Efexor and Avanza bind to opioid receptors

[Davevanza]

I am taking Efexor XR 300mg during the day, and Avanza ( Mirtazapine) 90mg before sleep.
Surprisingly, here is what research paper, Pubmed stated :

".......we found that the antinociceptive effect of Effexor XR (venlafaxine) is influenced by opioid receptor subtypes (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) combined with the alpha2-adrenergic receptor, whereas the antinociceptive effect of Avanza (mirtazapine) mainly involves mu- and kappa3-opioid mechanisms. This opioid profile of the two drugs may be one of the explanations to their efficacy in severe depression, unlike the SSRIs and other antidepressants which lack opioid activity."

the link is http://www.ncbi.nlm.nih.gov/pubmed/11931344
Title : Venlafaxine and mirtazapine: different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects--a possible opioid involvement in severe depression?


Personally, I find that, 2 Panadeine forte works better than these 2 antidepressants.

I am a bit confused about it, as it is stated that Efexor and Avanza are the only antidepressants that bind to opioid receptors, but I derived no benefit from them.
( Tramadol works better, binding to "mu" receptor, and being an SNRI too)

Any input is greatly appreciated.

 

[Oxycondone]

Sorry I can't add to the discussion but I'd just like to say great article! I'm really interested in the benefits these anti-depressants could have helping people who are withdrawing from opiates and are having psychological problems.

 

[drug_mentor]

I have never taken either of these anti depressants but that is rather interesting, it does make sense that mild opioid receptor affinity could increase their effectiveness as anti depressants as I seem to recall reading (and certainly experiencing ) opioids were quite good anti depressants if it weren't for the drawback of addiction.

I am surprised I never heard/read this before since that was published in 2002! Definately an interesting find. I have known a couple of people that seemed to find Avanza quite helpful for depression and anxiety as far as anti depressants go, although in some cases that isn't saying a lot.

 

[Mr Blonde]

Interesting find, Dave! I wish I had full access to that article; I wonder exactly what their binding profiles are like for the opioid receptors. The reason that you don't experience opioid effects from them is probably because they do not bind too strongly to those receptors.

I've never been on Efexor, but I've used mirtazapine with opioids before for it's sedative and antihistamine properties and found that it was OK with opioids, I still preferred other antihistamines though.

 

[Jakeperson]

Mirtaz does nothing, until you stop taking it then it makes you wanna kill yourself.

 

[Seith]

Mirtaz does nothing, until you stop taking it then it makes you wanna kill yourself.

Thanks for the warning, was just switched over to it from 300mg of venlafaxine per day

Go anti-depressants go!

 

[Jakeperson]

You'll sleep lots at first but once that wears off it's practically nothing.

 

[belarki]

Thanks for the warning, was just switched over to it from 300mg of venlafaxine per day

Go anti-depressants go!

Good luck tapering off the effexor.... completely fucked me up even with zoloft to ease the taper. I didn't have the same negative effects from mirtazapine as Jakeperson though. I'd even consider giving it a second try as an antidepressant if it didn't make me stack on like 5kg in a month 8)

 

[Jakeperson]

Yeah that the great thing about me, I'm still around 75kg on Mirtaz, tiny before.

I did notice that mirtaz seemed to potentate Fentanyl quite a lot.

 

[Jabberwocky]

i've always liked the idea of seeing tramadol used more widely as an anti-depressant/mood stabiliser (it is used off label in instances) because of it's unique effects; sert, norepinephrine reuptake inhibitor and low μ-opioid receptor activity.

interesting read, thanks for posting.

 

[Davevanza]

Just my personal experience, the SolTab Avanza is less sedating, as it melts and delivers the full amount of the active ingredient at once, I notice, the higher the dose( I take up to 3 SolTabs 45mg), is less sedating.
I notice a mellow effect, which potentiates any Opiates, it's a calm feeling I noticed.

However, with the regular tab, it works like zombie, I feel disoriented, declining in cognitive function, and worst, it doesn't alleviate any pain.

I tried the SolTab 45mg, on its own, it works like an Opiate, as it binds to mu and kappa-3 receptors in the brain.
This is a bit of info which I experience.

As with Effexor XR, I just take it in the morning, 300mg.

But just make sure, when taking these 2 AD, it has a mild inhibitory effect on CYP450 2D6, making Codeine Phosphate less effective,as the transformation to Morphine is slightly blocked.

( An option is to take a corticosteroid, used for inflammation, called Dexamethasone, this induces CYP450 2D6, making it easier to transform Codeine to Morphine).

Other ADs, esp Paxil, is a strong inhibitor of that isoenzyme. Best avoid it. The same with TCa.

 

[Jakeperson]

Yeah higher doses seem to be less sedating and I get a bit of RLS from 90mg Mirtaz. My tolerance means I don't feel anything when I take it, do you reckon halving my dose could induce more sedation?

 

[Davevanza]

I dislike taking regular Avanza tab, I tried it, both high dose and low dose, 15mg and 90mg respectively, gives me RLS, mental cloudiness, even worsens my depression.
I switch to the quick acting SolTab (Soluble Tablet that has orange flavour), on high dose, 90mg, works better. It's not giving me "moody feeling" nor restlessness.
I combine it with Tramadol, up to 4tabs of 200mg SR form. Chewing it gives me a "buzz". But my main concern is seizure, as it's been reported in literature. To overcome this, I take Carbamazepine, on very low dose, just half the 100mg tab. As carbamazepine is an enzyme inducer,it speeds up the clearance of Tramadol. As my personal experience, I took 400mg of carbamazepine by mistake, and combined it with Avanza 90mg. The result, I couldn't even walk straight, much like drinking 2bottles of pure DXM.
Literature and MIMS are mostly theoretical,until I try it myself. It said that Carbamazepine would decrease the blood concentration of Avanza. Welll, it's only a theory until I experienced it, unable to walk straight, visual hallucination,lasting 24 hrs.

 

[Mr Blonde]

^ You're posts don't make a lot of sense, and you took that CYP2D6 bit from a post I made. I tried it over the weekend, I believe it helped quite bit but at the same time dexamethasone also induces CYP3A4 enzymes, so I used grapefruit to counter that.

Also, steroidal anti-inflammatories aren't drugs to mess around with; I wouldn't recommend trying it as a booster if you have diabetes or have already had GI problems. Long term use of them is a bad idea as well.

 

[Jakeperson]

I don't like the sound of this binding to my opioid receptors, since one day I will have to stop taking it and last time I tried to stop, I went on an oxy binge so felt no ill effects until after I ran out but I was mixing MXE inbetween oxy doses and after the oxy run out so who knows if there was any withdrawals. I was horribly suicidal/depressed after all that though.

 

[Jakeperson]

Also do you let the tabs dissolve? If I have lemonade I let them bubble in my mouth and swallow if not I just swallow them because tastes like shit at the end.