899

Organizational Barriers to Using Long-Acting Injectable Antipsychotics in Practice

​John M. Kane, MD

Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks; the Department of Psychiatry, Hofstra North Shore-Long Island Jewish School of Medicine, Uniondale; and Behavior Health Services, North Shore-Long Island Jewish Health System, New Hyde Park, New York

Schizophrenia is a chronic illness from which patients generally do not completely recover.1 Furthering the challenges for recovery is the high risk of relapse, which can increase hospitalization rates and health care costs.2 A main cause of relapse in patients with schizophrenia is the lack of adherence to oral medications, which can be a result of the patient’s lack of understanding of the illness and the need for continuous treatment, an overly complex treatment regimen, the patient’s cognitive impairment, and a disorganized home environment.3 Physicians must regularly ask patients about their medication-taking habits and address any identified problems with adherence on an individual basis. One solution is the use of long-acting injectable (LAI) antipsychotics. If adherence is improved with LAI antipsychotic treatment, then the resulting decrease in relapses and rehospitalizations can potentially keep overall health care costs lower than with oral antipsychotic treatment (AV 1).1,4–6

AV 1. Hospitalization and Relapse Rates and Costs for Patients With Schizophrenia Using LAI Vs Oral Antipsychotics (N = 788) (00:35)

Data from Olivares et al5

Guidelines for LAI Antipsychotic Use

Several guidelines exist for the use of LAI antipsychotics, with similar recommendations.7–9 The best candidates for treatment with these agents are patients with recurrent relapses related to nonadherence or those who prefer LAI formulations. Because LAIs can take longer to reach a stable steady state than oral antipsychotics, they are generally used more often in the maintenance phase than in the acute phase. However, a transition from an oral to an injectable formulation can begin early in treatment if adherence is problematic.7

Despite guideline recommendations to prescribe LAI antipsychotics for schizophrenia, they are infrequently used in the United States, in part due to numerous organizational barriers.1,10

Organizational Barriers

Leadership buy-in and logistics. One barrier stems from a lack of understanding on the part of organizational leadership about the potential advantages of LAI antipsychotics. Without buy-in from leaders, organizations cannot provide the financial support and infrastructure needed to acquire and store these medications. Additionally, LAI antipsychotics require logistical planning, since only qualified medical technicians can prepare and administer the injections.10 If an organization does not designate a nurse or technician for that role, physicians would then have to locate someone trained to provide the injection or administer it themselves. Further, clinics must have a well-trained staff who all agree on the effectiveness of LAI antipsychotics and can promote a streamlined approach for administering them to patients and answering patient and caregiver questions about the medications in a positive manner. Having even one member of the treatment team who discourages the patient from using an LAI antipsychotic can undermine the entire treatment plan.

Physicians’ concerns. Because LAI antipsychotics are costly, their use may be fiscally challenging for many patients.10 Other factors that might discourage doctors from prescribing LAIs include the patient’s refusal (actual or anticipated) to try this method of treatment, few second-generation antipsychotics in this formulation, the perceived inconvenience of the injection procedure, the perception of interference with patient’s autonomy, complexity of the dosing strategy, and injection-site side effects.2

AV 2. Physician Concerns Over LAI Antipsychotics (02:35)

 

Physicians who determine whether or not to use LAI drugs must believe in the value of such treatments for particular patients (AV 2). Once physicians feel comfortable with using LAI antipsychotics and discussing them with patients, they, in turn, can help patients feel comfortable with the concept. Physicians must explain, with conviction, the importance of adherence and the benefits of LAI medications to the patient. Motivational interviewing skills may be needed.3 Physicians must also be able to answer questions and return to this conversation over time because the choice to use an LAI medication may be decided over multiple visits. In clinical experience, most patients are ultimately willing to accept a therapeutic trial of an LAI.

More

Efficacy of LAI Antipsychotics

Antipsychotic treatment can prevent relapse, and, conversely, failure to take medication as prescribed is a strong predictor for relapse.2 A review3 of studies of nonadherence to medication among patients with psychotic disorders showed nonadherence rates of 12% to 58% in naturalistic studies and 2% to 37% in RCTs. In clinical practice, both patients and physicians may overestimate the level of medication adherence.11 Not recognizing adherence problems can contribute to physicians’ hesitation in prescribing LAI antipsychotics.2

Studies of LAI versus oral antipsychotics have shown mixed results regarding adherence and relapse; however, study design can influence these results.12 For example, some studies exclude nonadherent patients, which reduces the possibility of showing benefit of LAI medications in this patient population.13 In fact, a meta-analysis14 of RCTs failed to show superior efficacy of LAI antipsychotics over oral antipsychotics; the analysis used relapse prevention as the outcome measure. Other types of studies, though, show opposite results. A meta-analysis15 of mirror-image studies demonstrated decreased hospitalizations with LAI medications compared with oral agents. A nationwide cohort study16 also showed stronger efficacy of LAIs over oral antipsychotics in preventing rehospitalization. Patients consenting to RCTs might not be representative of those prescribed LAIs in real-world settings, particularly with increasing stringency of consent processes. Because adherence among patients in RCTs tends to be better than that in the real world, RCTs may not be the ideal way to study whether LAI antipsychotics can improve adherence.17

