Second-generation long-acting injectable : 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, long-acting injectable (LAI),1 in 2003, 6 additional second-generation LAIAs have been approved: • LAI • LAI • pamoate LAI • palmitate monthly • 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

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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 approved 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 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 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. The frequency of the maintenance doses for all second-generation LAIAs var- Overlap with an oral antipsychotic ies from every 2 weeks to 12 weeks (Table 1,1-7 might be necessary page 26). Paliperidone palmitate 3-month Administration of several of the LAIAs LAI is the only LAIA that is administered may require overlap with an oral antipsy- every 12 weeks.3 Some dosages of aripipra- chotic (Table 31,2,4-7). Patients who refuse to zole lauroxil LAI are administered every 6 or take oral medications may benefit from 8 weeks.6 All other second-generation LAIAs one of the LAIAs that does not require oral are given every 2 to 4 weeks. overlap—paliperidone palmitate monthly injection, olanzapine pamoate LAI, and ris- peridone LAI for SQ.2,5,7 Risperidone LAI Start with an oral antipsychotic requires overlap with oral risperidone for Before starting any LAIA, patients should 3 weeks.1 receive the oral formulation of that antipsy- Aripiprazole is available in 2 LAI for- chotic to establish tolerability.1-7 Four of the mulations: aripiprazole LAI and aripipra- 7 available LAIAs have an oral-to-LAI dose zole lauroxil LAI. Aripiprazole lauroxil is equivalency recommendation in their pre- a of aripiprazole, and these 2 LAI scribing information (Table 2,2,5-7 page 26). medications differ in available dose options This can help clinicians estimate the LAIA and dosing frequency.4,6 Aripiprazole LAI maintenance dose required to control a requires an oral overlap for 2 weeks after patient’s symptoms. If a dose adjustment is the first injection, whereas aripiprazole needed once a patient starts an LAIA, the lauroxil LAI requires 3 weeks of oral over- dose adjustment can be made when the lap unless aripiprazole lauroxil 675-mg next injection is due.2 LAI is administered (Figure,6 page 29).4,6,10 There are 2 important considerations Aripiprazole lauroxil 675-mg LAI is for- when prescribing olanzapine pamoate LAI. mulated with drug particles that are smaller First, the recommended dose for olanzapine than those in aripiprazole lauroxil LAI.11 pamoate LAI based on oral olanzapine doses The smaller particle size results in faster Current Psychiatry 28 March 2020 differs during the first 8 weeks of treatment dissolution and a more rapid increase in Figure Initiating aripiprazole lauroxil long-acting injectable

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Give aripiprazole lauroxil 675-mg LAI AND 1 dose of 30-mg oral aripiprazole Yes AND 1st aripiprazole lauroxil LAI dose

Will the patient receive aripiprazole lauroxil 675-mg LAI?

