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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 21 of 21. This is the beginning of the thread.
Posted by Ada Marie on December 9, 2012, at 19:07:42
Hello,
I am new to this forum; this is my first post actually. So, I have Dysthymic Disorder with episodes of MDD, atypical type. I have 1-2 episodes of MDD per year. The first time I was treated for MDD, I was 18 years old. I am 30+ now. I have been on SSRIs, SNRIs, Atypical Antidepressants, and combinations of each. No medication has been effective for longer than 12 months. I have never had a manic episode, but I do notice mood instability. My episodes of depression are worsening. I also have some symptoms of ADHD, but do not meet criteria for ADHD, inattentive type. I take Effexor 150, Vyvanse 30, and Trazadone 75. I am wondering if it is best to augment Effexor with Lamictal (or something else) or move to a TCA or an MAOI. I will not continue to take a medication if it causes over 5# of weight gain. I am wondering if anyone has experienced what I am experiencing and what was most helpful. I will appreciate your feedback very much!
Posted by jono_in_adelaide on December 9, 2012, at 22:00:00
In reply to Augment Effexor or TCS or MAOI or other?, posted by Ada Marie on December 9, 2012, at 19:07:42
Can I suggest replacing the Effexor with either
An SSRI (Zoloft or Lexapro) plus desipramine 150mg/day - this combination is a better SNRI than Effexor, and will be better against your dysthymic symptoms. Weight gain should be minimal
or
If the above fails, Parnate would be a good one to try, and it will be unlikely to cause significant weight gain.
Posted by SLS on December 9, 2012, at 23:28:56
In reply to Re: Augment Effexor or TCS or MAOI or other?, posted by jono_in_adelaide on December 9, 2012, at 22:00:00
> Can I suggest replacing the Effexor with either
>
> An SSRI (Zoloft or Lexapro) plus desipramine 150mg/day - this combination is a better SNRI than Effexor,The selection of desipramine makes a great deal of sense, especially because it is often helpful when treating ADHD and avoids weight-gain. However, without empirical evidence suggesting otherwise, I don't think one can conclude that (Zoloft or Lexapro) plus desipramine is universally more effective than Effexor at treating depression, despite theoretical considerations. Such a combination is certainly worth a try, though. It is a good suggestion. I would just offer that it might make more sense to add desipramine to Effexor first, and then switch from Effexor to an SSRI if necessary. If this fails, it is reasonable to switch from the SSRI to Parnate while retaining the desipramine, depending on the degree of treatment resistance.
> and will be better against your dysthymic symptoms.
Why do you say this?
- Scott
Posted by Ada Marie on December 9, 2012, at 23:57:59
In reply to Re: Augment Effexor or TCS or MAOI or other?, posted by jono_in_adelaide on December 9, 2012, at 22:00:00
Thanks Jono and SLS. What do you know about Trimipramine and weight gain? I believe I will be tapering off of Venlafaxine and begin taking Trimipramine. I am not sure if I will take only Trimipramine or if I will take a small dose of Venlafaxine with Trimipramine. My doctor is adding the Trimipramine so I do not have to have a complete washout (no medication) until an MAOI is started. Venlafaxine did not cause weight gain, so is it right to think Trimipramine might not cause weight gain either? I appreciate your feedback!
Posted by SLS on December 10, 2012, at 5:31:45
In reply to Re: Augment Effexor or TCS or MAOI or other?, posted by Ada Marie on December 9, 2012, at 23:57:59
> Thanks Jono and SLS. What do you know about Trimipramine and weight gain? I believe I will be tapering off of Venlafaxine and begin taking Trimipramine. I am not sure if I will take only Trimipramine or if I will take a small dose of Venlafaxine with Trimipramine. My doctor is adding the Trimipramine so I do not have to have a complete washout (no medication) until an MAOI is started. Venlafaxine did not cause weight gain, so is it right to think Trimipramine might not cause weight gain either? I appreciate your feedback!
