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Home , Dopamine antagonist, Molindone

Antagonist Prescribing Practices in Patients With Parkinson Disease

Amie L. Peterson, MD; Joseph Quinn, MD; Brenna Lobb, MS, MPH; Marsha N. Andrews, MSW; and John G. Nutt, MD

This study examines clinician prescribing habits at 3 VAMCs to see whether a change in the electronic medical record at 1 VAMC leads to a change in prescribing patterns of dopamine antagonists in patients with Parkinson disease compared with the other 2 centers.

sychosis and are com- In the 1990s, 2 studies on antipsy- prescribing in patients with PD, the mon problems in patients chotic use in PD in the United States Portland VAMC implemented a med- with Parkinson disease (PD) found that 88% to 99% of prescribed ication comment in the electronic or- and are often treated with do- were contraindicated dering system beginning June 2004. P 5,6 pamine antagonists, that typical antipsychotics. A later study can worsen . In 2 sur- in Canada in patients with PD found MATERIAL AND METHODS veys of clinic patients with PD, 24.4% the rate of typical use Permission to search the Veterans complained of nausea at least once in had decreased from 56% in 1998 to Data Warehouse was granted by the the month before the clinic visit, and 9% in 2002.7 In the Canadian study, Portland VAMC Institutional Review 39.8% experienced hallucinations in and (which Board. The data were examined in the 3 months before the visit.1,2 can cause extrapyramidal signs) were 12-month intervals for 4 years before Historically, atypical antipsychot- included as acceptable medications. and 3 years after June 2004 when ics were felt to have a lower risk for These studies reported the percentage Portland implemented the medica- worsening parkinsonism. Through of prescribed antipsychotics that were tion comment (June 2000 – May most of the 1990s , olan- contraindicated, not the percentage 2001, June 2001 – May 2002, June zapine, , and risperidone of patients with PD on contraindi- 2002 – May 2003, June 2003 – May were felt to be appropriate to treat cated medications. There are no re- 2004, July 2004 – June 2005, July in PD. However, over time cently published data in an American 2005 – June 2006, and July 2006 – some atypical antipsychotics pro- population on antipsychotic use June 2007) for the 3 largest centers duced extrapyramidal signs. The or dopamine antagonists: within Veterans Integrated Service most restrictive recommendations, , , Network (VISN) 20. When an order published in 2001, suggested that and . for a was re- only quetiapine or clozapine be pre- In order to determine the current quested at the Portland VAMC, the scribed.3 A 2006 American Academy state of contraindicated dopamine statement, “this is con- of Neurology (AAN) practice param- antagonist prescribing practices, we traindicated in patients with Parkin- eter came to the same conclusion.4 determined the number of times son disease,” would appear in the these medications (, comment section of the electronic Dr. Peterson is an instructor, Dr. Quinn and Dr. , metoclopramide, molin- ordering system. June 2004 was not Nutt are codirectors, and Ms. Lobb and Ms. An- done, olanzapine, prochlorperazine, included in the analysis, because drews are program analysts all in the Neurology Department at the Portland VAMC in Portland, promethazine, risperidone, thiorida- it was not clear when during this Oregon. Dr. Peterson is also an assistant profes- zine, thiothixene, and ) month the medication comment was sor, Dr. Quinn is an associate professor, and Dr. were prescribed to patients with PD fully implemented. Nutt is director of the Parkinson Center of Oregon all at the Oregon Health and Science University in in 3 VAMCs in the Pacific North- To most accurately identify the Portland, Oregon. west. To avoid dopamine antagonist number of patients with PD, the

FEBRUARY 2012 • FEDERAL PRACTITIONER • 39 DOPAMINE ANTAGONISTS IN PD

14.0 M E VISN 20 database was queried for all 12.0 D Portland patients who were diagnosed with PD I Puget Sound (ICD 9 Code = 332.0) during each 12- 10.0 C Spokane month period that was evaluated in A the Portland, Puget Sound, or Spo- T 8.0 I kane VAMCs. Patients who also had O a diagnosis of bipolar, , and schizoaffective disorders (ICD 9

N 6.0 Codes = 295.xx, 296.xx, 311.xx, or C O V11.0) were excluded. The number of 4.0 M patients who joined (obtained a new M diagnosis of PD) and the number of 2.0 E patients who left (died or were lost to N a follow-up), were calculated for every dopamine antagonist prescription (%) T 0.0 12-month period.

