49 replies to this topic

[Tom_]

Another update. Nearly two weeks on the venlafaxine, going up in dose either tomorrow or Tuesday to 225. There is what is almost certainly a treatment response although it could just be normal mood fluctuation. I'm still experiencing irritability, moderate to severe avolition, significant anhedonia, somewhat blunted affect, attention problems, executive dsyfunction, easily fatiguable, a desire to die with no imminent intent and low affect but these symptoms have improved. I'm sleeping a fairly healthy 8ish hours a day but with fatigue, nightmares 1 or 2 a week and sleep drunkness on awakening for up to two hours. I don't think the Agomelatine is doing much good, it may even be making me worse we all know NDDI drugs can be dangerous. I intent to ask my psychiatrist when I see him next about stopping it and either starting something else then or the time after when I see him. Likely something stimulating.

Headache is still around, cock problems are present and blood pressure has lowered a lot...stress reduction I imagine.

I'm going to see the neuropsychiatrist on Tuesday who will likely prescribe Modafinil alongside my other drugs. I want to discuss other options with him, including Nortriptyline (strongest stimulating TCA in England), traditional stimulants and anything else he feels appropriate, however Modafinil seems reasonable to me. Would you guys have any stimulating drugs to recommend?

[Tom_]

Been prescribed modafinil 50mg. I will be increasing the dose if necessary in three weeks at my review appointment. Currently on:

Venlafaxine 225, Mofainil 50mg, Agomelatine 50mg & Melatonin 3mg.

[nowayout]

A tangential question. My doctor suggested agomelatine for sleep. However, if melatonin does nothing for me, do you think agomelatine is likely to do anything for me? I guess I have a hard time figuring out what makes agomelatine better than just straight cheap melatonin (or perhaps extended release melatonin).

[nowayout]

Never mind. I just answered my own question. Agomelatine also antagonizes 5HT-2C.

[Tom_]

antagonising 5HT-2c is stimulating it acts as an NDDI (noradrenaline and dopamine dis-inhibitor). I find Agomelatine to be a little sedating, there is certainly no real reason not to give it a try. Its been shown fairly effective in depressive disorders, some early evidence for OCD and anxiety etc...

[elemerendero1]

A tangential question. My doctor suggested agomelatine for sleep. However, if melatonin does nothing for me, do you think agomelatine is likely to do anything for me? I guess I have a hard time figuring out what makes agomelatine better than just straight cheap melatonin (or perhaps extended release melatonin).

the antagonism of 5-HT2C receptors (agomelatine), enhances slow wave sleep (deep sleep) ... so yeah, could improve the quality of your sleep

hello Tom_, like I said I do not support the use of SSRIs, however, I sincerely hope that the treatment you are pursuing you both benefit. How's it going?

[nowayout]

antagonising 5HT-2c is stimulating it acts as an NDDI (noradrenaline and dopamine dis-inhibitor). I find Agomelatine to be a little sedating, there is certainly no real reason not to give it a try. Its been shown fairly effective in depressive disorders, some early evidence for OCD and anxiety etc...

I dislike the stimulating part but apparently it is also anxiolytic, which would be a good thing. Perhaps I could combine it with something like Clonidine if it enhances NE too much.

5HT-2C antagonism has a bunch of other effects, on the adrenal and sexual hormonal axes, for example, which sound as if they could be beneficial to me. It can also be pro-sexual apparently, which would be welcome if it works.

Right now I am in remission from depression, but insomnia is terrible. I would want to use it right now primarily for insomnia and hopefully to reduce future depressive episodes, which are sure to happen otherwise.

A family member with horrible post-partum insomnia claims agomelatine fixed her up, but it took 4 months. Hard to say if she would have recovered anyway.

Edited by nowayout, 04 July 2013 - 06:21 AM.

[elemerendero1]

antagonising 5HT-2c is stimulating it acts as an NDDI (noradrenaline and dopamine dis-inhibitor). I find Agomelatine to be a little sedating, there is certainly no real reason not to give it a try. Its been shown fairly effective in depressive disorders, some early evidence for OCD and anxiety etc...

I dislike the stimulating part but apparently it is also anxiolytic, which would be a good thing. Perhaps I could combine it with something like Clonidine if it enhances NE too much.

