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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by NewHampshireGuy on June 9, 2008, at 8:39:52
Hello,
I am currently on Lamictal for Bipolar NOS, mild form of it so far. The only thing is I believe the serotonin effect it is having, no matter how small, is causing problems, even though the mood stablizing part seems to be working
Any med I have taken that has any effect on serotonin makes things MUCH worse than they were before unfortunatly
Is there a mood stabilizer that literally has no or very little affect on serotonin? How about depakote or lithuim? Thanks
Posted by Horned One on June 9, 2008, at 10:46:51
In reply to Mood Stablizer with ZERO serotonin effect?, posted by NewHampshireGuy on June 9, 2008, at 8:39:52
I didn't think lamotrigine had any significant activity at serotonin receptors, but someone may come along and correct me. Lithium certainly does exert some of its clinical effects via the serotonin system - it shouldn't normally be combined with SSRIs becuase there's a risk of serotonin toxicity. I don't think Depakote has any serotonin activity, but are you sure the side effects you're having with lamotrigine are purely due to serotonin? There may be some other cause.
-Horny
Posted by SLS on June 10, 2008, at 5:59:59
In reply to Re: Mood Stablizer with ZERO serotonin effect?, posted by Horned One on June 9, 2008, at 10:46:51
Hi.
Lamictal probably exerts its antidepressant effects via a reduction in the amount of glutamate released in the thalamus. This in turn increases dopamine release in the nucleus accumbens, the reward, pleasure, and motivational center in the limbic system. To the best of my knowledge, there is no direct or indirect effect of Lamictal on serotonin pathways.
- Scott
Posted by linkadge on June 10, 2008, at 7:32:40
In reply to Re: Mood Stablizer with ZERO serotonin effect?, posted by SLS on June 10, 2008, at 5:59:59
>This in turn increases dopamine release in the >nucleus accumbens, the reward, pleasure, and >motivational center in the limbic system
Is this true? The only reason I ask is because lamotrigine has dopamine depleting activity in certain brain regions.
http://www.medscape.com/viewarticle/418015_3
In support of conclusions regarding our patient, lamotrigine exerted prodystonic effects in Syrian hamsters with primary generalized dystonia.[22] It also reduced dopamine synthesis in the striatum of mice.[23]
Linkadge
Posted by NewHampshireGuy on June 10, 2008, at 8:11:59
In reply to Re: Mood Stablizer with ZERO serotonin effect?, posted by linkadge on June 10, 2008, at 7:32:40
Thanks Linkadge and all
either way I feel much better on this med
my mind is slowly starting to wind down and the racing thoughts/songs in head slowly diminishing.
I feel normal and that's good, except I am still relying on a sleeping pill to put me to sleep.
will lamictal balance whatever is unbalanced that I am not sleeping? I know that's a general question, but just curious if it acts on sleep
Posted by SLS on June 10, 2008, at 11:10:29
In reply to Re: Mood Stablizer with ZERO serotonin effect?, posted by linkadge on June 10, 2008, at 7:32:40
> >This in turn increases dopamine release in the >nucleus accumbens, the reward, pleasure, and >motivational center in the limbic system
> Is this true?
I don't know for sure. The theory is uniquely mine. My conclusion is based on:
1. Lamotrigine reduces glutamate release in the thalamus.
2. Thalamic glutamatergic pathways leading to the nucleus accumbens are muted.
3. The function of these pathways is to inhibit dopamine release in the nucleus accumbens.
4. Reduced firings of these glutamatergic pathways disinhibits dopamine release in the nucleus accumbens, thereby increasing dopaminergic activity there.
> The only reason I ask is because lamotrigine has dopamine depleting activity in certain brain regions.
I can see that the article concerns itself more with the basal ganglia and striatum than with the thalamus or nucleus accumbens.
From the article:
"In support of conclusions regarding our patient, lamotrigine exerted prodystonic effects in Syrian hamsters with primary generalized dystonia"
I wonder whether such effects would be expressed had the hamsters not had dystonia in the first place. I really don't know where else the anti-glutamatergic properties of lamotrigine are exerted. Perhaps it is the sodium channel antagonism that produces the dystonia. It would be interesting to look at a brain map with detailed circuitry to determine the interaction between GLU, GABA, and DA. It sounds like a lot of work, though.
Would the vulnerability to lamotrigine-induced dystonia be greater in epileptics than in non-epileptics? How about people previously exposed to neuroleptics? I have very little reason to think this, but if lamotrigine can directly enhance DAergic neurotransmission in other structures of the brain, perhaps upregulated postsynaptic receptors are overly sensitive to any increase in DAergic activation induced by lamotrigine.
- Scott
Posted by SLS on June 10, 2008, at 14:55:22
In reply to Re: Mood Stablizer with ZERO serotonin effect? » linkadge, posted by SLS on June 10, 2008, at 11:10:29
Sorry about the inaccuracy. I confused the thalamus with the hippocampus.
