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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 27. This is the beginning of the thread.
Posted by cakethread on October 22, 2016, at 0:36:31
I've tried most things from TCAs to atypical antipsychotics to MAOIs. I think I may have unusual neurophysiology or am a non-responder.
At this point I've been researching alternatives. Some things I've been looking into:
Nootropics for depression (i.e., http://www.focuswish.com/nootropics-for-depression/) - especially tianeptine
NSI-189 (Anyone heard of this? It's unobtainable but promising)
ECT
TMS
Ketamine
Scopolamine?
A few of these ideas are far out/unlikely to work..which reflects my current state of desperation.
Any ideas?
Posted by SLS on October 22, 2016, at 8:44:53
In reply to Best alternative treatments for depression?, posted by cakethread on October 22, 2016, at 0:36:31
Hi.
I suggest that ketamine taken intranasally be at the top of your list. It works on a large percentage of treatment-resistent depression. It is only a minority of people who will not benefit from it at all. Unfortunately, I am in that minority. I have seen several people attain full remission with ketamine. Genetics seems to determine the responsivity to it. There are three alleles for the gene on chromosome 11 that controls BDNF production. There is one good one (val66val), one middle one (val66met), and one really bad one (met66met). The good one occurs in 75 percent of people, so you have a good chance of responding to it. Some people can dose once every 5 days to maintain remission. If ketamine is to work, it should work within a few days to a week. Side effects are minimal. I did not experience any.
- Scott
Posted by Lamdage22 on October 22, 2016, at 11:00:36
In reply to Best alternative treatments for depression?, posted by cakethread on October 22, 2016, at 0:36:31
i wouldnt do ECT. Ketamine first definitely. I cant do it as i am schizo affective. I think anything "schizo" and Ketamine dont agree.
Posted by SLS on October 22, 2016, at 13:38:23
In reply to Re: Best alternative treatments for depression?, posted by Lamdage22 on October 22, 2016, at 11:00:36
> i wouldnt do ECT. Ketamine first definitely. I cant do it as i am schizo affective. I think anything "schizo" and Ketamine dont agree.
It would be interesting to know if you respond to the major ketamine metabolite, hydroxynorketamine (HNK). HNK does not interact with NMDA receptors nor does it produce a psychotic reaction when administered. Apparently, NMDA receptor antagonism is not required for ketamine to exert its antidepressant effects. It is more likely that the mechanism involves the activation of AMPA glutamatergic neurons. NMDA receptor antagonism does increase AMPA somewhat. However, this site is located upstream, and its effects are not very robust. When AMPA stimulation increases, BDNF (brain-derived neurotrophic factor) and mTOR (mammalian target of rapamycin) are increased in the hippocampus and prefrontal cortex. It may also be that increasing AMPA also increases catacholamine neurotransmitters (NE and DA) acutely. This might explain why the initial antidepressant effect is so rapid, but I'm not sure.
I would not hesitate to try HNK if it were to become available. As you comb through the literature, keep an eye out for drugs that stimulate AMPA receptor glutamatergic activity and BDNF production. Have you ever tried amitriptyline? What about sarcosine?
- Scott
Posted by Lamdage22 on October 23, 2016, at 10:04:23
In reply to Re: Best alternative treatments for depression? » Lamdage22, posted by SLS on October 22, 2016, at 13:38:23
I have tried nortriptyline but not amitryptiline. Sarcosine gave me akathisia! It helped a tad with mood but not enough to make it worthwile.
I am not a fan of sexual side effects being 27.
if HNK increases DA, doesnt that mean its a bad idea for me? I am looking forward to Glyx-13
Posted by SLS on October 23, 2016, at 10:42:38
In reply to Re: Best alternative treatments for depression?, posted by Lamdage22 on October 23, 2016, at 10:04:23
> I have tried nortriptyline but not amitryptiline. Sarcosine gave me akathisia! It helped a tad with mood but not enough to make it worthwile.
>
> I am not a fan of sexual side effects being 27.
>
> if HNK increases DA, doesnt that mean its a bad idea for me? I am looking forward to Glyx-13What causes sexual side effects?
How does HNK increase DA while GLYX-13 doesn't?
- Scott
Posted by TriedEveryMedication on October 23, 2016, at 11:25:31
In reply to Best alternative treatments for depression?, posted by cakethread on October 22, 2016, at 0:36:31
I tried NSI-189, or what was purported to be NSI-189. (I did diligence - I believe it was actually NSI-189)
The effects were very subtle, if at all. I don't believe it had any benefit for me. But there are people on longecity who swear it works great. But those might be sockpuppet accounts for those who sell it.
To me it seems pretty doubtful that it is efficacious.
Especially since it has an unknown MOA, and appears to have no known receptor activity.
If my insurance shiznit gets straightened out, I will be trying out rTMS soon.
Ketamine seems very promising, but my doctor says it has to be slowly infused for it to work right.
Posted by Lamdage22 on October 23, 2016, at 12:04:05
In reply to Re: Best alternative treatments for depression? » Lamdage22, posted by SLS on October 23, 2016, at 10:42:38
> > I have tried nortriptyline but not amitryptiline. Sarcosine gave me akathisia! It helped a tad with mood but not enough to make it worthwile.
