Five New Bipolar Depression Treatments You Don’t Know About – Part 1

People with bipolar disorder 2 spend 35 times more time depressed than hypomanic. As a person with bipolar type 2, I can tell you how true this is. Bipolar type 2 is more like a depressive disorder than a bipolar one. However, this doesn’t mean bipolar disorder 2 can just be treated like unipolar depression. If only life were that simple.

Bipolar disorder type 2 depression treatments must not induce hypomania or mania, and antidepressants used alone often do that. For this reason bipolar 2 depression treatment is generally like happy hour (full of cocktails). And many of us are very frustrated with the fact no new medications are being developed for our mental illness.

So here’s some hope. Here are five bipolar depression treatment areas you probably don’t know about.

Note: I don’t have to tell you this, but these are research areas some of which some clinicians are using and some of which they are not. Don’t even think about trying this at home. Talk to a doctor.

FDA-Approved Bipolar Depression Medication

For those of you wondering, only quetiapine and a fluoxetine/olanzapine combination are FDA-approved for the treatment of bipolar depression. (That’s an antipsychotic and an antidepressant/antipsychotic combination. It’s odd that lamotrigine isn’t on the list because it’s one of the biggies for treating bipolar depression.)

Two psychiatric medications. Just two. Chocolate and vanilla. Heaven help you if you like rocky road.

Glutamate and Bipolar Depression

Everyone has heard of serotonin and dopamine – two neurotransmitters antidepressants commonly target. Glutamate is another neurotransmitter, this one of the amino acid variety. Glutamate is essential in things like learning and memory. [pull]Glutamate fact of the day – nicotine affects glutamate in the brain and may be one reason why so many people with a mental illness smoke.[/pull]

Genetic and other abnormalities in the glutamate receptor complex have been found in people with bipolar disorder. Two medications targeting the glutamate receptor complex appear to have antidepressants effects: riluzole and ketamine. Both of these drugs are FDA approved for other uses.

Riluzole appears to have very early and small-scale evidence of an antidepressant effect in bipolar depression while there has been significant interest and study of ketamine and depression.

Bipolar Depression Treatment Surprise

Ketamine is an anesthetic (and a street drug), but when used at lower doses, appears to alleviate bipolar depression extremely quickly – like 40 minutes kind of quickly (when used with lithium or valproic acid). However, the effects only last for three days, the administration is intravenous and there is that issue of it being an anesthetic and producing dissociative type side effects.

If I had to guess, I’d say glutamate will be big in upcoming treatments. I’m very interested to see where this one goes.

Anti-Inflammatory Medication and Bipolar Depression

This area is extremely experimental but basically abnormal function in the inflammatory network has been found in bipolar depression and bipolar mania. One of the things lithium does is modulate the inflammatory network.

One small study shows a non-steroidal anti-inflammatory (NSAID) with an antipsychotic or mood stabilizer, given to people with bipolar 1/2 depression, had statistically significant improvement over placebo after one week. However, this effect was not seen at six weeks.

An additional study found a similar antidepressant effect using aspirin and fluoxetine in depression treatment resistant rats (really).

What I get from this is anti-inflammatories seem to make antidepressants work faster, but are not in and of themselves antidepressants.

More Bipolar Depression Treatments to Come

Next I’ll review metabolic, antioxidant and dopamine modulation treatments.

Information Reference

The information in this article is primarily from: Novel Treatment Avenues for Bipolar Depression By Roger S. McIntyre, MD and Danielle S. Cha. Clinical Psychopharmacology. April 19, 2011.

See the article for all the nitty gritty details about the above.

Psychotropic Drug Brand Names

Fluoxetine – Prozac
Fluoxetine and olanzapine combined – Symbax
Lamotrigine – Lamictal
Olanzapine – Zyprexa
Quetiapine – Seroquel
Riluzole – Rilutek
Valproic Acid – Depakote or Epival


About Natasha Tracy

Natasha Tracy is an award-winning writer, speaker and consultant from the Pacific Northwest. She has been living with bipolar disorder for 18 years and has written more than 1000 articles on the subject.

Natasha’s New Book

Find more of Natasha’s work in her new book: Lost Marbles: Insights into My Life with Depression & Bipolar. Media inquiries can be emailed here.

