64 replies to this topic

[Animal]

Hey there, I have been taking Agomelatine/Valdoxan for almost 3 months now, in an effort to attenuate my dysthymia and anhedonia. I began taking 25mg/day at night, and I must admit it is essentially side-effect free for me. It is also extremely subtle in it's effects unfortunately. I definitely noticed a generally improved mood and increased ability to experience pleasure, it just wasn't what I was hoping for.

2 weeks ago I began taking 50mg/day, this was an experiment of sorts, but based on studies and anecdotal evidence I have come across, the difference in the effect of this increased dose is dramatic. An example of which is that at 25mg/day over 20% of subjects had some form of sexual dysfunction, placebo was at approximately 5% and the 50mg/day subjects had less then a 3% occurrence of sexual dysfunction, lower then placebo! This was important to me as I've had lingering, but gradually improving sexual issues ever since I took Citalopram, which I discontinued over 3 months ago. It's important to note that I began taking Agomelatine immediately after ceasing the Citalopram, so there is the possibility that the Agomelatine has compounded any recovery of sexual functionality.

Apparently the 5-HT2C antagonism and the resulting down-regulation does not increase in a linear fashion with increasing dosage, but instead has an up-down cyclical regulatory response, whereby the greater the degree of down-regulation the more rapid the resulting constitutive up-regulation. This results in the Agomelatine achieving a sort of peak equilibrium of up-down regulation that is dependent on dose. In essence, by doubling the dosage I have raised the peak equilibrium point of the down-regulation, but it is not double the down-regulation of the half dose. Remember that even the endogenous ligand of the receptor results in down-regulation when it binds because of the inversely proportional inhibition of DA and NE that activation of the receptor creates. This also implies that the acceleration of down-regulation will also increase with the greater dosage, meaning that results will be noticeable more rapidly.

The reason that I have taken so long to make the decision to increase the dosage to 50mg/day is because it is prohibitively expensive, but I have recently received a partial payment on a contract so decided to at least try it for a few months. It is costing me £160 per month, including postage.

Well I have to say that the difference has been huge after only 2 weeks, my mood, energy, motivation and libido have improved significantly. I am taking multiple other supplements and medicaments, with the only recent additions being Cordyceps and Schizandra, but I do not believe they are responsible for the improvements. If anything my sex drive is somewhat over-active now, along with a great improvement in general sexual performance. But I cannot complain since this is what I wanted, but if I was single it would definitely be frustrating.

I am wondering what experiences other individuals have had with Agomelatine, especially as it relates to an increase in dosage. I would also recommend that individuals who have experimented with 25mg/day dosages of Agomelatine and found it unsatisfactory, should consider trying it again at an increased dosage. I know Funkodyssey is one of those people, try it at 50mg/day if you can Funk!

[medievil]

So looks like your finding a regime that is helping your problems, good news!

[Animal]

So looks like your finding a regime that is helping your problems, good news!

Yeah well my current regime is working extremely effectively, I am so much more functional then I was. With this great improvement brought about by the Agomelatine at 50mg/day, as long as it lasts there is only one more substance I wish to try. It's important to note though that drastic changes in lifestyle have also been involved in my recovery. Personally I don't think medication/supplements alone are capable of solving any psychological issue entirely, but they can be very enabling.

I can't believe I actually managed to get my PhD with how terrible I used to feel. I've only been truly improving over the last 6 months or so.

[medievil]

What other substance do you want to try?

[Animal]

What other substance do you want to try?

Hydergine! Ergots and the dynamics of their interaction with the 5-HT2A receptor subtype fascinate me.

[Thorsten3]

What other substance do you want to try?

Hydergine! Ergots and the dynamics of their interaction with the 5-HT2A receptor subtype fascinate me.

Hi Animal what is it about Hydergine that fascinates you? Forgive my ignorance but isn't that a substance that is involved in negative health issues with the heart? So considering your experience I am presuming there is more to it than that - maybe theraputic doses with significantly lowered risk?

