Clomipramine | The "Gold Standard" when it comes to Depression and OCD?

[AlphaMethylPhenyl]

They phased out opioids for depression in the 50' due to abuse and lesser efficacy comparatively. Dexamyl was taken off the market in 82 I believe.

 

[Bravoncius Roxford]

I believe SSRI/SNRI's are considered the gold standard for depression (by doctors).

Not really. Psychiatrists who treat severe depression will tell you that the most potent antidepressants are either imipramine or the non-selective MAOIs like phenelzine. General practitioners prescribe much more the SSRIs because they treat less severely depressed patients, and because they are not comfortable and experienced in dealing with the side effects and pharmacological interactions of those drugs.

 

[ChemicallyEnhanced]

Not really. Psychiatrists who treat severe depression will tell you that the most potent antidepressants are either imipramine or the non-selective MAOIs like phenelzine. General practitioners prescribe much more the SSRIs because they treat less severely depressed patients, and because they are not comfortable and experienced in dealing with the side effects and pharmacological interactions of those drugs.

The thing was MAOI's is it is SOOO easy to kill yourself on them. Red wine and a steak would do it.

 

[AlphaMethylPhenyl]

The thing was MAOI's is it is SOOO easy to kill yourself on them. Red wine and a steak would do it.

That danger is real, but it isn't so much of a danger as doctors were initially lead to believe. The waters can be tested very carefully.

SSRIs are safe, and usually effective. TCA's and MAOIs may very well be more effective for depression, but the risk of overdose and hypertension/stroke make them not ideal agents to give to someone who doesn't have a great regard for their safety.

 

[Bravoncius Roxford]

The thing was MAOI's is it is SOOO easy to kill yourself on them. Red wine and a steak would do it.

You are wrong. There have actually been very few deaths caused by MAOIs since they were first introduced in 1959. The few deaths, usually resulting from subarachnoid hemorrhage from massive increases of systolic blood pressure to 200+, resulting from people on tranylcypromine after ingesting massive amounts of tyramine. I am talking here 200-400 mg in one sitting. That is because cheeses back in the 1950's and early 1960's contained 10 X more tyramine than today due to the bacterial cultures that were used. Most old cheeses now contain only 40 mg of tyramine per serving, and if you are on a non-selective MAOI, that will give you a 30+ BP increase and a bad headache, but the risk of stroke or death is very, very low. Remember, also, that was only with tranylcypromine, and even back in those days that were no deaths involved with people eating massive amounts of tyramine while ion phenelzine. TCP is not only a potent non-selective MAOI, but also a norepinephrine releaser with about 10% the potency of amphetamine(it is an amphetamine derivative).

But you are right in a way. Tranylcypromine is not a first-line antidepressant. It is an antidepressant for people that are seriously sick. It markedly increases the extracellular concentrations of all the monoamines involved in depression, serotonin, norepinephrine and dopamine, as well as trace amines like phenylethylamine and benzylamine. The increase is more pronounced than what you get from SS(N)RIs, and the increase is not of only 1 or 2 transmitters like with the SS(N)RIs, but all 3. The fact that the increase of individual transmitters is stronger, and also that it increases all 3 transmitters and not only 1 or 2 like the SS(N)RIs, explains why it is more effective for severe depression.

In general, the people that respond the better to the non-selective MAOIs are profoundly apathetic people that show little energy, little reactivity, low appetite and general inability to feel pleasure. People that are very depressed with delusional thoughts, psychosis and intense anxiety respond better to clomipramine. Clomipramine is a very powerful SNRI that inhibits the reuptake of serotonin more powerfully than the SSRIs, and the reuptake of norepinephrine than NRIs like reboxetine. It is ideal for severe anxious/psychotic depression because it increases serotonin very strongly, but without also increasing dopamine like the non-selective MAOIs. Raising dopamine is not ideal for these depressives since it tends to make their delusional thoughts and anxiety even worse. The SSRIs are no better than placebo for severe depression of any type, although they work significantly better than placebo for mild depression.

 

[Skorpio]

S-citalopram is, honestly, the best anxiolytic I have ever taken. It is as good or better than clonazepam, but without the brutal hangovers. But as an antidepressant it is not very effective, unless your "depression" is mostly severe anxiety and angsty feelings. (S)citalopram is not very good to lift melancholia.

Of course, all SSRIs have this problem: somewhat effective as anxiolytics, but not very effective at lifting truly depressed mood. The only SSRI that has ever shown any effectiveness at treating severe melancholic depression is paroxetine. And I suspect that has more to do with it's anti-muscarinic effect than it's SSRI ability. Of course, paroxetine is a very powerful SRI, much more potent than the other SSRIs and almost as potent as clomipramine. The extreme potency at inhibiting serotonin reuptake coupled with it's muscarinic receptor antagonism probably explains it's superior effectiveness for serious depression. I actually took paroxetine as a teenager for severe social anxiety, and while it made my shyness go away, it make me feel sleepy and grogged out all day long. And after about a couple weeks, I felt like I had no emotion at all. No anger, or joy, or sadness, or anxiety. I became a robot basically. It is a nasty drug, and probably the only SSRI that should be reserved for serious depression and prescribed only as a second or third-like treatment for depression.

