Psycho-Babble Medication Thread 13781

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Thanks for the laugh! (nm) » Cloud 9

Posted by Willow on December 10, 2001, at 22:18:20

In reply to Re: Effexor and GAD » Willow, posted by Cloud 9 on December 10, 2001, at 11:54:23

 

Re: Effexor an opiate? » dhldn

Posted by JANNBEAU on December 12, 2001, at 11:53:16

In reply to Effexor an opiate?, posted by dhldn on December 8, 2001, at 11:40:37

>My God! So that's why I felt I was going to DIE when my so-called "pain management specialist" put me on Effexor XR (37.5 mg qday) AND tramadol (50 mg every six hours up to a maximum of 6 tabs per day) without warning me of interactions! I stayed on this regimen for one week, then got what I can only figure was "serotonin syndrome" (completely unable to function-- memory loss; cognitive dysfunction; dizziness; possible seizure activity; somnolence; nervousness; sweating; tremors; nausea; anorexia; somnolence). DC'd tramadol--within hours, I was back to "normal"--at least I could function again and remember my name!

By the way, in the U.S., Ultram is NOT yet a controlled substance (although there are rumors that the FDA is moving that way--I figured out the narcotic properties of tramadol by reading the literature on the drug).

Is it possible that tramadol has some sort of "mixed" profile in that the parent drug may act primarily on serotonin, norepinephrine, and, perhaps, dopamine, while the principal metabolite has a higher affinity for the mu opioid receptors? Certainly, pain relief from tramadol seems to be delayed for several hours (6 hrs--the time it takes to get significant AUC for principal metabolite?).

If anything is deceiving, it is that the manufacturer of tramadol has claimed for five years that tramadol (Ultram in the U.S.) is not addictive! We've heard that one before, haven't we? You might not remember the hype when DARVON was first approved, but I do (I'm old!). Same story with Ultram! Again, as you stated above, 'history repeats itself' and 'history is repeatedly ignored!' I resent it that I received NONE of this information for Effexor (venlafaxine) OR tramadol prescribed concomitantly. Although I may (probably) would have chosen to go through with treatment, I would have been better able to make an INFORMED decision had I been given the facts! I wonder if the physician who prescribed these meds for me even KNOWS the facts?

I WOULD like to state that I noticed an immediated and dramatic reduction in my pain level when I started EFFEXOR XR (37.5 mg qd; I have chronic "intractable" pain from extensive degenerative changes in my cervical and thoracic spine, costochondral joints, knees, etc). Although I THINK the doc was prescribing Effexor as an AD, the pain relief makes sense in light of the structural similarity of Effexor and Ultram, as does the interaction between the two that I suffered. Thus, beware of drug interactions between Effexor and Ultram!

The structure and opiod properties of Effexor may, also, account for the stories of difficulty discontinuing Effexor. The signs and symptoms are strangely similar to those of any narcotic withdrawal syndrome, are they not?

Interestingly, the antidepressant effects of Effexor (if there WERE any) seem to have diminished dramatically after about two months, but the pain-relieving effects are still potent.

Forgive the disorganization. My apologies; there is a lot to say and I don't have much time to organize.

 

Questions

Posted by melmel on December 12, 2001, at 13:11:30

In reply to Anyone had success on Effexor XR? , posted by jp on October 24, 1999, at 14:59:14

hi! i'm new to taking effexor xr and have some questions. i usually wake up at 3am and can't go back to sleep. should i take it in the morning instead of at night? i'm taking 3 pills a day (225 mg), should i split the dosage? any help or tips would be great. thanks!

 

Going off Effexor

Posted by Allen F. on December 12, 2001, at 13:22:32

In reply to Re: Effexor an opiate? » dhldn, posted by JANNBEAU on December 12, 2001, at 11:53:16

Met with my Phycritist today and discussed the side-effects I was having (agian). He wants me to discontinue Effexor and see if they go away. He said to reduce the dosage to 37.5mg for a week, then half that for a week, and then go off completly. Then if the side-effects go away he will know its the drugs, if they don't then we will know its something else.

I have to admit I am very nervous about this, I DON'T want to have withdrawal problems.

Any ideas?

 

Re: Questions

Posted by JANNBEAU on December 12, 2001, at 14:28:38

In reply to Questions, posted by melmel on December 12, 2001, at 13:11:30

> hi! i'm new to taking effexor xr and have some questions. i usually wake up at 3am and can't go back to sleep. should i take it in the morning instead of at night? i'm taking 3 pills a day (225 mg), should i split the dosage? any help or tips would be great. thanks!

That's the way I was, too--at first. I set a clock and took mine about five or six hours before I wanted to wake up (usually set clock for about 2:00 A.M.). Did this for ab't three weeks, then gradually worked backwards til I could take them just before bedtime.

 

Re: Effexor an opiate? Probably not. » JANNBEAU

Posted by Elizabeth on December 12, 2001, at 15:29:04

In reply to Re: Effexor an opiate? » dhldn, posted by JANNBEAU on December 12, 2001, at 11:53:16

> By the way, in the U.S., Ultram is NOT yet a controlled substance (although there are rumors that the FDA is moving that way--I figured out the narcotic properties of tramadol by reading the literature on the drug).

It's true; Ultram is an opioid agonist, albeit a very weak one. I think it will probably be placed in Schedule IV. (BTW: "narcotic" really is more of a legal term than a medical one and probably isn't appropriate to use in a medical context because of its ambiguity.)

> Is it possible that tramadol has some sort of "mixed" profile in that the parent drug may act primarily on serotonin, norepinephrine, and, perhaps, dopamine, while the principal metabolite has a higher affinity for the mu opioid receptors?

I don't know what contributions are made by tramadol itself vs. O-desmethyltramadol (M1), but Ultram does have weak effects on serotonin and norepinephrine reuptake (I've never seen anything suggesting it's also a dopamine reuptake inhibitor). It's unclear how clinically significant these effects are, however.

> Certainly, pain relief from tramadol seems to be delayed for several hours (6 hrs--the time it takes to get significant AUC for principal metabolite?).

The reports that I've heard have suggested it's more like three hours. Still quite a delay, though.

> If anything is deceiving, it is that the manufacturer of tramadol has claimed for five years that tramadol (Ultram in the U.S.) is not addictive! We've heard that one before, haven't we?

< g > Did you know that heroin was originally (when it was marketed as a cough syrup) supposed to be a less addictive form of morphine?

Personally, I don't get any mood elevation from tramadol at the doses that are accepted as safe. FWIW.

> You might not remember the hype when DARVON was first approved, but I do (I'm old!).

Yeah, you're really dating yourself here! :-)

> I resent it that I received NONE of this information for Effexor (venlafaxine) OR tramadol prescribed concomitantly.

I really doubt that Effexor is an opioid (or if it is, it's probably *extremely* weak), although it might be interesting to try to find out for sure. But there is a risk (of the "serotonin syndrome") when Effexor or SSRIs are prescribed with tramadol -- generally the combination isn't recommended. Again, this applies to SSRIs (and MAOIs, for that matter), not just Effexor. It definitely does not mean that Effexor is an opioid.

> I WOULD like to state that I noticed an immediated and dramatic reduction in my pain level when I started EFFEXOR XR (37.5 mg qd; I have chronic "intractable" pain from extensive degenerative changes in my cervical and thoracic spine, costochondral joints, knees, etc).

A lot of ADs relieve pain (tricyclics were the first ones used for this); it doesn't mean they're opioids. Nardil relieved my back pain completely for the entire time I was taking it. I didn't notice the effect (the pain has had a relapsing and remitting course) until I stopped taking Nardil the second time and the pain came back with a vengeance immediately.

> The structure and opiod [sic] properties of Effexor may, also, account for the stories of difficulty discontinuing Effexor.

No. Effexor withdrawal symptoms are not similar to opioid withdrawal. They do, however, resemble the withdrawal symptoms that are often reported with SSRIs (especially Paxil, but also sometimes others).

> The signs and symptoms are strangely similar to those of any narcotic withdrawal syndrome, are they not?

What withdrawal symptoms associated with Effexor do you think are similar to opioid withdrawal? I haven't heard of any such thing.

-elizabeth

 

Re: Questions

Posted by Elizabeth on December 12, 2001, at 15:31:57

In reply to Questions, posted by melmel on December 12, 2001, at 13:11:30

> i'm new to taking effexor xr and have some questions. i usually wake up at 3am and can't go back to sleep. should i take it in the morning instead of at night?

Yes, that's a good idea.

> i'm taking 3 pills a day (225 mg), should i split the dosage?

If you're taking regular Effexor (tablets), you might want to ask about Effexor XR. It's better suited to higher doses, as it can be taken once a day (most people do better taking it in the morning).

-elizabeth

 

Re: Questions

Posted by melmel on December 12, 2001, at 15:56:29

In reply to Re: Questions, posted by Elizabeth on December 12, 2001, at 15:31:57

i am taking the xr. i think i will try taking it in the morning. thanks!

