Bipolar Depression Pharmacological Treatments and Challenges With Dr Tohen

Mauricio Tohen, MD, DrPH, University of New Mexico School of Medicine, Albuquerque, New Mexico, gives the main takeaways from his recent American Psychiatric Association 2022 Annual Meeting session titled, "Bipolar Depression: Outcome and Pharmacological Treatment." He explores the primary challenges for clinicians working with patients with bipolar depression, diagnosis, pharmacological and neuromodulation treatments, and more.

Watch the conclusion of this 2 part video series here: The Best Treatment for Bipolar Depression and Symptomatic Interventions With Dr Tohen

Mauricio Tohen, MD, DrPH, MBA is university distinguished professor and chairman of the Department of Psychiatry & Behavioural Sciences at the University of New Mexico HSC in Albuquerque New Mexico. In 2014 Dr Tohen was recognized in Thomson Reuter’s “The World’s Most Influential Scientific Minds, 2014”. He is one of 100 scientists worldwide recognized in the psychiatry/psychology category. Dr Tohen has published over 350 publications and has over 20,000 scientific citations. In 2016 the International Society for Bipolar disorders awarded him the Mogens Schou Award for Education and Teaching. In 2017 and again in 2021, Dr Tohen was Recognized by Expertscape as having the top % 0.12 expertise in bipolar disorder worldwide based on citations of published articles between 2007-2017 and 2010-2021

Read the Transcript:

Meagan Thistle, Associate Digital Editor, Psych Congress Network: Hi, Psych Congress Network family. Thank you so much again for joining us. We are here today with Dr Tohen. If you'd like to introduce yourself.

Dr Mauricio Tohen: Thank you, Meagan. I am Mauricio Tohen. I'm a distinguished Professor and Chairman of the Department of Psychiatry at the University of New Mexico, in Albuquerque New Mexico. And it is my pleasure to be here today. Thanks for inviting me.

Thistle: Of course. Thank you so much for taking the time to chat with us today. So let's jump right in. You're going to be at APA 2022. Very exciting. We would love to talk with you about that session. So what are the main takeaways from your session titled “Bipolar Depression, Outcome and Pharmacological Treatment?”

Dr Tohen: Yes. The prevalence of bipolar depression is higher than we expect. In fact, within bipolar disorder, patients spend more time being depressed than being manic. And in addition to that, if you look at relapses, there's more relapses into depression than into mania. And furthermore, when people are having depressive symptoms, even mild depressive symptoms, the inability to function is higher, even compared to when patients have mild manic symptoms.

So, it is again, a condition that is prevalent, and within bipolar disorder as I've mentioned, depression more frequent than mania. And in addition to that, when there's mild symptoms of depression, the functional outcomes are worse compared to when there's mild symptoms of mania. So it is something that our patients struggle a lot with, so we need to learn more about it and find new ways to serve our patients.

Thistle: So, in addition to some of those challenges, you just mentioned, what other primary challenges for clinicians working with patients and bipolar depression can share?

Dr Tohen: Well, we will start with diagnosis. And the main differential diagnosis is bipolar depression and unipolar depression. And let's say we just take the DSM-5. According to the DSM-5, if you have a patient with depression, the only way to make the differential diagnosis is, if in the past the patient either had a manic episode that's bipolar I, or if they had a hypermanic episodes, bipolar II. The latter is actually especially difficult to diagnose, because patients with bipolar disorder, especially when they're hypermanic, they're not aware that they're hypermanic. So, this is frequently missed, the bipolar II face of depression.

That's why it is key to get collateral information. I treat bipolar patients. I've been treating bipolar patients for the last 20, 30 years. And one of the key things that I always emphasize is that it's very important for me to be able to have collateral information from a significant other in order to go back to the history. I ask, "Has your loved one experienced at any time manic episodes and more difficult to remember is hypomanic episodes?" Because sometimes as I mentioned, patients themselves are not aware or they don't recognize that they had symptoms of hypermania.

Thistle: So, in your session you go into this a bit, if you wouldn't mind sharing more with us, what does the polarity of patients' first reported mood episode suggest?

Dr Tohen: Yes. Thank you for that question, Meagan. That's a very interesting finding is that the type of the first episode mania, or depression, actually predicts the outcome of the condition across the years.