  1. I’m on generic Ritalin twice daily and Vistaril. It seems that Ritalin treats my bipolar even better than Seroquel did. Maybe many people have a form of ADD/ADHD and is mistakenly or misdiagnosed as bipolar when there is s different condition.

  2. Can anyone comment on Riluzole in regards to Bipolar and Cognition! I am looking for resources to give to my Doc to introduce him to the new medication. I just wonder if a GP or a specialist will prescribe it for me.

  3. Is very useful,
    Somebody have information regarding TRILEPTAL Oxcarbacepine?

  4. All tehe information we share is very useful,
    Somebody knows something, or have information about Trileptal (Oxcarbamacepine), is an enhancement from the Tegretol, works similar than the Lamotrigine (Lamictal).

  5. Definitely a very good study done with a lot of research done. Thanks Natasha for helping a lot of us around who would love to try various ways to get rid of this depression that once set itself does not want to go away. Anti – Inflammatory medication to treat bipolar depression seems promising though I feel a lot of research is required in this area. I agree with you that bipolar 2 although seems simple is equally lethal a problem as are bipolar 1 and hypomania. Thanks for giving all of us a ray of hope. Well appreciated.

  6. hi i love ur website. i just held a seminar with the police dept to give mental health awareness. shoot me an email.

  7. Hi. Can anyone tell me what the effects of just taking an anti-inflamatory each day without mood stabilizers has on Bipolar.

    • Hi Michele,

      When I originally looked at the data it’s like I said, anti-inflammatories potentiate the effect (make work better, in this case faster) the effect of other medication but they are not in and of themselves useful.

      – Natasha Tracy

  8. “As in all things, it’s complicated.

    …“failed” and didn’t fail, depends on how you look at it.” — Natasha

    Them thar some mighty powerful words!

    Kind of reminds me about the write-ins to CMS for approval of VNS Therapy for Depression.

    Sure, the sponsor f-upped the protocol for the depression study because they designed it along the lines of a pharmaceutical study which it is not, so on and so forth. More amazingly had one taken the time to carefully read the comments of over 200 medical professionals and especially those commenting about patient histories of extremely severe cases that they encountered where no other therapy benefitted the patient that for the first time something was working.

    And so your comment is in my opinion so apropos, “…”failed” and didn’t fail, depends on how you look at it.” A number of those medical professionals concluded from their observations and results as did I that the results were truly remarkable despite the published data. I’ve learned from the medical professionals they all don’t reach the same conclusions.

    It is complicated. That is why psychiatry; researching and treating these disorders are so very difficult and complicated.


    • Hi Herb,

      “It is complicated. That is why psychiatry; researching and treating these disorders are so very difficult and complicated.”

      Yup. Simple would be a nice change.

      – Natasha Tracy

  9. Natasha,
    Great information. Thank you for doing so much research. As far as I know, lamotrigine failed the research test with regard to depression. They first tested it for seizures, which of course it passed, and then they tested it for depression. There were no significant findings so they could not get it approved for that. That’s the research story I’ve understood, but I could be wrong. Anyway, I’m on it and attest to its antidepressant qualities in me. I’m on just 37.5 mg to lift me just a bit from the low end due to the amount of lithium I must take.

    • Hi Meredith,

      As in all things, it’s complicated.

      Lamotrigine “failed” and didn’t fail, depends on how you look at it. From my main man Dr. Phelps:

      “After one article which found lamotrigine was not really any better than a placebo… the same author participated in another meta-analysis… which found that sure enough, lamotrigine was quite strongly effective in people with severe depression. It was not so impressive in people with mild-moderate depression.”

      That’s from here: but all the nitty gritty details are here: in case you were wondering :)

      As to why it doesn’t have FDA approval for depression? Couldn’t say. Probably not the right trials and too much money to set up another one now that it’s gone generic. I’m glad it’s working for you. I’ve always been a fan.

      It’s true, I’m a research-slut. I love it and I loathe it. I love having data to back things up so it doesn’t appear that I’m just making things up but it’s laborious. I hope it helps people though. Real facts are the way we move forward with more clarity and hopefully get better.

      – Natasha Tracy