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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 31. This is the beginning of the thread.
Posted by sowhysosad on March 31, 2009, at 22:30:18
I'm currently weening off imipramine with a view to starting a new med in mid-May, which is most likely to be an SSRI.
Prior to the imipramine I'd been taking escitalopram (Lexapro/Cipralex) for 3 1/2 years. I then suffered awful akathisia when I switched to sertraline back in the autumn, although I suspect this was caused by me absent-mindedly tripling the dose one day (by taking the old dose AM/new dose PM).
Slight problem with returning to SSRI's: I have a movement disorder in my jaw which my neuro agrees may be due to depleted dopamine in the basal ganglia caused initially by the escitalopram, but persisting with the other serotonergic meds.
To rectify the deficiency and get relief from my depression I'm contemplating either:
1) adding NADH supplements to fluoxetine, or
2) giving sertraline another go, as it has significant activity for boosting dopamine according to Ken Gillman (http://www.psychotropical.com/SSRIs_Sertraline.shtml)(FYI: they don't prescribe Bupropion for depression in the UK, and an MAOI's not an option as increased norepinephrine makes me feel terrible - hence ditching the imipramine. I'm also certain neither the pdoc nor the neuro will prescribe any other dopaminergic drugs either.)
So, a couple of questions:
*Have you or anyone you know managed to return to an SSRI which has previously caused akathisia, avoiding a recurrence and achieving remission from depression?
*Given that fluoxetine appears to increase the concentration of dopamine in the prefrontal cortex in a region-specific manner (http://www.ncbi.nlm.nih.gov/pubmed/11919662), would adding NADH overly augment dopamine in this region and cause over-stimulation, anxiety or similar? Do you have any experience of using a fluoxetine + NADH combo?
I don't have any other conditions apart from depression and SSRI's are normally pretty effective for me.
Posted by desolationrower on April 1, 2009, at 4:30:28
In reply to Fluoxetine/sertraline and dopamine, posted by sowhysosad on March 31, 2009, at 22:30:18
hi, sounds like you already know a lot about whats going on.
i don't have expereicne with the meds your situation, but have you considered:
DA agonists like pramiprexole
low dose of selegiline - doc may say 'sure no problem' if she's got lots of pensioners, or freak out at ssri+maoi combo
i'm not totally sure the cause of akathisia, but one of the 5ht receptor blockers might help. my guess is to get the sertraline to be dopaminergic the dose will really have to be pushed, so if 5ht is causing the problems it could be problematic. my guess is that fluoxetine would be better, but who knows. st johns wort might be worth trying, at least part of the moa seems to be serotonergic but it also has some dopaminergic component, among other things.
-d/r
Posted by desolationrower on April 1, 2009, at 4:33:11
In reply to Re: Fluoxetine/sertraline and dopamine, posted by desolationrower on April 1, 2009, at 4:30:28
also, manic street preachers name? most of the rest of their songs would make me thing you need a better antidepressant, soon.
-d/r
Posted by Phillipa on April 1, 2009, at 12:51:24
In reply to Re: Fluoxetine/sertraline and dopamine » desolationrower, posted by desolationrower on April 1, 2009, at 4:33:11
I've heard akathesia is horrible. So please be careful. Love Phillipa
Posted by sowhysosad on April 1, 2009, at 16:55:06
In reply to Re: Fluoxetine/sertraline and dopamine, posted by desolationrower on April 1, 2009, at 4:30:28
> hi, sounds like you already know a lot about whats going on.
>
> i don't have expereicne with the meds your situation, but have you considered:
>
> DA agonists like pramiprexole
>
> low dose of selegiline - doc may say 'sure no problem' if she's got lots of pensioners, or freak out at ssri+maoi combo
>
> i'm not totally sure the cause of akathisia, but one of the 5ht receptor blockers might help. my guess is to get the sertraline to be dopaminergic the dose will really have to be pushed, so if 5ht is causing the problems it could be problematic. my guess is that fluoxetine would be better, but who knows. st johns wort might be worth trying, at least part of the moa seems to be serotonergic but it also has some dopaminergic component, among other things.
