Recently, I wrote a piece for PsychCentral that outlined some recommendations for treatment-resistant bipolar disorder. This piece talked about first-line and second-line agents for the treatment of bipolar disorder but I wanted to delve a little further into the novel agents that are now being studied for the treatment of bipolar depression. These are medications that are not typically used to treat bipolar disorder, work in new ways and show promise in recent studies. This is cutting edge and if you’re treatment-resistant this is an area that can offer you hope.
Why Are Novel Agents Needed in the Treatment of Bipolar Depression?
The reason why this piece is about unusual bipolar depression medication and not medication for mania is because the medications we have for mania are quite effective for most people. It is the bipolar depression that, typically, is very hard to treat. Additionally the two Food and Drug Administration (FDA)-approved bipolar depression treatments (quetiapine and an olanzapine/fluoxetine combination) tend to carry very serious side effects like weight gain, risk of diabetes including diabetic ketoacidosis and others. We also know that most people with bipolar disorder spend vastly more time in a depressed state than in a manic state.
According to Dr. Prakash Masand, CEO and founder of Global Medical Education, “Less than 30% of bipolar patients achieve remission that is maintained long term. There are great unmet needs in the treatment of bipolar depression. Innovative approaches are needed rather than ‘me-too’ agents that offer little incremental benefit.”
Dr. Masand notes the following are new, novel agents that look promising in the treatment of bipolar depression.
Armodafinil in the Treatment of Bipolar Depression
This drug has been of interest for some time in the treatment of bipolar depression. Armodafinil binds to the dopamine transmitter and inhibit dopamine reuptake. In other words, this drug makes more dopamine available to your brain and works similarly to selective serotonin reuptake inhibitors (SSRI) antidepressants but does so with dopamine rather than serotonin. Doses of 150 mg have been shown to effectively treat bipolar depression when used as an adjunct to treatment and more trials are pending.
Riluzole in the Treatment of Bipolar Depression
Riluzole is a drug that’s approved to treat a motor neuron disease and works to modulate glutamate (a neurotransmitter I’ve been talking about for a while). In doses of 50-200 mg/day, Riluzole has shown efficacy in treatment-resistant bipolar depression both as monotherapy and as an adjunct to lithium.
N-Acetylcysteine in the Treatment of Bipolar Depression
This is one of my personal favorites because it’s sort of not a drug; N-acetylcysteine (NAC) is a supplement and available without a prescription. Again, this compound works on glutamate function, as Dr. Masand explains, “NAC increases central and peripheral glutathione and modulates glutamate function, is anti-inflammatory and increases neurogenesis [birth of new brain cells].” At doses of 2 g/day, it has been shown to treat bipolar depression but its maintenance benefits are unknown. (More on NAC and bipolar depression here.)
(NOTE: just because this is a supplement doesn’t mean you shouldn’t discuss it with your doctor. You absolutely need consultation before starting this, just like with any substance.)
Pramipexole in the Treatment of Bipolar Depression
Pramipexole is FDA-approved in the treatment of Parkinson’s disease and is a dopamine agonist, meaning, like armodafinil, it makes more dopamine available to your brain. At doses of 0.375-4.75 mg/day pramipexole has shown superiority to placebo as an adjunct to mood stabilizers for treating bipolar depression. Note that this drug can have serious side effects, however, like a worsening of psychosis, confusion and heart failure.
Ketamine in the Treatment of Bipolar Depression
I’ve mentioned ketamine before and while many people know ketamine as a street drug it’s actually shown great promise in treating bipolar depression. Ketamine is an N-Methyl-D-aspartic acid (NMDA) antagonist that has been shown to treat bipolar depression in a matter of minutes when given intravenously. However, effects wear out quickly due to its short half-life although in some instances benefits may last 3-4 weeks. Intranasal and sublingual ketamine has also been studied and it is dosed every 3-7 days. I consider the study of sublingual ketamine to be extremely promising as that is a more workable way of delivering this drug than intravenously.
Trying Out a Novel Bipolar Depression Treatment
If you think some of this research is interesting, take it to your doctor and have a discussion. I can’t promise your doctor will get on board, but I can say that more knowledge and more discussion is a good thing.
Please note that while Dr. Masand is a psychiatrist, nothing in this article is to be considered medical advice. Always work with your doctor to find the best treatment for you.
Unmet Needs in the Treatment of Bipolar Disorder
Do you want to thank Dr. Masand for this information? Then please take this short survey. This survey is designed to pinpoint the unmet needs in the treatment of bipolar, and we all know there are many. It’s important as it’s one way that patients can speak directly to doctors and make their thoughts known.