With regards to Agomelatine it's pretty astronomical at that price but I can understand why you'd consider it to be worth it. I find it a very macho sort of substance with its raw noradrenalin and dopamine releasing properties (Not in the slightest bit aggressive but still pretty butch!). I find with chronic dosing the effects build and get stronger so for me I have to take things during the day to try and calm my CNS down. I don't suffer with any form of anxiety at present so I can afford to live with these effects fortunately. I find it makes me overly extroverted and activities such as eating food, having sex and socializing all become far more pleasurable. Despite these wonderful effects I'm probably going to go back to Tianeptine when my new order finally arrives. Although libido is still pretty high on Tianeptine, it doesn't become my primary focus like it does on Agomelatine (becomes too distracting for me). Tianeptine also makes me only slightly more extroverted and I appreciate the positive effects it has on cognition and memory. In fact it's a quality nootropic in my opinion. I think it's more suitable for me personally.

Back to Agomelatine I hope you wouldn't mind clarifying some questions I have. Do you happen to know what relevance the drug plays at the 5-HT2B receptor?

Also what do you think the long term implications are with taking Agomelatine? Any downregulation issues?



Finally I'm copying and pasting this from the psychonauts group (Hope the guy - 'nobrainer' doesn't mind. He posted this about the CYP1A2 enzyme). For anyone who doesn't know, this enzyme is responsible for metabolizing Agomelatine.

CYP1A2 INHIBITORS

galangin (galangal root)
curcumin (turmeric)
tea polyphenols
naringenin (grapefruit)
quercetin
Scutellaria baicalensis (Baikal Skullcap)
tangeritin (tangerine and other citrus
peels)
(trans-resveratrol)

fluvoxamine
ciprofloxacin
enoxacin

CYP1A2 INDUCERS
coffeine
Polycyclic Aromatic Hydrocarbons (smoking)
glycyrrhizin (liquorice)

Edited by Thorsten, 19 September 2010 - 07:47 PM.

[FunkOdyssey]

I am wondering what experiences other individuals have had with Agomelatine, especially as it relates to an increase in dosage. I would also recommend that individuals who have experimented with 25mg/day dosages of Agomelatine and found it unsatisfactory, should consider trying it again at an increased dosage. I know Funkodyssey is one of those people, try it at 50mg/day if you can Funk!

I'm actually taking a combination of 5mg escitalopram and 30mg mirtazapine right now. There is some reasoning and evidence to suggest the SSRI becomes prosexual in this combination (by selectively activating 5HT1A receptors):

Hum Psychopharmacol. 2008 Jun;23(4):321-6.
Mirtazapine augmentation in depressed patients with sexual dysfunction due to selective serotonin reuptake inhibitors.

Ozmenler NK, Karlidere T, Bozkurt A, Yetkin S, Doruk A, Sutcigil L, Cansever A, Uzun O, Ozgen F, Ozsahin A.

Gulhane School of Medicine, Department of Psychiatry, Ankara, Turkey.
Abstract

OBJECTIVE: To evaluate the effect of mirtazapine augmentation in patients with sexual dysfunction induced by current selective serotonin reuptake inhibitor (SSRI) treatment.

METHODS: Forty-nine outpatients in remission from major depressive disorder with SSRI treatment and experiencing treatment-emergent sexual dysfunction were invited to participate and 33 (25 women and 8 men) were included in this 8-week open-label study. All patients continued her/his current SSRI treatment (dosages unchanged) and started on mirtazapine augmentation of 15 mg/day during the first week and 30 mg/day throughout the rest of the study. The Hamilton rating scale for depression (HAM-D), the psychotropic-related sexual dysfunction questionnaire (PRSexDQ), and the Golombok and Rust Inventory of Sexual Satisfaction (GRISS) were given to all patients at baseline and at each follow-up (end of the first, second, fourth, sixth, and eight weeks).

RESULTS: Mirtazapine augmentation led to significant reductions in HAM-D, PRSexDQ, and GRISS scores throughout the study especially after week 4 and 48.5% of patients (n = 16) reported that they had no overall sexual dysfunction at the end of the study.

CONCLUSIONS: Mirtazapine augmentation is a good choice for the treatment of SSRI-induced sexual dysfunction, and the results are typically seen later after 4-8 weeks.