5HT-2C antagonism has a bunch of other effects, on the adrenal and sexual hormonal axes, for example, which sound as if they could be beneficial to me. It can also be pro-sexual apparently, which would be welcome if it works.

Right now I am in remission from depression, but insomnia is terrible. I would want to use it right now primarily for insomnia and hopefully to reduce future depressive episodes, which are sure to happen otherwise.

A family member with horrible post-partum insomnia claims agomelatine fixed her up, but it took 4 months. Hard to say if she would have recovered anyway.

Quiet ... antagonism at 5-HT2C receptors is very anxiolytic.

Why not try mirtazapine then? It 'an antagonist at 5-HT2C receptors (indeed I think is a inverse agonist, which in addition to antagonize also decreases the number of receptors and is even better in this case), and also of the 5-HT2A receptors and other ... is also an antihistamine, so in addition to increase slow-wave sleep (5-ht2c/2a) also induces drowsiness. All this without agonize melatonin receptors, which as you say would promote sleep, decreased fertility (sperm-level) and reduced testosterone ... and among other things to me melatonin has never done anything for sleep.

[nowayout]

antagonising 5HT-2c is stimulating it acts as an NDDI (noradrenaline and dopamine dis-inhibitor). I find Agomelatine to be a little sedating, there is certainly no real reason not to give it a try. Its been shown fairly effective in depressive disorders, some early evidence for OCD and anxiety etc...

I dislike the stimulating part but apparently it is also anxiolytic, which would be a good thing. Perhaps I could combine it with something like Clonidine if it enhances NE too much.

5HT-2C antagonism has a bunch of other effects, on the adrenal and sexual hormonal axes, for example, which sound as if they could be beneficial to me. It can also be pro-sexual apparently, which would be welcome if it works.

Right now I am in remission from depression, but insomnia is terrible. I would want to use it right now primarily for insomnia and hopefully to reduce future depressive episodes, which are sure to happen otherwise.

A family member with horrible post-partum insomnia claims agomelatine fixed her up, but it took 4 months. Hard to say if she would have recovered anyway.

Quiet ... antagonism at 5-HT2C receptors is very anxiolytic.

Why not try mirtazapine then? It 'an antagonist at 5-HT2C receptors (indeed I think is a inverse agonist, which in addition to antagonize also decreases the number of receptors and is even better in this case), and also of the 5-HT2A receptors and other ... is also an antihistamine, so in addition to increase slow-wave sleep (5-ht2c/2a) also induces drowsiness. All this without agonize melatonin receptors, which as you say would promote sleep, decreased fertility (sperm-level) and reduced testosterone ... and among other things to me melatonin has never done anything for sleep.

I tried mirtazapine. It didn't help for sleep except the first night (I'm immune to the sedation effect of antihistaminics). Instead it made sleep worse (caused vivid and utterly exhausting nightmares all the time when I did sleep.) Mirtazapine is a very "dirty" drug, hitting a whole shitload of receptors indiscriminately. Why should I possibly expect anything good to come of antagonizing ALL of those receptors? I didn't like the way it made me feel.

Agomelatine is in this sense a much much cleaner drug. Hits melatonin receptors and 5HT-2C receptors. That is all.

As for the hormonal effects of melatonin, you make a valid point, BUT agomelatine is not melatonin. Also, agomelatine's 5HT-2C antagonism should have a beneficial effect on sex and adrenal hormones (Wikipedia 5HT-2C page has a good entry level discussion of these hormonal effects). Specifically, it should raise testosterone, and it lower the elevated cortisol characteristic of chronic anxiety and of certain subtypes of depression. It has been shown in many studies not to have sexual sides, and google gives me several anecdotal accounts of pro-sexual effects of agomelatine.

Agomelatine has also ben shown in studies to normalize circadian rhythm and improve sleep architecture. Like its antidepressive effect, this likely is a consequence of both the melatonergic and 5HT-2C effects in concert.

Edited by nowayout, 05 July 2013 - 07:51 AM.

[hullcrush]

Can anyone think of a faster-acting anti-suicidal cocktail than Li/MAOI, other than Ketamine? I simply could not (hypothetically) function on 30 mg Mirtazapine and 200 mg Venlafaxine, although tolerability seems good. Riluzole is another option that would have highly variable response I'd assume.

