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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by Chris A. on May 10, 2001, at 12:39:46
My consultant recommended Tamoxifen as a mood stabilizer. It is the estrogen
antagonist prominent in breast cancer treatment. I haven't started it, as I have been
taking high dose estrogen for it's much touted neuro-protective effects. He says the
evidence that estrogen is neuro-protective is very weak and has been over publicized.
At 48 I have just gone off of my estrogen to see where I'm at, and as a possible
intermediate step towards Tamoxifen. In reading Dr. Manji's research results, I'm
feeling that this is a tentative treatment with a lot of risks. It's supposed to be a PKC
inhibitor like depakote and lithium. It is also aimed at refractory mania. Since my
experience is 95% depressive in nature I am concerned that it might leave me flattened
out at the bottom at best, like Nimodipione did. I am diagnosed mixed bipolar and the
only mood stabilizer that I've tolerated is Lamictal. Ziprasidone caused really bad
akithisia, so I don't want to go back on it with a beta blocker (another pill to take and
opay for, not to mention dealing with more side effects - aaarrrgghh!) It would be nice
not to be so internally restless that I can't sit through my daughter's graduation. At least
there is another milestone that it is important to stay alive for. If it weren't for milestones
I wouldn't have survived thus far.If anyone has had experience with Tamoxifen I would like to hear about your
experience.Thanks in advance,
Chris A.
Posted by SLS on May 10, 2001, at 21:44:38
In reply to Tamoxifen - experience with as a mood stabilizer?, posted by Chris A. on May 10, 2001, at 12:39:46
Hi Chris.
> My consultant recommended Tamoxifen as a mood stabilizer. It is the estrogen antagonist prominent in breast cancer treatment. I haven't started it, as I have been taking high dose estrogen for it's much touted neuro-protective effects. He says the evidence that estrogen is neuro-protective is very weak and has been over publicized. At 48 I have just gone off of my estrogen to see where I'm at, and as a possible intermediate step towards Tamoxifen.> In reading Dr. Manji's research results, I'm feeling that this is a tentative treatment with a lot of risks. It's supposed to be a PKC inhibitor like depakote and lithium. It is also aimed at refractory mania. Since my experience is 95% depressive in nature I am concerned that it might leave me flattened out at the bottom at best, like Nimodipione did. I am diagnosed mixed bipolar and the only mood stabilizer that I've tolerated is Lamictal. Ziprasidone caused really bad akithisia, so I don't want to go back on it with a beta blocker (another pill to take and opay for, not to mention dealing with more side effects - aaarrrgghh!) It would be nice not to be so internally restless that I can't sit through my daughter's graduation. At least there is another milestone that it is important to stay alive for. If it weren't for milestones I wouldn't have survived thus far.
What about taking Klonopin (clonazepam)? Maybe Ativan (lorazepam) as needed?
I thought it might be worth mentioning that estrogen has been infrequently reported to produce mania and induce rapid-cycling. Is your estrogen a preparation of estradiol? I am not familiar with its neuroprotective effects. Why do you feel it is necessary to use something with neuroprotective effects? What about using something like Mirapex instead? Are you trying to prevent neuroleptic-induced changes? Lithium has the ability to coax the neuron to secrete neuroprotectors and neurotrophic growth factors, and to inhibit the neuron from producing its own neurotoxins.
Which paper are you referring to? Do you have the full text?
What are the risks of taking tamoxifen?
Just a thought - perhaps tamoxifen does not fully antagonize estrogen globally. Is it possible that some of the antidepressant effects of estrogen augmentation persist despite tamoxifen administration? Another thought is that taking both estrogen and progesterone together in the right ratio might produce a more stable mood. Have you tried supratherapeutic dosages of thyroid (both T3 and T4)? Sorry. I think too much and know too little. :-)
I would think that tamoxifen might be depressogenic for some people, at least for women. I don't know the Manji paper, but I wonder if he took into consideration gender differences. My guess is that the antiestrogen effects of tamoxifen are unwanted and that direct protein kinase-C (PKC) inhibition is the target. I think lithium and valproate affect PKC activity indirectly via adenylyl cyclase, cAMP, or some other second messengers. Perhaps a direct PKC inhibitor produces more robust effects. Is that how tamoxifen works?