PMID: 18278806

Psychopharmacology (Berl). 2004 Jan;171(3):250-8. Epub 2003 Nov 13.
Influence of mirtazapine on the sexual behavior of male rats.

Benelli A, Frigeri C, Bertolini A, Genedani S.

Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, via G. Campi 287, 41100 Modena, Italy. benelli.augusta@unimo.it
Abstract

RATIONALE: Impairment of sexual activity is one of the most frequent side effects of antidepressant drugs. The increase in the synaptic concentrations of serotonin seems to be mainly responsible. Mirtazapine is a novel antidepressant that increases the synaptic concentrations of both noradrenaline and serotonin; moreover, it is an antagonist at 5-HT(2C) receptors, whose activation is considered to be responsible for some typical effects of serotonin on the ejaculation process (retardation of ejaculation, anorgasmia).

OBJECTIVES: To study the influence of mirtazapine on copulatory performance and sexual motivation in male rats, in comparison-or in combination-with fluoxetine.

METHODS: Copulatory performance was studied either in sexually experienced or in sexually naive rats; sexual motivation was studied in sexually experienced rats. Mirtazapine (1, 5 or 10 mg/kg), fluoxetine (10 mg/kg), and the combination of mirtazapine + fluoxetine (10+10 mg/kg) were subcutaneously (s.c.) administered either acutely or daily for 13 days.

RESULTS: After acute administration, mirtazapine decreased mount latency (ML) and intromission latency (IL), and increased mount frequency (MF) and ejaculation latency (EL). Fluoxetine had no significant effect on any of the sexual behavior parameters. After a 13-day treatment, mirtazapine increased ML, IL and MF; fluoxetine increased ML, IL and the intercopulatory interval (ICI); the addition of mirtazapine to fluoxetine produced a reduction of ICI and an increase of MF. Moreover, mirtazapine significantly improved the performance of rats in the sexual motivation test.

CONCLUSIONS: The present results show that, on the whole, the acute administration of mirtazapine improves several parameters of the copulatory performance of male rats and strongly stimulates sexual motivation, while the repeated administration produces minor, conflicting effects. This effect of mirtazapine on male rat sexual behavior is to be ascribed to the antagonism at brain alpha(2) adrenergic auto- and hetero-receptors, with consequent increased release of noradrenaline and serotonin, and antagonism at 5-HT(2C) receptors, which are involved in the negative influence of serotonin on male sexual behavior.

PMID: 14615872

why would mirtazapine + SSRI be better than either alone [for sexual function]?

Synergy. Alpha-2 antagonism disinhibits cortical monoamine release, in addition to increasing NAc catecholamine release. Similarly, 5-HT2C antagonism disinhibits NAc/VTA firing action, biasing toward increasing 5-HT action at pro-sexual receptor sites.

I just started the mirtazapine a few days ago so its too early to give feedback, other than it seems to generally agree with me and was only very sedating the first day. I still have a large stash of agomelatine so I may try that in the future at the higher dose if this doesn't work out. I wonder what it would do in combination with escitalopram and mirtazapine -- maybe the additional 5-HT2C antagonism on top of mirtazapine's would be synergistic? Hmm

Edited by FunkOdyssey, 19 September 2010 - 09:11 PM.

[KimberCT]

Mirtazapine is actually a very potent 5-HT2C inverse agonist. Adding agomelatine may actually reduce its effect in that regard.

[FunkOdyssey]

Mirtazapine is actually a very potent 5-HT2C inverse agonist. Adding agomelatine may actually reduce its effect in that regard.

Doh. Thanks Kimber

[John Barleycorn]

Also what do you think the long term implications are with taking Agomelatine? Any downregulation issues?

That's the whole point. 5HT-2C receptors are a rare example of those that downregulate with antagonism. This is desirable because of the downstream limbic dopamine boost. Here's a free text article on the topic: Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Agomelatine has a comparatively clean spectrum of effects, barring its actions on melatonin receptors. This could be the reason for disturbed sleep with chronic use.

Finally I'm copying and pasting this from the psychonauts group (Hope the guy - 'nobrainer' doesn't mind. He posted this about the CYP1A2 enzyme). For anyone who doesn't know, this enzyme is responsible for metabolizing Agomelatine.

