological and clinical profile of mirtazapine | journal = CNS Drug Rev | volume = 7 | issue = 3 | pages = 249–64 | year = 2001 | pmid = 11607047 | doi = | url = }}</ref> Importantly, duloxetine is a moderate affinity inhibitor of the [[CYP2D6]] enzyme, thereby increasing the plasma concentration of the substrate, mirtazapine, to between 2-5 times the normal levels.<ref name=Flockhart>{{cite web |author=Flockhart DA |title=Drug Interactions: Cytochrome P<sub>450</sub> Drug Interaction Table |publisher=[[Indiana University School of Medicine]] |year=2007 |url=http://medicine.iupui.edu/flockhart/table.htm}} Retrieved on July 2011</ref> After beginning use of this regimen, symptoms such as prolonged headache, fatigue, and even a periodic worsening of psychological symptoms tend to predominate for 3 weeks before going away. Therapeutic effects set in 3-4 weeks after beginning use, even if one has just discontinued a previous antidepressant.<ref name="SSNRI Profiles">{{cite web|last1=Aiken|first1=Chris|title=SSNRI Profiles.|url=http://www.moodtreatmentcenter.com/snri.pdf.|website=Mood Treatment Center.|accessdate=December 14, 2017}}</ref>

::This is strange. This review "{{cite journal | vauthors = Anttila SA, Leinonen EV | title = A review of the pharmacological and clinical profile of mirtazapine | journal = CNS Drug Rev | volume = 7 | issue = 3 | pages = 249–64 | year = 2001 | pmid = 11607047 | doi = | url = }}" does not even mention duloxetine?
::And neither does this one[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728667/] [[User:Doc James|<span style="color:#0000f1">'''Doc James'''</span>]] ([[User talk:Doc James|talk]] · [[Special:Contributions/Doc James|contribs]] · [[Special:EmailUser/Doc James|email]]) 04:49, 16 December 2017 (UTC)

Revision as of 04:49, 16 December 2017

Heading

Unclear what sources support this stuff?

Doc James (talk · contribs · email) 01:12, 7 December 2017 (UTC)[reply]

"The duloxetine + mirtazapine combination is a particularly effective tool in the antidepressant arsenal. Duloxetine is a very high affinity blocker of both the serotonin and norepinephrine transporters, at 0.8 for the SERT and 7.5 for the NET respectively, resulting in increased serotonergic and noradrenergic neurotransmission, which results in improvements in mood, cognition, desire to work, motivation, greater skill at performing tasks effectively, memory, alertness, and keenness, while also alleviating depression, anxiety, and obsessive-compulsive ideation. Mirtazapine’s antagonism of the α2 receptors further preserves and enhances serotonergic and noradrenergic neurotransmission and its very high antagonism of the 5-HT2 receptors also alleviates depression and anxiety. Importantly, duloxetine is a moderate affinity inhibitor of the CYP2D6 enzyme, thereby increasing the plasma concentration of the substrate, mirtazapine, to between 2-5 times the normal levels. After beginning use of this regimen, symptoms such as prolonged headache, fatigue, and even a worsening of psychological symptoms tend to predominate for 3 weeks before going away. Therapeutic effects set in 3-4 weeks after beginning use, even if one has just discontinued a previous antidepressant.[1][2]"

Another version

"The duloxetine + mirtazapine combination is a particularly effective tool in the antidepressant arsenal.[3][4] Duloxetine is a very high affinity blocker of both the serotonin and norepinephrine transporters, at 0.8 for the SERT and 7.5 for the NET respectively,[5] resulting in increased serotonergic and noradrenergic neurotransmission, which results in improvements in mood, cognition, desire to work, motivation, energy, greater skill at performing tasks effectively, memory, alertness, and keenness, while also alleviating depression, anxiety, and obsessive-compulsive ideation.[6][7][8] Mirtazapine’s antagonism of the α2 receptors further preserves and enhances serotonergic and noradrenergic neurotransmission and its very high antagonism of the 5-HT2 receptors also alleviates depression and anxiety.[9] Importantly, duloxetine is a moderate affinity inhibitor of the CYP2D6 enzyme, thereby increasing the plasma concentration of the substrate, mirtazapine, to between 2-5 times the normal levels.[10] After beginning use of this regimen, symptoms such as prolonged headache, fatigue, and even a periodic worsening of psychological symptoms tend to predominate for 3 weeks before going away. Therapeutic effects set in 3-4 weeks after beginning use, even if one has just discontinued a previous antidepressant.[11]

This is strange. This review "Anttila SA, Leinonen EV (2001). "A review of the pharmacological and clinical profile of mirtazapine". CNS Drug Rev. 7 (3): 249–64. PMID 11607047." does not even mention duloxetine?
And neither does this one[1] Doc James (talk · contribs · email) 04:49, 16 December 2017 (UTC)[reply]
  1. ^ "SNRI-NaSSA combination therapy for treatment-resistant depression". Opinion/Wiley. doi:10.1002/pnp.153/pdf.
  2. ^ Stahl, Steven. "Serotonin Receptors Explained". http://www.universitypsychiatry.com/clientuploads/stahl/Stahl_3rd_ch12_Part2.pdf. University Psychiatry. {{cite web}}: |access-date= requires |url= (help); External link in |website= (help); Missing or empty |url= (help)
  3. ^ Meagher, David J; Hannan, Noel; Leonard, Maeve. "Duloxetine-mirtazapine combination in depressive illness: The case for Limerick 'rocket fuel'". Research Gate. Retrieved Dec 12, 2017.
  4. ^ "SNRI-NaSSA combination therapy for treatment-resistant depression". Opinion/Wiley. doi:10.1002/pnp.153/pdf.
  5. ^ Cite error: The named reference pmid11750180 was invoked but never defined (see the help page).
  6. ^ Moret, Briley, Chantal, Mike (May 31, 2011). "The importance of norepinephrine in depression". Pub Med Center. doi:10.2147/NDT.S19619. PMC 3131098.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  7. ^ Jenkins, Trisha A.; Nguyen, Jason C.D.; Polglaze, Kate E.; Bertrand, Paul P. (January 20, 2016). "Influence of Tryptophan and Serotonin on Mood and Cognition". Nutrients. doi:10.3390/nu8010056. PMC 4728667. Retrieved December 14, 2017.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ "Low Norepinephrine and Depression: Is there a link?". Mental Health Daily.
  9. ^ Anttila SA, Leinonen EV (2001). "A review of the pharmacological and clinical profile of mirtazapine". CNS Drug Rev. 7 (3): 249–64. PMID 11607047.
  10. ^ Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. Retrieved on July 2011
  11. ^ Aiken, Chris. "SSNRI Profiles". Mood Treatment Center. Retrieved December 14, 2017.
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