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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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Sorted by citations
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“First, as LAIs allow a complete tracking of the drug consumption, theymay prevent thedevastating impact of the loss of even few doses of antipsychotic in early stages of the disease (Llorca et al., 2013; Patel, 2005; Stahl, 2014; Tiihonen et al., 2011).”
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“In the present study, the panel of experts recommended SGA LAIs as a first line treatment of schizophrenia in patients with cognitive impairment and poor functioning, since the lesser negative impact of SGA-LAIs on cognitive symptoms compared to FGA-LAIs allow for more productive involvement of the patient in rehabili…”
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“Furthermore, the French Association for Biological Psychiatry and Neuropsychopharmacology guidelines for the use and management of antipsychotic depots in clinical practice recommend LAI antipsychotics be considered as first-line treatment in the majority of patients who require long-term therapy [32].”
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“16,18,36 Although disadvantages of LAIs include longer time to achieve steady state and less flexibility with dose adjustments, 1 LAIs may also simplify the treatment regimen and reduce patient medication-taking burden.”
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“…LAIAs as best practice: there are highly respected CPG that recommend LAIAs as maintenance treatment from the first episode of schizophrenia (Llorca et al., 2013), contrary to the recommendations in the 2016 RANZCP CPG. Proposal for change: re-engineering the first hospital admission for…”
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“However, their use in the dementia population is disturbing because it is not evidence based and also not recommended by clinical experts [41].”
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“Lastly, the French Association for Biological Psychiatry and Neuropsychopharmacology recommends LAI as first-line treatment to patients with schizophrenia during maintenance treatment.(44)”
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“Currently, LAI FGAs are not recommended for the maintenance treatment of bipolar disorder due to little evidence (Llorca et al., 2013).”
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“, 2013) and as maintenance treatment following the initial episode (Llorca et al., 2013).”
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“However, they have potential advantages such as complete tracking of the drug consumption and full adherence in early stages of the disease.(45,46) In addition, LAIs do not need daily administration, which may be perceived by patients as a practical advantage, and minimize the risk of harmful drug use.”
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“One hypothesis could be that the recent development of specific French guidelines for the use and management of LAI antipsychotics in serious mental disorders [11,25], using a consensus-based methodology involving practitioners, facilitated their adherence and their use in clinical practice.”
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“The French Association of Biological Psychiatry and Neuropsychopharmacology clinical guideline recommends the use of second-generation LAIs as first-line treatment in the maintenance of patients after a first psychotic episode and in recent-onset schizophrenia [27].”
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“However, they should avoid starting depot antipsychotic at primary care level, as it involves the risk of serious side effects like Neuroleptic malignant syndrome.[55]”
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“In addition, the guidelines for the use and management of LAI antipsychotics in clinical practice by the French Assoc ia t ion for Bio log ica l Psychia t ry and Neuropsychopharmacology (AFPBN) suggest systematic offering of LAI antipsychotics as first line treatment to patients with schizophrenic who need maintenance…”
BackgroundEvaluating Monitoring Guidelines of Clozapine-Induced Adverse Effects: a Systematic Review
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“Recent epidemiological studies have found that the prescription rates of LAI in clinical settings vary between 20 and 40% in European countries (23, 24, 36), but only 10.”
