Available Long-Acting Injectable (LAI) Antipsychotics
The currently available LAI antipsychotics include both first-generation agents (haloperidol decanoate and fluphenazine decanoate) and second-generation agents (risperidone, paliperidone palmitate, olanzapine pamoate, and aripiprazole), with second-generation LAIs being preferred due to better tolerability and fewer neurological side effects. 1
First-Generation LAI Antipsychotics
- Haloperidol decanoate is available as a first-generation depot formulation 2, 3
- Fluphenazine decanoate is available as a first-generation depot formulation 4, 2, 3
- The use of these first-generation depot agents has declined since the advent of second-generation options due to inferior tolerability profiles 2
Second-Generation LAI Antipsychotics
Risperidone LAI
- Risperidone microspheres (intramuscular) was the first depot formulation of an atypical antipsychotic, prepared by encapsulating risperidone into biodegradable microspheres 2, 3
- Available in vial kits of 12.5 mg, 25 mg, 37.5 mg, and 50 mg, administered every 2 weeks 5
- Requires oral risperidone supplementation for the first 3 weeks after initial injection to ensure adequate therapeutic plasma concentrations 5
- Multiple emerging formulations include intramuscular, subcutaneous, long-acting oral, and implantable options 6
Paliperidone Palmitate
- Paliperidone palmitate is an aqueous suspension of nanocrystal molecules 2
- Available in both once-monthly and 3-monthly injection formulations, with the 3-monthly being the first LAI agent to extend dosing administration beyond the typical monthly period 7
- No cases of postinjection delirium/sedation syndrome (PDSS) were demonstrated in clinical trial databases 3
Olanzapine Pamoate
- Olanzapine pamoate is a microcrystalline salt of olanzapine and pamoic acid suspended in aqueous solution 2, 3
- Associated with postinjection delirium/sedation syndrome (PDSS) occurring in approximately 0.07% of injections or 1.4% of patients 3
Aripiprazole LAI
- Aripiprazole monohydrate and aripiprazole lauroxil are available as LAI formulations 7, 8
- Initially available as once-monthly formulations, with aripiprazole lauroxil now offering every 6-week and 8-week administration preparations 7
Clinical Considerations
- Second-generation LAIs demonstrate comparable efficacy to their oral counterparts with similar safety and tolerability profiles, excluding injection site reactions 7
- All second-generation LAI preparations have demonstrated superiority over placebo 7
- When compared head-to-head, first-generation and second-generation LAI agents show comparable efficacy, with adverse event profiles matching the expected side effects of each specific drug 7