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Dr. Bob is Robert Hsiung, MD,
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Posted by desolationrower on December 13, 2008, at 14:02:07
In reply to Re: Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 13, 2008, at 5:08:27
I don't see you mention stimulant augmentation with MAOIs - also with hypersomnia, MAOI + AMP + modafinil? Also NMDA antagonists as augmentations. For me the depression isn't the intractable issue so i've less personal experience to add, but welcome sounds like you havhe some interesting experiences to share
-d/r
Posted by CaptainAmerica1967 on December 13, 2008, at 14:24:43
In reply to Re: Treatment Resistant (Refractory) Depression, posted by polarbear206 on December 13, 2008, at 8:25:35
No, I live in Houston, TX (I grew up in upstate
New York around the Finger Lakes), but I know Dr. Goldberg and have gotten a consult with him via the email. He's one of the most knowledgeable people on TRD.His emails to me
" Hi . . .
The short answer is that the combinations most often used are:
phenelzine + amitriptyline and tranylcypromine + amitriptylineBest regards . . .
Ivan
Hi . . .
I find the combination of one of the MAOIs + (TCA or psychostimulant) to be a very powerful treatment for people with hard to treat depressions. The combination is even more effective when potentiated by lithium.
I am not convinced that TMS is a very useful treatment, but of course the people I get to see are the TMS failures. It looks as if deep brain stimulation, currently being researched at Columbia and Mass General is going to turn out to be a much better treatment.
Best regards . . .
Ivan
Thanks for suggesting Dr. Goldberg though and your thoughts.
I applied for the deep brain stimulation study in Dallas, TX, but because I had several seizures while on trazodone and at one time was diagnosed as having petit mal seizures (although they went away after going off trazodone and never had any more seizures and don't take any meds for it), I couldn't enter the study. I don't think the vagus nerve stimulator is effective nor were the 70 ECT's I had in 1985-1986.
Regards,
Jeff
Posted by CaptainAmerica1967 on December 13, 2008, at 14:39:28
In reply to Re: Treatment Resistant (Refractory) Depression, posted by desolationrower on December 13, 2008, at 14:02:07
Thanks,
Currently taking Parnate/Nortriptyline/Lithium Orotate.
Tried Lacmital, and Tegretol (had some petit mal seizure while on trazodone and receiving the 70 plus ECT's during 1986 which resulted in the mentioned car accident that killed my mother) in the past without big success.
Atypicals antipsyhcotic like Abilify sent me into even a more severe depression.
I tried Namenda (memantine) without noticing any affect or effect. I looked into getting into a Ketamine study at the NIMH in Bestheda, MD, but didn't want to go off the meds and I have a falling after only being off meds for a day or two. I've cheated (even though being risky) when going off/on different meds like Nardil to Cymbalta and Cymbalta to Parnate without any washout at all and started the next day without any serotonin syndrome effects.
Thanks for the suggestions.
Regards,
Jeff
Posted by CaptainAmerica1967 on December 13, 2008, at 15:33:09
In reply to Re: Treatment Resistant (Refractory) Depression, posted by SLS on December 12, 2008, at 11:24:18
" I wish clorgyline were still around."
Was it removed from the market because of FDA laws or just stopped being made? If it's still legal, then it can be manufactured by a chemist. I used to take GHB from health food stores and it was removed from them by the FDA and prior to the Xyrem RX form of GHB coming out, I had a compounding pharmacist, chemist make it for me.
Did it work well for you?
Posted by Racer on December 13, 2008, at 17:27:07
In reply to Re: Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 13, 2008, at 15:33:09
Hello, and welcome.
I've had my share of rides on the Medication-Go-Round, and finally found myself at an acceptable level of partial remission. I think I agree with both SLS and PolarBear, because I'm going to suggest a few things that are pretty similar to some of what you've already tried.
First, I'll add a vote for trying Provigil if you haven't already tried it with what you're on.
I had a less than pleasant response to Lamictal -- it was depressogenic for me, as were BuSpar, Seroquel, EMSAM, and I think Abilify. (I can't remember with Abilify -- it might just have made me too edgy?)
I did have a far better response to Trileptal -- it really made a surprising difference, despite my long standing dx of unipolar depression. (Unfortunately, I also had an electrolyte imbalance from it, so not taking it.)