I've already told you lot what the Google forum tip is for increasing the bioavailability substantially, and it involves bypassing the liver (at least on the first pass).

[bacopa]

Hey there, I have been taking Agomelatine/Valdoxan for almost 3 months now, in an effort to attenuate my dysthymia and anhedonia. I began taking 25mg/day at night, and I must admit it is essentially side-effect free for me. It is also extremely subtle in it's effects unfortunately. I definitely noticed a generally improved mood and increased ability to experience pleasure, it just wasn't what I was hoping for.

2 weeks ago I began taking 50mg/day, this was an experiment of sorts, but based on studies and anecdotal evidence I have come across, the difference in the effect of this increased dose is dramatic. An example of which is that at 25mg/day over 20% of subjects had some form of sexual dysfunction, placebo was at approximately 5% and the 50mg/day subjects had less then a 3% occurrence of sexual dysfunction, lower then placebo! This was important to me as I've had lingering, but gradually improving sexual issues ever since I took Citalopram, which I discontinued over 3 months ago. It's important to note that I began taking Agomelatine immediately after ceasing the Citalopram, so there is the possibility that the Agomelatine has compounded any recovery of sexual functionality.

Apparently the 5-HT2C antagonism and the resulting down-regulation does not increase in a linear fashion with increasing dosage, but instead has an up-down cyclical regulatory response, whereby the greater the degree of down-regulation the more rapid the resulting constitutive up-regulation. This results in the Agomelatine achieving a sort of peak equilibrium of up-down regulation that is dependent on dose. In essence, by doubling the dosage I have raised the peak equilibrium point of the down-regulation, but it is not double the down-regulation of the half dose. Remember that even the endogenous ligand of the receptor results in down-regulation when it binds because of the inversely proportional inhibition of DA and NE that activation of the receptor creates. This also implies that the acceleration of down-regulation will also increase with the greater dosage, meaning that results will be noticeable more rapidly.

The reason that I have taken so long to make the decision to increase the dosage to 50mg/day is because it is prohibitively expensive, but I have recently received a partial payment on a contract so decided to at least try it for a few months. It is costing me £160 per month, including postage.

Well I have to say that the difference has been huge after only 2 weeks, my mood, energy, motivation and libido have improved significantly. I am taking multiple other supplements and medicaments, with the only recent additions being Cordyceps and Schizandra, but I do not believe they are responsible for the improvements. If anything my sex drive is somewhat over-active now, along with a great improvement in general sexual performance. But I cannot complain since this is what I wanted, but if I was single it would definitely be frustrating.

I am wondering what experiences other individuals have had with Agomelatine, especially as it relates to an increase in dosage. I would also recommend that individuals who have experimented with 25mg/day dosages of Agomelatine and found it unsatisfactory, should consider trying it again at an increased dosage. I know Funkodyssey is one of those people, try it at 50mg/day if you can Funk!

I am interested in Agomaletine for my anhedonia/lethargy, as well...keep us posted!

[Nooby]

That's the whole point. 5HT-2C receptors are a rare example of those that downregulate with antagonism. This is desirable because of the downstream limbic dopamine boost. Here's a free text article on the topic: Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Agomelatine has a comparatively clean spectrum of effects, barring its actions on melatonin receptors. This could be the reason for disturbed sleep with chronic use.

That's great thanks for clarifying.

I've already told you lot what the Google forum tip is for increasing the bioavailability substantially, and it involves bypassing the liver (at least on the first pass).

Huh? Sorry I'm not following here. If you'd care to elaborate here on what you mean, that would be peachy.

[Nooby]

Hey there, I have been taking Agomelatine/Valdoxan for almost 3 months now, in an effort to attenuate my dysthymia and anhedonia. I began taking 25mg/day at night, and I must admit it is essentially side-effect free for me. It is also extremely subtle in it's effects unfortunately. I definitely noticed a generally improved mood and increased ability to experience pleasure, it just wasn't what I was hoping for.

