19 replies to this topic

[Chanterix]

I had good success treating depression with tianeptine several years ago, but need some augmentation strategies at the present.

There is an article (can't post links yet) called "NMDA and AMPA receptors are involved in the activity of tianeptine in the forced swim test in mice."

L-701,324, a glycine site NMDA antagonist boosted the effects of tianepine.



I am looking for a glycine site NMDA antagonist, it doesn't matter if it is weak as I am mainly looking for something to augment tianeptine.

Are there any such compounds available (herbs, pharms, research, etc.)?

(also, sildenafil boosts brain concentrations of tianeptine so that may be another option).

Edited by Chanterix, 23 January 2014 - 03:20 AM.

[Tom_]

Using off licence drugs isn't a great idea. Furthermore when agumenting an antidepressant the aim should be to hit receptors that aren't already being touched rather than banging your head against the same door. Your best bet is to combine with an SSRI. Fluoxetine has been shown to augment Tianeptine in humans - which is the best evidence you are going to get when it comes to Tianpetine augmentation. NMDA antagonists also often come with nasty cognitive side effects.

If Tianeptine is an SSRE (something I doubt) then combining it with a Serotoninergic antagonist (Mirtazapine or Trazadone) may prove an effective way to go. Both are effective antidepressants anyway and adding one of those in should do the trick anyway.

Another option is Bupropion which acts as a NDRI primarily in the pre-frontal cortex as well as an Nictonic antagonist.

But before you decide to use another drug are you on a maximum dosage (50mg) and have you been on it for four to six weeks? If the answer is no the chances are you won't need another drug and a simple dose increase by 12.5mg is all that's needed.

[Chanterix]

Thanks you for your solid advice.

l will go ahead and try something with a different mechanism of action.

I'll give agomelatine a try at 1 tablet each night.

I think the tianeptine is working well at 60% symptom relief and something to push it up to 80% would be all that's needed.

I was a medical student until some traumatic events and my depression kicked my ass.
Hopefully, I will recover and be back at my studies next year.

[Tom_]

Sorry to hear that.

Are you on 50mg of Tianeptine? If you aren't its worth increasing the dose rather than adding in another medication. And have you considered psychotherapy, its the ideal adjunct to medication and approximately as effective by itself. Medication AND psychotherapy is more effective than medication alone.

Agomelatine is quite a specialised antidepressant and doesn't have a great evidence base. Its may be particularly effective in depression that has obvious and severe circadian disturbances or insomnia symptoms (although Mirtazapine or Trazadone are still likely to be better options). I would recommend an SSRI, SNRI or Mirtazapine over due to a much greater evidence base.

[Chanterix]

Thanks for the tip on SSRIs/SNRIs, but I am a non-responder to those medications (well tested on me).
Trazodone and mirtrazapine seem to have some negative side effects (weight gain, sexual), so I want to try agomelatine first.

I do have a very inconsistent sleep/wake cycle at the moment which may be helped.

[Tom_]

That is fair enough, Agomelatine is a good option.

While ADs might help with sleep the best treatment for persistant insomnia or fucked sleep/wake cycle is sleep hygine.

[Chanterix]

Yes, lifestyle changes are the best way to improve quality of life. Medications simply augment healthy diet, exercise, and intellectual stimulation.

[Tom_]

That entirely depends on the condition you are talking about. If its a moderate to severe major depressive episode then research consistently shows medication to be the most effective followed closely by psychotherapy and then lifestyle changes following quite far behind.

If its a personality disorder psychotherapy takes the lead followed by lifestyle changes and medication.

If its schizoprhenia or Bi-polar medication are by the far most effective treatment effective treatment followed by lifestyle changes and psychotherapy is typically less effective.

Each disorder responds better to different treatments.

[Chanterix]

Well, I can agree with that. Its too bad that there are so few effective antidepressants and precious few good psychotherapists.

Tianeptine was wonderful several years ago, but it is no longer doing as well as it did in the past. The good thing is that I know that there are solutions to these problems. After having experienced how well tianeptine brightened my mood and without a serious depressive relapse in years, I know that there are things out there that work.

I'm looking forward to trialing agomelatine. A recent study shows that 5ht2c antagonists exert a fast antidepressant effect.

Edited by Chanterix, 28 January 2014 - 03:01 AM.

[Tom_]

There are over 40 marketed antidepressants, all of them have proved to be effective. However some people prove not to respond to them, often because of psudoresistance and sometimes because of genuenine resistance. People tend to respond about in equal parts to a psychotherapy and to the psychotherapist, there are plenty of good psychotherapists but not everyone is matched up to the appropiate psychotherapy and/or psychotherapaist.

Taking testosterone supplementation is dangerous unless you actually have clinical hypotestosteronism and there is certainly no reason to believe provided you are within range it will do you any good.

[Joe Monroe]

low dose ketamine?

[Tom_]

He isn't severely depressed with an ultra high risk of suicide, with failed ECT. Low dose IV ketamine is clearly not indicated.

