![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 17 of 17. This is the beginning of the thread.
Posted by Meltingpot on May 17, 2009, at 11:35:34
Hi,
In the last 8 years by some flukey quirk of fate I've only responded to 40mg of Seroxat and then it stopped working after 2 years. I've since been unable to recapture the feeling.
As I've tried adding a lot of different meds to seroxat to no avail, around 12 weeks ago I decided to try clomipramine partly because I read on this board that clomipramine has the highest affinity for 5HT after Seroxat.
Now clomipramine at 150mg does seem to help the depression/anxiety a bit but it is also making me really, really tired all of the time. Therefore I don't think it is working that well. When the seroxat worked for me I had an increase in energy and could stay up later and needed less sleep.
I'm now trying to kid myself or reassure myself that the one good thing that might come out of this trial and other trials is that if I stay off all SSRIs for a year then maybe I could go back on Seroxat at the beginning of next year and have it work again. However, I know that there is no evidence to suggest that this would be the case.
My question is, do tricyclics drugs affect exactly the same 5HT pre-synaptic receptors as SSRIS and do all SSRIs hit the same 5HT pre-synaptic receptors.
My thinking (grasping for ideas) is that if I have a complete break from SSRIs for a year and take tricyclics or MAOIs instead then after a year maybe I could go back on Seroxat and have it work for me again.
I'm not sure what else to do anymore, I'm just looking for some hope and some ideas.
Denise
Posted by ricker on May 17, 2009, at 12:35:38
In reply to 5HT Receptors, posted by Meltingpot on May 17, 2009, at 11:35:34
Hi Denise, I'm no expert with the neurotransmitter workings so I can't say for sure if the clomipramine works the same way, I would think it would.
I was on clomipramine though from 1989 to 1999 at 150 mg. It was probably the best drug for my depression / anxiety..... the daytime sleepiness past after several months for me.
Unfortunately, I met this young, upandcoming p/doc who suggested I give ssri's a go as they were all the rave!! He said it would help with my dry mouth and a few other side-effect that were quite mild?
Well, 10 years later and a whirlwind of meds, clomipramine is beginning to look real good again, I may go back on it.
Stopping the Seroxat for a year or so may give it a kick-start, or, it may not be as efficient as the first time you took it, no one could say for sure. I bet if you stayed on the clompramine for the year, you may not want to switch back!
Whatever you decide, I hope you find success. :-)Regards, Rick
Posted by desolationrower on May 19, 2009, at 0:42:59
In reply to 5HT Receptors, posted by Meltingpot on May 17, 2009, at 11:35:34
well TCAs (at least the tertiary ones, like clomipramine, that affect serotonin) do the same thing wrt 5ht reuptake. they both block the reuptake into the presynaptic neurone. afaik there aren't variation on reutake pumps. if you mean 'do all ssris have the same effect on receptor up/down regulation' well they _should_, but results aren't always consistant.
I'm not too sure what people's singly ssris positive result means. have you tried lamictal?
-d/r
Posted by Meltingpot on May 21, 2009, at 11:31:43
In reply to Re: 5HT Receptors, posted by ricker on May 17, 2009, at 12:35:38
Hi,
I've been on Clomipramine since around March of this year. Although I am better than I was when I first started taking it (I was having constant suicidal thoughts) I'm feeling very sluggish on it.
I dont think it is working as it should work although there are some benefits.
I was hoping that I could turn something bad into something good by telling myself if I just stuck it out for a year on Clomipramine then maybe Seroxat would work again if I revisited it next year. I guess there is no way of knowing.
Denise
Posted by Meltingpot on May 21, 2009, at 11:35:41
In reply to Re: 5HT Receptors, posted by desolationrower on May 19, 2009, at 0:42:59
Hi d/r,
Thanks for the clarification, I was hoping that by taking a tricyclic that I was somehow hitting different neurones to those that were affected by Seroxat and that if I stayed on the tricyclic for a year, the seroxat affected neurones would somehow normalise so that I could go back on the Seroxat again after a year with the same success I had before.
However, if SSRIs and tricyclics do the same thing then I guess that hits my theory on it's head.
I've tried Lamictal and it didn't seem to do anything apart from make me really drowsy and tired when I took it up to 400mg, thanks for the suggestion though.
Denise
Posted by Brainbeard on July 29, 2009, at 16:13:22
In reply to 5HT Receptors, posted by Meltingpot on May 17, 2009, at 11:35:34
Hello there,
Answering your real question is too difficult for me without tedious research, but..
