![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 54. This is the beginning of the thread.
Posted by rose45 on September 10, 2021, at 8:40:49
I was on phenelzine and it stopped working after 15 years. Then on parnate which I liked and was on for 6 years . I then went a bit high on it, so reduced it and it just stopped working altogether. Was put on lamotrigine and that worked for 3 months and then just stopped.
Im not talking about poop out, but totally stopped working as in tachyphylaxis and increasing the dose made no difference in all those cases. Now suffering from the most dreadful anxiety. Has anyone else had this? Is it a sign of some kind of bipolarity? Im in England under the NHS which is hopeless. Have asked for Marplan, but dont know if they will agree. Has anyone had this experience of drugs working just for a while ? And what can be done about it?
Posted by SLS on September 10, 2021, at 9:18:22
In reply to Why do meds constantly stop working for me?, posted by rose45 on September 10, 2021, at 8:40:49
Hi.
> I was on phenelzine and it stopped working after 15 years. Then on parnate which I liked and was on for 6 years . I then went a bit high on it, so reduced it and it just stopped working altogether. Was put on lamotrigine and that worked for 3 months and then just stopped.
>
> Im not talking about poop out, but totally stopped working as in tachyphylaxis and increasing the dose made no difference in all those cases. Now suffering from the most dreadful anxiety. Has anyone else had this? Is it a sign of some kind of bipolarity? Im in England under the NHS which is hopeless. Have asked for Marplan, but dont know if they will agree. Has anyone had this experience of drugs working just for a while ? And what can be done about it?
I am currently headed for remission taking:Nardil - 75 mg/day
nortriptyline - 75 mg/day
Lamictal - 300 mg/day
lithium - 300 mg/day
You most likely have Bipolar Disorder: Depressive Subtype with drug-induced manias. Like you, my baseline state is one of severe, unremitting depression. The only times I became manic was during treatment combinations using MAOIs.I would go back to Nardil 60-90 mg/day. You must titrate gradually. If you go higher than your optimal dosage, you will be over-medicated and can relapse. Try each dosage for 3-6 weeks before making a dosage adjustment.
I would begin taking lamotrigine 200-300 mg/day first, and leave it onboard while you try other medications.
1. What drugs have you tried?2. What other drugs made you feel at all better, regardless of how briefly?
3. What combinations have you tried?
4. How would you best describe the symptoms of your depression?
My guess is that you are far from trying everything, but answering those questions might help steer you in the right direction.You'll get there. Be patient if you can. Hope is your friend and savior.
Good luck.
- Scott
Posted by rose45 on September 10, 2021, at 12:19:12
In reply to Re: Why do meds constantly stop working for me? » rose45, posted by SLS on September 10, 2021, at 9:18:22
Dear Scott,
Thank you very much for your thougtful message. I have been reading your recent posts and am thrilled for you that finally after years of suffering, as well as helping others, you are feeling yourself again.Like you I had never been manic before taking Nardil, but had suffered from mainly anxiety and depression. Had insomnia for 12 years before I broke down. Nardil made me manic most of the time,but psychs in those days, even though they knew, did nothing about it. This is the UK. It was the first anti depressant i had taken and I had always thought that my meditation and yoga practice would carry me through without meds. Parnate has been much better for me than nardil.
To answer your questions, i am still on parnate as the psychs here were trying to augment it, and have not taken me off it. They are telling me that if I want to come off it, it would tke 9 months.
Nardil may be difficult to get here as it is now no longer available, except in capsule form for those who have been on it for years Nardil did work for me at 45 mg for 15 years, but to be honest, I preferred parnate, which had fewer side effects. I have asked for Marplan as it is the only maoi i have not tried yet, and waiting to hear if they will approve it. Otherwise, they have said that my options are lithium or ECT., which is really scary. I asked about low dose lithium, but they insist that they have to go by the blood tests. You see what we have to contend with here in the UK.Lamotrigine stopped working after 3 months at 180mg. I am still on 125mg of lamotrigine, although that also is no longer working. My only hesitancy about increasing the dose, is that it has made me lose my memory, as well as my hair. It worked well between 100-200mg. I am still taking 125mg though it is no longer working
You are right, I have not tried many things, but the maois suit me well, and I dont feel like experimenting with ssris. I am barely functioning as it is.