Isn't paroxetine like two orders of magnitude more potent at SERT than at the muscarinic receptors? I'm getting my numbers from the paper linked on the Wikipedia page. What sources are you using for your claims?

A comparative review of escitalopram, paroxetine, and sertraline: are they all alike?

It is known that newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), provide advantages in tolerability over antidepressants such as the tricyclics. However, even within the SSRI class, differences in efficacy or tolerability ...

www.ncbi.nlm.nih.gov

 

[dopamimetic]

Opioids definitely work for a certain subgroup of people, even more so when combined with a stimulant and/or an NMDA antagonist. Oh yeah I know I've said the opioids were useless, and indeed it feels that way, like you've changed and the only thing what remains is addiction, some sort of limiting sedation and that's it but well after quittig the morphine (200mg XR/d), which really isn't that hard if you do it right, all the little things came back after a while. Morphine definitely is a mood-stabilizing agent, a powerful anxiolytic and heavily suppresses anger/aggression. Just that it doesn't really increase your mood even when combined with a SSRI, the combo with d-amph does and memantine too.
At least w/o access to RCs I'd give much now to get back on morphine ... if it just wasn't so strangely effective in inducing positive symptomatic like hearing voices out of nowhere.

Paroxetine, umm this was actually the first med to induce sleep deprivation in me after I couldn't sleep just one minute at night even with z-drugs. Vortioxetine is similar, citalopram to a lesser degree but they all worsen impulse control unfortunately.

Which tricyclic is the most effective one btw which doesn't touch NE too much? Think I only know doxepine in low dose and opipramol, both more or less useless.

 

[Mask0ff]

S-citalopram is, honestly, the best anxiolytic I have ever taken. It is as good or better than clonazepam, but without the brutal hangovers. But as an antidepressant it is not very effective, unless your "depression" is mostly severe anxiety and angsty feelings. (S)citalopram is not very good to lift melancholia.

Of course, all SSRIs have this problem: somewhat effective as anxiolytics, but not very effective at lifting truly depressed mood. The only SSRI that has ever shown any effectiveness at treating severe melancholic depression is paroxetine. And I suspect that has more to do with it's anti-muscarinic effect than it's SSRI ability. Of course, paroxetine is a very powerful SRI, much more potent than the other SSRIs and almost as potent as clomipramine. The extreme potency at inhibiting serotonin reuptake coupled with it's muscarinic receptor antagonism probably explains it's superior effectiveness for serious depression. I actually took paroxetine as a teenager for severe social anxiety, and while it made my shyness go away, it make me feel sleepy and grogged out all day long. And after about a couple weeks, I felt like I had no emotion at all. No anger, or joy, or sadness, or anxiety. I became a robot basically. It is a nasty drug, and probably the only SSRI that should be reserved for serious depression and prescribed only as a second or third-like treatment for depression.

#1 - what dose did you take?
#2 - have you ever tried fluvoxamine?

I am considering these two SSRIs due to what i suspect is genetic or phenotypical disposition towards low 5HT production. Also, your posts fucking rock; appreciate the work you've put in.

 

[plumbus-nine]

Personally, after years on various S/NRIs (venlafaxine, paroxetine, ex/citalopram, sertraline, mirtazapine, mianserin), let alone all the other meds, I'd heavily suggest to try ketamine first.
SSRIs do potentially permanently alter your brain - just think of the ability for long term sexual dysfunction and extrapolate this to the mind. It's certainly less severe than with antipsychotics but long term SSRI shares some of similar effects on metabolism and mood. I don't wanna say they were outright bad but would compare it to getting on opioids. Maybe you'll benefit enough for the long term changes to be less relevant. Maybe you can get off it easy, maybe you'll need it forever. One just can't know before but one can make a wise choice.

Low 5HT production - did you try 5-HTP?

 

[abc1986]

My personal experience with SSRI's is that they make me worse. They turn anxious depression into a lethargic depression of pure apathetic despair. They also make my adhd a ton worse and destroy my attention and focus to the point I don't even feel safe driving a car or operating machinery or power tools. One of my P-docs response was that 6 weeks wasn't long enough and I needed to increase the dose!!! I had some luck with nortriptyline, but I've had my best luck with tianeptine. Bromantane and memantine do a decent job for adhd. I've only had limited success with controlling anxiety with this trio. There's things that help with anxiety I know of but they dull my wits and make me numb and aren't acceptable for me. The trio I'm on now, I source myself and decide for myself and I've never had better results. It's a shame it's so expensive for meds to get through the FDA b/c then all kinds of meds that are first line with different MOA's then SSRI's available in Europe and Russia would be American doctor's arsenals like tia.

