This is the second edition in my “farewell to oral meds” articles, welcome to “Lurasidone.” (Trade Name: Latuda)
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All of the standard caveats about atypical antipsychotics aside, Lursaidone has some differences with other agents…
From a safety and efficacy standpoint, Lurisdone has FDA approval for treating bipolar depression and schizophrenia. It’s a Sunovion product, and it was initially approved in 2010.
They never got around to a mania indication. I think this is because the amount of money necessary would've added no additional value.4 Sunovion knew it had a “hit” with the bipolar depression indication, which is uncommon5, and thus getting the research done on its utility in mania6 is not in their economic interest.7
Pearl: It Doesn’t Cause Weight Gain (maybe)
This drug does not lead to weight gain in their clinical trials in adults8. Real-world follow-up demonstrated modest weight gain in adult patients (0.77kg over a year9), less than in patients treated with other worse options. It was similarly tolerable in adolescents when it comes to weight gain.
Aside: this is true enough but largely ignores the fact that most people with bipolar disorder will be gaining weight10 because most people gain weight when they have a serious psychiatric illness and are surrounded by an ocean of terrible food that is poisonous.
What Time of Day Should One Take Lurasidone?
The annoying thing about lurasidone, as a theoretically weight-neutral drug, is that it is mildly sedating…and you have to eat with it. It needs to be taken with 350 kcal of food. This can also be soda—anything with 350 cal counts.
The bioavailability of the drug is how much gets into your system. With Lurasidone, below 350 kcal of food? No. Not absorbed enough.
Sunovion11 did the assessments at 100 cal, 150, 200, 250, etc., and it wasn’t bioavailable enough. Humans only absorb 20% of the drug into their blood if they take it on an empty stomach or with less than 350 kcal. It is sedating— in keeping with a before-bed medication— but needs food like a “with meals” drug. Either you take it with dinner or with food before bed, which is not ideal.
Pearl: So you must eat, or you (effectively) are not taking the drug you think you are.
What dose to use? Another contentious question. My initial read of the studies was that: “In bipolar depression, 20 mg is the only dose you need.”
They didn’t power the studies to see a difference between the doses. Subsequent analysis of the two approval trials demonstrated a dose-response curve to increasing effect with titration12:
Net drug effect after 6 weeks of treatment was estimated to be a 6.0-point decrease in MADRS score per 100 mg of lurasidone.
Now here is the annoying part…lurasidone comes in 20mg, 40mg, and up to 160mg. So the improved dose-response for more drugs is on the order of 0.06 MADRAS13 points per mg…and there is an increasingly adverse effect profile when it comes to movement side effects at higher doses, though it can be seen at lower doses too.14
Movement Disorder Adverse Effects are relatively common; this means “your jaw or foot shaking uncontrollably.” From a patient perspective, if this is a side effect you get, it may mean this is not the right drug for you. As usual, if you are the person who needs treatment—talk to your doctor about side effects! We can’t think through what to do without you!
Pearl: It’s Safe Enough, and Should Probably Be Used Earlier in The Treatment Algorithms?
Large-scale long-term follow-up has been done. The major side effects that make a treatment like Olanzapine a bad long-term choice (e.g. massive weight gain and dyslipidemia) are not the case.15 Over two years, in bipolar disorder, the discontinuation rates were: 19.7% of discontinued, including 6.6% due to adverse events and 1.6% due to insufficient efficacy. The discontinuation rates and lack of efficacy are, on average higher in schizophrenia.
Pearl: It’s Class B in Pregnancy— that is, doctorglish for “Safe Enough*.”
Doctors don’t love to say “safe.” It is very definitive. Safe Enough doesn't sound reassuring. We avoid getting in trouble for making overbroad statements by being endlessly equivocal about everything, which probably is worse in the long run.
Pregnancy is a thing doctors worry about because—thalidomide and “flipper babies.” Birth defects can’t be taken lightly, and Lurasidone is among the safer medications that work in bipolar depression and schizophrenia without risking known birth defects in animal studies. Class A is no known risk in human studies, which is hard to do— “Let us expose human children in utero to a drug to see if it harms them” is not an ethical trial.
It is safer than other options like valproic acid and lithium, which have known birth defect risks. All that being said, having untreated bipolar disorder or schizophrenia while pregnant and with a new baby is not safe either. There is always a balance of risks.
Conclusion: Lurasidone is “good enough”…and less harmful on average.
It is an effective treatment for bipolar depression and schizophrenia.
It either doesn’t cause weight gain or is so much less risky than other options that it makes little difference.
As I have written about, it has side effects of involuntary movements in some people, including Tardive Dyskinesia.
You need to take it with a significant amount of food.
It has a dose-dependent benefit, but it’s not much of one.
It’s good, unlikely to harm in the most common ways, but not GREAT (the effect size is only 0.5, which is modest).
I hope this has been helpful!
I promise
I mean, maybe.
I know, it’s extraordinary. I get it.
It takes about $2b to bring one of these medications to market, given the global market is $16.14 billion in 2023, growing to $24.35 billion by 2030; these have been a very profitable class of medications.
Sánchez-Rivero, I. (2022). Lurasidone in treatment of manic episode. European Psychiatry, 65(Suppl 1), S400. https://doi.org/10.1192/j.eurpsy.2022.1013
So they left that for the academics!
At the end of the FDA approval trials, the proportion of patients with at least a 7% increase in body weight was 4.8% for Latuda-treated patients and 3.3% for placebo-treated patients. For example, in a 70 kg (154 lb) person, a weight gain of 7% is equal to 4.9 kg (10.8 lb).
Meyer, J. M., Ng-Mak, D. S., Chuang, C., Rajagopalan, K., & Loebel, A. (2017). Weight changes before and after lurasidone treatment: A real-world analysis using electronic health records. Annals of General Psychiatry, 16. https://doi.org/10.1186/s12991-017-0159-x
before the era of GLP-1s
I spoke in some detail with the drug company about this topic at APA in 2017.
Chapel S, Chiu YY, Hsu J, Cucchiaro J, Loebel A. Lurasidone Dose Response in Bipolar Depression: A Population Dose-response Analysis. Clin Ther. 2016 Jan 1;38(1):4-15. doi: 10.1016/j.clinthera.2015.11.013. Epub 2015 Dec 22. PMID: 26730454.
Das S, Andi BS. Severe Extrapyramidal Syndrome Caused by Lurasidone Low Dose. J Neurosci Rural Pract. 2018 Jul-Sep;9(3):446-448. doi: 10.4103/jnrp.jnrp_571_17. PMID: 30069116; PMCID: PMC6050779.
Pikalov, A., Tsai, J., Mao, Y., Silva, R., Cucchiaro, J., & Loebel, A. (2017). Long-term use of lurasidone in patients with bipolar disorder: Safety and effectiveness over 2 years of treatment. International Journal of Bipolar Disorders, 5(1), 1-8. https://doi.org/10.1186/s40345-017-0075-7