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What’s New in Bipolar Depression?

What’s New in Bipolar Depression?



There’s a slight imbalance in our therapeutics for bipolar disorder. While patients spend most of their time in the depressed phase, the FDA-approved treatments for mania outnumber those for depression 4 to 1. Three years ago Jim Phelps looked at ways to fill that gap in this column, and it’s a good time for an update.

First, my biases. Outside the FDA-approved options, I’ll consider any treatment with at least one randomized, controlled trial supporting its merits. I tend to favor those with large effect sizes (eg, pramipexole) or low risks (eg, omega-3 fatty acids). I also value treatments with long-term data, even when their short-term benefits are debatable (eg, lamotrigine, psychotherapy). This is, after all, a chronic condition.

Mood-lifting stabilizers

The ideal treatment for bipolar depression would lift mood in the short term and prevent new episodes in the years to come. Examples of these mood-lifting stabilizers include lamotrigine, lithium, a few atypical antipsychotics (olanzapine-fluoxetine combination, quetiapine, lurasidone, cariprazine), and possibly valproate.1,2

Bipolar disorder may be chronic, but its episodes need not be.

How to choose among them? Collaborate. Adherence hovers around 50% in bipolar disorder, so it behooves us to ask patients about their hopes and fears in treatment. If fast results are desired, the atypical antipsychotics may be best. More often, patients value tolerability, in which case lamotrigine and lithium might come first. Practitioners often question lamotrigine’s efficacy and lithium’s tolerability, but new research suggests those reputations may be undeserved.3,4

Non-antidepressants for bipolar disorder

Next in line are medicines that can treat acute bipolar depression without destabilizing mood. These are best paired with a mood stabilizer as they won’t prevent new episodes on their own. I’ve left antidepressants off this list because their mood-destabilizing potential has not escaped the eye of controlled studies.5 To be fair, all the options on this list probably have some mood-destabilizing potential, as this problem is notoriously difficult to detect in research (and in practice). The non-antidepressants that made the cut are pramipexole, modafinil, armodafinil, thyroid augmentation, omega-3 fatty acids (with more than 60% eicosapentaenoic acid), N-acetylcysteine, L-methylfolate, pioglitazone, and celecoxib.1,6-8

Pramipexole is worth note as it has a large effect size (0.77 - 1.1) and lacks detrimental effects on weight, sexuality, and cognition.8 Modafinil and armodafinil also share that side-effect profile, though the research on these agents is not as clearly positive as it is for pramipexole.1 In my experience, these novel stimulants rarely break through severe depression but often improve residual symptoms such as cognition and fatigue. For patients, however, that can make the difference between staying in bed and returning to work.

Thyroid augmentation is particularly useful in lithium-treated patients, in whom keeping the thyroid-stimulating hormone level close to 2.6 mIU/L lowers the risk of depressive relapse.9


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