As far as antidepressants go, Wellbutrin is my good and trusted friend, although it certainly can't be monotherapy. (Honestly, I'm not sure it's really doing much, or if it's just a sort of totem at this point.) Strattera, the ADHD drug, was pretty helpful for me, and might be worth a try if you get to that point.
It sounds as though you already know a lot of the usual suspects, and have tried most of them. There were a few articles a while back about a very short course of low dose dexamethasone to kickstart response -- it's certainly worthwhile to look into that. Although you haven't mentioned it, I'm sure you're on top of your thyroid levels, so I won't mention that.
All I can come up with to suggest, actually, would be trying Provigil -- and looking into a course of steroids. The articles I've read looked very, very promising.
Best luck, and again -- welcome to Babble.
Posted by CaptainAmerica1967 on December 13, 2008, at 19:05:23
In reply to Re: Treatment Resistant (Refractory) Depression » CaptainAmerica1967, posted by Racer on December 13, 2008, at 17:27:07
Thanks for the info.
I had tried Provigil, but that was after going off the Nardil and going onto Cymbalta. Not sure if it helped as I was on so many other meds at the time, Pindolol, Lamictal, Thyroid, Androgel, Lithium, Wellbutrin, Selegiline and some other amphetamines as well. I've never tried Strattera I believe. Atypical antipsyotics like Abilify and Seroquel made my depression worse. I also was able to get a hold of and try the dopaminergic TCA called Survector (amineptine) which helped some and boosted my libido.
I've always wondered about the cortisol or cortitropin releasing factor impairment. Several CHF antagonist/blockers are being studied and are in stage II or III. (www.neurotransmitter.net/newdrugs.html)
Thanks again for your input.
Regards,
Jeff
Posted by Phillipa on December 13, 2008, at 19:22:48
In reply to Re: Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 13, 2008, at 5:05:06
Jeff my apolgies I missed this thread just seeing it now. If you like babblemail me and I'll explain things in detail to you. Somehow I feel like I already know you. Just click my posting name Phillipa in blue and a screen appears and it would be like private e-mail to me. I feel terrible I missed this. My sincerest apologies. Love Phillipa looking forward to hearing from you.
Posted by azalea on December 13, 2008, at 21:36:47
In reply to Re: Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 13, 2008, at 19:05:23
You mentioned LiOr in a previous post. I'm assume you're referring to lithium orotate. Have you tried lithium carbonate?
Also, I believe production of Survector (amineptine) has been discontinued in all countries. Amineptine is the predecessor of tianeptine, currently marketed as Stablon by Servier, the same company that made Survector.
I hope you find useful info here.
> Thanks for the info.
>
> I had tried Provigil, but that was after going off the Nardil and going onto Cymbalta. Not sure if it helped as I was on so many other meds at the time, Pindolol, Lamictal, Thyroid, Androgel, Lithium, Wellbutrin, Selegiline and some other amphetamines as well. I've never tried Strattera I believe. Atypical antipsyotics like Abilify and Seroquel made my depression worse. I also was able to get a hold of and try the dopaminergic TCA called Survector (amineptine) which helped some and boosted my libido.
>
> I've always wondered about the cortisol or cortitropin releasing factor impairment. Several CHF antagonist/blockers are being studied and are in stage II or III. (www.neurotransmitter.net/newdrugs.html)
>
> Thanks again for your input.
>
> Regards,
>
> Jeff
Posted by darwinsmunky on December 13, 2008, at 23:41:16
In reply to Re: Treatment Resistant (Refractory) Depression » CaptainAmerica1967, posted by azalea on December 13, 2008, at 21:36:47
I dont mean for this to come off the wrong way but for someone suffering from a severe and chronic form of depression you certainly have shown a great deal of motivation. From trying damn near every alternative to meds, to writing an autobiography (and yet poor at school?). Perhaps part of the problem is not the depression, but rather the obsession you have with it and in turn the possibilty of you creating a psychosomatic response.
Posted by desolationrower on December 13, 2008, at 23:41:35
In reply to Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 12, 2008, at 1:42:34
did you say if you have tried opioids? low dose naltrexone? salvia?
