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Dr. Bob is Robert Hsiung, MD,
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Posted by Phillipa on August 4, 2006, at 16:40:28
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow. » SLS, posted by theo on August 4, 2006, at 16:04:36
Good luck Scott. I really mean it. Love Jan
Posted by SLS on August 4, 2006, at 17:52:24
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow. » SLS, posted by theo on August 4, 2006, at 16:04:36
> Isn't Meridia an obesity drug?
Yup.
It was originally developed as an antidepressant.
Sibutramine and its metabolites are reuptake inhibitors of serotonin, norepinephrine, and dopamine. During clinical trials for depression, I guess weight-loss showed up as a predominant side effect, and the rest was history...
The clinical trials of sibutramine for depression do not appear on Medline. They are probably too old. I guess one would have to leave cyberspace temporarily and travel to an actual library to search out real medical journals. However, one could review the studies involving binge-eating and note the effect sibutramine has on mood in that disorder.
Back in the old days, I don't particularly care how well sibutramine performed compared to placebo or imipramine. All it has to do now is perform well for me. N=1
Interestingly, sibutramine was the only antidepressant tested that rapidly downregulated NE alpha-2 presynaptic autoreceptors.
1: Psychopharmacology (Berl). 1992;107(4):497-502.A comparison of various antidepressant drugs demonstrates rapid desensitisation of alpha 2-adrenoceptors exclusively by sibutramine hydrochloride.
Heal DJ, Prow MR, Gosden J, Luscombe GP, Buckett WR.
Boots Pharmaceuticals Research Department, Nottingham, UK.
The functional status of presynaptic and postsynaptic alpha 2-adrenoceptors in murine brain was respectively monitored using the hypoactivity (sedation) and mydriasis (pupil dilatation) responses to clonidine (0.1 mg/kg IP). Both responses were attenuated 24 h after 3 days of injection of sibutramine hydrochloride (3 mg/kg IP). To ascertain whether this property was exclusive to sibutramine, the following antidepressant drugs were also tested for their ability to down-regulate alpha 2-adrenoceptors rapidly: amitriptyline, doxepin, nomifensine, desipramine, amoxapine, fluoxetine, zimeldine, tranylcypromine and mianserin. When given for 3 or 5 days at the low dose of 3 mg/kg IP, none of the other antidepressants reduced clonidine-induced hypoactivity or mydriasis. Furthermore, increasing the dose of amitriptyline, doxepin, nomifensine, desipramine, amoxapine and tranylcypromine to 10 mg/kg IP did not enable these antidepressants to attenuate the alpha 2-adrenoceptor-mediated responses after 3 days of treatment. An electroconvulsive shock (ECS; 200 V, 2 s) given once daily attenuated clonidine-induced mydriasis, but not hypoactivity, when administered for 3 days and both responses when administered for 5 days. In conclusion, this comparative study using antidepressant treatments with differing pharmacological modes of action demonstrated that sibutramine was the only drug which rapidly down-regulated pre- and postsynaptic alpha 2-adrenoceptors. ECS down-regulated postsynaptic alpha 2-adrenoceptors when given for 3 days, but required 5 days to desensitise both alpha 2-adrenoceptor populations.
PMID: 1351304 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1351304&dopt=Abstract
- Scott
Posted by mayzee on August 4, 2006, at 20:17:23
In reply to Sibutramine (Meridia) - Starting it tomorrow., posted by SLS on August 4, 2006, at 12:37:42
Scott, do you mind sharing what is your diagnosis (-es)?
Wishing you great success with this,
--mayzee
Posted by SLS on August 4, 2006, at 22:03:09
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow. » SLS, posted by mayzee on August 4, 2006, at 20:17:23
> Scott, do you mind sharing what is your diagnosis (-es)?
>
> Wishing you great success with this,
>
Hi Mayzee.I have the type of bipolar disorder where you are depressed all of the time except for the rare occasion when a drug provokes a manic reaction. At one point, this was to be named Bipolar III. Now, I don't know what it is to be named in the new classification scheme.
