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Dr. Bob is Robert Hsiung, MD,
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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
Posted by SLS on December 17, 2008, at 5:29:10
In reply to Re: Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 16, 2008, at 20:39:02
I would like to add that a treatment strategy that can be very effective is to add an atypical neuroleptic, of which Abilify and Geodon are emerging as the most effective.
- Scott
Posted by SLS on December 17, 2008, at 5:43:01
In reply to Re: Treatment Resistant (Refractory) Depression, posted by desolationrower on December 16, 2008, at 21:56:34
I understand that lithium is thought to directly inhibit the reuptake of glutamate, but I am still unclear as to how it can stabilize and limit glutamatergic excitation. I recall something involving NMDA receptors, but I don't know if lithium acts directly to change the conformation of the transporter molecule. What else does lithium do to influence glutamate activity? How might protein kinase-C inhibition affect glutamate?
Thanks.
- Scott
Posted by CaptainAmerica1967 on December 17, 2008, at 10:05:57
In reply to Re: Treatment Resistant (Refractory) Depression, posted by desolationrower on December 16, 2008, at 21:56:34
Thanks for your response.
"acetyl cysteine or aniracetam"- yes I tried both of these; I've been into holistic health for years (Life Extension Foundation) and have taken acetyl cysteine before.
I've tried aniracetam and some other "smart drugs" after reading the book "Smart Drugs & Nutrients years ago by Ward Dean, M.D..I've been very interested in NMDA receptor antagonists after the news of ketamine having such a profound and lasting effect on TRD and looked into going to the NIMH in Bethesda, MD, for a ketamine study on treatment resistant depression but it would have meant having to go off the antidepressant I was taking at the time or any antidepressant for that matter for a washout time and I get severely non functional just after being off them for two days. I've tried memantine without any benefit and have thought about trying the med for ALS(Lou Gehrig's Disease) called Riluzole which is also a potent glutamate blocker or NMDA receptor antagonist (clinicaltrials.gov), but the cost is phenomenol at $10-$20 per pill and the dose of at least two per day.
I thought about trancranial magnetic stimulation (TMS), but since I failed a course of 70 ECT treatments, the TMS wouldn't likely to anything.
I'm also interested in cortisol blockers being studied.
Jeff
Posted by SLS on December 17, 2008, at 10:18:43
In reply to Re: Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 17, 2008, at 10:05:57
I suffered a negative reaction from taking Provigil. Nevertheless, I am suspicious that it might make a good adjunct to MAOIs.
By the way, what treatments are you aware of that you have not yet tried?
- Scott
Posted by CaptainAmerica1967 on December 17, 2008, at 20:18:14
In reply to Re: Treatment Resistant (Refractory) Depression, posted by SLS on December 17, 2008, at 10:18:43
"By the way, what treatments are you aware of that you have not yet tried?"
Deep brain stimulation-hopefully it will continue to show promise in treating severe treatment resistant depression and will be approved even though I don't like surgery as there's always a risk.
Other than that, there's not much I haven't tried except some drugs going through clinical trials.
http://neurotransmitter.net/newdrugs.html
or www.clinicaltrials.gov
-CRF antagonistsI'm still really interest in ketamine (NMDA antagonsit), but cannot or will not get off my current meds (was out) in order to be able to participate in the study. http://clinicaltrials.gov/ct2/show/NCT00088699?cond=%22Depression%22&rank=35
Riluzole(an inhibitor of glutamate release)-indicated for ALS, but studies on going like ketamine.
Also meds that increase brain-derived neurotrophic factor (BDNF) as antidepressants and physical exercise increase levels in the brain and those with depression have reduced levels.
Cysteamine bitartrate (Cystagon), an FDA approved med for the treatment nephropathic cystinosis, has been shown to increase BNDF in neuronal tissue, and to stimulate cell growth.
Posted by SLS on December 17, 2008, at 20:55:15
In reply to Re: Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 17, 2008, at 20:18:14
I did not respond to riluzole. Nothing good - nothing bad.
I also tried mifepristone. I did not like it. I felt very washed-out at the end of the week, and less well overall.
Did you ever combine Provigil with an MAOI?
- Scott
Posted by CaptainAmerica1967 on December 17, 2008, at 21:11:43
In reply to Re: Treatment Resistant (Refractory) Depression, posted by SLS on December 17, 2008, at 20:55:15
No, I haven't used Provigil with an MAOI. I used Provigil with other meds such as Cymbalta but I still felt sleeply most of the time, however, I was taking so many other meds at the time too such as pindolol, thyroid, various amphetamines, Lamictal.
Currently I'm taking Parnate, Nortriptyline, Lithium Orotate and amineptine.
Vigorous physical exercise can make feel completely normal for temporary afterwards as can total sleep deprivation.
Posted by desolationrower on December 17, 2008, at 23:01:12
In reply to Re: Treatment Resistant (Refractory) Depression, posted by CaptainAmerica1967 on December 17, 2008, at 21:11:43
If you haven't tried buprenorphine or lowdose naltrexone, i think that would be the obvious thing. I think they either could be taken with current regimine.
Dextromethorphan has some similarities to ketamine. It has strong affinity for the SERT (i think, info is hard to come by) so definatly not something you can take with parnate. I think it has some specific dopaminergic activity as well, and sigma. Of course, i have no idea if this would be benefical long-term, but it is another easily avilible uncompetitive NMDA antagonist
Did you try the memantine with the current drugs, and did you take at least 40mg? It seems to be more effective at higher doses. I'm asking again as some of the studies show subtherapeutic mem+tca or other AD results in full antidepressant effect.
Also, have you tried adding NAC to your current drugs.
Scott, you've mentioned modafinil+MAOI as synergistic, any particular reason? I haven't noticed any strong effect from adrafinil with parnate and my other stuff, n=1. Oh and wherever it was mentioned, i don't know about specific Li/Glu interaction or PCK. I believe it increases glu uptake chronically. Given Mgs role in the NMDA receptor, i'd think it interacts in some fashion.
-d/r
Posted by CaptainAmerica1967 on December 18, 2008, at 4:06:01
In reply to TRD --SLS, CPTAmerica, posted by desolationrower on December 17, 2008, at 23:01:12
Thanks for your feedback.
I haven't tried buprenorphine, but have been interested in it as I'm interested in almost anything that could bring about a better life. I'm not sure about the drug interaction with Parnate and would have to do some more research on it. I have a gut feeling my depression could be related to some sort of malfuncition with the hypothalamus-pituitary-adrenal axis (hot flashes or feeling warm all the time)-cortisol, endorphins, neurotransmitters. Obviously exercise affects mood as a result from many different physiological mechanisms, but it's only the intense physical exercise that produces the slight euphoria and antidepressant effect I feel which could be attributed to endorphins hence buprenorphine or naltrexone might help. Also, my father got "hooked" on heroin the first time he tried it in 1972 and died from an accidental overdose (sad to know that the following day he was suppose to go in for treatment, but never made it) so this could point to my depression as having some type of opioid dysfunction. Dextromethorphan would be interesting to try too if I weren't on an MAOI.
I cannot recall the dose of memantine (10mgs twice day or whatever the dose was BID). NAC is in my life extension multivitamin mix and I've used it for years.
Regards,
Jeff
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