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From American Journal of Health-System Pharmacy

Practitioner Versus Medication-Expert Opinion on Psychiatric Pharmacotherapy of Mentally Retarded Patients with Mental Disorders
Nick C. Patel, M. Lynn Crismon, A. John Rush, and Allen Frances Published: 10/01/2001

Abstract and Introduction

Abstract

The agreement of practicing psychiatrists with medication experts regarding how psychotropic drugs should be used to treat behavioral and psychiatric problems in patients with mental retardation was studied. The medication survey used in developing guidelines on the treatment of behavioral and psychiatric problems in mental retardation was sent to 85 psychiatrists who had been identified as caring for the mentally retarded in the Texas public mental health system. The comparison of these practitioners with the medication experts included first-line and secondline treatment choices. Survey analysis was based on using 95% confidence intervals (CIs) to determine the type of rating. If the 95% CIs for the practitioners' responses overlapped the 95% CIs for experts, the two groups were judged to be in agreement. Thirty-seven practitioners (43.5%) completed and returned the survey. Few differences between the practitioners and the medication experts were found with respect to treatments for specific mental-illness diagnoses. However, the practitioners rated venlafaxine and mirtazapine higher than the medication experts. Lithium augmentation of therapy with selective serotonin-reuptake inhibitors for non-psychotic depression was rated first-line by the practitioners and second-line by the medication experts. Practicing psychiatrists and medication experts generally agreed about the use of psychotropic drugs for mental illness in patients with mental retardation.
Introduction

Most believe that "mental retardation" refers specifically to a developmental disorder characterized by a deficit in general intellectual and adaptive functioning. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) describes mentally retarded individuals as having "an IQ of approximately 70 or below" and limitations in at least two of the following skill areas: communication, self-care, home living, social and interpersonal skills, use of community resources, self-direction, functional academic skills, work, leisure, health, and safety.[1] To be classified as mentally retarded, a person must show intellectual impairment before the age of 18 years. In earlier decades, many incorrectly believed that mentally retarded people do not have the psychological processes necessary to foster the onset of mental illness.[2] In fact, people with mental retardation can develop the same mental disorders as individuals with normal intellectual functioning, and the prevalence of these comorbid conditions in the mentally retarded is increasing.[3] A number of studies have been conducted to determine the prevalence of mental illness among the mentally retarded; most of these focused on institutionalized rather than community-based patients. Singh et al.[4] reviewed prevalence studies conducted in the late 1970s and early 1980s and concluded that (1) 8-10% of individuals with mental retardation have a severe mental disorder requiring treatment, (2) about 50% of institutionalized patients with mental retardation are likely to have at least one mental disorder, (3) about 60% of mentally retarded adults in institutions have at least one severe or minor mental disorder, (4) 20-30% of mentally retarded children in institutions have a mental disorder, and (5) 20-35% of mentally retarded children in the community have a diagnosable mental disorder. In addition, mental illness is four to five times as frequent in the mentally retarded as in the general population.[1] Mentally

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retarded people show the full range of psychiatric disorders, including most frequently schizophrenia, adjustment disorders, personality disorders, and anxiety disorders.[5] The increased prevalence of co-morbid conditions in mentally retarded people is associated with an increased use of psychotropic medications. Spreat et al.[6] reported that 22% of mentally retarded adults were prescribed antipsychotics; 9.3%, anxiolytics; and 5.9%, antidepressants. Pharmacologic treatment is indicated to suppress the abnormal thought processes and behavior associated with psychotic disorders and to treat the morbidity associated with depression and other mood disorders. Aggression, stereotypy, hyperactivity, and self-injurious behavior are relatively common symptoms and can result in harm to the mentally retarded patient, other patients, and the caregiver. Thus, all of these symptoms indicate a need for guidelines regarding the appropriate use of psychotropic medications in individuals with mental retardation. We studied the extent to which practicing psychiatrists agreed with a set of such guidelines.

