There is a certain irony here:
"Ugh, tricyclics! Low selectivity for the serotonin transporter over the noradrenaline transporter, and what's with all the antagonism at histamine, alpha and 5HT2A receptors? Dirty stuff! Thankfully this is the 90's, and we have Selective Serotonin Reuptake Inhibitors!"
"...eh, maybe you do need a bit of a noradrenaline boost on top. Thankfully this is 2000, and we have SNRI's!"
"...and maybe it would be nice to have some histamine/5HT2-antagonism-mediated anti-anxiety action, too. It's 2010, try some Seroquel or Mirtazapine on top of your antidepressant!"
"...and we do want some alpha1-adrenergic receptor antagonism to normalize the HPA axis! And some FIASMA / BDNF would be nice. R&D, get started! It's 2018!"
"...or just have a tricyclic."
I would not be surprised if they try to market anticholinergics as new groundbreaking anxiolytics in a few years from now...
I've been reading the following articles:
Seems to be a pretty potent drug: SNRI, antagonist of the alpha1-adrenergic receptor, the histamine H1 receptor, the serotonin 5-HT2A, 5-HT2C receptors, the dopamine D1, D2, and D3 receptors, and the muscarinic acetylcholine receptors. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system; so that speaks for itself.
The reviews on drugs.com and other sites also are quite positive.
The following ranking is interesting: http://slatestarcodex.com/2015/04/30/prescriptions-paradoxes-and-perversities/
These numbers are based on aggregated patient ratings. Top 4 drugs:
# Nardil 1.25
# Parnate 1.23
# Chlomipramine 1.22
# Emsam/selegeline 1.07
=> Clomipramine roughly on pair with MAOI, followed by Nefazodone (R.I.P) and Imipramine. Imipramine is also a potent SNRI, but lacks the strong 5HT-antagonism compared to Clomipramine. I suppose that's the pharmacological difference which makes Clomipramine superior... ?
Clomipramine exhibits some antagonism of dopamine D1, D2 and D3 receptors... can one expect some clinical & therapeutic benefits from this?
Clomipramine acts as a functional (potent!) inhibitor of acid sphingomyelinase (FIASMA): http://en.wikipedia.org/wiki/FIASMA
Some interesting graphs regarding antidepressant FIASMAs: http://d-nb.info/1011278227/34
Who here has been on Clomipramine and what were your experiences with it?
It's the time of year again when I start having trouble sleeping, and I've tried numerous meds for insomnia (and at the same time I have hypersomnia too... go figure...). My insurance doesn't cover Silenor, brand-named doxepin in 3 mg and 6 mg micro-doses, so my pdoc gave me Sinequan (doxepin) 50 mg. I've tried doxepin before, but at 75 mg, which for some stupid reason my insurance treats as tier IV non-preferred brand name, but all the other doses my insurance is like "oh you're cool, that's tier II..." Anyway...
So the doxepin 50 mg worked extremely well the first night, and the first night only. After that, I have trouble initiating and maintaining sleep, so I get anywhere from 3-4 hours of fragmented sleep according to my Fitbit. Then I'm tired all day, but I can't really nap because of my stimulant, which is nice because it keeps me going and whatnot, but I don't feel like keeping going because I'm exhausted. So I tried taking two doxepin one night for 100 mg and I actually felt a little stimulated and got about 2 hours of sleep.
So I have two questions for those who have taken doxepin:
If 50 mg isn't working for sleep, do I need to go lower in dose? Like 25 mg or even 10 mg? Does doxepin actually become stimulating in higher doses like some of the TCAs? Thanks in advance for any input!
I've been taking Sertraline (50mg daily) for 9 months now.
Reason for taking Sertraline: Depression & SAD. Maybe some GAD.
So Sertraline treats my baseline anxiety quite well, also got rid of digestion problems, but I am struggling with side effects:
Motor restlessness, agitation. I've always been quite "hyperactive", but Sertraline has worsened it by a good amount. I cannot sit still, I feel I have to walk, to pace. I move my fingers and toes to "release" some of the energy. Also lots of fidgeting, rocking back and forth. I have the urge to crawl out of my skin.
_ Indifference, amotivation, apathy, lethargy. I get less things done on Sertraline than before Sertraline. Just want to sit around and do nothing. It is really disconcerting, because things would happen like a major car malfunction or someone f*ck*ng me over and I'd be thinking "this SHOULD piss me off, but, meh.. whatever.."! I've been doing some reading & research and there is the hypothesis that SSRI-induced-stimulation of 5HT2C & 5HT2A receptors dampens the dopaminergic transmission in the prefrontal cortex thus causing these specific SSRI side effects. Antagonism / Inverse Agonism of these receptors should theoretically resolve the problem. What medications do antagonize / inverse agonize these receptors? Are there any other reliable theories on what is causing this? And what could help?
_ Sleep disturbances, f*ck*d up sleep cycle, crappy sleep. Falling asleep is difficult, shallow sleep, waking up a lot in the night => daytime fatigue. (This week I've been sleeping a lot, maybe because the body wants to compensate for last months's bad sleep?)
_ Heat intolerance + hot flashes. My entire life I've been loving warmth and heat. I was the guy who could sit at the top row in the sauna for 20min @ 100°C (212 °F), but right now I cannot even stand a mild summer. And I have been getting hot flashes lasting between 10-15 mins several times a day (I am a 29 year old male, so pretty sure it is not menopause related)
_ I also lost quite a bit of weight, partially due to loss of appetite, but also due to increased metabolic rate. My appetite is back to normal, but I am still not gaining any weight. BMI 20 right now.
_ Palpitations (BUM BUM BUM BUM. BUM . . . BUM . . . BUM)
_ mild headaches and "pressure" in my neck. Nothing bad, but very annoying in the mid and long term. Now I don't know what to do. I need some meds with "less" side effects. I haven't tried any combination of medications yet. To my dismay my doc prefers the SSRI merry go around aka SSRI carousel. I found a new psychiatrist and I will have a first appointment in about a month, but I don't know what to suggest to him. Has anybody some experience with a similar situation? Which antidepressant would be suitable for me? If there is someone who had the same problem and found some solution: please write me. Thank you. Greetings from Germany!
Researching TCA's because it may be something I will bring up to pdoc. I have only tried 1 (Nortryptaline).
Does anyone know how to choose a TCA by the "binding profiles?" Like for example if someone wants something less sedating with little potential for weight gain, which TCA would be better?