Mental Health Venlafaxine(Effexor): the opioid based antidepressant?

One week ago when my pdoc added this drug to my weekly meds (20mg Diazepam and 150mg Pregabalin per day) I had no idea at all what this was about.. I only knew the new med was an antidepressant, and it was a SNRI this time, not a SSRI like some others that didn't make absolutely nothing. She explained that what she "likes" about Venlafaxine in particular, is that every person can "tune" their dose more or less to what they need, at low doses it mostly works on Serotonin, and moderate doses also on Noradrenaline, while at higher doses it directly impacts on Dopamine. She also made me know that this drug was given in cases of major depression (when the person has many problems, does not have any will at all to continue, is in a bad situation with suicide thoughts, etc.) sorta like telling me "this is the best antidepressant we could come for your enormous depression, you have to make this work".

Back at home, when I searched about it on the internet, my first stop was Wikipedia, and I was surprised to see how similar was to Tramadol (a drug god only knows how much I have abused) the drug even worked on all opiates receptors "Venlafaxine indirectly affects opioid receptors (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) as well as the alpha2-adrenergic receptor, and was shown to increase pain threshold in mice." (https://en.wikipedia.org/wiki/Venlafaxine). I even found an extensive clinical report that finished stating "These results suggest that µ-opioid receptors play an important role in the modulation of the antidepressant-like effect of Venlafaxine." (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171132/)
I kept searching, and even found thread of people on random forums comparing Venlafaxine with Tramadol; I didn't understand, so naturally, I used the search function on good ol' BL and didn't found many threads about it's mechanism (and if any, they ended in nothing), I also found some threads closed for no reason.

So far I have been taking 75mg every day for a week and I could list the pros and cons moderately easily:
+No stomach discomfort
+No huge change of mental perception when adapted to the drug (my first night on it I couldn't sleep at all)
+More willingness to do things (just a little, nothing world changing, maybe it's a time or dose dependant thing)
+Pleasant tingling in limbs, specially in the legs (which helps me relaxes a little)
-Sweat. Lots of sweat.
-Sometimes it makes me sleepy, which is weird.
-Loss of libido.
-Loss of appetite.

I would appreciate a lot if someone else has ever felt something "nice" out of this drug, if someone knows the history of how it came to be, and why it is so similar to Tramadol, and finally for those who taken it or are taking it, if it improved your life feeling less depressant (or not), how and what were the doses? Thanks in advance.

Don't mix this stuff with dxm you could die

Od -> MH

Effexor was one of the worst drugs I've ever taken. Apart from the psychosis (cutting myself, hearing voices, suicidal thoughts), the sweating was unbearable. I took Effexor for 2 months and it took 3 months for the head pin prick feeling to go away.

I went on it aftet caring for my terminally ill father 4 years ago. I never had depression or any other mental health issues, just got the blues after my father's death.

Maybe you will have sucess with it.

I took Effexor for a short period time (less than a month... probably about a week) as one of the many "trial and error" meds for anxiety. (Currently taking pregabalin 100 mg x 3 times per day). I believe I didn't want to continue taking it because it doesn't mix as well with amphetamines.
Through my research, I didn't notice that about opioid receptors, I'm curious to do a bit more research now. Although I still won't go back personally.

llama112 said:

I took Effexor for a short period time (less than a month... probably about a week) as one of the many "trial and error" meds for anxiety. (Currently taking pregabalin 100 mg x 3 times per day). I believe I didn't want to continue taking it because it doesn't mix as well with amphetamines.
Through my research, I didn't notice that about opioid receptors, I'm curious to do a bit more research now. Although I still won't go back personally.

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I see, as I said I was given 150mg Pregabalin per day too, I asked more because I feel really good and natural at the same time, but my doc said no. And after my depression got worse she added the Venlafaxine.

Question, do you take 300mg only for depression or for other problems too, like say, neuropathic pain? because if you research on Venlafaxine, it is prescribed off label for the treatment of neuropathic pain, same as Pregabalin. Do you remember what was your initial dose on Venlafaxine and how it made you feel?

Could anyone help me how to know when to up the dose from 50mg daily to 100mg? thanks in advance.

llama112 said:

I took Effexor for a short period time (less than a month... probably about a week) as one of the many "trial and error" meds for anxiety. (Currently taking pregabalin 100 mg x 3 times per day). I believe I didn't want to continue taking it because it doesn't mix as well with amphetamines.
Through my research, I didn't notice that about opioid receptors, I'm curious to do a bit more research now. Although I still won't go back personally.

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llama112, What was your experience with venlafaxine and amphetamines? >150mg dose of venlafaxine?

I have heard of patients that end up on prescription opiates (with some success) in their quest to treat depression. Is this bad practice? Maybe, maybe not. Theres certainly a link between physical and emotional pain somewhere.
venlafaxine is similar but its not an opiate at all. The only worry I would have about that, is whether it makes discontinuation any more difficult later on. The two SNRIs seem to have a reputation for a tough discontinuation, if you are prone to that. But there are strategies to help with that.

cr33py said:

llama112, What was your experience with venlafaxine and amphetamines? >150mg dose of venlafaxine?

I have heard of patients that end up on prescription opiates (with some success) in their quest to treat depression. Is this bad practice? Maybe, maybe not. Theres certainly a link between physical and emotional pain somewhere.
venlafaxine is similar but its not an opiate at all. The only worry I would have about that, is whether it makes discontinuation any more difficult later on. The two SNRIs seem to have a reputation for a tough discontinuation, if you are prone to that. But there are strategies to help with that.

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cr333py, I assure you, two or three hours after I did Venlafaxine, I feel the classic opioid tingling in my limbs and specially legs. The higher the dose, the more strong the feeling. And I'm talking about low doses, 50~100mg; combined with Pregabalin or not, I get the mild opioid sensation anyway (although is more pleasant with a little Pregabalin).
It is not placebo, I have been taking this med for quite some time now and the feeling is very reminiscent of a very low dose of Tramadol. I have taken Tramadol for years, I have also a fast CYP2D6 metabolism. Is it just me or what ?

Do you find venlafaxine is good for minor pain? I have some experience using some other psych meds for pain. at the moment the TCAs and anticonvulsants are the ones Im more comfortable with.
you could look into a metabolic panel.. I forget exactly what its called. Would tell you if youre metabolizing drugs faster than the norm. You can then either adjust the dose or deliberately add another drug that inhibits specific enzymes to normalize the actual dose, eg. fluoxetine + desipramine (CYP2D6).

I would believe that I am one of the lucky persons with fast CYP2D6 metabolism, I suspect that's why I have tried Oxycodone and Dihydrocodeine, but Tramadol was always stronger and more pleasurable in the end for me.
I do get pleasure from Venlafaxine, I swear to god, sometimes in the morning it's very hard to me to get up because it feels so good specially in the legs. The feeling is almost exactly like Tramadol or a high dose of classic Codeine but obviously a little milder.
Today I was switched from Effexor 50mg (2 per day) to Effexor XR 150mg (one per day), I expect it still works as good as the classic version.

I'm not crazy, I feel like taking a small dose of Tramadol on Venlafaxine. And I guess the more you take, the more it interacts with the opiate receptors.

Only thing I worry about is what happens when it comes time to discontinue venlafaxine? I have discontinued other meds for mild pain such as TCAs and AEDs and havent had any issue or extra pain rebound.
I used to take desipramine before I went to sleep.. so that I could wake up in the morning. Worked very well.