Formulations Matter: The Approval of Olanzapine Extended-Release Injectable Suspension for Schizophrenia

Last week, the FDA approved olanzapine (Weltruza) for extended-release injectable suspension, as the first and only once-monthly subcutaneous long-acting injectable (LAI) formulation of olanzapine for adults with schizophrenia that can help support stabilization for people living with schizophrenia.¹

As a reminder for some readers, a long-acting antipsychotic formulation is considered to be superior to the oral counterpart of the same medication to offer maintenance antipsychotic for long-term treatment of schizophrenia. There has been a longstanding debate over the desirability of shifting long-acting versions of antipsychotic to be a default approach for schizophrenia.

Despite consensus in the field that expanding LAIs to become more routine would result in better outcomes on a population basis, the vast majority of individuals with schizophrenia are prescribed oral versions of their medication. The apparent reluctance to change practice routines is a complicated topic, but there are a few key points that matter, and these key points explain why the arrival of Weltruza could be a major opportunity to revisit what is standard practice.²

• All antipsychotics are available as an oral option but there are fewer options when using long-acting formulations.
• Developing safe long-acting formulations is hard to do and there often is a 10-year delay between the approval of an oral antipsychotic until the arrival of the first long-acting counterpart.
• In general, when used properly, the safety of the prescribed medication depends on the actual profile of the specific antipsychotic, not the way it is delivered.
• The major exception to the equivalent safety rule of thumb had been olanzapine. While a long-acting formulation of olanzapine had been available as an IM prodrug olanzapine pamoate, using this formulation would risk a severe sedation/delirium syndrome. For practical purposes, this limitation took olanzapine off the list of LAI options.
• Until now, that is. This FDA approval means that clinicians will be able to add olanzapine to the list of unique antipsychotics available in the family of LAI options.

Transforming an oral pill into different formulation released slowly, safely, and effectively to be given over weeks or months is incredibly difficult. The actual drug reaching the target site in the CNS is unchanged but almost everything else is uncharted territory. A new formulation that is amenable to pharmacokinetic goals of an LAI able to support monthly injections will make it much more likely that the range of long-acting options will come closer to meeting the specific needs of individual patients who need all the options available when facing a challenging condition like schizophrenia.

Dr Weiden is a clinical professor of psychiatry at the Renaissance School of Medicine at Stony Brook University in New York. He is Psychiatric Times' Schizophrenia and Psychosis Section Editor.

References

1. Campbell P. Olanzapine LAI (Weltruza) receives FDA approval for schizophrenia. Psychiatric Times. October 9, 2026. https://www.psychiatrictimes.com/view/olanzapine-lai-weltruza-receives-fda-approval-for-schizophrenia

2. Weiden PJ. Lies and LAIs: why accuracy of information is the key to understanding the benefits and the resistance to using long-acting formulation. CNS Spectrums. 2025;30:S37-S42.