I tried amitryptiline when I was younger and just slept and ate a lot. I hated it. Also tried paroxetine and had no result whatsoever - like eating a sugar pill.
So the only drugs that have made me feel better are Nardil, Parnate and lamotrigine, although i had to take low dose olanzapine with lamotrigine to feel myself.
My depression is mainly strong anxiety.
In England, they would never give me noritryptiline with an maoi, and unfortunately I am limited by their guidelines. I had to fight for parnate 6 years ago. I was very happy on it, but reduced it slightly and it stopped working. By chance I then added low dose olanzapine, and it started working again. Stupidly I reduced the olanzapine and the whole thing stopped working. I dont know why whenever I reduce the dose of maois in particular, they just stop workingI am feeling really desperate, as my mind is so crippled with anxiety it feels as if it is not working,and the anxiety is unbearable. And I am taking all these meds which are not working.
Posted by SLS on September 12, 2021, at 0:40:35
In reply to Re: Why do meds constantly stop working for me? » SLS, posted by rose45 on September 10, 2021, at 12:19:12
Hi, Rose.
It's 1:30 AM, and I should have been bed four hours ago.
You reply deserves a more thorough response. However, something jumped out at me right away. If you can tolerate it, you should bring lamotrigine up to 300 mg/day and leave it there indefinitely while you trial antidepressants. Besides ALL of the generic lamotrigine products suck. The best generic was the original TEVA pink tablets, and it was as good as Lamictal. They stopped manufacturing that product and used the factory they bought as part of the acquisition of another company.
I'll try to get back to this tomorrow.
My current effective regime is:
Nardil - 75 mg/day
Nortriptyline - 75 mg/day
Lamictal - 300 mg/day
Litium - 300 mg/dayTake care.
- Scott
Posted by rose45 on September 12, 2021, at 5:46:44
In reply to Re: Why do meds constantly stop working for me? » rose45, posted by SLS on September 12, 2021, at 0:40:35
Thank you Scott, its kind of you to respond, and any other response would be appreciated, when you hve time.
Only generics are available to me here in uk, and the brand seems to change with every prescription. Right now the lamotrigine I have Torrent and Relonchem. I envy you in USA with your choice of psychiatrists and meds.
I also know of someone who went up to 400 lamotrigine and it also stopped working, but in his case after 2 years - but it did help him during that time.
It is so scary that meds stop working. I was so well on Parnate alone. But it seems as soon as I reduce meds they stop working.
I did suffer from bad memory loss on lamotrigine, and feel afraid of increasing so much - it would take time, and I dont trust the opinion of the pschychiatrist here, who I rarely see anyway. Lamotrigine between 100-200 was not that different, it stopped the anxiety - but when it stopped working after 3 months, I decreased it. Do you really think I should ask to increase it again? Would it help if they do decide to give me marplan and have me come off parnate, which they have said would be very painful and drawn out, after 6 years on it.
Im sorry for blabbering on. I am in so much pain and fear, can barely type. Thank you for your help. Its nice to know that someone so knowledgeable is trying to help.
Posted by SLS on September 12, 2021, at 13:16:23
In reply to Re: Why do meds constantly stop working for me?, posted by rose45 on September 12, 2021, at 5:46:44
Hi, Rose.
Lamotrigine did very little for me at 200 mg/day. 300 mg/day produces results, but not by itself. When I first started it as monotherapy, it helped substantially, but only for a few weeks. I tried going up to 450 mg/day, but with zero results except major memory impairments. For me, memory problems appeared almost immediately. However, they were tolerable. It didn't take very long for them to mitigate with continued treatment.
I'm surprised that lamotrigine helped you for so long before quitting on you. Before doing anything else raise the dosage of lamotrigine gradually to 300 mg/day. Maybe add 50 mg every two or three weeks. Try not to pass judgment on memory impairment right away.
Keep taking lamotrigine in the background at 300 mg/day for as long as you continue to trial other drugs. That you responded so well and so long to lamotrigine indicates to me that you are most likely bipolar, which would explain your manic reactions to antidepressants. As you move forward, consider taking the newer drugs that have been found to be effective in bipolar depression. These include two newer antipsychotics, asenapine (Saphris) and lurasidone (Latuda). Latuda is approved for bipolar depression, but I think asenapine will work better for some people.
