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Dr. Bob is Robert Hsiung, MD,
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Posted by dgramovska on October 12, 2011, at 14:13:48
Dears all,
I am an ultrarapid/ultradian cycler, and I'm curious about Agomelatine, 5HT2C receptors and antipsychotics, and how these relate to my condition.
I cycle in waves. I'll go for one week or so in a euthymic and/or hypomanic mood (hard to distinguish), then for a week or so in a mildly/moderately depressive mood. Either way, my mood starts to rev up sometime between 1:00pm to 4:00pm, regardless of whether I'm in a depressed mood or a manic one. If depressed, I just feel fine or much better around this time, and if I'm euthymic or manic, I tend to start getting a higher and higher mood as the evening wears on. Also, though I cycle quickly, I only get some mild-moderate depressions (the provigil got me at the top end of hypomania once, and caused a severe depression thereafter), and my hypomania is under control (mostly). And I no longer have those agitated depressions that got me in lots of trouble with my girlfriend.
Also, I've noticed that my body temperature gets colder when I'm depressed (I have to wear a jacket even in a warm room), and when manic I'm warmer (I often have to wear a tshirt when everyone else is cold).
I remember reading a while ago that this sort of diurnal variation, especially with the body temperature fluctuations and ultrarapid/ultradian cycling can be indicative of a circadian system out of synch. Perhaps my body is sleeping while I'm awake (depressed), and perhaps my being awake happens only starts around noon-4:00pm. In the past I read a lot of literature to support this, but I've only got one piece at the moment: http://www.psychiatrictimes.com/bipolar-disorder/content/article/10168/54751
So I'm considering starting on agomelatine. According to the paper linked above, ultra rapid cyclers are possibly affected by their messed up circadian rhythms. If agomelatine supposedly synchs the circadian rhythms, perhaps it would be of some benefit to me..? My biggest concern is that it might trigger a manic episode and/or worsen the course of my illness over time. As an antidepressant, regardless of the mechanism of action, I've been told that it is likely to cause trouble. And given its 5HT2C antagonist properties, where it disinhibits dopamine and norepinephrine in the prefrontal cortex, I wonder if it could be harmful in this way.
Especially for someone like me, who's only ever had a more serious manic episode from dopamine-related drugs. That is, adderall for me causes a moderate hypomania right away, and provigil causes pretty much the same feeling, but longer lasting. Provigil also caused the most intense mania I've had about 3 weeks into using it chronically. I crashed into a severe depression after that. My guess is that these drugs are more dopaminergic than the SSRIs, and that I'm particularly susceptible to dopamine-induced mania.
So is this 5HT2C antagonist going to push me into mania via its disinhibition of dopamine? Apparently zyprexa (which I'm taking) and some other antipsychotics (especially quetiapine) have 5HT2C antagonist properties. And surely they would not be prescribed routinely if this caused mania.
I guess I'm just confused as to how 5HT2C antagonism would not be considered likely to cause mania, especially given that quetiapine's anti-depressant potential is partly due to its 5HT2C antagonist properties.
Anyone with any help, ideas, questions, etc., no matter how trivial or irrelevant it may seem, are encouraged to post here.
Sorry for the long post. And if you've got this far, thank you so much for reading.
Alcxo
Here is my current drug regimen:
Lamotrigine 2x200mg am and 2x200mg pm
Zyprexa 15mg pm
Lithium 2x 300mg am and 4x 300mg pm
Levothyroxine 7.5 micrograms am
Propanolol - not sure about mg- I think 5mg am and 5mg pm
Posted by linkadge on October 14, 2011, at 15:50:11
In reply to 5HT2C antagonism, Agomelatine, Antipsychotics, posted by dgramovska on October 12, 2011, at 14:13:48
Interesting topic. I have been questioning my possible bipoliarity. My sleep cycles constantly. I have taken a *lot* of different sleep meds, but one of the strongest has been the combination of cyproheptadine and melatonin.
Cyproheptadine is a 5-ht2c antagonist with some antihistamine and calcium channel blockade.
The latter two would distinguish the drug from agomelatine (which I can't get in canada AFAIK).
Anyhow, my *big* problem is sleep. I known that the 5-ht2c receptors play some role in the regulation of circadian rythem.
Linkadge
Posted by dgramovska on October 14, 2011, at 16:30:36
In reply to Re: 5HT2C antagonism, Agomelatine, Antipsychotics, posted by linkadge on October 14, 2011, at 15:50:11
Interesting, this cyproheptadine. So a quick scan on wikipedia says nothing about its potential as an antidepressant. But mustn't it have such potential, given its 5HT2C antagonist properties?
Also, I'd like to condense my original post. What I'm most interested in is whether 5HT2C antagonism has any likelihood of producing a manic reaction. It seems that with its and norepinephrine dopamine-releasing in the prefrontal cortex, it should be possible for it to induce mania.
That said, antipsychotics have 5HT2C antagonist properties, but we know they don't cause mania...
Posted by linkadge on October 15, 2011, at 15:23:38
In reply to Re: 5HT2C antagonism, Agomelatine, Antipsychotics, posted by dgramovska on October 14, 2011, at 16:30:36
>It seems that with its and norepinephrine >dopamine-releasing in the prefrontal cortex, it >should be possible for it to induce mania.
Well...possibly. The ability of atypicals to enhance cognative function in schizophrenia / bipolar is supposedly linked to their interaction with 5-ht2a/c.
I kind of think of the 5-ht2c effect as not being as strong as say the dopamine enhancing effect of stimulants (although I really have no comparison).
The antidepressant ketanserin is a relatively pure 5-ht2a/c antagonist. I think it has a low rate of mania, although it hasn't been used much clinically.
Talking with my doctor, drugs like tradazone, nefazaodone and remeron (which are all 5-ht2c antagonists) tend to produce less mania than the reuptake inhibitors. (He said he's never heard of a manic switch on trazadone).
Cyproheptadine is also a calcium channel blocker (which in theory could be antimanic).
Anyhow, I don't know how strong a pure 5-ht2c antagonist would be as an antidepressant.
Also, most 5-ht2c antagonists are also 5-ht2a antagonists which makes things confusing since 5-ht2a antagonists have some antimanic effects.
Some mania is actually caused by prefrontal hypofunction (executive dysfunction).Any of the drugs I've taken with 5-ht2c antagonist effects almost seems more like a mood stabilizer than a pure antidepressant.
Apparently lithium interacts (in an inhibitory way) with the 5-ht2c receptor.
Linkadge
This is the end of the thread.
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