I've been on Seroxat too. The withdrawal was so bad that I promised myself never to take an SSRI anymore. Still, seversal years later, my p-doc pursuaded me to try fluvoxamine (Luvox). It was a completely different SSRI! I have also tried clomipramine and Prozac, and am on sertraline (Zoloft) now. I have learned meanwhile that the SSRIs are actually drugs with very different chemical profiles if you go into the details. They all do SRI, but after that, the roads depart. This is why trying another SSRI can always help.
An attempt at summarizing the different pharmacological and experiential profiles:
* paroxetine/Seroxat/Paxil: strong SRI, also anticholinergic effects (dry mouth!) and H1-antagonism; some affinity for dopamine receptor and also noradrenergic effects; both sedating and activating, can induce (hypo)mania; of all the SSRIs the most likely to induce weight gain in the long term
* fluvoxamine/Luvox: stronger affinity for 5HT3-receptor, which means more initial nausea but more eventual anti-anxiety and anti-OCD (at least in theory..); most sedating of the SSRIs.
* sertraline/Zoloft: some affinity for dopamine reuptake pump, Stahl has even called it a SDRI; activating profile; strong SRI -> strong serotonergic side-effects (sexual, nausea, diarrhoea)
* citalopram/Celexa: one enantiomer is highly selective for 5HT, the other one is counterproductive; affinity for H1 receptor; can lead to faster weight gain; reportedly good for depression + anxiety
* escitalopram/Lexapro: most selective of the SSRIs (only Celexa's good enantiomer); very strong SRI, yet a good side-effects profile; like Celexa, reportedly good for depression + anxiety
* Prozac/ fluoxetine: least selective of the SSRIs; is actually a more potent 5HT2C-blocker, thereby raising dopamine and noradrenaline levels; metabolite is stronger SRI than mother-drug and has an exotic long half-life of more than a week; very strong 2D6-inhibitor -> drug interactions!!; both activating and sedating.
I found fluvoxamine to be too apathizing, until I added the clomipramine. Paxil/Seroxat made me hypomanic and fat, eventually, and the withdrawal depression was worse than my initial complaints. Prozac was pretty cool in low doses (5-10mg), but it made me gain weight fast. I'm on low dose Zoloft right now, just 25mg, and I think it's not bad - though I combine it with low dose Geodon, Buspar, the occasional modafinil, selegiline, amisulpride and tianeptine, and daily bits of imipramine and amitriptyline.
I think the SRI most subjectively close to Seroxat might actually be Effexor, but that drug seems to have an even worse withdrawal syndrome.
Posted by Phidippus on November 2, 2009, at 12:54:59
In reply to Re: 5HT Receptors, posted by Brainbeard on July 29, 2009, at 16:13:22
Brainbeard,
Is that you from Crazymeds? This is your buddy who sent you the Dexedrine. Thanks for the Solian by the way-it makes me high.
P
Posted by Brainbeard on November 2, 2009, at 14:18:56
In reply to Re: 5HT Receptors » Brainbeard, posted by Phidippus on November 2, 2009, at 12:54:59
> Brainbeard,
>
> Is that you from Crazymeds? This is your buddy who sent you the Dexedrine. Thanks for the Solian by the way-it makes me high.
>
> PHey Phidippus! Good to see you show up here!! You seemed to have gone up in smoke.
I got the D alright. Thanks! I'm still waiting for the right moment to try it though. I'm a little nervous about it. Not knowing what to expect and all.
Posted by Phidippus on November 2, 2009, at 14:40:13
In reply to Re: 5HT Receptors, posted by Brainbeard on November 2, 2009, at 14:18:56
> You seemed to have gone up in smoke.
Crazymeds keeps kicking me out!
> I'm a little nervous about it. Not knowing what to expect and all
Focus and mood lift :) It diminishes the noise in my head. Effects of the drug last about 6 hours, so it won't be a long trip.
P
Posted by Phidippus on November 2, 2009, at 14:48:35
In reply to Re: 5HT Receptors, posted by Brainbeard on July 29, 2009, at 16:13:22
You forgot one of the most important attributes of Luvox:
It behaves as a potent agonist at the sigma-σ1 receptor and has the highest affinity of any SSRI for doing so. Sertraline and Lexapro also hit this receptor.
> * fluvoxamine/Luvox: stronger affinity for 5HT3-receptor, which means more initial nausea but more eventual anti-anxiety and anti-OCD (at least in theory..); most sedating of the SSRIs.
TURN YOUR BABBLEMAIL ON
P
Posted by Brainbeard on November 3, 2009, at 12:38:01
In reply to Re: 5HT Receptors » Brainbeard, posted by Phidippus on November 2, 2009, at 14:48:35
> You forgot one of the most important attributes of Luvox:
>
> It behaves as a potent agonist at the sigma-σ1 receptor and has the highest affinity of any SSRI for doing so. Sertraline and Lexapro also hit this receptor.
