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RU486, Celebrex, Mirapex, and Zonisamide 4 BP Dep

Posted by inanimate peanut on January 3, 2010, at 21:32:37

I just read a really interesting article on treating bipolar depression. I'm happy to send it along to anyone who babbles me. Anyway, they mentioned several things that were tried off label for bipolar depression and worked in small trials. Mifepristone (RU486), Celebrex, Mirapex, and Zonisamide all improved depression levels (plus things we've already talked about here like Provigil and NAC and fish oil). Granted these were small trials, but they were at least pointing for the need for more research. I'd love to hear if epople have tried these or what they think. Here's that excerpt of the article below:

Novel medications and complimentary agents
Antiglucocorticoids
High cortisol levels have been associated with melancholia, and it has therefore been hypothesised that antiglucocorticoid treatments (e.g., mifepristone, ketoconazole, and metyrapone) may be able to improve the symptoms of depression (136). A Cochrane review of the efficacy and safety of antiglucocorticoids in the treatment of depressive episodes (mainly unipolar) concluded that the use of antiglucocorticoids is still at the 'proof of concept' stage and that further research is warranted (137). However, in a bipolar disorder trial, the addition of mifepristone to existing treatment resulted in a significant improvement in depressive symptoms and neurocognitive functioning (138).

Celecoxib. Celecoxib, a cox-2 inhibitor, has been investigated for its potential to accelerate the antidepressant effect in bipolar depression. In patients with a bipolar depressed or mixed episode, a small, double-blind, placebo-controlled trial of celecoxib adjunctive to usual treatment showed trends toward an improvement on depression symptoms during the first week of the trial for the celecoxib group overall, and the initial improvement was significant for those subjects who went on to complete the trial (139).

N-acetyl cysteine (NAC). Oxidative stress disrupts glutathione metabolism and has been identified in a number of neuropsychiatric disorders, including bipolar disorder. When prescribed as an adjunct to usual medication, NAC, a precursor of glutathione, has been found to significantly improve depressive symptoms in a placebo-controlled, randomised trial for bipolar disorder (140).

Modafinil. Modafinil is a stimulant medication that is usually used to treat sleep disorders and is now being trialled in the treatment of bipolar depression. A six-week, randomised, controlled study in bipolar I and II depression reported that both response and remission rates for modafinil, in addition to lithium or an anticonvulsant, were superior to adjunctive placebo (141).

Pramipexole. Small RCTs of pramipexole, a dopamine agonist, have demonstrated significant antidepressant effects in preliminary trials for the treatment of bipolar II depression (142) and refractory bipolar I depression (143).

Zonisamide. A small, eight-week, open trial demonstrated significant improvements in depression ratings after the addition of zonisamide, a sulphonamide anticonvulsant, to usual treatment. However, interpretation of the findings is limited by the fact that half of the sample dropped out of the study due to adverse effects (144).

Omega-3 fatty acids. There is increasing interest in the link between omega-3 fatty acid deficiency and the development of bipolar depression. In particular, the long-chain omega-3 fatty acid ethyl-eicosapentaenoate (EPA) that is administered as a supplement has been investigated in three clinical trials for its antidepressant effect in bipolar disorder. The first clinical trial was conducted by Stoll and colleagues (145), where EPA as an adjunctive treatment significantly delayed the onset of a new depressive episode. More recently, however, there have been mixed findings. A four-month trial of EPA at 6 g/day adjunctive to usual treatment for bipolar depression and rapid-cycling bipolar disorder did not report any significant benefits in either group (146); however, a separate three-month trial of EPA at 1 g or 2 g/day produced a significant improvement in both depression scores and overall functioning as compared to controls (147). The different doses that have been administered across these studies hamper direct comparison; however, unipolar depression research studies suggest that doses of EPA at 1 g/day may be more effective than higher doses (148).

In summary, a number of novel medications and complimentary agents that employ new and different mechanisms of action demonstrate variable efficacy in the treatment of bipolar depression. Preliminary findings appear to be promising but further rigorous studies are needed.


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poster:inanimate peanut thread:932402
URL: http://www.dr-bob.org/babble/20100103/msgs/932402.html