![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 4 to 28 of 37. Go back in thread:
Posted by SLS on June 27, 2010, at 15:43:12
In reply to Re: A thread for SLS, posted by ed_uk2010 on June 27, 2010, at 15:26:15
> > Is agomelatine available in the UK yet?
> Yes, it's been available for some time now but it's rarely used.That's interesting. How do you account for that? Are UK psychiatrists usually slow to embrace new treatments?
What are your impressions of agomelatine? The drug company certainly touts is as being effective for severe depression.
I hope life is treating you well.
Take care, Ed.
- Scott
Posted by ed_uk2010 on June 27, 2010, at 16:35:11
In reply to Re: A thread for SLS » ed_uk2010, posted by SLS on June 27, 2010, at 15:43:12
>That's interesting. How do you account for that? Are UK psychiatrists usually slow to embrace new treatments?
Yes, they seem to be reluctant to do or prescribe anything new or different.
>What are your impressions of agomelatine?I think it's too early to say what role it will have in the treatment of severe depression. It seems to be well tolerated but the occasional elevation of liver enzymes can be a concern.
Med_amorphosis, in an earlier thread, has reported benefits from an MAOI + Surmontil combination. Have you tried this Scott?
Posted by SLS on June 27, 2010, at 18:35:12
In reply to Re: A thread for SLS, posted by ed_uk2010 on June 27, 2010, at 16:35:11
> Med_amorphosis, in an earlier thread, has reported benefits from an MAOI + Surmontil combination. Have you tried this Scott?
I once tried Surmontil by itself. I think that I get more out of nortriptyline. I'm glad to know that Surmontil and an MAOI can be combined safely. I'll keep it in mind, but I wouldn't discontinue nortriptyline at this juncture.
Thanks.
This is a difficult time for me.
- Scott
Posted by Dinah on June 28, 2010, at 9:49:01
In reply to Re: A thread for SLS » ed_uk2010, posted by SLS on June 27, 2010, at 18:35:12
I've no advice. I just wanted to say that I'm sorry this is a difficult time for you. I wish nothing but the best for you.
Posted by SLS on June 28, 2010, at 19:05:49
In reply to Re: A thread for SLS » SLS, posted by Dinah on June 28, 2010, at 9:49:01
> I've no advice. I just wanted to say that I'm sorry this is a difficult time for you. I wish nothing but the best for you.
Thanks, Dinah. That means a lot to me.
- Scott
Posted by Phillipa on June 30, 2010, at 13:53:30
In reply to Re: A thread for SLS » Dinah, posted by SLS on June 28, 2010, at 19:05:49
Same here Phillipa
Posted by ed_uk2010 on June 30, 2010, at 14:43:33
In reply to Re: A thread for SLS » ed_uk2010, posted by SLS on June 27, 2010, at 18:35:12
Hi Scott,
Am I right that you're restarting Nardil? I hope it helps. Are you planning on titrating to a higher dose this time?
Posted by SLS on June 30, 2010, at 15:35:59
In reply to Re: A thread for SLS » SLS, posted by ed_uk2010 on June 30, 2010, at 14:43:33
> Hi Scott,
>
> Am I right that you're restarting Nardil? I hope it helps. Are you planning on titrating to a higher dose this time?
I'm going to target 90mg, which is the same dosage I used the last time. Maybe having lithium on board this time will help. Going back to Nardil this time is, in a way, an admission of defeat.
- Scott
Posted by ed_uk2010 on June 30, 2010, at 15:46:33
In reply to Re: A thread for SLS » ed_uk2010, posted by SLS on June 30, 2010, at 15:35:59
>Going back to Nardil this time is, in a way, an admission of defeat.
Try to think of it as a temporary measure until you decide on a new treatment strategy.
Posted by Justherself54 on June 30, 2010, at 18:55:57
In reply to Re: A thread for SLS » ed_uk2010, posted by SLS on June 30, 2010, at 15:35:59
It's not defeat in my eyes, Scott..it's strength. My thoughts are with you..
