Introduction: Recent trials have failed to demonstrate differences in efficacy between first generation antipsychotics (FGAs) and second generation antipsychotics (SGAs). To reduce costs, many health care systems have restricted the availability of SGAs through use of prior authorizations. Restrictions for the off-label use of SGAs and the use of dual-antipsychotic therapy have also been implemented in many health care systems. At the South Texas Veterans Health Care System (STVHCS), a restricted drug request (RDR) method has been implemented to manage costs and improve patient safety. Risperidone, due to its lower cost and equal efficacy, is the first-line option of SGAs. If one wishes to prescribe an SGA other than risperidone, an RDR is submitted and reviewed by Veterans Integrated Service Network (VISN) pharmacists. Since the introduction of these policies at the STVHCS, the impact of the RDR has not been assessed.

Rationale: The primary aim of this study was to determine the effects of the RDR policy on the care of STVHCS veterans as evidenced by changes in hospitalization rates of veterans with a denied request for an SGA due to initial criterion failure. Secondary outcomes included: impact of antipsychotic RDR denial on mental health as evidenced by changes in no-shows and cancellations for follow-up psychiatric appointments, psychiatric emergency department visits, presence of suicidal ideation, change in weight, hemoglobin A1c, number of psychotropic medications prescribed, and extrapyramidal symptoms.

Methods: A retrospective chart review of veterans denied an initial SGA request was conducted from 3 months prior to denial to 3 months post request denial (index date). Data collected included: patient demographics, indication for SGA request, reason for SGA denial, length of time for request evaluation, number of psychiatric hospitalizations, number of no-shows and cancellations for mental health appointments, number of psychiatric emergency department visits, number of reports of suicidal ideation or attempts, weight, hemoglobin A1c lab results, presence of extrapyramidal symptoms, and number of prescribed psychotropic medications. The health care utilization data collected pre- and post-index date, were compared. Results were analyzed using Fisher's Exact, 2-tailed standardized t-tests, and descriptive statistics appropriately matched to data type.

Results: Results for both primary and secondary outcomes were not statistically significant. No differences were found in the number of veterans hospitalized pre- versus post-index date [0/33 (0%) versus 2/33 (6%), p=0.492.] The most requested indication for an SGA was PTSD [22/33 (66.7%)] and the most frequently denied SGA was quetiapine [16/33 (48.5%)].

Conclusions: Although outcomes were not statistically significant, several valuable conclusions were drawn from this research. Positive outcomes from a RDR policy were seen by the limitations placed on inappropriate medication prescribing. Also, it was observed that the number of approvals for SGAs was almost three times higher than denials. A subsequent finding from this research is the apparent lack of metabolic monitoring for veterans prescribed SGAs. Further research on these observations, as well as conducting a pharmacoeconomic analysis on the RDR policy, would also be beneficial information for health care providers.

Background

With the development of second-generation antipsychotics (SGAs), the use of these agents quickly surpassed that of first-generation antipsychotics (FGAs) due to the assumption that SGAs were safer and more effective than the former. Recent monumental trials comparing antipsychotic agents, however, provided some evidence that significant differences between the first and second generation agents may not actually exist.1–3 The National Institute of Mental Health (NIMH)-sponsored Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and the United Kingdom trial, Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study (CUtLASS), concluded that in terms of compliance, quality of life, and effectiveness, SGAs, with the possible exception of clozapine, do not significantly differ from FGAs.1–5 These studies not only found a lack of difference in efficacy between FGAs and SGAs, but also found no superior treatment efficacy between individual SGAs with the exception of clozapine.