Regarding the antidepressant properties of lamotrigine, my rationale is that:1. Lamotrigine reduces glutamate release in the hippocampus.
2. Hippocampal glutamatergic pathways leading to the nucleus accumbens are muted.
3. The function of these pathways is to inhibit dopamine release ("put the brakes on") in the nucleus accumbens.
4. Reduced firings of these glutamatergic pathways disinhibits dopamine release in the nucleus accumbens, thereby increasing dopaminergic activity there.
- Scott
Posted by linkadge on June 10, 2008, at 19:09:43
In reply to Re: Mood Stablizer with ZERO serotonin effect? » linkadge, posted by SLS on June 10, 2008, at 11:10:29
You could be right. I was just wondering.
Linkadge
Posted by Bob on June 11, 2008, at 11:09:58
In reply to Re: Mood Stablizer with ZERO serotonin effect?, posted by Horned One on June 9, 2008, at 10:46:51
Lithium certainly does exert some of its clinical effects via the serotonin system - it shouldn't normally be combined with SSRIs becuase there's a risk of serotonin toxicity.
>
> -HornyLithium shouldn't be combined with SSRIs? I thought it was actually a common augmenting strategy for that class of med.
Posted by Horned One on June 11, 2008, at 13:14:34
In reply to Re: Mood Stablizer with ZERO serotonin effect? » Horned One, posted by Bob on June 11, 2008, at 11:09:58
I can't remember the last time I heard of anyone combining lithium with an SSRI, but I have no doubt it happens. All of the lithium augmentation strategies I recall involved the use of TCAs and MAOIs. I just double checked, and lithium is reported to interact negatively with SSRIs.
__________________________________________________"The concomitant administration of lithium with selective serotonin reuptake inhibitors should be undertaken with caution as this combination has been reported to result in symptoms such as diarrhea, confusion, tremor, dizziness, and agitation." [Common symptoms of serotonin syndrome.]
http://www.rxlist.com/cgi/generic/lithium_ad.htm--------------------------------------------------
Interactions between lithium and Celexa (citalopram)
Major Drug-Drug Interaction lithium and citalopram (Major Drug-Drug)
MONITOR CLOSELY: Lithium may enhance the pharmacologic effects of selective serotonin reuptake inhibitors (SSRIs) and potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5HT1A receptors. The exact mechanism by which this interaction occurs is unknown. Conversely, SSRIs may elevate the plasma concentrations of lithium and increase the risk of lithium toxicity. The interaction has been associated with fluoxetine, while citalopram and paroxetine reportedly do not cause the interaction. Excessive somnolence has been reported with lithium and fluvoxamine.MANAGEMENT: Caution is advised if concomitant use of SSRIs and lithium is necessary. Lithium levels should be assessed regularly and the dosage adjusted accordingly. Close monitoring is recommended for signs and symptoms of lithium toxicity as well as excessive serotonergic activity such as CNS irritability, altered consciousness, confusion, myoclonus, ataxia, abdominal cramping, hyperpyrexia, shivering, pupillary dilation, diaphoresis, hypertension, and tachycardia.
http://www.drugs.com/drug-interactions/lithium_d00061_celexa_d04332.html
__________________________________________________-Horny
Posted by blueboy on June 12, 2008, at 8:44:50
In reply to Re: Mood Stablizer with ZERO serotonin effect?, posted by NewHampshireGuy on June 10, 2008, at 8:11:59
> my mind is slowly starting to wind down and the racing thoughts/songs in head slowly diminishing.
>
> I feel normal and that's good, except I am still relying on a sleeping pill to put me to sleep.
>
> will lamictal balance whatever is unbalanced that I am not sleeping? I know that's a general question, but just curious if it acts on sleepI'm just starting out on lamictal, but it doesn't seem to be aggravating my insomnia.
From what I've read and have been told by pdocs, its big strength is treatment of the depressive symptoms of BP II. I think they would have started me on something else if my primary complaint had been mania/hypomania. In other words, I would investigate further about whether you can expect lamictal to help with serious insomnia problems.
Also, at least in my case and in a great number of bipolar patients, it is difficult to judge the effect of treatment short term, because of the cyclical nature of the disease. I have experienced frequent periods of remission from the disorder independent of any treatment. It concerns me, because I could start taking a drug and feeling better, without any actual connection between the two. Not as a "placebo effect" but rather that I might actually experience a natural reduction of symptoms while taking a drug by sheer coincidence, especially since I'm more likely to seek treatment at a bad part of the cycle.
Posted by Zyprexa on June 14, 2008, at 20:52:37
In reply to Mood Stablizer with ZERO serotonin effect?, posted by NewHampshireGuy on June 9, 2008, at 8:39:52
How about Depakot? Just looked at it, could not find anything about serotonin.
This is the end of the thread.
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