Misc How important a role does noradrenaline (norepinephrine) play in depression?

[ChemicallyEnhanced]

I get noticeably more depressed when I don't have Tramadol. I am prescribed it for chronic pain, not depression. My weekly script tends to last me 3-4 days as I take more than I'm supposed to, especially when I am feeling down.
I am on a high dose of Sertraline (Zoloft) and also take Trazodone so I doubt a lack of serotonin is responsible. The depression lessens but still persists even if I take other opiates, too.
So all I can think is that it is the lack of noradrenaline reuptake. I don't know much about noradrenaline, really. Does it really have enough anti-depressant or mood-elevating effects to affect me so noticeably?

 

[falsifiedhypothesi]

The truth is no one knows exactly how depression works and it probably doesn't have one root cause even speaking purely about the nuerochemistry. You should not be combining all those serotonin effecting drugs, you are putting yourself at serious risk for serotonin syndrome which is not fun and in some cases can be deadly.

 

[ChemicallyEnhanced]

The truth is no one knows exactly how depression works and it probably doesn't have on root cause even speaking purely about the nuerochemistry. You should not be combining all those serotonin effecting drugs, you are putting yourself at serious risk for serotonin syndrome which is not fun and in some cases can be deadly.

I'm prescribed all of those medications (by the same doctor).

 

[kleinerkiffer]

Here's some food for thoughts:

Neither 5-HT nor NE depletion induced clinical depression in healthy subjects or worsened depression in unmedicated symptomatic patients with major depression. This finding suggests that the cause of depression is more complex than just an alteration in the levels of 5-HT and/or NE. For some patients, depression may be more directly caused by dysfunction in brain areas or neuronal systems modulated by monoamine systems.

https://www.ncbi.nlm.nih.gov/pubmed/10703757

Evidence for the involvement of NE in depression is abundant, and recent studies on neuronal pathways and symptoms highlight the specific role of NE in this disorder. NE plays a determinant role in executive functioning regulating cognition, motivation, and intellect, which are fundamental in social relationships. Social dysfunction is possibly one of the most important factors affecting the quality of life in depressed patients.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131098/


As falsifiedhypothesi said, your med combo can cause serotonin toxicity. While trazodone in low doses doesn't inhibit serotonin reuptake to a significant degree both tramadol and sertraline are potent SSRIs (tramadol and its main metabolite are SNRIs as well).
If it's prescribed by your doc and you don't show any symptoms it should be fine, but abusing the tramadol in a a short period of time could result in serotonin toxicity during the binge

 

[AlphaMethylPhenyl]

But taking more than they tell you brings issues.

Tramadol is a mu opioid agonist, along with (I may be off on this) SNRI activity and increases in serotonin as a separate mechanism. So there's something to be said for real antidepressant activity. And for it being used for pain. But it's mostly not useful as ana antidepressant, as the abuse potential can be very high from its effects on that opioid subtype.

SNRIs increase noradrenaline levels, per name. Effexor (at high doses), Pristiq, and Cymbalta are the main SNRIs.

The tricyclic antidepressants also have NRI properties. They're basically categorized based on if they have more serotonergic or adrenergic activity. But they also tend to be "dirty" in affecting lots of neurotransmitter systems.

But in opioid withdrawal, depression can result from hyperactive NE activity, which is why they give opioid addicts (or people otherwise getting off of opioids) autoreceptor agonists to prevent such high levels of NE.

It's about chemistry, setting, and many other more minor factors.

 

[ChemicallyEnhanced]

Here's some food for thoughts:

https://www.ncbi.nlm.nih.gov/pubmed/10703757

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131098/


As falsifiedhypothesi said, your med combo can cause serotonin toxicity. While trazodone in low doses doesn't inhibit serotonin reuptake to a significant degree both tramadol and sertraline are potent SSRIs (tramadol and its main metabolite are SNRIs as well).
If it's prescribed by your doc and you don't show any symptoms it should be fine, but abusing the tramadol in a a short period of time could result in serotonin toxicity during the binge

Thanks for all the information, it's interesting and very helpful .