> >
> > I am not a fan of sexual side effects being 27.
> >
> > if HNK increases DA, doesnt that mean its a bad idea for me? I am looking forward to Glyx-13
>
> What causes sexual side effects?Nortriptyline, Effexor, Cymbalta, Sertraline.
>
> How does HNK increase DA while GLYX-13 doesn't?I dont know!
> - Scott
Posted by SLS on October 23, 2016, at 12:07:28
In reply to Re: NSI-189 » cakethread, posted by TriedEveryMedication on October 23, 2016, at 11:25:31
> Ketamine seems very promising, but my doctor says it has to be slowly infused for it to work right.
Yes. When using ketamine IV, the dose is administered at a rate of 0.5 mg/kg over 40-minutes.
Ketamine *can* work just fine intranasally. Unfortunately, it had no effect on me. The only two other people I know of who tried it achieved remission and have maintained it for several years. One of them doses herself once every 5 days. The dose can be finessed by counting the number of inhalations performed. However, if one fails to respond to intranasal administration, one might still respond well to IV. I opted for intranasal to try first simply because of its convenience. You know within a week if it is going to work, so you aren't really wasting much time by trying it first.
I would like to emphasize that NMDA receptor antagonism is *not* necessary for ketamine or similar such drugs to exert an antidepressant effect. The focus on NMDA has been a bit of a distraction. The real site of action is AMPA glutamatergic neurons. In fact if you block AMPA receptors, ketamine doesn't work.
- Scott
Posted by Lamdage22 on October 23, 2016, at 12:08:24
In reply to Re: Best alternative treatments for depression? » Lamdage22, posted by SLS on October 22, 2016, at 13:38:23
Sunifiram and Unifiram?
Posted by SLS on October 23, 2016, at 12:10:50
In reply to Re: Best alternative treatments for depression?, posted by Lamdage22 on October 23, 2016, at 12:08:24
> Sunifiram and Unifiram?
I'm not familiar with those.
- Scott
Posted by SLS on October 23, 2016, at 12:44:57
In reply to Re: Best alternative treatments for depression?, posted by Lamdage22 on October 23, 2016, at 12:04:05
> > How does HNK increase DA while GLYX-13 doesn't?
> I dont know!I must have misunderstood you. Sorry.
- Scott
Posted by SLS on October 23, 2016, at 12:49:46
In reply to Re: NSI-189 » TriedEveryMedication, posted by SLS on October 23, 2016, at 12:07:28
> > Ketamine seems very promising, but my doctor says it has to be slowly infused for it to work right.
> Yes. When using ketamine IV, the dose is administered at a rate of 0.5 mg/kg over 40-minutes.
>
> Ketamine *can* work just fine intranasally. Unfortunately, it had no effect on me. The only two other people I know of who tried it achieved remission and have maintained it for several years. One of them doses herself once every 5 days. The dose can be finessed by counting the number of inhalations performed. However, if one fails to respond to intranasal administration, one might still respond well to IV. I opted for intranasal to try first simply because of its convenience. You know within a week if it is going to work, so you aren't really wasting much time by trying it first.
>
> I would like to emphasize that NMDA receptor antagonism is *not* necessary for ketamine or similar such drugs to exert an antidepressant effect. The focus on NMDA has been a bit of a distraction. The real site of action is AMPA glutamatergic neurons. In fact if you block AMPA receptors, ketamine doesn't work.Compounded ketamine is inexpensive. Hopefully, there is a compounding pharmacy near you.
http://ecompoundingpharmacy.com/
- Scott
Posted by Horse on October 23, 2016, at 15:29:06
In reply to Best alternative treatments for depression?, posted by cakethread on October 22, 2016, at 0:36:31
Vit D, thyroid, T3, light box, stimulants? Any combination. My Vit D has to be very high, just me. I need a combination of treatments plus exercise, sunlight. I also take an atypical ssri (trintellix). I don't know much else....segiline?
Just throwing stuff out there. I've heard good things about TMS if one is mildly depressed, although someone here may have different information.
good luck
Posted by Horse on October 23, 2016, at 15:29:49
In reply to Re: Best alternative treatments for depression? » cakethread, posted by Horse on October 23, 2016, at 15:29:06
sleep test > cpap?
Posted by Lamdage22 on October 23, 2016, at 15:52:23
In reply to Re: Best alternative treatments for depression? » cakethread, posted by Horse on October 23, 2016, at 15:29:06
to me vitD is crucial. See signature
Posted by Hugh on October 23, 2016, at 18:29:15
In reply to Best alternative treatments for depression?, posted by cakethread on October 22, 2016, at 0:36:31
Deep TMS penetrates 6 or 7 cm into the brain, while regular TMS penetrates 1.5 cm. JohnLA wrote this thread about his experiences with Deep TMS:
http://www.dr-bob.org/babble/20140717/msgs/1069147.html
Near-infrared light therapy (NILT) is being used at a clinic near Denver. This post contains information about this treatment:
http://www.dr-bob.org/babble/20160131/msgs/1086183.html
My depression and anxiety have been helped by neurofeedback. I suggest reading A Symphony in the Brain by Jim Robbins.