Since you have said MAOIs are the only drug to help, I assume you've mostly stayed on one or another of them while trying these others things mentioned as agumentation?
and since you've basically done it already, MAOI+ssri?
some people notice mood boost from pde5 inhibitors (i mean, besides the obvious)
do you meditate?
mifepristone?
amisulpride and/or clozapine?
done pretty much every medical lab test that has some reference value, and isn't for something like pregnancy?
anticholinergics, or maybe a short halflife acetylcholinesterase inhibitor?
living on a polyphasic sleep schedule?
-d/r
Posted by CaptainAmerica1967 on December 14, 2008, at 2:34:47
In reply to Re: Treatment Resistant (Refractory) Depression » CaptainAmerica1967, posted by azalea on December 13, 2008, at 21:36:47
Yes, I've tried the Lithium Carbonate as well.
I baught amineptine last year through a pharmaceutical chemist as it's still legal, but the companies have just stopped manufacturing it.
Thanks
Posted by CaptainAmerica1967 on December 14, 2008, at 2:36:18
In reply to Re: Treatment Resistant (Refractory) Depression, posted by darwinsmunky on December 13, 2008, at 23:41:16
I don't give up as I want the life I had prior to the depression.
Thanks
Posted by CaptainAmerica1967 on December 14, 2008, at 2:42:32
In reply to Re: Treatment Resistant (Refractory) Depression, posted by desolationrower on December 13, 2008, at 23:41:35
I've never tried opiates but read about one in particular (buphrenophine?).
Never dared to take MAOI plus SSRI or NSRI, but have switched within one day and never did the washout.
I do meditate and tried both amisulpride and clozapine.
Interested in the new CRF antagonists if they make it through approval. www.neurotransmitter.net/newdrugs/html
Thanks
Posted by SLS on December 14, 2008, at 8:26:15
In reply to Re: Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 13, 2008, at 15:33:09
> Did it work well for you?
As monotherapy, it produced episodic robust improvements, but proved to be an untenable therapy. I wish I were allowed by the NIMH protocol to add a therapeutic dosage of desipramine.
In my opinion, clorgyline, a specific MAO-A inhibitor, is the single most effective antidepressant in the world. It was considered by the NIMH to be their "ace-in-the-hole" when all else failed. Many people remained well on clorgyline for over a decade. Unfortunately, several people experienced cardiovascular events that convinced the NIMH to no longer support its use. It is unclear if these treatment-emergent events were caused by clorgyline.
Clorgyline is no longer manufactured for human consumption, but remains the paradigm for assaying MAO-A activity.
I don't think I would trust anyone to synthesize this particular chemical such that I would pass it down my throat. I wouldn't know how to find such a person, anyway.
- Scott
Posted by SLS on December 14, 2008, at 8:32:20
In reply to Re: Treatment Resistant (Refractory) Depression, posted by desolationrower on December 13, 2008, at 23:41:35
> and since you've basically done it already, MAOI+ssri?
That's about the only combination in psychiatry that will yield life-threatening effects at a rate nearing 100%. I have nothing against the idea of trying to potentiate the actions of antidepressants using drug combinations, but this one is really one that is dangerous.
- Scott
Posted by JadeKelly on December 15, 2008, at 12:14:29
In reply to Re: Treatment Resistant (Refractory) Depression » CaptainAmerica1967, posted by Racer on December 13, 2008, at 17:27:07
Hi Racer,
I have treatment resistant Dep for 2-3 yrs, was wondering about the articles you mentioned: Dexamethasone (never heard of it) and steroids. These are both used in trd? Were those articles on Babble or some where else? I'd love to take a look at those, or if easier can you give me a "brief" on how these work, and I can do my own research. I'm on Parnate. Thanks!
~Jade
Posted by CaptainAmerica1967 on December 15, 2008, at 16:18:53
In reply to Re: Treatment Resistant (Refractory) Depression » Racer, posted by JadeKelly on December 15, 2008, at 12:14:29
A good source to read from is www.biopsychiatry.com.
Dexamethasone suppression test involves giving cortisol to see if the depressed patient's body decreases or block it's own porduction as it should in normal non depressed individuals, but most hospitalized or refractory patients don't suppress their own production after the test. Excess cortisol blocks or interferes with serotonin.
