Section Free - Video Lectures

02. Understanding When to Prescribe LAIs

Published on June 1, 2025 Certification expiration date: June 1, 2028

Brian Miller, M.D., Ph.D., M.P.H.

Professor - Augusta University

Key Points

All second-generation LAI antipsychotics are approved for schizophrenia treatment, with some specifically approved for schizoaffective and bipolar disorders.
Patient preference is a key criterion for LAI candidacy, alongside recent-onset schizophrenia, frequent relapses, and non-adherence to oral medications.
Strongest evidence supports LAI use in patients with poor illness insight, unstable housing, multiple hospitalizations, and history of violence.

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Slides and Transcript

Slide 1 of 10

Let’s talk about understanding when to prescribe long-acting injectable antipsychotics.

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We’ll begin by talking about their approved indications. First of all, all second-generation agent LAIs are approved for the treatment of schizophrenia. Paliperidone palmitate is specifically approved for schizoaffective disorder either as monotherapy or an adjunct to mood stabilizers or antidepressants. Risperidone microspheres are approved for bipolar I disorder specifically maintenance treatment either as monotherapy or as an adjunct to lithium or valproate.

References:

Greenberg, W. M., & Citrome, L. (2015). Paliperidone Palmitate for Schizoaffective Disorder: A Review of the Clinical Evidence. Neurology and Therapy, 4(2), 81–91. https://doi.org/10.1007/s40120-015-0030-4
Riboldi, I., Cavaleri, D., Capogrosso, C. A., Crocamo, C., Bartoli, F., & Carrà, G. (2022). Practical guidance for the use of long-acting injectable antipsychotics in the treatment of schizophrenia. Psychology Research and Behavior Management, 15, 3915–3929. https://doi.org/10.2147/PRBM.S371991

Understanding When to Prescribe LAIs Slide 2 of 10

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Slide 3 of 10

And both of the first-generation antipsychotic LAIs are approved for patients requiring prolonged parenteral antipsychotic therapy, for example, patients with chronic schizophrenia.

References:

Riboldi, I., Cavaleri, D., Capogrosso, C. A., Crocamo, C., Bartoli, F., & Carrà, G. (2022). Practical guidance for the use of long-acting injectable antipsychotics in the treatment of schizophrenia. Psychology Research and Behavior Management, 15, 3915–3929. https://doi.org/10.2147/PRBM.S371991

Understanding When to Prescribe LAIs Slide 3 of 10

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All that said, LAIs are often used off-label for patients with both schizoaffective disorder as well as patients with bipolar disorder.

References:

D'Agostino, A., Aguglia, A., Barbui, C., Bartoli, F., Carrà, G., Cavallotti, S., Chirico, M., Ostinelli, E. G., Zangani, C., Martinotti, G., Ostuzzi, G., & STAR Network Depot Investigators. (2022). Off-label long acting injectable antipsychotics in real-world clinical practice: A cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study. BMC Psychiatry, 22(1), 442. https://doi.org/10.1186/s12888-022-04071-2

Understanding When to Prescribe LAIs Slide 4 of 10

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Slide 5 of 10

So let’s talk about now specific candidates for LAI antipsychotics. Importantly, we want to consider patient preference. If a patient prefers to be treated with an LAI, then that automatically makes them a good candidate.

References:

Correll, C. U., Citrome, L., Haddad, P. M., Lauriello, J., Olfson, M., Calloway, S. M., & Kane, J. M. (2016). The use of long-acting injectable antipsychotics in schizophrenia: Evaluating the evidence. The Journal of Clinical Psychiatry, 77(suppl 3), 1-24. https://doi.org/10.4088/JCP.15032su1
Sajatovic, M., Ross, R., Legacy, S. N., Correll, C. U., Kane, J. M., DiBiasi, F., Fitzgerald, H., & Byerly, M. (2018). Identifying patients and clinical scenarios for use of long-acting injectable antipsychotics – expert consensus survey part 1. Neuropsychiatric Disease and Treatment, 14, 1463-1474. https://doi.org/10.2147/NDT.S167394

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Other candidates include patients with recent onset schizophrenia, those with frequent illness relapses, patients who are non-adherent with oral antipsychotics as well as patients with risk factors for medication non-adherence, specifically those patients with severe symptoms, cognitive impairment, diminished insight into illness, substance use comorbidity as well as negative attitudes towards medications.