Two-thirds of people who suffer from depression have high levels of inflammation. New anti-inflammatories are being tested as a treatment for depression.
http://www.cnn.com/2016/10/18/health/anti-inflammatory-drugs-depression/
I recently started taking cetyl myristoleate, an esterified fatty acid that's supposed to increase IL-10 (an anti-inflammatory) production. It improves my mood.
http://www.swansonvitamins.com/swanson-ultra-celadrin-90-sgels
Posted by TriedEveryMedication on October 30, 2016, at 14:43:46
In reply to Re: Best alternative treatments for depression?, posted by Hugh on October 23, 2016, at 18:29:15
someone on longecity has found Infrared LED arrays on ebay/amazon for 40 bucks and has played around with it.
Posted by Jonhed on October 31, 2016, at 10:55:05
In reply to Re: NSI-189, posted by SLS on October 23, 2016, at 12:49:46
The thing about ampa receptors is interesting!
I have abused ketamine for a while and I find that when on memantine, I can't seem to get "high" of ketamine, and I think that it has to do with the ampa receptors being blocked in some way or just that memantine is voltage gate dependant and doesn't "allow" ketamine to shut down my glutamate receptors..
Just an interesting thing.
I also know that when iv'ing ketamine you activate the u-opioid receptor to a much greater extent than when you use it intranasal. Mostly because you need very high doses to make it function as an full agonist at that site.
And yeah, you are definitely right about the ampa receptors being the necessary site to block, cause the glutamate site just gives you the dissociative effect.
Posted by Jonhed on October 31, 2016, at 10:56:40
In reply to Re: NSI-189, posted by Jonhed on October 31, 2016, at 10:55:05
*read "have abused". I don't do it now a day's.
Posted by Hugh on November 2, 2016, at 0:22:15
In reply to Re: infrared treatment » Hugh, posted by TriedEveryMedication on October 30, 2016, at 14:43:46
Interesting. Thanks. I like the price. I posted the following about my experiences with near-infrared light therapy:
http://www.dr-bob.org/babble/alter/20160521/msgs/1090458.html
Posted by SLS on November 2, 2016, at 5:42:16
In reply to Re: infrared treatment » TriedEveryMedication, posted by Hugh on November 2, 2016, at 0:22:15
> Interesting. Thanks. I like the price. I posted the following about my experiences with near-infrared light therapy:
>
> http://www.dr-bob.org/babble/alter/20160521/msgs/1090458.htmlIt is interesting that the frequency at which rTMS is applied to the left forehead is 10 MHz.
- Scott
Posted by elanor roosevelt on November 2, 2016, at 18:28:08
In reply to Best alternative treatments for depression?, posted by cakethread on October 22, 2016, at 0:36:31
I have some tianeptine and use it as-needed. I find it to be good as a mod lifter. have to take it throughout the day or may get headaches. For me it's pro-social and pro-sexual. Sadly, it triggers my nervous mouth habits and I can only take it for 2 or 3 days before the damage I do to my mouth gets to be too much.
Tried to buy amineptine online last year and lost $400 into cyberspace rip off land
Posted by SLS on November 2, 2016, at 20:35:12
In reply to tianeptine, posted by elanor roosevelt on November 2, 2016, at 18:28:08
> I have some tianeptine and use it as-needed. I find it to be good as a mod lifter. have to take it throughout the day or may get headaches. For me it's pro-social and pro-sexual. Sadly, it triggers my nervous mouth habits and I can only take it for 2 or 3 days before the damage I do to my mouth gets to be too much.
> Tried to buy amineptine online last year and lost $400 into cyberspace rip off landHave you tried Viibryd (vilazodone) or Trintellix (vortioxetine)? Both drugs are a sort of serotonin system modulator. I found Viibryd to be devoid of sexual side effects and transiently effective. The properties of Trintellix include serotonin 5-HT7 antagonism. I haven't tried Trintellix, but my doctor likes it. It is known to improve cognition.
- Scott
Posted by elanor roosevelt on November 4, 2016, at 0:41:25
In reply to Re: tianeptine » elanor roosevelt, posted by SLS on November 2, 2016, at 20:35:12
> > I have some tianeptine and use it as-needed. I find it to be good as a mod lifter. have to take it throughout the day or may get headaches. For me it's pro-social and pro-sexual. Sadly, it triggers my nervous mouth habits and I can only take it for 2 or 3 days before the damage I do to my mouth gets to be too much.
> > Tried to buy amineptine online last year and lost $400 into cyberspace rip off land
>
> Have you tried Viibryd (vilazodone) or Trintellix (vortioxetine)? Both drugs are a sort of serotonin system modulator. I found Viibryd to be devoid of sexual side effects and transiently effective. The properties of Trintellix include serotonin 5-HT7 antagonism. I haven't tried Trintellix, but my doctor likes it. It is known to improve cognition.
>
>
> - Scottthanks scott
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