In an effort to reduce costs, many federal and private agencies have restricted the availability and prescribing of SGAs through the use of prior authorizations and “fail-first” treatment algorithms.6–10 Restrictions of off-label and dual-antipsychotic therapy use of SGAs have also been implemented. For patients receiving these drugs at Department of Veterans Affairs hospitals, the United States General Accounting Office has concluded that the lower cost of risperidone and equivalence of efficacy compared to other SGAs, makes this drug a first choice treatment agent among SGAs.10 

Research evaluating the impact of antipsychotic restrictions on patient care has shown patients have been both positively and negatively affected by formulary restrictions and prior authorizations.7–9,11,14–17 The positive effects on patients through the use of prior authorizations may include patients receiving better care through the enforcement of step-therapy as first line treatment options are usually based on treatment guidelines. Requiring certain clinical criteria be met before approving the medication may also benefit the patient as this helps reduce off-label prescribing. Lastly, restriction policies may prevent high-dose and dual antipsychotic prescribing, leading to reductions in patient morbidity.11 In short, restriction policies help prevent patients from being prescribed unnecessary medications at potentially harmful doses.

Negative effects of restriction policies have also been observed, however. Specifically, a higher rate of hospitalizations and emergency room visits,6,8,9,13 increased rates of medication discontinuation,7,9,12 and increased rates of suicide14 have been found in patients affected by medication access problems due to restrictions on SGA prescribing. The proposed cost-benefit that would occur through the restriction of SGAs has not been widely found in the researched restriction polices,8,15,18 or has shown only minimal increases in savings.8 In many instances, an increase in the rate of hospitalizations has been found to offset potential savings through SGA restriction policies.6,15 An increase in metabolic side effects associated with specific SGAs may also further decrease any potential cost-savings through SGA restriction.12 

Objective

At the Veterans Integrated Service Network (VISN) that includes the South Texas VA Health Care System (STVHCS), it was discovered that a higher number of SGA prescriptions were being dispensed compared to the national average. This was concerning as it meant not only an increase in expenditures on SGAs but also a possible increase in inappropriate and off-label prescribing. As a result of this finding, a restricted drug request (RDR) for SGAs was implemented in February 2011. This new policy stated that providers must file a restricted drug request (RDR) for SGAs, whether it is a new start medication or a medication renewal. In order to prescribe a SGA, the provider must complete an electronic justification form which includes the reason for prescribing and whether or not the patient tried and failed preferred first-line medications. The electronic request is submitted to a specific team of pharmacists that reviews the request and determines if the medication requested is appropriate and then notifies the prescriber with their decision. Since the introduction of this policy at STVHCS, analyses of this healthcare utilization policy had not been conducted. Therefore, the main objective of this study was to determine if changes in psychiatric hospitalization rates among veterans at STVHCS occurred as a result of the implementation of this policy.

Subjects

A retrospective chart review of veterans denied an initial or renewal SGA request was conducted. A report of all restricted drugs denied for the months of April, May and June 2011 was generated and second-generation antipsychotic denials were pulled and data were collected. Baseline demographic information was collected for each patient and included age, gender, and mental health diagnosis. Chart examination was conducted covering the 3 months prior to denial and 3 months after the denial for each patient. Data were de-identified and recorded in a secure spreadsheet on the STVHCS computer network behind the research firewall. Institutional review board approval was obtained. Inclusion criteria were adult patients for whom a provider had placed a RDR for SGAs within the months of April, May and June 2011. No exclusion criteria were used.

Outcomes

The primary outcome compared the number of psychiatric hospitalizations among veterans 3 months prior to rejection of the SGA request compared to the 3 months post SGA request. Secondary outcomes included a comparison of the 3 month treatment history prior to rejection of SGA request to the 3 month treatment history post SGA request as evidenced by: no-shows for follow-up appointments, emergency department visits for mental-health changes and substance abuse, suicide ideation, changes in weight and HbA1c, changes in the number of psychotropic medications prescribed and evidence of extrapyramidal symptoms. The length of time for providers to be notified of the SGA request rejection was also included as a secondary outcome.