- Scott
Posted by SLS on August 5, 2006, at 8:50:06
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow., posted by SLS on August 4, 2006, at 17:52:24
> The clinical trials of sibutramine for depression do not appear on Medline. They are probably too old.
I am wrong.
Sibutramine was discovered in 1987.
I don't know why they don't appear. They might not have demonstrated sufficient efficacy. However, many authors were left with the impression that it had a promising future as an antidepressant.
Sibutramine was approved in 1997 as an anorexiant to treat obesity. It acts as an appetite suppressant and activates brown adipose tissue (BAT) to stimulate thermogenesis.
Other patents for sibutramine have been filed to treat Parkinsons, Tourettes, non-Tourettes tics, fibromyalgia, PTSD, OCD, CFS, ADD, and several other organic brain disorders.
http://www.freepatentsonline.com/6323242.html
- Scott
Posted by theo on August 5, 2006, at 15:05:05
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow., posted by SLS on August 4, 2006, at 17:52:24
> > Isn't Meridia an obesity drug?
>
> Yup.
>
> It was originally developed as an antidepressant.Let me know how it goes, I'm always game for being creative and trying new things that could help this lovely illness. I don't want to paint a bad picture of EMSAM, but felt the worse I've ever felt on the first day of a med. I'm really having a hard time considering putting on another 1/4 patch. I had to go out of town to visit family today and there was no way I could attach one. I'll have retry Monday if I decide to ride that pony.
Posted by Maximus on August 5, 2006, at 18:10:10
In reply to Sibutramine (Meridia) - Starting it tomorrow., posted by SLS on August 4, 2006, at 12:37:42
> My doctor and I agreed to give sibutramine a try. I'll be at 10mg for a week, and then 20mg.
>
>
> So, beginning tomorrow:
>
> nortriptyline 100mg
> Lamictal 150mg
> Topamax 100mg
> Abilify 10mg
> sibutramine 10mg
Hi Scotty,Wow, another drug! I think this will be the one you have been looking for a while, i hope so. I think being on Meridia feels like being on a huge dose of Effexor. Give it a good trial.
On what do you attribute your "ultra-resistance" to treatment, if you don't mind?
Bye.
Posted by SLS on August 6, 2006, at 8:13:03
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow. » SLS, posted by Maximus on August 5, 2006, at 18:10:10
Hi.
> Wow, another drug! I think this will be the one you have been looking for a while, i hope so. I think being on Meridia feels like being on a huge dose of Effexor. Give it a good trial.
Thanks for the well-wishes.
> On what do you attribute your "ultra-resistance" to treatment, if you don't mind?
Some very efficient negative feedback loop that serves to maintain an errant homeostasis. I just don't know where the mechanism lies that facilitates this process. I used to think that it was a presynaptic thing, but it happens so fast. My system will adapt within three days of responding to medication. I'm not sure what to think. Got any ideas?
- Scott
Posted by Maximus on August 6, 2006, at 13:13:49
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow. » Maximus, posted by SLS on August 6, 2006, at 8:13:03
> Some very efficient negative feedback loop that serves to maintain an errant homeostasis. I just don't know where the mechanism lies that facilitates this process. I used to think that it was a presynaptic thing, but it happens so fast. My system will adapt within three days of responding to medication. I'm not sure what to think. Got any ideas?
Do you have a good environment without too much stress?
For the medication, i'm not sure. The thing is you have already taken some extra powerful and very clever combination of meds. Personally i would ask for some Lithium, on top of all your current meds.
I'm "fascinating" by your perseverance. Don't stop buddy! Bye.
Posted by ed_uk on August 7, 2006, at 13:37:57
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow., posted by SLS on August 4, 2006, at 22:03:09
Hi Scott
Why did you decide that you will increase your sibutramine dose from 10mg to 20mg, when 15mg is the usual maximum dose?
Hope the sibutramine helps :) It seems like quite a 'stimulating' drug.
Ed
Posted by SLS on August 7, 2006, at 19:47:41
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow. » SLS, posted by ed_uk on August 7, 2006, at 13:37:57
> Hi Scott
>
> Why did you decide that you will increase your sibutramine dose from 10mg to 20mg, when 15mg is the usual maximum dose?