One last thing. Lithium works for me as an adjunct that I have kept in the background for years. However, I found that low dosages (300 mg/day) helps to reduce the severity of my bipolar depression, while higher dosages - the dosages necessary to treat or prevent mania - make me feel worse.
Two recent findings:
1. Lithium bimodal activity in bipolar depression. Clinical investigations confirm my observations that people with bipolar depression feel good at low dosages and relapse at higher dosages.
2. Lithium has bimodal activity on glutamate activity. At low dosages, lithium increases glutamate while high dosages decrease it. Glutamate is the brain's most widespread excitatory neurotransmitter, and its activity is tied to mood state.
Low glutamine = depression
High glutamate = maniaThe main reason why I decided ten years ago to keep taking low-dosage lithium is that there are enumerable investigations that indicate lithium prevents Alzheimer's Dementia, which, coincidentally, my mother developed just 2 years ago.
- Scott
Posted by rose45 on September 13, 2021, at 7:28:08
In reply to Re: Why do meds constantly stop working for me? » rose45, posted by SLS on September 12, 2021, at 13:16:23
Hi Scott,
Im not sure why you say you are surprised that lamotrigine lasted so long for me. If you look at my last posts , it lasted just 3 months and then stopped working. It started working at 100 and there was not much change between 100 and 200mg. After 3 months at 200, it just stopped working and increasing the dose made no difference. I note it took a higher dose to work for you, but I do tend to take lower doses of all meds, than most people.
I also had to add low dose olanzapine, because without it, the lamotrigine on its own made my mind very cloudy and I did not feel like myself at all.
I hesitate to increase the dose at this point as it has severely affected my memory. I cant remember how to do the simplest tasks on the computer and this creates so much anxiety for me.
Does this make sense to you?
Do you agree that low dose antipsychotics act very differently to higher doses ? This was certainly true of olanzapine - 2.5 mg of olanzapine got the Parnate to work again. But yet again, when I reduced the olanzapine slightly, the parnate stopped working altogether.
I wonder whether the two anti-psychotics you mention would have a similar effect? I wish I could try just a small amount of them, but they are so expensive here I doubt our NHS would agree to let me have them. If you think there is any possiblity they might potentiate the parnate, I could try to obtain a small quantity privately.
I would appreciate your thoughts on this. I am still taking 2.5mg olanzapine as it does help me to sleep, but it no longer augments the parnate as it did the first time I took it.
From what others have said to me low dose olanzapine increases dopamine, or words to that effect. Aripiprazole did not have that same effect, so I dont know whether the other anti psychotics you mention could act like olanzapine as dopamine enhancers. Sorry I am not at all technical and dont understand most technical terms.
Posted by SLS on September 13, 2021, at 15:03:24
In reply to Re: Why do meds constantly stop working for me?, posted by rose45 on September 13, 2021, at 7:28:08
Hi, Rose.
> Sorry I am not at all technical and dont understand most technical terms.
Phew...
I'm not really technical either, but I've learned how to fake it by watching the truly smart people here.
I will definitely keep that in mind when I write to you.
I have no idea why I was under the impression that you were taking lamotrigine for over a year. 3 months sounds about right, though. Do you think that you could remain on 200 mg/day of lamotrigine without resorting to taking something else to offset cognitive and memory side effects?
Thank you so much for describing your experiences with olanzapine. I learned some important things from you. I, too, noticed an incredible clearing up of my thoughts within hours of taking my first dose to treat a drug-induced mania produced by Nardil.
I think people here will help produce alternatives.
Stay strong.
- Scott
Posted by undopaminergic on September 14, 2021, at 10:27:27
In reply to Re: Why do meds constantly stop working for me?, posted by rose45 on September 13, 2021, at 7:28:08
>
> From what others have said to me low dose olanzapine increases dopamine, or words to that effect.
>I haven't heard of that. Not about olanzapine, but about some others, especially aripiprazole and amisulpride.