No Give 1st aripiprazole lauroxil LAI dose AND 3 weeks oral aripiprazole Clinical Point Because there are both short- LAI: long-acting injectable Source: Reference 6 and long-acting injections of olanzapine, be sure to choose the correct plasma aripiprazole levels. Aripiprazole factors, it may not be possible for patients lauroxil 675-mg LAI is a single injection that to receive their injection on the specified formulation should be given with one 30-mg dose of oral day. The prescribing information for some aripiprazole.10 This combination results in LAIAs provides a dosing window (Table 4,1-7 aripiprazole concentrations that are compa- page 30). The prescribing information for rable to aripiprazole lauroxil LAI and oral risperidone LAI, olanzapine pamoate LAI, aripiprazole overlap for 3 weeks after the and risperidone LAI for SQ does not specify first injection.10 how many days the injection can be admin- The starting dose of aripiprazole lau- istered before or after the due date; however, roxil LAI may be administered on the same the prescribing information for risperidone day as aripiprazole lauroxil 675-mg LAI LAI for SQ indicates that if the injection is not and the 30-mg oral aripiprazole dose, or it given on the due date, it should be adminis- may be administered up to 10 days after.10 tered as soon as possible after that.1,5,7 Aripiprazole lauroxil LAI and aripiprazole Paliperidone palmitate monthly injection lauroxil 675-mg LAI are not interchange- and paliperidone palmitate 3-month LAI able due to differing pharmacokinetic pro- have the clearest recommendations for a dos- files.6,10 Aripiprazole lauroxil 675-mg LAI ing window. Paliperidone palmitate monthly may be used to re-initiate treatment in a injection may be administered 7 days before patient who missed doses of aripiprazole or after the 4-week due date, and paliperidone lauroxil LAI.10 Aripiprazole lauroxil LAI palmitate 3-month LAI can be administered and aripiprazole lauroxil 675 mg should not 14 days before or after the 12-week due date.2,3 be injected together into the same deltoid or Aripiprazole LAI should not be admin- gluteal muscle. istered sooner than 26 days after the previ- ous injection, which means that it can be administered up to 2 days before the 4-week Be mindful of differences in due date.4 If administered after the due dosing windows date, it should be given as soon as possible, Each LAIA has a specific frequency recom- although oral overlap is not needed until ≥7 Current Psychiatry mendation, but due to scheduling or other days past the due date.4 Vol. 19, No. 3 29 continued Table 4 Dosing windows for LAIAs Medication Paliperidone Paliperidone Olanzapine palmitate monthly palmitate Risperidone Aripiprazole LAI Aripiprazole lauroxil LAI pamoate LAI injection 3-month injection Risperidone LAI LAI for SQ Number of days No sooner than 26 No sooner than 14 days after Not specified 7 days 14 days Not specified Not specified Injectable injection can be days after previous previous injection antipsychotics given BEFORE injection due date Number of days As soon as possible; As soon as possible; oral Not specified 7 days 14 days Not specified As soon as injection can be oral overlap needed overlap/starting dose is needed possible given AFTER due for ≥7 days since if it has been ≥2 to 4 weeks date due date since due date (depending on dose and frequency the patient is receiving) LAI: long-acting injectable; LAIAs: long-acting injectable antipsychotics; SQ: subcutaneous Source: References 1-7 Clinical Point

Risperidone LAI for Table 5 SQ is the only LAIA Second-generation LAIAs: Route of administration, injection site, and storage that is administered Medication as an SQ abdominal Aripiprazole Paliperidone Aripiprazole Aripiprazole lauroxil Olanzapine Paliperidone palmitate palmitate Risperidone LAI injection LAI lauroxil LAI 675-mg LAI pamoate LAI monthly injection 3-month injection Risperidone LAI for SQ Route of IM IM IM IM IM IM IM SQ administration Injection site Deltoid Deltoid (441 mg Deltoid or Gluteal Starting doses must be Deltoid Deltoid Abdominal or gluteal only) or gluteal gluteal given in the deltoid, but or gluteal or gluteal (all doses) maintenance doses can be given in the deltoid or gluteal Storage Room Room Room Room Room Room Refrigerated (may Refrigerated (may temperature temperature temperature temperature temperature temperature be kept at room be kept at room temperature for temperature for up to 7 days) up to 7 days) LAI: long-acting injectable; LAIAs: long-acting injectable antipsychotics; SQ: subcutaneous Source: References 1-7,10

Aripiprazole lauroxil LAI has similar managing missed LAIA doses in Current recommendations to aripiprazole LAI in Psychiatry July 2018. This article is available that it should not be administered sooner at mdedge.com/psychiatry/article/168776/ than 14 days after the previous injection.6 If schizophrenia-other-psychotic-disorders/ it is given after the due date, it should be long-acting-injectable.12 administered as soon as possible; oral over- lap/starting dose is needed if it has been ≥2 to 4 weeks since the due date, depending Consider patient preference on which dose and frequency the patient is Patient preference for the type and location receiving.6 of the injection may factor into a clinician’s choice of LAIA (Table 51-7,10). Risperidone LAI for SQ is the only LAIA that is admin- Recommendations for missed doses istered as an SQ abdominal injection.7 All Each LAIA has specific recommenda- other LAIAs are IM injections in the deltoid tions for missed dosing. Carpenter and or gluteal muscle.1-6 All doses of risperidone Current Psychiatry 30 March 2020 Wong12 reviewed the recommendations for LAI, paliperidone palmitate 3-month LAI, Table 4 Table 6 Dosing windows for LAIAs Clinical pearls for LAIAs

