Cost Comparison of Atypical Antipsychotics: Paliperidone ER and Risperidone

Abstract

Purpose: Paliperidone and risperidone are atypical antipsychotics that are structurally and therapeutically similar. Risperidone is metabolized by the liver via cytochrome (CYP) 2D6 to an active metabolite, 9-hydroxyrisperidone. The atypical antipsychotic paliperidone is 9-hydroxyrisperidone formulated separately as an extended-release (ER) tablet and is considerably more expensive than risperidone. The purpose of this retrospective drug utilization review is to evaluate the prescribing patterns of paliperidone ER and evaluate potential cost savings by converting paliperidone ER orders to risperidone at an inpatient psychiatric hospital’s formulary. Methods: This retrospective drug utilization review includes 100 patients, older than 18 years old, who were prescribed oral paliperidone ER at an inpatient, psychiatric hospital between January 1, 2017, and June 2, 2017. The data were collected through the electronic medical records. Patients who were prescribed oral paliperidone ER and refused to take paliperidone ER were excluded from the study population. The cost of each patient’s oral paliperidone ER pharmacotherapy was calculated using average wholesale prices. An equivalent total dose of risperidone therapy was calculated using a 2:3 paliperidone ER to risperidone conversion. The cost savings were then analyzed by comparing the total costs of paliperidone ER with risperidone therapy. Results: The results indicate that from January through June 2017, approximately 68% of all paliperidone ER utilization was for its approved indication of schizophrenia and schizoaffective disorder. The other 32% of utilization was either off-label or for approved indications of risperidone. The total paliperidone ER therapy cost for 100 patients was approximately $17 000, while the cost of risperidone therapy would be approximately $400 for the same patients over 6 months. Overall, this would provide an estimated cost savings of over $33 000 per year or about $169 in savings per patient. Conclusion: The study analysis demonstrates that there are opportunities for cost savings through therapeutic interchange of paliperidone ER to risperidone.

Background

Paliperidone extended-release (ER) and risperidone are atypical antipsychotics commonly used for treatment of schizophrenia and schizoaffective disorder.^1,2 Risperidone is metabolized by the liver via cytochrome (CYP) 2D6 to an active metabolite, 9-hydroxyrisperidone.² Paliperidone is 9-hydroxyrisperidone formulated separately as an ER tablet. Both antipsychotics have demonstrated similar efficacy and established tolerability profile and are frequently used interchangeably in the psychiatric setting.³ These antipsychotics have similar receptor-binding profiles, the only difference being that paliperidone ER has a higher affinity for the alpha-2-adrenergic receptor.⁴ Both risperidone and paliperidone ER are dosed once daily due to their elimination half-lives of 20 and 23 hours, respectively.^1,2 Although both agents have a similar pharmacokinetic profile, a 1:1 conversion does not exist because paliperidone is less bioavailable (28%) compared with risperidone (70%).^1,2 Both paliperidone and risperidone have long-acting injectable (LAI) formulations, in which risperidone tablets are often used to stabilize the patients before transitioning to either LAI formulation.⁵

Despite the pharmacologic and therapeutic similarities of paliperidone ER and risperidone oral tablets, paliperidone ER is considerably more expensive than risperidone. Average wholesale price (AWP) for paliperidone ER tablets range from $13 to $20 per tablet, while the AWP of risperidone tablets range from $0.20 to $0.50.⁶ A key objective of the pharmacy and therapeutics committee in inpatient hospitals is to maintain the hospital formulary through selection of the most cost-effective agents with minimal therapeutic redundancy. Many inpatient hospitals carry multiple antipsychotics on the formulary to accommodate patients with different response profiles; however, in this instance, a response to risperidone or paliperidone should predict a response to the either agent. Therefore, there is limited necessity in maintaining both agents on formulary with the expected similar therapeutic response and tolerability to both agents and the cost of paliperidone.

Methods

The Institutional Review Board approved this retrospective study.

