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Guidelines for the use and management of long-acting injectable antipsychotics in serious mental illness
Open accessAbstract
Background: Long-acting injectable (LAI) formulations are not widely used in routine practice even though they offer advantages in terms of relapse prevention. As part of a process to improve the quality of care, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) elaborated guidelines for the use and management of antipsychotic depots in clinical practice. Methods: Based on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations concerning 3 fields: target-population, prescription and use, and specific populations. We contacted 53 national experts, 42 of whom (79%) completed the survey. The options were scored using a 9-point scale derived from the Rand Corporation and the University of California in the USA. According to the answers, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. The first-line option was defined as a strategy rated as 7–9 (extremely appropriate) by at least 50% of the experts. The following results summarize the key recommendations from the guidelines after data analysis and interpretation of the results of the survey by the scientific committee. Results: LAI antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder, delusional disorder and bipolar disorder. LAI second-generation antipsychotics are recommended as maintenance treatment after the first episode of schizophrenia. LAI first-generation antipsychotics are not recommended in the early course of schizophrenia and are not usually appropriate in bipolar disorder. LAI antipsychotics have long been viewed as a treatment that should only be used for a small subgroup of patients with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. Recommendations for medication management when switching oral antipsychotics to LAI antipsychotics are proposed. Recommendations are also given for the use of LAI in specific populations. Conclusion: In an evidence-based clinical approach, psychiatrists, through shared decision-making, should be systematically offering to most patients that require long-term antipsychotic treatment an LAI antipsychotic as a first-line treatment.
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“The current and future increasing availability of LAIs will enrich the choice for the clinicians who intend to use a long-acting formulation [67].”
From The role of shared decision-making in improving adherence to pharmacological treatments in patients with schizophrenia: A clinical review (2020) · cites this paper as [67]
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Items 101–188 of 188
Tatini, L., D’Anna, G., Pietrini, F., Calligaris, E., Ballerini, A., & Ricca, V. (2021) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000359 · Cited by 9
“…2018): (1) Outpatient status (2) PANSS total score ≤ 120 (Leucht et al., 2005) (3) MADRS total score 30 (Müller et al., 2003) (4) YMRS total score 25 (Lukasiewicz et al., 2013) (5) A score ≤ 4 on each of the following PANSS items: delusions (P1), conceptual disorganization (P2), suspiciousness…”
BackgroundOlanzapine pamoate for the treatment of schizophrenia – a safety evaluation
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“42 However, currently available LAI antipsychotics are not licensed for use in pregnant and breastfeeding women due to uncertainties about their safety.”
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“Before an LAI is administered, it is recommended that the patient be trialed on the oral formulation first to establish tolerability and efficacy.(21) However, there are no specific recommendations on how long this oral trial should last.”
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“In an evidence-based clinical approach, psychiatrists should offer more systematically and through shared decision-making an LAI antipsychotic as a first-line treatment to all patients who require long-term antipsychotic treatment [42,43].”
BackgroundSelf-citationComparison of Paliperidone Palmitate and Risperidone Long-Acting Injection in Schizophrenic Patients
Limosin, F., Belhadi, D., Comet, D., Pacou, M., Bouju, S., Impe, K. V., & Guillon, P. (2017) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000827 · Cited by 7
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“antipsychotics (the exception being paliperidone palmitate) to ensure adequate plasma levels of LAI antipsychotics [8, 17].”
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“Clinical guidelines recommend LAIs over oral formulations of antipsychotics for individuals who display nonadherence, have frequent relapses, or pose a safety risk to others [6, 12, 13].”
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“The LAI prescription rate was estimated to range between 10 and 30% on the basis of previous research data [29–31].”
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“7,8 However, there is limited literature available to guide providers in the decision of when to initiate LAIs in regards to the inpatient or outpatient treatment setting.”
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“However, some studies suggest that long-acting injectable antipsychotics (LAI) should be considered earlier in therapy.(20,40) In such a situation, not only maintenance of symptomatic improvement but also early symptomatic improvement should be required for LAI.”
BackgroundMurphy, A. L., Suh, S., Gillis, L., Morrison, J., & Gardner, D. M. (2023) · Pharmacy · doi:10.3390/pharmacy11020045 · Cited by 5
“, schizophrenia, schizoaffective disorder [1]).”
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“4%), especially since at least one third of all prescriptions in our study were associated with psychotic disorders, and long-acting forms should theoretically be systematically proposed to all patients with psychotic disorders (21).”
BackgroundSelf-citationBrasso, C., Beoni, A. M., Colli, G., Mariani, G. N., & Rocca, P. (2025) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253251367591 · Cited by 4
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“For example, LAI was prescribed at 23.5% in France and 29% in the UK, which were already higher than anywhere else in Europe (44).”
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Attitudes of Croatian psychiatrists towards long-acting injectable antipsychotics.
