Long-acting injectable antipsychotics during COVID-19 How to determine if your patient should continue an LAI, and how to do so safely

Kristina Schnitzer, MD ong-acting injectable antipsychotics (LAIs) are an essential tool Fellow, Public and Community Psychiatry Massachusetts General Hospital in the treatment of patients with psychotic disorders, allowing Boston, Massachusetts for periods of stable drug plasma concentration and confirmed L 1 Sarah MacLaurin, PMHNP-BC adherence. The current coronavirus disease 2019 (COVID-19) pan- Freedom Trail Clinic of North Suffolk Mental demic presents unique challenges for administering LAIs and requires Health Association a thoughtful and prospective approach in order to ensure continuity of Massachusetts General Hospital Boston, Massachusetts psychiatric care while minimizing the risk of infection with COVID-19. Oliver Freudenreich, MD, FACLP Ideally, patients should be seen in person as infrequently as clinically Co-Director, MGH Schizophrenia Clinical and prudent during this public health emergency; however, LAI administra- Research Program tion necessitates direct physical contact between patient and clinician. Associate Professor of Psychiatry Harvard Medical School Patients with serious mental illness (SMI), who comprise the majority Boston, Massachusetts of individuals who receive LAIs, are at heightened risk for cardiovascu- Disclosures lar and pulmonary comorbidities. These factors are the primary reason Dr. Freudenreich has received grant or research support the life expectancy of a patient with SMI is nearly 30 years shorter than from Alkermes, Avanir, Janssen, Otsuka, and Saladax, 2-5 and has served as a consultant to Alkermes, Janssen, that of the general population. The risk of health care workers becom- Neurocrine, Novartis, and Roche. Drs. Schnitzer and ing infected or inadvertently spreading COVID-19 is heightened when MacLaurin report no financial relationships with any companies whose products are mentioned in this article, working with patients in group living environments (ie, a shelter or or with manufacturers of competing products. group home), who have both increased exposure and increased risk of doi: 10.12788/cp.0087 further transmission.6 Additional patient populations, including older adults, immunocompromised individuals, and those with preexisting conditions, are at heightened risk for serious complications if they were to contract COVID-19.7,8 Thus, the questions of whether LAIs should be administered, and how to do so safely (both during the ongoing, acute phase of the pan- demic as well as during the subsequent recovery period until the pan- demic abates) need to be carefully considered. In this article, we provide concrete advice for clinicians and clinics on these topics, with the goal of

Current Psychiatry

GARY WATERS GARY Vol. 20, No. 2 9 Table 1 environment and health-vulnerability Considerations for LAI of the patient and the individuals living administration during COVID-19 with them. If the risk calculation does not point Should an LAI be continued? strongly towards a need for continuing Which LAI should be administered? the LAI, it may be prudent to temporar- When should the LAI be administered? ily transition the patient to the corre- LAIs during Where can the LAI be administered? sponding oral antipsychotic preparation. COVID-19 Who can administer the LAI? Table 2 (page 11) lists all LAIs available in the United States and their approximate What safety measures can be put in place to minimize risk to all parties? equivalent oral dosing. It is important to COVID-19: coronavirus disease 2019; LAI: long-acting note that such transitions are not without injectable antipsychotic clinical risk, to emphasize to the patient that the transition is intended as a tempo- rary measure, and to discuss a proposed timeline for re-initiating the LAI. Also, Clinical Point maintaining patients’ psychiatric stability emphasize to the patient and family that In some cases, it while protecting patients, health care work- this transition does not diminish the pre- ers, and the broader society from COVID-19 vious reasoning for needing an LAI, but may be prudent to infection. Table 1 summarizes the ques- is a temporary measure taken in light of temporarily transition tions regarding LAIs that clinicians need to weighing the risks and benefits during a the patient to the address during this crisis. While we focus pandemic. corresponding on outpatient care, inpatient teams should keep these considerations in mind if they oral antipsychotic are starting and discharging a patient on Which LAI should be preparation an LAI. More than ever, close collaboration administered? and communication between inpatient and If continuing the LAI is determined to be outpatient teams is critical. clinically necessary, consider switching the patient to a longer-acting preparation to maximize intervals between administra- Should an LAI be continued? tions and minimize the potential for infec- An important first step to approaching tion. From a public health perspective, the this challenge is to create a spreadsheet longest clinically prudent interval between for all patients receiving LAIs. Focusing injections may be the most important con- on a population-based approach is help- sideration, provided the patient can receive ful to be systematic and ensure that no a dose necessary to retain stability, and the patients fall through the cracks during LAI should be chosen accordingly. Deltoid this public health emergency.9 Once all injections may be able to be administered patients have been identified, the treat- with reduced contact, or on a “drive-up” ment team should review each patient to basis.10 Consider transitioning a patient determine if continuing to administer the who is receiving olanzapine pamoate antipsychotic as an LAI formulation is to an alternate LAI or oral formulation, essential, taking into account the patient’s because the 3-hour observation period current psychiatric status, historical medi- that is required after olanzapine pamoate cation adherence, potential severity and administration is particularly problematic. Discuss this article at dangerousness of decompensation if While it may not be ideal to make medica- www.facebook.com/ nonadherent, and structures to support tion changes during a pandemic, it is worth MDedgePsychiatry stability. For example, can a patient move carefully weighing the patient’s stability in with family who can monitor medica- and historical experience with other LAIs to tion adherence during the pandemic? Is determine if a safer/longer-spaced option it possible for the group home to assume is worth trying.11 medication administration? Additional We recommend only switching among Current Psychiatry 10 February 2021 consideration should be given to the living similar antipsychotics (ie, risperidone to Table 2 Long-acting injectable antipsychotics and equivalent oral dosing