> Aripiprazole did not have that same effect, so I dont know whether the other anti psychotics you mention could act like olanzapine as dopamine enhancers.
>I suggest sulpiride, 50 mg/dose. It is an old one and should be cheap.
The first time I tried it, I got a stimulant effect stronger than from methylphenidate (Ritalin, Concerta). It did not work for long, but maybe you have better lack.
-undopaminergic
Posted by SLS on September 14, 2021, at 13:22:43
In reply to Re: Why do meds constantly stop working for me?, posted by undopaminergic on September 14, 2021, at 10:27:27
Hi, guys and gals.
From what I've read, amisupride is the best antipsychotic to treat the negative symptoms of schizophrenia. People on PB tried it for depression years ago. I don't have a solid impression as to how many people responded well to it, and stayed well. However, there was a consensus that the best dosages of sulpride to treat depression, and perhaps even dysthymia, were low. It was most often effective at dosages of 50 mg/day or less.
- Scott
Posted by rose45 on September 14, 2021, at 17:14:09
In reply to Re: Why do meds constantly stop working for me?, posted by undopaminergic on September 14, 2021, at 10:27:27
Thanks, I might try it. I think olanzapine works differently at a low dose, and it definitely made the Parnate work again.
It was one of the recommendations from the Maudsley Hospital in London for augmenting Parnate. Their other recommendation was T3/Liothyronine which I have just ordered from India, because it is excessively expensive in the UK.
I have read conflicting reviews of Amisulpride.
I guess the only way to find out if it works with Parnate is to try it.
Posted by rose45 on September 14, 2021, at 17:25:47
In reply to Re: Why do meds constantly stop working for me?, posted by SLS on September 14, 2021, at 13:22:43
Im a bit confused. Are we talking about amisulpride or sulpride? Are they not two different things?
Posted by rose45 on September 14, 2021, at 17:32:09
In reply to Re: Why do meds constantly stop working for me?, posted by rose45 on September 14, 2021, at 17:25:47
All the links to sulpride that I have found mention its augmentation use for schizophrenia. Not one article for its use in augmentation of anti depressants, or maois in particular.
Posted by SLS on September 14, 2021, at 21:11:05
In reply to Re: Why do meds constantly stop working for me?, posted by rose45 on September 14, 2021, at 17:32:09
> All the links to sulpride that I have found mention its augmentation use for schizophrenia. Not one article for its use in augmentation of anti depressants, or maois in particular.
Darn. I meant amisulpride as opposed to sulpiride. Sorry.
They are similar in that they are both selective for dopamine presynaptic autoreceptors. Those are the receptors on the first neuron at the synapse. When they "see" too much dopamine, they turn off the manufacture and release of dopamine. So, when an antagonist makes the first neuron "blind" to the excess dopamine, it continues to release it anyway. These presynaptic autoreceptors are "stickier" (higher binding affinity) than are the postsynaptic receptors on the second neuron. At low dosages, the presynaptic binding predominates, so dopamine release is increased without the postsynaptic receptors being antagonized (blocked). The postsynaptic neuron can still see dopamine and can be stimulated by it.
Anyway, like I said, amisulpride was of great interest on Psycho-Babble perhaps 20 years ago. I think there are several papers on amisulpride being a good treatment for dysthymia. Zyprexa is an entirely different beast, and I don't know how it augments MAOIs pharmacologically. 5-HT2a/c antagonism maybe? I'm sure someone will know. Zyprexa is what's called an inverse-agonist at those receptors. Basically, this means that it actually suppresses activity even more that a pure antagonist does. It's sort of like a super-antagonist.
- Scott
Posted by rose45 on September 20, 2021, at 9:01:15
In reply to Re: Why do meds constantly stop working for me? » rose45, posted by SLS on September 14, 2021, at 21:11:05
Scott, To my amazement the NHS has just approved marplan for me. Its hard to believe, because they just dont normally prescribe it.
The problem is they will insist on a long drawn out reduction of the parnate which I am on, and a 2 week wash out.I am dreading it, as I have been on parnate for 8 years or so.
I seem to remember that you had a post where you substituted one maoi for another without the washout and landed up in hospital? Is that correct? Or maybe it was someone else?