Posted by Bob on July 1, 2010, at 0:20:05
In reply to Re: A thread for SLS » ed_uk2010, posted by SLS on June 30, 2010, at 15:35:59
> > Hi Scott,
> >
> > Am I right that you're restarting Nardil? I hope it helps. Are you planning on titrating to a higher dose this time?
>
>
> I'm going to target 90mg, which is the same dosage I used the last time. Maybe having lithium on board this time will help. Going back to Nardil this time is, in a way, an admission of defeat.
>
>
> - Scott
By your measure of defeat, I've had countless instances. I seem to have run out of options long ago, and all I see to do now is limp along with treatments that don't work and hope for the best. The best is not very good.- Bob
Posted by Ron Hill on July 1, 2010, at 21:48:15
In reply to Re: A thread for SLS, posted by ed_uk2010 on June 27, 2010, at 15:26:15
>>So far, we cannot find any evidence for there being a contraindication against doing this. Do you know of any?
> I am not aware of any contra-indication. I suppose it's just a case of there not being any evidence to support the safety of combined use.
---------------------------Ed,
Sorry for the length of this post.
Scott and I are both interested in adding 25 mg/day of agomelatine (Valdoxan) to 90 mg/day of Nardil.
My previous p-doc would have trusted me to CARFULLY try the addition of agomelatine to my current combo (see below). But, he changed jobs and went to work as a p-doc in the U.S. Veterans Administration. I am not a Veteran, so I no longer have access to him.
My new p-doc is a good doc, but is totally into CYA (cover his butt) and refused my request to add agomelatine. But, Im not going to give up. Please respond to the following:
Can Valdoxan be combined with Nardil (phenelzine), if done carefully under the direct supervision and care of a qualified psychiatrist? In the Valdoxan - Summary of Product Characteristics document, MAOIs are not contraindicated. Also, it is not contraindicated in this document: http://www.ema.europa.eu/humandocs/PDFs/EPAR/valdoxan/H-915-PI-en.pdf
Clearly, there is not any risk of serotonin syndrome, since Valdoxan does not release serotonin.
So, my question comes down to this: Since Valdoxan is an antagonist of post-synaptic 5-HT2c receptors; does the disinhibition (NDDI), resulting in the release of dopamine and norepinephrine in the frontal cortex, cause an unacceptable risk of a hypertensive crisis when 25 mg/day of Valdoxan is added to 90 mg/day of Nardil?
My p-doc is afraid of the risk a of hypertensive crisis. But, I am super safe when adding a med with some risk. I would start by trying ¼ of a 25 mg tablet. I would monitor my blood pressure continually for the first couple of hours, and I would have one of my nifedipine capsules close at hand.
Anecdotally, there are reports of this being done:
http://www.dr-bob.org/babble/20100305/msgs/939363.html
Ed, do you agree with the following paragraph? Beware of the source (see link below).
Notably, although phenelzine inhibits the breakdown of norepinephrine and epinephrine (which in concept should lead to increased levels of these two respective neurotransmitters), it actually typically significantly decreases their overall activity with time via a complex interaction with octopamine. This is the cause of the side effect of orthostatic hypotension commonly seen with phenelzine and the other MAOIs. Importantly, it has been demonstrated that the antidepressant effects of serotonin are actually mediated through norepinephrine. [9] As a result, this depletion of norepinephrine and epinephrine may significantly inhibit the full therapeutic potential of phenelzine and the other MAOIs. For this reason, augmenting with an adrenergic agent such as a norepinephrine reuptake inhibitor (NRI) or releasing agent (NRA) in conjunction may be desirable, though strict professional supervision is advised to minimize the risk of a potentially dangerous drug interaction such as hypertensive crisis.
http://wapedia.mobi/en/Phenelzine
If the above is true, agomelatine would improve the effectiveness of Nardil.
Ed, here is the home page for Valdoxan. Please click around.