> > i'm new to taking effexor xr and have some questions. i usually wake up at 3am and can't go back to sleep. should i take it in the morning instead of at night?
>
> Yes, that's a good idea.
>
> > i'm taking 3 pills a day (225 mg), should i split the dosage?
>
> If you're taking regular Effexor (tablets), you might want to ask about Effexor XR. It's better suited to higher doses, as it can be taken once a day (most people do better taking it in the morning).
>
> -elizabeth

 

Re: Effexor an opiate? Probably not. » Elizabeth

Posted by JANNBEAU on December 12, 2001, at 16:57:04

In reply to Re: Effexor an opiate? Probably not. » JANNBEAU, posted by Elizabeth on December 12, 2001, at 15:29:04

Hello, Elizabeth. WELL! I have to say, your posting upset me rather much. With respect, I was responding to a posting by dldh (I think) who purports to be a D. Psych (what ever that is) named Gillman: Here's a copy of his posting. It was posted on 12/12/01, but I cannot find it right now). Anyway, maybe you can see whence I speak. I will respond to your specific comments below after the quote.

From Dr. Gillman's posting:
"It is concerning that venlafaxine has a close structural similarity to tramadol (a new narcotic analgesic). There is evidence that it has analgesic effects that are blocked by naloxone; that suggests it may be acting partly as an opioid drug.
>
> It seems that venlafaxine may be particularly prone to interact with MAOIs and thus be implicated in fatal serotonin syndrome reactions.
>
> Venlafaxine, when used in larger doses of over ~150 mg, may cause hypertension in some people, another problem that requires monitoring and may debar its use in some patients.
>
> What the place of venlafaxine should be at lower doses (i.e. up to ~150 mg) in primary care is hard to judge. It shares the low interaction propensity (via CYP450) of sertraline and citalopram; but at lower doses probably has no particular advantages and is much more toxic in over-dose than any of the SSRIs or even than some of the old tricyclic antidepressants.
>
> It behooves us all to be especially cautious about drugs when there is uncertainty over the mechanism of their action. Venlafaxine's toxicity in over-dose and its similarities to the narcotic analgesic 'tramadol' warrant close monitoring and caution.
>
> My evaluation of the current evidence is that venlafaxine should be used sparingly in primary care settings with care and due recognition of the uncertainties surrounding it; whether it will prove suitable as a treatment for generalised anxiety disorder may become a contentious issue.
>
> History repeatedly demonstrates that new is not always better. History is repeatedly ignored.
>
>
> The FDA have now officially amended the product information on venlafaxine (2000) as follows:--
>
> Discontinuation symptoms have been systematically evaluated in patients taking venlafaxine.... Abrupt discontinuation or dose reduction... is associated with the appearance of new symptoms, the frequency of which is increased at higher doses and with longer duration of treatment.
> Reported symptoms:--
> agitation, anorexia, anxiety, confusion, coordination impaired, diarrhea, dizziness, dry mouth, dysphoric mood, fasciculation, fatigue, headaches, hypomania, insomnia, nausea, nervousness, nightmares, sensory disturbances (including shock-like electrical sensations), somnolence, sweating, tremor, vertigo, and vomiting.
> It is therefore recommended that the dosage of Effexor be tapered gradually and the patient monitored. The period required for tapering may depend on the dose, duration of therapy and the individual patient.
>
> Subscribe to 'Psychopharmacology update notes' to see a fuller analysis and references."
>
That's the end of Dr. Gillman's (??--interesting similarity to the great Gilman of "Goodman and Gilman" Pharmacotherapy"--


> > By the way, in the U.S., Ultram is NOT yet a controlled substance (although there are rumors that the FDA is moving that way--I figured out the narcotic properties of tramadol by reading the literature on the drug).

O-desmethyltramadol, according to my sources, has an affinity for mu opioid receptors that is about six times greater than that of the parent compound. It is interesting to note that the pain-relief associated with tramadol occurs around the time the o-desmethyltramadol reaches a "therapeutic" level in the bloodstream. This is presumptive evidence that the primary action of the o-desmethyltramadol is that of an opioid. I have found this factoid in the literature and, if I am NOT WRONG, which I well may be, since I am working from memory here, the manufacturer, McNeil actually states that the analgesic activity may be related, in part, at least, to M1 activity at the mu receptor.

>
> It's true; Ultram is an opioid agonist, albeit a very weak one. I think it will probably be placed in Schedule IV. (BTW: "narcotic" really is more of a legal term than a medical one and probably isn't appropriate to use in a medical context because of its ambiguity.)
>
According to Stedman's Medical Dictionary, 27th edition, Lippincott Williams & Wilkins, Philadelphia, 2000, page 1182, and I quote: "Narcotic 1. Originally, any drug derived from opium or opium-like compounds with potent analgesic effects associated with both significant alteration of mood and behavior and potential for dependence and tolerance. 2. More recently, any drug, synthetic or naturally occurring, with effects similar to those of opium and opium derivatives, including meperidine and fentanyl and its derivatives. 3. Capable of inducing a state of stuporous analgesia [from the Greek: narkotikos, benumbing]." In none of these definitions is there ANY mention of a medico-legal definition of "narcotic analgesic". Therefore, although I see your point, as a pharmacologist/toxicologist, I don't agree with your definition. I am not a lawyer--so I don't know the subtle legalese. Note that Gillman uses the term "narcotic analgesic" in the same way I meant it to be taken!


> > Is it possible that tramadol has some sort of "mixed" profile in that the parent drug may act primarily on serotonin, norepinephrine, and, perhaps, dopamine, while the principal metabolite has a higher affinity for the mu opioid receptors?
>
> I don't know what contributions are made by tramadol itself vs. O-desmethyltramadol (M1), but Ultram does have weak effects on serotonin and norepinephrine reuptake (I've never seen anything suggesting it's also a dopamine reuptake inhibitor). It's unclear how clinically significant these effects are, however.
>
Don't hold your breath with regard to specificity!

> > Certainly, pain relief from tramadol seems to be delayed for several hours (6 hrs--the time it takes to get significant AUC for principal metabolite?).
>
> The reports that I've heard have suggested it's more like three hours. Still quite a delay, though.
>
Three, six, whatever--probably depends upon the individual's metabolic capacity to convert tramadol to o-desmethyltramadol. Whatever--I need relief within 30 minutes, as with the well-accepted opioids that I take: hydrocodone (5 mg 2X per day) or Darvocet (2 tabs at bedtime). At LEAST, someone could have told me the analgesic effects are delayed. Also indicates, in my humble opinion, that tramadol cannot be relied upon to give acute relief, as one would have to keep a certain blood level of M1 to retain the analgesic effects, implying regular dosing. I often take no medication until I hurt really badly because I don't think of it if I am not hurting..

> > If anything is deceiving, it is that the manufacturer of tramadol has claimed for five years that tramadol (Ultram in the U.S.) is not addictive! We've heard that one before, haven't we?
>
> < g > Did you know that heroin was originally (when it was marketed as a cough syrup) supposed to be a less addictive form of morphine?
>
Yes, I was fully aware of this!

> Personally, I don't get any mood elevation from tramadol at the doses that are accepted as safe. FWIW.
>
I have noticed that tramadol (as well as hydrocodone and codeine) wake me up. I, therefore, would take these drugs only in the daytime, reserving Darvocet, which does NOT give me insomnia nor does it give me nightmares (hydrocodone and oxycodone both do).

> > You might not remember the hype when DARVON was first approved, but I do (I'm old!).
>
> Yeah, you're really dating yourself here! :-)
>
> > I resent it that I received NONE of this information for Effexor (venlafaxine) OR tramadol prescribed concomitantly.
>
> I really doubt that Effexor is an opioid (or if it is, it's probably *extremely* weak), although it might be interesting to try to find out for sure. But there is a risk (of the "serotonin syndrome") when Effexor or SSRIs are prescribed with tramadol -- generally the combination isn't recommended. Again, this applies to SSRIs (and MAOIs, for that matter), not just Effexor. It definitely does not mean that Effexor is an opioid.
>
I did not mean to imply that Effexor is a known opioid, but it does have a structure similar to that of tramadol (see the posting above from a Dr. Gillman (cannot find it in postings or I'd just refer you) below that I've pasted into this one). If structure-activity relationships mean anything, then the effects of both drugs may be similar, may have an additive effect, or even a synergistic effect. (I do realize that they might antagonize each other, too. I've had quite a bit of pharmacology and toxicology in my long life; however, antagonism was not my experience!)

> > I WOULD like to state that I noticed an immediated and dramatic reduction in my pain level when I started EFFEXOR XR (37.5 mg qd; I have chronic "intractable" pain from extensive degenerative changes in my cervical and thoracic spine, costochondral joints, knees, etc).
>
> A lot of ADs relieve pain (tricyclics were the first ones used for this); it doesn't mean they're opioids. Nardil relieved my back pain completely for the entire time I was taking it. I didn't notice the effect (the pain has had a relapsing and remitting course) until I stopped taking Nardil the second time and the pain came back with a vengeance immediately.
>
I am aware of the analgesic effects of AD's--at doses much lower than those used for the AD effects--and I am certainly aware that antidepressants are not classed as opioids. In fact, most are more closely related, at least in activity, to the amphetamines. Again, I caution: Don't rely too heavily on the so-called "specificity" of any drug, especially those that act on CNS receptors.

Did you know that the tricyclics are very similar to many older antihistamines? In fact, did you know that the tricyclic AD's were discovered by people researching antihistiminic effects? The discovery of tricyclics was, thus, serendipitous, as are the discoveries of many therapeutic modalitie and/or alternative uses for medications.