I can't guarantee that you won't gain weight from taking trimipramine. I didn't. However, it is antihistaminergic. Antihistamines have a tendency to cause weight gain. It is possible that your doctor chose trimipramine because it is neither a NE nor 5-HT reuptake inhibitor. Theoretically, this should be safe. Hopefully, your doctor already has experience doing this. Another option is to use desipramine instead of trimipramine and continue taking it when you add the Parnate. You could probably do the same thing with trimipramine, but I haven't seen it done. I have combined Parnate and desipramine a few times.
- Scott
Posted by jono_in_adelaide on December 10, 2012, at 16:41:09
In reply to Re: Augment Effexor or TCS or MAOI or other? » jono_in_adelaide, posted by SLS on December 9, 2012, at 23:28:56
"Why do you say this?"
Because desipramine hits noradrenalin much harder than effexor, and antidepressants acting on noradrenalin are generaly better against dysthymic symptoms than ones actingmainly on seretonic (eg standard doses of Effexor)
Effexor only has a clinicaly significant effect on NA at doses of 300mg a day, which few patients ever reach, at doses of 75-150mg 9the ones commonly prescribed) it isnt clinicaly superior to Zoloft or Lexapro.
The reason I suggested Zoloft/Lexapro + desipramine instead of Effexor + desipramine is cost effectiveness, there isnt a down side to taking Effexor instead of an SSRI, but there inst realy an upside, and the cost is significantly more.
Posted by jono_in_adelaide on December 10, 2012, at 16:47:05
In reply to Re: Augment Effexor or TCS or MAOI or other? » jono_in_adelaide, posted by SLS on December 9, 2012, at 23:28:56
Another option would be an SSRI (or even Effexor) plus Welbutrin
Having said that, you have a long term disabeling disease, the statement that you will refuse any treatment that causes more than 5lb weight gain is dogmatic and might need to be reevaluated if you truly want to get better.
Posted by Ada Marie on December 10, 2012, at 17:14:26
In reply to Re: Augment Effexor or TCS or MAOI or other? » jono_in_adelaide, posted by SLS on December 9, 2012, at 23:28:56
Thanks for the feedback. I trust my doctor very much; I am a little scared about switching to a class of medicines that have more side effects. So, I want to hear from others who have been down the road I am about to take. Just recently, in an effort to avoid TCAs and MAOIs, my doctor added 150 mg (then 300mg) of Wellbutrin to my current regimen. This combination was too stimulating and caused me to feel edgy. I hear you Jono about sounding dogmatic. I am trying to accept how serious my condition is--just typing that now feels like I am dramatizing :)-- and that I may have to tolerate side effects to get out of this. What I don't want is what I see happening when people take atypical antipsychotics and gain 30# or more. Would beginning to exercise more when I begin the TCA help to prevent weight gain? I ask because I hear people saying they are eating not much differently and exercising and do not understand why they gained so much weight. Thanks for your help!
Posted by jono_in_adelaide on December 10, 2012, at 17:20:22
In reply to Re: Augment Effexor or TCS or MAOI or other? » SLS, posted by Ada Marie on December 10, 2012, at 17:14:26
Desipramine causes little or no weight gain, you shouldnt have any issues there.
Some of the more sedating tricyclics such as amitriptyline and doxepin can as you say, stack the weight on very fast, but desipramine largely doesnt.
Taking a daily walk and watching that you dont start to eat more should be enough. A daily brisk walk will also be good for you mentaly
Best of luck
J
Posted by SLS on December 11, 2012, at 2:31:56
In reply to Re: Augment Effexor or TCS or MAOI or other?, posted by jono_in_adelaide on December 10, 2012, at 16:41:09
> "Why do you say this?"
>
> Because desipramine hits noradrenalin much harder than effexor, and antidepressants acting on noradrenalin are generaly better against dysthymic symptoms than ones actingmainly on seretonic (eg standard doses of Effexor)Is there any science behind this? You might be right, but I would like to know where you got this idea from?
> Effexor only has a clinicaly significant effect on NA at doses of 300mg a day,
According to whom?
> which few patients ever reach, at doses of 75-150mg 9the ones commonly prescribed)
If this is true, then I think it would be better said that few doctors ever reach doses of 75-150mg. Are you suggesting that few patients can tolerate dosages over 150mg?