Unique PD patients prescribed a contraindicated 2000 2001 2002 2003 June 2004 2005 2006 To determine the number of pa- 2004 tients with PD prescribed a contra- 12-month grouping of issue date indicated dopamine antagonist, the records of the patients identi- Figure 1. Percentage of patients with PD by location on contraindicated dopamine an- fied above were queried for those tagonists for each 12-month period. aData for June 2004 are not included in the analysis, prescribed a dopamine antagonist because it was not clear when during this month the medication comment was fully (fluphenazine, haloperidol, meto- implemented. clopramide, , olanzapine, prochlorperazine, promethazine, ris- peridone, , thiothixene, Portland and ziprasidone) from June 1, 2000 Olanzapine Puget Sound to June 31, 2007. Prescriptions where Spokane the issue date or the dispense date Metoclopramide equaled the cancellation date were re- moved. For each 12-month period, Risperidone the number of prescriptions of con- traindicated and the number of unique patients were identified for Prochlorperazine each VAMC. The percentage of pa- tients with PD at each center on these Promethazine medications was determined. All prescriptions were included whether Fluphenazine written by a primary care doctor, psy- chiatrist, or neurologist. Haloperidol RESULTS Thioridazine The number of patients with PD in- creased substantially between 2000 and 2007 in all 3 centers. The Port- 0.0 5.0 10.0 15.0 land PD census increased by more Percentage than 100% (240 patients to 492 pa- tients), Puget Sound by 83% (280 Figure 2. Cumulative distribution of specific prescriptions for 3 VAMCs between 2000 and patients to 512 patients), and Spo- 2006. kane by 66% (122 patients to 203 patients). One hundred fifty-six pre-

40 • FEDERAL PRACTITIONER • FEBRUARY 2012 DOPAMINE ANTAGONISTS IN PD

scriptions of contraindicated dopa- mine antagonists were used in the Table 1. Change in prescription rates before and after analysis. a medication comment The percentage of unique patients with PD who were prescribed a dopa- Before medication After medication mine antagonist decreased from 4.5% comment comment to 1.2% at the Portland VAMC, 3.6% (% on contraindicated (% on contraindicated P to 1.0% at the Puget Sound VAMC, Location medication) medication) value and 12.3% to 1.5% at the Spokane Portlanda 2.95 0.83 .08 VAMC (Figure 1). Our data show that the number of dopamine an- Puget 3.1 0.97 .07 tagonists prescribed in all locations Soundb decreased by roughly 80% to 90% be- c tween 2000 and 2007. Spokane 6.35 1.4 .12 The specific contraindicated dopa- a The medication comment was only implemented in Portland. mine antagonists prescribed at each b There was no statistically significant difference in the change in contraindicated prescriptions VAMC were fairly similar. Olanzap- before and after the comment in Portland compared with Puget Sound (P > .05). c Spokane did have a significant difference in the change in contraindicated prescriptions before and ine, metoclopramide, and risperidone after the comment compared with Portland (P < .01). This change, however, was more prominent in were the first, second, and third most Spokane, suggesting no effect of the comment. frequently prescribed, respectively. Each center had slightly different pre- lower prescribing rates. The decrease were metoclopramide, olanzapine, scription distributions, but 1 of these in prescriptions is likely due to in- and risperidone. Considering that 3 drugs was the first or second most creased awareness that these medica- until 2001 olanzapine and risperi- commonly prescribed dopamine tions are contraindicated in patients done were the accepted standard of antagonists at each center. Figure 2 with PD. In searching for psychosis care for patients with PD and psy- shows the specific prescriptions, by and PD in PubMed, the numbers of chosis, it is not surprising that these center, for the 7-year period that was papers on this topic increased over were commonly prescribed.3 The use examined. the time of the study from 25 papers of in PD is, to our knowl- published in 2000 to 40 papers pub- edge, unique as all prior studies on DISCUSSION lished in 2007. Unique to Portland dopamine antagonists focused only From 2000 to 2007, the numbers is the medication comment, which on antipsychotics. Metoclopramide, of patients with PD in VISN 20 dra- was implemented in June 2004. This prochlorperazine, and promethazine matically increased. The increase is comment, which appears when a represented 34.6% of dopamine an- probably a combination of aging of clinician enters an order in the elec- tagonists prescribed to patients with the veteran population, better recog- tronic medical record for a contrain- PD. The number of prescriptions for nition of the disease, and more pa- dicated dopamine antagonist, states medications also decreased during tients seeking care in the VA system. that this medication is contraindi- the study. Adding up all centers, there During the same period, the number cated in patients with PD. Apparently, was an average of 16 prescriptions of patients with PD transferring care the medication comment did not de- per year between June 2000 and June to the VA increased, more than likely crease the number of prescriptions 2004, decreasing to an average of 5 because of concerns over medication of contraindicated medications, be- prescriptions per year between June costs. cause a clear trend of a decrease in 2004 and June 2006. The number of contraindicated these prescriptions in patients with The number of patients with PD dopamine antagonists prescribed PD already existed before the com- who were in our VISN 20 data set to patients with PD has greatly im- ment was instituted (Table 1). Also, is a strength of this study; the rela- proved over the last 7 years at all the reduction in the contraindicated tively small number of prescriptions centers. Overall, the VA Puget Sound dopamine antagonists was similar in for contraindicated medications is a Health Care System and the Portland the centers that did not employ the weakness. Some weaknesses are in- VAMC, which have specialized Par- medication comment. herent to a large database search. One kinson disease centers, had slightly The most common prescriptions major concern is that some patients

