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Dr. Bob is Robert Hsiung, MD,
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Posted by linkadge on September 19, 2006, at 11:47:34
In reply to Re: Nicotine and Depression, posted by saturn on September 17, 2006, at 20:29:08
I never really got a buzz from nicotine. It felt like a sedative.
Linkadge
Posted by linkadge on September 19, 2006, at 11:53:24
In reply to Re: Nicotine and Depression, posted by saturn on September 17, 2006, at 20:29:08
The clomipramine doesn't really matter. There are too many other negative health consequences associated with the TCA class. Its too risky.
Three members of our family had TCA associated cardiac events.Clomipramine was giving me some form of seizure. Simple partial (?) Not sure what the doctor called it. No loss of contiousness, but muscle stuff associated with strange experiences / abdominal stuff.
Couldn't pee either.
Can't really remember, much of being on the drug was a haze.
Linkadge
Posted by Questionmark on September 24, 2006, at 18:08:34
In reply to Re: Nicotine and Depression, posted by saturn on September 17, 2006, at 20:29:08
> I can still recall my first cigarette buzz back in high school-- almost orgasmic.
Yeah, back in high school when i only rarely had a cigarrette, the buzz would be so wonderful: a strong, beautiful euphoria i fell in love with. I miss it.By the way Scott/SLS and Linkadge you guys made some really good points in this thread.
Posted by MrBrice on October 2, 2006, at 5:49:25
In reply to Re: Nicotine and Depression, posted by Questionmark on September 24, 2006, at 18:08:34
Nicotine DOES work, when i take 2-3 nicotine sublilingual tablets (6mg's), i actually feel the dopamine creeping in and the anxiety going away.
makes me long for an maoi.
Posted by SLS on October 2, 2006, at 5:55:58
In reply to Re: Nicotine and Depression, posted by MrBrice on October 2, 2006, at 5:49:25
> Nicotine DOES work, when i take 2-3 nicotine sublilingual tablets (6mg's), i actually feel the dopamine creeping in and the anxiety going away.
>
> makes me long for an maoi.
Why would you long for an MAOI if nicotine works for you?What is inadequate about nicotine?
- Scott
Posted by SLS on October 2, 2006, at 6:17:59
In reply to Re: Nicotine and Depression » MrBrice, posted by SLS on October 2, 2006, at 5:55:58
> > Nicotine DOES work, when i take 2-3 nicotine sublilingual tablets (6mg's), i actually feel the dopamine creeping in and the anxiety going away.
> >
> > makes me long for an maoi.
>
>
> Why would you long for an MAOI if nicotine works for you?
>
> What is inadequate about nicotine?
What is your total daily dosage?How many times a day do you take it?
How long have you been taking it at a consistent dosage every day?
- Scott
Posted by MrBrice on October 2, 2006, at 11:24:33
In reply to Re: Nicotine and Depression » MrBrice, posted by SLS on October 2, 2006, at 5:55:58
hey sls,
it works really well for me but note this:
1 nicotine tablet works for about 2 hours...
you have to constantly take nicotine pills all day long if you want to feel good all day.I'm really develloping a SERIOUS addiction here.
wouldn't it be easier to have something that i take once dayly...
Posted by SLS on October 2, 2006, at 13:05:30
In reply to Re: Nicotine and Depression SLS, posted by MrBrice on October 2, 2006, at 11:24:33
> hey sls,
>
> it works really well for me but note this:
> 1 nicotine tablet works for about 2 hours...
> you have to constantly take nicotine pills all day long if you want to feel good all day.
>
> I'm really develloping a SERIOUS addiction here.
>
> wouldn't it be easier to have something that i take once dayly...
How about using a patch?In what ways would you say that you are addicted? Perhaps you simply want to feel better. Do you actually feel cravings for the pills?
- Scott
Posted by MrBrice on October 2, 2006, at 16:26:39
In reply to Re: Nicotine and Depression SLS, posted by SLS on October 2, 2006, at 13:05:30
I don't feel craving for the pills, i take them cause i sometimes need them to act normally in society (school in my case).
