So Many Drugs for Schizophrenia

Our next issue includes an article on lumateperone (Caplyta – Intracellular Therapies), a new oral treatment for schizophrenia. Lumateperone is the 13th second-generation drug for this indication, and there are 8 first-generation drugs still out there as well.

Why are 21 drugs with more-or-less similar mechanisms of action being marketed for the same disease? One reason might be that close to 1% of the population has schizophrenia, which typically first appears in adolescents or young adults and never goes away. That adds up to a lot of doses.

Another plausible reason for the plethora of antipsychotics could be that none of them stands out as especially effective. That doesn’t work here because clozapine (Clozaril, and others) clearly wins out on that score, but unfortunately clozapine is also unique in its toxicity, including side effects like severe neutropenia (granulocytopenia) and toxic megacolon. So, we would have to say that no drug has offered a combination of efficacy and safety that lifts it above the pack.

Perhaps, given the large need for antipsychotic drugs, new drugs try to compete by offering similar efficacy and safety at a lower price. Only a visitor from another planet would seriously consider that. The discrepancies in price of drugs in general (see our issue 1521, May 22, 2017) and antipsychotic drugs in particular defy any imaginable explanation. A month’s supply of generic aripiprazole carries a wholesale cost of $2.10; the brand name product (Abilify) costs $892. Generic risperidone costs $6; Risperdal costs $901.40. Newer drugs with a much shorter track record cost $1200. I have heard and read explanations for how that can be, but I have to confess I never understood them.

And what about the new drug? Lumateperone has a poorly understood mechanism of action that leaves room for optimistic speculation about all the entities it could treat. But does it work? That gives us pause. Schizophrenia is a lifelong disease. Can two 4-week trials and one 6-week trial tell us what we need to know? Perhaps not. In the 6-week trial, a low dose of risperidone, the active control, was significantly more efficacious than placebo, but lumateperone was not. And in one of the 4-week trials, the recommended dose of lumateperone was superior in efficacy to placebo, but twice the dose was not. I can’t remember ever seeing that before.

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  1. Philip Charney MD says:

    You are right on the mark. We have a lot to learn about mental illness. Perhaps then we can develop better treatment options.

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