References:

Correll, C. U., Citrome, L., Haddad, P. M., Lauriello, J., Olfson, M., Calloway, S. M., & Kane, J. M. (2016). The use of long-acting injectable antipsychotics in schizophrenia: Evaluating the evidence. The Journal of Clinical Psychiatry, 77(suppl 3), 1-24. https://doi.org/10.4088/JCP.15032su1
Sajatovic, M., Ross, R., Legacy, S. N., Correll, C. U., Kane, J. M., DiBiasi, F., Fitzgerald, H., & Byerly, M. (2018). Identifying patients and clinical scenarios for use of long-acting injectable antipsychotics – expert consensus survey part 1. Neuropsychiatric Disease and Treatment, 14, 1463-1474. https://doi.org/10.2147/NDT.S167394

Understanding When to Prescribe LAIs Slide 6 of 10

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Slide 7 of 10

An adage from my clinical training is that you don’t diagnose anything that you don’t ask about. By analogy, you won’t prescribe long-acting injectable antipsychotics if you don’t talk with your patients about them. So here, I advocate for principles of shared and collaborative decision making with our patients.

References:

Fiorillo, A., Barlati, S., Bellomo, A., Corrivetti, G., Nicolò, G., Sampogna, G., Stanga, V., Veltro, F., Maina, G., & Vita, A. (2020). The role of shared decision-making in improving adherence to pharmacological treatments in patients with schizophrenia: a clinical review. Annals of General Psychiatry, 19, 43. https://doi.org/10.1186/s12991-020-00293-4

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What does the evidence tell us for good candidates for LAIs? Well, a survey of over 40 research experts and high prescribers with extensive experience with these medications found that the strongest factors for selecting appropriate patients for LAIs, those are items that received the highest rating by over half of the respondents, included patients with poor insight into their illness and need for treatment, those who are homeless or have unstable housing situations, patients with multiple hospitalizations for illness relapses and patients with a history of violence towards others.

References:

Sajatovic, M., Ross, R., Legacy, S. N., Correll, C. U., Kane, J. M., DiBiasi, F., Fitzgerald, H., & Byerly, M. (2018). Identifying patients and clinical scenarios for use of long-acting injectable antipsychotics – expert consensus survey part 1. Neuropsychiatric Disease and Treatment, 14, 1463-1474. https://doi.org/10.2147/NDT.S167394

Understanding When to Prescribe LAIs Slide 8 of 10

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Slide 9 of 10

So our key points for this section is that all second-generation LAI antipsychotics have approval for schizophrenia but they’re often used off-label for schizoaffective disorder and bipolar disorder as well.

Understanding When to Prescribe LAIs Slide 9 of 10

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Specific candidates for LAIs include patients with frequent illness relapses or hospitalizations, patients who are non-adherent with oral antipsychotics and those with poor insight but also those who prefer treatment with LAIs. And ultimately, clinicians should discuss LAIs as a treatment option with their patients.

Understanding When to Prescribe LAIs Slide 10 of 10

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Next Section

03. Why Choose LAIs? Benefits in Schizophrenia

Learning Objectives:

After completing this activity, the learner will be able to:

Identify appropriate candidates for long-acting injectable (LAI) antipsychotics.
Compare the clinical benefits of LAI antipsychotics versus oral medications.
Describe the pharmacological characteristics of different LAI antipsychotic formulations, including dosing intervals, administration requirements, and oral supplementation needs for various first and second-generation agents.

Original Release Date: June 1, 2025

Expiration Date: June 1, 2028

Expert: Brian Miller, M.D.

Medical Editor: Flavio Guzmán, M.D.

Relevant Financial Disclosures:

Brian Miller declares the following interests:

- Bristol Myers Squibb: Data Safety Monitoring Board

All of the relevant financial relationships listed above have been mitigated by Medical Academy and the Psychopharmacology Institute.

None of the other faculty, planners, and reviewers for this educational activity have relevant financial relationships to disclose during the last 24 months with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

Contact Information: For questions regarding the content or access to this activity, contact us at support@psychopharmacologyinstitute.com

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Participants must complete the activity online during the valid credit period that is noted above.

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This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education through the joint providership of Medical Academy LLC and the Psychopharmacology Institute. Medical Academy is accredited by the ACCME to provide continuing medical education for physicians

Credit Designation Statement

Medical Academy designates this enduring activity for a maximum of 0.75 AMA PRA Category 1 credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.