Posted by SLS on September 20, 2021, at 9:37:27
In reply to Re: Why do meds constantly stop working for me?, posted by rose45 on September 20, 2021, at 9:01:15
Hi, Rose.
> Scott, To my amazement the NHS has just approved marplan for me. Its hard to believe, because they just dont normally prescribe it.
>
> The problem is they will insist on a long drawn out reduction of the parnate which I am on, and a 2 week wash out.I am dreading it, as I have been on parnate for 8 years or so.
>
> I seem to remember that you had a post where you substituted one maoi for another without the washout and landed up in hospital? Is that correct? Or maybe it was someone else?
Yes. My doctor thought it could be done. When I switched from Nardil to Parnate within a day, I became delirious and who knows what else. In the ambulance, I got pricked in the penis with a catheter for urine. My senses were generally numb, but I sure as heck felt that!
I don't have the time to look back, but have you tried Nardil yet?1. What was your highest dosage?
2. How long were you on the highest dosage for?
3. Did it help with depression? In what wasys were you improved?
4. What were your side effects?
* 5. What other drugs did you combine it with?
- Scott
Posted by rose45 on September 20, 2021, at 11:19:06
In reply to Re: Why do meds constantly stop working for me? » rose45, posted by SLS on September 20, 2021, at 9:37:27
Hi Scott,
I was on Nardil for 15 years and then it totally stopped working and anxiety came back in full force.
I would take it up to 60 mg which was pretty unbearable with side effects, but as soon as it worked, I stayed on it for 2 or 3 weeks, and then went down to 45mg and that was my maintenance dose.
This was the classical way of titrating up at the maudsley hospital where i was an inpatient.I did feel very happy on it, but later realised it was making me manic.... i started gambling, spending money etc. which i had never done before. I told the doctors but being uk and conservative, they said it was better to stay on one med, than add lithium, as i had suggested to them.
It had loads of side effects, putting on weight, constipation being the main ones. I far preferred parnate.
Strangely, I was able to sleep on nardil, though I had suffered from insomnia for most of my life.
I never combined it with other drugs. In the UK they dont like doing that, as they do in the usa. But it worked fine on its own for the 15 years i was on it.
When it stopped working, i tried to increase but it didnt make any difference. Psychs added seroquel and I suffered terribly as they increased the seroquel for 6 months. Finally they agreed to switch to parnate, and parnate was almost side effect free, except for the insomnia
I hope that answers your questions. Here in the UK, they simply dont believe in taking several meds at the same time. You re much more fortunate in the USA.
Posted by SLS on September 20, 2021, at 21:52:38
In reply to Re: Why do meds constantly stop working for me?, posted by rose45 on September 20, 2021, at 11:19:06
Hi, Rose
> I hope that answers your questions. Here in the UK, they simply dont believe in taking several meds at the same time. You re much more fortunate in the USA.
The NHS is so backwards. According to the most recent diagnositic criteria in the DSM 5, you fit the description of Bipolar Disorder (Depressive subtype) with Drug-Induced-Mania as a qualifier. From now on, I would use treatment strategies found to be effective in that Bipolar subtype. I think lamotrigine is a candidate as an augmenter. I think Undopaminergic could provide some information about this. In my personal experience and from what the medical literature yields, the range of dosages of Nardil are usually between 60-90 mg/day.
What about France?
- Scott
Posted by undopaminergic on September 21, 2021, at 0:19:54
In reply to Re: Why do meds constantly stop working for me? » rose45, posted by SLS on September 20, 2021, at 21:52:38
> I think lamotrigine is a candidate as an augmenter. I think Undopaminergic could provide some information about this.
>I'm sorry that I'm not any kind of expert on lamotrigine. Indeed it sounds to me that you might know better, as you have suggested a minimum dose (whereas I wouldn't know).
-undopaminergic
Posted by rose45 on September 21, 2021, at 6:54:40
In reply to Re: Why do meds constantly stop working for me? » rose45, posted by SLS on September 20, 2021, at 21:52:38
Scott, I think we have crossed wires.
My earlier message was to say that to my great surprise, the NHS here in UK have agreed to put me on Marplan.
I did not think they would agree to it as it is very expensive, and the alternatives they gave me were lithium or ECT, neither of which I was keen on.