Data Collection

Rates of hospitalization, no-shows for psychiatric follow-up appointments, psychiatric-related emergency department visits, incidence of suicidal ideation or attempts, the number of reports of extrapyramidal symptoms including parkinsonism, tardive dyskinesia, dystonia, and akathisia, as noted by primary care provider, or mental health provider, changes in weight, changes in HbA1c lab results, and changes in the total number of psychotropic medication prescriptions (antipsychotics, antidepressants, mood stabilizers, benzodiazepines, insomnia-related or other medications used off-label for treating refractory symptoms) were collected from manual chart review. Other data collected included the reason for RDR request and denial, the length of time for RDR evaluation, the type and dose of antipsychotic denied, and the number of denial appeals.

Statistical Analysis

Results were analyzed using appropriate tests for data type. Fisher's Exact test was utilized for comparison of hospitalization rates, no-shows, emergency department visits, occurrence of suicidal ideation or attempts, and reports of extrapyramidal symptoms. A two-tailed standard t-test was used for analysis of the total number of prescriptions data. Remaining data were analyzed using descriptive statistics.

Baseline Characteristics

The population demographics showed mostly male veterans, mean age of 59 (range 24–89), with the majority having more than one psychiatric diagnosis. The most requested indication for an SGA was Post Traumatic Stress Disorder (PTSD), and the medication denied most frequently was quetiapine (Table 1).

Table 1:

Demographics, Clinical Characteristics, and Descriptive RDR Results

Demographics, Clinical Characteristics, and Descriptive RDR Results
Demographics, Clinical Characteristics, and Descriptive RDR Results

Primary Outcome

There were no differences in hospitalization rates before and after the RDR denial. Before the denial, no veterans were hospitalized in the 3 month time period prior to denial compared to after the denial at which time 2 veterans out of 33 were hospitalized within 3 months after the RDR denial[0/33 (0%) vs. 2/33 (6%), p=0.492].

Secondary Outcomes

Secondary analyses found no significant results. No-show rates to psychiatric appointments, visits to the emergency department, incidence of suicidal ideation, rates of extrapyramidal symptoms, and changes to the total number of prescriptions were all similar pre-and-post denial (Table 2, Figure 1).

Figure 1:

Total Number of Prescriptions

Figure 1:

Total Number of Prescriptions

Close modal
Table 2:

Secondary Analysis Results

Secondary Analysis Results
Secondary Analysis Results

Among the 33 veterans, changes in weight occurred with 12 veterans experiencing weight loss compared to 7 experiencing weight gain. Weight changes were not significant and 14 patients were not included due to missing weight recordings either pre- or post-RDR denial.

Missing data also affected HbA1c data as only 5 subjects had lab measurements recorded within the chart examination time period. Three of these subjects showed decreases in their HbA1c after the denial while the remaining 2 remained unchanged. None of these 5 subjects had continued use of SGAs after the denial (Figure 2).

Figure 2:

Weight Change

Post-Hoc Analysis

Seven veterans continued to receive SGA therapy after the RDR denial due to refills not being discontinued. After elimination of these 7 subjects from data analysis, no statistically significant changes in primary and secondary outcomes were found. (Table 3)

Table 3:

Post-Hoc Analysis Results

Post-Hoc Analysis Results
Post-Hoc Analysis Results

This retrospective chart review of outcomes following the implementation of a RDR at STVHCS for veterans being prescribed SGAs found that two veterans were hospitalized within 3 months of the RDR denial. One veteran had been taking two SGAs, olanzapine and risperidone, and an RDR for a risperidone continuation of therapy was denied. The patient was placed on fluphenazine, and olanzapine was continued. Within three months, the patient decompensated and required inpatient admission. The second hospitalization occurred in a patient denied quetiapine for impulse control. This patient was hospitalized for suicidal ideation related to cocaine abuse. Although the results of the primary outcome were not found to be significant, this may have largely been due to a small sample size.