BackgroundPortela, R., Wainberg, M. L., Castel, S., de Oliveira, H. N., & Ruas, C. M. (2022) · BMC Psychiatry · doi:10.1186/s12888-022-03794-6 · Cited by 19
Perlstein, I., Wagner, A. M., Goméni, R., Lamson, M. J., Harary, E., Spiegelstein, O., Kalmanczhelyi, A., Tiver, R., Loupe, P. S., Levi, M., et al. (2022) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.1078 · Cited by 18
Fond, G. B., Falissard, B., Nuss, P., Collin, C., Duret, S., Rabbani, M., Chefdebien, I. D., Tonelli, I., Llorca, P., & Boyer, L. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02154-4 · Cited by 19
Self-citationMisdrahi, D., Bayle, F., Tessier, A., & Bouju, S. (2015) · Patient Preference and Adherence · doi:10.2147/ppa.s89748 · Cited by 18
Changes in attitude towards LAI antipsychotic maintenance treatment: A two-year follow-up study
Pietrini, F., D’Anna, G., Tatini, L., Talamba, G. A., Andrisano, C., Calderani, E., Manetti, M., Prodi, P. R., Ricca, V., & Ballerini, A. (2018) · European Psychiatry · doi:10.1016/j.eurpsy.2018.06.002 · Cited by 18
“a) age between 18 and 65 years, b) hadbeenclinicallystableon astabilizedsingleoral AMTwitheither olanzapine, paliperidone or aripiprazole for more than 4 weeks, c) were about to be switched to the equivalent maintenance regimen with the LAI formulation of the same antipsychotic (olanzapine pamoate [39], paliperidone p…”
BackgroundMethodResultInfluentialYang, K., Liao, Y., Yang, Y. K., Lin, S., Liang, C., & Bai, Y. (2021) · CNS Drugs · doi:10.1007/s40263-021-00838-5 · Cited by 18
Iwata, N., Inagaki, A., Sano, H., Niidome, K., Kojima, Y., & Yamada, S. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01396-w · Cited by 18
Schizophrenia, the forgotten disorder: the scenario in Brazil
Matos, G., Guarniero, F. B., Hallak, J. E. C., & Bressan, R. A. (2015) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2015-1827 · Cited by 18
Pilon, D., Alcusky, M. J., Xiao, Y., Thompson‐Leduc, P., Lafeuille, M., Lefèbvre, P., & Benson, C. J. (2017) · Journal of Medical Economics · doi:10.1080/13696998.2017.1379413 · Cited by 16
Chue, P. S., & Chue, J. (2016) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s81581 · Cited by 16
“LAIs in the management of SCA, with specific consideration of an SGA-LAI as the first-line strategy.(56,57) The development of an SGA-LAI for the treatment of SCA represents a logical step for an illness characterized by both psychotic and affective symptoms and is associated with poor adherence to oral therapies and…”
MethodGarcía-Carmona, J. A., Simal-Aguado, J., Campos-Navarro, M. P., Valdivia-Muñoz, F., & Galindo‐Tovar, A. (2020) · Clinical Drug Investigation · doi:10.1007/s40261-020-00913-7 · Cited by 16
Vita, G., Pollini, D., Canozzi, A., Papola, D., Gastaldon, C., Correll, C. U., Barbui, C., & Ostuzzi, G. (2024) · Psychiatry Research · doi:10.1016/j.psychres.2024.116124 · Cited by 15
“As LAIs might have advantages over oral formulations in terms of medication adherence, timely use of LAIs has been recommended by evidence-based guidelines (Kane and Garcia-Ribera, 2009; Llorca et al., 2013).”
BackgroundPharmacological Treatments of Negative Symptoms in Schizophrenia—An Update
Tsapakis, E.-M., Treiber, M., Mitkani, C. A., Drakaki, Z., Cholevas, A., Spanaki, C., & Fountoulakis, K. Ν. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13185637 · Cited by 16
“Moreover, the French guidelines on the use of long-acting antipsychotics state that SGA LAIs should be used as a second line of treatment for negative symptoms in schizophrenia [146].”
BackgroundBogomolova, A., Kaberov, L. I., Sedláček, O., Filippov, S. K., Štěpánek, P., Král, V., Wang, X. Y., Liu, S., Ye, X., & Hrubý, M. (2016) · European Polymer Journal · doi:10.1016/j.eurpolymj.2016.09.010 · Cited by 15
Perceptions of Psychiatrists Toward the Use of Long-Acting Injectable Antipsychotics
Grover, S., Sahoo, S., & Mehra, A. (2019) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001109 · Cited by 15
“The indications of LAIs are currently not limited to only schizophrenia, but these have also been recommended for management of patients with schizoaffective disorder, delusional disorder, and bipolar disorder.(32) It has also been recommended in patients with firstepisode schizophrenia with proven benefits with regar…”
BackgroundAlphs, L. D., Brown, B., Turkoz, I., Baker, P. C., Fu, D., & Nuechterlein, K. H. (2022) · Schizophrenia Research · doi:10.1016/j.schres.2022.02.019 · Cited by 16
“Clinical guidelines recommend treatment with LAIs in patients who prefer the injectable formulation and/or are at high risk of nonadherence and suggest consideration of LAIs in first-episode schizophrenia (American Psychiatric Association, 2020b; Kane and Correll, 2019; Llorca et al., 2013; National Council for Behavi…”
Pietrini, F., Spadafora, M., Talamba, G. A., Godini, L., Lelli, L., Arcabasso, S., Manetti, M., & Ballerini, A. (2014) · International Journal of Psychiatry in Clinical Practice · doi:10.3109/13651501.2014.988268 · Cited by 15
“…are), the decision to change treatment strategy was made according to current clinical guidelines for the use and management of LAI antipsychotics (Llorca et al. 2013), suggesting that they should be considered and systematically proposed as a treatment option to any patient for whom maintenance…”
MethodFagiolini, A. M., de Bartolomeis, A., Vaggi, M., & Vampini, C. (2016) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s96214 · Cited by 15
“Some guidelines, eg, the French Association for Biological Psychiatry and Neuropsychopharmacology guidelines, recommend that LAI antipsychotics should be considered as first-line therapy in any patient requiring long-term antipsychotic therapy.(47) While Italian experience with LAI antipsychotics in patients with firs…”
Pietrini, F., Spadafora, M., Tatini, L., Talamba, G. A., Andrisano, C., Boncompagni, G., Manetti, M., Ricca, V., & Ballerini, A. (2016) · European Psychiatry · doi:10.1016/j.eurpsy.2016.05.008 · Cited by 15
“The decision to change treatment strategy was made according to current clinical guidelines for the use and management of LAI antipsychotics [40], suggesting that they should be considered and systematically proposed as a treatment option to any patient for whom maintenance antipsychotic treatment is indicated.”