>Not sure if I forgot it, but you're right, I didn't mention it. I AM well aware of it.
> TURN YOUR BABBLEMAIL ON
Got ya.
Posted by metafunj on November 3, 2009, at 14:46:11
In reply to Re: 5HT Receptors, posted by Brainbeard on November 3, 2009, at 12:38:01
How do you turn babblemail on?
Posted by Phidippus on November 3, 2009, at 21:48:28
In reply to Re: 5HT Receptors » Brainbeard, posted by metafunj on November 3, 2009, at 14:46:11
go to http://www.dr-bob.org/cgi-bin/pb/settings.pl
P
Posted by mtdewcmu on January 2, 2010, at 10:55:44
In reply to Re: 5HT Receptors, posted by Brainbeard on July 29, 2009, at 16:13:22
> Hello there,
>
> Answering your real question is too difficult for me without tedious research, but..
>
> I've been on Seroxat too. The withdrawal was so bad that I promised myself never to take an SSRI anymore. Still, seversal years later, my p-doc pursuaded me to try fluvoxamine (Luvox). It was a completely different SSRI! I have also tried clomipramine and Prozac, and am on sertraline (Zoloft) now. I have learned meanwhile that the SSRIs are actually drugs with very different chemical profiles if you go into the details. They all do SRI, but after that, the roads depart. This is why trying another SSRI can always help.
>
> An attempt at summarizing the different pharmacological and experiential profiles:
>
> * paroxetine/Seroxat/Paxil: strong SRI, also anticholinergic effects (dry mouth!) and H1-antagonism; some affinity for dopamine receptor and also noradrenergic effects; both sedating and activating, can induce (hypo)mania; of all the SSRIs the most likely to induce weight gain in the long term
>
> * fluvoxamine/Luvox: stronger affinity for 5HT3-receptor, which means more initial nausea but more eventual anti-anxiety and anti-OCD (at least in theory..); most sedating of the SSRIs.I'm not sure what you mean by this. Do you mean that Luvox directly interacts with the 5-HT3 receptor? Or that somehow it interacts more strongly with the 5-HT transporter at synapses with 5-HT3 receptors?
Posted by Brainbeard on January 2, 2010, at 15:12:53
In reply to Re: 5HT Receptors, posted by mtdewcmu on January 2, 2010, at 10:55:44
> > * fluvoxamine/Luvox: stronger affinity for 5HT3-receptor, which means more initial nausea but more eventual anti-anxiety and anti-OCD (at least in theory..); most sedating of the SSRIs.
>
> I'm not sure what you mean by this. Do you mean that Luvox directly interacts with the 5-HT3 receptor? Or that somehow it interacts more strongly with the 5-HT transporter at synapses with 5-HT3 receptors?
>I'm not sure either; I think the latter.
Posted by mtdewcmu on January 2, 2010, at 17:18:43
In reply to Re: 5HT Receptors, posted by Brainbeard on January 2, 2010, at 15:12:53
> > > * fluvoxamine/Luvox: stronger affinity for 5HT3-receptor, which means more initial nausea but more eventual anti-anxiety and anti-OCD (at least in theory..); most sedating of the SSRIs.
> >
> > I'm not sure what you mean by this. Do you mean that Luvox directly interacts with the 5-HT3 receptor? Or that somehow it interacts more strongly with the 5-HT transporter at synapses with 5-HT3 receptors?
> >
>
> I'm not sure either; I think the latter.
>Maybe it tends to stay in the body rather than accumulating in the brain, and therefore attacks the gut. Prozac is the opposite; brain concentrations wind up much higher than concentrations in the blood.
Posted by Brainbeard on January 3, 2010, at 10:31:23
In reply to Re: 5HT Receptors, posted by mtdewcmu on January 2, 2010, at 17:18:43
> Maybe it tends to stay in the body rather than accumulating in the brain, and therefore attacks the gut. Prozac is the opposite; brain concentrations wind up much higher than concentrations in the blood.
Well, it doesn't just seem to be a 'gut thing'; Luvox is supposed to work especially well for OCD, and this is supposed to be related to its action on 5HT3 receptors. 5HT3 receptors play a role in the release of dopamine and dopamine release plays a role in the reward mechanism of compulsive acts. 5HT3 antagonism blocks this reward mechanism.
Your theory is an interesting one.
This is the end of the thread.
Psycho-Babble Neurotransmitters | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
[email protected]
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.