Second-generation long-acting injectable antipsychotics: A PRACTICAL GUIDE Understanding each of these medications’ unique properties can optimize patient care Brittany L. Parmentier, PharmD, MPH, here are currently 7 FDA-approved second-generation long-acting BCPS, BCPP 1-7 Clinical Assistant Professor injectable antipsychotics (LAIAs). These LAIAs provide a Department of Pharmacy Practice Tunique dosage form that allows patients to receive an antipsy- The University of Texas at Tyler Fisch College of Pharmacy chotic without taking oral medications every day, or multiple times per Tyler, Texas day. This may be an appealing option for patients and clinicians, but Disclosure The author reports no financial relationships with any because there are several types of LAIAs available, it may be difficult to companies whose products are mentioned in this article, or with determine which LAIA characteristics are best for a given patient. manufacturers of competing products. Since the FDA approved the first second-generation LAIA, risperidone long-acting injectable (LAI),1 in 2003, 6 additional second-generation LAIAs have been approved: • aripiprazole LAI • aripiprazole lauroxil LAI • olanzapine pamoate LAI • paliperidone palmitate monthly injection • paliperidone palmitate 3-month LAI • risperidone LAI for subcutaneous (SQ) injection. When discussing medication options with patients, clinicians need to consider factors that are unique to each LAIA. In this article, I describe the similarities and differences among the second-generation LAIAs, and address common questions about these medications. A major potential benefit: Increased adherence One potential benefit of all LAIAs is increased medication adherence com- pared with oral antipsychotics. One meta-analysis of 21 randomized con- trolled trials (RCTs) that compared LAIAs with oral antipsychotics and Current Psychiatry GEORGE MATTEI/SCIENCE SOURCE GEORGE MATTEI/SCIENCE Vol. 19, No. 3 25 Table 1 Second-generation LAIAs: Indications, starting doses, maintenance doses, and maintenance doses frequency Medication Paliperidone Aripiprazole lauroxil Olanzapine Paliperidone palmitate palmitate Risperidone Injectable Aripiprazole LAI LAI pamoate LAI monthly injection 3-month injection Risperidone LAI LAI for SQ antipsychotics FDA- Schizophrenia Schizophrenia Schizophrenia Schizophrenia Schizophrenia Schizophrenia Schizophrenia approved Bipolar I disorder Schizoaffective disorder Bipolar I disorder indications Starting 400 mg 441, 662, 882, or 210, 300, or Day 1: 234 mg Based on the 25 to 50 mg 90 or dose 1,064 mg, depending 405 mg, depending Day 8: 156 mg last dose of 120 mg, based on the oral dose and on the oral dose paliperidone on the oral frequency preference palmitate monthly dose injection Maintenance 300 to 400 mg 441 to 1,064 mg 150 to 405 mga 39 to 234 mg 273 to 819 mg 25 to 50 mg 90 or Clinical Point dose 120 mg One potential Maintenance Every 4 weeks 441 mg: every 4 weeks Every 2 to 4 weeks Every 4 weeks Every 12 weeks Every 2 weeks Every 4 weeks benefit of all long- dose 662 mg: every 4 weeks frequency acting injectable 882 mg: every 4 or 6 weeks antipsychotics is 1,064 mg: every increased medication 8 weeks adherence aMaintenance dose for olanzapine pamoate LAI differs during the first 8 weeks of treatment and after 8 weeks of treatment; see Table 2 LAI: long-acting injectable; LAIAs: long-acting injectable antipsychotics; SQ: subcutaneous Source: References 1-7 Table 2 Oral-to-LAI dose equivalency recommendations Risperidone LAI Medication Aripiprazole lauroxil LAI Paliperidone palmitate monthly injection Olanzapine pamoate LAI for SQ Oral daily dose 10 mg 15 mg ≥20 mg 3 mg 6 mg 9 mg 12 mg 10 mg 15 mg ≥20 mg 3 mg 4 mg LAI equivalency 441 mg 662 mg every 882 mg 39 to 117 mg 156 mg 234 mg During the first 8 weeks 90 mg 120 mg every 4 weeks every 78 mg of treatment 4 weeks 4 weeks OR 219 mg 300 mg 300 mg 882 mg every every every every 6 weeks 2 weeks 2 weeks 2 weeks OR OR 1,064 mg every 405 mg 8 weeks every 4 weeks After 8 weeks of treatment 150 mg 210 mg 300 mg Discuss this article at every every every www.facebook.com/ 2 weeks 2 weeks 2 weeks MDedgePsychiatry OR OR 300 mg 405 mg every every 4 weeks 4 weeks LAI: long-acting injectable; LAIAs: long-acting injectable; SQ: subcutaneous Current Psychiatry Source: References 2,5-7 26 March 2020 Table 1 included 5,176 patients found that LAIAs had a similar efficacy to oral antipsychotics Second-generation LAIAs: Indications, starting doses, maintenance doses, 8 and maintenance doses frequency in preventing relapse. However, a meta- analysis of 25 mirror-image studies com- MDedge.com/psychiatry Medication paring LAIAs with oral antipsychotics that Paliperidone included 5,940 patients found that LAIAs Aripiprazole lauroxil Olanzapine Paliperidone palmitate palmitate Risperidone were superior in preventing hospitalization.9 