>
> -d/rThanks d/r - some great ideas there.
Unfortunately I'm not entirely sure selegiline is approved for depression in the UK and, even if it is, I wouldn't hold out much hope on an NHS pdoc prescribing it. They don't seem to like handing out unusual meds or combos if they can help it.
I had to protest VERY loudly before they'd even let me discontinue imipramine, even though it was evidently making my depression much worse (they actually suggested upping the dose by 25mg as a solution!).
Ditto with dopamine agonsists I'm afraid. I can't see the neuro prescribing one, as he's loathe to do anything that could interfere with my other meds. He previously mentioned a benzo like clonazepam, but based on my previous experience with diazepam I don't think it'll have much impact.
Posted by sowhysosad on April 1, 2009, at 16:55:58
In reply to Re: Fluoxetine/sertraline and dopamine » desolationrower, posted by desolationrower on April 1, 2009, at 4:33:11
> also, manic street preachers name? most of the rest of their songs would make me thing you need a better antidepressant, soon.
>
> -d/rlol! Well spotted d/r!
Posted by raisinb on April 2, 2009, at 9:18:25
In reply to Fluoxetine/sertraline and dopamine, posted by sowhysosad on March 31, 2009, at 22:30:18
I'd go with the Zoloft first. Here is a last-ditch idea--do they prescribe Zyban for smoking cessation? It's the same as Wellbutrin. Of course, it is never a good idea to start smoking if you don't already, but if buproprion is truly the answer for you, perhaps that's worth a shot.
Posted by sowhysosad on April 2, 2009, at 9:54:59
In reply to Re: Fluoxetine/sertraline and dopamine » sowhysosad, posted by raisinb on April 2, 2009, at 9:18:25
> I'd go with the Zoloft first. Here is a last-ditch idea--do they prescribe Zyban for smoking cessation? It's the same as Wellbutrin. Of course, it is never a good idea to start smoking if you don't already, but if buproprion is truly the answer for you, perhaps that's worth a shot.
I'd contemplated going down that route, and coincidentally I have started smoking again recently.
However, I've read that Zyban/Welbutrin's active metabolite is more powerful than the drug itself and causes largely norepinephrine reuptake rather than that of dopamine, so overall it boosts the former way more than the latter. So I'd be back to the norepinephrine "sense of impending doom" and heightened startle reflex which has made imipramine so unpleasant.
Posted by desolationrower on April 2, 2009, at 12:05:25
In reply to Re: Fluoxetine/sertraline and dopamine, posted by sowhysosad on April 2, 2009, at 9:54:59
i think most of bupropion's effects of through immune modulation, as its effect on reuptake is quite weak. i don't know if there is a similarity in how tca responders find buprpion.
-d/r
Posted by raisinb on April 2, 2009, at 13:21:12
In reply to Re: Fluoxetine/sertraline and dopamine, posted by sowhysosad on April 2, 2009, at 9:54:59
That's interesting--are you sure about the source? I was on bupropion for awhile and it was definitely a dopamine drug for me. The experts on babble should be able to weigh in here.
Posted by sowhysosad on April 2, 2009, at 17:23:56
In reply to Re: Fluoxetine/sertraline and dopamine, posted by desolationrower on April 2, 2009, at 12:05:25
> i think most of bupropion's effects of through immune modulation, as its effect on reuptake is quite weak. i don't know if there is a similarity in how tca responders find buprpion.
>
> -d/rStill no chance whatsoever that a British pdoc will prescribe bupropion for depression, but the geek in me is interested to find out.
Does anyone have experience of taking (separately) Wellbutrin and a tricyclic like imipramine or cloripramine? Are the feelings of stimulation/agitation/edginess similar at all?
I'm down to 2/3 of my previous imipramine dose and already I'm feeling better as my norepinephrine levels drop (although I'm feeling the negative effects of the drop in serotonin too!). I guess noradrenergic meds just aren't for me.