> > The structure and opioid properties of Effexor may, also, account for the stories of difficulty discontinuing Effexor.
>
> No. Effexor withdrawal symptoms are not similar to opioid withdrawal. They do, however, resemble the withdrawal symptoms that are often reported with SSRIs (especially Paxil, but also sometimes others).
>
> > The signs and symptoms are strangely similar to those of any narcotic withdrawal syndrome, are they not?
>
> What withdrawal symptoms associated with Effexor do you think are similar to opioid withdrawal? I haven't heard of any such thing.
>
So what are the differences? I looked up opiod withdrawal symptoms and came up with: nervousness; sweating; nightmares; shaking chills; insomnia; somnolence; memory lapses; cognitive dysfunction, diarrhea, vomiting, nausea, anxiety, dysphoria; fatigue; hypomania; etc.

These following signs/symptoms of Effexor withdrawal are published in the physician's insert for this drug. I quote from Gillman's posting (above): agitation, anorexia, anxiety, confusion, coordination impaired, diarrhea, dizziness, dry mouth, dysphoric mood, fasciculation, fatigue, headaches, hypomania, insomnia, nausea, nervousness, nightmares, sensory disturbances (including shock-like electrical sensations), somnolence, sweating, tremor, vertigo, and vomiting. At any rate, I certainly got these signs/symptoms from combining tramadol and venlafaxine.

So, again, I ask you, just what are the differences?. There may be subtle gradations in the manifestations of withdrawal dependent upon the drug in question, but both constitute a strikingly similar withdrawal syndrome (withdrawal, by the way, is a nonspecific term associated with any syndrome precipitated by abrupt cessation of any drug to which the body has become habituated. In most instances, one would find it difficult, perhaps, to distinguish what the patient was withdrawing from simply by observing him/her. One would be far better in today's world at least if one knows what drug the patient has been taking. Drug history IS important).

Forgive any typos (as in opiod for opioid) in my earlier posting. I don't have time to check everything. In fact, I probably should not be drawn into these discourses as I don't know the qualifications of those to whom I write.

Cheers,
JANNBEAU

> -elizabeth

 

Re: withdrawal

Posted by ArtChee on December 12, 2001, at 19:49:50

In reply to Re: withdrawal, posted by Cam W. on April 12, 2000, at 19:27:33

Cam -- You seem somewhat knowledgeable about the withdrawal aspects of EFFEXOR. I was prescribed Effexor two years ago for long term, chronic depression. Started the graduated dosages up to 150mg/day. Stayed on it for maybe two months, & got nothing but minor, nuisance side effects. Came off gradually - no noticable problems.
Two months ago, my psychotherapist recommended trying antidepressants to supplement "talk therapy." Same psychiatrist from before recommended EFFEXOR XR in twice the dosage as the first time. Did the graduation up to 300mg/day. AGAIN, got the side effects without the 'FRONT' effects. As I graduated to the 300mg/day, I became anxious to the point of picking, with index finger nails, the quick on both thumbs, and pulling off the flicks of skin that were broken. (Nothing new, do this when experiencing anxiety. I figure it's better than an ulcer.) Have to band-aide around both thumbs to prevent them from being raw.

Side effects this time are more noticable: sweats, shortness of breath, not sleeping well at night, light-headedness - wozziness, drymouth, headaches (which normally don't have), AND further depression at the fact that I am non-responsive to treatment. After 10 weeks of this, and getting worse, requested info on how to get off. Dr. prescribed 3 days at -75mg until off completely; which took 9 days.

The second day of being completely off EFFEXOR XR, I am extremely wozzy, unable to focus my attention, and pretty much non-functional: MAJOR side effects. Called the doctor, who says this is not abnormal, nor serious as it does not lead to anything more serious (providing, of course, I don't find myself in an automobile accident due to loss of mental functions.) Said to call him again in a couple of days if it doesn't subside.

With all due respect, most of what he has told me to this point has been inaccurate IN MY CASE. My question here - to CAM, or anyone else with any experience or knowledge of withdrawal effects of coming off 300mg of EFFEXOR XR is: can these symptoms subside in a week? ...after being on the medication - that takes 2 to 4 weeks to take affect - for 10 or more weeks??

 

Re: Effexor an opiate? Probably not. » JANNBEAU

Posted by Elizabeth on December 12, 2001, at 22:52:26

In reply to Re: Effexor an opiate? Probably not. » Elizabeth, posted by JANNBEAU on December 12, 2001, at 16:57:04

> Hello, Elizabeth. WELL! I have to say, your posting upset me rather much.

I'm sorry, although I have a hard time understanding why you're so upset about it. I certainly didn't mean anything personally, even though I might have been critical of what you said.

(BTW, I did indeed read dhldn's post, and I posted a brief direct reply. I think it's a mistake to conclude that since venlafaxine and tramadol have some structural similarity, venlafaxine must be an opioid, or even that it's especially likely that it is. You can read my response at http://www.dr-bob.org/babble/20011202/msgs/86335.html. dhldn listed some potential dangers of Effexor and seemed to be jumping to the conclusion that Effexor is an opioid.)

I think it's important to recognize that we don't know everything about the pharmacologic mechanisms of *any* of the drugs we use -- not just Effexor. All drugs may have effects we don't know about. At the same time, we know how to screen for affinities for various receptors, and it's likely that most drugs available today have been tested for opioid receptor affinity. Now, it's possible that if a drug company doesn't want to know that a drug they have is an opioid, they could do a very cursory test and accept the negative finding from that test. I think, though, that Effexor has been around long enough that if it were an opioid, this would have been discovered by now.

> O-desmethyltramadol, according to my sources, has an affinity for mu opioid receptors that is about six times greater than that of the parent compound.

Actually, I went ahead and looked this one up, and according to the PI, the affinity of O-desmethyltramadol (let's call it ODT for short) for mu receptors is about *200* times that of the parent compound; interestingly, the PI adds that ODT is about six times as potent an *analgesic* as tramadol. (Hard to know what to make of this.)

As for the word "narcotic," it's ambiguous. Politicians use it to mean any illegal drug; they often include cocaine and marijuana in the category "narcotics." This also makes the word politically loaded, so it's probably better to use a more neutral word, since one is available. Also, there's the question of whether drugs with partial or mixed opioid agonist activity (such as buprenorphine, butorphanol (Stadol), pentazocine (Talwin), nalbuphine (Nubain), etc.) which have little or no significant abuse potential should be considered "narcotics."

> > The reports that I've heard have suggested it's more like three hours. Still quite a delay, though.
> >
> Three, six, whatever--probably depends upon the individual's metabolic capacity to convert tramadol to o-desmethyltramadol.

I meant that people I know who are taking it say it takes around three hours to work. This is acutely -- if Ultram is taken around-the-clock, allowing ODT to build up, it may take effect in an hour or less when you first take it in the morning.

> At LEAST, someone could have told me the analgesic effects are delayed.

From the PI: "Analgesia in humans begins approximately within one hour after administration and reaches a peak in approximately two to three hours." Sort of ambiguous, I agree.

> I have noticed that tramadol (as well as hydrocodone and codeine) wake me up.

All effective opioids do this to me, or at least, all the effective opioids I've taken do at the doses I've taken. (Ultram and codeine do not, which might be due to a deficiency in the enzyme cytochrome P450 2D6 -- this would lead to poor metabolism of tramadol to ODT and codeine to morphine.)

> I, therefore, would take these drugs only in the daytime, reserving Darvocet, which does NOT give me insomnia nor does it give me nightmares (hydrocodone and oxycodone both do).

Huh. Can't think of an explanation why they would have this side effect (nightmares, that is).

> > I really doubt that Effexor is an opioid (or if it is, it's probably *extremely* weak), although it might be interesting to try to find out for sure. But there is a risk (of the "serotonin syndrome") when Effexor or SSRIs are prescribed with tramadol -- generally the combination isn't recommended. Again, this applies to SSRIs (and MAOIs, for that matter), not just Effexor. It definitely does not mean that Effexor is an opioid.
> >
> I did not mean to imply that Effexor is a known opioid, but it does have a structure similar to that of tramadol (see the posting above from a Dr. Gillman (cannot find it in postings or I'd just refer you) below that I've pasted into this one). If structure-activity relationships mean anything, then the effects of both drugs may be similar, may have an additive effect, or even a synergistic effect. (I do realize that they might antagonize each other, too. I've had quite a bit of pharmacology and toxicology in my long life; however, antagonism was not my experience!)

Umm, not sure what you meant by that last bit. What I'll say here is that there are *many* drugs that are structurally similar to venlafaxine, and there really isn't a reason to list them all in the PI for Effexor; noting the similarity to tramadol alone, meanwhile, would be misleading. The structural similarity to tramadol does suggest that it might be worthwhile to test venlafaxine to see if it's an opioid. If venlafaxine were shown to be an opioid, that information would be appropriate to include in the PI.

Anyway, the structural similarity is not the reason for the risk of interaction; the serotonin reuptake inhibition by both drugs is most likely to blame there. There have been a number of reports of the serotonin syndrome resulting from combinations of tramadol with SSRIs or Effexor. Most opioids don't have this problem and can be used safely with the serotonin reuptake inhibitor ADs.

> Did you know that the tricyclics are very similar to many older antihistamines?

Sure. So are the phenothiazines. Indeed, most of the tricyclics and the phenothiazines *are* antihistamines. But agani, this information (their affiniaty for H1 receptors), not their structural similarity to known antihistamines, would be appropriate to include in their PIs (it generally isn't because they are old drugs).