Background
The Expert Consensus Guideline Series is a series of practical clinical guidelines for treating major psychiatric disorders: schizophrenia, obsessive-compulsive disorder, bi-polar disorder, posttraumatic stress disorder, agitation in older persons with dementia, and psychiatric and behavioral problems in mental retardation. [7-12] Each set of guidelines is based on a survey of expert opinion and provides various strategies for treatment. The survey itself is based on evidence from the scientific and professional literature and is constructed by an editorial board consisting of experts in the discipline being surveyed and in scientific methodology. The main purpose of the series is to aid in the decision-making of physicians, pharmacists, and other health care providers when confronted with these psychiatric disorders. There is a great need for clinical guidelines on the pharmacotherapy of mental illness in the mentally retarded. Research and experience are lacking in this specific field. With the emergence of new psychotropic medications, the confusion only increases. The "Expert Consensus Guideline Series: Treatment of Psychiatric and Behavioral Problems in Mental Retardation" (hereafter called PBPMR guidelines) provides practitioners with appropriate clinical guidelines and algorithms for the treatment of mental illness in the mentally retarded.[12] The Texas Department of Mental Health and Mental Retardation (TXMHMR) operates 11 regional state schools and contracts for out-patient care through 42 community centers statewide. The state schools are intermediate care facilities for the mentally retarded, and patients' medical needs are placed in the hands of general and family practice physicians. Psychiatrists are consulted when a mentally retarded patient manifests a psychiatric disorder or behavioral disturbance. In the community center setting, mentally retarded clients receive a variety of services intended to improve their adaptive functioning, and they are seen by a psychiatrist only if a psychiatric disorder or behavioral problem occurs. Although behavioral programs are used as interventions to stabilize pathological behavior, pharmacologic treatment may be necessary. This is largely agreed upon if a patient's symptoms meet DSM-IV criteria for a given disorder. Even then, there are difficulties with respect to patient assessment and monitoring, and no uniform guidelines previously existed regarding the preferred pharmacologic approach. The situation is even more difficult for patients with symptoms and behavior that interfere with daily functioning but do not meet DSM-IV criteria for a psychiatric disorder. Until the publication of the PBPMR guidelines, there was no clear consensus on the best methods for patient assessment, when to use medications, and the preferred medication strategies. Our study examined how closely TXMHMR psychiatrists agreed with the PBPMR guidelines.

Methods
PBPMR guidelines

The editors of the PBPMR guidelines first created a skeleton document based on the standard literature to identify key decision points in the everyday treatment of behavioral and psychiatric problems in mental retardation.[12] They highlighted points on which the literature was indefinite and then developed a written questionnaire concerning these

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treatment issues. The questionnaire used a 9-point scale slightly modified from a survey format developed by the RAND Corporation for ascertaining expert consensus. Scores in the range of 7-9 were used to indicate the degree of appropriateness; 4-6, the degree of equivocal opinion; and 1-3, the degree of inappropriateness. Anchor points were also provided to further distinguish the 9-point rating scale.[13,14] The experts were asked not to consider cost when making their ratings. The editors asked questions about 40 clinical situations.[12] The questionnaire was sent in the spring of 1999 to 51 leading U.S. experts on pharmacotherapy of mental illness in mental retardation, who were identified from recent research publications, recipients of research grants, presenters at the Nisonger International Consensus Conference, and College of Psychiatric and Neurologic Pharmacists members. In analyzing the survey results, the editors first calculated the mean, standard deviation, and 95% confidence interval (CI) for each item. The 95% CI is a statistically calculated range that tells the reader that, if the survey were repeated with a similar group of experts, there is a 95% chance the mean score would fall within that range.[15] The editors designated a rating of first-line, second-line, or third-line treatments for each item for which there was consensus. This rating was determined by the category in which the 95% CI of its mean score fell. First-line treatments were those strategies the expert panel believed were usually appropriate as initial treatments for a given situation. "Treatment of choice," when it appeared, was an especially strong first-line recommendation (having been rated a 9 by at least half the experts). In choosing among several first-line recommendations, or in deciding whether to use a first-line treatment at all, practitioners should consider the overall clinical situation, including the patient's prior response to treatment, adverse effects, general medical problems, and patient preferences. Second-line treatments were reasonable choices for patients who could not tolerate or did not respond to the first-line choices. Alternatively, practitioners could select a second-line choice as initial treatment if the first-line options were deemed unsuitable for a particular patient. For some questions, second-line ratings dominated, especially when the experts did not reach any consensus on firstline options. In such cases, to differentiate within the group, the editors labeled items whose 95% CIs overlapped those of the first-line category as "high second-line." Third-line treatments were usually inappropriate or were used only when preferred alternatives were not effective. For each item in the survey, the editors used a chi-square test to determine whether the experts' distribution of responses differed from a chance distribution and to find some items for which there was no convergence of expert opinion. After survey analysis and assignment of ratings, the experts' recommendations were translated into clinical guidelines.
TXMHMR Survey