>
> Hope the sibutramine helps :) It seems like quite a 'stimulating' drug.If I can tolerate it, why not? There really is no guideline for depression. I don't want to waste time being a guinea pig on some dosage finding mission. If it works, I can try reducing it later. Peter Mueller, MD has used 20mg for his patients with fibromyalgia and various CNS disorders. They seem to do well with it. We'll see how I tolerate the 10mg first.
- Scott
Posted by Phillipa on August 7, 2006, at 20:41:54
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow. » ed_uk, posted by SLS on August 7, 2006, at 19:47:41
Scott you sound so determined and strong. I know it will work. You deserve it with all you've been through. Love Jan
Posted by theo on August 8, 2006, at 9:54:55
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow., posted by SLS on August 4, 2006, at 22:03:09
> I have the type of bipolar disorder where you are depressed all of the time except for the rare occasion when a drug provokes a manic reaction. At one point, this was to be named Bipolar III. Now, I don't know what it is to be named in the new classification scheme.
>
>
> - ScottWow, sounds like me. By the way, I noticed in your cocktail, no more Keppra? Did you find it not doing much?
How's the Meridia?
Posted by SLS on August 8, 2006, at 10:03:15
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow. » SLS, posted by theo on August 8, 2006, at 9:54:55
> > I have the type of bipolar disorder where you are depressed all of the time except for the rare occasion when a drug provokes a manic reaction. At one point, this was to be named Bipolar III. Now, I don't know what it is to be named in the new classification scheme.
> >
> >
> > - Scott
>
> Wow, sounds like me. By the way, I noticed in your cocktail, no more Keppra? Did you find it not doing much?Keppra is a funny drug. I found that it actually made my depression noticeably worse at higher dosages. At lower dosages, I was experiencing diminishing returns, so I decided it wasn't worth taking anymore.
> How's the Meridia?Nothing yet. Today is day 4. I can't feel anything at all. No side effects. I'll probably stay at 10mg for a few more days.
- Scott
Posted by ed_uk on August 8, 2006, at 15:16:50
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow. » ed_uk, posted by SLS on August 7, 2006, at 19:47:41
Hi Scott
Let us know how it helps :)
Ed
Posted by SLS on August 9, 2006, at 20:23:23
In reply to Re: Sibutramine (Meridia) - Starting it tomorrow. » SLS, posted by ed_uk on August 8, 2006, at 15:16:50
5 days @ 10mg
So far, so good. That means I don't feel any worse, and I'm not experiencing any significant side effects.
I have noticed a bit of spaciness and more difficulty concentrating when reading.
My appetite has actually increased rather than decreased.
I noticed that I am urinating more without having increased my fluid intake. I believe this is an indicator of fat mobilization (lipolysis). I hope so. I could afford to lose a bit of weight.
So that's about it.
Currently:
nortripyline 100mg
Lamictal 150mg
Topamax 100mg
Abilify 10mg
sibutramine 10mg
- Scott
Posted by Phillipa on August 9, 2006, at 20:26:32
In reply to Re: Sibutramine (Meridia) - Day 5, posted by SLS on August 9, 2006, at 20:23:23
Scott I'm exited for you!!!!!Love Phillipa
Posted by SLS on August 9, 2006, at 20:53:18
In reply to Re: Sibutramine (Meridia) - Day 5 » SLS, posted by Phillipa on August 9, 2006, at 20:26:32
> Scott I'm exited for you!!!!!Love Phillipa
Thanks.
:-)
- Scott
Posted by SLS on August 11, 2006, at 6:27:52
In reply to Re: Sibutramine (Meridia) - Day 5, posted by SLS on August 9, 2006, at 20:23:23
6 days @ 10mg
I am experiencing some dysphoria that I attribute to the sibutramine. It is not a normal feature of my depression. There is also a sort of "muddiness" to the way I am feeling. I don't like it. Hopefully, it will pass. I will probably increase the dosage to 20mg tomorrow.
