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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by nelag on April 24, 2012, at 22:53:07
Hi All,
I am not completely new to psychobabble but have not posted in more than ten years. I could use advice from anybody who can give it.
Here is my situation. I have had episodes MDD since I was 27; I am now nearly 60. When the MDD was finally diagnosed after a brutal 2 years I was put on four medications for sufficient time at a sufficient dose. None worked. I don't remember the names of the meds but two were tricyclics and two SSRIs. After these four failed my pdoc put me on Parnate. It was slow to take hold but after it did it worked fine for a number of years and gave me few problems with side effects.
Not long after Effexor came out I switched to it for the convenience of a restriction free diet. Effexor has also also worked well for me, at first at a dose of 225mg. After a couple of years I crashed and was titrated up to 450 Effexor. During this rapid titration I began Welbutrin at 300mg as augmentation. This combo held me for a couple of years and then I crashed again. I titrated to 600mg Effexor, keeping the Welbutrin in place. My doctor was one of the few who seemed to have acurately read the PDR to say that 350 was highest dose found effective during a brief clinical trial. Quite different than saying that higher doses taken over a longer stretch of time could never be effective or that doses over 350 were dangerous. Over a period of several more years I titrated incrementally until stopping at 1,200. At one time I thought this might constitute a world record but I was disabused of this bragging right by a gentleman on another site who said he was currently at 1,500. In any case, this dose was effective until about six years ago when I began having breakthroughs of depression lasting from several days to several weeks. Since then these breakthroughs have become steadly more frequent to the point that I sense the Effexor losing its puncb altogether. So I will probably make a change soon.
Here is my question (finally!). Should I take option number one and return to Parnate or option two, which would be to add a second augmenting drug to the Effexor? The chief downside of the first option is having to take two or three weeks to get off Effexor, (I have always been able to get off and on meds quickly.)followed by two weeks of washout until beginning Parnate and waiting another month for it to, I hope, kick in. When I switched in the other direction many years back I spent I spent a number of weeks in bed unable to get up for any activity aside from showering.
The possible downside of option two is that I don't know if a second titrating med is likely to potentiate the Effexor. And if so, which drug or drugs would be most likely to do this. MDD is my only diagnosis--no bipolar,ADHD or any other malady on board.
If anybody can share their experience, perspective,knowledge or advice on the augmenting issues, especially what medication to use, it would help me a lot. My original pdoc moved out-of-state and the two I have seen since then have sometimes known less than I do, an alarming fact since I don't know much. This point is driven home everytime I read one of SLS's excellent posts.
Thanks,
nelag
Posted by SLS on April 25, 2012, at 1:07:44
In reply to Augment Effexor or go to Parnate, posted by nelag on April 24, 2012, at 22:53:07
Dear Nelag.
First of all, thank you for your generous mention of me. It is nice to be appreciated, although it is even nicer to see people get well.
I have never heard of anyone taking as much Effexor as you do. I thought 600 mg was as high as anyone went. Yet you actually need twice that dosage to respond. What I find most obvious is that Effexor doesn't really hit norepinephrine (NE) nearly as much as it does serotonin (5-HT). The ratio most often quoted is 1:30. Your brain might be telling you that you need huge doses of Effexor in order to get enough NE reuptake inhibition to glean an antidepressant response. Perhaps adding a secondary-structure tricyclic (TCA) like desipramine or nortriptyline would give you the NE activity you are attempting to fill with high-dosage Effexor, but without adding any more 5-HT activity. Both tricyclics are selective for NE; with desipramine being the most potent. You might then be able to reduce your dosage of Effexor once you add a TCA. Have you had an EKG? It might be a good idea, especially if you intend to go with desipramine. I am a little uncomfortable with your adding any drug while you are still taking so much Effexor. Would you be able to lower Effexor before you begin taking the tricyclic? I don't know that this is necessary, but this is uncharted territory. I found the combination of Effexor and nortriptyline to be partially effective when neither one alone did anything. At the time, I was taking 75 mg of nortriptyline. I later discovered during a subsequent drug trial that 150 mg was the optimum dosage of nortriptyline for me. I am a rapid metabolizer of tricyclics. It seems to me that people will either respond to 75 mg or they will respond to 150 mg, but not respond to anything in between. Nortriptyline is the TCA studied most for associating blood levels with clinical response. I would suggest starting at a low dosage and work your way up to 75 mg first. Take a blood test to assess your nortriptyline levels, and make decisions using the results as a guideline. Too much nortriptyline is no good. When you exceed your therapeutic window, it becomes less effective. The range of effective therapeutic blood levels for nortriptylne is 50 - 150 ng/ml. At 150 mg, my level approaches 150 ng/ml.