The survey used in developing the PBPMR guidelines was sent in the fall of 1999 to psychiatric consultants at the TXMHMR state schools and to psychiatrists identified by their medical directors as spending a significant amount of their time treating mentally retarded clients with mental disorders in community centers. A $75 honorarium was paid to the psychiatrists for completing and returning the survey. Survey analyses and ratings were conducted in the same manner as the PBPMR guidelines and then compared with those guidelines.
Comparison of PBPMR guideline experts with TXMHMR practitioners

Results from the PBPMR guideline survey and the TXMHMR survey were compared by using the following approach. First-line treatment choices and high second-line choices in the PBPMR guideline survey were compared with

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responses to the same item from the TXMHMR practitioner survey. If the 95% CIs for the responses of the TXMHMR practitioners (hereafter called the practitioners) overlapped with those of the PBPMR guideline experts (hereafter called the medication experts), the responses were judged to be in agreement.

Results
Thirty-seven (43.5%) of 85 practitioners completed and returned the medication survey. The responding practitioners ranged in age from 36 to 74 years (mean S.D., 53.2 9.1 years), and 83% were men. All 37 practitioners specialized in psychiatry, with 18.3 9.8 years having passed since terminal training. Seventy-one percent were board-certified in psychiatry. Their practice with mentally retarded patients was 20.0% 36.3% inpatient and 63.0% 42.3% outpatient.
Agreement between practitioners and medication experts

Practitioners and medication experts generally agreed regarding the preferred pharmacologic treatments for specific DSM-IV diagnoses and target symptoms in patients not meeting criteria for a DSM-IV diagnosis. Valproate was considered the treatment of choice for patients diagnosed with bipolar disorder, manic episode. Both medication experts and practitioners rated newer atypical antipsychotics as treatments of choice for schizophrenic patients who are compliant with oral medications. Selective serotonin-reuptake inhibitors (SSRIs) were the treatments of choice for obsessive-compulsive disorder and major depressive disorder. Psychostimulants were the treatments of choice for patients with attention-deficit hyperactivity disorder. Newer atypical antipsychotics were considered first-line therapy for self-injurious behavior. For patients with nonaggressive agitation, anticonvulsants-mood stabilizers were rated first-line by both groups. Antidepressants were the treatments of choice for patients with suicidal ideation or behavior. Agreement between the practitioners and the medication experts was further evident in their choices of preferred medications within different classes for the treatment of target symptoms in patients not meeting the criteria for a DSMIV diagnosis. Risperidone was preferred among antipsychotics for treating self-injurious behavior and aggressive or destructive behavior. Divalproex and valproate were preferred anticonvulsants-mood stabilizers for the treatment of self-injurious behavior, aggressive or destructive behavior, and psychiatric or behavioral problems in patients with comorbid epilepsy. SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) were preferred by both groups when an antidepressant was indicated for depressive symptoms, self-injurious behavior, aggressive or destructive behavior, nonaggressive agitation, or anxiety. SSRIs were also the preferred anxiolytics for treating anxiety, selfinjurious behavior, and aggressive or destructive behavior.
Differences between practitioners and medication experts

Significant differences between practitioners and medication experts were apparent in the recommendations regarding uses of venlafaxine, mirtazapine, and lithium (Table 1). The practitioners considered venlafaxine a first-line agent for major depressive episodes and the target symptom of depression. The medication experts rated it high second-line therapy for these clinical presentations. The practitioners also considered venlafaxine first-line as an alternative agent when no response was seen with SSRIs in patients with nonpsychotic depression, whereas the medication experts rated it high second-line. The practitioners favored mirtazapine more than the medication experts when treating the target symptoms of depression, self-injurious behavior, and aggressive or destructive behavior. The practitioners considered mirtazapine first-line as an alternative agent when no response was seen with SSRIs in patients with nonpsychotic depression. Assuming a partial response to an adequate trial of an SSRI for nonpsychotic depression, the practitioners considered lithium augmentation first-line adjunctive therapy, whereas the medication experts rated lithium second-line. The practitioners rated the following medications higher than the medication experts in terms of long-term safety and adverse-effect profiles (if maintained at a steady dosage and with minimal monitoring): "other newer antidepressants" (bupropion, venlafaxine), "newer atypical antipsychotics" (olanzapine, quetiapine, risperidone), and

