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Barriers to utilizing long-acting injectable antipsychotic medications

Hayley Getzen, MPH

Wayne State University, School of Medicine, Detroit, Michigan, USA

Marie Beasley, DO

Department of Psychiatry, Michigan State University, East Lansing, Michigan, USA

Dale A. D’Mello, MD

Department of Psychiatry, Michigan State University, East Lansing, Michigan, USA

BACKGROUND: Long-acting injectable (LAI) antipsychotic medications are superior to their oral equivalents in reducing relapse, yet schizophrenia treatment guidelines favor oral formulations. A minority of eligible patients receive LAI preparations in the United States. The purpose of the present study is to examine barriers faced by psychiatrists in implementing the use of LAI antipsychotics.

METHODS: An internet survey sent to Michigan State University-affiliated psychiatrists examined psychiatrists’ practice locations and characteristics, access, opinions, and barriers to utilizing LAI antipsychotic medications in patients with schizophrenia. Thirty-six psychiatrists completed the survey.

RESULTS: Thirty-three psychiatrists (83%) acknowledged having patients in their practices who would benefit from LAI antipsychotics; however, only 22 (61%) had the capacity to utilize these formulations. Barriers to utilizing LAI antipsychotic medications included: 1) lack of ancillary support at the practice location; 2) personal preference for oral compounds; and 3) limited insurance coverage. Psychiatrists who had the capability of administering LAI antipsychotic compounds were 10 times more likely to utilize them when compared with others who lacked the capacity to do so (9.67% [SD=10] vs 1.43% [SD=3]; df=1; F=8.59; P < .005).

CONCLUSIONS: Psychiatrists practicing in Michigan face formidable barriers to utilizing LAI agents. Strategies to mitigate these barriers are reviewed.

KEYWORDS: long-acting, injectable, antipsychotics, barriers



Lack of insight is a common feature in patients with schizophrenia. Insight in psychiatric illness comprises of awareness of illness, the capacity to recognize symptoms as pathological, and an appreciation of the need for treatment.1 Lack of insight is associated with greater symptom severity, poorer treatment compliance, impaired treatment outcomes, and higher relapse rates.2,3 Relapse is associated with loss of brain tissue4 and diminished probability of achieving a full recovery. Antipsychotic medications, a cornerstone in the pharmacopeia for managing schizophrenia, help prevent relapse.5 Despite this, patients often discontinue treatment of these medications due to intolerance or lack of insight.2,6 Antipsychotic discontinuation increases the risk of relapse 5-fold.7

Long-acting injectable (LAI) antipsychotics were developed to enhance treatment adherence and reduce the risk of relapse. They are typically initiated after a patient’s failure to comply with oral antipsychotics.7,8 It is sometimes difficult to ascertain whether noncompliance is the cause or consequence of relapse. For many patients, LAI antipsychotics clarify this dilemma because the variable of medication adherence is removed.9 The lower serum levels associated with LAI antipsychotics has been shown to improve tolerance and enhance patient acceptance.10

In a study involving 2,588 patients hospitalized for schizophrenia, 54% either did not fill their initial antipsychotic prescription or used their medication for <30 days.10 LAI antipsychotic medications were associated with a 59% lower risk of treatment discontinuation and a 30% reduced rate of relapse compared with their oral equivalents. A recent mirror-image longitudinal study confirmed the pharmacoeconomic benefits of LAI antipsychotics over oral compounds.11 Conversely, a 24-month follow-up study failed to find an advantage for LAI risperidone over oral antipsychotics in reducing relapse.12 However, the comparison was confounded in that patients in the oral arm of the study received the psychiatrist’s choice of an antipsychotic rather than risperidone. Furthermore, 12% of patients who were randomized to the oral arm of the study continued to receive long-acting risperidone for an average of 5 months into the trial.

Although 40% to 60% of schizophrenia patients are partially or completely nonadherent with their antipsychotic regimens, current treatment guidelines recommend initial treatment with oral medications. Worldwide, the rates of utilization of LAI antipsychotics vary from 12% to 20% in the United States and Germany, to 50% in Sweden and Austria.13

In the United States, access to LAI compounds is limited.13 In 7 states, LAI antipsychotics are considered a “medical” benefit rather than the more accessible “pharmacy” benefit. As a “medical” benefit, the medical practice that administers the LAI antipsychotic is required to bulk purchase and store the drug, and submit a bill for service to the insurance company only after a dose has been administered. Michigan is 1 of 7 states where this exception exists.