> it isnt clinicaly superior to Zoloft or Lexapro.
Oh. That's a pretty conditional statement. Are we to handicap drugs now by limiting the dosages we use to compare them?
> The reason I suggested Zoloft/Lexapro + desipramine instead of Effexor + desipramine is cost effectiveness,
Do you mean in terms of money or in terms of pain suffered?
> there isnt a down side to taking Effexor instead of an SSRI, but there inst realy an upside,
...except that it might work better for the individual. I don't think we are doing anyone a service by excluding drug treatments from consideration based upon our laymen monoamine theories of depression and drug mechanisms. I am not saying that all of the information scientists have collected is useless. I think much of it can be used as a primitive guide, and I would not want to be without that information. If you were to discover that Effexor was also a sigma-1 receptor agonist in addition to being a SNRI, might you then reconsider your conclusions?
http://www.ncbi.nlm.nih.gov/pubmed/17532136
Actually, this study proves nothing other than to suggest that an intact system of sigma-1 receptor function is required for an antidepressant to work. It is something to think about, though. Do Psycho-Babblers know enough about disease and drugs to predict patient reactions to those drugs - especially in light of the admission by neuroscientists that they do not?
http://www.ncbi.nlm.nih.gov/pubmed/15089113
What about NMDA receptors? If you were to learn that Effexor affects the expression of the NR2B subtype while Lexapro does not, would you continue to assert that there is no "upside" to using Effexor?
http://www.ncbi.nlm.nih.gov/pubmed/21755298
I would like to see empirical evidence that (Zoloft/Lexapro) + desipramine is interchangeable with Effexor. Who is it that you always cite regarding the Zoloft + nortriptyline combination? I forget.
As for me, I benefited more from combining Effexor + nortriptyline than to Zoloft + nortriptyline. I had considered remaining on the Effexor combination based upon my positive response to it, even though it had plateaued. An argument can be made that something must be different between Effexor and Zoloft other than NE reuptake inhibition.
The more I learn, the dumber I get.
Okay.
I think I have laid the foundation for the understanding that "different is different". That's a pretty simple concept. I imagine that there are cases for which Zoloft + nortriptyline polypharmacy is more effective than high-dose Effexor monotherapy. However, I am sure that Effexor and Zoloft are not interchangeable when combined with nortriptyline. Something is different. The box may no longer be black, but it is still quite dark in there.
You know things that I do not. Perhaps you can provide evidence for why you would tell someone to abandon Effexor in favor of Zoloft + nortriptyline. I know you keep referring to a doctor who believes this. What is his name? It would be hard to argue with real-world results.
I think the best argument for switching out Effexor for an SSRI now is that Effexor was producing diminishing returns, and a new drug might recapture a robust antidepressant response. But without a biological test to prove otherwise, I think that it would be counterproductive to tell someone that (Zoloft + desipramine) is a better SNRI than Effexor.
I cannot predict the results of antidepressant treatments by performing a theoretical mixing and matching of monoamine reuptake inhibitions. That leaves me feeling pretty dumb.
- Scott
Posted by SLS on December 11, 2012, at 15:51:15
In reply to Re: Augment Effexor or TCS or MAOI or other? » jono_in_adelaide, posted by SLS on December 11, 2012, at 2:31:56
> > Effexor only has a clinicaly significant effect on NA at doses of 300mg a day,
> According to whom?Okay. Here we are.
I found an interesting study that compared NE function at low versus high dosages of Effexor (venlafaxine) based upon in vivo activity models (an indirect measurement). It gives evidence that NE reuptake inhibition is not significant at dosages below 225 mg/day.
http://www.ncbi.nlm.nih.gov/pubmed/16690006
- Scott
Posted by jono_in_adelaide on December 11, 2012, at 17:14:27
In reply to Re: Augment Effexor or TCS or MAOI or other? » jono_in_adelaide, posted by SLS on December 11, 2012, at 2:31:56
Different is different, however, most large scale studies have asserted that at standard doseages, there isnt a clinicaly significant difference between Effexor and the better of the SSRI's in terms of improvement of illness.