CRF (corticotropin releasing factor) is secreted from the pituary but is faulty in depression and continues to be secreted to increase or stimulate cortisol production from the adrenal cortex despite a normal amount of cortisol in the body. Normally there's a feedback mechanism by which if you have normal levels in the blood stream then the pituary "recognizes" that one doesn't need more cortisol and suppresses CRF.
CRF antagonists (blockers) are being developed by pharmaceutical companies to treat depression.
www.biopsychiatry.com/crf1.htm
www.neurotransmitter.net/newdrugs/html
Posted by YOGI BRONX on December 16, 2008, at 16:23:03
In reply to Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 12, 2008, at 1:42:34
Dear Jeff,
We have something in common. I found that only extreme cardiovascular exercise alleviated my profound lifelong depression until Paxil in 1995. I have completed over twenty marathon foot races. (With a PR of 2:56! I try to squeeze in this fact regardless of the conversation.) High dosage Paxil, (90mg./day) worked for me for ten years. Subsequently, Lexapro at normal dosage did.
However, I still want more for myself and for others of whom I care whose depressions are still refractory.
The FDA was supposed to act on the approval of a drug named, "Ixel, (Milnacipran)", by the end of last October. Its an SNSRI, a Selective Norepinephrine Serotonin Reuptake Inhibitor". It inhibits the reuptake of noephinephine/serotonin at a ratio of 3/1. The other drugs curretly on the US market that inhibit reuptake of these neurotransmitters, (Effexor & Cymbalta), inhibit the uptake of serotonin/norepinephine at the rate of 33/1. The effect increases the availability of norephinephrine at a massively higher rate, and, obviously, at a more even pace with serotonin.
It is the only truly NEW drug for depression of which I know, rather than a reformulation of an existing drug or family of drugs.
The FDA failed to meet the October deadline and, instead, sent out a notice to that effect without posting a new deadline.
Thereupon, I ordered the drug from Great Britain. I'm not sure of the legality of this. If it hasn't been designated a prescription drug in the US, is one prohibited from buying it?
Various health product websites in Great Britain sell it openly to US residents, but not the residents of GB or the EU where it has been prescribed for ten years.
My experience, in the one day that I took it earlier this month, at a dosage of 25 mg. in the morning and 25 mg. at night, (half the normal adult dosage), was that in that one day I experienced a significant improvement in energy alertness, and, "drive", (for want of a better word), in the afternoon, a problem time for me. (I can't judge its specific antidepressant effect because I am doing OK on Lexapro at the moment. However, I find Lexapro's sexual side effect to be annihilating even to the concept of sex.) I was pleased and hopeful.
However, after taking the second 25 mg. dosage at bedtime, I experienced terrible ischuria all night long, having to get up to urinate every ninety minutes. Each time, I was able to coax just enough urine out to stop my bladder from hurting before returning to bed and repeating the entire drill 90 minutes later. It was a long, long night.
I took no more Milnacipran and the ischuria disappeared gradually the next day.
Upon further research, I have learned that this is a not uncommon side effect, (although the literature states that it affects only 2.7% of patients), that it can be alleviated with, "Flomax", and that patients have found success with it at as low a dosage as 15 mg./day, (v. 100 mg./day according to the patient instruction sheet).
One member on this board said that he used it successfully, after a refractory depression that defeated every drug in the world AND a failed course of ECT, at 6mg, 3X daily.
The same poster said that he actually didn't know of anyone who DIDN'T benefit from the drug, those people who discontinued it having to do so because of side-effects, (principally hypertension, dysuria, and what I would describe as hypertense, staring uselessness.)
He also said that the dysuria went away over time.
I haven't recommenced the drug yet but I intend to do so at the 6 mg. 3 x daily dose rate initially. Currently, I am trying to figure out how to divide, conveniently, one 25 mg. capsule into four 6 mg. doses at a bulk level. I am also waiting until the time feels absolutely right to do begin again.
Hope you find this helpful and that I am not carrying coals to Newscastle.
Cordially,
YOGI
Posted by West on December 16, 2008, at 16:45:14
In reply to Re: Treatment Resistant (Refractory) Depression » CaptainAmerica1967, posted by YOGI BRONX on December 16, 2008, at 16:23:03
I hope i'm not letting anyone down (yogi) by saying i am proof that milnacipran doesn't work for everyone. Proper doses are hard on the heart and orthostatic hypotension was as bad as i've ever experienced. Pity, as it did seem promising at the lower end of the dosage range. I'm not sure how reliable it's thought to be in terms of efficacy.
