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Will the Best Atypical Stand Up?

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Daily dispatches from the International Bipolar Disorders Conference. There are four atypical antipsychotics that treat bipolar depression, but which have the best balance of efficacy and tolerability?

Published On: 6/29/2020

Duration: 5 minutes, 15 seconds


Will the Best Atypical Stand Up?

This week we’re podcasting from the International Society for Bipolar Disorders 2020 conference, and there’s so much here that we’re trying out a new format. We’ll bring you a new episode each day. If you like the daily format, leave us a review in your podcast store and we’ll keep up the pace if we get enough shouts.

Today, an unpublished paper from Leslie Citrome and colleagues on how the atypical antipsychotics measure up in bipolar depression.

Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report. And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.

We have four atypicals that work in bipolar depression: cariprazine, lurasidone, olanzapine-fluoxetine combination (or OFC), and quetiapine. Among them, only OFC is supposed to be used with an antidepressant ─ that’s the only way they got olanzapine to work in the clinical trials ─ the other 3 work on their own.

Now if you’re thinking that the other atypicals probably work because these four do, you’re betting on hope. Two of them ─ aripiprazole and ziprasidone ─ were tested in bipolar depression and failed. The others are untested. If we have to rest our hope on one, maybe it’s asenapine (Saphris). Asenapine has never been studied for acute bipolar depression but it does have good evidence to prevent depressive episodes in bipolar disorder, while the other atypicals ─ outside of the FDA-approved four ─ do not.

So that’s what works, but how well do they work? Leslie Citrome and colleagues looked into that question with the Likelihood to be Helped or Harmed ratio – which tells us which med has the best ratio of efficacy and tolerability. It’s based on the more familiar Numbers Needed to Treat or Harm. Here’s what they found:

Lurasidone (Latuda) rose to the top in nearly every category.

The “categories” were based on the side effect. When we’re talking about efficacy, we’re talking about one thing: treating depression. But side effects are many, so they measured the Likelihood to be Helped or Harmed in several categories of side effects:

Weight gain, EPS, fatigue, akathisia, nausea, and drop out due to any adverse effect.

I should note the study was sponsored by Sunovion, the maker of lurasidone. But I have reviewed the data in other less biased sources and agree with the general consensus there. Lurasidone is one of the better tolerated antipsychotics, and with a number needed to treat of 5 it stands comfortably alongside OFC and quetiapene ─ those two are high on efficacy but lower on tolerability.

OFC – olanzapine fluoxetine combination ─ was actually a close second to lurasidone in most category except weight gain. Quetiapine, on the other hand, sank to the bottom in most categories. Although Quetiapine ranks high for both short- and long-term efficacy in bipolar disorder mania and depression, it’s also the atypical that patients are most quit in the short term, and its side effects like fatigue and hypotension are the reason.

What about cariprazine/Vraylar? It’s basically the less effective cousin of lurasidone. The two have never gone head-to-head, but cariprazine’s number needed to treat indicates it’s about ½ as effective as lurasidone. It does have two advantages, however ─ it works in mania, and it’s among the most tolerable of the atypical antipsychotics.

Lurasidone does not have any studies in mania, but it did work for mixed states and a new poster presentation ─ sponsored by the industry ─ brought some reassurance to those of us who worry that it may make mania worse like so many antidepressants do. They re-analyzed lurasidone’s main clinical trials ─ again none of these were done in mania but they looked at manic symptoms and found they did tend to improve, and not get worse, with treatment.

Join us tomorrow for a peak at the first clinical trial of A Diet for Bipolar Disorder. We’ll have more updates in our print issue, including unpublished results on a new medication for bipolar depression and a full review of the modafinils in bipolar disorder.

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