Also, enter the following as a medical professional (which you are). The first four options, counting from left to right, all get you to the same place with good information. The fifth one leads you to the laymans watered down version.
http://www.valdoxan.co.uk/landing.aspx?redirect=/frequently-asked-questions-about-Valdoxan.aspx
FWIW, I sent in a Medical Enquiry to Servier, but they did not reply.
Ed, thank you for reviewing this information and providing your accessment. I am particularly interested in agomelatine because, as a BP II ultra rapid cycler, I want to take advantage of the tx of circadian rhythms.
However, I cannot merely replace Nardil with agomelatine, because the latter does not have enough antidepressant horsepower in and of itself. I need my Nardil.
Further, I am fully convinced, based on my reaction to other meds, that Valdoxan without Nardil will cause me to become irritable. This is due to the lack of a serotoninergic component.
My bottom line is that the addition of agomelatine to Nardil is simillar in risk to the careful addition of a p-stim to Nardil. This is done often.
Aside from the potential liver issue, is 25 mg/day of Valdoxan safe to add-on to Nardil?
-- Ron
dx: Bipolar II with ultra rapid cycling, and mild OCPD
600 mg/day Trileptal
200 mg/day Lamictal
500 mg/day Keppra
90 mg/day Nardil3.75 mg/day Deplin (taken with 2500 mcg/day of sublingual methyl B-12, and 12.5mg/day of sublingual P-5-P)
35 ml of Calsons Bottled Fish Oil
100 mg/day phosphatidylserene
Centrum Chewable Multi-vitamins; Only 100% of all the usual vitamins
2000 IU Vitamin E
850 mg/day of Mg 212% of RDA (as 5 grams of MgMalate).
Dark therapy via LowBlueLight glasses (When I remember)
Whats next to add:25 mg/day agomelatine (if my p-doc wakes up and smells the roses due to my submitted research) {Valdoxan}
300 mg/day of lithum carbonate
CoQ10
NAC, + 8 to 10 glasses of water, + Acetyl-L-Carnitine, + Alpha-Lipoic Acid, + Vitamin C
GTF Chromium
Cromium Picolinate
Cinnamon
Posted by Ron Hill on July 1, 2010, at 21:56:16
In reply to Re: Agomelatine add-on to Nardil » ed_uk2010, posted by Ron Hill on July 1, 2010, at 21:48:15
One link in my above post is not active. Here it is activated:
Valdoxan - Summary of Product Characteristics
http://www.valdoxan.com/index.php/summary-of-product-characteristics/
-- Ron
Posted by Bob on July 1, 2010, at 22:37:37
In reply to Re: Agomelatine add-on to Nardil » ed_uk2010, posted by Ron Hill on July 1, 2010, at 21:48:15
> >>So far, we cannot find any evidence for there being a contraindication against doing this. Do you know of any?
>
> > I am not aware of any contra-indication. I suppose it's just a case of there not being any evidence to support the safety of combined use.
> ---------------------------
>
> Ed,
>
> Sorry for the length of this post.
>
> Scott and I are both interested in adding 25 mg/day of agomelatine (Valdoxan) to 90 mg/day of Nardil.
>
> My previous p-doc would have trusted me to CARFULLY try the addition of agomelatine to my current combo (see below). But, he changed jobs and went to work as a p-doc in the U.S. Veterans Administration. I am not a Veteran, so I no longer have access to him.
>
> My new p-doc is a good doc, but is totally into CYA (cover his butt) and refused my request to add agomelatine. But, Im not going to give up. Please respond to the following:
>
> Can Valdoxan be combined with Nardil (phenelzine), if done carefully under the direct supervision and care of a qualified psychiatrist? In the Valdoxan - Summary of Product Characteristics document, MAOIs are not contraindicated. Also, it is not contraindicated in this document: http://www.ema.europa.eu/humandocs/PDFs/EPAR/valdoxan/H-915-PI-en.pdf
>
> Clearly, there is not any risk of serotonin syndrome, since Valdoxan does not release serotonin.
>
> So, my question comes down to this: Since Valdoxan is an antagonist of post-synaptic 5-HT2c receptors; does the disinhibition (NDDI), resulting in the release of dopamine and norepinephrine in the frontal cortex, cause an unacceptable risk of a hypertensive crisis when 25 mg/day of Valdoxan is added to 90 mg/day of Nardil?