Medication Dosing schedule MDedge.com/psychiatry Abilify Aristada 882 mg 1,064 mg 882 mg 662 mg 441 mg q4wks q8wks q6wks q4wks q4wks Abilify Maintena 400 mg 300 mg 300 mg 300 mg 200 mg q4wks q4wks q4wks q4wks q4wks Abilify (PO) 20 mg 15 mg 15 mg 15 mg 10 mg Fluphenazine decanoate 25 mg 12.5 mg q3wks q2wks Fluphenazine (PO) 20 mg 10 mg Haldol decanoate 200 mg 100 mg q4wks q4wks Haldol (PO) 20 mg 10 mg Invega Trinza 819 mg 546 mg 410 mg 273 mg q12wks q12wks q12wks q12wks Invega Sustenna 234 mg 156 mg 117 mg 78 mg 39 mg Clinical Point q4wks q4wks q4wks q4wks q4wks If an LAI is necessary, Invega (PO) 12 mg 9 mg 6 mg 3 mg 1.5 mg consider switching Risperdal Consta 50 mg 37.5 mg 25 mg 12.5 mg q2wks q2wks q2wks q2wks to a longer-acting Perseris (subcutaneous) 120 mg 90 mg preparation q4wks q4wks to maximize Risperidone (PO) 4 mg 3 mg 2 mg 1 mg Zyprexa Relprevv 300 mg 405 mg 210 mg 300 mg 150 mg intervals between q2wks q4wks q2wks q4wks q2wks administrations Zyprexa (PO) 20 mg 15 mg 15 mg 10 mg 10 mg Source: Adapted from reference 1 PO: by mouth; q2wks: once every 2 weeks; q3wks: once every 3 weeks; q4wks: once every 4 weeks; q8wks: once every 8 weeks; q12wks: once every 12 weeks