> So what are the differences? I looked up opiod withdrawal symptoms and came up with: nervousness; sweating; nightmares; shaking chills; insomnia; somnolence; memory lapses; cognitive dysfunction, diarrhea, vomiting, nausea, anxiety, dysphoria; fatigue; hypomania; etc.
>
> These following signs/symptoms of Effexor withdrawal are published in the physician's insert for this drug. I quote from Gillman's posting (above): agitation, anorexia, anxiety, confusion, coordination impaired, diarrhea, dizziness, dry mouth, dysphoric mood, fasciculation, fatigue, headaches, hypomania, insomnia, nausea, nervousness, nightmares, sensory disturbances (including shock-like electrical sensations), somnolence, sweating, tremor, vertigo, and vomiting. At any rate, I certainly got these signs/symptoms from combining tramadol and venlafaxine.

The list from the Effexor PI is pretty exhaustive. That's not surprising since the PIs typically list every reported side effect and could be expected to do the same with withdrawal symptoms.

The most common recognized opioid withdrawal symptoms include gooseflesh; hot and cold flashes; insomnia; cramps and diarrhea; shivering; nausea and vomiting; dysphoric mood; drippy eyes and nose; dilated pupils; aches and pains; and fever. It's like having the flu. Sometimes people will have elevated pulse, respiratory rate, and/or blood pressure as well.

Common Effexor withdrawal symptoms can be found by reading about the subject in the Psycho-Babble archives. The ones I recall reading about most often are the electric-shock type sensations, nightmares and disturbed sleep, dizziness, sweating, nausea, vertigo, headaches, fatigue, tinnitus, and dysphoria. (I could be missing some, but I don't believe that all the symptoms listed in the PI are especially common.) Some of them are also common symptoms of opioid withdrawal, but the overall picture doesn't suggest that the two syndromes are related. The common symptoms (sweating, nausea, dysphoria) are pretty generic ones, too.

> In most instances, one would find it difficult, perhaps, to distinguish what the patient was withdrawing from simply by observing him/her.

Actually, there are pretty specific withdrawal syndromes for different classes of substances, although these are best defined for drugs of abuse. Opioid withdrawal is particularly specific. On the other hand, there are some withdrawal symptoms that are pretty common with various types of drugs, such as sweating, nausea, dysphoria, sleep disturbance, and fatigue. (I even had problems with nausea from discontinuing Klonopin too rapidly -- that's *not* a typical benzo withdrawal symptom.)

Anyway, I wouldn't worry about Effexor being an opioid. One thing that Effexor does have in common with opioids, though, is that its withdrawal symptoms, though very unpleasant, are not going to kill you.

-elizabeth

 

Re: Effexor an opiate? Probably not. » Elizabeth

Posted by JANNBEAU on December 13, 2001, at 11:41:32

In reply to Re: Effexor an opiate? Probably not. » JANNBEAU, posted by Elizabeth on December 12, 2001, at 22:52:26

> > Hello, Elizabeth. Sorry I overreacted to your initial message. I'm rather new at this. I actually enjoyed your second posting. I've written some responses below. Please take them in the same spirit that you offered your comments.

Cheers,
JANNBEAU
>
> (BTW, I did indeed read dhldn's post, and I posted a brief direct reply. I think it's a mistake to conclude that since venlafaxine and tramadol have some structural similarity, venlafaxine must be an opioid, or even that it's especially likely that it is. You can read my response at http://www.dr-bob.org/babble/20011202/msgs/86335.html. dhldn listed some potential dangers of Effexor and seemed to be jumping to the conclusion that Effexor is an opioid.)

Read your posting to dhldn. Didn't say much. Perhaps you could go into the detail with dhldn that you went into with me. I'd like to see HIS response.

>
> I think it's important to recognize that we don't know everything about the pharmacologic mechanisms of *any* of the drugs we use -- not just Effexor. All drugs may have effects we don't know about. At the same time, we know how to screen for affinities for various receptors, and it's likely that most drugs available today have been tested for opioid receptor affinity. Now, it's possible that if a drug company doesn't want to know that a drug they have is an opioid, they could do a very cursory test and accept the negative finding from that test. I think, though, that Effexor has been around long enough that if it were an opioid, this would have been discovered by now.

I do know that we don't have a clue about the myriad effects of today's meds. Not much different from the Middle Ages, huh, except there are so many more of them with which to contend. I am bothered most by the fact that doctors prescribing them don't seem to think of this and do not discuss potential interactions, side effects. I always ask for the PI so that I will at least recognize an effect as being -perhaps- due to the new medication. Both my husband and daughter are physicians and I stress to them the importance of knowing your drugs and telling your patients what to expect. Not everyone has access to the information that we do nor do they have the sophistication to interpret it. I take many Rx drugs for various things (HTN, hypercholesterolemia, etc) along with those I take for pain and, believe me, even if I knew nothing about the state of the "art" of developing, or more precisely, marketing new drugs (I worked in clinical pharmaceutical development for several years), I would be skeptical and watchful whenever I'm prescribed a "new" medication.
>
> > O-desmethyltramadol, according to my sources, has an affinity for mu opioid receptors that is about six times greater than that of the parent compound.
>
> Actually, I went ahead and looked this one up, and according to the PI, the affinity of O-desmethyltramadol (let's call it ODT for short) for mu receptors is about *200* times that of the parent compound; interestingly, the PI adds that ODT is about six times as potent an *analgesic* as tramadol. (Hard to know what to make of this.)
>
OK, I'll give you that one! As I said, I was working from memory and have only scanned the literature on Effexor.

> As for the word "narcotic," it's ambiguous. Politicians use it to mean any illegal drug; they often include cocaine and marijuana in the category "narcotics." This also makes the word politically loaded, so it's probably better to use a more neutral word, since one is available. Also, there's the question of whether drugs with partial or mixed opioid agonist activity (such as buprenorphine, butorphanol (Stadol), pentazocine (Talwin), nalbuphine (Nubain), etc.) which have little or no significant abuse potential should be considered "narcotics."
>
I stand by the dictionary's definition of narcotic analgesic. The dictionary does not suggest ambiguity. The term is used routinely in both clinical practice and in research, along with others. I am not a politician nor am I interested in arguing the politicians' uninformed views and imprecise use of the English language. Simply because some segments of the population have misused a term does not invalidate the definition. However, if you prefer, I can use "opioid analgesic" if this is the term to which you refer. It doesn't matter as long as each party understands the concept.

Now, for the second point. Research has shown that one cannot predict which medications will become "drugs of abuse" or "street drugs" by the structure, intended use, or class of drug, although pure opioid agonists tend to be most heavily abused as do some stimulants, of course. Illegal use of a drug often occurs because of "hype" or "fad" potential. Whether a drug is abused seems to have some significant psychological component, as well as the factor of "availability." For instance, OxyContin (extended-release hydrocodone) is not very different from MSContin (long-acting morphine sulfate) in pain relieving activity, yet one has become a popular street drug (OxyContin) while the other (MS Contin) never became a popular street drug, despite the fact that MS Contin is formulated similarly and should give the same "high" from snorting or injection of the crushed tablets.

With respect to your final comment re mixed opioid agonists, check the history of Talwin (pentazocine). You might find, as I have read, that when pentazocine was first marketed, it rapidly became a "drug of abuse" or "street drug." Such abuse did not stop until the manufacturer reformulated the drug to add an opioid antagonist to prevent the "high" accompanying illegal use. This would argue against the statement that mixed opioid agonists have "little or no potential for abuse."


> I meant that people I know who are taking it say it takes around three hours to work. This is acutely -- if Ultram is taken around-the-clock, allowing ODT to build up, it may take effect in an hour or less when you first take it in the morning.
>
I agree that around the clock dosing is probably important for this drug.

> From the PI: "Analgesia in humans begins approximately within one hour after administration and reaches a peak in approximately two to three hours." Sort of ambiguous, I agree.
>
I read the PI and did not expect that I would hurt for six hours after taking the med. I used it for about a week with Effexor before developing what I assume was serotonin syndrome; at no time did I get any significant pain relief. In fact, I was probably overdosing myself because I continued to hurt, despite Effexor's analgesic potential.

> > I have noticed that tramadol (as well as hydrocodone and codeine) wake me up.
>
> All effective opioids do this to me, or at least, all the effective opioids I've taken do at the doses I've taken. (Ultram and codeine do not, which might be due to a deficiency in the enzyme cytochrome P450 2D6 -- this would lead to poor metabolism of tramadol to ODT and codeine to morphine.)
>
Ultram has this effect on me as does codeine.

> Nightmares or "vivid" dreams have been associated with oxycontin. Why would one not expect the same from other drugs of like action?

> > > I really doubt that Effexor is an opioid (or if it is, it's probably *extremely* weak), although it might be interesting to try to find out for sure. But there is a risk (of the "serotonin syndrome") when Effexor or SSRIs are prescribed with tramadol -- generally the combination isn't recommended. Again, this applies to SSRIs (and MAOIs, for that matter), not just Effexor. It definitely does not mean that Effexor is an opioid.

I have to accept the above comment, qualified by your following statement. Perhaps I've been led astray by the good doctor's posting?
> > >
> > What I'll say here is that there are *many* drugs that are structurally similar to venlafaxine, and there really isn't a reason to list them all in the PI for Effexor; noting the similarity to tramadol alone, meanwhile, would be misleading. The structural similarity to tramadol does suggest that it might be worthwhile to test venlafaxine to see if it's an opioid. If venlafaxine were shown to be an opioid, that information would be appropriate to include in the PI.

