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.
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> It seems that venlafaxine may be particularly prone to interact with MAOIs and thus be implicated in fatal serotonin syndrome reactions.
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> 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.
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> 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.
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> 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.
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> 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.
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> History repeatedly demonstrates that new is not always better. History is repeatedly ignored.
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> The FDA have now officially amended the product information on venlafaxine (2000) as follows:--
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> 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.
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> Subscribe to 'Psychopharmacology update notes' to see a fuller analysis and references."
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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.
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> 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.)
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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?
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> 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.
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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?).
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> The reports that I've heard have suggested it's more like three hours. Still quite a delay, though.
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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?
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> < 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?
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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.
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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!).
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> Yeah, you're really dating yourself here! :-)
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> > I resent it that I received NONE of this information for Effexor (venlafaxine) OR tramadol prescribed concomitantly.
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> 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.
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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).
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> 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.
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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.
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> 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).
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> > The signs and symptoms are strangely similar to those of any narcotic withdrawal syndrome, are they not?
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> What withdrawal symptoms associated with Effexor do you think are similar to opioid withdrawal? I haven't heard of any such thing.
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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
poster:JANNBEAU
thread:13781
URL: http://www.dr-bob.org/babble/20011202/msgs/86726.html