Aripiprazole LAI LAI pamoate LAI monthly injection 3-month injection Risperidone LAI LAI for SQ In these mirror-image studies, participants FDA- Schizophrenia Schizophrenia Schizophrenia Schizophrenia Schizophrenia Schizophrenia Schizophrenia received oral antipsychotics first and then approved Bipolar I disorder Schizoaffective disorder Bipolar I disorder switched to LAIAs, and the 2 study periods indications were compared. Because mirror-image stud- Starting 400 mg 441, 662, 882, or 210, 300, or Day 1: 234 mg Based on the 25 to 50 mg 90 or ies are observational, participants do not dose 1,064 mg, depending 405 mg, depending last dose of 120 mg, based Day 8: 156 mg engage with research teams to the extent that on the oral dose and on the oral dose paliperidone on the oral 9 frequency preference palmitate monthly dose they do in RCTs. Although mirror-image injection studies have limitations, participants in these studies may be a better representation Maintenance 300 to 400 mg 441 to 1,064 mg 150 to 405 mga 39 to 234 mg 273 to 819 mg 25 to 50 mg 90 or dose 120 mg of patients encountered in clinical practice Clinical Point due to the extensive monitoring and follow- Maintenance Every 4 weeks 441 mg: every 4 weeks Every 2 to 4 weeks Every 4 weeks Every 12 weeks Every 2 weeks Every 4 weeks Paliperidone up RCT participants typically receive.9 dose 662 mg: every 4 weeks palmitate monthly frequency 882 mg: every 4 or injection is the only 6 weeks Differences in FDA-approved LAIA approved for 1,064 mg: every indications 8 weeks schizoaffective The 7 currently available LAIAs vary in aMaintenance dose for olanzapine pamoate LAI differs during the first 8 weeks of treatment and after 8 weeks of treatment; see Table 2 disorder terms of FDA-approved indications, dose LAI: long-acting injectable; LAIAs: long-acting injectable antipsychotics; SQ: subcutaneous Source: References 1-7 options, frequency, need for oral antipsy- chotic overlap, route of administration, and other factors. Table 11-7 (page 26) summa- rizes some of these differences. Although all Table 2 second-generation LAIAs are approved for Oral-to-LAI dose equivalency recommendations schizophrenia,1-7 risperidone LAI and aripip- razole LAI are also approved for bipolar I Risperidone LAI 1,4 Medication Aripiprazole lauroxil LAI Paliperidone palmitate monthly injection Olanzapine pamoate LAI for SQ disorder. Paliperidone palmitate monthly injection is the only LAIA approved for treat- Oral daily dose 10 mg 15 mg ≥20 mg 3 mg 6 mg 9 mg 12 mg 10 mg 15 mg ≥20 mg 3 mg 4 mg ing patients with schizoaffective disorder.2 LAI equivalency 441 mg 662 mg every 882 mg 39 to 117 mg 156 mg 234 mg During the first 8 weeks 90 mg 120 mg every 4 weeks every 78 mg of treatment 4 weeks 4 weeks OR 219 mg 300 mg 300 mg Starting doses 882 mg every every every every 6 weeks 2 weeks 2 weeks 2 weeks For most LAIAs, the starting dose is the same as the maintenance dose (Table 1,1-7 OR OR page 26). One exception is paliperidone pal- 1,064 mg every 405 mg 8 weeks every mitate monthly injection, which requires a 4 weeks 234-mg dose on Day 1 followed by a 156-mg After 8 weeks of treatment dose on Day 8 for all patients, regardless of 2 150 mg 210 mg 300 mg the maintenance dose required. The 156-mg every every every dose may be given 4 days before or after Day 2 weeks 2 weeks 2 weeks 8.2 The first maintenance dose of paliperi- OR OR done palmitate monthly injection should be 300 mg 405 mg administered 5 weeks after the 234-mg dose every every on Day 1.2 Before starting paliperidone pal- 4 weeks 4 weeks mitate 3-month injection, patients should be LAI: long-acting injectable; LAIAs: long-acting injectable; SQ: subcutaneous stable on paliperidone palmitate monthly Current Psychiatry Source: References 2,5-7 injection for 4 months, and the 2 most recent Vol. 19, No. 3 27 Table 3 Is overlap with an oral antipsychotic needed? Medication Overlap needed? Aripiprazole LAI YES: 2 weeks after 1st injection Aripiprazole lauroxil LAI NO: If receiving aripiprazole lauroxil 675-mg LAI YES: 3 weeks after 1st injection if NOT receiving aripiprazole lauroxil 675-mg LAI Injectable Olanzapine pamoate LAI NO antipsychotics Paliperidone palmitate NO monthly injection Risperidone LAI YES: 3 weeks after 1st injection Risperidone LAI for SQ NO LAI: long-acting injectable; SQ: subcutaneous Source: References 1,2,4-7 Clinical Point Some dosages of doses of paliperidone palmitate monthly compared with after 8 weeks of treatment injection should be the same.3 (Table 2,2,5-7 page 26). Additionally, because aripiprazole lauroxil there are both short-acting and long-acting LAI are administered injections of olanzapine, it is essential to every 6 or 8 weeks Maintenance doses choose the correct formulation when pre- Dosing frequency may be an important factor scribing this medication.5 for some patients when deciding to receive a LAIA.