Agreed
>
> Anyway, the structural similarity is not the reason for the risk of interaction; the serotonin reuptake inhibition by both drugs is most likely to blame there. There have been a number of reports of the serotonin syndrome resulting from combinations of tramadol with SSRIs or Effexor. Most opioids don't have this problem and can be used safely with the serotonin reuptake inhibitor ADs.

I understand this concept. I do not argue that Effexor is not an SRI (not an SSRI), just that it may have more than ONE mechanism of action and that the results of this "mixed" mechanism may be different from what one would expect with a "pure" SRI.

> > Did you know that the tricyclics are very similar to many older antihistamines?
>
> Sure. So are the phenothiazines. Indeed, most of the tricyclics and the phenothiazines *are* antihistamines. But agani, this information (their affiniaty for H1 receptors), not their structural similarity to known antihistamines, would be appropriate to include in their PIs (it generally isn't because they are old drugs).
>
I think we're splitting hairs here!

> > So what are the differences? I looked up opiod withdrawal symptoms and came up with: nervousness; sweating; nightmares; shaking chills; insomnia; somnolence; memory lapses; cognitive dysfunction, diarrhea, vomiting, nausea, anxiety, dysphoria; fatigue; hypomania; etc.
> >
> > These following signs/symptoms of Effexor withdrawal are published in the physician's insert for this drug. I quote from Gillman's posting (above): agitation, anorexia, anxiety, confusion, coordination impaired, diarrhea, dizziness, dry mouth, dysphoric mood, fasciculation, fatigue, headaches, hypomania, insomnia, nausea, nervousness, nightmares, sensory disturbances (including shock-like electrical sensations), somnolence, sweating, tremor, vertigo, and vomiting. At any rate, I certainly got these signs/symptoms from combining tramadol and venlafaxine.
>
> The list from the Effexor PI is pretty exhaustive. That's not surprising since the PIs typically list every reported side effect and could be expected to do the same with withdrawal symptoms.

>I am aware of the FDA's requirements for listing side effects and withdrawal effects.

> The most common recognized opioid withdrawal symptoms include gooseflesh; hot and cold flashes; insomnia; cramps and diarrhea; shivering; nausea and vomiting; dysphoric mood; drippy eyes and nose; dilated pupils; aches and pains; and fever. It's like having the flu. Sometimes people will have elevated pulse, respiratory rate, and/or blood pressure as well.
>
> Common Effexor withdrawal symptoms can be found by reading about the subject in the Psycho-Babble archives. The ones I recall reading about most often are the electric-shock type sensations, nightmares and disturbed sleep, dizziness, sweating, nausea, vertigo, headaches, fatigue, tinnitus, and dysphoria. (I could be missing some, but I don't believe that all the symptoms listed in the PI are especially common.) Some of them are also common symptoms of opioid withdrawal, but the overall picture doesn't suggest that the two syndromes are related. The common symptoms (sweating, nausea, dysphoria) are pretty generic ones, too.
>
OK, point taken.

> Actually, there are pretty specific withdrawal syndromes for different classes of substances, although these are best defined for drugs of abuse. Opioid withdrawal is particularly specific. On the other hand, there are some withdrawal symptoms that are pretty common with various types of drugs, such as sweating, nausea, dysphoria, sleep disturbance, and fatigue. (I even had problems with nausea from discontinuing Klonopin too rapidly -- that's *not* a typical benzo withdrawal symptom.)
>
> Anyway, I wouldn't worry about Effexor being an opioid. One thing that Effexor does have in common with opioids, though, is that its withdrawal symptoms, though very unpleasant, are not going to kill you.

I'm not worried! This was supposed to be an intellectual discussion. I take hydrocodone a couple of times a day and propoxyphene at night. Why would I be "worried" about the proposed "opioid" effects of Effexor? The drug seems to help me and I have no intention of stopping it unless it exacerbates my HTN too much. That's probably my biggest worry-since I am taking several drugs for HTN, I don't need anything that causes a sustained increase in my BP. I also have NEVER had difficulty stopping any drug I took, so don't expect to die from discontinuing Effexor.

Again, I've just enjoyed the intellectual stimulation of this conversation.
JANNBEAU
> -elizabeth

 

Re: Effexor an opiate? Probably not. » JANNBEAU

Posted by Elizabeth on December 13, 2001, at 20:06:59

In reply to Re: Effexor an opiate? Probably not. » Elizabeth, posted by JANNBEAU on December 13, 2001, at 11:41:32

> Hello, Elizabeth. Sorry I overreacted to your initial message. I'm rather new at this.

Don't worry about it. I think it's easy to misinterpret stuff over the net because there's no body language, facial expressions, etc. Just about everybody does it sometimes. It's still surprising to be at the other end of it, though! :-)

> I actually enjoyed your second posting. I've written some responses below. Please take them in the same spirit that you offered your comments.

Of course.

> Read your posting to dhldn. Didn't say much. Perhaps you could go into the detail with dhldn that you went into with me. I'd like to see HIS response.

My response to you also responded to his comments in greater depth. But he didn't post a response to my post. I'm not sure if he's a regular here, though.

Anyway, credentials don't mean much to me (especially since they're generally unproven on this forum). This is in part due to some of my experiences with psychiatrists who didn't know what they were talking about, but also to my general skepticism: I don't take what I hear as fact just because someone says it, regardless what letters that someone has after his or her name. :-) I expect everyone (not just laypeople) to show an understanding of what they're writing about.

> I do know that we don't have a clue about the myriad effects of today's meds. Not much different from the Middle Ages, huh, except there are so many more of them with which to contend.

I think our approach differs greatly from that of the Middle Ages, although some attitudes expressed by a lot of people (including medical and even scientific professionals) bear a disturbing resemblance to aspects of the Medieval world-view.

> I am bothered most by the fact that doctors prescribing them don't seem to think of this and do not discuss potential interactions, side effects.

Sometimes psychiatrists don't keep up with research on the drugs they prescribe, or on new off-label treatments. This is a serious problem. I think that part of it is that they assume that if another doctor is going to prescribe a drug that might interact, the other doctor will point out the interaction. Of course, this precludes the possibility that the patient have any control over his/her treatment.

> I always ask for the PI so that I will at least recognize an effect as being -perhaps- due to the new medication.

The trouble with the PI is the reverse: it includes every reported "side effect," even some which probably don't have anything to do with the drug. This can scare patients, to say the least, even making them unwilling to try the drug. It's misleading because most of these "side effects" are rare (especially the most serious ones), and *nobody* gets all or even most of them. I think that showing these lengthy lists to patients can do more harm than good. Unfortunately, the "patient information sheets" that pharmacies often keep are condescendingly lacking in real information.

> Not everyone has access to the information that we do nor do they have the sophistication to interpret it.

And that's the trouble with using the PI to educate patients about a drug.

> I take many Rx drugs for various things (HTN, hypercholesterolemia, etc) along with those I take for pain and, believe me, even if I knew nothing about the state of the "art" of developing, or more precisely, marketing new drugs (I worked in clinical pharmaceutical development for several years), I would be skeptical and watchful whenever I'm prescribed a "new" medication.

I recently moved from Boston, and now I'm in, well, a place where there's not so much psychiatry research (to euphemize). And I've been finding that medications that are considered "new" or "cutting edge" here are ones that were in use in Boston several years ago. As a result I've grown very pessimistic about finding a doctor here who'll be willing (or even knowledgeable enough) to prescribe the things that have worked best for me (opioids, which are still stigmatized in most places) or to try new things which may help me and which I haven't tried already (because they don't know anything about any drugs that I would consider "new").

> > Actually, I went ahead and looked this one up, and according to the PI, the affinity of O-desmethyltramadol (let's call it ODT for short) for mu receptors is about *200* times that of the parent compound; interestingly, the PI adds that ODT is about six times as potent an *analgesic* as tramadol. (Hard to know what to make of this.)
>
> OK, I'll give you that one! As I said, I was working from memory and have only scanned the literature on Effexor.

But I'm still wondering -- how is it that ODT is 200 times as potent a mu agonist as tramadol, but only 6 times as potent an analgesic? That's the mystery to me.

> I stand by the dictionary's definition of narcotic analgesic.

I'm not saying it doesn't have a meaning, or even a medical meaning -- but it's outdated, and there are words

> The term is used routinely in both clinical practice and in research, along with others.

Clinical practice, sure. I recently came across a doctor who referred to buprenorphine as a "narcotic." (He was also very ignorant of its effects.) Recent research that I'm familiar with uses "opioid" or "opioid agonist."

> It doesn't matter as long as each party understands the concept.

I don't agree entirely. While I understood that you meant "opioid agonists" by "narcotics," your use of the word "narcotics" suggested a political bias which I've heard called "opiophobia." I don't believe you have this bias, though, so I suggest that you use the more modern and less politically loaded term.

> For instance, OxyContin (extended-release hydrocodone) is not very different from MSContin (long-acting morphine sulfate) in pain relieving activity, yet one has become a popular street drug (OxyContin) while the other (MS Contin) never became a popular street drug, despite the fact that MS Contin is formulated similarly and should give the same "high" from snorting or injection of the crushed tablets.