AND i feel that the dosulepin that i'm being given, which is a tricyclic, is not really working. My doc tough, is of mind that the dosulepin needs 1 YEAR before it really helps, so he wants to keep me on it, and so of MAOI, for at least another 6 months.I respect his decision cause he's allready proven that he knows his job, but i think a dopamine treatment would be more succesfull.
sometimes now i take not less then 7 of these nicotine pills and feel the dopamine enlichtening me...
brice
Posted by SLS on October 3, 2006, at 1:17:18
In reply to Re: Nicotine and Depression SLS, posted by MrBrice on October 2, 2006, at 16:26:39
> I don't feel craving for the pills, i take them cause i sometimes need them to act normally in society (school in my case).
Yes. I understand.
> AND i feel that the dosulepin that i'm being given, which is a tricyclic, is not really working. My doc tough, is of mind that the dosulepin needs 1 YEAR before it really helps,
I have never heard of such a thing. Of course, it is worth the investment if it works. It's a hell of a gamble, though. I have spent over a year on nortripyline, and it hasn't worked. I hope there is something particularly magic about dosulepin. If it works, please come back to Psycho-Babble and let us know. It might be worth for some of us in the US to import this stuff.
> sometimes now i take not less then 7 of these nicotine pills and feel the dopamine enlichtening me...
Are the patches expensive? I don't know how much nicotine they deliver. They might not deliver the amount necessary for you to sustain an antidepressant effect. You should probably take between 3.5-7.0mg per day.
- Scott
Posted by MrBrice on October 3, 2006, at 5:28:20
In reply to Re: Nicotine and Depression SLS, posted by SLS on October 3, 2006, at 1:17:18
k scott,
i'm meeting my doc today, i'll be discussing this very thing with him.
he'll probably keep me on nicotine i think, we'll see..
greets ;)
Posted by SLS on October 3, 2006, at 6:12:30
In reply to Re: Nicotine and Depression SLS, posted by MrBrice on October 3, 2006, at 5:28:20
> k scott,
>
> i'm meeting my doc today, i'll be discussing this very thing with him.
>
> he'll probably keep me on nicotine i think, we'll see..
>
> greets ;)Good luck.
Maybe you can bring him this:
-------------------------------------------
Psychopharmacology (Berl). 2006 Sep 15; [Epub
Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial.
McClernon FJ, Hiott FB, Westman EC, Rose JE, Levin ED.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA, mccle011@mc.duke.edu.
RATIONALE: Despite established links between nicotine dependence and depression, little research has examined the effects of nicotine on depression symptoms. OBJECTIVE: This study evaluated the acute and chronic effects of transdermal nicotine in nonsmokers with baseline depression symptoms during a 4-week, double-blind, placebo-controlled trial. METHODS: Nonsmokers with scores >/=10 on the Center for Epidemiological Studies Depression scale (CES-D) were recruited from the community. Mood and cognitive performance were measured at baseline (day 0) and at 1, 8, 21, and 28 days. Participants were randomly assigned to wear a placebo or nicotine patch for 4 weeks (3.5 mg/day during weeks 1 and 4; 7 mg/day during weeks 2 and 3). The final sample consisted of 11 nonsmokers with a mean baseline CES-D score of 27.36 (SD=10.53). RESULTS: Salivary nicotine levels indicated the majority of participants were compliant with treatment. Acute nicotine did not alter mood. After adjusting for baseline values, chronic nicotine resulted in a significant decline in CES-D scores at day 8 (3.5 mg/day), but returned to placebo levels by the last visit. This return to baseline levels was coincident with a decrease in nicotine administration from 7 to 3.5 mg/day. A similar trend for improved response inhibition as measured by the Conners Continuous Performance Task was also observed. Reported side effects were infrequent and minimal. CONCLUSION: These findings suggest a role for nicotinic receptor systems in the pathophysiology of depression and that nicotinic compounds should be evaluated for treating depression symptoms.