>
> My p-doc is afraid of the risk a of hypertensive crisis. But, I am super safe when adding a med with some risk. I would start by trying ¼ of a 25 mg tablet. I would monitor my blood pressure continually for the first couple of hours, and I would have one of my nifedipine capsules close at hand.
>
> Anecdotally, there are reports of this being done:
>
> http://www.dr-bob.org/babble/20100305/msgs/939363.html
>
> Ed, do you agree with the following paragraph? Beware of the source (see link below).
>
> Notably, although phenelzine inhibits the breakdown of norepinephrine and epinephrine (which in concept should lead to increased levels of these two respective neurotransmitters), it actually typically significantly decreases their overall activity with time via a complex interaction with octopamine. This is the cause of the side effect of orthostatic hypotension commonly seen with phenelzine and the other MAOIs. Importantly, it has been demonstrated that the antidepressant effects of serotonin are actually mediated through norepinephrine. [9] As a result, this depletion of norepinephrine and epinephrine may significantly inhibit the full therapeutic potential of phenelzine and the other MAOIs. For this reason, augmenting with an adrenergic agent such as a norepinephrine reuptake inhibitor (NRI) or releasing agent (NRA) in conjunction may be desirable, though strict professional supervision is advised to minimize the risk of a potentially dangerous drug interaction such as hypertensive crisis.
>
> http://wapedia.mobi/en/Phenelzine
>
> If the above is true, agomelatine would improve the effectiveness of Nardil.
>
> Ed, here is the home page for Valdoxan. Please click around.
>
> http://www.valdoxan.com/
>
> Also, enter the following as a medical professional (which you are). The first four options, counting from left to right, all get you to the same place with good information. The fifth one leads you to the laymans watered down version.
>
> http://www.valdoxan.co.uk/landing.aspx?redirect=/frequently-asked-questions-about-Valdoxan.aspx
>
> FWIW, I sent in a Medical Enquiry to Servier, but they did not reply.
>
> Ed, thank you for reviewing this information and providing your accessment. I am particularly interested in agomelatine because, as a BP II ultra rapid cycler, I want to take advantage of the tx of circadian rhythms.
>
> However, I cannot merely replace Nardil with agomelatine, because the latter does not have enough antidepressant horsepower in and of itself. I need my Nardil.
>
> Further, I am fully convinced, based on my reaction to other meds, that Valdoxan without Nardil will cause me to become irritable. This is due to the lack of a serotoninergic component.
>
> My bottom line is that the addition of agomelatine to Nardil is simillar in risk to the careful addition of a p-stim to Nardil. This is done often.
>
> Aside from the potential liver issue, is 25 mg/day of Valdoxan safe to add-on to Nardil?
>
> -- Ron
>
> dx: Bipolar II with ultra rapid cycling, and mild OCPD
> 600 mg/day Trileptal
> 200 mg/day Lamictal
> 500 mg/day Keppra
> 90 mg/day Nardil
>
> 3.75 mg/day Deplin (taken with 2500 mcg/day of sublingual methyl B-12, and 12.5mg/day of sublingual P-5-P)
> 35 ml of Calsons Bottled Fish Oil
> 100 mg/day phosphatidylserene
> Centrum Chewable Multi-vitamins; Only 100% of all the usual vitamins
> 2000 IU Vitamin E
> 850 mg/day of Mg 212% of RDA (as 5 grams of MgMalate).
> Dark therapy via LowBlueLight glasses (When I remember)
>
>
> Whats next to add:
>
> 25 mg/day agomelatine (if my p-doc wakes up and smells the roses due to my submitted research) {Valdoxan}
> 300 mg/day of lithum carbonate
> CoQ10
> NAC, + 8 to 10 glasses of water, + Acetyl-L-Carnitine, + Alpha-Lipoic Acid, + Vitamin C
> GTF Chromium
> Cromium Picolinate
> Cinnamon
>
>
>
Agomelatine is not available in the US, right?