MethodLong-acting injectable antipsychotics for the treatment of schizophrenia in Spain
Arango, C., Baeza, I., Bernardo, M., Cañas, F., de Dios, C., Díaz-Marsá, M., García-Portilla, M., Gutiérrez-Rojas, L., Olivares, J., Rico-Villademoros, F., et al. (2019) · Revista de Psiquiatría y Salud Mental (English Edition) · doi:10.1016/j.rpsmen.2018.03.004 · Cited by 28
“In agreement with these recommendations from expert professionals in the Spanish setting, the French Association of Biological Psychiatry and Neuropsychopharmacology has published (2013) a guideline on the use and management of long-lasting injectable antipsychotics in severe mental disorder; the first-line recommenda…”
ResultKane, J. M., Eshet, R., Harary, E., Tohami, O., Elgart, A., Knebel, H., Sharon, N. A., Suett, M., Franzenburg, K. R., Davis, G. L., et al. (2024) · CNS Drugs · doi:10.1007/s40263-024-01102-2 · Cited by 14
“Clinicians may also have misconceptions about patients’ perceptions of injection site pain and may focus on procedure rather than potential gains [33–36].”
Orsolini, L., Sceusa, F., Pompili, S., Mauro, A., Salvi, V., & Volpe, U. (2021) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2021.1928634 · Cited by 14
“the long-term treatment of such severe patients [17,18].”
BackgroundGuidelines for the use of second-generation long-acting antipsychotics
Jarema, M., Wichniak, A., Dudek, D., Samochowiec, J., Bieńkowski, P., & RYBAKOWSKI, J. K. (2015) · Psychiatria Polska · doi:10.12740/pp/39370 · Cited by 14
Bossie, C. A., Turkoz, I., Alphs, L. D., Mahalchick, L., & Fu, D. (2016) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0000000000000646 · Cited by 14
“However, evidence suggests that their early initiation is associated with greater responsiveness, reduced risk for relapse, and improved long-term functioning (Heres et al., 2014; Kane et al., 2015; Llorca et al., 2013; Subotnik et al., 2015).”
Si, T., Zhuo, J., Turkoz, I., Mathews, M., Tan, W., & Feng, Y. (2017) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2017.1401608 · Cited by 14
“within 5 years of diagnosis), in addition to their therapeutic use in chronic schizophrenia [30,48].”
BackgroundResultCordiner, M., Shajahan, P., McAvoy, S., Bashir, M., & Taylor, M. (2016) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125315623168 · Cited by 16
Jakovljević, M. (2014) · PubMed · Cited by 13
Sajatovic, M., DiBiasi, F., & Legacy, S. N. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s139557 · Cited by 12
“40 A consensus rating scale was used in which respondents expressed levels of agreement or disagreement with survey questions, and these responses were then interpreted as recommended indications for first, second, or third-line treatment strategies for each diagnosis.”
InfluentialBotha, U. A., Coetzee, M., Koen, L., & Niehaus, D. J. H. (2017) · Archives of Psychiatric Nursing · doi:10.1016/j.apnu.2017.12.002 · Cited by 12
Fagiolini, A. M., Alfonsi, E., Amodeo, G., Cenci, M., Lella, M. D., Farinella, F., Ferraiuolo, F., Fraguas, D., Loparco, N., Gutiérrez-Rojas, L., et al. (2016) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2016.1155553 · Cited by 12
Masuda, S., Yasuhara, Y., Tanioka, T., Atsuta, A., Motoki, K., Takase, K., & Locsin, R. C. (2016) · Open Journal of Psychiatry · doi:10.4236/ojpsych.2016.62025 · Cited by 12
“Also, in an evidence-based clinical approach, psychiatrists should be systematically offering to all patients that require long-term antipsychotic treatment, through shared decision-making, a LAI antipsychotic as a first-line treatment [2].”