Ciglar, M., Bjedov, S., & Maleković, H. (2016) · PubMed · Cited by 4
Álvarez, J. C. G., Sánchez, L. G., Garcı́a-Resa, E., Llácer, J. M. B., Rodríguez, A. R., Esquerdo, B. P., & Martínez, E. P. (2020) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651501.2019.1711130 · Cited by 4
“Thus, the switch from oral to depot treatment is recommended for the long-term maintenance of patients and prevention of relapses, acute exacerbations and poor adherence (Jeong and Lee 2013; Llorca et al. 2013; Kane et al. 2014).”
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“In addition, this finding may contribute to the expanding body of evidence supporting the use of PP1M therapy during the acute phase as recent evidence and guidelines suggest that LAIs must also be considered earlier in therapy [53, 54].”
ResultThe Role of Long-Acting Injectable Antipsychotics in the Early Treatment of Schizophrenia
Harrison, S. J., Antunes, J., Knight, K., Johnston, K., Mehawej, J., Sanchez, P., & Correll, C. U. (2026) · CNS Drugs · doi:10.1007/s40263-026-01294-9 · Cited by 3
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“Timing of follow-up psychiatric appointments in the outpatient setting should be aligned whenever possible with maintenance LAI-AP frequency requirements (32).”
InfluentialCapuzzi, E., Forti, C. L. D., Caldiroli, A., Cova, F., Surace, T., Buoli, M., & Clerici, M. (2023) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000516 · Cited by 3
“In contrast with international clinical guidelines supporting an early and broad use of LAI antipsychotics (Llorca et al ., 2013), our findings paint the picture of a use of these compounds in chronic patients.”
ResultCatatonia-related adverse outcomes after long-acting injectable antipsychotics: Case series
Dragonetti, J. D., Posada, J. G., Key, R. G., & Kugler, J. (2024) · SAGE Open Medical Case Reports · doi:10.1177/2050313x241229008 · Cited by 3
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“patients with frequent relapses or who pose a risk to others) [28].”
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“22 Oral tolerability with a new AP should be established first, and oral supplementation should only be given if an LAI does not reach therapeutic levels quickly.”
An analysis of the clinical application of paliperidone palmitate injection based on real-world
Liu, R.-X., Liu, C., Hu, D., Wang, L., Feng, D., Guo, T., & Wang, Y. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1501701 · Cited by 2
Abdel‐Baki, A., Poulin, É., Medrano, S., Padilha, P. P. D. O., Stip, É., & Potvin, S. (2022) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651501.2022.2079531 · Cited by 2
“…was to study the functional outcome of patients according to their initial route of antipsychotic medication management strategy in real-life settings, as some guidelines suggest early use of LAI-AP in FEP despite little evidence (Group, 2016; Llorca et al., 2013; NICE, 2014; Stip et al., 2019).”
MethodAripiprazole injectable à libération prolongée dans le traitement de maintenance de la schizophrénie
Samalin, L., Charpeaud, T., & Llorca, P. (2014) · L Encéphale · doi:10.1016/j.encep.2014.09.002 · Cited by 2
Self-citationPrescribing patterns of long-acting injectable antipsychotics in a community setting in South Africa
Veyej, N., & Moosa, M. Y. H. (2022) · South African Journal of Psychiatry · doi:10.4102/sajpsychiatry.v28i0.1809 · Cited by 2
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“Medicaid was the primary insurance type at index for nearly half of”
BackgroundSzmulewicz, A., Martínez‐Alés, G., Logan, R. W., Joober, R., Ferrara, M., Kelly, C., Fredrikson, D. H., Thorpe, L. E., Conderino, S. E., Díaz‐Caneja, C. M., et al. (2025) · Nature Mental Health · doi:10.1038/s44220-025-00407-5 · Cited by 1
“For example, LAI therapy is often offered to more severely ill patients; conversely, those who accept LAI therapy may have better insight or everyday functioning 9,10 .”
de Filippis, R., Aloi, M., Cimino, A., Carbone, E. A., Rania, M., D’Onofrio, E., Kane, J. M., Schoretsanitis, G., Segura‐Garcìa, C., & Fazio, P. D. (2026) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253251403263 · Cited by 1
“6–8 One obvious clinical benefit is related to better adherence compared to their oral counterparts.”
Initial physical health assessment for psychosis in Australia and New Zealand: 2026 recommendations
Warren, N., O’Gorman, C., Dark, F. L., Every‐Palmer, S., Halstead, S., Korman, N., Lappin, J., Lawn, S., O'Donoghue, B. N., Suetani, S., et al. (2026) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/00048674261435740 · Cited by 1
“Guidelines were developed by international groups (Hasan et al., 2017; Kane et al., 2003; Keshavan et al., 2006; Skikic and Arriola, 2020; Stahl et al., 2013) and national organisations: Australia/ New Zealand (2016) (Galletly et al., 2016), Canada (Addington et al., 2017), Chile (Gaspar et al., 2019), Finland (2020),…”
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“17 General and focused guidelines regarding the treatment of bipolar disorder have mentioned the use of LAIs as first line for maintenance therapy.”