Medication Medication Clinical pearls MDedge.com/psychiatry Paliperidone Paliperidone Aripiprazole If patient experiences adverse Olanzapine palmitate monthly palmitate Risperidone LAI reactions to 400-mg dose, Aripiprazole LAI Aripiprazole lauroxil LAI pamoate LAI injection 3-month injection Risperidone LAI LAI for SQ consider reduction to 300 mg Number of days No sooner than 26 No sooner than 14 days after Not specified 7 days 14 days Not specified Not specified Aripiprazole Not interchangeable with injection can be days after previous previous injection lauroxil LAI aripiprazole lauroxil 675-mg LAI given BEFORE injection Aripiprazole Not interchangeable with due date lauroxil aripiprazole lauroxil LAI Number of days As soon as possible; As soon as possible; oral Not specified 7 days 14 days Not specified As soon as 675-mg LAI injection can be oral overlap needed overlap/starting dose is needed possible Olanzapine REMS program: Patients must given AFTER due for ≥7 days since if it has been ≥2 to 4 weeks pamoate LAI be observed for 3 hours after date due date since due date (depending on receiving dose due to risk dose and frequency the patient of PDSS is receiving) LAI: long-acting injectable; LAIAs: long-acting injectable antipsychotics; SQ: subcutaneous Paliperidone Administering the 2 starting Source: References 1-7 palmitate doses in the deltoid muscle monthly helps attain therapeutic injection concentrations rapidly Clinical Point Table 5 Paliperidone Patients should be stable on Most of the second- palmitate paliperidone palmitate monthly Second-generation LAIAs: Route of administration, injection site, and storage 3-month injection for 4 months prior to generation LAIAs can injection starting 3-month LAI Medication be administered in Risperidone When increasing dose, clinical Aripiprazole Paliperidone LAI effects of new dose should the deltoid or gluteal Aripiprazole Aripiprazole lauroxil Olanzapine Paliperidone palmitate palmitate Risperidone LAI not be expected earlier than LAI lauroxil LAI 675-mg LAI pamoate LAI monthly injection 3-month injection Risperidone LAI for SQ muscle 3 weeks after the higher dose Route of IM IM IM IM IM IM IM SQ Risperidone Patients stable on LAI for SQ risperidone dose of <3 or Injection site Deltoid Deltoid (441 mg Deltoid or Gluteal Starting doses must be Deltoid Deltoid Abdominal >4 mg/d may not be candidates or gluteal only) or gluteal gluteal given in the deltoid, but or gluteal or gluteal (all doses) maintenance doses can LAI: long-acting injectable; LAIAs: long-acting injectable antipsychotics; PDSS: post-injection delirium/sedation be given in the deltoid or syndrome; REMS: Risk Evaluation and Mitigation gluteal Strategy; SQ: subcutaneous Storage Room Room Room Room Room Room Refrigerated (may Refrigerated (may Source: References 1-7,10 temperature temperature temperature temperature temperature temperature be kept at room be kept at room temperature for temperature for up to 7 days) up to 7 days) LAI: long-acting injectable; LAIAs: long-acting injectable antipsychotics; SQ: subcutaneous Source: References 1-7,10 may be administered in the deltoid or glu- teal muscle, but all other doses of aripipra- zole lauroxil LAI should be administered only in the gluteal muscle.6 aripiprazole LAI, and aripiprazole lauroxil 675-mg LAI can be administered in the del- toid or gluteal muscle.1,3,4,10 Deltoid admin- Storage istration is required for the 2 starting doses Most LAIAs can be stored at room tem- of paliperidone palmitate monthly injection, perature2-6; however, risperidone LAI and but maintenance doses can be administered risperidone LAI for SQ need to be stored in in the deltoid or gluteal muscle. Because the refrigerator. Both risperidone LAI and administration into the deltoid results in a risperidone LAI for SQ may be kept at room higher concentration of the drug compared temperature for up to 7 days. If they are not with gluteal administration, administering used within 7 days at room temperature, the 2 starting doses of paliperidone palmi- they should be discarded.1,7 tate monthly injection into the deltoid helps to rapidly attain therapeutic concentrations.2 Olanzapine pamoate LAI should be admin- Clinical pearls for specific LAIAs istered only in the gluteal muscle.5 The Aripiprazole LAI. The recommended start- Current Psychiatry 441-mg dose of aripiprazole lauroxil LAI ing and maintenance dose for aripiprazole Vol. 19, No. 3 31 see the clinical effects of the new dose earlier Related Resources than 3 weeks after initiating the higher dose, • Correll CU, Citrome L, Haddad PM, et al. The use of because the main release of the medication long-acting injectable antipsychotics in schizophrenia: 1 evaluating the evidence. J Clin Psychiatry. 