PMID: 16977477 [PubMed - as supplied by publisher]
Posted by florence on October 4, 2006, at 1:28:37
In reply to Re: Nicotine and Depression, posted by SLS on September 17, 2006, at 11:15:39
> The mistake that I see often made in the interpretation of such studies is that they are demonstrating that a system must be intact for a drug to work. It does not demonstrate that that system is the site of action of the drug. That was the mistake made with Provigil (modafinil) and NE alpha-1 receptors.
>
>
> - Scott
Scott, could you explain the mistake with Provigil and NE alpha-1 receptors or give me a link Thanks...Florence
Posted by SLS on October 4, 2006, at 6:14:16
In reply to Re: Nicotine and Depression » SLS, posted by florence on October 4, 2006, at 1:28:37
Hi Florence.
> > The mistake that I see often made in the interpretation of such studies is that they are demonstrating that a system must be intact for a drug to work. It does not demonstrate that that system is the site of action of the drug. That was the mistake made with Provigil (modafinil) and NE alpha-1 receptors.
> Scott, could you explain the mistake with Provigil and NE alpha-1 receptors or give me a link Thanks...Florence
In the early 1990s, several investigators pronounced that modafinil produced increased alertness and vigilence via the direct stimulation of central NE alpha-1 receptors and that it was thus a ligand agonist. They based this conclusion on the observation that the increase in locomotor activity seen in mice when modafinil was applied was reversed by prazosin, a NE alpha-1 antagonist. This was an inappropriate conclusion. At most, this only demonstrated that pathways containing NE alpha-1 receptors needed to be intact for modafinil to exert its locomotor properties.
For what it is worth, around the year 2000, a friend of mine met with one of the developers of adrafinil and modafinil at a conference. The developer confirmed that the conclusion by investigators had been incorrect, and that the exact mechanisms of drug had not been worked out. However, by that time they had already been looking at glutamate and hypocretin. Now, I believe much of the focus is on hypocretin and the hypothalamus, although it does promote the release of glutamate in the thalamus.
The manufacturer's label goes out of its way to explain the historic error:
"Modafinil does not appear to be a direct or indirect alpha-adrenergic agonist. Although modafinil-induced wakefulness can be attenuated by the a1-adrenergic receptor antagonist, prazosin, in assay systems known to be responsive to a1-adrenergic agonists, modafinil has no activity."
http://www.rxlist.com/cgi/generic2/modafinil_cp.htm
- Scott
Posted by SLS on October 4, 2006, at 7:32:29
In reply to Re: Nicotine and Depression SLS, posted by MrBrice on October 3, 2006, at 5:28:20
> k scott,
>
> i'm meeting my doc today, i'll be discussing this very thing with him.
>
> he'll probably keep me on nicotine i think, we'll see..
>
> greets ;)
Well, what did the doctor have to say?
- Scott
Posted by FredPotter on October 4, 2006, at 15:13:06
In reply to Re: Nicotine and Depression SLS, posted by SLS on October 3, 2006, at 1:17:18
An AD that takes a year to work is NO USE at all to a depressed person. 4-6 weeks is asking an awful lot, particularly if suicidal
Posted by SLS on October 4, 2006, at 16:05:30
In reply to Re: Nicotine and Depression SLS, posted by FredPotter on October 4, 2006, at 15:13:06
> An AD that takes a year to work is NO USE at all to a depressed person. 4-6 weeks is asking an awful lot, particularly if suicidal
Can you amplify your remarks?
- Scott
Posted by FredPotter on October 4, 2006, at 16:30:01
In reply to Re: Nicotine and Depression SLS, posted by SLS on October 4, 2006, at 16:05:30
Scott I just meant that it's too long to wait when you're in mental agony Fred
Posted by MrBrice on October 5, 2006, at 5:39:13
In reply to Re: Nicotine and Depression SLS » MrBrice, posted by SLS on October 4, 2006, at 7:32:29
> > k scott,
> >
> > i'm meeting my doc today, i'll be discussing this very thing with him.