Posted by sowhysosad on April 2, 2009, at 17:42:48
In reply to Re: Fluoxetine/sertraline and dopamine » sowhysosad, posted by raisinb on April 2, 2009, at 13:21:12
> That's interesting--are you sure about the source? I was on bupropion for awhile and it was definitely a dopamine drug for me. The experts on babble should be able to weigh in here.
I may have read it on Dr Ken Gillman's psychotropical site, but upon searching all I can find is this:
http://www.psychotropical.com/Antidepressants_Bupropion_Zyban.shtml
He doesn't mention the active metabolite's affinity for the norepinephrine transporter in that article, but he does say it's only a weak DRI but probably has some other unknown dopamine-enhancing effect.
I've read elsewhere that bupropion is also a weaker DRI than sertraline, interestingly.
Posted by sowhysosad on April 2, 2009, at 17:48:44
In reply to Bupropion - norepinephrine uptake, posted by sowhysosad on April 2, 2009, at 17:42:48
> > That's interesting--are you sure about the source? I was on bupropion for awhile and it was definitely a dopamine drug for me. The experts on babble should be able to weigh in here.
>
> I may have read it on Dr Ken Gillman's psychotropical site, but upon searching all I can find is this:
>
> http://www.psychotropical.com/Antidepressants_Bupropion_Zyban.shtml
>
> He doesn't mention the active metabolite's affinity for the norepinephrine transporter in that article, but he does say it's only a weak DRI but probably has some other unknown dopamine-enhancing effect.
>
> I've read elsewhere that bupropion is also a weaker DRI than sertraline, interestingly.Ah! Hang on - try this article from the highly-regarded psychopharmaceutical source "Bodybuilding.com":
http://www.bodybuilding.com/fun/par13.htm
"most of bupropion's "antidepressant" action is attributed to its noradrenergic mechanisms. How can this be? Bupropion's active metabolite, hydroxybupropion has almost equal affinity for the NA re-uptake pump as bupropion yet its concentrations during clinical treatment reach 6-fold that of the parent drug"
Posted by desolationrower on April 3, 2009, at 4:09:38
In reply to Re: Bupropion - norepinephrine uptake, posted by sowhysosad on April 2, 2009, at 17:48:44
oh, theres also amantadine. many of these are availible via less than reputable means.
And nicotine is actually a pretty good dopaminergic.
And for non-dopaminergic antiakithisia meds, cyproheptadine and clonidine have been used (5ht antagonist makes more sense given that an ssri is causing it).
theres no clear answer on what bupropion does; theres not much incentive to research it as its off patent and all, though one metabolite was looked into a bit. conventional wisdom is NA/DA reuptake inhibitor, theres some theorizing that its an NE releaser, and i think its mostly tnf-alpha inhibitor, and the da does a little bit.
-d/r
Posted by sowhysosad on April 3, 2009, at 17:12:18
In reply to Re: Bupropion - norepinephrine uptake, posted by desolationrower on April 3, 2009, at 4:09:38
> oh, theres also amantadine. many of these are availible via less than reputable means.
>
> And nicotine is actually a pretty good dopaminergic.
>
> And for non-dopaminergic antiakithisia meds, cyproheptadine and clonidine have been used (5ht antagonist makes more sense given that an ssri is causing it).
>
> theres no clear answer on what bupropion does; theres not much incentive to research it as its off patent and all, though one metabolite was looked into a bit. conventional wisdom is NA/DA reuptake inhibitor, theres some theorizing that its an NE releaser, and i think its mostly tnf-alpha inhibitor, and the da does a little bit.
>
> -d/rThanks d/r. Funny you should mention nicotine, as I've been smoking a fair few cigs every day this week. And I've started dabbling with caffeine after abstaining for months, plus doing some moderate exercise.
The net result is that I felt quite agitated at times yesterday and today, and I've had a raging libido. That would suggest high dopamine, wouldn't it? And yet my movement disorder seems unchanged.