Of course there may be individuals where Effexor is far better, but they arnt common if the studies are to be beleived. if everybody was treated with the newest, most expensive drug as a first option because of supposed marginal improvements in response over standard drugs, costs would be vastly decreased while most patients would get no extra benifit.
Take a patient with high cholesterol for example, he could have generic simvastatin for $4 per month, or Crestor for $200 per month. For 99% of patients, there would be no difference, so it makes sense to start everybody on simvastatin, and only use Crestor for those where simvastatin fails. I am not saying "dont use effexor ever" just use it discriminatingly.
I am not saying "never use effexor", I'm saying start off with the sertaline because of its lower cost and equal efficiacy in blind controlled studies, if that doesnt work, move onto other things.
I also was basing my recomendations of those of Dr Ken Gillman, we well respected British/Australian psychiatrist who has shown that sertaline + nortriptyline is a superior antidepressant to effexor alone.
I understand your points SLS, but the point that ciast effectiveness matters is also valid
Posted by Phillipa on December 11, 2012, at 18:07:59
In reply to Re: Augment Effexor or TCS or MAOI or other?, posted by jono_in_adelaide on December 11, 2012, at 17:14:27
Check the archives for the effexor horror stories. True some do well but a lot sure didn't. I myself could not tolerate even the lowest dose. And didn't the poster say he doc was discontinuing the effexor in lu of the TCA? Phillipa
Posted by jono_in_adelaide on December 11, 2012, at 19:53:32
In reply to Re: Augment Effexor or TCS or MAOI or other? » jono_in_adelaide, posted by SLS on December 11, 2012, at 2:31:56
"Perhaps you can provide evidence for why you would tell someone to abandon Effexor in favor of Zoloft + nortriptyline"
Because Effexor isnt working, and she needs to try somthing else.
A very well respected british/australian psychiatrist, Dr Ken Gillman has found in his practice over many years that Sertaline + Nortriptyline often sucseeds where Effexor has failed. I'm not saying Effexor doesnt work, I'm saying that real world evidence suggests that an NARI such as nortriptyline plus an SSRI such as sertaline gives a better ballance of NE/5HT reuptake than Effexor does.
It was a laymans suggestion, just the same as your suggestions were those of a layman, not a prescription from a mental health professional.
The poster is free to accept or reject my suggestions (and yours) as she pleases.
if everybody was to gett he most potent combination treatment, then all people with depression would be on tranylcypromine plus nortriptyline plus a low dose atypical plus lithium, but of course, not everybody needs that.
I feel that my suggestion of an SSRI plus a full dose of desipramine was an appropriate suggestion for a person who had failed on standard doses of Effexor and was concerned about weight gain on other treatments, you may feel that it wasnt appropriate, but att he end of the day, we are both just expressing laymans opinions
Posted by jono_in_adelaide on December 11, 2012, at 20:20:06
In reply to Re: Augment Effexor or TCS or MAOI or other?, posted by jono_in_adelaide on December 11, 2012, at 19:53:32
Sertaline and Escitalopram best of "new" antidepressants:
http://www.eurekalert.org/pub_releases/2009-01/l-ass012709.php
Dr Ken Gillman on Effexor
"It is one thousand times weaker than desipramine as a noradrenalin reuptake inhibitor in 'test tube' assays (ie 'in vitro') and more than 100 times less potent than amitriptyline or nortriptyline. This indicates that it may not be justified to classify it as an serotonin and noradrenalin reuptake inhibitor (SNRI) and that additional evidence that it has such actions in humans is required before the proposition of dual action can be accepted with any confidence"
http://www.psychotropical.com/index.php/anti-depressants/135-antidepressants-venlafaxineDr Ken Gillman on SNRI combinations:
"Safe and flexible dual action combinations (of an SSRI with an NRI, e.g. sertraline + nortriptyline) probably allow better efficacy and less side effects"
Posted by SLS on December 11, 2012, at 20:45:33
In reply to Re: Augment Effexor or TCS or MAOI or other?, posted by jono_in_adelaide on December 11, 2012, at 17:14:27
http://www.ncbi.nlm.nih.gov/pubmed/19165525
According to the studies that I have encountered, the only SSRI that approaches the efficacy of Effexor is Lexapro.