Study Design and Patient Population

This was a retrospective drug utilization review conducted at an inpatient psychiatric hospital. The primary objective was to evaluate prescribing patterns of paliperidone ER tablets and to assess potential cost savings if risperidone replaced paliperidone ER on the formulary.

The study population included 100 patients, 18 years and older, receiving oral paliperidone ER over a 6-month period. Patients who were prescribed paliperidone ER, but never received or refused doses were excluded. The data were obtained via the electronic medical record. The data collected included patient demographics (age, sex, and race), indication of paliperidone therapy, dose of the medication, and the length of stay. The cost of each patient’s oral paliperidone ER pharmacotherapy was calculated using pricing obtained from the hospitals wholesaler details expected AWP per tablet (Table 1). Total paliperidone ER cost was calculated by using the AWP of the corresponding milligram tablet multiplied by the amount of tablets used for each patient. An equivalent total dose of risperidone therapy was calculated using 3:2 paliperidone ER to risperidone conversion.⁷ Patients on 3, 6, or 9 mg paliperidone ER tablets were accurately converted to the equivalent oral risperidone doses of 2, 4, and 6 mg, respectively, and multiplied by the AWP.⁷ The total amounts of paliperidone ER tablets taken during the whole length of stay were taken into account. The cost savings were then analyzed by comparing the total costs of paliperidone ER with risperidone equivalents by the breakdown of costs by indication.

Table 1.

^6,7Average Wholesaler Price Per Tablet.

Paliperidone Extended-Release		Risperidone
Strength	Price	Strength	Price
3 mg	$16.05	2 mg	$0.23
6 mg	$13.90	4 mg	$0.36
9 mg	$18.87	6 mg	$0.46

Results

In the 6-month study period, approximately 68% (62) of all paliperidone ER utilization was for its approved indication of schizophrenia and schizoaffective disorder. The other 32% (38) of utilization was either off-label or for approved indications of risperidone (Table 2).

Table 2.

Baseline Characteristics and Prescribing Patterns.

Baseline characteristics	Schizophrenia (n = 62)	Major depressive disorder (n = 5)	Bipolar (n = 22)	Other (n = 11)
Age (years), mean	38	35	36	29
Male, n (%)	36 (58)	0 (0)	15 (68)	5 (45)
Ethnicity
Caucasian, n (%)	13 (21)	1 (20)	9 (41)	1 (9)
African American, n (%)	24 (39)	3 (60)	6 (27)	6 (55)
Asian, n (%)	8 (13)	0 (0)	5 (23)	1 (9)
Other, n (%)	16 (26)	1 (20)	2 (9)	3 (27)
Length of stay (days), mean	23	44	18	23
Total (mg) of paliperidone extended-release taken, mean	71	139	64	55

The total sum of paliperidone ER therapy cost for 100 patients in the span of 6 months was $17 338.36. If all the paliperidone ER therapy were to be converted to risperidone, the cost of therapy for the same 100 patients over the 6-month therapy would be $436.43. The potential cost savings when converting patients from paliperidone ER to risperidone would be $16 901.93 per 100 patients. Per year, this would yield projected savings of approximately $33 800 per year per 100 patients prescribed paliperidone, assuming the prescribed doses remain consistent with current mean doses. The projected savings is based on the same 100 study patients having consistent paliperidone ER usage for a year. Average cost savings of per patient with conversion is estimated at $169 per patient.

Average cost per milligram of paliperidone per patient across all indications was $2.77, while risperidone cost was $0.09, yielding a cost difference of $2.68 per milligram of drug per patient for all recorded indications. Average cost of risperidone per milligram per patient was about the same for all indications at $0.09, while for paliperidone, cost varied minimally depending on the indication. The lowest average cost was seen in patients with schizophrenia ($2.73), while indications in the “other” category (not schizophrenia, major depressive disorder, nor bipolar disorder) had the highest average cost (Table 3).

Table 3.

Average Cost Difference Per Milligram Per Patient.