If I was to get akathisia again, its recognition seems so poor in the UK that they'd probably just give me a week's low dose diazepam again.
Posted by desolationrower on April 4, 2009, at 1:44:23
In reply to Re: Bupropion - norepinephrine uptake, posted by sowhysosad on April 3, 2009, at 17:12:18
i think all it would suggest a cold shower :)
(i've never heard of a link of nicotine and libido, even though the both are related to DA.)
-d/r
Posted by Garnet71 on April 4, 2009, at 8:47:47
In reply to Re: Bupropion - norepinephrine uptake » sowhysosad, posted by desolationrower on April 4, 2009, at 1:44:23
Don't understimate the power of cold showers. :) Actually, water therapy has been used by all different cultures for thousands of years so I thought it was worth another look.
And there's no known side effects or dependency issues. Look at the end of the summary - cold water therapy does not appear to "cause dependence". (LMAO)
Summary
Depression is a debilitating mood disorder that is among the top causes of disability worldwide. It can be characterized by a set of somatic, emotional, and behavioral symptoms, one of which is a high risk of suicide. This work presents a hypothesis that depression may be caused by the convergence of two factors: (A) A lifestyle that lacks certain physiological stressors that have been experienced by primates through millions of years of evolution, such as brief changes in body temperature (e.g. cold swim), and this lack of thermal exercise may cause inadequate functioning of the brain. (B) Genetic makeup that predisposes an individual to be affected by the above condition more seriously than other people.
To test the hypothesis, an approach to treating depression is proposed that consists of adapted cold showers (20°C, 23min, preceded by a 5-min gradual adaptation to make the procedure less shocking) performed once or twice daily. The proposed duration of treatment is several weeks to several months.
The following evidence appears to support the hypothesis: Exposure to cold is known to activate the sympathetic nervous system and increase the blood level of beta-endorphin and noradrenaline and to increase synaptic release of noradrenaline in the brain as well. Additionally, due to the high density of cold receptors in the skin, a cold shower is expected to send an overwhelming amount of electrical impulses from peripheral nerve endings to the brain, which could result in an anti-depressive effect. Practical testing by a statistically insignificant number of people, who did not have sufficient symptoms to be diagnosed with depression, showed that the cold hydrotherapy can relieve depressive symptoms rather effectively. The therapy was also found to have a significant analgesic effect and it does not appear to have noticeable side effects or cause dependence. In conclusion, wider and more rigorous studies would be needed to test the validity of the hypothesis.
http://www.medical-hypotheses.com/article/S0306-9877(07)00566-X/abstract
Posted by sowhysosad on April 4, 2009, at 14:03:49
In reply to Re: Bupropion - norepinephrine uptake, posted by Garnet71 on April 4, 2009, at 8:47:47
> Don't understimate the power of cold showers. :) Actually, water therapy has been used by all different cultures for thousands of years so I thought it was worth another look.
>
> And there's no known side effects or dependency issues. Look at the end of the summary - cold water therapy does not appear to "cause dependence". (LMAO)
>
> Summary
>
> Depression is a debilitating mood disorder that is among the top causes of disability worldwide. It can be characterized by a set of somatic, emotional, and behavioral symptoms, one of which is a high risk of suicide. This work presents a hypothesis that depression may be caused by the convergence of two factors: (A) A lifestyle that lacks certain physiological stressors that have been experienced by primates through millions of years of evolution, such as brief changes in body temperature (e.g. cold swim), and this lack of thermal exercise may cause inadequate functioning of the brain. (B) Genetic makeup that predisposes an individual to be affected by the above condition more seriously than other people.
>
> To test the hypothesis, an approach to treating depression is proposed that consists of adapted cold showers (20°C, 23min, preceded by a 5-min gradual adaptation to make the procedure less shocking) performed once or twice daily. The proposed duration of treatment is several weeks to several months.