How much cheaper is generic Zoloft than generic Effexor?
The cost effectiveness of an antidepressant is evaluated using quite a few parameters. Besides the cost of the medication, one must take into account the medical expenses attendant to failure to respond to it, including the number of days spent in the hospital, diagnostic tests, lost wages, etc.
I would like to see the work of Ken Gillman that you refer to here. Do you recall where you saw it?
Out of curiosity, which antidepressant does your doctor choose first when treating an index episode of Major Depressive Disorder? I haven't asked my doctor this in a long time. I'll try to remember to do so at my next visit.
- Scott
Posted by SLS on December 11, 2012, at 20:46:50
In reply to Re: Augment Effexor or TCS or MAOI or other?, posted by jono_in_adelaide on December 11, 2012, at 20:20:06
Posted by SLS on December 12, 2012, at 6:09:11
In reply to Re: Augment Effexor or TCS or MAOI or other?, posted by jono_in_adelaide on December 11, 2012, at 20:20:06
Jono,
I apologize for the rant. I'll try to keep an open mind regarding the use of NE and 5-HT reuptake inhibition potencies to recommend treatments. Still, efficacy must be demonstrated clinically, and this is what I would like to see documented. In any event, it makes sense to say that SSRI + (desipramine or nortriptyline) has a better chance of promoting an antidepressant response than SSRI alone.
You cited the following:
http://www.eurekalert.org/pub_releases/2009-01/l-ass012709.php
I agree with everything this article has to say. It summarizes an unusually relevant study; the results of which agree with my own observations. Although this summary does not describe a direct comparison between Effexor and Zoloft or Lexapro regarding efficacy, I agree that Effexor has some disadvantages in terms of tolerability.
I had thought that Ada Marie retained a partial response to Effexor. I don't know what made me think this. I misread his/her posts.
- Scott
Posted by Ada Marie on December 12, 2012, at 19:11:09
In reply to Re: Augment Effexor or TCS or MAOI or other? » jono_in_adelaide, posted by SLS on December 12, 2012, at 6:09:11
Hi,
I appreciate all feedback...anecdotal and research findings. A combination of Effexor and Vyvanse worked for me for a period of time, but has not worked as well for about 4 months. Thank you!
Posted by SLS on December 12, 2012, at 20:21:06
In reply to Re: Augment Effexor or TCS or MAOI or other?, posted by Ada Marie on December 12, 2012, at 19:11:09
> Hi,
>
> I appreciate all feedback...anecdotal and research findings. A combination of Effexor and Vyvanse worked for me for a period of time, but has not worked as well for about 4 months. Thank you!
It would be nice to have a crystal ball at times like this.What dosage of Effexor are you taking?
If you have already tried Zoloft and Lexapro without responding to them at all, and you are still partially responsive to Effexor, I would think that adding desipramine now would make more sense than going back to a SSRI. I would keep the Vyvanse. You could also add Wellbutrin instead of desipramine. They are not interchangeable, so you might respond to one and not the other. Both drugs have the potential to treat depression and ADHD. Neither drug should cause weight gain or sexual side effects.
There are some people who respond better to Pristiq than Effexor. Just something to think about.
- Scott
Posted by SLS on December 14, 2012, at 8:26:47
In reply to Re: Augment Effexor or TCS or MAOI or other?, posted by Ada Marie on December 12, 2012, at 19:11:09
> A combination of Effexor and Vyvanse worked for me for a period of time, but has not worked as well for about 4 months. Thank you!
Out of curiosity, has anything in your life changed recently that might have produced stress?
Even when someone has been stabilized on medication, the application of excessive stress can cause a relapse. This is sometimes called "medication breakthrough", and is one reason for the occurence of tachyphylaxis ("poop-out"). Increasing the dosage of an antidepressant during these times is sometimes helpful.
- Scott
This is the end of the thread.
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