I prefer nortripytline to desipramine because its side effects are milder, although you might need the punch of desipramine to respond. An individual can respond to one TCA, but not the other. I also don't like the idea of adding a potent NE drug like desipramine to your treatment regime while you are taking so much Effexor. 300 mg would be safe. You might want to take a EKG (ECG) before adding the tricyclic, and repeat the test at some point while titrating. I am concerned about cardiotoxicity when adding a TCA to such high dosages of Effexor.
Effexor + Wellbutrin = good response
Effexor + nortriptyline = good response
Wellbutin + nortripytline = ?
Effexor + Wellbutin + nortripytline = ?It might be interesting to leave the Wellbutrin in place, just in case there is some therapeutic dynamic occurring between it and the nortriptyline. I would really like to see the Effexor come down first. Despite my belief in the great value to be found in rational polypharmacy, I try to remain wary of dangerous adverse effects. The problem is that I simply don't know enough about these drugs to be able to predict the outcome of the many permutations of drugs possible. I am more conservative than many people give me credit for. They think I am some sort of cavalier cowboy shooting bullets in all directions indiscriminantly.
I feel pretty strongly that you will find something that works. You have demonstrated that your brain is not dead or immoveable.
I currently take:
Parnate 80 mg
nortriptyline 150 mg
Lamictal 200 mg
Abilify 10 mg
lithium 300 mg
prazosin 12 mg
You'll get there.
- Scott
Posted by SLS on April 25, 2012, at 1:21:39
In reply to Re: Augment Effexor or go to Parnate » nelag, posted by SLS on April 25, 2012, at 1:07:44
I found this to be reassuring:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686075/
"This study suggests that for the majority of cases, significant cardiotoxicity does not occur with venlafaxine overdose and the common cardiovascular effects are tachycardia and mild hypertension, consistent with it being a noradrenergic reuptake inhibitor. Malignant arrhythmias did not occur based on continuous telemetry. Abnormal QT intervals and widening of the QRS interval were uncommon, possibly associated with larger ingestions (>8 g), and were not grossly abnormal."
"Venlafaxine remains a commonly prescribed antidepressant and will continue to be taken in overdose. Severe cardiotoxicity with arrhythmias and/or hypotension does not appear to be a major feature of venlafaxine overdose except in massive ingestions of >8 g, when other features such as neurotoxicity and serotonin toxicity are probably more important. Routine cardiac monitoring is unlikely to be necessary in the majority of cases, but all patients should have at least one ECG"
- Scott
> Dear Nelag.
>
> First of all, thank you for your generous mention of me. It is nice to be appreciated, although it is even nicer to see people get well.
>
> I have never heard of anyone taking as much Effexor as you do. I thought 600 mg was as high as anyone went. Yet you actually need twice that dosage to respond. What I find most obvious is that Effexor doesn't really hit norepinephrine (NE) nearly as much as it does serotonin (5-HT). The ratio most often quoted is 1:30. Your brain might be telling you that you need huge doses of Effexor in order to get enough NE reuptake inhibition to glean an antidepressant response. Perhaps adding a secondary-structure tricyclic (TCA) like desipramine or nortriptyline would give you the NE activity you are attempting to fill with high-dosage Effexor, but without adding any more 5-HT activity. Both tricyclics are selective for NE; with desipramine being the most potent. You might then be able to reduce your dosage of Effexor once you add a TCA. Have you had an EKG? It might be a good idea, especially if you intend to go with desipramine. I am a little uncomfortable with your adding any drug while you are still taking so much Effexor. Would you be able to lower Effexor before you begin taking the tricyclic? I don't know that this is necessary, but this is uncharted territory. I found the combination of Effexor and nortriptyline to be partially effective when neither one alone did anything. At the time, I was taking 75 mg of nortriptyline. I later discovered during a subsequent drug trial that 150 mg was the optimum dosage of nortriptyline for me. I am a rapid metabolizer of tricyclics. It seems to me that people will either respond to 75 mg or they will respond to 150 mg, but not respond to anything in between. Nortriptyline is the TCA studied most for associating blood levels with clinical response. I would suggest starting at a low dosage and work your way up to 75 mg first. Take a blood test to assess your nortriptyline levels, and make decisions using the results as a guideline. Too much nortriptyline is no good. When you exceed your therapeutic window, it becomes less effective. The range of effective therapeutic blood levels for nortriptylne is 50 - 150 ng/ml. At 150 mg, my level approaches 150 ng/ml.