Posted by Ron Hill on July 2, 2010, at 0:01:42
In reply to Re: Agomelatine add-on to Nardil » Ron Hill, posted by Bob on July 1, 2010, at 22:37:37
> Agomelatine is not available in the US, right?
Bob,You are correct. In the U.S., Novartis has conducted six Phase III trials as an antidepressant. However, the results were less than stellar.
Therefore, Novartis is conducting more Phase III tests prior to submission to the U.S. FDA. Novartis expects agomelatine to be available in the U.S. sometime in 2012.
But, in answer to what I think is the heart of your question, the U.S. FDA allows the import of overseas medications in three month lots. Any p-doc can order a three months supply of an overseas medication, like Valdoxan (i.e.; agomelatine). Then, in three months the p-doc can order another three months supply, and-on-and-on.
-- Ron
Posted by inanimate peanut on July 2, 2010, at 1:16:05
In reply to Re: Agomelatine add-on to Nardil » Bob, posted by Ron Hill on July 2, 2010, at 0:01:42
Please keep us posted if/as you try this. I'm really interested in it as a potential add-on to Parnate. I was making the choice between trying Valdoxan or nortriptyline first and decided the evidence was obviously stronger for the nortrip at this point along with the fact that the Valdoxan I found was $90-$180 depending on dose. Valdoxan is high on my list if nortrip fails, though, so I will follow your journey with interest.
Posted by Bob on July 2, 2010, at 1:22:46
In reply to Re: Agomelatine add-on to Nardil » Bob, posted by Ron Hill on July 2, 2010, at 0:01:42
> > Agomelatine is not available in the US, right?
>
> Bob,
>
> You are correct. In the U.S., Novartis has conducted six Phase III trials as an antidepressant. However, the results were less than stellar.
>
> Therefore, Novartis is conducting more Phase III tests prior to submission to the U.S. FDA. Novartis expects agomelatine to be available in the U.S. sometime in 2012.
>
> But, in answer to what I think is the heart of your question, the U.S. FDA allows the import of overseas medications in three month lots. Any p-doc can order a three months supply of an overseas medication, like Valdoxan (i.e.; agomelatine). Then, in three months the p-doc can order another three months supply, and-on-and-on.
>
> -- Ron
>
Ron-Wow, 6 phase III trials? It sounds like the efficacy is questionable. I don't understand how drug after drug like this one get approved in
Europe but then don't make it to approval over here.I wasn't aware that a 3-month supply could be obtained from my doctor like that. Thanks for the info.
-Bob
Posted by Ron Hill on July 2, 2010, at 2:03:13
In reply to Re: Agomelatine add-on to Nardil » Ron Hill, posted by inanimate peanut on July 2, 2010, at 1:16:05
> Please keep us posted if/as you try this.
----------------Inanimate Peanut,
Will do.
I see my p-doc on 7/7/10 to present my research. Nowhere, absolutely NOWHERE, have I found any statement saying that agomelatine and MAOI's are contraindicated.
But, a lot of p-docs run the red flag up the pole and plug their ears when the patient says the all dangerous word; MAOI. MAOIs demand respect and wisdom, but they are powerful meds; albeit with a lot of side effects.
Clearly, adding agomelatine with Nardil has risk. But, if done very carefully, a prudent patient and p-doc can use very small doses with rigorous blood pressure monitoring to determine a safe dosage (if any). The combination clearly needs to be treated with respect, in the same way that adding a pstim to an MAOI must be treated with respect.
As I'm sure you know, Parnate is typically more prone to producing a hypertensive crisis than Nardil. So, even if I do find success combining agomelatine with Nardil, that does not mean it can safely be combined with Parnate.
Nice talking to you, IP. I will post if I am allowed to give the combination a trial.
-- Ron
Posted by Ron Hill on July 2, 2010, at 3:00:52
In reply to Re: Agomelatine add-on to Nardil » Ron Hill, posted by Bob on July 2, 2010, at 1:22:46
> Wow, 6 phase III trials? It sounds like the efficacy is questionable.