Furthermore, psychiatrists, guided by treatment algorithms, favor oral medications and consider long-acting compounds only after successive relapses due to antipsychotic nonadherence.13-15 Patients who stand to gain the most from LAI antipsychotics are those who are least compliant. Court-mandated treatment for patients who lack decisional capacity often comprise the population referred for treatment with LAI antipsychotics. However, these patients typically are excluded from clinical trials. As a result, rigorous studies that examine the relative efficacy of LAI antipsychotics compared with oral equivalents may underestimate the magnitude of their true advantage.14 Although LAIs were developed to encourage treatment compliance in patients with chronic schizophrenia, their utilization rate is highly variable. This could be due in part to negative attitudes and beliefs by both psychiatrists and patients concerning this antipsychotic formulation.16 Patel et al examined the influence of psychiatrists’ beliefs, attitudes, and knowledge on prescribing behaviors.16 Psychiatrists believed that: 1) patients were less likely to accept LAIs than oral medications (69.2%); 2) patients would feel stigmatized if asked to take an LAI (47.9%); and 3) friends and families were more accepting of oral medications than LAI medications (66.4%). Conversely, psychiatrists also believed that with LAIs: 1) compliance was better (80.9%); 2) monitoring compliance was easier (95.1%); and 3) relapse was less likely (93.7%).16 However, the barriers faced by psychiatrists in the use of LAI antipsychotics have not been clearly elucidated.

The purpose of the current study is to identify the barriers faced by Michigan State University-affiliated psychiatrists in using LAI antipsychotic medications in patients with schizophrenia.


Study population

We sent an internet survey to all psychiatrists (N=156) practicing in Michigan, all of whom were affiliated with the Department of Psychiatry at Michigan State University (MSU). The diverse practice environments of MSU psychiatrists resemble those of psychiatrists practicing nationwide. Michigan is of particular interest because it is 1 of only 7 states in the United States where LAIs are considered a “medical” rather than the more accessible “pharmacy” benefit.

Data collection

Epocrates, a mobile health software application for the iPhone that provides information about drugs and various diagnostic tools, was used to check Michigan drug formulary access to LAI haloperidol decanoate. Haloperidol decanoate, which is administered every 4 weeks, was chosen as representative of an inexpensive, generic, first-generation LAI antipsychotic compound. This is in contrast to the more costly second-generation LAI preparations such as paliperidone palmitate, olanzapine pamoate, and aripiprazole LAI.

With information on drug formulary access in Michigan, an internet survey was created and administered using Survey Monkey, an online tool that allows users to design their own survey instruments. Following approval by the MSU institutional review board, an e-mail detailing the specific aims and goals of the study was sent out to MSU-affiliated psychiatrists, along with a link to the survey.

The survey instrument (TABLE) was designed to gain insight into practice characteristics, geographic locations, access, and capacity to administer LAI antipsychotic medications, as well as opinions and potential barriers to using LAI antipsychotics when treating patients with schizophrenia. The survey gauged psychiatrists’ knowledge of the differences between a formulary “medical” vs “pharmacy” benefit, and awareness of regional pharmacies that were able to bulk purchase “medical” benefit drugs such as LAI antipsychotic medications.


Barriers to the utilization of long-acting antipsychotic medications

  1. Which of the following best describes your primary practice setting?
    a. Community mental health center
    b. Academic clinic
    c. Veterans medical center
    d. Private practice
    e. Hospital-based
    f. Other (please specify)

  2. How would you characterize your treatment location?
    a. Urban
    b. Suburban
    c. Rural
    d. Other (please specify)

  3. Do you have any patients in your practice who would potentially benefit from long-acting intramuscular (IM) antipsychotic medications?
    a. Yes
    b. No

  4. Does your practice setting have the capability to administer long-acting antipsychotic medications?
    a. Yes
    b. No

  5. If your practice setting does not possess the capability of administering long-acting IM antipsychotics, which of the following barriers represent your situation?
    a. Staffing issues (absence of nursing staff to administer IM injections)
    b. Inadequate insurance coverage of depot antipsychotic medications
    c. Geographical barriers to the clinic
    d. Personal preference for oral antipsychotics
    e. Other (please specify)

  6. If access to long-acting IM antipsychotic medications was achieved by training competent family members to safely administer the injections, would you be more willing to prescribe them?
    a. Yes
    b. No

  7. Approximately what percent of patients with schizophrenia or schizoaffective disorder, in your current practice, are maintained on long-acting IM antipsychotics?