Engelke, C., Cordes, J., Kahl, K. G., & Schmidt-Kraepelin, C. (2019) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001063 · Cited by 1
“Benefits include the facilitation andmonitoring of compliance, more balanced and predictable plasma levels, frequent contact with health care professionals, and, therefore, a reduced probability of relapse and rehospitalization,(2,3) all of which have a positive impact on patients' subjective quality of life.(2,3) Con…”
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Une utilisation optimale des antipsychotiques au profit d’un meilleur pronostic de la schizophrénie
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Self-citationUso de medicación antipsicótica durante el embarazo
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Quelle modalité de traitement médicamenteux ?
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“Long-acting injectable (LAI) antipsychotics have been introduced in 1996 to address concerns encountered with oral antipsychotic medications 9–12 and has since been incorporated in clinical practice guidelines for the treatment of schizophrenia 5,13,14 .”
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“The management of LAIs can be complicated and requires specific knowledge about practical issues such as dosing and switching to a LAI (Correll et al., 2016); there are insufficient data and recommendations within the literature (Llorca et al., 2013).”
BackgroundResultInfluentialSecond-generation long-acting injectable antipsychotics in clinical practice
Петрова, Н. Н., & Grigorieva, E. V. (2022) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro2022122021115
Clinical use of long-acting antipsychotics for the treatment of bipolar disorder type I patients
Uyar, B., Atlı, A., & BİLEN, D. G. (2022) · Çukurova medical journal (Online)/Çukurova medical journal · doi:10.17826/cumj.1089059
Tarchi, L., Monaco, F. D., FALCONE, D., Ballerini, A., Ricca, V., & D’Anna, G. (2023) · Minerva Psychiatry · doi:10.23736/s2724-6612.21.02293-4
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Advancing Long-Acting Formulations for Treating Chronic Diseases
Nayan, M. U., Sultana, A., Le, N. T. H., Poluektuva, L. Y., Edagwa, B., & Gendelman, H. E. (2024) · Springer eBooks · doi:10.1007/978-3-031-68237-7_37
Benzodiazepines: a descriptive study of prescription patterns in Tabriz, Iran, 2021–2022
Fakhari, A., Farahbakhsh, M., Matinkia, M., Khameneh, A., Azimian, A., & Aghajani, E. (2025) · Discover Health Systems · doi:10.1007/s44250-025-00245-3
“Ongoing endeavors are being made to enhance the selection of patients who might require long-term benzo-diazepines [14].”
Ward, T. M., Xu, J., Hall, D. B., Chen, X., Benavides, S., Young, H. N., & Caballero, J. (2025) · Early Intervention in Psychiatry · doi:10.1111/eip.70063
“It appears SGA are the most common class of antipsychotics prescribed by physicians for child and adolescent psychiatric disorders (Llorca et al. 2013; Seida et al. 2012).”
Hodson, N., Majid, M., Vlaev, I., & Singh, S. P. (2025) · BMC Psychiatry · doi:10.1186/s12888-025-07165-9
“While some feared that incentives would not be effective, others were concerned that it would be harder to persuade patients to stop LAI treatment, despite acknowledging that services have not previously had difficulty persuading patients to cease LAI treatment (interview 3).”
Wong, K. O., Klarenbach, S. W., Martins, K. J. B., Chue, P., Dursun, S. M., Snaterse, M., Guigue, A., So, H., Luu, H., Vu, K., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20221939
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“This attitude-behavior discordance may reflect the mandatory nature of LAI treatment—even when patients harbor negative subjective attitudes, the external treatment structure can maintain adherence [57].”
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Metadata
- Authors
- Llorca, P. M., Abbar, M., Courtet, P., Guillaume, S., Lancrenon, S., & Samalin, L.
- Affiliations
- Centre Hospitalier Universitaire de Nîmes (FR)
- Inserm (FR)
- Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
- Corresponding author
- Samalin, Ludovic
- Venue
- BMC Psychiatry
- Published
- 2013-12
- Volume
- 13
- Issue
- 1
- Pages
- 340-340
- ISSN
- 1471-244X (ISSN-L)
- PMC
- PMC3898013
- OpenAlex
- W1982746840
- Cited by
- 188
- References
- 66
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 14 · 2023: 14 · 2022: 24 · 2021: 16 · 2020: 10 · 2019: 18 · 2018: 11 · 2017: 17 · 2016: 20 · 2015: 12 · 2014: 8
- FWCI
- 9.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Clinical Psychology › Psychiatric care and mental health services
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- long-acting injectable antipsychotics, severe mental illness, schizophrenia, bipolar disorder, schizoaffective disorder, delusional disorder, long-term antipsychotic treatment, relapse prevention, medication adherence, medication management, atypical antipsychotics, typical antipsychotics, shared decision-making
- MeSH terms
- Adult, Aged, Attitude of Health Personnel, Mental Disorders, Delayed-Action Preparations, Female, Humans, Injections, Intramuscular, Male, Middle Aged, Practice Patterns, Physicians', Schizophrenia, Severity of Illness Index, Antipsychotic Agents, United States, Practice Guidelines as Topic
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