2016;77(suppl starts at 3 weeks after the injection. 3):1-24. Risperidone LAI for SQ has specific • Peters L, Krogmann A, von Hardenberg L, et al. Long-acting recommendations for the LAI dose based injections in schizophrenia: a 3-year update on randomized controlled trials published January 2016-March 2019. Curr on whether the patient was stable when Injectable Psychiatry Rep. 2019;21(12):124. receiving 3 or 4 mg/d of oral risperidone. If antipsychotics Drug Brand Names patients are stable on <3 or >4 mg/d, they Aripiprazole • Abilify Paliperidone palmitate may not be candidates for risperidone LAI Aripiprazole long-acting monthly long-acting for SQ.7 injectable • Abilify Maintena injection • Invega Sustenna 1-7,10 Aripiprazole lauroxil Paliperidone palmitate Table 6 (page 31) lists additional fac- extended-release injectable 3-month injection tors to consider when prescribing a spe- • Aristada • Invega Trinza Aripiprazole lauroxil Risperidone • Risperdal cific LAIA. 675 mg • Aristada Initio Risperidone long-acting Olanzapine pamoate injection • Risperdal Consta References long-acting injection Risperidone long-acting 1. Risperdal Consta [package insert]. Titusville, NJ: Janssen Clinical Point • Zyprexa Relprevv injection for SQ • Perseris Pharmaceuticals, Inc.; 2019. 2. Invega Sustenna [package insert]. Titusville, NJ: Janssen Olanzapine pamoate Pharmaceuticals, Inc.; 2019. 3. Invega Trinza [package insert]. Titusville, NJ: Janssen LAI has a REMS due Pharmaceuticals, Inc.; 2019. to the potential LAI is 400 mg monthly, unless the patient 4. Abilify Maintena [package insert]. Rockville, MD: Otsuka America Pharmaceutical, Inc.; 2019. for post-injection has drug interactions or other factors that 5. Zyprexa Relprevv [package insert]. Indianapolis; IN: Eli require dose adjustment. If patients expe- Lilly and Co.; 2019. delirium/sedation 6. Aristada [package insert]. Waltham, MA: , rience adverse reactions to the 400-mg syndrome Inc.; 2019. dose, a reduction to 300 mg monthly could 7. Perseris [package insert]. North Chesterfield, VA: Indivior, be considered.4 Inc.; 2018. 8. Kishimoto T, Robenzadeh A, Leucht C, et al. Long-acting Olanzapine pamoate LAI has a Risk injectable vs oral antipsychotics for relapse prevention Evaluation and Mitigation Strategy (REMS) in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull. 2014;40(1):192-213. due to the potential for post-injection delir- 9. Kishimoto T, Nitta M, Borenstein M, et al. Long-acting ium/sedation syndrome (PDSS). Prescribing injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image clinicians, dispensing pharmacies, and studies. J Clin Psychiatry. 2013;74(10):957-965. administering health care facilities must all 10. Aristada Initio [package insert]. Waltham, MA: Alkermes, Inc.; 2019. be certified to prescribe, dispense, or admin- 11. Jain R, Meyer J, Wehr A, et al. Size matters: the impor- ister olanzapine pamoate LAI. The patient tance of particle size in a newly developed injectable for- mulation for the treatment of schizophrenia. CNS Spectr. must also be enrolled in the REMS pro- 2019:1-8. gram.13 Patients must be observed by health 12. Carpenter J, Wong KK. Long-acting injectable antipsychotics: what to do about missed doses. Current Psychiatry. care staff for 3 hours after receiving a dose 2018;17(7):10-12,14-19,56. of olanzapine pamoate LAI to monitor for 13. US Food and Drug Administration. Approved Risk 5 Evaluation and Mitigation Strategies (REMS) zyprexa signs and symptoms of PDSS. relprevv (olanzapine). https://www.accessdata.fda.gov/ Risperidone LAI. When increasing the scripts/cder/rems/index.cfm?event=IndvRemsDetails. page&REMS=74. Updated April 11, 2019. Accessed dose of risperidone LAI, do not expect to January 27, 2020.

Bottom Line Second-generation long-acting injectable antipsychotics (LAIAs) have the potential to increase medication adherence. There are important differences among the 7 currently available LAIAs. For effective prescribing, clinicians need to understand each medication’s unique aspects, including dosing options, frequency, need for Current Psychiatry 32 March 2020 oral antipsychotic overlap, and route of administration.