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Here, allow me to blow up your current understanding of generalized anxiety disorder and PTSD and borderline personality disorder and maybe ADHD too. By the end of this Quick Take, I hope to help you rebuild it somewhat.
Jim Phelps here for the Psychopharmacology Institute. As you know, in the DSM-5, mixed states became a specifier that can be added to a diagnosis of unipolar depression effectively creating a spectrum approach to the diagnosis of mixed mood disorders. What the DSM manic symptoms allowed for mixed depression were confusing. Here are 2 papers that simplify things.
First, the CANMAT and ISBD recommendations paper, which is linked here at the Psychopharmacology Institute, presents a spectrum approach to mixed states, specifically in Figure 4. Rather than thinking about bipolar disorder like the North and the South Pole, think of plotting symptoms on a graph—number of manic symptoms on one axis, number of depressive symptoms on the other axis, so that full manic and full depressive symptoms would be in the upper right hand corner of the graph. That was the DSM-IV version of mixed states. But in the CANMAT, the entire territory of the graph is mixed. Any admixture of depressive and manic symptoms is possible. They’re inviting you to forget the DSM rules about what manic symptoms count and which don’t and instead focus on the most common manic symptoms found in mixed states.
Combining his findings with earlier research on mixed states, Roger McIntyre calls these the 4 A’s, the most clinically important manic symptoms in patients with mixed depression. Ready? They are agitation, anger, anxiety’ and attention problems’ such as can’t concentrate, thoughts going all over the place. Seen any patients lately who had depression plus a couple of those 4 A’s—agitation, anger, anxiety, and attention problems? Well, of course, you have because these are common symptoms of generalized anxiety disorder and PTSD and borderlinity. The attention thing invokes ADHD. So, does the patient have major depression plus ADHD or a unipolar mixed state? Is it major depression plus generalized anxiety disorder or a unipolar mixed state? And so on. How are you supposed to tell these apart? I submit to you that it’s basically impossible. The overlap in symptoms is just too extensive. It’s as though you’ve been lied to all this time by being told that these are separate conditions that can be identified by DSM rules. That’s just false. True, some people have so much borderlinity, it’s almost unmissable. Desperate attempts to avoid abandonment and chronic emptiness, you can just feel it. But the rest of the borderline criteria overlap almost 100% with depression plus the big 4. So, there’s the mess I promised you.
Now, to clean up. What if you just accept that you can’t differentiate these things and focus instead on your treatment options with an eye toward “first do no harm”? The patient presents with depression and all 4 A’s. What are you going to do? If it’s psychotherapy, exercise, fish oil, helping them develop a regular sleep pattern closer to the sun’s rhythm, fine; go for it. The crux is antidepressants. That’s when you need to know, “Would this be a mixed state?” because antidepressants can induce mixed states, make them worse, and make them treatment resistant. So, how can you tell if it’s a mixed state? Not from the symptoms, right? No. Instead you need the other 4 dimensions of the Bipolarity Index that I discussed in the last Quick Take 52.1. Remember, those are family history, age of onset, course of illness, and response to treatment, mainly an energized negative reaction to an antidepressant. Use the MoodCheck Questionnaire, which can be found in the related references, to gather that information quickly and easily document that you did.
Finally, here’s an even more common conundrum. The patient presents with depression and 3 or 4 of the 4 A’s—agitation, anger, anxiety, or attention problems—and they’re already on an antidepressant. Now, you have to wonder, could the antidepressant be inducing a mixed state? Is it possible that instead of adding anything, the best solution might be to gradually taper the antidepressant? In the latter part of my career, I was being referred patients with terrible mood and anxiety problems who had tried everything, but I almost always had at least 1 treatment offer that they’d never had: Keep what you’ve got and gradually taper the antidepressant. If it doesn’t work, at least you’ll be on 1 less medication, I’d say. A resident and I published a case series of 12 such patients whose anxiety diminished substantially with this approach. It was so commonly effective it became one of my main treatment options, as nearly everyone arrived on an antidepressant. But unfortunately, that’s all the data I’ve got to support this strategy.
In summary, mixed states are dimensional. Any admixture is possible and the 4 A’s are clinically the most important —agitation, anger, anxiety, and attention problems. Diagnostically, it’s disastrous, but treatment options are not as complicated. You just got to wonder, could this be a mixed state?
Abstract
Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) Recommendations for the Management of Patients With Bipolar Disorder With Mixed Presentations
Lakshmi N Yatham, Trisha Chakrabarty, David J Bond, Ayal Schaffer, Serge Beaulieu, Sagar V Parikh, Roger S McIntyre, Roumen V Milev, Martin Alda, Gustavo Vazquez, Arun V Ravindran, Benicio N Frey, Verinder Sharma, Benjamin I Goldstein, Soham Rej, Claire O’Donovan, Valerie Tourjman, Jan-Marie Kozicky, Marcia Kauer-Sant’Anna, Gin Malhi, Trisha Suppes, Eduard Vieta, Flavio Kapczinski , Shigenobu Kanba , Raymond W Lam , Sidney H Kennedy , Joseph Calabrese , Michael Berk , Robert Post.
Objectives: The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided-a critical gap which the current update aims to address.
Method: Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion.
Results: No agents met threshold for first-line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second-line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second-line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first-line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second-line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first-line, and lithium and olanzapine identified as second-line options.
Conclusion: The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.
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Reference
Yatham, L. N., Chakrabarty, T., Bond, D. J., Schaffer, A., Beaulieu, S., Parikh, S. V., McIntyre, R. S., Milev, R. V., Alda, M., Vazquez, G., Ravindran, A. V., Frey, B. N., Sharma, V., Goldstein, B. I., Rej, S., O’Donovan, C., Tourjman, V., Kozicky, J. M., Kauer-Sant’Anna, M., Malhi, G., … Post, R.(2021). Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations. Bipolar Disorders, 23(8), 767-788.
Related References
- MoodCheck questionnaire as pdf https://www.ohsu.edu/sites/default/files/2019-06/Moodcheck-Bipolar-Screener-Adult_0.pdf
- MoodCheck questionnaire as edit-able Word document https://psycheducation.org/wp-content/uploads/2021/12/MoodCheck.2021.doc
- Suppes, T., Eberhard, J., Lemming, O., Young, A. H., & McIntyre, R. S. (2017). Anxiety, irritability, and agitation as indicators of bipolar mania with depressive symptoms: a post hoc analysis of two clinical trials. International Journal of Bipolar Disorders, 5(1), 1-11.
- Phelps, J., & Manipod, V. (2012). Treating anxiety by discontinuing antidepressants: a case series. Medical Hypotheses, 79(3), 338-341.