paliperidone), or between different prepara- with oral medications. For patients who tions of the same drug (ie, Abilify Maintena are in quarantine, it may be better to delay to Aristada), if possible, as these are the low- an injection until the patient ends their est risk transitions with regards to relapse. quarantine than to deliver the dose dur- Table 3 (page 12) provides examples. ing quarantine. Administering an injec- tion earlier also is usually safe; off-cycle visits may help minimize patient contact When should the LAI be (ie, if the patient happens to be coming administered? into the vicinity of the clinic, or requires The pharmacokinetics of LAIs allow for phlebotomy for therapeutic drug monitor- some flexibility in terms of when an LAI ing), and assist in planning for possible needs to be administered. The package resurgences. When appropriate, and after inserts of all second-generation LAIs considering the risk of worsening adverse include missed-dose guidelines. These effects, administering a higher dose than guidelines provide information on how the usual maintenance dose would pro- long one can wait before the next injec- vide a buffer if the next injection was to tion is due, and what additional measures be delayed. Therapeutic drug monitoring must be taken when beyond that date. can help to optimize dosing and avoid low Delaying an injection may be prudent, and plasma drug levels, which may be not be the missed dose guidelines will indicate sufficient, particularly during this time Current Psychiatry when one must consider supplementing of stress.12 To provide optimal protection Vol. 20, No. 2 11 Table 3 Considerations for longer-interval LAIs If patient is currently receiving: Consider: Abilify Maintena or q1mo Aristada q2mo Aristada Invega Sustenna Invega Trinza Risperdal Consta Invega Sustenna or Trinza LAIs during Haldol 100 mg q2wks Haldol 200 mg q4wks COVID-19 LAIs: long-acting injectable antipsychotics; q1mo: once every month; q2mo: once every 2 months; q2wks: once every 2 weeks; q4wks: once every 4 weeks

