It’s not often that I encounter a completely unfamiliar antipsychotic at this point in my career, but while speaking with a few brilliant MSLs recently, I was introduced to a drug called amisulpride—a selective D2/D3 antagonist used widely across Europe and other parts of the world. I was immediately intrigued. How had this slipped under my radar? And more importantly, why isn’t it available in the U.S.?
As I dug deeper, what I found was a story not just about pharmacology, but about economics, regulation, and clinical priorities—and how those factors shape what tools we as psychiatric providers have access to.
Amisulpride is a second-generation antipsychotic that’s been used for decades abroad—particularly in Europe, Australia, and India—for the treatment of schizophrenia and, at lower doses, persistent dysthymia. What makes it unique is its selectivity: amisulpride primarily targets dopamine D2 and D3 receptors, with very little action at histaminergic, adrenergic, muscarinic, or serotonergic receptors.
This receptor profile is important. Because of its selective mechanism, amisulpride causes far less sedation than agents like olanzapine or quetiapine. It avoids the anticholinergic burden we worry about with drugs like clozapine. It produces robust antipsychotic effects, particularly in cases marked by negative symptoms, and at lower doses it may even act presynaptically to enhance dopamine transmission, giving it utility in persistent dysthymia or treatment-resistant depression.
Sounds pretty good, right?
In short: no one ever tried.
Despite being on the market for over 20 years and going generic after its patent expired in 2008, no U.S. pharmaceutical company ever submitted a New Drug Application (NDA) for amisulpride's psychiatric indications. That’s it. No FDA rejection, no black box scandal—just a lack of financial incentive.
Today, the only FDA-approved form of amisulpride is Barhemsys, an IV formulation used for postoperative nausea and vomiting. It’s manufactured by Acacia Pharma and was approved in 2020. But the oral version for mental health conditions? Still unavailable.
This isn’t because the science isn’t solid—on the contrary, amisulpride has been studied in large-scale trials and has shown impressive efficacy, particularly for first-episode schizophrenia, negative symptoms, and even depressive disorders. The issue is that, once a drug is generic and widely available elsewhere, the cost of running trials and submitting to the FDA becomes hard to justify for pharmaceutical companies.
At a psychopharmacology lecture years ago, I remember someone in the audience asking Dr. Prakash Masand whether Latuda’s efficacy data applied to non-white populations. He paused and said something I’ll never forget: “In many countries, the attitude is: if it’s good enough for the United States, it’s good enough for us.”
That statement speaks volumes about the credibility and rigor of the FDA, and for good reason. The FDA requires exhaustive safety and efficacy data, often in diverse and representative populations. It is a gold standard—but sometimes, being the gold standard means we become slow adopters of globally effective treatments.
In this case, many other countries have moved forward with amisulpride, while the U.S. remains on the sidelines—not due to scientific caution, but corporate inertia.
If amisulpride were available in the U.S., it could be a valuable option for clients who cannot tolerate sedation, anticholinergic effects, or weight gain. It might be particularly effective for individuals with negative symptom–dominant schizophrenia, where many of our current treatments underperform. Low-dose amisulpride could also offer an underutilized strategy for persistent dysthymia or SSRI-resistant depression.
The drug’s side effect profile is relatively clean. Hyperprolactinemia is common, yes, but unlike clozapine or olanzapine, amisulpride tends to avoid causing sedation, orthostasis, or significant metabolic derangement. For clients who are early in their illness course, medically fragile, or sensitive to typical side effects, amisulpride could offer a uniquely tolerable option.
Yes—and not just because it’s good, but because psychiatry desperately needs more tools. We are often limited by tolerability, comorbidity, and stigma around side effects. Having a selective agent with a unique dosing window and minimal poly receptor involvement could be game-changing for certain populations—especially those with first-episode psychosis, cognitively vulnerable clients, or individuals with limited access to regular lab monitoring.
But until someone makes the economic case to the FDA—or until compounded or parallel import options open up—we’re left watching from the sidelines as other countries benefit from a medication we never really gave a chance.
In an era when precision medicine is growing, why are we still treating psychosis with blunt instruments? Amisulpride may not be the answer for everyone, but it deserves a seat at the table—and U.S. clinicians deserve the option to decide for themselves.
Schedule an appointment today to get diagnosed, receive a prescription, and continue your journey towards mental peace.