2 weeks ago I began taking 50mg/day, this was an experiment of sorts, but based on studies and anecdotal evidence I have come across, the difference in the effect of this increased dose is dramatic. An example of which is that at 25mg/day over 20% of subjects had some form of sexual dysfunction, placebo was at approximately 5% and the 50mg/day subjects had less then a 3% occurrence of sexual dysfunction, lower then placebo! This was important to me as I've had lingering, but gradually improving sexual issues ever since I took Citalopram, which I discontinued over 3 months ago. It's important to note that I began taking Agomelatine immediately after ceasing the Citalopram, so there is the possibility that the Agomelatine has compounded any recovery of sexual functionality.

Apparently the 5-HT2C antagonism and the resulting down-regulation does not increase in a linear fashion with increasing dosage, but instead has an up-down cyclical regulatory response, whereby the greater the degree of down-regulation the more rapid the resulting constitutive up-regulation. This results in the Agomelatine achieving a sort of peak equilibrium of up-down regulation that is dependent on dose. In essence, by doubling the dosage I have raised the peak equilibrium point of the down-regulation, but it is not double the down-regulation of the half dose. Remember that even the endogenous ligand of the receptor results in down-regulation when it binds because of the inversely proportional inhibition of DA and NE that activation of the receptor creates. This also implies that the acceleration of down-regulation will also increase with the greater dosage, meaning that results will be noticeable more rapidly.

The reason that I have taken so long to make the decision to increase the dosage to 50mg/day is because it is prohibitively expensive, but I have recently received a partial payment on a contract so decided to at least try it for a few months. It is costing me £160 per month, including postage.

Well I have to say that the difference has been huge after only 2 weeks, my mood, energy, motivation and libido have improved significantly. I am taking multiple other supplements and medicaments, with the only recent additions being Cordyceps and Schizandra, but I do not believe they are responsible for the improvements. If anything my sex drive is somewhat over-active now, along with a great improvement in general sexual performance. But I cannot complain since this is what I wanted, but if I was single it would definitely be frustrating.

I am wondering what experiences other individuals have had with Agomelatine, especially as it relates to an increase in dosage. I would also recommend that individuals who have experimented with 25mg/day dosages of Agomelatine and found it unsatisfactory, should consider trying it again at an increased dosage. I know Funkodyssey is one of those people, try it at 50mg/day if you can Funk!

I am interested in Agomaletine for my anhedonia/lethargy, as well...keep us posted!

If you can afford it dfowler I'd highly recommend it (for the above reasons you list). I started it last week and so far I am noticing very positive results.

Edited by Nooby, 20 September 2010 - 07:32 AM.

[Animal]

I've already told you lot what the Google forum tip is for increasing the bioavailability substantially, and it involves bypassing the liver (at least on the first pass).

Which is?

dfowler, I would just start trialling it mate if you can afford it. It is essentially without risk since the side-effect profile is almost non-existant, and it helps with sleep which I know you have an issue with.

If you actually have a depressed mood though I would strongly recommend you try first low dose amisulpride i.e. 50mg/day. It obliterates most of the negative symptoms of dysthymia for me, but does little for my energy, libido and anhedonia. So to clarify, it stops me being depressed, but I still found it almost impossible to enjoy myself. The Agomelatine takes care of that, I've found it especially good for anhedonia.

[John Barleycorn]

Which is?

I'm tempted to emulate your good self and say something like do the bloody research! (like perform a search on me + agomelatine). However, since I'm such a sweet, accommodating bloke, the answer is essentially sublingual/buccal absorption (and maybe rectal for any desperados out there). I have a strong feeling that girls aren't part of this current discussion, so let's not consider their extra option. Most of those on the Google forum seem to be dissolving the ago in a small amount of alcohol, however (without having tried it), I would wager that the relatively small, pulverised pill could absorb directly. The saliva should be alkaline enough to free the amine base, if the pills come in salt form. They might even dissolve in the mouth like selegiline (some brands), obviating the need for crushing. If someone objects to alcohol, try a food-grade emulsifier like lecithin. Don't do a whole pill - it seems to be too much.

Edited by John Barleycorn, 21 September 2010 - 03:06 AM.