[Chanterix]

Ketamine is available to those who have the money. Private clinics offer the treatment for moderate/severe depression that is resistant to available drugs. The main factor is having the cash to pay for it. I have also read reports of people successfully treating depression with subcutaneous or IM injections of ketamine at home. However, since tianeptine is already having an effect on the glutamate system, it is possible that ketamine would not be effective in my case. Clearly, a trial of agomelatine would be much cheaper and safer than a trial of ketamine, so that is the first line of treatment.

Drugs that I have previously trialed and failed on (many years ago): multiple SSRIs, SNRIs, a TCA(one with effects on SE and NE), NDRIs (including stimulants), and last but not least, MAOIs(3 different ones). Partial success with lamotrigine which may act by inhibiting glutamate release and complete success with tianeptine which may act by affecting the AMPA/NMDA balance. This seems to point in the direction of drugs acting on the glutamate system. Already I am adding the supplements magnesium and NAC with moderate benefits. Two drugs worth trialing are memantine and acamprosate. God, psychopharmacology is fascinating. If it paid well, I would consider a career as a psychiatrist (but they don't earn well where I live). I'll probably end up in a surgical specialty. Good motivation to work to get out of this rut and back to studies.

[Tom_]

I didn't realise you were this treatment resistant. Can you list the names of the drugs you have tried?

[Chanterix]

SSRI
citalopram-not effective
escitalopram-not effective
paroxetine-not effective

SNRI
venlafaxine-not effective

Stimulant type
bupropion-not effective
modafinil-moderately stimulating, not useful longterm
amphetamine-moderately stimulating, not useful longterm
methylphenidate-very stimulating, not useful longterm


MAOI
selegiline-not effective as antidepressant, low doses good for attention/focus
phenelzine-not effective
tranylcypromine-not effective

TCA
amytriptiline-mild effect on mood, very sedating

Benzodiazepine
clonazepam-not useful long term
temazepam-sedative, not useful


Dopamine Antagonist
low dose sulpiride-mild stimulation, not effective

Opiate
buprenorphine- dulling, not useful
hydrocodone- not useful long term

Mood stabilizer
lithium-no effect

Thyroid
T3- modest positive effect

Glutamate
N-acetylcysteine-modest positive effect
lamotrigine-partial success
tianeptine-successful

Nicotine
cigarettes-modest positive effect

Nutrition/supplements
restricted calorie intake/healthy food-helpful
SAM-e-modest positive effect
creatine-modest positive effect
sulbutiamine-unclear, mild

Behavior
sleep deprivation-temporarily helpful
psychotherapy- sometimes helpful
exercise-successful

UPCOMING trials:
acamprosate
memantine
methylfolate
cannabidiol
agomelatine


Retrial:
T3 (25-50 mcg)

Current medicines:
tianeptine

Current supplements:
creatine
SAM-e (will taper off, effects do not justify the price)

Behavior:
get back on a diet and exercise program!
start therapy (cognitive-behavioral)
light therapy lamp

[Tom_]

If you already had a course of CBT it might be worth trying a more analytic and/or group therapy. IPT has an equally high success rate.

Treatment with standard mono-amine drugs may well work - very well - but longer trials might be needed or supra-theraputic doses. The one class of drugs you haven't really tried are antipsychotics and they are some of the most successful at treating refactory mood disorders. You did try Sulpride but at low doses it acts as an antagonist to pre-synaptic receptors actually increasing dopamine out-put. A trial of Quetiapine may prove more effective although Aripiprazole a dopamine partial agonist with 5ht1a parital agonism (both have serotonergic antagonisic properties a drug trait I've noticed you haven't tried) may also prove very effective. The minimum trial time before you decide they are no good is around 10-12 weeks (as with most drugs). Mirtazapine may also be worth a shot.

You also mentioned a re-trial of t3. If you do for it with careful monitoring I think you should try a higher dose. Start with 25 and titrate to between 50-80mcg. Doses as high as 150 have been used successfully without conversion to hypothryoidism but I think a proper trial of an atypical antipsychotic at mood stabilizing doses may be the best option.

Edited by Tom_, 28 January 2014 - 09:22 PM.

[Chanterix]

Oh. Forgot to mention:
Buspirone:not effective for depression, OK anxiolytic.
Hydroxizine: potent anxiolytic, weight gain


I had a friend go on aripiprazole an he hated it. Said it kept him from feeling sad but didn't allow any pleasure either. Weight gain, hyperprolactinemia/sexual dysfunction, and movement disorders don't sound like fun.

I would rather try some other treatments.
T3, methylfolate, competitive and noncompetive NMDA antagonists, agomelatine

People like Steven Stahl (of Stahl's psychopharmacology) push the drugs that make the most profit for big companies. Things like T3, ketamine therapy, and drugs by smaller companies(agomelatine) get overlooked. These treatments seem much more appealing than antipsychotics. I'm a med student so I know many doctors are pretty stupid, corrupt, and uncaring so I disregard mainstream medical wisdom.

Edited by Chanterix, 31 January 2014 - 07:06 PM.

[Joe Monroe]

you can get ketamine on silk road 2.0 for ... well depends where you live but a gram wouldn't cost more than 90 bucks. Which is kinda pricey but you know what you're getting if you use a reputable vendor

[Chanterix]

Hello

What an interesting discussion.

Edited by Chanterix, 06 February 2022 - 06:21 PM.

[sensei]

Have you tried LOW DOSE naltrexone?