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Hi! Jim Phelps here with a preface to this volume. These are my last 5 Quick Takes, and a team of specialists will be taking over henceforth. For this last set, unlike the past, I have selected the articles. So, whereas healthy skepticism is always a good thing, perhaps a bit more of it is warranted for these articles, as I’m using them to present my personal point of view before I leave. Thanks for listening. And now, for the first Quick Take of the volume.
In 2022, the Royal Australian and New Zealand College of Psychiatrists published the most recent clinical guidelines for the treatment of mood disorders. The introduction to these guidelines describes a mood spectrum, depressions ranging from purely unipolar to fully bipolar with people all the way along in between. In other words, in these guidelines, the authors have switched from the categorical diagnostic system of the DSM to a dimensional approach. If you have any doubt about this, see their Figure 3 entitled, “The Mood Spectrum”, in the article linked here at the Psychopharmacology Institute. This shift from categorical to dimensional represents the evolution of a concept I first encountered back in the 1990s, a concept made formal in 2002 in an invited review for the Canadian Journal of Psychiatry. Nassir Ghaemi and Fred Goodwin, both highly respected authors, presented research literature supporting a spectrum approach to mood disorders.
I contrast these 2 papers from 2002 and 2022 to highlight 2 things. First, change can be slow. This reconceptualization of mood disorders from categorical yes/no bipolar or unipolar to a dimensional view has taken nearly my entire practicing lifetime. Second, although the new guidelines ought to end any further debate about how to diagnose bipolar disorders, they won’t, because many psychiatric specialists rightly worry that including more patients under a bipolar umbrella could do harm. So, let’s look closely at that.
At the bipolar end of the mood spectrum, nearly everyone agrees—don’t use antidepressants as monotherapy. At the unipolar end, for want of a better term, although this includes numerous kinds of depression, antidepressants are routine. And what about the middle? How much bipolar features should a patient have for you to switch strategies from antidepressants to a mood stabilizer with antidepressant effects, such as lamotrigine or low-dose lithium? How much bipolarity warrants this change in treatment approach? Well, that hasn’t been studied because until now, there was no middle of the mood spectrum officially, only the 2 ends of bipolar and unipolar. So, without research guidance, after you’ve discussed nonpharmacologic options, your clinical decision boils down to, in my view, antidepressants vs lamotrigine or maybe low-dose lithium, especially if suicidality is a concern. This decision will be based on your estimate of the treatment’s benefits and risks but also crucially on your estimate of the consequences of being wrong.
Suppose you prescribe lamotrigine in what’s actually a unipolar depression. There’s the 1 in 2000 rash risk and likely no efficacy beyond placebo, although a placebo is a very substantial drug, right? Antidepressants are not a whole lot better on average. Compare prescribing an SRI in a patient with significant bipolarity. The probability of benefit is significant here, but there are the risks of SRIs that anyone faces—weight gains, sexual dysfunction, and a potential for severe withdrawal when discontinuing—plus, in this case, the risk of inducing rapid cycling, mixed states, and treatment resistance. I think these latter risks are substantial based on 20 years during which I had the luxury of 25- or sometimes 50-minute appointments. So, I got to hear lots of detail about patients’ experience on antidepressants. As a result, my risk–benefit analysis leads me to consider lamotrigine much farther down the mood spectrum than many of my colleagues. Notice we’re not talking about quetiapine or some of the other second-generation antipsychotics as a mood stabilizer. That would be concerning in terms of the risk–benefit ratio because I fear we’re grossly underestimating the impact of inducing metabolic syndrome. So, if the choice between an antidepressant and lamotrigine depends on, how much bipolar features does this patient have, how are you supposed to determine that?
Ghaemi and Goodwin’s paper from 20 years ago detailed the answer. In the middle of the mood spectrum, mania is by definition absent and hypomania will be subtle or even less evident. So, instead, you assess nonmanic markers that are statistically associated with bipolar disorder but not in the DSM—family history, age of onset of the first depression that is, course of illness, how cyclic, how recurrent it is, and response to treatment, particularly really energized adverse reactions to antidepressants. These form the Bipolarity Index, a thrice-validated measure in which nonmanic markers are given 80% of the diagnostic weight, whereas the DSM manic symptoms get only 20%. That’s how important these other 4 domains are—family history, age of onset, course of illness, and response to treatment. I think they’re so important that I’m going to say that again: Family history of bipolar disorder, which granted is always a little tricky.; age of onset, namely early 18–24; course of illness, namely highly recurrent, episodic; and response to treatment, adverse reactions to antidepressants in particular.
To help you gather these essential diagnostic data, a 1-and-a-half-page questionnaire gets you all of them as well as DSM symptoms. It’s called MoodCheck. You can download it from the references. Because you simply can’t answer the key question, “How bipolar is this patient?” without those. Ghaemi and Goodwin made that case 20 years ago, and the new guidelines make it, well, almost official now.
Abstract
“Cade’s Disease” and Beyond: Misdiagnosis, Antidepressant Use, and a Proposed Definition for Bipolar Spectrum Disorder
S Nassir Ghaemi, James Y Ko, Frederick K Goodwin
The diagnosis and treatment of bipolar disorder (BD) has been inconsistent and frequently misunderstood in recent years. To identify the causes of this problem and suggest possible solutions, we undertook a critical review of studies concerning the nosology of BD and the effects of antidepressant agents. Both the underdiagnosis of BD and its frequent misdiagnosis as unipolar major depressive disorder (MDD) appear to be problems in patients with BD. Underdiagnosis results from clinicians’ inadequate understanding of manic symptoms, from patients’ impaired insight into mania, and especially from failure to involve family members or third parties in the diagnostic process. Some, but by no means all, of the underdiagnosis problem may also result from lack of agreement about the breadth of the bipolar spectrum, beyond classic type I manic-depressive illness (what Ketter has termed “Cade’s Disease”). To alleviate confusion about the less classic varieties of bipolar illness, we propose a heuristic definition, “bipolar spectrum disorder.” This diagnosis would give greater weight to family history and antidepressant-induced manic symptoms and would apply to non-type I or II bipolar illness, in which depressive symptom, course, and treatment response characteristics are more typical of bipolar than unipolar illness. The role of antidepressants is also controversial. Our review of the evidence leads us to conclude that there should be less emphasis on using antidepressants to treat persons with this illness.
Download PDF and other files
Reference
Ghaemi, S. N., Ko, J. Y., & Goodwin, F. E. I. K. (2002). “Cade’s disease” and beyond: misdiagnosis, antidepressant use, and a proposed definition for bipolar spectrum disorder. The Canadian Journal of Psychiatry, 47(2), 125-134.
Related References
- Malhi, G. S., Bassett, D., Boyce, P., Bryant, R., Fitzgerald, P. B., Fritz, K., … & Singh, A. B. (2015). Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Australian & New Zealand Journal of Psychiatry, 49(12), 1087-1206.
- Aiken, C. B., Weisler, R. H., & Sachs, G. S. (2015). The Bipolarity Index: a clinician-rated measure of diagnostic confidence. Journal of Affective Disorders, 177, 59-64.
- 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
- Moodcheck references https://psycheducation.org/blog/moodcheck-bipolar-screening/