[FunkOdyssey]

So I'm probably going to try this (50mg agomelatine), in conjunction with SJW which I've taken before and seen only a partial response with (mood, energy, and anxiety improved, still had anhedonia and amotivation).

I found some specific in vivo data on the impact of curcumin and quercetin on CYP1A2 in human volunteers. At 1000mg once daily, curcumin inhibited CYP1A2 by 28%. At 500mg once daily, quercetin inhibited CYP1A2 by 10%.

Animal- I can't help but wonder how much you are confounding your results with cordyceps, which is actually a very potent supplement and could be providing some of the benefits you are enjoying. Would you be willing to stop that temporarily in the name of science to observe what benefits persist and which disappear?

You aren't getting any fatigue at 50mg? That seems to be the major complaint on the psychonauts group at that dose.

Edited by FunkOdyssey, 23 September 2010 - 03:34 AM.

[chrono]

Glad it's working so well for you! I was just reading through ago psychonauts this morning, and so many of the people there seem to be disillusioned of its usefulness at this point.

I'd be interested in hearing a comparison with tianeptine, since they're so often mentioned in the same breath.

[FunkOdyssey]

I don't think it works as well for serious depression and anxiety problems which many of those people have. I think it's more effective for anhedonia/dysthmia/amotivation. That, and regulating disrupted circadian rhythms.

This is my fifth day on 50mg agomelatine combined with SJW. I'll keep you guys posted.

Edited by FunkOdyssey, 27 September 2010 - 12:15 PM.

[YoungSchizo]

I don't think it works as well for serious depression and anxiety problems which many of those people have. I think it's more effective for anhedonia/dysthmia/amotivation. That, and regulating disrupted circadian rhythms.

This is my fifth day on 50mg agomelatine combined with SJW. I'll keep you guys posted.

I'm on 50mg agomelatine for 2 weeks, it definitely cancels the zombifying effect of 15mg Zyprexa.

[medievil]

I don't think it works as well for serious depression and anxiety problems which many of those people have. I think it's more effective for anhedonia/dysthmia/amotivation. That, and regulating disrupted circadian rhythms.

This is my fifth day on 50mg agomelatine combined with SJW. I'll keep you guys posted.

Dude everytime i see you mentioning your regime its something completely differend lol .

[FunkOdyssey]

I don't think it works as well for serious depression and anxiety problems which many of those people have. I think it's more effective for anhedonia/dysthmia/amotivation. That, and regulating disrupted circadian rhythms.

This is my fifth day on 50mg agomelatine combined with SJW. I'll keep you guys posted.

Dude everytime i see you mentioning your regime its something completely differend lol .

LOL I know, alot of changes recently. I'm going to stick with this one for awhile though, I know and like SJW and agomelatine requires a good 4+ weeks to properly evaluate.

[stablemind]

Funk, would you say this kind of anhedonia is just general lack of interest in things? Like you're very bored all the time?

[YoungSchizo]

Funk, would you say this kind of anhedonia is just general lack of interest in things? Like you're very bored all the time?

Correct me if I'm wrong, enhedonia is bored (lack of interest) in the things that you enjoyed (to do) in the past.

Edited by YoungS, 28 September 2010 - 04:49 PM.

[FunkOdyssey]

Funk, would you say this kind of anhedonia is just general lack of interest in things? Like you're very bored all the time?

Yes, nothing seems exciting or interesting.

[medievil]

Funk, would you say this kind of anhedonia is just general lack of interest in things? Like you're very bored all the time?

Yes, nothing seems exciting or interesting.

Except all my own posts here, no anhedonia can make them less exciting and interesting .

Just kidding funk, hopefully this regime will work for you!

[Animal]

I don't think it works as well for serious depression and anxiety problems which many of those people have. I think it's more effective for anhedonia/dysthmia/amotivation. That, and regulating disrupted circadian rhythms.

This is my fifth day on 50mg agomelatine combined with SJW. I'll keep you guys posted.

Do you think your mood disturbances are related to your current romantic status, or a result of lyme disease?

I'm not really in a very good position to give you an objective evaluation of the effectiveness of the Agomelatine at this point due to to some shit going on in my life that is definitely a confounding variable.