OxyContin is sustained-release oxycodone, not hydrocodone. The media have portrayed it as some new drug, when in fact it's just Percocet without the Tylenol and in a slow-release formulation. Its potential for abuse is greater than that of MS Contin because oxycodone has greater bioavailability than morphine when taken orally. Injecting the sustained-release drugs is pretty difficult and dangerous, BTW, because they contain so many binders. Hard-core addicts have been known to do it, but it's not trivial and the risk is significant.

> With respect to your final comment re mixed opioid agonists, check the history of Talwin (pentazocine). You might find, as I have read, that when pentazocine was first marketed, it rapidly became a "drug of abuse" or "street drug."

I've heard that story. I think that it's unlikely that a heroin addict would be interested in Talwin; it's likely that a heroin user would feel *worse* on Talwin. So I think that it's most likely that the people "abusing" these drugs were not hard-core addicts, but young people who were going through a phase of "experimenting" with drugs, and that the attraction of the drugs to these people lay in their "forbidden" status (since they had been identified as opioids or "narcotics").

Anyway, kappa opioids don't have much attraction for people who prefer mu agonists. The other partial/mixed agonists are the partial mu agonists, such as buprenorphine and dezocine. There have been some reports of buprenorphine "abuse," but (having plenty of personal experience with this drug) I'm skeptical. Buprenorphine is a poor substitute for heroin, but an addict in withdrawal is liable to be willing to take whatever s/he can get, and buprenorphine does block withdrawal symptoms. It can also be used to detox oneself and causes hardly any withdrawal symptoms of its own. For recreational or experimental users, buprenorphine could indeed have appeal due to its ability to produce feelings of contentment. Any or all of these uses may have been considered "abuse" by the authors of the reports. One thing that a lot of professionals do not seem to realize (although it should have been covered in their educations) is that using a drug to feel better does not necessarily constitute abuse, even if the drug use is illegal. This is but one of many ways that the government has invaded the doctor's office: by leading doctors to believe that the legal status of a drug defines whether its use is pathological or not.

> Such abuse did not stop until the manufacturer reformulated the drug to add an opioid antagonist to prevent the "high" accompanying illegal use.

The addition of naloxone prevents injection, actually (naloxone isn't orally active, and pentazocine taken orally is really unimpressive, even moreso than it is when injected).

> I read the PI and did not expect that I would hurt for six hours after taking the med.

I'm still surprised that it took *that* long for it to work for you. It might be that you are slower at metabolizing drugs through this pathway (cytochrome P450 2D6); there might have been other factors at work as well (too low a dose of Ultram, for example).

> I used it for about a week with Effexor before developing what I assume was serotonin syndrome; at no time did I get any significant pain relief.

What symptoms did you have? Like I said, I never found Ultram to be worth using for pain -- or for depression, for that matter -- and the evidence (high measured TCA levels, odd reactions to dextromethorphan) suggests that I'm deficient in CYP 2D6. This lends credence to your hypothesis that most of the analgesic activity of Ultram is due to ODT.

> In fact, I was probably overdosing myself because I continued to hurt, despite Effexor's analgesic potential.

I'll let you know if I get any pain relief from Effexor; my back pain continues so far (mainly in the morning, when I haven't recently taken buprenorphine), but I'm only taking 75 mg/day of Effexor.

> Ultram has this effect on me as does codeine.

Well, then you're probably metabolizing them normally, or close enough to normally.

> Nightmares or "vivid" dreams have been associated with oxycontin. Why would one not expect the same from other drugs of like action?

I wasn't aware that vivid dreaming was associated with any opioid. They tend to suppress REM sleep, if anything, and they don't have the peculiar effects on REM sleep that are seen with SSRIs and Effexor (where REM density is increased -- this is thought to lead to the vivid dreaming often seen as a side effect of SRI antidepressants).

> I have to accept the above comment, qualified by your following statement. Perhaps I've been led astray by the good doctor's posting?

I'm not going to question somebody's claim of credentials, although in this case I'm not sure what the credential means. But as I said above, I've seen too many cases where people didn't live up to their credentials -- and many cases of lay-people having surprising knowledge that they attained by themselves -- to pay much attention to a person's credentials or lack thereof.

> I understand this concept. I do not argue that Effexor is not an SRI (not an SSRI), just that it may have more than ONE mechanism of action and that the results of this "mixed" mechanism may be different from what one would expect with a "pure" SRI.

Generally what we've seen with Effexor has suggested that its original marketing as "Prozac with a punch" was pretty accurate: it can have nastier side effects than SSRIs (but the same general *type* of side effects), and it also can work in situations where SSRIs aren't so effective (e.g., severe or melancholic depression). The NE reuptake inhibition is likely responsible for the hypertension sometimes caused by Effexor (most TCAs block alpha1-adrenergic receptors, which may tend to lower blood pressure, canceling out this effect; Effexor, like the SSRIs, doesn't have the antagonist effects at histaminergic, cholinergic, and noradrenergic receptors that are seen with most of the TCAs).

> > The list from the Effexor PI is pretty exhaustive. That's not surprising since the PIs typically list every reported side effect and could be expected to do the same with withdrawal symptoms.
>
> I am aware of the FDA's requirements for listing side effects and withdrawal effects.

Then you're aware that this list of withdrawal symptoms should not be taken as a list of symptoms all of which anyone discontinuing Effexor is liable to experience! Only a few of them are all that common.

> I'm not worried! This was supposed to be an intellectual discussion.

Good! My favorite kind.

> I take hydrocodone a couple of times a day and propoxyphene at night. Why would I be "worried" about the proposed "opioid" effects of Effexor?

I wasn't just addressing you there, but anyone who's reading this conversation. I would hate for people to avoid Effexor (a pretty good AD, though it often has nastier side effects and w/d symptoms than the SSRIs) for fear that they might become opioid-dependent!

> I also have NEVER had difficulty stopping any drug I took, so don't expect to die from discontinuing Effexor.

Some drugs -- such as alcohol, barbiturates, and (to a *much* lesser degree) benzodiazepines -- have the potential to cause serious, even fatal withdrawal symptoms (generalized seizures, for example). Opioid withdrawal is exceedingly unpleasant (even for people who are just watching it, not experiencing it!), but it's *not* fatal.

> Again, I've just enjoyed the intellectual stimulation of this conversation.

Thanks. Me too. :-)

-elizabeth

 

Re: Questions » melmel

Posted by Spencer on December 14, 2001, at 3:18:31

In reply to Questions, posted by melmel on December 12, 2001, at 13:11:30

I take 150mg Effexor XR in the early morning. I also suffer from a disrupted sleep pattern (sleeping and waking several times a night). When I mentioned it to my psychiatrist she said that taking it in the morning is the best as far as sleep is concerned. I occasionally take half a Stilnox at bedtime and this gives me a better night's sleep.

Effexor XR has been such a great help to me that I'm happy to live with some insomnia. My psychiatrist suggested I take it for a year to avoid any relapse into depression.

The other thing is that I found that I had quite a few side effects early on but these went away after about two to three months.

 

Re: Questions Spencer

Posted by melmel on December 14, 2001, at 10:34:21

In reply to Re: Questions » melmel, posted by Spencer on December 14, 2001, at 3:18:31

thanks. i started taking it in the morning yesterday morning and i did sleep a little better last night. i seemed a little sleepier during the day though, but i can live with that. the effexor has done wonders for me as well. i was just diagnosed with crohn's disease also, and if not for effexor i would be doing awefully. i've got constant nausea, but i had that from the crohn's before i started the effexor. looking at all the post on here had me worried, but i haven't had any problems like mentioned on here.

 

Effexor ... tapering off

Posted by Allen F. on December 14, 2001, at 14:49:10

In reply to Anyone had success on Effexor XR? , posted by jp on October 24, 1999, at 14:59:14

I have been on 75 mg of Effexor for three months. I take 37.5 mg in the morning and then again at night. I have had difficulty with side effects so my Doctor wants me to go off Effexor and see if they subside.

I am to take 37.5 mg per day for the first week, then half that for the second, and then supposedly I am off. I have been taking just one of 37.5 mg capsels in the morning for the past two days and have felt very strange.

My neck is sore, I am jumpy, sleep has been strange, ... Are these withdrawal symptoms? Would it be beter if I took half the 37.5 mg in the morning and the remainder at night since I have been taking it morning and night.

I have also heard that you should taper off of Effexor slowly and not sure that two weeks meets that definition ... does anyone have experience with this? The biggest concern is depression, I don't want a relapse ... has this happened to others?

Thanks,

a

 

Re: Effexor ... tapering off

Posted by cmcdougall on December 14, 2001, at 16:54:10

In reply to Effexor ... tapering off, posted by Allen F. on December 14, 2001, at 14:49:10

I took 300mg effexorXR for 18 months. My pdoc had me taper down over 6 weeks. As I was getting off effexor, I was adding celexa. I ended up in the hospital because of effexor withdrawal.

If you can spread the dose out, do it. It might help and it sure won't hurt. The way you are feeling now is definately withdrawal...

I don't know, but it seems to me that your dose of effexor was pretty low, and if side effects were a real problem, you should have been switched to a different drug sooner. Usually it takes at least 6 months of treatment for depression to abate. Hopefully you won't be like me. I have to take meds for the rest of my life, and even when I find a combo that works its only a matter of time before it poops out.