W
Posted by YOGI BRONX on December 16, 2008, at 16:55:04
In reply to Milnacipran, posted by West on December 16, 2008, at 16:45:14
Dear West,
Rats! But the poster did say that people discontinued it because of unmanageable side effects rather than because of lack of efficacy.
Cordially,
YOGI
Posted by CaptainAmerica1967 on December 16, 2008, at 20:39:02
In reply to Re: Treatment Resistant (Refractory) Depression » CaptainAmerica1967, posted by YOGI BRONX on December 16, 2008, at 16:23:03
Hi YOGI,
Thanks for your input and experience.
Yes, I've tried Ixel (milnacipran)and have researched it extensively, but like most other meds except the MAOI (type A's), milnacipran was a failure. It may be approved (clinicaltrials.gov) for fibromyalgia soon in the USA. I purchased it via www.antiaging-systems.com in Great Britian.
The only thing beyond the MAOI(A)+TCA+Psychostimulant+Lithium that I feel will provide relief to those with severe TRD is the deep brain stimulation device that Dr. Helen Mayberg founded showing that virtually all of those with depression suffer from an overactive (PET scans) part of the brain in the prefrontal cortex called Brodmann Area (25). Broadmann Area always returns to normal or becomes less active upon recovery from depression, but those who never or only partially recovery from depression continue to show overactivity in this specific spot. I tried to enter one of the studies being done in Dallas, but since I had several seizures while receiving trazodone and ECT (70 of them) in 1986, I was unable to participate in the study. Those wishing to learn more can visit www.BroadenStudy.com.
The other hopeful meds in the pipeline can be viewed on www.neurotransmitter.net/newdrugs/html.
Thanks,
Jeff
Posted by CaptainAmerica1967 on December 16, 2008, at 20:42:07
In reply to Milnacipran, posted by West on December 16, 2008, at 16:45:14
I experienced the same cardiovascular reactions as you had. Studies show that milnacipran is now more and maybe even less effective than the time tested standard TCA imipramine.
Posted by desolationrower on December 16, 2008, at 21:56:34
In reply to Re: Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 16, 2008, at 20:39:02
> The only thing beyond the MAOI(A)+TCA+Psychostimulant+Lithium that I feel will provide relief to those with severe TRD is the deep brain stimulation device that Dr. Helen Mayberg founded showing that virtually all of those with depression suffer from an overactive (PET scans) part of the brain in the prefrontal cortex called Brodmann Area (25). Broadmann Area always returns to normal or becomes less active upon recovery from depression, but those who never or only partially recovery from depression continue to show overactivity in this specific spot. I tried to enter one of the studies being done in Dallas, but since I had several seizures while receiving trazodone and ECT (70 of them) in 1986, I was unable to participate in the study. Those wishing to learn more can visit www.BroadenStudy.com.
>
> The other hopeful meds in the pipeline can be viewed on www.neurotransmitter.net/newdrugs/html.
>
> Thanks,
>
> JeffThe new somatic treatments do look quite interesting. transcranial mag stimulation as well, even outside affective disorders, it has potential for autism, or even for inducing creative and altered states of consciousness at the touch of a button. It woudl be facinating to sit down and become extrondinarily creative or experience a different personality. There is also ultrasound treatment on the horizon that promises a more accurate targeting of brain region for stimulation. Its too bad you can't try out a new treatment.
Also, looking at your combination, only Li directly affects the glutamate system. I think that might be the area where new drugs become availible. have you tried adding something glu related, like a supplement like acetyl cysteine or aniracetam to MAOI(A)+TCA+Psychostimulant+Lithium? I really believe that for the hardest disorders, multifactorial approach is needed. Even one flat tire is a problem, even if you've got the other 3 aired up.
-d/r
Posted by JadeKelly on December 16, 2008, at 23:03:36
In reply to Agomelatine -) 67 days before EMEA decision., posted by CaptainAmerica1967 on December 15, 2008, at 16:18:53
Posted by Neal on December 17, 2008, at 2:28:44
In reply to Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 12, 2008, at 1:42:34
I would like to hear from others and what they've found to be effective in dealing with tough to treat refractory depression.
Effective for me was the usual ADs + bupernorphine
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