I've just finished with my girlfriend after getting back with her for 2 months after an initial break-up; I'm ill with some sort of persistent rhinovirus which has affected my mood and energy levels, though I seem to be recovering; I experimented with discontinuation of Amisulpride recently, the result being a relapse of dysthymia 5 days after discontinuation. I'm back on it now though and things seem to be going well.

The Agomelatine really helps with energy, anhedonia and amotivation for me, but it obviously isn't sufficient on it's own to counter the refractory dysthymia I suffer from.

Despite all this I still feel better psychologically then I have in a long time, and compared to my reaction the first time I'm taking the break-up with my girlfriend extremely well, though it is still affecting my mood a bit negatively.

I've been on 50mg/day for a month; the turning point for when I clearly noticed the effects at 25mg/day was 6 weeks, so I'm waiting until then to truly evaluate it. For now, I believe the positive effects certainly justify the absurd price. Oh and just to add, my sex drive is still very healthy/too healthy, but now I have no girlfriend to release it's fury on. Still, I love the fact that I feel horny regularly, it just feels healthy somehow, compared to my indifference in the past.

[FunkOdyssey]

Do you think your mood disturbances are related to your current romantic status, or a result of lyme disease?

Actually I think I'm mostly rid of Lyme and am basically left with CFS (many symptoms gone, but no further improvement with antibiotics). I'm waiting for the results of XMRV culture and serology tests, but at the moment I'm assuming I have XMRV. And I think that is primarily responsible for these issues as I had them even when my circumstances were "good" previously.

There may be a link between chronic infection and increased 5-HT2C expression which would make agomelatine the ideal agent to counter it:

Conditions that increase cytokine levels in the human body may have potential to raise 5-HT2C gene expression in the brain. This could possibly comprise a link between viral infections and associated depression. Cytokine therapy has been shown to increase 5-HT2C gene expression, resulting in increased activity of 5-HT2C receptors in the brain.

The Agomelatine really helps with energy, anhedonia and amotivation for me, but it obviously isn't sufficient on it's own to counter the refractory dysthymia I suffer from.
...
I've been on 50mg/day for a month; the turning point for when I clearly noticed the effects at 25mg/day was 6 weeks, so I'm waiting until then to truly evaluate it. For now, I believe the positive effects certainly justify the absurd price. Oh and just to add, my sex drive is still very healthy/too healthy, but now I have no girlfriend to release it's fury on. Still, I love the fact that I feel horny regularly, it just feels healthy somehow, compared to my indifference in the past.

The effects you describe are exactly what I'm looking for. I think the most valuable piece of information you provided was that 6 week timeframe to wait before judging the effects. That will help with my patience. Thanks for the reply!

Edited by FunkOdyssey, 28 September 2010 - 10:18 PM.

[Animal]

The effects you describe are exactly what I'm looking for. I think the most valuable piece of information you provided was that 6 week timeframe to wait before judging the effects. That will help with my patience. Thanks for the reply!

It is important to give Agomelatine sufficient time to down-regulate 5-HT2C to a degree that you notice the positive effects. It has a very subtle and gradual onset, and because of the almost complete lack of side-effects you don't even know if you're having any response at all initially. The 6 week point was when I could distinctly recognise the difference in general temperament that the Agomelatine had wrought, this continued to improve until the 8 week mark, at which point it plateaued in effects.

I've already noticed positive effects from the increase to 50mg/day, which I hypothesised I would given the pharmacokinetic receptor dynamics of the substance. I'm looking forward to the 6 week point just so I can make a definite comparison with 25/mg a day. But so far I am very happy with the investment, I just need to de-stress so I can enjoy it properly.

Edited by Animal, 29 September 2010 - 09:40 PM.

[Ungomma]

I would apprecitate an update from those on agomelatine - did you get the expected results, encounter any issues?

[aLurker]

I would apprecitate an update from those on agomelatine - did you get the expected results, encounter any issues?

+1

I'd love to hear if anyone has long-term success with this. Considering it as a part of my own regimen to combat delayed sleep phase (although melatonin seems to be working quite well at the moment) and ADD-ish procrastination/motivational/focus issues.