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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by Babak on September 10, 2002, at 8:01:43
Thank you for reading my posting.
I live in UK and the docs here are not familiar with Tianeptine, which is the only thing, left for me to try before going into hospital for ECT.
So I would be grateful if anyone can advise me on taking Tianeptine with Mirtazapine.
Do these two counter-act each other? Is the combination dangerous?
I have just spent a month coming off Effexor and I don't really like to go through another discontinuation with Mirtazapine. I would rather take the two together if possible.
Thanks again
Posted by seweryn on September 10, 2002, at 12:41:17
In reply to Mirtazapine with Tianeptine, posted by Babak on September 10, 2002, at 8:01:43
Do not take it together tianeptine is serotonin acting dru and it improved my mood but if you are seriously depressed try to add zyprexa 5 mg to remeron-this helped me with suicidal thoughts and acted very rapidly after thre-four days after adding.( I added zyprexa to zoloft-it was added by doctors in hospital)I think it can be added to remeron but consult it with your duck yet.
Good luck
Posted by Shawn. T. on September 11, 2002, at 2:35:51
In reply to Mirtazapine with Tianeptine, posted by Babak on September 10, 2002, at 8:01:43
You shouldn't have any problems with that combination, although consulting with your pharmacist on the issue would be advisable. Mirtazapine would likely offset tianeptine's potential side effect of insomnia. I could see tianeptine as a potential augmentation strategy especially for mirtazapine-resistant anxiety symptoms (some reports link high synaptic levels of serotonin to anxiety). As tianeptine efficacy has been shown to be highly correlated with REM density, mirtazapine would likely be an effective augmentation strategy due to its REM sleep enhancing qualities. See http://www.thieme.de/abstracts/pharmaco/agnp-abstracts1999/daten/147.html for a double bind clinical study of this phenomenon. You may want to check out Pineyro and Blier's excellent review on the autoregulation of serotonin neurons for an in depth pharmacological account of what is currently known about tianeptine. http://pharmrev.aspetjournals.org/cgi/content/full/51/3/533
If you decide that tianeptine may not be your best option, you could check out http://www.mhsource.com/pt/p020750.html for a decent discourse on currently known augmentation strategies for treatment resistant depression (the description of lithium's mechanism of action is unsubstantiated). Note that the combination of mirtazapine and bupropion is not mentioned, although I personally find the two to mix quite well (other personal reports support this notion, although no clinical studies have been conducted on the matter).
Shawn
Posted by cybercafe on September 12, 2002, at 0:53:29
In reply to Re: Mirtazapine with Tianeptine, posted by Shawn. T. on September 11, 2002, at 2:35:51
hmm.... does mirtazepine inhibit the serotonin uptake transporter? .... if so.. by what means? and how does tianeptine potentiate it's actions... and what would happen if they both tried to do the same thing at once, on a molecular level ?
> You shouldn't have any problems with that combination, although consulting with your pharmacist on the issue would be advisable. Mirtazapine would likely offset tianeptine's potential side effect of insomnia. I could see tianeptine as a potential augmentation strategy especially for mirtazapine-resistant anxiety symptoms (some reports link high synaptic levels of serotonin to anxiety). As tianeptine efficacy has been shown to be highly correlated with REM density, mirtazapine would likely be an effective augmentation strategy due to its REM sleep enhancing qualities. See http://www.thieme.de/abstracts/pharmaco/agnp-abstracts1999/daten/147.html for a double bind clinical study of this phenomenon. You may want to check out Pineyro and Blier's excellent review on the autoregulation of serotonin neurons for an in depth pharmacological account of what is currently known about tianeptine. http://pharmrev.aspetjournals.org/cgi/content/full/51/3/533
>
> If you decide that tianeptine may not be your best option, you could check out http://www.mhsource.com/pt/p020750.html for a decent discourse on currently known augmentation strategies for treatment resistant depression (the description of lithium's mechanism of action is unsubstantiated). Note that the combination of mirtazapine and bupropion is not mentioned, although I personally find the two to mix quite well (other personal reports support this notion, although no clinical studies have been conducted on the matter).
>
> Shawn
Posted by babak on September 12, 2002, at 1:00:54
In reply to Re: Mirtazapine with Tianeptine, posted by cybercafe on September 12, 2002, at 0:53:29
Thanks for all your comments, especially Shawn. T..
I think I'll give combination a go. It appears that the reduction is 5-HT concentration due to Tianeptine is a secondary effect of the drug and it is only manifested in the absence of other agents inhibiting its uptake.
Posted by Shawn. T. on September 12, 2002, at 6:49:07
In reply to Re: Mirtazapine with Tianeptine, posted by cybercafe on September 12, 2002, at 0:53:29
> hmm.... does mirtazepine inhibit the serotonin uptake transporter? .... if so.. by what means? and how does tianeptine potentiate it's actions... and what would happen if they both tried to do the same thing at once, on a molecular level ?
