Tamoxifen

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Chrismander

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Has anyone used this for acute mania?

I've read over the years several pilot studies on it, based on rational design looking for protein kinase C inhibitors. It always seemed very "outside the box" and not ready for primetime.

Well I was reading CANMAT--apparently Canada's bipolar guidelines (http://www.canmat.org/resources/CANMAT Bipolar Disorder Guidelines -2009 Update.pdf) , and it's listed as a third line agent right alongside Clozaril, Haldol, and mood stabilizer + haldol combos.

Have any of our Canadian colleagues lurking on this board seen it used? Has anyone else tried it or heard of it being tried?

We have a patient with severe mania right now that for a number of reasons can't do lithium, depakote, tegretol, clozapine. And all atypicals are failing, including haldol + atypical combos. Benzos seem to make him worse. He's been hospitalized for 4 weeks at a private hosp prior to transfer here, and has steadily declined. His brother, also bipolar, is maintained on clozaril but that's not an option in him. ECT isn't done at our facility and he's too sick to transfer out for ECT to a private hospital that would do it.

So if Tamoxifen is a third line agent to Canadians, how far out there is it to start him on a trial?
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Interesting post. Any chance he's withdrawing from any substance(s)? And not to digress, but have you considered verapamil or keppra (or reserpine??)?
 
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firedoor said:
Interesting post. Any chance he's withdrawing from any substance(s)? And not to digress, but have you considered verapamil or keppra (or reserpine??)?
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How much evidence base is there for keppra or verapamil? Have you tried them?

Reserpine isn't a bad option, though we're hitting him pretty good with typical and atypicals, so I don't know how much more dopamine depletion vs. blockade will help.
 
Chrismander said:
How much evidence base is there for keppra or verapamil? Have you tried them?

Reserpine isn't a bad option, though we're hitting him pretty good with typical and atypicals, so I don't know how much more dopamine depletion vs. blockade will help.
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I have not used them.

Not a ton of data on keppra, but here is some:

http://www.gjpsy.uni-goettingen.de/gjp-article-mohamadi.pdf

http://altcancerweb.com/bipolar/nov...evetiracetam-adjunctive-treatment-bipolar.pdf

Perhaps verapamil is less than promising:

http://ajp.psychiatryonline.org/cgi/content/full/155/7/972

Also, reserpine is antiserotonergic (as are thorazine and propanolol) and antinoradrenergic (NE probably plays a major role in the switch to mania), not just antidopaminergic, and so theoretically may confer different mechanistic and/or therapeutic benefits than antipsychotics. And I wholeheartedly agree with nitemagi about ruling out delirium (including "toxic delirium"--i.e. iatrogenic).

Any substance history?
 
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I would experiment with the first generation antipsychotics. I have never witnessed mania so severe antipsychotics and benzos didn't work. My experience with mania is that it should be stamped out as swiftly and quickly as possible. I recently had a patient that was verbally and physically hostile, delusional, flights of ideas, banging his head on the wall and the sandman was knocking on his door after haldol 5mg, seroquel 800mg, 2 ativan, 50 benadryl. Have you been using high enough doses of antipsychotics? Take advantage of the broad therapeutic index. Stabilizing mania by titrating and weighing the side effects is another story.
 
Also keep in mind that manic patients can really chew up meds (metabolically speaking), so don't be afraid to go higher in doses. Plus med inducers (including cigarettes) that may lead to a need of higher doses.

I'm actually surprised tamoxifen gets a rating. I have seen much beyond a case series supporting it. I'd put it in the "experimental" category, along with ketamine for refractory depression.
 
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nitemagi said:
I'm actually surprised tamoxifen gets a rating. I have seen much beyond a case series supporting it. I'd put it in the "experimental" category, along with ketamine for refractory depression.
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The recommendation for tamoxifen in the CANMAT guidelines was based on a small RCT of tamoxifen, so the evidence goes far beyond a case series : http://www.ncbi.nlm.nih.gov/pubmed/18316672 and has since been replicated: http://www.ncbi.nlm.nih.gov/pubmed/20843556 - though both these studies are rather small the sad truth is much of what passes is quite weak (how did abilify ever get FDA approval for bipolar maintenance?!)

I am unclear why pt cannot take the usual potions but with these difficult to treat patients always go back to basics:
1. is this mania? if so is it mania alone? (delirium and substance withdrawal have already been suggested, i would throw in r/o endocrinopathies - have seen cushing's really ratchet up mania and would like to know HIV status)
2. is there anything about the current environment that is exacerbating his behavioral disturbance? is there anything he has been given that is exacerbating his behavioral disturbance?
3. can you really not use any of the usual potions? (i.e. is the risk of using depakote etc greater than the risk of untreated mania bearing in mind in the old days it was not uncommon for people to die of manic exhaustion)
4. have the medications that have been tried tried at the maximal therapeutic doses?
5. has the patient been placed in a darkened environment?
6. has the patient been plied with benzos for sedation?
7. has the patient been plied with phenothiazine or thiothixene antipsychotics (remember than butyrophenones in particular can sometimes cause a paradoxical rxn and worsen mania, have seen this with risperidone too - the lower potency conventional antipsychotics like thorazine or zuclopentixol may be better)

personally, assuming the pt is experiencing acute severe mania, i would knock him out as best as possible and have him transferred for ECT. it is regrettable he was not transferred to a facility with ECT on site in the first place.

i don't think tamoxifen is the worst idea in the world, but there is much stronger evidence supporting knocking someone out and ECT. if you can't knock him out for a few hours either you have failed to mention some comorbidity that puts him at major risk of respiratory depression or you're not trying hard enough.

 
If he's still breathing manically, you probably haven't used enough Ativan.

I'm also very saddened to hear that you have an ECT facility that can't handle a bread and butter psychiatric issue.
 
What is the reason he can't take lithium?
 
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I've read a lot of data showing this med has a mood stabilizer benefit, but I never gave it for that reason because the data wasn't to the point where it was on the order of the existing mood stabilizers. Further, I speculate that it could help in some cases where the patient may have gynecomastia caused by antipsychotics because it prevents growth of breast tissue.

E.g. guy has schizoaffective disorder, bipolar type, the guy was on Risperdal, got gynecomastia, Tamoxifen could be a possible option. Problem is the lack of data as far as I know.
 
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