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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by TH on May 15, 2019, at 3:40:28
Last month I wrote a post asking for opinions on how to deal with Tranylcypromine Tachyphylaxis. At the time I was taking a dose of 30mg and had been for ~5 months. Having suddenly dropped back into a depressed state, I was concerned that the medication had permanently lost effectiveness.
I arranged to see my doctor to increase the dose to 40mg daily, however even before I could attend the appointment, my mood began to improve again. Nevertheless, I followed through with the new dose of 40mg, and have been at this dose now for 3 weeks.
While it is still too soon for me to say that the new dose has taken full effect, ever since that first dip in mood I have found myself trapped in a cycle of oscillating moods. These fluctuations seem to have a period of 3 - 7 days.
The low periods are marked by tiredness, apathy, boredom, return of food cravings, and (to a lesser degree) the agitation that I felt before I started tranylcypromine.
The high(er) periods seem to be a return to a more peaceful state. If that initial 5 month honeymoon period could be described as 80% recovery, these higher periods feel maybe 60%. Compared to the initial effect, I feel less driven to complete tasks, and take less pleasure in doing them. It is as if the symptoms are beginning to remit and I am feeling "okayish", but before this happens it seems to drop away again.Possible scenarios I can imagine that *might* cause this sort of thing include:
- a latent bipolar disorder
- an initial placebo effect having worn off
- the improvement having come from tranylcypromine's dopamine releasing properties, and having developed a level of tolerance
- some sort of self-perpetuating cycle to do with tranylcypromine being metabolised by MAO
Against the possible bipolar scenario:
I would not have described the "higher" point of the cycle as a hypomania. It does not meat the diagnostic criteria, and is really more of a "lessening of negative symptoms" than a swing into the positive. The periods also seem to be suspiciously short for a bonafide bipolar disorder. In addition to this, there is no history of bipolar in my family.Nonetheless, it warrants consideration. The only mention of this "fluctuating effect" has been in the following pamphlet:
http://cdn.neiglobal.com/content/pg/live/tranylcypromine.pdf
>Some patients may experience apparent
lack of consistent efficacy due to activation
of latent or underlying bipolar disorder, and
require antidepressant discontinuation and
a switch to a mood stabilizerAnother curious detail is that the periods of low mood are accompanied by a total disappearance of side effects, and the higher mood periods begin a day or two after the side effects resume.
It is worth noting that while I did have mood-swings before tranylcypromine, they have never resembled this before, in dichotomous nature, or in time scale. It *is* possible that this type of mood fluctuation has been happening for some time, but on such a large time scale that it has gone unnoticed (> 6 months).
I have done my best to keep any external circumstances constant over this period. Sleep schedule has remained constant, doses taken at the same time, on an empty stomach.
I'd greatly appreciate any opinions on the situation. In any case, I don't intend to take any action to try correct this situation for, at minimum, several more weeks, to give the new dose a fair chance to stabilise.
Posted by rose45 on May 15, 2019, at 12:41:28
In reply to Tranylcypromine - Fluctuating Effects, posted by TH on May 15, 2019, at 3:40:28
Hi TH,
Since we are in a similar situation, I thought I would briefly respond. We are not in quite the same situation, as I stupidly reduced my dose as I was feeling rather 'high' on it and that was the beginning of all the trouble.
During the 5 years I was on 30 mg, I did have highs and lows, mainly related to what was going on in my life. Towards the beginning I also thought maybe the med was not working that well, but I stayed on the same dose, and when my life became happier, for various reasons, I was very very happy on that same dose.
I have just been to a private psychiatrist here in London, who costs a fortune, as they all do. He is very old and very experienced, and has 6 other patients on parnate, on doses up to 60 mg. He did agree that parnate is the most powerful med there is.
He wanted to put me on a mood stabliser, but then decided better to just up the dose to 4.5mg to see if that will make a difference.I dont know how relevant this is to your situation, but thought I would mention it. I do hope you get responses from other parnate users.
Posted by Christ_empowered on May 16, 2019, at 10:14:28
In reply to Re: Tranylcypromine - Fluctuating Effects, posted by rose45 on May 15, 2019, at 12:41:28
hi. i dont take maoi drugs, so i cannot answer from personal experience.
the late Dr.Ivan Goldberg was a fan of Parnate. His approach seems to have been one that was popular in the 60s...Parnate, if that doesn't do the trick, Parnate+dexedrine, possibly parnate+dexedrine+antipsychotic.