> >
> > he'll probably keep me on nicotine i think, we'll see..
> >
> > greets ;)
>
>
> Well, what did the doctor have to say?
>
>
> - Scott
>
He told me that nicotine is for the moment probably the best i can take for now.
He is sure that his dosulepin-plan will work and thus will keep me on it for at least another 4 months. During those 4 months he wants to stretch time and keep me happy with the nicotine.I myself am in doubt of wether or not an maoi would be good for me. I've heard they have some terrible side-effects (insomnia for example, man i would hate that) so i don't really know what is the best for me.
After some research i did find out why it probably is the nicotine is helping me. There are 2 reasons:
First the nicotine stimulates a whole series of receptors in the brain, including ofcourse the nicotine receptor itself. This causes a release of noradrenaline i believe. This gives me a small boost and keeps me focused, it's nice when you need to 'be cool' and stay focused.Secondly, after +- 30 minutes, the noradrenaline is broken off into dopamine. This injection i feel very well, and it makes me relaxed and more enjoyable.
I wouldn't know what would be best for me right now, but for the moment, i will follow my doc and just go on with my current treatment.
If it fails, after 4 months we will know, we will switch to nardil and take away the sulpiride and dosulepin.grtz,
Brice
Posted by MrBrice on October 5, 2006, at 5:41:29
In reply to Re: Nicotine and Depression SLS, posted by FredPotter on October 4, 2006, at 16:30:01
> Scott I just meant that it's too long to wait when you're in mental agony Fred
you're completely right fred, it's hard allright. + I don't believe that if the AD doestn't work after 7 months, it will after 1 year.
Posted by SLS on October 5, 2006, at 6:21:13
In reply to Re: Nicotine and Depression SLS, posted by MrBrice on October 5, 2006, at 5:39:13
My thing with nicotine is that, if it is going to be an effective antidepressant, it has to produce a broad spectrum of action, and be consistent all day long, every day. Now, these guys used a patch at 7.0mg per day. The improvement they observed at 8 days disappeared by 28 days, but they had, for some unexplained reason, lowered the dose to 3.5mg. I want nicotine to work. If it works for you, it might work for me. It is still my suspicion, though, that it has only acute and subacute effects. Basically, you'll get a buzz off of it whenever you take it after a period of abstinence (over a period of hours) and perhaps a feeling of slight improvement that will last a week or so. However, if it will bring you any kind of relief, perhaps it makes sense to use it as a bridge until you find an antidepressant that works well.
How do you plan to administer the nicotine?
Nicoderm® nicotine comes in 7mg/day, 14mg/day, and 21mg/day patches.
It would be a big help if you could keep a daily log of your progress.
- Scott
Posted by SLS on October 5, 2006, at 7:52:36
In reply to Re: Nicotine and Depression SLS, posted by FredPotter on October 4, 2006, at 16:30:01
> Scott I just meant that it's too long to wait when you're in mental agony Fred
I had thought you were talking about the nicotine.
:-)
Yes, this is the first time that I have heard of a doctor assert with such confidence that a drug treatment would take 1 year to work such that he actually prescribes that way.
You know, it seems that VNS might take 6-12 months to work for some people with TRD. For the life of me, I don't know what motivated them to stay on it for so long without results. I guess once you spend $15,000 and accept having wires routed through your neck and a pulse-generator implanted in your chest, it's not such an easy decision to just quit.
- Scott
Posted by MrBrice on October 5, 2006, at 9:13:22
In reply to Re: Nicotine and Depression » MrBrice, posted by SLS on October 5, 2006, at 6:21:13
> My thing with nicotine is that, if it is going to be an effective antidepressant, it has to produce a broad spectrum of action, and be consistent all day long, every day. Now, these guys used a patch at 7.0mg per day. The improvement they observed at 8 days disappeared by 28 days, but they had, for some unexplained reason, lowered the dose to 3.5mg. I want nicotine to work. If it works for you, it might work for me. It is still my suspicion, though, that it has only acute and subacute effects. Basically, you'll get a buzz off of it whenever you take it after a period of abstinence (over a period of hours) and perhaps a feeling of slight improvement that will last a week or so. However, if it will bring you any kind of relief, perhaps it makes sense to use it as a bridge until you find an antidepressant that works well.