Mirtazapine antagonizes alpha-2 adrenergic heteroreceptors on serotonergic neurons. This results in an inhibition of the K+ current evoked release of serotonin by neurons in the dorsal raphe nucleus (where the majority of serotonin neurons reside in the brain). An alternate pathway to enhanced serotonergic activity is through the activation of alpha-1 adrenoceptors mediating serotonin cell firing. These receptors will be indirectly activated as a result of the enhanced noradrenaline release caused by mirtazapine's antagonism of alpha-2 autoreceptors.
See De Boer et al. (1994) for verification.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7912194&dopt=AbstractThe combination of tianeptine and mirtazapine could be looked at from a few different directions, the REM augmentation idea is one. On the topic of a shared activity at the molecular level, they could hypothetically interact at the level of K+ current evoked release of serotonin. A similar situation takes place in a drug free individual as serotonin auto and heteroreceptors are affected through various pathways (in addition to positive affectors such as alpha-1 adrenoceptors).
Whitton et al. (1991) have shown that in the hippocampus, tianeptine reduces the K+ evoked rise in extracellular serotonin. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=2046875&dopt=Abstract
Now considering that tianeptine may reduce extracellular serotonin in some brain areas via K+ currents while mirtazapine could increase extracellular serotonin levels, the two drugs would potentially offset each other in a fashion similar to the effect seen when mixing tianeptine and the SSRI citalopram (Celexa). Thus, tianeptine might be seen as a way to "fine-tune" extracellular serotonin levels for a person taking mirtazapine. Ideally, the CNS should maintain a relative balance between low and high serotonin levels while a person is awake (serotonin levels drop during sleep). Low extracellular serotonin levels are generally associated with depression and high levels are generally associated with anxiety, this might be seen as a spectrum from low alertness to a high level of alertness.
If tianeptine's effectiveness is correlated with levels of REM sleep, then combining it with a drug shown to improve REM sleep should result in added efficacy. See Schittecatte et al. (2002) (note that metirzapine, not mirtazapine is the selective alpha-2 antagonist, although mirtazapine has this quality among others)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11850045&dopt=AbstractFor information on metirzapine's action on REM sleep, see Ruigt et al. 1999
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2373128&dopt=AbstractFor information on 5-HT2 receptor involvement in mirtazapine's actions on sleep, see Thase (2000)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10926055&dopt=AbstractCarley and Radulovacki (1999) have shown that 5-HT3 receptor antagonism may play a role in mirtazapine's effects upon REM related sleap apnea
http://ajrccm.atsjournals.org/cgi/content/full/160/6/1824My personal speculation (e.g. lacking any concrete scientific evidence) on tianeptine's direct mechanism of action is that it binds to the low-affinity 5-HT-moduline binding site on 5-HT1B/1D receptors. This would imply that tianeptine prevents binding of 5-HT-moduline to its high-affinity binding site. Also implied is that tianeptine is a 5-HT-moduline antagonist as described by Plantefol et al. (1999)
http://www.jneurochem.org/cgi/content/full/73/6/2617?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=%225-ht-moduline%22&searchid=1031829084064_183&stored_search=&FIRSTINDEX=&fdate=1/1/1965&tdate=8/31/2002&journalcode=jneurochemI'll have to check into this idea some more; it seems to have some evidence in its favor.
Shawn
Posted by cybercafe on September 12, 2002, at 15:42:11
In reply to Re: Mirtazapine with Tianeptine » cybercafe, posted by Shawn. T. on September 12, 2002, at 6:49:07
hey shawn, good to see you again, i am interested in the endocrinological side of things now too, what was it you were talking about before? .... can you give me some terms to search for to find the messages you posted on hormones... was it mainly DHEA or cortisol or .... ??