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"newer sedating antidepressants" (mirtazapine, nefazodone). The practitioners were more inclined than the medication experts to initially treat self-injurious behavior and other symptoms disruptive to the patient's family and caregivers with a psychotropic medication. In addition, the practitioners were more apt than the medication experts to continue pharmacologic treatment for the clinical factors of nonresponse to psychosocial interventions and symptoms disruptive to the patient's family and caregivers.

Discussion
The psychiatrists treating mentally retarded patients in the TXMHMR system were largely in agreement on pharmacologic treatments and strategies for mental illness in the mentally retarded (as indicated by the narrowness of the 95% CIs for their responses). The practitioners agreed with each other regarding the initial treatments of choice for specific DSM-IV psychiatric disorders and some of the severe and persistent psychiatric and behavioral target symptoms for which reliable diagnoses cannot be made (physical aggression toward people or property, anxiety, and suicidal ideation or behavior). Although guidelines for the treatment of mental illness in mentally retarded patients have not been implemented in the TXMHMR facilities, the overall consensus among the practitioners is noteworthy. Practitioners have been criticized as not basing their daily practice on solid scientific evidence.[16] But realistically, they cannot both evaluate all the current data on treatment that might affect their daily practice decisions and care for patients. Thus, the overall agreement in the survey findings between the practitioners and medication experts is encouraging. In addition, the concordance between the two groups provides face validity to the PBPMR guidelines. The practitioners were more inclined than the medication experts to use the newer antidepressants venlafaxine and mirtazapine for the treatment of specific DSM-IV psychiatric disorders and some of the severe and persistent target symptoms for which reliable diagnoses cannot be made. Several possible reasons exist for this finding. First, practitioners are susceptible to the pharmaceutical industry's marketing strategies, especially the influence of sales representatives. Up to 87% of physicians and 51% of medical residents have interactions with pharmaceutical company representatives several times per month.[17] The passage of time (six to seven months) between publication of the PBPMR guidelines and this study may have allowed for more contact between the practitioners and sales representatives. These interactions can influence physicians and residents to prescribe new drugs preferentially.[18] Venlafaxine and mirtazapine -- recent additions to the market -- are marketed as first-line alternatives to more established antidepressants, such as SSRIs. Second, the medication experts may have been more likely than the practitioners to base their decisions on scientific evidence. Efficacy and adverse-effect studies of newer anti-depressants used in mentally retarded people are few, and medication experts could conceivably be more cautious in using these medications as first-line agents. This is most obvious in the use of mirtazapine for the target symptom of aggressive or destructive behavior. Despite there being no published reports of mirtazapine's efficacy for this problem, the practitioners rated it as high second-line to first-line therapy. The medication experts, on the other hand, considered mirtazapine to be second-line. Third, the Texas Medication Algorithm Project (TMAP) has rated these newer antidepressants as first-line alternatives in the treatment of major depressive disorder in the non-developmentally impaired population. [19] These guidelines and treatment algorithms have been widely disseminated throughout Texas, and some community mental health and mental retardation centers had received training on the treatment algorithm for major depressive disorder at the time of the survey. Even though the TMAP recommendations apply only to treatment of major depressive disorder, this may have influenced the practitioners' responses. Venlafaxine and mirtazapine have shown some superiority in efficacy for severe depression compared with SSRIs, and they have desirable safety profiles in the event of overdose and few documented drug interactions.[20-23] Mirtazapine has sedative effects that theoretically may be beneficial in the treatment of behavioral or aggressive target symptoms.[22] Even in the absence of conclusive data, these potential advantages of the newer antidepressants may promote their use by clinicians for patients who are severely depressed, suicidal, taking multiple medications, or showing behavioral or aggressive target symptoms.