  8. Michigan is one of 7 states in which long-acting IM antipsychotics are considered to be a formulary “medical” benefit rather than a “pharmacy” benefit. Are you aware of the difference between these benefits?
    a. Yes
    b. No

  9. In light of recent research, would you consider using a long-acting IM antipsychotic medication in the treatment of first-episode schizophrenia?
    a. Yes
    b. No

  10. Several pharmacies located in metropolitan areas are able to bulk purchase “medical” benefit drugs such as long-acting IM antipsychotics. Are you aware of the pharmacies in your practice location that provide this service?
    a. Yes
    b. No

Statistical analysis

The Statistical Package for the Social Sciences (SPSS) software was used to analyze the survey responses. Pearson chi-squared and Fisher exact tests were used to determine statistical significance between multiple study outcome variables. The Crosstabs feature of Survey Monkey also was used to compare psychiatrists’ capability of administering LAIs with the outcome variables. The outcome measures of interest were practice setting and location, capability of administering LAIs, willingness to administer LAIs, knowledge of the difference between “medical” and “pharmacy” benefits, and the impact of these barriers on outcomes.


Characteristics of study population

Thirty-six of 156 psychiatrists (23%) responded to the survey. Of the respondents, 10 (27.7%) worked in community mental health centers, 8 (22.2%) in private practices, 7 (19.4%) in hospitals, 6 (16.7%) in an academic clinic, and 2 (5.6%) at veteran medical centers. There was a striking, statistically significant difference between practice setting and percentage use of LAI antipsychotic medications (F=3.086; P=.031). LAI antipsychotic usage was 12.5% in hospitals, 10% in community mental health centers, 5% in veterans medical centers, 3.2% in private practice, and 0% in academic clinics. A diversity of geographic locations were represented, with 16 of 36 psychiatrists (44.4%) characterizing their treatment location as “urban,” 30.6% as “suburban,” and 19.4% as “rural.”

Analytic sample

Thirty-three surveyed psychiatrists (83.3%) acknowledged having ≥1 patients in their practice who would benefit from an LAI antipsychotic medication. However, only 22 (61.1%) had the capacity to deliver these medications to eligible patients in their practice settings; 11 (22%) did not have this capability. Fifty percent of psychiatrists who practice in an urban setting, 66.7% of those in suburban locations, and 20% of those in rural locations reported having patients who could benefit from LAI medications.

The leading barriers to utilizing LAI antipsychotics were: 1) lack of nursing support at the practice location; 2) psychiatrist personal preference for oral compounds; and 3) limited insurance coverage. Inadequate insurance coverage of depot antipsychotic medications was the leading barrier in urban locations (66.7%); staffing issues (56.3%), such as the absence of nursing staff to administer intramuscular injections, was the most prevalent barrier in suburban locations; and inadequate insurance coverage (33.3%) and personal preference for oral antipsychotic medications (28.6%) were the leading barriers in rural locations. Among psychiatrists who were knowledgeable about the “medical” benefit status of LAIs, utilization rates differed between those who had the capability to administer them (22.7%) and those who did not (7.1%), though the difference was not statistically significant (P=.3705).

The Fisher exact test showed a significant variance in utilization of LAIs by geographical practice location (P=.0036). Among psychiatrists in urban treatment settings, 50% were able to administer LAIs compared with 13.6% in suburban locations and 31.8% in rural areas.

The majority (66.7%) of respondents were unaware that LAI antipsychotic medications are considered a “medical” rather than a “pharmacy” benefit in Michigan, and 83.3% were unaware of the few pharmacies in the state that provide the option of the drug as a “pharmacy” benefit. Remarkably, despite the benefits of LAI antipsychotic medications in first-episode schizophrenia,17 only 55% of psychiatrists in urban settings, 25% in suburban settings, and 10% in rural settings considered using this formulation in the treatment of early psychosis.

Finally, only 13 of the 37 insurance drug formularies (35.1%) in Michigan provide patients access to generic long-acting haloperidol decanoate.