Edited by hullcrush, 30 July 2013 - 05:14 AM.

[Reformed-Redan]

Can anyone think of a faster-acting anti-suicidal cocktail than Li/MAOI, other than Ketamine? I simply could not (hypothetically) function on 30 mg Mirtazapine and 200 mg Venlafaxine, although tolerability seems good. Riluzole is another option that would have highly variable response I'd assume.

No professional advice; but, anti-psychotics might help if thoughts are getting overwhelming. Then start a SSRI, maybe?

[Tom_]

Depending on your depressive symptoms a TCA or MAOI may be more useful - however until you have given a good trials for other drugs I wouldn't bother moving to them - as they prove little to no more effective and are much less tolerable.

I'm against the use of Riluzole, the evidence base just isn't there.

Now reducing suicidal thoughts in the short term is unfortunately best managed by behavioual-psycho-social interventions. Distraction, self soothing, talking and pleasure - I'm happy to give you more information on the matter but will wait for you to ask for it.

Drug wise you have a few options - although this is not something I would recommend traditional pharmacological drugs for (apart from perhaps stimulants). DLPA as a precursor to dopamine and noradrenaline is a good option at doses of 500-2000mg in one go and should provide some relief from low mood within the hour. There is some very poor quality & quantity research showing paradoxically that a nicotine patch can improve severe depressive symptoms for a few hours in nicotine naive people. Caffeine acting as a stimulant may also be beneficial. Mixing the three at slightly lower doses is a good option - following this, get yourself out and about and doing something, talking to someone, exercise, a movie w/e.

[Reformed-Redan]

I would not combine DLPA, Caffeine, and nicotine. That seems like a mixture that will induce severe anxiety.

[Tom_]

Its better than suicide/attempt. Often due to shared pathophsyology if you can reduce the depressive symptoms anxiety becomes less of a problem and if the anxiety is there the you can always use mono/di therapy or lower doses a lot.

[Reformed-Redan]

Its better than suicide/attempt. Often due to shared pathophsyology if you can reduce the depressive symptoms anxiety becomes less of a problem and if the anxiety is there the you can always use mono/di therapy or lower doses a lot.

I personally think talking it out is a much better option than turning up the knob with more the possibility of a panic attack or something like that. Too much caffeine makes me feel shitty. DLPA makes me feel spaced out in large doses and too much nicotine makes me want to puke. Mix all of that together and it doesn't look pretty.

[hullcrush]

Just to clarify, I'm not asking for personal help. Posting for Tom, based on MAOI/Lithium cocktail on case reports.

[nowayout]

Been prescribed modafinil 50mg. I will be increasing the dose if necessary in three weeks at my review appointment. Currently on:

Venlafaxine 225, Mofainil 50mg, Agomelatine 50mg & Melatonin 3mg.

An anecdotal update regarding my response to agomelatine 25 mg. I think it is really helping my sleep, and the onset of effectiveness was quite rapid. That's really remarkable, given my history of refractory insomnia that has been discussed here before (and my resistance to melatonin itself). I know it's the agomelatine since I'm not on any other psych drugs. As for anxiety it is difficult to say since we are in the middle of a couple of family emergencies. Hope it helps you too Tom.

Edited by nowayout, 01 August 2013 - 09:10 AM.

[Tom_]

Venlafaxine pooped out. Agomelatine I was resistant to before hand. Modafinil sees to me making me worse.

[nowayout]

Onset of agomelatine for my sister took 2 months. Full normalization of sleep for her about 4. I assume you gave it enough time, right? Did you try the lower dose first? Also, could the other drugs have masked its effect, which is quite subtle?

I have definitely been sleeping better with it but it is early for full effect and I do use a benzo as a rescue medication some nights when I still get anxiety related sleep latency issues. What happens for me with it is I still wake up several times a night BUT fall asleep again easily, which is new. I have to take it right before bed, doesn't seem to work well if I take it and then read a book.

Edited by nowayout, 02 August 2013 - 06:09 AM.

[Tom_]

I was on it for three months as a monotherapy. I did try 25mg first.