I'd be careful about making a diagnosis of bipolar of any sort based on response to a powerful maoi. having said that, depending on the sort of problems remaining, adding an antiseizure drugs, possibly maybe an antipsychotic, might be something worth talking over with your pdoc.
way back when, combo pills were very common in psychiatry. one combo pill was parnate+stelazine, an older, high potency, phenothiazine-type (same family as thorazine) antipsychotic. i think it was 10mgs/Parnate + 1 mgs/ stelazine. anyway...
i wouldn't personally go for stelazine--higher risk of TD, lots of akathisia--but clearly there's a longstanding practice of using tranquilizers with parnate to enhance response, improve tolerability (I'm guessing it would help with stimulation and maybe add some to the overall effects, by reducing anxiety, agitation, and tension?), etc.
ok. hope this helps a bit.
Posted by TH on May 16, 2019, at 16:47:51
In reply to Re: Tranylcypromine - Fluctuating Effects, posted by rose45 on May 15, 2019, at 12:41:28
> I have just been to a private psychiatrist here in London, who costs a fortune, as they all do. He is very old and very experienced, and has 6 other patients on parnate, on doses up to 60 mg. He did agree that parnate is the most powerful med there is.
> He wanted to put me on a mood stabliser, but then decided better to just up the dose to 4.5mg to see if that will make a difference.
That's good to hear, Rose. I'm glad you've found someone to help find the right way forward. I hope it does turn out to be helpful.
Posted by TH on May 16, 2019, at 17:01:02
In reply to Re: Tranylcypromine - Fluctuating Effects, posted by Christ_empowered on May 16, 2019, at 10:14:28
> hi. i dont take maoi drugs, so i cannot answer from personal experience.
>
> the late Dr.Ivan Goldberg was a fan of Parnate. His approach seems to have been one that was popular in the 60s...Parnate, if that doesn't do the trick, Parnate+dexedrine, possibly parnate+dexedrine+antipsychotic.
>
> I'd be careful about making a diagnosis of bipolar of any sort based on response to a powerful maoi. having said that, depending on the sort of problems remaining, adding an antiseizure drugs, possibly maybe an antipsychotic, might be something worth talking over with your pdoc.
>
> way back when, combo pills were very common in psychiatry. one combo pill was parnate+stelazine, an older, high potency, phenothiazine-type (same family as thorazine) antipsychotic. i think it was 10mgs/Parnate + 1 mgs/ stelazine. anyway...
>
> i wouldn't personally go for stelazine--higher risk of TD, lots of akathisia--but clearly there's a longstanding practice of using tranquilizers with parnate to enhance response, improve tolerability (I'm guessing it would help with stimulation and maybe add some to the overall effects, by reducing anxiety, agitation, and tension?), etc.
>
> ok. hope this helps a bit.
Thanks for the reply. It's interesting to hear that so many people must have struggled with tolerability. While there certainly are some obvious side effects, I've found the relief that accompanies them to be far greater than any discomfort they bring.I'm surprised to hear that agitation is also a concern for some as I have found Tranylcypromine to be very grounding. Unmedicated, agitation is usually one of my biggest problems, however on the medication it almost completely disappears.
I think you're totally correct about it being unwise to infer some sort of bipolar disorder, or other condition, at this stage. From my current, more positive, mindset I can see that it is still far too soon to be considered at a steady state, and that there is every chance that things will change over the next few weeks / months. If this pattern did continue for a great length of time, it may be worth thinking seriously about, but at this stage it is probably not worth the worry.
That being said, I have certainly noticed that those low periods have been accompanied by an obsession with medication / diagnosis, and overthinking my mental state. So watch this space I guess.
Posted by SLS on May 17, 2019, at 11:15:30
In reply to Tranylcypromine - Fluctuating Effects, posted by TH on May 15, 2019, at 3:40:28
Your propositions are very logical.