Are you seeing a regular doctor for your depression? GPs usually don't have a lot of experience with antidepressants and prescribe low doses. You didn't mention starting on another drug. In my experience, if the side effects of one drug are intolerable, I don't just stop taking it. I start another one at the same time. This usually helps with withdrawal symptoms too. In fact, I read somewhere that people coming off effexor can be helped by prozac.

Good luck.

Carly

> I have been on 75 mg of Effexor for three months. I take 37.5 mg in the morning and then again at night. I have had difficulty with side effects so my Doctor wants me to go off Effexor and see if they subside.
>
> I am to take 37.5 mg per day for the first week, then half that for the second, and then supposedly I am off. I have been taking just one of 37.5 mg capsels in the morning for the past two days and have felt very strange.
>
> My neck is sore, I am jumpy, sleep has been strange, ... Are these withdrawal symptoms? Would it be beter if I took half the 37.5 mg in the morning and the remainder at night since I have been taking it morning and night.
>
> I have also heard that you should taper off of Effexor slowly and not sure that two weeks meets that definition ... does anyone have experience with this? The biggest concern is depression, I don't want a relapse ... has this happened to others?
>
> Thanks,
>
> a

 

Re: 7 WEEKS--EFFEXOR FREE

Posted by Carlos on December 17, 2001, at 23:50:33

In reply to Re: 7 WEEKS--EFFEXOR FREE » Leo, posted by Pattyk on April 5, 2001, at 18:29:55

For the three 2 1/2 weeks I was on Effexor XR, it gave me nothing but trouble. Trying to stop gave me the worst withdraw symtoms of my life. I thought I was dying.

On the other hand, some people report that this drug is a life saver. You have to take everything into perspective. I don't see (as of now) any long term side-effects of this drug.

 

Re: Effexor ... tapering off » Allen F.

Posted by Spencer on December 18, 2001, at 2:34:23

In reply to Effexor ... tapering off, posted by Allen F. on December 14, 2001, at 14:49:10

Allen F

Are you taking Effexor or Effexor XR?. If you are taking the shorter half-life Effexor in the morning you could be feeling withdrawal by night time. You should ask your doctor.

Also, I suffered side effects for about two months but then most of them went away. I only suffer from difficulty in staying asleep now.

 

Effexor XR cold turkey

Posted by jammy on December 18, 2001, at 21:40:14

In reply to Anyone had success on Effexor XR? , posted by jp on October 24, 1999, at 14:59:14

I've been cold turkey from effexor xr 150mg since yesterday (mainly because I've not been able to get to a doctor, but also because i've been more bloody depressed since i started taking it than i ever felt before!) I know that I shouldn't just stop it but... anyone got any hints as to how long it'll take before the dizziness, tingling and (so much fun!) scary hallucinatory dreams stop? It feels like my brain's trying to swell out of my skull at the moment!

 

Re: Anyone had success on Effexor XR?

Posted by care on December 18, 2001, at 22:06:29

In reply to Re: Anyone had success on Effexor XR? , posted by Parks on January 4, 2000, at 16:10:07

> > My husband has shown great progress with effexor xr 75mg...He is a new person...His main problems have been some occasional very negative dreams, for a short time sexuall disfunction, and it has elevated his blood preasure (however he has had juvinile hypertension)...This dug as worked better than any other!!!
> Hi there,
> >
> > Anyone care to comment on the use of Effexor? Anyone
> > "happy" with it? I have tried Prozac (too much anxiety),
> > Serzone (too sedating). I am currently on Buspar for anxiety.
> >
> > Been reading many different reports... Effexor seems
> > to have a lot of success...
>

Effexor xr has been a life saver for me. I noticed a
difference right away. Side effects are mild. The only thing
I have noticed is strange dreams and night sweats. I
can handle these side effects and now I have my life back


 

Re: Anyone had success on Effexor XR?

Posted by care on December 18, 2001, at 22:08:19

In reply to Re: Anyone had success on Effexor XR? , posted by Parks on January 4, 2000, at 16:10:07

> > My husband has shown great progress with effexor xr 75mg...He is a new person...His main problems have been some occasional very negative dreams, for a short time sexuall disfunction, and it has elevated his blood preasure (however he has had juvinile hypertension)...This dug as worked better than any other!!!
> Hi there,
> >
> > Anyone care to comment on the use of Effexor? Anyone
> > "happy" with it? I have tried Prozac (too much anxiety),
> > Serzone (too sedating). I am currently on Buspar for anxiety.
> >
> > Been reading many different reports... Effexor seems
> > to have a lot of success...
>

Effexor xr has been a life saver for me. I noticed a
difference right away. Side effects are mild. The only thing
I have noticed is strange dreams and night sweats. I
can handle these side effects and now I have my life back


 

Re: Effexor XR cold turkey » jammy

Posted by girlie on December 19, 2001, at 14:21:16

In reply to Effexor XR cold turkey, posted by jammy on December 18, 2001, at 21:40:14

I hate to tell you this, but there's a good possibility things are only going to get worse. My GOOD days after trying to stop effexor after weaning down to 37.5 were the first 2 days. After that things got worse each day and, after 5 days, I had my doctor paged and she called in 25mg tablets for me. Going from 150 to 0 can be dangerous. Get in touch with your doctor and WEAN off of it!

girlie

> I've been cold turkey from effexor xr 150mg since yesterday (mainly because I've not been able to get to a doctor, but also because i've been more bloody depressed since i started taking it than i ever felt before!) I know that I shouldn't just stop it but... anyone got any hints as to how long it'll take before the dizziness, tingling and (so much fun!) scary hallucinatory dreams stop? It feels like my brain's trying to swell out of my skull at the moment!

 

Re: Effexor an opiate? Probably not. » Elizabeth

Posted by JANNBEAU on December 19, 2001, at 14:32:05

In reply to Re: Effexor an opiate? Probably not. » JANNBEAU, posted by Elizabeth on December 13, 2001, at 20:06:59

Hey, Elizabeth! Thanks for your third (?) posting. It was fun to read. Thought you'd disappeared. Instead, I find that I don't really know how to find specific responses to my postings.--Thread is also getting long--unwieldy--sstart a new one?

--I think it's easy to misinterpret stuff over the net---

Thanks for reminding me of the difficulties of communicating without visual and aural cues! Again, sorry to put you in such a position! : )

Seems you know far more about this subject than I. Though I've had many courses in pharmacokinetics/toxicokinetics, etc., I don't use most of it anymore. I'm still "cocky" sometimes, however. You've set me straight!!

I found in clinical drug research that most is a farce, driven entirely by the profit motive and by drug companies and researchers who seek to obey the letter of the law but not the spirit of said regulations. I, too, then, am skeptical. I try to educate myself, whence some of my misinformation! (All the rest of you out there, disregard my comments and listen to E-Beth!)

--I actually enjoyed your second posting.

I enjoyed yours, too. That's why I'm back!
>
--My response to you also responded to his comments in greater depth---

We can forget that posting, I think!
>
--Anyway, credentials don't mean much to me (especially since they're generally unproven on this forum

Well said!

--I think our approach differs greatly from that of the Middle Ages,

Of course!

>although some attitudes expressed by a lot of people (including medical and even scientific professionals) bear a disturbing resemblance to aspects of the Medieval world-view.
>
Well, true. We've made progress. We have the "scientific method;" we have great potential to distribute our information; we know volumes more about physiology and psychophysiology than the Medievalists knew, just as we have a much better understanding of the psychopathology than we knew even fifty years ago. Have you ever seen the movie "The Snake Pit" or read about "Bedlam", the famous London institution? That's what I mean!
Bedlam is, by the way, a shortened form of the name for "Bethlehem" Asylum--interesting, yes? Ironic, perhaps?

>
-- The trouble with the PI is the reverse: it includes every reported "side effect," even some which probably don't have anything to do with the drug. This can scare patients, to say the least, even making them unwilling to try the drug. It's misleading because most of these "side effects" are rare (especially the most serious ones), and *nobody* gets all or even most of them. I think that showing these lengthy lists to patients can do more harm than good. Unfortunately, the "patient information sheets" that pharmacies often keep are condescendingly lacking in real information.

All true, especially the lack of balance between the "information for the patient" and the PI. However, I think that, if we are an educated patient, we should be able to take the information from the PI and distill it, using what pertains to ourselves and discarding extraneous information. However, we DO need to know the PURPOSE of the PI, which is mainly to fulfil the requirements of the Code of Federal Regulations and other laws governing drug research, manufacture, and distribution, yes? The physician should make this very clear to the patient. A patient should know his/her ability to digest and use the information. It also helps to know one's pharmacist well; these folks can be really helpful with respect to side effects and drug interactions. I, of course, have a PDR and another huge tome that gives the percentage of the effects in controlled trials in both placebo or comparator drug and the drug under test. But, then, again, you must know how to interpret the numbers! What constitutes a significant difference between inactive or placebo and the medication, for instance? I could go on and on--

> I recently moved from Boston, and now I'm in, well, a place where there's not so much psychiatry research (to euphemize).

Bummer! Boston would be a hard act for anyplace to follow!

And I've been finding that medications that are considered "new" or "cutting edge" here are ones that were in use in Boston several years ago.

Where in the world are you, Timbuctu?

