(updated 12/2014)



A reader just wrote and explained that she was thinking about trying to talk her provider into lurasidone because she was afraid of the rash with lamotrigine. Oh my gosh. Time for a page on lurasidone. I generally do not use new medications for as long as I can stand it. I have yet to write a prescription for lurasidone, as of December 2014. In my opinion, when a new medication comes out, the best thing to do is let everyone else use it for a while until we find out what the problems really are.

However, I’m almost there. A paper was just presented showing no significant weight gain in a year on lurasidone.  In fact, there was some slight loss, but that’s probably because people had been switched to it from similar medications that had already caused a lot of weight gain. Patients on risperidone for a year gained 5 pounds, while those on lurasidone lost 2 pounds.  After the study was over patients had an option to switch to lurasidone.  Those who did lost 5 pounds in the next 6 months. (presented at a European conference, reported in Psychiatric News Dec 2014).

Those data were from a study that was surely sponsored by the manufacturer, so still suspicious, but those numbers are enough for me to start trying this — if everything else that’s affordable hasn’t worked. Lurasidone is going to be far too expensive for anyone facing a 50% copay, as many will, for quite a while yet.

The Good Side

Like quetiapine, lurasidone has quite solid evidence for benefit in the treatment of bipolar depression. As they do with quetiapine, some mood experts would advocate for consideration of lurasidone before something like lamotrigine, because of the data showing lurasidone actually working are quite good compared to lamotrigine. Here.is one of the study results, where you can see lurasidone outperforming placebo by a substantial margin (down is good;
the graph shows amount of change in a standard measure of depression from the beginning of the study ):



These results earned lurasidone an FDA indication for bipolar depression. That is why they can spend so much money on marketing it now.

The Bad Side

The results above show that this medication works much better than a placebo. Fine. That can be done with a six-week study, as shown. But how long does it take to show that a medicine is safe?

For a medication is released for use by the general public, by the FDA, the manufacturer has to show that it does not do anything particularly dangerous in short-term use. they do not have to show safety in long-term use. That comes
with experience — the experience of the first patients to use it.

Think about it. How long did it take for us prescribers to figure out that olanzapine/Zyprexa can very frequently cause dramatic weight gain? That was probably a year or two, although many of us began to suspect it within less than a year. And weight gain with olanzapine is a very dramatic, very common side effect. So a risk that takes months to show up will take several years to being recognized. If the risk is is uncommon, determining that it is really coming from the new medicine will take much longer to figure out.

So, how often is it that we find out that a new medicine causes some bad problem after months or years of use? Take citalopram/Celexa, an antidepressant which up until recently was probably the most widely used of all of the “SRI’s” (serotonin reuptake inhibitors). it seemed to have slightly fewer side effects than the older ones like fluoxetine/Prozac and sertraline/Zoloft. After about 10 years of use, the FDA put out a warning saying that at doses over 40 mg, it can cause an abnormality in cardiac rhythm that can be dangerous. There are many such examples.

Therefore one should not use a brand-new medicine for as long as one can avoid it, leaving time for others to be the pioneers, the ones who find out the bad news down the road, if there is going to be any. Of course, there might not be any such bad news, in which case I will have made my patients wait too long. They could have benefited earlier. So for any new medication, we just have to balance the possibility of significant risks emerging with more experience with the medicine, versus the potential for benefits — and then compare the same risk/benefit balance for the other treatment options we might consider at that point.

Comparing lurasidone and other options at this time

At minimum, at this time (December 2013), I think that lamotrigine beats lurasidone by a country mile in terms of risk/benefit ratio. The risk side for lurasidone is such an unknown yet, and based on our experience with other medicines, it is wise to presume that we will find issues over time. At minimum we already know it can raise prolactin levels, a problem with risperidone and other older antipsychotics. And lurasidone is very likely to cause tardive dyskinesia, although it will take a while to figure out how often. Lamotrigine has neither of these problems.

Does lurasidone increase blood glucose, and thereby cause diabetes in some people, as most of its antipsychotic cousins do? So far we only have data from short-term studies. (The longer studies only look at people who did not get pulled off the medicine for any reason, so can not be used to put a number on long-term risk). In these short studies, the risk of having blood glucose going from normal up to the point where a doctor would be warning patients about the strong possibility of diabetes (blood glucose greater than 126; from the FDA-based prescribing information) was:

placebo: 8.6%

lurasidone: 10-14%

( depending on dose; no upward trend with dose)


Finally, one of the only reasons that lurasidone beats quetiapine for bipolar depression (which also has very good evidence for benefit there) is that lurasidone is supposed to cause less weight gain. But that was what they said about aripiprazole/Abilify when it first came out, and we have since seen that it too causes weight gain. Just not as much as quetiapine. How much weight gain lurasidone actually causes will take a while to figure out. (We are not going to trust the manufacturer to tell us…)