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Fourth, these response differences might reflect more rapid adoption of new treatments by practitioners than by medication experts. The practitioners, but not the medication experts, rated lithium augmentation as first-line adjunctive therapy for a partial response to SSRIs for nonpsychotic depression. Again, a possible explanation for this difference may be the TMAP recommendations, which advise lithium augmentation as a first-line option in patients demonstrating no response or a partial response to antidepressant monotherapy.[19] Lithium has been widely studied as augmentation treatment in depressed patients who respond partially to antidepressants. Favorable responses to lithium augmentation have been seen in controlled studies involving several classes of antidepressants, including SSRIs, tricyclic antidepressants, and monoamine oxidase inhibitors.[24,25] Other differences between the practitioners' and the medication experts' opinions may have been influenced by the treatment environment. When symptoms were disruptive to patients, their families, or caregivers, the practitioners tended to prefer drug therapy management. On the other hand, the medication experts were more inclined to recommend psychosocial and behavioral therapy before initiating drug therapy. In the clinical setting, the safety of the patient, the family, caregivers, and other patients is of great importance, and practitioners are often encouraged to "do something" immediately. Psychosocial and behavioral interventions require time to work, but in some circumstances rapid control of symptoms is of the essence. Although research evidence supports the use of behavioral therapy, the availability of consistent behavioral therapy in the community is often inadequate. Behavioral treatment is not often well received in mental health care settings and meets resistance in the form of organizational barriers, lack of knowledge, a tendency to punish patients, and staff opposition.[26,27] Staff members sometime believe that behavioral therapy is "common sense," and as a result this pessimistic attitude can have negative effects on patients' behavior. This study has limitations. The number of responding practitioners (n = 37) was smaller than the number of medication experts (n = 51). Possible explanations include practitioner relocation, lost surveys in the mail, and unwillingness to complete and return the survey. Another limitation is that practitioner responses may or may not reflect actual practice behavior. Several studies suggest that practitioners' behavior may not be consistent with their opinions about certain clinical circumstances and treatment guidelines. For example, Pathman et al.[28] found that only 30.1% of physicians followed the hepatitis B vaccination recommendation for infants, even though 98.4% were aware of it. Christakis and Rivara [29] found that, although 66% of pediatricians were familiar with the American Academy of Pediatrics hyperbilirubinemia guidelines, only 28% adhered to them. Follow-up studies are needed to determine if physicians' practice behavior is consistent with their responses in this survey.

Conclusion
Practicing psychiatrists and medication experts were in general agreement regarding the use of psychotropic medications for mental illness in patients with mental retardation.
References

1. Diagnostic and statistical manual of mental disorders, fourth edition. Washington, DC: American Psychiatric Association; 1994. 2. Sovner R, Hurley AD. Do the mentally retarded suffer from affective illness? Arch Gen Psychiatry. 1993; 40:617. 3. Reiss S, Aman MG, eds. Psychotropic medication and developmental disabilities: the international consensus handbook. Columbus, OH: Ohio State University Nisonger Center; 1998. 4. Singh NN, Sood A, Sonenklar N et al. Assessment and diagnosis of mental illness in persons with mental retardation. Behav Modif. 1991; 15:419-41. 5. Stark JA, Menolascino FJ, Albarelli MH et al. Mental retardation and mental health. New York: Springer-Verlag; 1988. 6. Spreat S, Conroy JW, Jones JC. Use of psychotropic medication in Oklahoma: a statewide survey. Am J Ment