I took a quick peak at tamoxifen and bipolar disorder stuff on Medline. I didn't find more than a handful of citations. I think it is worth noting that tamoxifen was referred to specifically as being effective to treat acute mania without being referred to as a mood stabilizer. Maybe I'm just knit-picking. However, I doubt that any mood stabilizing effects that tamoxifen might possess could be ascertained from the few anecdotal successes when treating patients during a manic episode. Either way, it might help with your 95% depression by preventing its being setup for by paroxysmal manias. Usually, depression occurs immediately after and probably directly from mania whereas mania more often appears during a period of relatively normal mood. The inverse pattern is supposed to be more difficult to treat. That is, excluding drug-induced switches, depression appears during a normothymic period and is followed immediately by mania.
The NIMH was real optimistic about nimodipine when I was a guinea-pig there in 1992-93. I don't see that much has become of it, but I think it is still to be considered when treating extremely refractory and rapid-cycling presentations. I'm sorry it didn't work out for you. It is prohibitively expensive to use on a regular basis. I believe its primary use is to mitigate the damage that immediately follows a CVA (stroke). I guess the pills/person ratio for this indication is too small to encourage the drug company to sell it any cheaper.
It is so easy to suggest things from the other side of someone's fence. I think you have to take into consideration not only the risk versus benefit of any one drug or drug combination, but also the number of unexplored alternatives available versus the chronicity and severity of your illness. I really don't have to tell you that. You probably know better than I.
Anyway, to answer your question, I have not taken tamoxifen, so I have nothing to say. :-)
With prayers and the sincerest of sentiments,Scott
Posted by Chris A. on May 11, 2001, at 13:06:29
In reply to Re: Tamoxifen - experience with as a mood stabilizer?, posted by SLS on May 10, 2001, at 21:44:38
Thanks for all your thoughts. My left brain doesn't work very well so I can't organize intelligent responses to all of your queries.
In the links to grand rounds there is a lecture Manji gave entitled "Molecular mechanisms underlying mood stabilization in Manic - Depressive illness." (March 5th). I did find papers of his on medline. Most of it is above my head, but I do get the gist of it, that Tamoxifen is a PKC inhibitor like lithium and depakote. As far as gender differences go, I know nothing. I haven't even studied the PDR info yet.
Since I am not doing too badly at the moment other than vegetating and getting upset once in a while (knock on wood) my next step will probably be to add galantamine for my cognitive difficulties and then to add ziprasidone with whatever beta blocker required as the need arises. If I can handle the akathisia it is probably my best bet since is supposed to have AD effects.
Side effects often leave me taking meds at sub-therapeutic doses. Often I wish that Lithium had worked and ADs didn't cause me to cycle. Stabilization has been possible, but it has always been on the very low end of the spectrum - not acceptable.Perhaps you can suceed in getting me to think!
Blessings (and thanks for the prayers),
Chris A.
> Which paper are you referring to?
> Scott
Posted by SalArmy4me on May 11, 2001, at 23:07:52
In reply to Tamoxifen - experience with as a mood stabilizer?, posted by Chris A. on May 10, 2001, at 12:39:46
I am only aware of one study (which you mentioned) that links Tamoxifen with mood-stability, and that one has to do with bipolar mania rather than bipolar depression. I wouldn't try Tamoxifen and risk some serious side-effects based on such poor evidence for its efficacy.
Bebchuk, Joseph M. MD, FRCPC. Arfken, Cynthia L. PhD. Dolan-Manji, Suzanne RN. Murphy, Joanne RN. Hasanat, Khondakar MD. Manji, Husseini K. MD, FRCPC. A Preliminary Investigation of a Protein Kinase C Inhibitor in the Treatment of Acute Mania. Archives of General Psychiatry. 57(1):95-97, January 2000.