In long-term treatment of schizophrenia, the difference in relapse rates between intramuscular LAI antipsychotics and their oral equivalents approximates the difference in efficacy between oral antipsychotics and placebo.18 However, psychiatrists practicing in Michigan face overwhelming barriers to utilizing LAI antipsychotics. These obstacles include lack of nursing support, preference for oral compounds, fear of liability, and inadequate insurance coverage. Practice settings and location further influence the decision-making process. Underutilization of LAI antipsychotics also may result from lack of awareness of regional pharmacies that stock these medications. In urban settings, 66.7% of psychiatrists were aware of the pharmacies in their practice location that provide LAI antipsychotic medications, compared with only 16.7% of psychiatrists in both suburban and rural locations. LAI antipsychotics are generally unavailable to adolescents and young adult patients experiencing first-episode schizophrenia because these patients are likely to be maintained on their parents’ private health insurance. Following hospitalization, first-break patients frequently receive follow-up psychiatric care in private practice and academic settings, which have the lowest rates of utilization of LAI antipsychotics.

Whereas several previous studies have examined attitudes and patterns of use of LAI antipsychotic agents,13,14,16 we are not aware of any previous research that has specifically examined “barriers” to utilizing this class of compounds. The strengths of this study include the broad representation of psychiatrists from a variety of practice settings and the originality of the study. There were several limitations of the study, 1 being its regional rather than national sample. Michigan is 1 of 7 states where LAI antipsychotics are considered a “medical” rather than a “pharmacy” benefit. It is conceivable that offering a “pharmacy” benefit may increase access and therefore, utilization. Moreover, the number of psychiatrists surveyed (36) represents only a small fraction of practicing psychiatrists. It is possible that the respondents represented a subgroup of psychiatrists with a particular interest in the topic and a greater likelihood of using LAI antipsychotics compared with the entire population of psychiatrists. Epocrates is widely used as a formulary reference, and we have identified instances in which the information provided regarding drug formulary access was inaccurate. Furthermore, many practicing psychiatrists have access to samples of selected proprietary LAI antipsychotics, such as paliperidone, olanzapine, and aripiprazole, and this was not captured by our survey. Finally, multiple comparisons were not controlled for, making the results of the current study preliminary.

Despite a growing consensus for the superiority of LAI antipsychotic agents over oral equivalents, findings from available published studies are far from unanimous. For example, a 24-month follow-up study reported no differences between the relapse rates for patients who received LAI risperidone and those who received oral antipsychotics.12 However, patients in the LAI antipsychotics arm of the study scored higher on the Drug Attitude Inventory than those in the oral arm. The authors12 cited 2 additional reports suggesting equivalency between LAI and oral antipsychotics. However, the first of these reports19 was an 8-week noninferiority comparison of oral vs LAI risperidone. The second20 was a pharmacokinetic dose-finding study of LAI risperidone.

A meta-analysis of randomized controlled trials of LAI antipsychotics and oral equivalents in >800 participants failed to find an advantage for LAI formulations in the prevention of relapse. However, as the authors acknowledged, patients participating in controlled clinical trials are generally compliant with oral medications. In clinical practice, patients who achieve the greatest benefit from LAI antipsychotics are those who lack insight and are noncompliant with recommended treatment. Patients who lack insight are not likely to participate in clinical trials research.21

Patients with schizophrenia generally have less favorable attitudes toward LAI antipsychotics compared with their psychiatrists and family members.22 Concerns raised by patients include perceived loss of autonomy in medical decision-making and injection site pain. However, less than one-third of patients receive any information about the vital role of LAI antipsychotics in the management of schizophrenia.22


In conclusion, if LAI antipsychotics are truly superior to their oral equivalents in the prevention of relapse and hospitalization in patients with schizophrenia, then it is important that psychiatrists reevaluate their attitudes toward prescribing these compounds, advise their patients about the advantages of these formulations, and include nursing personnel in their practice settings. Insurance carriers may consider revising their formularies to provide easier access to LAI antipsychotics.11 Special delivery services such as depot clinics, home treatment teams, or community outreach facilities should consider increasing access and improving delivery of LAI antipsychotics.13 Finally, treatment algorithms may need to consider including LAI antipsychotics as an option for the initial treatment of schizophrenia.15,17,23,24

ACKNOWLEDGEMENTS: The authors thank the University of Michigan School of Public Health and the University of Michigan Center for Statistical Consultation and Research for their help in the organization, analysis, and interpretation of the results of this study. The authors would also like to thank Dr. Eric Achtyes and Loren Friedman for their helpful review and criticism of the manuscript.

DISCLOSURE: The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.


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CORRESPONDENCE: Hayley Getzen, MPH Wayne State University School of Medicine 540 East Canfield St. Detroit, MI 48201 USA E-MAIL: getzenha@umich.edu