>
> How do you plan to administer the nicotine?
>
> Nicoderm® nicotine comes in 7mg/day, 14mg/day, and 21mg/day patches.
>
> It would be a big help if you could keep a daily log of your progress.
>
>
> - Scott
>
i'm happy to do that if it is of any help to you scott.For now, i HATE the fact that i have to take my microtabs (i take little sublingual tablets of 2 mg's) every 1-2 hours.
A patch that lasts all day would be perfect, i didn't know it existed...?i'll keep you updated.
grtz,
Brice
Posted by Questionmark on October 6, 2006, at 1:35:31
In reply to Re: Nicotine and Depression SLS, posted by MrBrice on October 5, 2006, at 5:39:13
Brice,
I have to say what a few others have in that I have never heard of a doctor advocating one year on a psychiatric drug in order for it to be effective or even fully effective. And it really makes very little practical sense to me-- much less pharmacological sense (though of which of course i am no expert). Even with complex receptor changes and adaptations, it seems like *any* drug would begin to show benefit after several months or so.
That said, however, the confidence that your doctor has in this treatment route makes me wonder if he actually has some substantiated basis for it-- as in, maybe previous patients have, for whatever reason, derived benefit from this medication after such a length of time. ... Either that or he is displaying another extreme example of psychiatric hubris.
I really think you should ask him, though, why he thinks that it will or should begin to work after 3 or 4 more months-- is it anecdotal experience with past patients, a convincing body of literature, or something else?. It might be helpful to know if he has any good reasons for this recommendation.Oh and just so you know, I must tell you that nicotine is relatively nothing like an MAOI, especially Nardil.
And in regard to nicotine's actions: one of its most well-known and probably significant (and definitely addictive) properties is its stimulation of dopamine release in the reward areas of the brain (e.g., nucleus accumbens). This is almost definitely the primary reason behind its euphoric properties as well. Also, the (cholinergic) nicotine receptors are involved in cognition, and their stimulation/agonism promotes enhanced cognitive capabilities (enhanced focus, etc.).
I don't know of any direct involvement with norepinephrine (but there very well may be)-- or any other specific actions, although I'm sure there are. But the two mentioned above are I think two of the most significant if not the most.By the way, yes, at least in the U.S. here nicotine pathes are readily available over-the-counter and in many stores & pharmacies. They are quite expensive however.
(I have something else to say on nicotine tolerance but i'll save that for the next post).
In any case, good luck!
> He told me that nicotine is for the moment probably the best i can take for now.
> He is sure that his dosulepin-plan will work and thus will keep me on it for at least another 4 months. During those 4 months he wants to stretch time and keep me happy with the nicotine.
>
> I myself am in doubt of wether or not an maoi would be good for me. I've heard they have some terrible side-effects (insomnia for example, man i would hate that) so i don't really know what is the best for me.
>
>
> After some research i did find out why it probably is the nicotine is helping me. There are 2 reasons:
> First the nicotine stimulates a whole series of receptors in the brain, including ofcourse the nicotine receptor itself. This causes a release of noradrenaline i believe. This gives me a small boost and keeps me focused, it's nice when you need to 'be cool' and stay focused.
>
> Secondly, after +- 30 minutes, the noradrenaline is broken off into dopamine. This injection i feel very well, and it makes me relaxed and more enjoyable.
>
> I wouldn't know what would be best for me right now, but for the moment, i will follow my doc and just go on with my current treatment.
> If it fails, after 4 months we will know, we will switch to nardil and take away the sulpiride and dosulepin.