I gave the wrong impression. Three of the trials clearly showed efficacy. For example, one study showed that agomelatine has as a similar antidepressant effect as the trial comparisons, Paxil and Zoloft. The other three Phase III trials were more questionable, as stated here:
http://wapedia.mobi/en/Agomelatine#1.
<Start Quote>
Although some controlled studies in humans have shown that agomelatine is as effective as the SSRI antidepressants paroxetine and sertraline in the treatment of major depression [8] , there are unpublished randomised controlled trials which have failed to show that agomelatine is more effective than placebo [9] [9] . Agomelatine appears to cause fewer sexual side effects and discontinuation effects than sertraline and paroxetine. Additionally, possibly because of its action on melatonin receptors, agomelatine appears to improve sleep quality, with no reported daytime drowsiness [7] . Agomelatine has demonstrated anxiolytic properties [10] . Its efficacy in generalized anxiety disorder has been assessed by Stein et al (2008) who reported it significantly more effective than placebo treatment. [11]
<Stop Quote>
>I don't understand how drug after drug like this one get approved in Europe but then don't make it to approval over here.It was difficult to get it approved in the EU as well:
http://wapedia.mobi/en/Agomelatine
<Start Quote>
Agomelatine was discovered and developed by the European pharmaceutical company Servier Laboratories Ltd. Servier continued to develop the drug and conduct phase III trials in the European Union. In March 2005 Servier submitted agomelatine to the European Medicines Agency (EMEA) under the trade names Valdoxan and Thymanax. [12] On 27 July 2006 the Committee for Medical Products for Human Use (CHMP) of the EMEA recommended a refusal of the marketing authorisation of Valdoxan/Thymanax (agomelatine). The major concern was that efficacy had not been sufficiently shown. The CHMP had no special concerns about the side effects. [12] In September 2007, Servier submitted a new marketing application for Valdoxan (agomelatine) to the EMEA. [13] On 20 November 2008, Valdoxan was given a positive opinion, with restrictions, [14] by the EMEA [13] , and was subsequently given marketing authorisation in the European Union on 20 February 2009. [15] Release dates for agomelatine will depend on marketing arrangements in the individual countries of the EU.
In March 2006, Servier announced it had sold the rights to market agomelatine in the United States to Novartis. [16] Agomelatine is currently undergoing phase III clinical trials in the US. [17]
Novartis currently lists the drug as scheduled for submission to the FDA no earlier than 2012.
<Stop Quote>
I feel sure agomelatine will be approved in the U.S.
Keep in mind that I am interested in agomelatine for its potential treatment of circadian rhythm problems in hopes that it will reduce the severity of my bipolar II ultra rapid cycling (15 day cycle; 9 days in full remission and 6 days in debilitating depression. The 15 day cycle repeats over and over and ... without end).
Nardil is my heavy-hitter antidepressant, and I must keep it on board. The puny amount of antidepressant effect that I expect to be contributed by agomelatine will be just gravy on my Nardil meat and potatoes.
> I wasn't aware that a 3-month supply could be obtained from my doctor like that. Thanks for the info.
You bet.
-- Ron
Posted by Ron Hill on July 2, 2010, at 4:49:36
In reply to Re: A thread for SLS, posted by ed_uk2010 on June 27, 2010, at 15:26:15
Ed,
I'm sure you would do this without me stating it, but I'll mention it anyway. {Can you say OCPD?}
After you enter the following link as a medical professional, click on the links along the header. The good information are presented in links on the pages that come up after clicking on the header options.
http://www.valdoxan.co.uk/landing.aspx?redirect=/frequently-asked-questions-about-Valdoxan.aspxSorry to be anal. I just wanted to make sure you found the good stuff. {Can you say OCPD?}
-- Ron
Posted by Ron Hill on July 2, 2010, at 5:30:56
In reply to Re: A thread for SLS, posted by ed_uk2010 on June 27, 2010, at 15:26:15
Ed,
Add to previous post from me to you.