I think one of the biggest problems with the way depression is treated is that so many doctors try to treat depression as the same disorder. That's why I think you have such low efficacy rates. It's been some time since I've looked up but people who try multiple classes have much much better remission rates and I think that's why. It's like giving everyone who's got a fever, sore throat, and runny nose the same diagnosis and medicine! I like Dr. Amen's take on this. Actually using brain imaging to help with diagnosis. I don't imagine at all that he's got it all figured out but I think he's going in the right direction.

 

[plumbus-nine]

They'd need to measure 5-HT in brain before giving SSRI but that's afaik impossible to date. Some do quackery like measuring 5-HT in blood or urine. Anxiety is not depression is not psychosis and schizophrenia is no fucking basket for all the failed diagnoses....

Oh yeah fully agree the only requirement for med approval should be relative safety. No diagnosis, no treatment, just chemical agents like with RCs, and then fucking real specialists with real experience, or the internet. At least here they started to do it this way, you buy meds by the chemical name, no prescription (besides antibiotics, benzos, opioids w/exception of codeine), leaflet, or healing promise. But it's more for to save money and approval seems to be the same like everywhere, unfortunately. The irreversible MAOIs aren't even available, nor are things like lisuride, selegiline patches, etc.pp.

SSRIs are damaging more lives than they save**, imho. Just start with the sexual dysfunction which I thankfully didn't even get fully, I "just" can't perform without an SSRI anymore. Stays for months.
Pregabalin is a very good med if you ask me but it of course has too its side effects. It is the only non-narcotic and non-dissociative (both somewhat doubtful) which is able to switch off anxiety. Morphine can be good but its downstream hormonal suppressive effect is the real downside in younger population, when using all the possibilities, withdrawal becomes background worry - I've gone off morphine at least 4 times, while venlafaxine still has me in its claws.

Stronger antipsychotics / D2 antagonists should be scheduled and only prescribed in treatment resistant psychosis with either violence or the individual wanting them. I've only seen people relatively new on them who liked them and these with years or decades had altogether horrible side effects. Even from just quetiapine. They certainly felt like that.

They completely neglect NMDA antagonists, dopamine agonists/allosteric modulators, same for 5-HT 2a, and delta (& mu in some places like here) and more. It's like they throw the good out and sell us the toxic remainders. Politically required.

** which is exactly the reason for these rigid approval processes. That they want to filter out what doesn't happen, instead pharm corps throw out promising things for concentrating on yet another cash cow or charge like $10.000/pill for less common sicknesses..

Raising dopamine is not ideal for these depressives since it tends to make their delusional thoughts and anxiety even worse. The SSRIs are no better than placebo for severe depression of any type, although they work significantly better than placebo for mild depression.

Have to disagree. Anxiety might be the most limiting symptom I had and the only thing which really helps are dopaminergics, while norepinephrine worsens. Memantine is a good one too, for example. I didn't get worsening of psychotic features on memantine up to crazy high dosages, or on your regular dissociative (careful with them if you had psychosis before but not "psychotic depression" which imo doesn't really exist), while stims do cause psychosis pretty readily.1

Unsure here, but dopamine isn't just D2. Some dopamine receptors are excitatory, others are inhibitory, there are autoreceptors etc.. will have to try amisulpride 25-50mg/d to compare memantine (D2-high) to natural dopamine. Natural DA will eventually end up as NE due to beta-hydroxylase while agonists rather cause lower NE (hypotension).
Still I believe that NE is at least heavily anxiogenic, if not also contributing to psychosis. In dopamine agonist withdrawal we see much the same symptoms like in mild morphine withdrawal, a surge in NE which causes many bad symptoms.
Yeah, too little NE for too long causes depression, I've learned it the hard way when taking 150mcg/d clonidine for sleep over months. But depression/anxiety doesn't equal to too less NE.

Oh, 1cP-LSD (200mcg if that's a low dose and I'm correct) actually accelerated healing from toxic psychosis due to abuse of darknet adulterated dissociatves. Even when you hear voices, sometimes the docs are wrong and your brain knows what it wants to do, but can't because of blocked 5ht2a. No more voices for around a whole year now, and I didn't take a single antipsychotic for more than 2 following days each because they just felt even more toxic.
Edit: I've been able to do full conversation with my voice from time to time, it was like a child in some ways - maybe just a mirror of myself (unless I took anticholinergics, it was just one, and somehow I began to think of it as a part of my brain which was cut off from the rest and reached through to find a solution) ... it wanted me to do DMT. Wasn't available but the coincidence brought me 1cP-LSD xD lol sometimes things are weird. Remember somebody around here whose psychosis was to take morphine, he was arrested trying to rob a pharmacy but well it might have been a solution ...

 

[speedlimitssuck89]

I did some gnarly bad stuff on EMSAM, like seriously bad I should have been fined at least lol.

what was your experience with emsam? what were some good and bad aspects?