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Author
Kyla Truman -
Co-Author
Ashley Meyer, Jayant Totlani, Catherine William, Haze Brown, Shaishav Shah, Drew Hirsch, Mohamed Salem, Tiffany Chang, Rasha Abdelsalam, Sabrina Renteria, Nathalie Murphy, Rebecca Hedrick, Itai Danovitch, Robert N Pechnick, Waguih William IsHak
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Abstract Title
Systematic Review of Long-Acting Injectable Antipsychotic Medications Approved from 2008 to October 2024 and Agents in Phase 3
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Abstract Description
Title: Systematic Review of Long-Acting Injectable Antipsychotic Medications Approved from 2008 to October 2024 and Agents in Phase 3
Author: Kyla Truman
Area of Concentration: Antipsychotics
Specialty: Psychiatry
Keywords: Antipsychotics, psychopharmacology, schizophrenia
Background: Long-acting injectable (LAI) antipsychotic medications were developed to, and demonstrate efficacy in, improving compliance and enhancing patient outcomes, such as reduced time to relapse or number of hospitalizations. Some studies have also shown that LAIs reduce healthcare utilization and overall costs associated with the treatment of schizophrenia. Several new LAI antipsychotic medications achieved FDA approval in the past 15 years. Research has demonstrated that LAIs are superior to placebo, and despite a need for more evidence to compare LAIs to their oral counterparts, there is strong research that suggests that patients may be safely switched from oral antipsychotics to LAIs without a loss in efficacy. Given the myriad of factors that contribute to nonadherence to oral antipsychotics and the link between nonadherence and relapse, LAIs are poised to be a powerful tool for clinicians in the treatment of schizophrenia, particularly among vulnerable populations. Psychiatric medications including LAI antipsychotic medications undergo intensive research and clinical trials to obtain FDA approval for clinical use. Despite this, the utilization of approved medications in clinical practice and attitudes toward LAIs remain substantially variable largely due to a lack of familiarity and understanding of the effectiveness of newer agents.
Objective: The purpose of this systematic review is to provide a detailed summary of the long-acting injectable antipsychotic medications approved by the Food and Drug Administration (FDA) between 2008 to October 2024. We aim to provide an overview of the mechanism of action, indications for both labeled and off-label uses, evidence for efficacy, dosing, and the adverse effects of each drug.
Methods: Studies published from 2008 to October 1, 2024, were identified from the PubMed database, using the keywords: 'long-acting injectables' OR 'LAI*'AND 'psychopharm*" OR 'schizophrenia'. The authors conducted a focused analysis independently and reached a consensus on the recently approved long-acting injectable antipsychotic medications to be included in this systematic review. Key findings were derived from the full text in order to create the tables from selected studies.
Results: A total of 13 long-acting injectable antipsychotic medications for the treatment of schizophrenia were FDA-approved between 2008 and October 1, 2024. One long-acting injectable antipsychotic is currently being investigated in a Phase 3 clinical trial. The indications, evidence, practical implementation issues, and adverse effects of each drug are discussed in this review.
Table 1: Summary descriptions of FDA-approved LAI antipsychotics 2008-September 1, 2024 (sorted by generic name then year approved)
Name,
Year approved
Mechanism
of Action
Route and Dose
Notes to clinicians
(effects on extrapyramidal tract, prolactin, QTc, sedation, and weight/lipids)
1
Aripiprazole
(Abilify Maintena), 2013
D2 partial agonist
5-HT1A partial agonist
5-HT2A antagonist
IM injection 400mg
monthly
Akathisia: 11% vs. 4% (PBO).
Sedation: 5% vs. 1% (PBO).
Weight gain (>7% from baseline):17% vs. 7% (PBO).
2
Aripiprazole Lauroxil
(Aristada), 2015
IM injection 441mg or 882mg monthly, or
1064 mg bimonthly
Akathisia: 5% (441mg), 7% (882mg) vs. 4% (PBO.
Weight gain (>7% from baseline): 10% (441mg), 9% (882mg) vs. 6% (PBO).
3
Aripiprazole
(Aristada Initio), 2018
IM injection 674mg plus a single dose of 30mg oral aripiprazole for initiation
4
Aripiprazole
(Abilify Asimtufii), 2023
IM injection 960mg every 2 months
Akathisia: 11.4% vs. 3.5% (PBO)
Sedation: 5.4% vs. 1.2% (PBO).
Weight gain: 16.8% vs. 7.0% (PBO).
5
Olanzapine Pamoate
(Zyprexa Relprevv), 2009
Dopamine D2 and serotonin 5-HT2A antagonist
IM injection 210mg every 2 weeks, 300mg every 2 weeks, or 405mg every 4 weeks
Sedation: 8% (210mg), 13% (300mg), 13% (405mg) vs. 7% (PBO).