Opps! Links at the bottom of pages, as well. From an OCPD pt, over-and-out.
-- Ron
Posted by ed_uk2010 on July 2, 2010, at 17:36:29
In reply to Re: Agomelatine add-on to Nardil » ed_uk2010, posted by Ron Hill on July 1, 2010, at 21:48:15
Hi Ron,
>Can Valdoxan be combined with Nardil (phenelzine), if done carefully under the direct supervision and care of a qualified psychiatrist?
There is no evidence to support the safety of this combination, nor is there any evidence to support its efficacy. It simply hasn't received any study whatsoever. There are no reports of interactions.
>Since Valdoxan is an antagonist of post-synaptic 5-HT2c receptors; does the disinhibition (NDDI), resulting in the release of dopamine and norepinephrine in the frontal cortex, cause an unacceptable risk of a hypertensive crisis when 25 mg/day of Valdoxan is added to 90 mg/day of Nardil?
I can only make an educated guess. My guess is that there is no increased risk of hypertension with this combination. MAOI-associated hypertensive crisis is believed to occur due to peripheral adrenergic stimulation when interacting drugs/foods have been administered. It is not due to dopamine or NE being released in the frontal cortex.
>I would start by trying ¼ of a 25 mg tablet. I would monitor my blood pressure continually for the first couple of hours, and I would have one of my nifedipine capsules close at hand.
Starting with a low dose of agomelatine would be very sensible. Limited (in vitro) evidence suggests that Nardil inhibits various drug-metabolising enzymes, including CYP 1A2. Agomelatine is metabolised predominantly by CYP 1A2. If Nardil does indeed inhibit CYP 1A2, exposure to agomelatine would be substantially increased. This could lead to an increased risk of adverse effects from agomelatine eg. daytime drowsiness, nausea and possibly liver dysfunction. I would certainly recommend liver function tests prior to and during treatment with agomelatine. The initial pre-treatment test would be vital to establish a baseline.
>............If the above is true, agomelatine would improve the effectiveness of Nardil.
Possibly. I find it very difficult to say whether combined use is likely to be beneficial. If agomelatine metabolism was inhibited by Nardil, constant high levels of agomelatine may further disrupt circadian rhythms. The 5-HT2c antagonism may be beneficial but I'm not sure that the benefit would be robust.
In summary, I would only recommend this combination if other options have not been effective. So... I guess you are a candidate for treatment! Cautiously, of course.
By the way, are you sure that the Keppra is helping? Evidence of Keppra's efficacy in psych disorders is very limited.....and it seems to cause psychiatric adverse reactions quite frequently in its own right. Pehaps you should consider dropping the Keppra before adding any further medications? In some cases, complex polypharmacy can lead to more problems than it solves.
Best regards,
Ed
Posted by inanimate peanut on July 2, 2010, at 18:54:45
In reply to Re: Agomelatine add-on to Nardil » inanimate peanut, posted by Ron Hill on July 2, 2010, at 2:03:13
I wasn't aware that Parnate use made you more prone to a hypertensive crisis than Nardil use. Do you know why that is?
Posted by Ron Hill on August 15, 2010, at 0:14:12
In reply to Re: Agomelatine add-on to Nardil » Ron Hill, posted by ed_uk2010 on July 2, 2010, at 17:36:29
Ed,
Just a brief follow up.
About two weeks ago, I added 25 mg of Valdoxan (agomelatine) to my combo (combo listed below). No increase in blood pressure, and I really like the med. It feels like a mild antidepressant with a moodstablizer. But, the main thing is it's a great tx for circadian rhythm dysfunction and, therefore, a great tx for bipolar disorder.
500 mg/day of Keppra is very beneficial to me. However, 1000 mg/day causes depression.