Posted by judy1 on May 12, 2001, at 21:17:18
In reply to Tamoxifen - experience with as a mood stabilizer?, posted by Chris A. on May 10, 2001, at 12:39:46
Hi Chris,
Pretty extreme, but I know desperate. I was just talking to one of my sisters- wishing each other Happy Mother's Day (and to you too, right? :-) and she is also dxed bipolar/panic. We have a very strong genetic thing going on here. Anyway, her symptoms are not as severe as yours, but she has found relief with verapamil, a CCB. Just wondering if you have ever taken it? Take care, judy
Posted by SLS on May 13, 2001, at 10:51:40
In reply to Re: Tamoxifen - experience with as a mood stabilizer? » Chris A., posted by judy1 on May 12, 2001, at 21:17:18
> Anyway, her symptoms are not as severe as yours, but she has found relief with verapamil, a CCB. Just wondering if you have ever taken it? Take care, judyThat's not a bad idea. It might be worth a shot. There is some thought that certain L-type calcium channel blockers might be useful for treatment-resistant bipolar disorder. The only two drugs I know of that are consistently investigated are verapamil and nimodipine, both of which have been used with some success. The NIMH was also looking at isradipine My impression at the moment is that they are not effective in the majority of cases, and are not very useful as monotherapy, but they can work well when combined with mood-stabilizers like carbamazepine. I don't like nifedipine. I believe that nifedipine can actually cause depression, and has even been reported to reverse the remission produced by antidepressants (at least the tricyclics).
Chris, I would not extrapolate your negative reaction to nimodipine to verapamil. They are derived from completely different chemical families. I am not strongly suggesting that you try it, but is a good thought.
One of my motivations to stick my nose back in this thread was to comment on the desirability of discontinuing estrogen abruptly. My first reaction is that this would be analogous to the precipitous drop in estrogen postpartum that might be at least partially responsible for postpartum depression. The other thing is that it takes some time before the hypothalamo-pituitary-gonadal axis becomes resensitized so that the body resumes making estrogen on its own.
I don't know. Just a thought.
- Scott
Posted by NikkiT2 on May 13, 2001, at 16:18:30
In reply to Tamoxifen - experience with as a mood stabilizer?, posted by Chris A. on May 10, 2001, at 12:39:46
I am so interested and waiting for thisd to hit the UK. There is a strong hsitory of breast cancer in my family, and my mum was on this for a number of years.
I'd love to know if it helps.
nikki
> My consultant recommended Tamoxifen as a mood stabilizer. It is the estrogen
> antagonist prominent in breast cancer treatment. I haven't started it, as I have been
> taking high dose estrogen for it's much touted neuro-protective effects. He says the
> evidence that estrogen is neuro-protective is very weak and has been over publicized.
> At 48 I have just gone off of my estrogen to see where I'm at, and as a possible
> intermediate step towards Tamoxifen. In reading Dr. Manji's research results, I'm
> feeling that this is a tentative treatment with a lot of risks. It's supposed to be a PKC
> inhibitor like depakote and lithium. It is also aimed at refractory mania. Since my
> experience is 95% depressive in nature I am concerned that it might leave me flattened
> out at the bottom at best, like Nimodipione did. I am diagnosed mixed bipolar and the
> only mood stabilizer that I've tolerated is Lamictal. Ziprasidone caused really bad
> akithisia, so I don't want to go back on it with a beta blocker (another pill to take and
> opay for, not to mention dealing with more side effects - aaarrrgghh!) It would be nice
> not to be so internally restless that I can't sit through my daughter's graduation. At least
> there is another milestone that it is important to stay alive for. If it weren't for milestones
> I wouldn't have survived thus far.
>
> If anyone has had experience with Tamoxifen I would like to hear about your
> experience.
>
> Thanks in advance,
>
> Chris A.
This is the end of the thread.
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