Weight gain: 6% (210mg), 7% (300mg), 5% (405mg) vs. 5% (PBO).
6
Paliperidone Palmitate
(Invega Sustenna), 2009
IM injection 234 mg initial dose, then 156 mg on day 8, and then 234 mg monthly
Akathisia: 6% (234/234mg), 5% (234/156mg), 1% (234/39mg), 3% (156mg), 2% (78mg), 2% (39mg) vs. 3% (PBO).
EPS: 11% (156mg and 78mg), 12% (39mg), vs. 10% (PBO).
Low risk for prolonged QTc.
Sedation: 5% (234/234mg), 5% (234/156mg), 1% (234/39mg), 4% (156mg), 7% (78mg), 5% (39mg) vs. 3% (PBO).
Weight gain (>7% from baseline): 13.1% (234/234mg), 8.3% (234/156mg), 5.8% (234/39mg), 9% (156mg), 8.9% (78mg), 6% (39mg) vs 3.3% (PBO).
7
Paliperidone Palmitate
(Invega Trinza), 2015
IM injection 273mg, 410mg, 546mg, or 819mg every 3 months
Akathisia: 5% vs. 2% (PBO).
EPS: 8%, 10% (open label), vs. 3% (PBO).
Low risk for hyperprolactinemia.
Low risk for prolonged QTc.
Weight gain (>7% from baseline): 9.6% vs 0.7% (PBO).
8
Paliperidone Palmitate
(Invega Hafyera), 2021
IM ER injection
1092mg, or 1560mg every 6 months
Akathisia: 4% vs. 4% (Invega Trinza).
EPS: 7% vs. 5% (Invega Trinza).
Low risk for prolonged QTc.
Weight gain: 9% vs. 8% (Invega Trinza).
9
Paliperidone Palmitate
(Erzofri), 2024
IM injection
Initial dose of 351mg followed by monthly dosage of 39mg to 234mg
Injection site reactions, somnolence/sedation, dizziness, akathisia, and extrapyramidal disorder.
10
Risperidone SC
(Perseris), 2018
SC injection
90mg or 120mg monthly
Akathisia: 2.6% (90mg), 6.8% (120mg) vs. 4.2% PBO).
Low risk for hyperprolactinemia.
Sedation: 7.0% (90mg), 7.7% (120mg) vs. 0.0% (PBO).
Weight gain: 13.0% (90mg), 12.8% (120mg) vs. 3.4% (PBO).
11
Risperidone IM
(Rykindo), 2023
IM injection 12.5mg, 25mg, 37.5mg, or 50mg every 2 weeks
Akathisia: 4% (25mg), 11% (50mg) vs. 6% (PBO).
Sedation: 5% (25mg), 6% (50mg) vs. 3% (PBO).
Weight gain (>7% from baseline) 10% (25mg), 8% (50mg) vs. 6% (PBO).
12
Risperidone SC
(Uzedy), 2023
SC ER injection 50mg, 75mg, 100mg, or 150 monthly; or 100mg, 150mg, 200mg, or 250mg bimonthly
Akathisia: 10% (2-8mg and >8-16mg) vs. 3% (PBO).
Sedation: 10% (2-8mg), 5% (>8-16mg) vs. 2% (PBO).
Weight gain: (>7% from baseline): 8.7% (1-8mg), 20.9% (>8-16mg) vs. 2.9% (PBO).
13
Risperidone IM
(Risvan), 2024
IM injection 75-100mg monthly
Akathisia: 4% (75mg), 8% (100mg) vs. 2% (PBO).
Hyperprolactinemia: 6% (75mg), 9% (100mg) vs. 1% (PBO).
Sedation: 4% (75mg), 6% (100mg) vs. 3% (PBO).
Weight gain (>7% from baseline): 11.6% (75mg), 15.9% (100mg) vs. 4.1% (PBO).
Table 2: Summary descriptions of Phase 3 LAI antipsychotics as of September 1, 2024
Name,
Year approved
Mechanism of Action
Route and Dose
Side Effects
1
Olanzapine SC (TV-44749)
Dopamine D2 and serotonin 5-HT2A antagonist
SC injection monthly. Therapeutic dose pending.
Dizziness, constipation, weight gain, and akathisia.
Conclusions: Improved understanding of newly approved long-acting injectables is critical in the management of patients with schizophrenia. The FDA approval of long-acting injectables in the past 15 years creates hopeful options for clinicians to improve clinical outcomes and quality of life for their patients.
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Academic Medicine