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Retard. 1997; 102:80-5. 7. McEvoy JP, Scheifler PL, Frances A. The Expert Consensus Guideline Series: treatment of schizophrenia 1999. J Clin Psychiatry. 1999; 60(suppl 11):1-80. 8. March JS, Frances A, Carpenter D et al. The Expert Consensus Guideline Series: treatment of obsessivecompulsive disorder. J Clin Psychiatry. 1997; 58(suppl 4):1-72. 9. Sachs GS, Printz DJ, Kahn DA et al. The Expert Consensus Guideline Series: medication treatment of bipolar disorder 10. Postgrad Med Spec Rep. 2000; Apr:1-104. 11. Foa EB, Davidson JRT, Frances A. The Expert Consensus Guideline Series: treatment of posttraumatic stress disorder. J Clin Psychiatry. 1999; 60(suppl 16):1-76. 12. Alexopoulos GS, Silver JM, Kahn DA et al. The Expert Consensus Guideline Series: treatment of agitation in older persons with dementia. Postgrad Med Spec Rep. 1998; Apr:1-88. 13. Rush AJ, Frances A, eds. Expert Consensus Guideline Series: treatment of psychiatric and behavioral problems in mental retardation. Am J Ment Retard. 2000; 105:159-226. 14. Brook RH, Chassin MR, Fink A et al. A method for the detailed assessment of the appropriateness of medical technologies. Int J Technol Assess Health Care. 1986; 2:53-63. 15. Kahn DA, Docherty JP, Carpenter D et al. Consensus methods in practice guideline development: a review and description of a new method. Psychopharmacol Bull. 1997; 33(4):631-9. 16. Hinkle DE, Wiersma W, Jurs SG. Applied statistics for the behavioral sciences. 3rd ed. Boston: Houghton Mifflin; 1994. 17. Trivedi MH, Rush AJ, Crismon ML et al. Treatment guidelines and algorithms. In: Dunner DL, Rosenbaum JF, eds. Psychiatric Clinics of North America annual review of drug therapy 2000. Philadelphia: Saunders; 2000:122. 18. Wazana A. Physicians and the pharmaceutical industry: is a gift ever just a gift? JAMA. 2000; 283:373-80. 19. Peay MY, Peay ER. The role of commercial sources in the adoption of a new drug. Soc Sci Med. 1988; 26:1183-9. 20. Crismon ML, Trivedi M, Pigott TA et al. The Texas Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Major Depressive Disorder. J Clin Psychiatry. 1999; 60:142-56. 21. Hirschfield RM. Efficacy of SSRIs and newer antidepressants in severe depression: comparison with TCAs. J Clin Psychiatry. 1999; 60:326-35. 22. Schatzberg AF. Antidepressant effectiveness in severe depression and melancholia. J Clin Psychiatry. 1999; 60 (suppl 4): 14-21. 23. Nelson JC. Safety and tolerability of the new antidepressants. J Clin Psychiatry. 1997; 58(suppl 6):26-31. 24. Ereshefsky L, Riesenman C, Lam YW. Antidepressant drug interactions and the cytochrome P450 system: the role of cytochrome P450 2D6. Clin Pharmacokinet. 1995; 29(suppl 1):10-8. 25. Rouillon F, Gorwood P. The use of lithium to augment antidepressant medication. J Clin Psychiatry. 1998; 59 (suppl 5): 32-9. 26. Nelson JC. Augmentation strategies in depression 2000. J Clin Psychiatry. 2000; 61(suppl 2):13-9. 27. Hilton NZ, Simmons JL. Adverse effects of poor behavior management of an inpatient's difficult behaviors. Psychiatr Serv. 1999; 50:964-6. 28. Corrigan PW, McCracken SG, Edwards M et al. Staff training to improve implementation and impact of behavioral rehabilitation programs. Psychiatr Serv. 1997; 48:1336-8. 29. Pathman DE, Konrad TR, Freed GL et al. The awareness-to-adherence model of the steps to clinical guideline compliance. The case of pediatric vaccine recommendations. Med Care. 1996; 34:873-89. 30. Christakis DA, Rivara FP. Pediatricians' awareness of and attitudes about four clinical practice guidelines. Pediatrics. 1998; 101:825-30.

Authors and Disclosures

Nick C. Patel, Pharm.D., is a graduate student and psychiatric pharmacy resident, College of Pharmacy, The

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University of Texas at Austin (UTA). M. Lynn Crismon, Pharm.D., is Professor and Southwestern Drug Corporation Centennial Fellow in Pharmacy, College of Pharmacy, UTA, and Clinical Psychopharmacologist, Office of the Medical Director, Texas Department of Mental Health and Mental Retardation, Austin. A. John Rush, M.D., is Professor and Vice Chairman for Research, Betty Jo Hay Distinguished Chair in Mental Health and Rosewood Corporation Chair in Biomedical Science, Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas. Allen Frances, M.D., is Professor, Department of Psychiatry, Duke University, Durham, NC.

Acknowledgments The assistance of Ruth Ross, M.A., and David Ross, M.A., M.C.E., of Ross Editorial Services is acknowledged. Funding Information Supported in part by educational grants from Pfizer, Inc., and by the Texas Department of Mental Health and Mental Retardation. Submitted to the College of Pharmacy, UTA, in partial fulfillment of the requirements for the doctor of pharmacy degree (honors program). American Journal of Health-System Pharmacy. 2001;58(19) 2001 American Society of Health-System Pharmacists

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