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.
From categorical to dimensional approaches
The authors have switched from the categorical diagnostic system of the DSM to a dimensional approach.
If you have any doubt about this, see Figure 3 entitled, “The Mood Spectrum” from the guidelines.
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.
- Change can be slow.
The reconceptualization of mood disorders from categorical to a dimensional view has taken nearly my entire practicing lifetime. - Diagnostic debate will continue.
The new guidelines ought to end any further debate about how to diagnose bipolar disorders, but they won’t because many psychiatric specialists rightly worry that including more patients under a bipolar umbrella could do harm.
Treatment considerations across the mood spectrum
At the bipolar end of the mood spectrum, nearly everyone agrees—clinicians shouldn’t use antidepressants as monotherapy.
At the unipolar end, antidepressants are routine.
And what about the middle? How many bipolar features should a patient have to switch strategies from antidepressants to mood stabilizers 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, the 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 doctor’s estimate of the treatment’s benefits and risks, but also crucially on their estimate of the consequences of being wrong.
Suppose you are being prescribed lamotrigine in what’s actually a unipolar depression.
There’s a 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’ experiences with 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.
If the choice between an antidepressant and lamotrigine depends on how many bipolar features this patient has, how are clinicians supposed to determine that?
Ghaemi and Goodwin’s paper from 20 years ago detailed the answer.
The Bipolarity Index: using markers for the “middle of the spectrum”
In the middle of the mood spectrum, mania is by definition absent and hypomania will be subtle or even less evident.
Instead, clinicians assess nonmanic markers that are statistically associated with bipolar disorder but not in the DSM:
- family history early 18–24;
- age of onset of the first depression
- the course of illness (how cyclic/ 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%.
The MoodCheck as a diagnostic tool
To help clinicians 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.
Clinicians 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 almost official now.
Publisher’s note. This article was initially published as the Quick Take ” “Cade’s Disease” and Beyond: Misdiagnosis, Antidepressant Use, and a Proposed Definition for Bipolar Spectrum Disorder” at the Psychopharmacology Institute for a medical audience. It has been edited for clarity.