Several positive outcomes were noted while investigating the impact of the RDR, including the denial of medications being prescribed for inappropriate reasons. For example, the most frequent indication for requested SGAs was PTSD. Although in some cases, SGAs may be effective as an adjunctive medication, SGAs are not first-line treatment for PTSD.20–22 Data for treatment of PTSD with an SGA are limited as only a few controlled trials have been conducted that utilize SGAs as adjunct therapy. The most recent trial, evaluating the efficacy of risperidone as adjunct treatment in a large veteran population with military-related PTSD, found no differences in reduction of PTSD symptoms compared to placebo.22 An even smaller number of trials exist for SGA monotherapy and these results are inconclusive. One trial failed to find benefit with olanzapine treatment23; however, a later pilot study showed risperidone to be effective in women with PTSD related to sexual assault and domestic violence.24 Treatment guidelines continue to recommend SSRIs as first-line therapy and advocate the use of the alpha-adrenergic antagonist, prazosin, for treatment of nightmares.20,21 Patients denied a SGA for PTSD treatment had not been given an adequate trial of these recommended medications. Other positive findings included the time to notification of rejection and the actual number of approvals compared to denials. Although the RDR policy states that reviewers have up to 72 hours to notify providers of rejection, in most cases, the notification took place within 3 to 24 hours. The number of SGA approvals versus denials showed that the large majority of SGAs were for appropriate indications and veterans continued to receive or were able to begin use of a SGA for these indications. Almost three times as many RDRs were approved rather than denied in the three month evaluation period (109 approvals compared to 33 rejections).

Results from this small study highlight that metabolic monitoring of patients using SGAs was not adequately being conducted as evidenced by missing data for changes in weight and HbA1c measurements. Only about half of the patients, n= (57.6%) had recorded weights while only 5 patients (15.2%), had their HbA1c monitored. Several consensus guidelines have recommended close monitoring of weight, lipids, and glucose in patients receiving SGAs.25,26 The American Diabetes Association recommends measuring weight at baseline, 4 weeks, 8 weeks, 12 weeks, quarterly and then annually and also recommends obtaining fasting plasma glucose results at baseline, 12 weeks, and annually.25 Hemoglobin A1c results are a viable alternative if fasting glucose levels are unable to be obtained.26 

Limitations of this study may have led to inconclusive findings due to a small sample size but valuable information was also obtained as a result of some of these limitations. For example, it is clear that metabolic monitoring of patients either continuing to take SGAs or being initiated on these medications is not being conducted according to guideline recommendations. Data for this project were also evaluated close to initiation of the RDR policy and preliminary problems with the review process were evident. As mentioned previously, seven patients continued to have prescriptions available for their SGA medication after the denial of the RDR. This result points to a flaw in the reviewing procedure that does not take into account current refills for SGAs the patient may still have available to them. Also, it was discovered that providers were filling out the RDR incorrectly. One case involved switching the diagnosis in order to obtain the medication. A current review would help determine if these problems have been addressed. This being a retrospective review, medication compliance was not a measurement in this study. This is always an important issue as the researcher can only assume patients are taking their medications based on refill data or self-report if noted in the patient's chart. Patients may or may not have taken their medication regularly regardless of whether the prescription was available.

Improvements to this research could be made by including a larger sample size and evaluating a longer time period pre- and post-rejection as decompensation does not always occur quickly after a change in medication. The use of exclusion criteria (such as determining if patients are new starts to the medication the RDR is being requested for or if they have been stable on the SGA and the RDR is for a refill request) may also help with more conclusive results. In addition to these improvements, conducting a cost analysis of the actual savings through the use of the RDR policy at STVHCS would be a very informative addition to this research.

Although several recent studies evaluating the impact of restriction policies on patient healthcare have found negative results, this research helped highlight some of the positive outcomes a restriction policy can provide. Results from this study, although not statistically significant, helped point out that many veterans are being prescribed medications inappropriately and unnecessarily. Opponents to restriction policies may argue that cost is the driving factor behind these regulations and not patient care. However, if the restriction policy is developed with an equal intent to improve both areas, everyone may benefit.

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