On February 20, 2026, the FDA approved milsaperidone (Bysanti) for adults with schizophrenia or acute bipolar I manic or mixed episodes. Milsaperidone is an atypical antipsychotic and the active metabolite of iloperidone (Fanapt). The two drugs are best described as an interconverting pair, meaning they rapidly convert into each other through carbonyl reduction in the body.

Another term for this is a patent extender. Vanda Pharmaceuticals, which developed milsaperidone, is set to lose its patent on Fanapt in 2027 or 2028. In the old days, patent extenders had at least the pretense of bringing a new medication to market. Escitalopram and armodafinil launched on the strength of their own trials, even though both are contained in their parent compounds, citalopram and modafinil. Not so with milsaperidone, which was approved based on iloperidone’s clinical trials: three studies in schizophrenia and one in acute mania.

Milsaperidone and iloperidone share the same pharmacodynamic and pharmacokinetic profiles. Both block dopamine (D2 and D3) and serotonin (5-HT2A) receptors, and both block noradrenergic alpha-1 receptors—causing the orthostasis that is their most problematic side effect. Because the two parent drugs reach similar plasma concentrations of iloperidone and milsaperidone regardless of which one is prescribed, taking milsaperidone is functionally identical to taking iloperidone (www.tinyurl.com/ycwnbnmb).

From the Clinical Update
“FDA Approves Bysanti: Patent Extension Gone Wild”
by Chris Aiken, MD
The Carlat Psychiatry Report, Volume 24, Issue 9
September 2026
www.thecarlatreport.com

Efficacy in schizophrenia and mania
In schizophrenia, iloperidone sits near the bottom of the class for efficacy, with an effect size of 0.31 in a network meta-analysis of 438 randomized trials (Schneider-Thoma J et al, Lancet 2026;407(10531):876–891). Other low-efficacy agents include brexpiprazole, cariprazine, and lurasidone, though cariprazine may have an edge for negative symptoms. In direct comparisons, iloperidone’s efficacy fell below risperidone and haloperidol in schizophrenia, though the difference was not statistically significant. Higher doses (20–24 mg/day) outperformed lower ones (10–16 mg/day) (Citrome L et al, Hum Psychopharmacol 2012;27(1):24–32).

Iloperidone is also approved for acute mania, where its effect size is higher at 0.6—but that estimate rests on a single controlled monotherapy trial (Torres R et al, J Clin Psychiatry 2024;85(1):23m14966). Tolerability was poor: 30%–50% of patients dropped out, often due to palpitations, urinary urgency, and hypotension. With no data in the depressed or maintenance phases of bipolar disorder, iloperidone—and by extension milsaperidone—is a second- or third-line option there.

Tolerability
The risk profiles of milsaperidone and iloperidone are identical. Orthostatic hypotension is their biggest drawback, raising the risk of falls—especially in elderly patients or those already taking alpha-1 blockers such as prazosin, doxazosin, or tamsulosin. With this alpha-1 blockade comes a small risk of priapism (under 1%) and, through dilutional effects related to vasodilation, anemia (1%). Both drugs must be stopped before cataract surgery due to intraoperative floppy iris syndrome, another alpha-1 risk. They are also among the antipsychotics with the biggest risk of QTc prolongation (at 9 msec, similar to ziprasidone).

Weight gain and anticholinergic effects are significant, placing milsaperidone just below clozapine and olanzapine for those side effects. Elevated liver enzymes are a rare risk. In their favor, both drugs carry a lower risk of sedation and akathisia than many other antipsychotics.

Dosing is complicated. Both drugs require divided dosing and gradual titration to prevent orthostasis. Half-lives of 18–26 hours make once-daily dosing theoretically feasible, but peak concentrations with once-daily use can provoke hypotension. Drug interactions add another layer of complexity: CYP3A4 and CYP2D6 inhibitors significantly raise levels, as do poor metabolizer status at these enzymes.

The case for milsaperidone
We reached out to Vanda Pharmaceuticals to better understand what milsaperidone brings to the table, but they declined to comment. Their press release cites advantages of “market exclusivity” until 2044 and the “extensive clinical heritage” of iloperidone’s data that it rests on.

CARLAT VERDICT
Milsaperidone (Bysanti) is iloperidone under a new name. Whether you prescribe the brand or wait for generic iloperidone, patients will end up with nearly identical levels of both drugs. Given iloperidone’s modest efficacy and significant tolerability burden, this approval changes nothing for clinical practice.