Posted by Shawn. T. on September 12, 2002, at 18:02:54
In reply to Re: Mirtazapine with Tianeptine, posted by cybercafe on September 12, 2002, at 15:42:11
Rather than reading my old posts, you could check out http://www.neurotransmitter.net
The link under the stress heading would be a nice place to start. After you finish reading that, try the first link on the glucocorticoid page; it is the one by Bruce McEwen. The review by Wolkowitz and Reus is another one you'll probably want to read. Feel free to throw questions on those reviews that you might have at me; I should be able to answer them. I'll probably throw up a page on DHEA sometime; I haven't really done much research on that topic recently though.Shawn
Posted by cybercafe on September 12, 2002, at 21:34:34
In reply to Re: Mirtazapine with Tianeptine » cybercafe, posted by Shawn. T. on September 12, 2002, at 18:02:54
DHEA hmmm! i did ask to have my free testosterone checked as i have acne, lots of body hair, alopecia, pretty strong, and i tend to behave aggressively .... actually i do not fit in with the people at the local bipolar support group BUT i met some martial artists/bodybuilders on steroids who were VERY aggressive and moody and it was like looking in a mirror
supposedly the tests came back normal... i wonder if i just have a hyper gene expression of my testosterone receptors, Haah haah
or if i should have had free prolactin or DHEA tested, hmmmm... this is fascinating stuff
thanks for the link shawn -- i will check it out immediately
> Rather than reading my old posts, you could check out http://www.neurotransmitter.net
> The link under the stress heading would be a nice place to start. After you finish reading that, try the first link on the glucocorticoid page; it is the one by Bruce McEwen. The review by Wolkowitz and Reus is another one you'll probably want to read. Feel free to throw questions on those reviews that you might have at me; I should be able to answer them. I'll probably throw up a page on DHEA sometime; I haven't really done much research on that topic recently though.
>
> Shawn
Posted by cybercafe on September 12, 2002, at 22:00:06
In reply to Re: Mirtazapine with Tianeptine » cybercafe, posted by Shawn. T. on September 12, 2002, at 18:02:54
dammit shawn ... i am reading up on 5HT2A and i found four articles that contradict
1. 5HT2A increases firing in Naccumbens
2. 5HT2A decreases firing in Naccumbens
3. increased # of 5HT2A receptors found in suicide victims
4. decreased # of 5HT2A receptors found in suicide victimsi asked my doc about remeron for schiz once, and he said "don't get me started on that" with a condescending tone (towards *that*, not me :) )
Posted by Shawn. T. on September 13, 2002, at 3:01:12
In reply to Re: Mirtazapine with Tianeptine » Shawn. T., posted by cybercafe on September 12, 2002, at 22:00:06
>four articles that contradict
>
> 1. 5HT2A increases firing in Naccumbens
> 2. 5HT2A decreases firing in Naccumbens
> 3. increased # of 5HT2A receptors found in >suicide victims
> 4. decreased # of 5HT2A receptors found in >suicide victims1. that seems to be the case
2. where did you read that?
3. this data could possibly be interpreted as suicides that were caused by major depression
4. this data could possibly be interpreted as suicides that were caused by an anxiety disorder or bipolar disorder (where did you read this?)
I'll have to expand upon the Remeron(mirtazapine)/atypical antipsychotic connection sometime. 5-HT2 receptor antagonism combined with 5-HT1A activation seems to be a mechanism of efficacy in treating schizophrenia (check out the link at the bottom of the message). This implies that low dose Remeron wouldn't cut it for schizophrenia treatment; 30-45mg would likely be needed to see benefits (alpha-2 antagonism kicks in at higher doses). One link between 5-HT1A activation and 5-HT2A antagonism is that both actions cause K+ channels to close. That causes an increase in tyrosine hydroxylase, which is the rate limiting enzyme in the production of dopamine and noradrenaline (more tyrosine hydroxylase = more dopamine). It is interesting to note that Remeron has been shown to increase dopamine in the prefrontal cortex, which adds some clout to my claim. I'm beginning to realize that 5-HT2A antagonism without 5-HT2C antagonism results in some undesirable consequences. With regards to the nucleus accumbens, if 5-HT2A receptors are antagonized without 5-HT2C antagonism, dopamine is decreased in the nucleus accumbens. This is because 5-HT2C receptors in the ventral tegmental area exert a tonic inhibitory control upon dopamine release in the accumbens. The big downfall of M 100907 is that it is an inverse agonist at 5-HT2C receptors, which means that it activates the PLA-2-AA signalling cascade ... 5-HT2A receptors do the same thing. Regular agonists at 5-HT2A receptors normally activated the PLC beta2 signalling cascade (PLC beta2 -> IP3/DAG). See my pages on 5-HT2A and 5-HT2C for verification of these claims (I'm working on a Remeron page).
Ichikawa, Junji, Ishii, Hideo, Bonaccorso, Stefania, Fowler, Wiley L., O'Laughlin, Ian A., Meltzer, Herbert Y.
5-HT2A and D2 receptor blockade increases cortical DA release via 5-HT1A receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release
J Neurochem 2001 76: 1521-1531
"These results suggest that the atypical APDs via 5-HT2A and D2 receptor blockade, regardless of intrinsic 5-HT1A affinity, may promote the ability of 5-HT1A receptor stimulation to increase mPFC DA release, and provide additional evidence that coadministration of 5-HT2A antagonists and typical APDs, which are D2 antagonists, may facilitate 5-HT1A agonist activity." http://www.jneurochem.org/cgi/content/abstract/76/5/1521
This is the end of the thread.
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