>
> grtz,
> Brice
Posted by Questionmark on October 6, 2006, at 2:26:23
In reply to Re: Nicotine and Depression » florence, posted by SLS on October 4, 2006, at 6:14:16
I've always wondered about that (when reading some abstract or article/study that draws its conclusions of receptor action of a drug from this sort of over-simplicity)! It just didn't make any sense to come to those conclusions based on that. It never made any sense to me. These guys (with biochemistry and pharmacology Ph.D.s or whatever else) couldn't really be that illogical and naive, could they? So in my own naivete probably, I usually just assume that I'm probably just missing something and they know what they're doing and they know all the other factors for why that methodology works. But reading your post on this really gets me wondering again. Could they really be that illogical?! I mean, it shouldn't be something that difficult for any rational thinking person to identify, if they work in that field. I don't understand it. ARE we missing something?
Goodness no wonder psychiatry is so messed up! The practitioners are getting much of their information from a gross logical error (and monies, pressure, and advertising from the largest corporate sector in the world [or at least in the U.S.]).
But seriously though-- this really concerns me. When I think about it it seems like MANY of our modern theories about neuropharmacology and receptor pharmacology might have been derived from studies using this method. Is it possible that a lot of what we take for granted as being true regarding the receptor pharmacology of different psychiatric drugs is NOT necessarily true or substantiated?? ... This probably isn't the case now that I think about it-- when I try to think of specific examples. But I still wonder for some of them if this is true. What do you think?
This is probably why you get multiple varying pharmacological descriptions of certain drugs, especially the ones with several receptor actions (like some Atypical antipsychotics for instance).Anyway, I'll stop my rant now. But I'd really like to hear what your and others' specific thoughts are on this.
And I'm glad you mentioned that info about modafinil and NE alpha-1 receptors. I wasn't aware of that. .. Do you know how many times I read that modafinil is an alpha-1 agonist? Many. I always did think it was kind of strange too. Other drugs that stimulate alpha-1 Rs don't promote wakefulness and all that! In fact that action is responsible for some of their side effects!
Man we need more logicians in drug research. There need to be logicians that oversee & supervise these people. Okay i'll stop.Anyway, great point and thanks for bringing it to our attention.
> > > The mistake that I see often made in the interpretation of such studies is that they are demonstrating that a system must be intact for a drug to work. It does not demonstrate that that system is the site of action of the drug. That was the mistake made with Provigil (modafinil) and NE alpha-1 receptors.
>
> > Scott, could you explain the mistake with Provigil and NE alpha-1 receptors or give me a link Thanks...Florence
>
> In the early 1990s, several investigators pronounced that modafinil produced increased alertness and vigilence via the direct stimulation of central NE alpha-1 receptors and that it was thus a ligand agonist. They based this conclusion on the observation that the increase in locomotor activity seen in mice when modafinil was applied was reversed by prazosin, a NE alpha-1 antagonist. This was an inappropriate conclusion. At most, this only demonstrated that pathways containing NE alpha-1 receptors needed to be intact for modafinil to exert its locomotor properties.
>
> For what it is worth, around the year 2000, a friend of mine met with one of the developers of adrafinil and modafinil at a conference. The developer confirmed that the conclusion by investigators had been incorrect, and that the exact mechanisms of drug had not been worked out. However, by that time they had already been looking at glutamate and hypocretin. Now, I believe much of the focus is on hypocretin and the hypothalamus, although it does promote the release of glutamate in the thalamus.
>
> The manufacturer's label goes out of its way to explain the historic error:
>
> "Modafinil does not appear to be a direct or indirect alpha-adrenergic agonist. Although modafinil-induced wakefulness can be attenuated by the a1-adrenergic receptor antagonist, prazosin, in assay systems known to be responsive to a1-adrenergic agonists, modafinil has no activity."
>
> http://www.rxlist.com/cgi/generic2/modafinil_cp.htm
>
>
> - Scott
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Dr. Bob is Robert Hsiung, MD,
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Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
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