>
> I prefer nortripytline to desipramine because its side effects are milder, although you might need the punch of desipramine to respond. An individual can respond to one TCA, but not the other. I also don't like the idea of adding a potent NE drug like desipramine to your treatment regime while you are taking so much Effexor. 300 mg would be safe. You might want to take a EKG (ECG) before adding the tricyclic, and repeat the test at some point while titrating. I am concerned about cardiotoxicity when adding a TCA to such high dosages of Effexor.
>
> Effexor + Wellbutrin = good response
> Effexor + nortriptyline = good response
> Wellbutin + nortripytline = ?
> Effexor + Wellbutin + nortripytline = ?
>
> It might be interesting to leave the Wellbutrin in place, just in case there is some therapeutic dynamic occurring between it and the nortriptyline. I would really like to see the Effexor come down first. Despite my belief in the great value to be found in rational polypharmacy, I try to remain wary of dangerous adverse effects. The problem is that I simply don't know enough about these drugs to be able to predict the outcome of the many permutations of drugs possible. I am more conservative than many people give me credit for. They think I am some sort of cavalier cowboy shooting bullets in all directions indiscriminantly.
>
> I feel pretty strongly that you will find something that works. You have demonstrated that your brain is not dead or immoveable.
>
> I currently take:
>
> Parnate 80 mg
> nortriptyline 150 mg
> Lamictal 200 mg
> Abilify 10 mg
> lithium 300 mg
> prazosin 12 mg
>
>
> You'll get there.
>
>
> - Scott
Posted by Phillipa on April 25, 2012, at 10:00:03
In reply to Re: Augment Effexor or go to Parnate, posted by SLS on April 25, 2012, at 1:21:39
I wish you luck as truly can't imagine this high a dose of meds. I'm glad they worked though. Phillipa
Posted by Alexei on April 25, 2012, at 11:55:36
In reply to Augment Effexor or go to Parnate, posted by nelag on April 24, 2012, at 22:53:07
I also take effexor and am in the process of adding augmenting agents. Lamictal has treated me well at 100mg.
My doc has given me the choice of adding either abilify or seroquel to further enhance my regime. I'm having a difficult time determining which would be best. And he has given an endorsement for nortriptyline, also.
IMHO, if I were in your shoes, I might go all the way and try to d/c the effexor. Sooner or later, you are going to have to keep escalating the dose again... and wind up in the same predicament.
Posted by nelag on April 25, 2012, at 17:59:58
In reply to Re: Augment Effexor or go to Parnate » nelag, posted by Alexei on April 25, 2012, at 11:55:36
Thanks for your comments.
So far as Effexor is concerned,I am not planning to up the dose again and even if I wanted to I doubt my pdoc would permit it. I would love to decrease my dose (it costs me $1,100 a month and this is with insurance.)but periodic efforts had led to crashes. I am fortunate, though, that the high dose has produced few side effects. My mind still seems to function, hampered only by occasional short-term memory glitches. I have developed hypertension for which I take medication. I recently had several heart function tests and nothing dire looking was identified.
Scott,
Thanks for your detailed and thoughtful response.
It cheers me up to know that I am taking a record Effexor dose at least among those you know of! I am familiar with the fact that Effexor has only a weak secondary impact on Norepinephrine, though I didn't know the ratio was as low as 1:30.
I have just one more question for when you have the time. The meds you mention adding to Effexor will, I gather, increase levels of NE without actually potentiating the Effexor. Is this correct?
I have read psychobabble of and on over the years and continually over the past month. I am always impressed with your combination of erudition and lucidity. Not to mention your kindness is responding to so many of we Babblers. Thanks again.
nelag
This is the end of the thread.
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