Some researchers now suggest that one can have a bipolar diathesis (biological predisposition) without ever experiencing mania. Emil Kraeplin introduced the term "manic depression" as a diagnosis that included presentations that were unipolar. I experience mania only in association with taking MAOIs. It is probably significant that I was an ultra-rapid cycler for two years prior to treatment with antidepressants. I would oscillate between a severe depression lasting 8 days followed by a state approximating remission lasting 3 days. The cycle did not deviate. My cycling completely stopped upon the introduction of lithium. Thereafter, I was stuck in a state of unremitting depression, even after the lithium was discontinued.
In your situation, I would suggest that you consider adding low-dose lithium (300-600 mg/day) and/or lamotrigine to the Parnate. Adding Abilify is also something to consider. I have safely combined Parnate with desipramine, nortriptyline, and Wellbutrin.
The two reuptake inhibitors that I have had some success with are Effexor and Trintellix.
If you had some success with Wellbutrin, I would recommend combining it with a drug that inhibits the reuptake of serotonin - SSRI, SNRI, Viibryd, Trintellix, or perhaps clomipramine.
The simplest thing to do is to continue to increase the dosage of Parnate. Many people do respond to 40 mg/day, but some need to increase the dosage to between 60-80 mg/day. Are you prevented from doing this? What has been your experience with Nardil?
I hope you continue to post your experiences as you move forward.
- Scott
Posted by TH on May 17, 2019, at 16:32:03
In reply to Re: Tranylcypromine - Fluctuating Effects » TH, posted by SLS on May 17, 2019, at 11:15:30
Thanks for your input, Scott.
As far as medication changes, I am hesitant to do anything dramatic as Tranylcypromine has been the only useful therapy of the handful I have trialed.
Ideally, I'm hoping that it can remain a viable monotherapy. I dread the idea of adding / changing to drugs like TCAs; my brief experience with the H1 antagonism of Quetiapine was fairly unpleasant. Tranylcypromine has felt very clean and it would be a shame to lose that, however if I do reach a point of desperation, the potential benefit may begin to outweigh the cost.
If, after several weeks / months, this cycle remains, my first action would probably be to begin increasing the dose of TCP, however I am somewhat concerned about the possibility of repeatedly increasing dose if it is not the problem. Not that there would be any real way of knowing without trying.
Failing that, Lamotrigine or Lithium augmentation does seem like a suitable next step.
One roadblock to this is that my prescription for Tranylcypromine has been granted by a supportive GP. While I am grateful he has taken the chance with me, I'm sure that there would come a day where an ever escalating series of requests for psychiatric drugs would be too much for him to tolerate. The official New Zealand guidelines suggest a dose of 20 - 30mg TCP, so even pushing far beyond that may be an unreasonable request. Before seeking any radical medication regimes it would probably be wise to seek management under a psychiatrist, ideally one with experience using MAOIs. This could prove to be quite the search.
I have never trialed Phenelzine, so this may be another option, however its sedative effects do make it seem less attractive than Tranylcypromine.
One thing that makes me strongly suspect something strange is the fact that these periods of wellness are accompanied by the now familiar side effects and sensations of the drug, where as the periods of low mood are accompanied by their complete disappearance. It is as if, overnight, I had reverted to an unmedicated state.
At this point I don't feel that any dramatic changes are justified; for the most part I am very happy with Tranylcypromine. It has been the greatest glimmer of hope since this whole mess began. I am holding onto the idea that things will continue to improve and these effects will stabilize with time, and that any remaining fluctuation / defecit may be manageable with lifestyle change, or even simply be tolerable as a best case scenario. Things would have to turn for the worse before I seriously consider further medication adjustments.
Posted by SLS on May 17, 2019, at 20:06:27
In reply to Re: Tranylcypromine - Fluctuating Effects » SLS, posted by TH on May 17, 2019, at 16:32:03
Patience, something that I don't have enough of, is sometimes rewarded with a strong and stable antidepressant response. I have seen this reported sometimes with Nardil. People have waited for as long as 3 months to see results. With Nardil, I experienced some sedation during the first few weeks, but later felt more energized.
In many cases, the response to an antidepressant is not linear. It occurs more as a saw-tooth pattern with peaks and valleys, although trending towards improvement.
As an aside, I see more reports of poop-out with Nardil than I do with Parnate. However, it may be that more people use Nardil than Parnate. I don't know.
- Scott
This is the end of the thread.
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