-- Ron
dx: Bipolar II with ultra rapid cycling, and mild OCPD
600 mg/day oxcarbazepine (Trileptal)
200 mg/day lamotrigine (Lamictal)
500 mg/day Keppra (levetiracetam)
90 mg/day Nardil (phenelzine)
25 mg/day Valdoxan (agomelatine)
3.75 mg/day Deplin (taken with 2500 mcg/day of sublingual methyl B-12, and 12.5mg/day of sublingual P-5-P)45 ml of Carlsons Bottled Fish Oil
100 mg/day phosphatidylserene
Centrum Chewable Multi-vitamins; Only 100% of all the usual vitamins; NO VANADIUM!!
2000 IU Vitamin E
850 mg/day of Mg 212% of RDA (as 5 grams of Mg Malate).
Dark therapy via LowBlueLight glasses (When I remember)
Whats next to add?:300 mg/day of lithum carbonate
CoQ10
NAC, + 8 to 10 glasses of water, + Acetyl-L-Carnitine, + Alpha-Lipoic Acid, + Vitamin C
GTF Chromium
Cromium Picolinate
Cinnamon
---------------------------
> Hi Ron,
>
> >Can Valdoxan be combined with Nardil (phenelzine), if done carefully under the direct supervision and care of a qualified psychiatrist?
>
> There is no evidence to support the safety of this combination, nor is there any evidence to support its efficacy. It simply hasn't received any study whatsoever. There are no reports of interactions.
>
> >Since Valdoxan is an antagonist of post-synaptic 5-HT2c receptors; does the disinhibition (NDDI), resulting in the release of dopamine and norepinephrine in the frontal cortex, cause an unacceptable risk of a hypertensive crisis when 25 mg/day of Valdoxan is added to 90 mg/day of Nardil?
>
> I can only make an educated guess. My guess is that there is no increased risk of hypertension with this combination. MAOI-associated hypertensive crisis is believed to occur due to peripheral adrenergic stimulation when interacting drugs/foods have been administered. It is not due to dopamine or NE being released in the frontal cortex.
>
> >I would start by trying ¼ of a 25 mg tablet. I would monitor my blood pressure continually for the first couple of hours, and I would have one of my nifedipine capsules close at hand.
>
> Starting with a low dose of agomelatine would be very sensible. Limited (in vitro) evidence suggests that Nardil inhibits various drug-metabolising enzymes, including CYP 1A2. Agomelatine is metabolised predominantly by CYP 1A2. If Nardil does indeed inhibit CYP 1A2, exposure to agomelatine would be substantially increased. This could lead to an increased risk of adverse effects from agomelatine eg. daytime drowsiness, nausea and possibly liver dysfunction. I would certainly recommend liver function tests prior to and during treatment with agomelatine. The initial pre-treatment test would be vital to establish a baseline.
>
> >............If the above is true, agomelatine would improve the effectiveness of Nardil.
>
> Possibly. I find it very difficult to say whether combined use is likely to be beneficial. If agomelatine metabolism was inhibited by Nardil, constant high levels of agomelatine may further disrupt circadian rhythms. The 5-HT2c antagonism may be beneficial but I'm not sure that the benefit would be robust.
>
> In summary, I would only recommend this combination if other options have not been effective. So... I guess you are a candidate for treatment! Cautiously, of course.
>
> By the way, are you sure that the Keppra is helping? Evidence of Keppra's efficacy in psych disorders is very limited.....and it seems to cause psychiatric adverse reactions quite frequently in its own right. Pehaps you should consider dropping the Keppra before adding any further medications? In some cases, complex polypharmacy can lead to more problems than it solves.
>
> Best regards,
>
> Ed
Posted by ed_uk2010 on August 15, 2010, at 7:06:30
In reply to Re: Agomelatine add-on to Nardil » ed_uk2010, posted by Ron Hill on August 15, 2010, at 0:14:12
Hi Ron,
Glad that agomelatine is helping. Will you stay at 25mg? I imagine you are paying a lot for it even at this dose. Which country has it come from? UK?
>500 mg/day of Keppra is very beneficial to me. However, 1000 mg/day causes depression.
What symptoms does it help? Have you tried 250mg per day? eg. 125mg BID.
>300 mg/day of lithum carbonate
Have you tried lithium before? I can't remember.
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