As a result I've grown very pessimistic about finding a doctor here who'll be willing (or even knowledgeable enough) to prescribe the things that have worked best for me (opioids, which are still stigmatized in most places)--

How true it is! Some attempt to make us feel guilty for needing opioids (I will use this term as your arguments make sense in the context of "stigmatism") and attempt to discourage their use, when, for the kind of chronic pain I have, and that I suspect you also suffer, opioids should be the drugs of choice.

Talk about side effects of medications: Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are LOADED with, sometimes, lifethreatening side effects, and are not even particularly effective for many types of pain for which they are prescribed. NSAIDs give me asthma, stomach pain and bleeding, severe gingivitis, to name but a few! The COX-2 inhibitors seem especially insidious for these effects.

--or to try new things which may help me and which I haven't tried already (because they don't know anything about any drugs that I would consider "new").

I wish you luck in finding a physician near you who will have the knowledge and motivation to learn and to help you! I'm considering accupuncture. Have you tried it? Unfortunately, my insurance doesn't pay for it, but will pay for any drug the doc prescribes!
>
> But I'm still wondering -- how is it that ODT is 200 times as potent a mu agonist as tramadol, but only 6 times as potent an analgesic? That's the mystery to me.

I had an hypothesis about that, but it slips my mind at the moment! I'll get back to you when I remember it. (Oh, Lord, sometimes I'd give any thing to be drug-free so I could figure out whether I'm also getting Alzheimers!)
>
>
> I don't agree entirely. While I understood that you meant "opioid agonists" by "narcotics," your use of the word "narcotics" suggested a political bias which I've heard called "opiophobia." I don't believe you have this bias, though, so I suggest that you use the more modern and less politically loaded term.

Checkmate--game to you! Opioid agonist, it will be hereafter in these conversations! I certainly don't have this bias. I rely on hydrocodone and propoxyphene to keep my life bearable. I have attempted for many years to educate those close to me that the use of opioid agonists for severe acute or chronic pain is not only appropriate, it is the only HUMANE thing to do. (a personal experience watching my father die in agony brought me to this conclusion).

Those of us who use these medications for real pain do NOT generally abuse them. For
>
> > For instance, OxyContin (extended-release hydrocodone)--etc--

> OxyContin is sustained-release oxycodone, not hydrocodone.

Right--another slip of the fingers!

--The media have portrayed it (OxyContin) as some new drug, when in fact it's just Percocet without the Tylenol and in a slow-release formulation. Its potential for abuse is greater than that of MS Contin because oxycodone has greater bioavailability than morphine when taken orally. Injecting the sustained-release drugs is pretty difficult and dangerous, BTW, because they contain so many binders. Hard-core addicts have been known to do it, but it's not trivial and the risk is significant.
>
Good information. I am not very well up on addiction research. With regard to bioavailabiity with oral administration, would you just not take a larger dose of the morphine to get the same effect?

> I think that it's most likely that the people "abusing" these drugs were not hard-core addicts, but young people who were going through a phase of "experimenting" with drugs, and that the attraction of the drugs to these people lay in their "forbidden" status (since they had been identified as opioids or "narcotics").
>
I agree completely with this statement. I alluded to this phenomenon in my earlier posting!--the psychology of the "fad" drugs, etc.

> Anyway, kappa opioids don't have much attraction for people who prefer mu agonists.

Tell me more. I don't know much about this subject.

The other partial/mixed agonists are the partial mu agonists, such as buprenorphine and dezocine.

--an addict in withdrawal is liable to be willing to take whatever s/he can get, and buprenorphine does block withdrawal symptoms.

Understood.

It can also be used to detox oneself and causes hardly any withdrawal symptoms of its own.

Didn't know this.

--is that using a drug to feel better does not necessarily constitute abuse, even if the drug use is illegal. This is but one of many ways that the government has invaded the doctor's office: by leading doctors to believe that the legal status of a drug defines whether its use is pathological or not.

How true! Also, I have come to believe (personal observation) that some psychotropic or CNS active medications make permanent changes to the brain, meaning, perhaps, that the set points for the receptors may be changed, e.g., (I think, but don't quote me on this) that receptor physiology is permanently altered by some CNS medications--permanent receptor upregulation(?) or that presynaptic receptors are affected more than is realized? I refer specifically to the amphetamines and amphetamine-like medications (and there lies another whole discussion--the ability of the SRI's to alleviate depression. I have noticed that when the early "amphetamine" or NE agonist effect of the AD wears off, so does the antidepressant effect--I experienced that with Prozac, Paxil, and, NOW, just recently, with Effexor; took my first amphetamine (for weight control) when I was 19 years old (40 yrs ago) and, through the years, have felt "retarded" without them. Although I don't presently take stimulants, I always found small or prescribed doses to make me feel "better" and to increase my functional status. I think this is an iatrogenic (although inadvertant) effect that I'll always have to contend with--or perhaps, I was just congenitally depressed and the amphetamines treated that condition (?). Anyway, I agree with your contention that illegal isn't synonymous with pathological! I have struggled with this concept. You have enunciated it beautifully.
>
> > I used it for about a week with Effexor before developing what I assume was serotonin syndrome; at no time did I get any significant pain relief.
>
> What symptoms did you have?

Felt literally as if I was going to die!. Tremor, chilliness, cognitive deficits, memory loss, headache, "speeding", disorientation, somnolence; loss of sense of time; wildly fluctuating blood pressure (hypertension followed late in the evening by hypotension --110/62 which is much lower than my bp has been in years--dizziness; nausea--others that I cannot remember. DC's Ultram, returned to normal within 24 hours! Scared the dickens out of me. Totally out of my control until I figured out the interactive potential of these drugs.

Like I said, I never found Ultram to be worth using for pain -- or for depression, for that matter -- and the evidence (high measured TCA levels, odd reactions to dextromethorphan) suggests that I'm deficient in CYP 2D6. This lends credence to your hypothesis that most of the analgesic activity of Ultram is due to ODT.
>
Makes sense to me!

I'll let you know if I get any pain relief from Effexor; my back pain continues so far (mainly in the morning, when I haven't recently taken buprenorphine), but I'm only taking 75 mg/day of Effexor.

I've recently increased my dose of Effexor to 150 qd, because it was losing it's effectiveness as an AD. I've seen no further increase in pain relief, so I wonder if that effect may not occur at low doses as with the TCAs? However, I've also not seen a return of the antidepressant activity of Effexor so would like to drop back to 75 mg qd. Let me know how this goes for you.
>
> > Nightmares or "vivid" dreams have been associated with oxycontin. Why would one not expect the same from other drugs of like action?
>
> I wasn't aware that vivid dreaming was associated with any opioid. They tend to suppress REM sleep, if anything, and they don't have the peculiar effects on REM sleep that are seen with SSRIs and Effexor (where REM density is increased -- this is thought to lead to the vivid dreaming often seen as a side effect of SRI antidepressants).
>
> I'm not going to question somebody's claim of credentials, although in this case I'm not sure what the credential means.

It's British, I believe.

But as I said above, I've seen too many cases where people didn't live up to their credentials -- and many cases of lay-people having surprising knowledge that they attained by themselves -- to pay much attention to a person's credentials or lack thereof.

Very true.
>
> > Generally what we've seen with Effexor has suggested that its original marketing as "Prozac with a punch" was pretty accurate: it can have nastier side effects than SSRIs (but the same general *type* of side effects), and it also can work in situations where SSRIs aren't so effective (e.g., severe or melancholic depression). The NE reuptake inhibition is likely responsible for the hypertension sometimes caused by Effexor (most TCAs block alpha1-adrenergic receptors, which may tend to lower blood pressure, canceling out this effect; Effexor, like the SSRIs, doesn't have the antagonist effects at histaminergic, cholinergic, and noradrenergic receptors that are seen with most of the TCAs).
>
> > > The list from the Effexor PI is pretty exhaustive. That's not surprising since the PIs typically list every reported side effect and could be expected to do the same with withdrawal symptoms.
> >
> Then you're aware that this list of withdrawal symptoms should not be taken as a list of symptoms all of which anyone discontinuing Effexor is liable to experience! Only a few of them are all that common.
>
Yes.

--I would hate for people to avoid Effexor (a pretty good AD, though it often has nastier side effects and w/d symptoms than the SSRIs) for fear that they might become opioid-dependent!

Oh, of course! I tend to forget this is a public forum. Sorry, again, folks, E-beth is absolutely correct about Effexor.

Elizabeth, tell us how you know all of this stuff? Your knowledge seems far greater than that of the average "Joe"!!!

Cheers,
JANNBEAU

 

Re: Effexor XR cold turkey » jammy

Posted by Spencer on December 20, 2001, at 0:37:52

In reply to Effexor XR cold turkey, posted by jammy on December 18, 2001, at 21:40:14

How long were you taking Effexor? The first 6 weeks after I started taking the medication were hell...the depression was definitely worse, but I was warned by my doctor that this would happen. After that things improved very rapidly and I have been feeling very well since.

In any event please don't torture yourself when a visit to your doctor may help you.

Hope you get over this.

> I've been cold turkey from effexor xr 150mg since yesterday (mainly because I've not been able to get to a doctor, but also because i've been more bloody depressed since i started taking it than i ever felt before!) I know that I shouldn't just stop it but... anyone got any hints as to how long it'll take before the dizziness, tingling and (so much fun!) scary hallucinatory dreams stop? It feels like my brain's trying to swell out of my skull at the moment!


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