Conclusion

Patients with schizophrenia may benefit from using LAI antipsychotics if they have a problem taking oral agents daily. By increasing medication adherence, these agents have the potential to reduce relapse and rehospitalization. Organizational barriers to using LAIs are the main obstacles to prescribing them. In addition to cost, storage, and issues related to administering the drugs, physicians’ and the treatment team’s lack of knowledge and hesitation about using LAIs are also hurdles to overcome. Patients may initially be reluctant to try LAI antipsychotics, but if the physician is able to confidently discuss the treatment during a series of visits, patients may be willing to try LAIs as time goes on. Psychiatric practices of all types must be able to train the staff appropriately regarding the use and administration of LAI medications, which require resources and time. Once clinicians and staff better understand the benefits of LAI antipsychotics and address organizational barriers to their use, they can better help patients with schizophrenia who are struggling with adherence to avoid relapse and rehospitalization.

Clinical Points

  • When possible, address organizational barriers regarding LAI medications
  • Explain to patients that LAI antipsychotics can help with medication adherence and reduce relapse and rehospitalization
  • Consider study design when examining results of trials of LAIs and oral medication

Abbreviations

LAI = long-acting injectable

RCT=randomized controlled trial

References

  1. 1. Kaplan G, Casoy J, Zummo J. Impact of long-acting injectable antipsychotics on medication adherence and clinical, functional, and economic outcomes of schizophrenia. Patient Pref Adher. 2013;7:1171–1180. PubMed
  2. 2. Wehring HJ, Thedford S, Koola M, et al. Patient and health care provider perspectives on long-acting injectable antipsychotics in schizophrenia and the introduction of olanzapine long-acting injection. J Cent Nerv Syst Dis. 2011;2011(3):107–123. PubMed
  3. 3. Kane JM, Kishimoto T, Correll CU. Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies. World Psychiatry. 2013;12(3):216–226. PubMed
  4. 4. Peuskens J, Olivares JM, Pecenak J, et al. Treatment retention with risperidone long-acting injection: 24-month results from the Electronic Schizophrenia Treatment Adherence Registry (e-STAR) in six countries. Curr Med Res Opin. 2010;26(3):201–509. PubMed
  5. 5. Olivares JM, Rodriguez-Martinez A, Buron JA, et al. Cost-effectiveness analysis of switching antipsychotic medication to long-acting injectable risperidone in patients with schizophrenia: a 12- and 24-month follow-up from the e-STAR database in Spain. Appl Health Econ Health Policy. 2008;6(1):41–53. PubMed
  6. 6. Olivares JM, Rodriguez-Morales A, Diels J, et al. Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR). Eur Psychiatry. 2009;24(5):287–296. PubMed
  7. 7. Lehman AF, Lieberman JA, Dixon LB, et al. Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Published February 2004. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1665359. Accessed December 5, 2013.
  8. 8. Kreyenbuhl J, Buchanan RW, Dickerson FB, et al. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophr Bull. 2010;36(1):94–103. PubMed
  9. 9. National Institute for Health and Care Excellence. Schizophrenia: core interventions in the treatment and management of schizophrenia in adults in primary and secondary care. http://egap.evidence.nhs.uk/schizophrenia-cg82. Published March 2009. Accessed December 5, 2013.
  10. 10. Getzen H, Beasley M, D’Mello DA. Barriers to utilizing long-acting injectable antipsychotic medications. Ann Clin Psychiatry. 2013;25(4):E1–E6. PubMed
  11. 11. Velligan DI, Weiden PJ, Sajatovic M, et al. Assessment of adherence problems in patients with serious and persistent mental illness: recommendations from the Expert Consensus Guidelines. J Psychiatr Pract. 2010;16(1):34–45. PubMed
  12. 12. Kirson NY, Weiden PJ, Yermakov S, et al. Efficacy and effectiveness of depot versus oral antipsychotics in schizophrenia: synthesizing results across different research designs. J Clin Psychiatry. 2013;74(6):568–575. Full Text
  13. 13. Leucht C, Heres S, Kane JM, et al. Oral versus depot antipsychotic drugs for schizophrenia: a critical systematic review and meta-analysis of randomised long-term trials. Schizophr Res. 2011;127(1–3):83–92. PubMed
  14. 14. Kishimoto T, Robenzadeh A, Leucht C, et al. Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull. 2014;40(1):192–213. PubMed
  15. 15. Kishimoto T, Nitta M, Borenstein M, et al. Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. J Clin Psychiatry. 2013;74(10):957–965. Abstract
  16. 16. Tiihonen J, Haukka J, Taylor M, et al. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry. 2011;168(6):603–609. PubMed
  17. 17. Kane JM, Kishimoto T, Correll CU. Assessing the comparative effectiveness of long-acting injectable vs. oral antipsychotic medications in the prevention of relapse provides a case study in comparative effectiveness research in psychiatry. J Clin Epidemiol. 2013;66(8 suppl):S37–S41. PubMed
​​​​​