Hope for Treatment-Resistant Bipolar Depression

Hope for Treatment-Resistant Bipolar Depression

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

Bipolar Depression Treatment-Resistant TreatmentsThis 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.


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.

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