BackgroundLi, N., Feng, Y., Lu, H., Cai, S. L., Zhuo, J., Si, T., & Zhang, L. (2018) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s158353 · Cited by 12
Use of Long-Acting Injectable Antipsychotic in an Inpatient Unit of a Community Teaching Hospital
Olayinka, O. O., Oyelakin, A., Cherukupally, K., Virk, I., Ojimba, C., Khadka, S., Maksymenko, A., Fouron, P., Khandaker, T., Olupona, T., et al. (2019) · Psychiatry Journal · doi:10.1155/2019/8629030 · Cited by 12
“Similarly, while reviewing the extant literature to inform guidelines for LAI use in France, the authors found that LAI prescription rates are generally low across Europe; the United Kingdom reportedly had the highest LAI prescription rate of 29 percent [8].”
BackgroundMisdrahi, D., Dupuy, M., Dansou, Y., Boyer, L., Berna, F. S., Capdevielle, D., Chéreau, I., Coulon, N., d’Amato, T., Dubertret, C., et al. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02640-x · Cited by 11
“While the sample was composed of outpatients referred to the various expert centers for diagnosis or treatment issues, the 10 expert centers cover a large area of the French territory and as a result integrated a wide range of socioeconomic and cultural differences.”
BackgroundSelf-citationJoshi, K., Mao, L., Biondi, D. M., & Millet, R. A. (2018) · BMC Psychiatry · doi:10.1186/s12888-018-1594-1 · Cited by 11
Prescription patterns in psychiatric compulsory care: polypharmacy and high-dose antipsychotics
Kaikoushi, K., Karanikola, M. N. K., Middleton, N., Bella, E., & Chatzittofis, A. (2021) · BJPsych Open · doi:10.1192/bjo.2021.982 · Cited by 12
Si, T., Zhuo, J., Feng, Y., Lu, H., Di, H., & Zhang, L. (2019) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s191803 · Cited by 11
Pottie, K. C., Mathew, C. M., Mendonca, O., Magwood, O., Saad, A., Abdalla, T., Stergiopoulos, V., Bloch, G. C., Brcic, V., Andermann, A. A. J., et al. (2019) · Campbell Systematic Reviews · doi:10.1002/cl2.1048 · Cited by 9
“Lastly, long‐acting Injectable antipsychotics are effective for managing numerous serious mental disorders, such as schizophrenia, delusional disorder, and bipolar disorder (Llorca et al., 2013).”
Long-acting antipsychotic treatments: focus on women with schizophrenia
Brissos, S., & Balanzá‐Martínez, V. (2024) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253241263715 · Cited by 10
“3,5 Treatment guidelines have been very conservative on the use of LAI-APs, 6,7 especially regarding their early implementation, 6 even though some already state that ‘patients should be offered the option of depot/long-acting injectable AP medication for maintenance treatment, given the evidence…”
BackgroundNammas, M. (2025) · Cureus · doi:10.7759/cureus.85563 · Cited by 15
“Meta-analyses of LAI use in schizophrenia have shown significant improvements in medication adherence, symptom remission, and relapse prevention compared to oral anti-psychotics [53].”
Treatment Duration With Long-Acting Injectable Antipsychotics After In-hospital Initiation
Rittmannsberger, H., Rosenleitner, J., Malsiner‐Walli, G., Werl, R., Rittmannsberger, B., & Yazdi, K. (2017) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000672 · Cited by 10
“Some authors even argue that there is no evidence at all that use of LAI alone can improve patient adherence and that LAI should be given only to patients with a clear willingness to adhere.(18,19) Nevertheless, the statement that “poor insight and severe psychopathology in the absence of sufficient supervision favor…”
Benson, C. J., Joshi, K., Lapane, K. L., & Fastenau, J. M. (2015) · Current Medical Research and Opinion · doi:10.1185/03007995.2015.1050365 · Cited by 10
Pietrini, F., Tatini, L., Santarelli, G., Brugnolo, D., Squillace, M., Bozza, B., Ballerini, A., Ricca, V., & D’Anna, G. (2021) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651501.2021.1912358 · Cited by 10
“…service between January 2016 and July 2017 who required a long-term antipsychotic treatment was offered to switch to LAI AMT, according to current clinical guidelines suggesting that LAIs should be systematically considered and proposed to any patient for whom AMT is indicated (Llorca et al. 2013).”
BackgroundMethod
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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