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Posted by jedi on September 17, 2006, at 0:08:04
In reply to Re: Nicotine and Depression, posted by SLS on September 16, 2006, at 22:46:48
...
> Nicotine provides mild anxiolytic, reward, and euphoriant effects, but it is not a potent antidepressant. If it were, we wouldn't see so many depressed people smoking cigarettes. It would, of course, be the best kept secret in psychiatry.
>
> People who are depressed choose many different drugs and behaviors to self-medicate. This does not make these things antidepressants.
>
> Nicotine is not an antidepressant.
Scott,
Your logical thinking on this makes perfect sense. I guess I won't rush out to buy nicotine gum.
Jedi
Posted by linkadge on September 17, 2006, at 9:48:32
In reply to Re: Nicotine and Depression, posted by SLS on September 16, 2006, at 22:46:48
>Nicotine provides mild anxiolytic, reward, and >euphoriant effects, but it is not a potent >antidepressant.
That may not be true. When you have a substance like nicotine, the assumption is that it can have no theraputic effect because it has some addictive potential. To be honest, it hasn't been studied enough in such applications. As you are well aware, there are many products whoose antidepressant properties have been denounced (ie SJW) probably based on other factors. For instance, a study that prooved nicotine to be an antidepressant could encourage people to continue smoking.
We base the antidepressant effect of the TCA's, SSRI's, MAOI's, valdoxan, remeron etc on their efficacy in the flinders sensitive line, so why reject such a study that identifies nicotine in such a way?
>If it were, we wouldn't see so many depressed >people smoking cigarettes. It would, of course, >be the best kept secret in psychiatry.
Why. Thats like saying that antidperessants don't work, because we see a lot of depressed people taking them. There are plenty of non depressed people who smoke, who can become very depressed when they quit. It is possable that nicotine has been maintaining a state of euthemia in an otherwise depressive individual. Depressed people who smoke could perhaps be much worse without smoking. Its not that its a secret, it just hasn't been directly studied very much.>People who are depressed choose many different >drugs and behaviors to self-medicate. This does >not make these things antidepressants.
This is true, but allong the same lines, it does not mean they are *not* antidepressants.
>Nicotine is not an antidepressant.
Well thats the debate. Clearly, we know that how one agent affects a person is undrelated to how the agent affects another person. The definition of an antidepressant is simply an agent that can provide sustained relief of depressive symptoms.
I personally noticed a sustained improvement in a few symtpoms of depression while I was using a fixed dose of nicotine to counteract SSRI side effects. (3-4 months 4mg/day) The main improvements were reduction of feelings of guilt, sustained reduction in anhedonia, improved concentration, destinct psychosocial imrprovment (I was hanging out with friends again, I've slipped back to hiding in my apartment all day),
significantly reduced physical anxiety, improved
sleep, and improved feelings of worthlessness.
It was destinct to nicotine, I did not have any such AD effects on caffiene, ritaline, dexedrine etc.
Linkadge
Posted by linkadge on September 17, 2006, at 10:14:15
In reply to Re: Nicotine and Depression, posted by linkadge on September 17, 2006, at 9:48:32
I mean honestly, if you saw us group of depressed people sitting around on a porch step, popping our effexors, and our prozacs, you'd start to think that these agents were not antidepressants either :)
Here is a very instersting study that states that the Nicotine Actycholine receptors are respondiable for the antidepressant effects on the TCA drug amitryptaline. It states that mice lacking such receptors are resistant to its effects. The flinders sensitive line seem to show imballances in serotonin/acetycholine/dopamine. Nicotine administration itself produces a functional inhibition of these receptors.http://www.yaledailynews.com/Article.aspx?ArticleID=26692
Another study from:http://www.lorenbennett.org/nsmok.htm#patch
Transdermal nicotine patch lessens depression
The role of repeated nicotine administration on sleep and major depression was studied in tests. Twelve nonsmoking volunteers: six major depressed patients and six normal patients. All subjects underwent t: acclimatization, control night, four nicotine nights (transdermal patches) and one withdrawal night. Nicotine increased REM sleep time in both groups and an average reduction the seriousness of depression of 43.9% in the depressed patients. These findings suggest that nicotine receptor activation may be important in major depression, and shows that nicotine patches may be useful in the treatment of depression.