against relapse, consider administering a telehealth or from an acceptable distance. dose that puts patients at the higher range Medication should be drawn ahead of of plasma drug levels. time, and not in an enclosed space with the patient present. Strongly consider aban- Clinical Point doning the traditional enclosed room for Patients might be Where can the LAI be administered, the injection, and instead use larger spaces, and who can give it? doorways, or outside, if feasible. As previ- able to receive an For patients who usually travel to a clinic, ously noted, some clinics and clinicians LAI via a visiting consider arranging for a more local injec- have used a drive-up approach for LAI nurse association or tion (ie, at the patient’s primary care clinic administration, particularly for deltoid at their pharmacy in their hometown, or at a local mental injections.10 Individuals who administer health center), and explore if the patient the injections should wear personal pro- may be able to receive their injection in their tective equipment, and the clinic should home through a visiting nurse association obtain an adequate supply of this equip- (VNA). In many states (approximately 30 ment well in advance. currently), clinicians at pharmacies are also able to administer patient injections. Clinics would do well to at least plan for alternate Lessons learned at our clinic staffing models in the event of staff illness. In our community mental health center A pool of individuals should be available to clinic, planning around these questions has give injections; consider training additional allowed us to provide safe and continu- staff members (including MDs who may ous psychiatric care with LAIs during this have never previously administered an LAI public health emergency while reducing but could be quickly instructed to do so) the risk of infection. We have worked to to administer LAIs. Theoretically, during a transfer LAI administration to VNAs and public health emergency, family members, transition patients to longer-lasting formu- particularly those who have a background lations or oral medications where appropri- in health care, could be trained to give an ate, which has resulted in an approximately injection and provided education on LAI 50% decrease in in-person visits. Reducing storage and post-injection monitoring. This the number of in-person visits does not approach would not be consistent with need to result in less frequent clinical fol- FDA labeling, however, and should only be low-up. Telepsychiatry visits can make up considered as a last resort. for lost in-person visits and have generally been well accepted. As we are preparing for the next phase, What safety measures can be put routine medical health monitoring (eg, in place? metabolic monitoring, monitoring for tar- Face-to-face time for injection administra- dive dyskinesia) that has not been at the tion should be kept as brief as possible. forefront of concerns should be carefully Before the encounter, obtain the patient’s reintroduced. Challenges encountered have Current Psychiatry 12 February 2021 clinical information, ideally through included difficulty in having VNA accept patients for short-term LAI visits, changes to where on the body the injection is deliv- Related Resources ered, and patients with SMI and their fami- • American Association of Community Psychiatrists. Clinical Tip Series. Long acting antipsychotic medications. MDedge.com/psychiatry lies being reluctant to depart from previous https://drive.google.com/file/d/1unigjmjFJkqZMbaZ_ routines and administration schedules. ftdj8oqog49awZs/view?usp=sharing There is great value in the collective • SMI Adviser. What are clinical considerations for giving LAIs during the COVID-19 public health emergency? lessons learned during this public health https://smiadviser.org/knowledge_post/what-are-clinical- emergency (eg, the need for a flexible, pop- considerations-for-giving-lais-during-the-covid-19-public- health-emergency ulation health-based approach; acceptabil- • CDC. Infection control basics. https://www.cdc.gov/ ity of combination telehealth and in-person infectioncontrol/basics/index.html visits) that can lead to more person-centered Drug Brand Names and accessible care for patients with SMI. Aripiprazole • Abilify Paliperidone palmitate Acknowledgments Aripiprazole for extended- extended-release The authors thank North Suffolk Mental Health Association, the release injectable suspension • injectable suspension • Freedom Trail Clinic, and their patients. Abilify Maintena Invega Sustenna Aripiprazole lauroxil • Aristada Paliperidone palmitate Haloperidol • Haldol extended-release injectable References Haloperidol injection • suspension • Invega Trinza 1. Freudenreich O. Long-acting injectable antipsychotics. Haldol decanoate Risperidone • Risperdal Clinical Point In: Freudenreich O. Psychotic disorders: a practical guide. Olanzapine • Zyprexa Risperidone for extended- Springer; 2020:249-261. Olanzapine for release injectable Consider abandoning 2. Olfson M, Gerhard T, Huang C, et al. Premature mortality extended-release injectable suspension • Perseris among adults with schizophrenia in the United States. suspension • Zyprexa Relprevv Risperidone injection • the traditional JAMA Psychiatry. 2015;72(12):1172-1181. Paliperidone • Invega Risperdal Consta 3. Reilly S, Olier I, Planner C, et al. Inequalities in physical enclosed room comorbidity: a longitudinal comparative cohort study of people with severe mental illness in the UK. BMJ Open. for administering 2015;5(12):e009010. an LIA, and use 4. Brown S, Inskip H, Barraclough B. Causes of the excess mortality of schizophrenia. Br J Psychiatry. 2000;177:212-217. larger spaces 5. Goff DC, Cather C, Evins AE, et al. Medical morbidity and 10. Chepke C. Drive-up pharmacotherapy during the mortality in schizophrenia: guidelines for psychiatrists. COVID-19 pandemic. Current Psychiatry. 2020;19(5): J Clin Psychiatry. 2005;66(2):183-194. 29-30. 6. Baggett TP, Keyes H, Sporn N, et al. Prevalence of SARS- 11. Sajatovic M, Ross R, Legacy SN, et al. Initiating/ CoV-2 infection in residents of a large homeless shelter in maintaining long-acting injectable antipsychotics in Boston. JAMA. 2020;323(21):2191-2192. schizophrenia/schizoaffective or bipolar disorder - 7. CDC COVID-19 Response Team. Severe outcomes among expert consensus survey part 2. Neuropsychiatr Dis Treat. patients with coronavirus disease 2019 (COVID-19)— 2018;14:1475-1492. United States, February 12–March 16, 2020. MMWR Morb 12. Schoretsanitis G, Kane JM, Correll CU, et al; Mortal Wkly Rep. 2020;69(12):343-346. American Society of Clinical Psychopharmacology, 8. Docherty AB, Harrison EM, Green CA, et al. Features of Pharmakopsychiatrie TTDMTFOTAFNU. Blood levels 20 133 UK patients in hospital with covid-19 using the ISARIC to optimize antipsychotic treatment in clinical practice: WHO Clinical Characterisation Protocol: prospective a joint consensus statement of the American Society of observational cohort study. BMJ. 2020;369:m1985. doi: Clinical Psychopharmacology and the Therapeutic Drug 10.1136/bmj.m1985 Monitoring Task Force of the Arbeitsgemeinschaft für 9. Etches V, Frank J, Di Ruggiero E, et al. Measuring population Neuropsychopharmakologie und Pharmakopsychiatrie. health: a review of indicators. Annu Rev Public Health. J Clin Psychiatry. 2020;81(3):19cs13169. doi: 10.4088/ 2006;27:29-55. JCP.19cs13169

Bottom Line When caring for a patient with a psychotic illness during the coronavirus disease 2019 (COVID-19) pandemic, evaluate whether it is necessary to continue a long- acting injectable antipsychotic (LAI). If yes, reconsider which LAI should be administered, when and where it should be given, and by whom. Implement safety Current Psychiatry measures to minimize the risk of COVID-19 exposure and transmission. Vol. 20, No. 2 13