Treatment resistant 61 and in last 1/4 of life God will straighten it out latter it is your cross
In your discussion of N-acetylcysteine above, you reference a dosage of 2mg/day, however the study you provide a link to actually used 2000mg/day — could you either correct or clarify this, as it creates some confusion. Thank you.
Hi James,
You are correct. 2000 mg is 2 grams, which is what I meant. My apologies. I fixed it in the text. Thanks for pointing it out.
– Natasha Tracy
Hello Natasha.
I am medical doctor and myself just recently diagnosed with ultra-rapid cycling bipolar disorder ii, In retrospect it was quite clear that I have had this condition for many years. I have been on every AD out there and it ofcourse never worked and I think to some extent the AD have had me cycling very bad and made my condition even more treatment resistant.
I am now looking for treatment option for getting me “normal”. I have more proplem with the depressions and mixed state, not very many euphoric hypomais for me.
In my seach for treatment information I found your site. Just want to say how great it is. Thank you for sharing everying you have learnd about this illness.
I would like to add two other “novel” options in the treatment of bipolar depression, you might have covered them elswhere though.
1 . High dose thyroxin. Small studies, seems to work on rapid cycling WOMAN.
http://psycheducation.org/wp-content/uploads/2014/11/HighDoseThyroidReview.pdf
And
2. Scopolamine
http://www.ncbi.nlm.nih.gov/pubmed/21976067
Tanx again and sorry about the spelling, english is not my first language.
I take IV Ketamine treatments every two-three weeks. They work for my depression but are very expensive and not covered by my insurance. Recently, my doctor tried me on a MAOI and initally it felt like it worked and then when we started reaching recommended dosages I started to cross over and experience Bipolar 2 mania type symptoms. I guess I’m just going to keep doing the Ketamine for my depressive symptoms because little else seems to work and I can’t stand the symptoms of be mania. Thank you for this article, I will ask my doctor about the meds mentioned here.
I didnt know doctors were using IV Ketamine treatments.. My friend was told of this and he lives in a major metropolitan area and nobody does it.. are their any links you know of to doctors that use this.. I thought it was used only for pain management
I wanted to know whether these drugs actually r alternatives ie to be taken along with or alone also I wanted to know the latest bipolar meds
There are alternatives to psychotropics for those who seek them out …
can you expand. what are the alternatives?
Actually imo there are many, but they are all illegal pain killers. Hydrocodone (given after an out patient surgery) just made me feel totally normal. No ups no downs no extras. Same with Demerol. I didn’t feel high or drugged out, just clear minded and an even feeling of well being. I felt good on Codeine 3’s or 4’s also and that may be the same as Hydrocodone, idk. Since these drugs are illegal in taking for bipolar symptoms I’m forever phked.
I hope that one day these type of pain killers will be studied, and released in some form for those that suffer bipolar. Like my experience they may help lift depression and even them out. They really worked for me.
There must be something in them that helps? But of course we can’t have them! We’re crazy! Thanks America!
I guess what I’m saying is lithium isn’t an organic chemical, so it doesn’t interfere with the body’s normal functions. But NAC is organic, so it might interfere with the body’s functions. Like, it might affect other organs and not just the brain. I know that other chemicals can poison you at high amounts, any drug can, really. But NAC…it might interfere with the body in subtle ways. And really the testing is still in experimental stages. The other supplement I was thinking of that’s organic is SAMe. It’s similar because it makes up for a natural chemical in the body. But you always wonder if we know what the “right” amount to take is. Because it seems we have not tested it well yet to determine what the effects are. It doesn’t seem to be a targeted drug. This is just what I’ve concluded based on what I know about org chem, what I read, etc.
Everything we ingest, in excess or lacking, can wreak havoc on your body. I don’t know much about NAC but it seems the consensus is mostly positive and doesn’t seem to cause any adverse effects when taken at the correct dosage. Sounds like you’re comparing this to how lithium dosage is adjusted. In this case, the chances of reaching toxic levels is great, hence the need for monitoring. But if you suffered from devastating manic/depressive episodes, I think taking the risk is well worth it. At least, it is worth considering.
I’m glad someone is trying to find better drugs. The one thing I have to note is that Acetylcysteine, being composed of chemicals used in common bodily reactions, can in fact do long-term damage to the body. Just as it helps some functions it can harm others. Apparently that’s only for high doses but I still wouldn’t trust it. I’m actually studying this stuff and anyone with basic knowledge of org chem knows that these are common compounds used in the body’s chemical reactions that you don’t wanna mess with. So I wouldn’t really go out and buy it. Even after talking to a doctor. A similar chemical is being touted as an Alzheimer-preventing substance, but it can also cause long-term damage, for the same reason.
can you expand. what are the alternatives?
is 1200 mg daily ok?