How? Well, if the first episode was depression, the likelihood of having predominantly depressive episodes is higher compared to someone whose first episode is mania and vice versa? And how do we define predominance? And by consensus, we call it predominantly depressed. If more than two-thirds of the episodes have been of 1 type or the other.

So there's 2 things, the type of the first episode, and also the predominance. And that's why taking a clinical history is so important. When you get to history and the predominance of the episode has been of one type or the other, the likelihood is that the next episode is going to be whatever polar predominated in the past. And this is key, not only in terms of the prediction, of course, but more importantly treatment.
Because we have treatments that are better in preventing manias and treatments that are better in preventing depression. And when you have a patient in remission, you just don't know what the likelihood is of having one relapse or the other, unless you have a good clinical history.

Thistle:
So, on the line of treatment: how have new pharmacological and neuromodulation treatments improved those outcomes above of bipolar depression?

Dr Tohen: Let's start with pharmacology. In the past, not so distant past, we used to treat patients with bipolar depression with antidepressants. And initially there was a concern, "Well, we're going to switch the patient to mania." This can happen, but the most important thing is that bipolar depression patients with bipolar depression do not respond to the use of antidepressants monotherapy.

So, that is a key thing in terms of treatments, that antidepressants are not effective in the treatment of bipolar depression and also can cause harm such as, switching to mania.

So, do we have new treatments available for bipolar depression? The good news is that we do. The not-so-good news is that they're not always effective and they're not free of side effects. Studies have shown that the atypical antipsychotics are effective in the treatment of bipolar depression, both in monotherapy or in combination with mood stabilizers.

So that's in terms of pharmacology.

Now not all the atypical antipsychotics are the same in terms of efficacy.

Some show better efficacy and tolerance than others. And I can go into details, Meagan, if you want me to, in terms of the specific treatments. Now, you also mentioned neuromodulation. That is, of course, very promising. Well, within neuromodulation, we have electroconvulsive treatment. That's been around for a long time actually before pharmacology. And in fact, ECT is effective in the treatment of bipolar depression, for that matter is also effective in the treatment of mania. So that's that in terms of neuromodulation on what started.

And now we have TMS and other technologies. And it's still, in terms of bipolar depression, still it's been investigated. There are promising results. And there are other new treatments like the use of ketamine, the use of psychedelics. And that's still not clear to what extent they have efficacy, and for that matter safety.

So very promising in the area that we now know as Intervention Psychiatry.

Thistle: So we actually do have some time, if you did want to go into some of those treatments that you mentioned, anything else you'd like to share?

Dr Tohen: Yes. Let's get back to the antipsychotics, the typical antipsychotic. The first treatment that the Food and Drug Administration, the FDA, approved for bipolar depression was a combination of Olanzapine and Fluoxetine. Actually, I was involved in those studies. The efficacy was good, but the tolerability was not very good. As we know, Olanzapine causes increased appetite, metabolic syndrome and so on, but the efficacy was there. Then there were other atypical antipsychotics that also show good efficacy that included Quetiapine. Actually, the efficacy of Quetiapine was quite strong, but unfortunately, same side effects as Olanzapine. There were other atypical antipsychotics that in monotherapy did not show efficacy, that includes Ziprasidone and Aripiprazole. Those 2 atypical antipsychotics did not show efficacy in monotherapy. Risperidone, it has not been approved by the FDA for the treatment of bipolar depression.

There are a number of new atypical antipsychotics that have good efficacy and tolerability. The first one was Lurasidone. Good efficacy and tolerability in terms of metabolic syndrome and weight gain. The second one, Cariprazine, again similar. No weight gain, or very small. The major challenge of both of those treatments is there's the presence of akathisia in the 2, 3% of the patients. And there is a new medication also that has been approved by the FDA. That is Lumateperone. That has shown efficacy, and the tolerability also seems to be quite favorable. So all this is good news for our patients.

Now treating bipolar depression is of course the first step, because the second, and you could argue even perhaps more important step, are you going to keep the patient in remission? So that's still what we... And for how long? That's another question that we still do not have a clear answer. So quite promising, I would say, and from the point of view of pharmacological treatments pick.

Thistle: Great, always like to hear that things are heading in that direction for patients.