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Patient Outcomes Within Schizophrenia Treatment: A Look at the Role of Long-Acting Injectable Antipsychotics

Rimal B. Bera, MD
What Is Compliance?

In medicine, compliance refers to a patient following the treatment recommendation of the doctor. Compliance is a critical issue across all chronic conditions, including schizophrenia. It is critical to remember that compliance is not an all-or-nothing phenomenon. Patients with illnesses that require regular dosing of medications may vary in compliance in a spectrum from taking all medications as prescribed to partial compliance or complete noncompliance.1 Partial compliance is common in all long-term diseases and is a serious underappreciated problem.2,3 For the patient with schizophrenia, the potential consequences of poor compliance can include relapse and hospitalization, demoralization, loss of confidence, loss of job, family discord, and finally danger to self or others.4 The risk of relapse in first-episode patients has been shown to increase almost 5-fold (risk ratio = 4.89) when antipsychotic drug treatment was discontinued.5 Thus, there is a critical need to ensure continuous delivery of antipsychotic treatment for schizophrenia patients with a minimum of treatment interruptions.

Moving From Compliance to Adherence to Alliance: Did the Advent of Atypical Antipsychotics Introduce Change?

Given the potential connotation of the word compliance, the term adherence has been substituted. From a medical standpoint, adherence means that patients must constantly maintain their therapeutic regimen.

Atypical antipsychotic medications were expected to result in better adherence, primarily because of the improved efficacy and safety profile.6 However, atypical agents have poor adherence, irrespective of the type of atypical medication, making it difficult to predict who was taking their oral medications.7

Clinical Observations Regarding Potential Advantages and Obstacles of LAI Antipsychotics

Long-acting injectable (LAI) agents were found to minimize the fluctuations in peak and overall plasma levels compared with oral agents, indicating that they may provide more consistent and predictable administration.8 Based on clinical observation, there are several potential advantages in using LAIs: (1) dosage deviations are reduced; (2) guessing about adherence status is eliminated; (3) a start date of adherence/nonadherence can be documented; (4) they aid in disentangling reasons for poor response to medication; (5) the possible need for the patient to remember to take a pill daily is eliminated; (6) prescribers can avoid first-pass metabolism; (7) plasma levels are predictable and stable; (8) abrupt loss of efficacy from a missed dose is eliminated; and (9) possible patient preference.

There are, however, several potential obstacles to the use of LAIs that have been observed in our clinical experience, including a lack of infrastructure for the delivery and removal of injectables and the ease of use compared with the oral agents.

Switching from Oral to LAI Antipsychotic Medication

There are several strategies we have used in our clinical practice to assist in switching patients from oral antipsychotic medications to LAIs. Strategies to improve acceptance involve presenting the option with enthusiasm, ensuring proper goal setting, separating the timing of injections to minimize anxiety, educating the patient that this is not equivalent to emergency injections, and repeatedly recommending LAI therapy. Adherence can be improved by ensuring samples are available at all times.

CONCLUSIONS

Compliance is an important consideration for all chronic conditions, including schizophrenia. Partial compliance represent a serious problem that can result in abrupt dose changes leading to adverse effects and diminished efficacy, suggesting that it is important to ensure continuous delivery of schizophrenia medication. LAI agents have particular promise in minimizing the fluctuations in plasma levels associated with oral agents. Although these agents have a variety of advantages such as reducing dosage deviations, there may be obstacles to the use of LAIs, including a lack of infrastructure in clinical settings. Based on my clinical experience, several strategies have been developed that may increase the patient’s willingness to both initiate and continue LAI therapy. These include ensuring clinician enthusiasm about the treatment, minimizing anxiety surrounding injections, and informing patients that LAI therapy is not equivalent to emergency injections.

References
  1. Kane JM, Aguglia E, Altamura AC, et al. Eur Neuropsychopharmacol. 1998;8(1):55–66.doi:10.1016/S0924-977X(97)00045-X PubMed
  2. Cramer JA, Rosenheck R. Psychiatr Serv. 1998;49(2):196–201. PubMed
  3. Costa FV. Clin Exp Hypertens. 1996;18(3–4):463–472.doi:10.3109/10641969609088977 PubMed
  4. Keers R, Ullrich S, Destavola BL, et al. Am J Psychiatry. 2014;171(3):332–339.doi:10.1176/appi.ajp.2013.13010134 PubMed
  5. Robinson D, Woerner MG, Alvir JM, et al. Arch Gen Psychiatry. 1999;56(3):241–247.doi:10.1001/archpsyc.56.3.241 PubMed
  6. Markowitz JS, Brown CS, Moore TR. Ann Pharmacother. 1999;33(1):73–85.doi:10.1345/aph.17215 PubMed
  7. Dolder CR, Lacro JP, Dunn LB, et al. Am J Psychiatry. 2002;159(1):103–108.doi:10.1176/appi.ajp.159.1.103 PubMed
  8. Eerdekens M, Resmussen M, Vermeulen A, et al. Biol Psychiatry. 2000;47(8):S31. doi:10.1016/S0006-3223(00)00364-4
Rimal B. Bera, MD

Rimal B. Bera, MD

Department of Psychiatry and Human Behavior, University of California, Irvine

This Brief Report is derived from the roundtable meeting “Understanding the lifetime course of schizophrenia: a longitudinal perspective on neurobiology to promote better outcomes and recovery,” which was held October 15, 2013. The author acknowledges Healthcare Global Village for editorial assistance in developing the manuscripts.

The meeting, manuscript preparation, and dissemination of this brief report were supported by Otsuka America Pharmaceutical, Inc., and Lundbeck. All faculty received a fee for service from Otsuka America Pharmaceutical, Inc., and Lundbeck for participation in the meeting and preparation of the manuscripts.

Faculty Disclosure

Dr Bera received a fee for service from Otsuka America Pharmaceutical, Inc., and Lundbeck for participation in the meeting and preparation of this manuscript; has received grant/research support from Novartis and Otsuka America Pharmaceutical, Inc.; and has been on the speakers/advisory boards of Novartis, Otsuka America Pharmaceutical, Inc., AstraZeneca, Forest, Sunovion, and Teva.

Acknowledgment

The opinions expressed herein are those of the authors and do not necessarily reflect the opinions of the publisher, the American Society of Clinical Psychopharmacology, Healthcare Global Village, or the commercial supporters.

doi: 10.4088/JCP.13065br6

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