>
> The following evidence appears to support the hypothesis: Exposure to cold is known to activate the sympathetic nervous system and increase the blood level of beta-endorphin and noradrenaline and to increase synaptic release of noradrenaline in the brain as well. Additionally, due to the high density of cold receptors in the skin, a cold shower is expected to send an overwhelming amount of electrical impulses from peripheral nerve endings to the brain, which could result in an anti-depressive effect. Practical testing by a statistically insignificant number of people, who did not have sufficient symptoms to be diagnosed with depression, showed that the cold hydrotherapy can relieve depressive symptoms rather effectively. The therapy was also found to have a significant analgesic effect and it does not appear to have noticeable side effects or cause dependence. In conclusion, wider and more rigorous studies would be needed to test the validity of the hypothesis.
>
> http://www.medical-hypotheses.com/article/S0306-9877(07)00566-X/abstract
>Funnily enough, I recall my grandmother saying her father would have a daily cold bath!
Maybe he was on to something there.
Posted by garnet71 on April 5, 2009, at 9:53:24
In reply to Re: Bupropion - norepinephrine uptake, posted by sowhysosad on April 4, 2009, at 14:03:49
You're from the UK, right? Oh I have to ask anyway--did you ever see the Seinfeld episode where George had 'shrinkage' from a swimming pool?
lol
Posted by sowhysosad on April 5, 2009, at 15:41:31
In reply to Re: Bupropion - norepinephrine uptake » sowhysosad, posted by garnet71 on April 5, 2009, at 9:53:24
> You're from the UK, right? Oh I have to ask anyway--did you ever see the Seinfeld episode where George had 'shrinkage' from a swimming pool?
> lolI must admit I've never seen an episode of Seinfeld, even though the BBC showed all of them!
Posted by Alexanderfromdenmark on April 6, 2009, at 3:37:34
In reply to Re: Bupropion - norepinephrine uptake, posted by sowhysosad on April 5, 2009, at 15:41:31
Haha, I've been using cold showers for years to beat depression and fatigue! Fun to see it's actually being studied. Great for your skin too!
Posted by garnet71 on April 6, 2009, at 11:13:16
In reply to Re: Bupropion - norepinephrine uptake, posted by sowhysosad on April 5, 2009, at 15:41:31
Oh-that episode's called at the Hamptons. Here's a short clip:
http://www.youtube.com/watch?v=1cUNNKzj_Nc
Posted by garnet71 on April 6, 2009, at 11:21:43
In reply to Re: Bupropion - norepinephrine uptake, posted by garnet71 on April 6, 2009, at 11:13:16
I love this one-
The Opposite:
http://www.youtube.com/watch?v=IjXUgxR4Z10&NR=1I didn't know these were even on youtube..i coud watch these all day lol
omg gotta get back to work now
Posted by sowhysosad on April 7, 2009, at 22:43:49
In reply to Re: Fluoxetine/sertraline and dopamine, posted by desolationrower on April 1, 2009, at 4:30:28
> low dose of selegiline - doc may say 'sure no problem' if she's got lots of pensioners, or freak out at ssri+maoi combo
Just revisited d/r's earlier post and started researching selegiline. Looks like it's easily and cheaply available online. 5-10mg would be a "low dose", wouldn't it?
I'm rethinking SSRI's at the moment as I'm terrified of exarcerbating my issues with fine motor control in my jaw. As an alternative, I wonder if 5HTP would work OK in tandem with selegiline?
Presumably there's no risk of serotonin syndrome because a) 5HTP wouldn't prevent reuptake into the synapse and b) selegiline only inhibits MAO-B.
Just another thought about what may have caused the movement disorder: could it have been caused by supersensitive D2 receptors from the successive AD's I've been taking? ie. could it be over-sensitivity to dopamine rather than dopamine depletion?
Posted by desolationrower on April 8, 2009, at 8:24:48
In reply to Re: Fluoxetine/sertraline and dopamine » desolationrower, posted by sowhysosad on April 7, 2009, at 22:43:49
haven't really looked into mnovement disorders but why would 5htp not exacerbate it if ssris would?
-d/r
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