Currently:
nortripyline 100mg
Lamictal 150mg
Topamax 100mg
Abilify 10mg
sibutramine 10mg
- Scott
Posted by ed_uk on August 11, 2006, at 13:29:34
In reply to Re: Sibutramine (Meridia) - Day 6, posted by SLS on August 11, 2006, at 6:27:52
Hi Scott
>I will probably increase the dosage to 20mg tomorrow.
Why Scott? If you think you're having side effects it might be best not to increase the dose.
Regards
Ed
Posted by SLS on August 11, 2006, at 14:13:54
In reply to Re: Sibutramine (Meridia) - Day 6 » SLS, posted by ed_uk on August 11, 2006, at 13:29:34
> > I will probably increase the dosage to 20mg tomorrow.
> Why Scott? If you think you're having side effects it might be best not to increase the dose.
I guess I'm just being impatient. I was hoping to be at 20mg for two weeks before my next doctor's visit. I am doing better today. I'm not sure what I'll do yet.
Thanks for your concern.
What's up with you? Things still going OK? How's work?
- Scott
Posted by SLS on August 11, 2006, at 23:44:00
In reply to Re: Sibutramine (Meridia) - Day 6, posted by SLS on August 11, 2006, at 6:27:52
7 days @ 10mg
I continue to experience some dysphoria. However, it is not as acute today as it was yesterday. I will wait until tomorrow to increase the dosage to 20mg.
Currently:
nortripyline 100mg
Lamictal 150mg
Topamax 100mg
Abilify 10mg
sibutramine 10mg
- Scott
Posted by SLS on August 13, 2006, at 7:57:01
In reply to Re: Sibutramine (Meridia) - Day 7, posted by SLS on August 11, 2006, at 23:44:00
7 days @ 10mg
1 days @ 20mgI took the second daily dose of sibutramine last night for a total of 20mg for the day. I am experiencing an increase in dysphoria and anergia this morning. I'm not too happy about this. I am quickly losing hope that this drug will prove effective for me. I'm not giving up just yet, though.
Currently:
nortriptyline 100mg
Lamictal 150mg
Topamax 100mg
Abilify 10mg
sibutramine 20mg
- Scott
Posted by Racer on August 13, 2006, at 12:31:47
In reply to Re: Sibutramine (Meridia) - Day 8, posted by SLS on August 13, 2006, at 7:57:01
Scott, I know you have a history of responding for a couple of days, only to lose the response. Have you ever had it the other way around? That you feel worse for a few days as you titrate up, but get a better response later in treatment? Do you think there's a chance of such a thing happening this time around?
You know I'm really pulling for you on this one, and you know why, so I admit freely that I'm biassed in favor of giving it a good chance...
Still, I'm sorry you're not having a great ride. I hope it gets better.
Remind me again: have you ever had a good response that lasted for any length of time?
xoxo
Posted by SLS on August 13, 2006, at 13:10:29
In reply to Re: Sibutramine (Meridia) - Day 8 » SLS, posted by Racer on August 13, 2006, at 12:31:47
> Scott, I know you have a history of responding for a couple of days, only to lose the response. Have you ever had it the other way around? That you feel worse for a few days as you titrate up, but get a better response later in treatment?
Actually, my most recent trial of Wellbutrin followed that sort of pattern. It produced some mild dysphoria for about a week before I responded well to it.
> Do you think there's a chance of such a thing happening this time around?
Yes. I have this very silly little piece of brain tissue that always thinks there's a chance of something good happening. After all this time, I don't know why.
> You know I'm really pulling for you on this one, and you know why, so I admit freely that I'm biassed in favor of giving it a good chance...
Much of the dysphoria that I experienced this morning seems to have passed. There is still a little there, but that I am not feeling worse is a good thing.
> Still, I'm sorry you're not having a great ride. I hope it gets better.
Thanks.
> Remind me again: have you ever had a good response that lasted for any length of time?Yes. In 1987, at age 27, a combination of Parnate 60mg and desipramine 150mg produced a complete remission that lasted six months until the drugs were discontinued due to the appearance of mania. After being without medication for two months, I relapsed into depression. Without getting into the particulars of what transpired subsequently, I no longer respond to the same combination.
- Scott
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