Indication	Paliperidone extended-release cost/mg/patient	Risperidone cost/mg/patient	Cost difference mg/patient
Schizophrenia	$2.73	$0.09	$2.64
Major Depressive Disorder	$2.79	$0.09	$2.70
Bipolar	$2.83	$0.09	$2.74
Other	$2.91	$0.10	$2.81
Total average	$2.77	$0.09	$2.68

Based on the mean dosing of paliperidone used, potential cost savings per patient was calculated versus risperidone. Total costs of paliperidone therapy were calculated using mean doses in each indication and compared with total risperidone cost per patient. The indication of major depressive disorder had the highest potential cost savings of $379.48, due to the high mean total of paliperidone taken (139 mg). The lowest cost was under the indication of “other” at $156.38, with the lowest mean total dose taken of paliperidone (55 mg). Potential cost savings for indications of schizophrenia and bipolar disorder came in between $189.57 and $177.28, respectively (Table 4).

Table 4.

Potential Cost Savings Per Patient Based on Mean Doses.

Indication	Potential cost savings
Schizophrenia	$189.57
Bipolar	$177.28
Major Depressive Disorder	$379.48
Other	$156.38

Discussion

This retrospective analysis suggests there are potential opportunities for cost savings if paliperidone ER was to be substituted with risperidone. The average cost difference per milligram per patient for the treatment of schizophrenia is $2.64 per patient. Based on mean doses for schizophrenia, the potential cost savings per patient is about $190. Inpatient hospitals may consider removal of paliperidone from the formulary to reduce drug inventory and drug acquisition costs with no anticipated effect on patients.

According to the clinical antipsychotic trials of intervention effectiveness (CATIE) study, all antipsychotics are considered equal in efficacy, except for clozapine.⁸ It is reasonable to maintain a wide array of antipsychotics on formulary to accommodate variable response histories of psychiatric inpatients; however, this is not a concern when comparing risperidone and paliperidone. Because paliperidone is the active metabolite of risperidone, the likelihood of similar response to both agents is considered higher than when compared with other antipsychotics in the same class. Although patient-reported adverse effects may vary from patient-to-patient, the tolerability of each agent is considered comparable given their similar toxicity profile (Table 5).^1,2 Providers may be concerned that limiting prescribing to risperidone would eliminate the possibility of conversion to paliperidone palmitate, a commonly prescribed long-acting antipsychotic administered intramuscularly to promote medication adherence in patients with schizophrenia and schizoaffective disorder. However, this would also have no impact on transition because patients may be bridged to both risperidone microspheres and paliperidone palmitate with oral risperidone.

Table 5.

^1,2Incidence of Common Adverse Events of Paliperidone ER and Risperidone Oral Tablets.

	Hyperprolactinemia (%)	Parkinsonian-like syndrome (%)	Akathisia (%)	Weight gain (%)
Risperidone	4	8-25	5-11	4-21
Paliperidone ER	1	3-18	4-17	2-19

Note. ER = extended-release.

The impact of removal of paliperidone palmitate has the potential to demonstrate other unanticipated benefits by reducing the complexity of transitions of care and decreasing costs to outpatients. Many insurance plans consider paliperidone to be on a higher tier, resulting in denial of insurance claims on discharge, or high co-pays for the patient. Delays in pharmacotherapy can be detrimental to the patient’s health, and with a population that already has poor adherence, it is imperative to make the process of accessing these medications for patients as easy as possible. In general, one of the major factors of poor medication adherence is cost; when patients have high co-pays and are unable to pay for their medications, they are more likely to go without it.⁹

Limitations

This was a retrospective drug utilization over a short period of 6 months. Projected future savings were reported based on prescribing during the study period. Actual savings over the long-term are not reported.

Conclusion

This retrospective analysis evaluated the prescribing patterns of oral paliperidone and projected cost savings after converting all orders for oral paliperidone to oral risperidone at an inpatient psychiatric facility. Results suggest that therapeutic substitution of risperidone for paliperidone may yield significant cost savings for inpatient facilities. Future studies are warranted to evaluate actual cost savings associated with such changes and the impact on patient outcomes.