Some others:
http://www.jointogether.org/news/research/summaries/2006/nonsmokers-depression-lifted.html
http://www.sciencedaily.com/releases/2002/12/021211083430.htm
http://www.sciencenews.org/articles/20020511/note17ref.asp
Linkadge
Posted by SLS on September 17, 2006, at 10:46:51
In reply to Re: Nicotine and Depression, posted by linkadge on September 17, 2006, at 9:48:32
It did for you what I said it would. You did those things that those effects would promote. You are no longer taking it. It did not work. It is not an antidepressant.
- Scott
Posted by SLS on September 17, 2006, at 11:15:39
In reply to Re: Nicotine and Depression, posted by linkadge on September 17, 2006, at 10:14:15
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
Posted by linkadge on September 17, 2006, at 12:29:27
In reply to Re: Nicotine and Depression, posted by SLS on September 17, 2006, at 10:46:51
>It did for you what I said it would. You did >those things that those effects would promote. >You are no longer taking it. It did not work. It >is not an antidepressant.
No, that is absolutely not true. For the time I took nicotine gum, there was no significant tollerance to its effects. I was literally doing better for the whole time. I didn't stop because it didn't work, I stopped because I read that it might affect the cardiac muscle negitively.
Its the same with clomipramine. The drug worked, but I stopped because I read it was genotoxic.
Thats the truth.Linkadge
Posted by linkadge on September 17, 2006, at 12:41:20
In reply to Re: Nicotine and Depression, posted by SLS on September 17, 2006, at 11:15:39
I agree, its not conlcusive, but the research is suggestive.
The same thing goes with any research though.
Ie. Neurogenesis theory sounds good, based on the finding that blocking the formation of new brain cells blocks the AD effect, but its not conlcusive.We simply need to see more long term double blind studies comparing nicotine to placebo in the treatment of major depression. There aren't a whole lot, but they are what would make or break the case.
You can say, well its not an antidepressant its just a euphoriant etc. etc. But there are really no rules. Just because a substance causes mild euphoria doesn't mean it is devoid of other effects which could be at the heart of affective disorders. Caffiene causes some euphoria, but otoh we know that coffee statiscially reduces the risk of suicide. Thats signficant.
Its easy to just form black and white opinions about certain substances, and then lump them into good and bad boxes.
We put marajuanna into the bad box because it causes a little euphoria, but again, that does not mean it is devoid of theraputic effect. Ie HPA axis reulation, promotion of neurogenes etc etc.
Linkadge
Posted by SLS on September 17, 2006, at 14:26:45
In reply to Re: Nicotine and Depression, posted by linkadge on September 17, 2006, at 12:29:27
> >It did for you what I said it would. You did >those things that those effects would promote. >You are no longer taking it. It did not work. It >is not an antidepressant.
>
> No, that is absolutely not true. For the time I took nicotine gum, there was no significant tollerance to its effects. I was literally doing better for the whole time. I didn't stop because it didn't work, I stopped because I read that it might affect the cardiac muscle negitively.
>
> Its the same with clomipramine. The drug worked, but I stopped because I read it was genotoxic.
> Thats the truth.Well, then, I must apologize for jumping to conclusions. I am sorry.
I would reevaluate carefully the material you have read regarding clomipramine and genotoxicity. Your life may depend on it. If you found it online, maybe you could show it to us to take a look at. Fruit flies lie sometimes.
- Scott
Posted by saturn on September 17, 2006, at 20:29:08
In reply to Nicotine and Depression, posted by jedi on September 16, 2006, at 2:22:02
I can still recall my first cigarette buzz back in high school-- almost orgasmic.
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
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