Im not too sure why you asked about Nardil. Since it stopped working some years ago, and since Parnate also stopped working, it seemed to make sense to try Marplan, which is the only maoi I have never taken, even though people seem to think that it is weaker than the other maois.
I may well keep Lamotrigine going in the background, if the psychs agree.
France is a different country and I dont live there.
Posted by rose45 on September 22, 2021, at 7:50:48
In reply to Re: Why do meds constantly stop working for me? » rose45, posted by SLS on September 20, 2021, at 21:52:38
Scott,
I really do appreciate the time you have given to answering my posts, and opening my eyes to the fact that I am a sub-type of bipolar, and should carry on with the lamotrigine in the background.
You do not say anything about marplan, which, as I mentioned in my previous post, has just been approved for me by the NHS? Is that because you do not think that marplan would be an ideal solution, along with the lamotrigine?
Posted by SLS on September 23, 2021, at 7:52:03
In reply to Re: Why do meds constantly stop working for me? » SLS, posted by undopaminergic on September 21, 2021, at 0:19:54
> > I think lamotrigine is a candidate as an augmenter. I think Undopaminergic could provide some information about this.
> >
>
> I'm sorry that I'm not any kind of expert on lamotrigine. Indeed it sounds to me that you might know better, as you have suggested a minimum dose (whereas I wouldn't know).
>
> -undopaminergic
>
You are indeed a gentleman.:)
- Scott
Posted by SLS on September 23, 2021, at 8:13:59
In reply to Re: Why do meds constantly stop working for me?, posted by rose45 on September 21, 2021, at 6:54:40
Hi, Rose.
I would not consider my memory competent enough to remember all of your posts. I'm also too lazy to look back. So, please don't be insulted or frustrated by my lack of recall.
I mentioned Nardil *again* because if you haven't combined it with a tricyclic, some other antidepressant or augmenting drug, or a "mood stabilizer", you are far from done searching for an effective treatment for your depression. I mentioned lamotrigine specifically, as I am 100% sure that it works for me and is necessary for me to achieve remission. Lamotrigine is FDA approved to treat bipolar depression. So, I would suggest that lamotrigine, at as high a dosage as you can tolerate up to 300 mg/day (when given time for side-effects to wane) is worth keeping onboard indefinitely, just in case you respond to any treatment that requires its presence as an augmenter.
Are you bipolar? I think you should review the DSM 5 manual to investigate this question. You *must* read the list of "qualifiers" that are listed for bipolar disorder. You do indeed qualify. So, as I suggested, you might do better to use the DSM 5 diagnostic criteria and adjust your treatment plan accordingly. Your future choices of drug treatments might be greatly expanded using lists of treatment regimes recommended for bipolar depression.
That's just my opinion. I recommend that you do the reading I suggested in order to come to your own opinion.
Good luck.
- Scott
Posted by rose45 on September 23, 2021, at 17:57:13
In reply to Re: Why do meds constantly stop working for me? » rose45, posted by SLS on September 23, 2021, at 8:13:59
Not too sure where I can get an online copy of the DSM 5 Manual,is there one?
I have been reading the following website https://psycheducation.org/ by Jim Phelps which is very enlightening on the subject of the different types of bipolar.
Re. Lamotrigine, it worked well at 200mg for 3 months and then pooped out. So although Im still taking it, it is no longer working....it may well be that it is a generic which does not work like the original lamictal, but I have no choice re. which version I am given by the pharmacy unfortunately.
Posted by SLS on September 23, 2021, at 23:52:25
In reply to Re: Why do meds constantly stop working for me?, posted by rose45 on September 23, 2021, at 17:57:13
> Re. Lamotrigine, it worked well at 200mg for 3 months and then pooped out. So although Im still taking it, it is no longer working....it may well be that it is a generic which does not work like the original lamictal, but I have no choice re. which version I am given by the pharmacy unfortunately.
Rose:*** lamotrigine = 3OO mg/day!!! ***
What prevented you from continuing the titration of the lamotrigine dosage beyond 200 mg/day?
If you tried 300 mg/day, what happened? How many weeks did you allow for it to work?
- Scott
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