FEBRUARY 2012 • FEDERAL PRACTITIONER • 41 DOPAMINE ANTAGONISTS IN PD

with PD and psychosis have been Disclaimer 2. Fénelon G, Mahieux F, Huon R, Ziégler M. Hal- lucinations in Parkinson’s disease: Preva- inappropriately labeled as bipolar, The opinions expressed herein are lence, phenomenology, and risk factors. Brain. schizophrenic, or schizoaffective and, those of the authors and do not neces- 2000;123(4):733-745. 3. Olanow CW, Watts RL, Koller WC. An algorithm therefore, not included in the anal- sarily reflect those of Federal Practi- (decision tree) for the management of Parkinson’s ysis. Overall, it is encouraging that tioner, Quadrant HealthCom Inc., the disease (2001): Treatment guidelines. Neurology. fewer inappropriate dopamine antag- U.S. Government, or any of its agen- 2001;56(11)(suppl 5):S1-S88. 4. Miyasaki JM, Shannon K, Voon V, et al; Quality onists are being prescribed. l cies. This article may discuss unlabeled Standards Subcommittee of the American Academy or investigational use of certain drugs. of Neurology. Practice parameter: Evaluation and treatment of depression, psychosis, and dementia Acknowledgement Please review complete prescribing in- in Parkinson disease (an evidence-based review): This research was made possible with formation for specific drugs or drug Report of the quality standards subcommittee of the American Academy of Neurology. Neurology. support from the Portland Veterans combinations—including indications, 2006;66(7):996-1002. Affairs Parkinson Disease Research, contraindications, warnings, and ad- 5. Lapane KL, Fernandez HH, Friedman JH. Preva- lence, clinical characteristics, and pharmacologic Education, and Clinical Center (PA- verse effects—before administering treatment of Parkinson’s disease in residents in long- DRECC) by UPSHS grant NS38175. pharmacologic therapy to patients. term care facilities. SAGE Study Group. Pharmaco- therapy. 1999;19(11):1321-1327. 6. Lieberman A. Managing the neuropsychiatric symp- Author disclosures REFERENCES toms of Parkinson’s disease. Neurology. 1998:50(6) The authors report no actual or poten- 1. Edwards LL, Quigley EM, Pfeiffer RF. Gastrointes- (suppl 6):S33-S38. tinal dysfunction in Parkinson’s disease: Frequency 7. Marras C, Kopp A, Qiu F, et al. Antipsychotic use in tial conflicts of interest with regard to and pathophysiology. Neurology. 1992;42(4):726- older adults with Parkinson’s disease. Mov Disord. this article. 732. 2007;22(3):319-323.

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