Anticipated Benefits of Care (ABC): psychometrics and predictive value in psychiatric disorders.

BACKGROUND: Attitudes and expectations about treatment have been associated with symptomatic outcomes, adherence and utilization in patients with psychiatric disorders. No measure of patients' anticipated benefits of treatment on domains of everyday functioning has previously been available. METHOD: The Anticipated Benefits of Care (ABC) is a new, 10-item questionnaire used to measure patient expectations about the impact of treatment on domains of everyday functioning. The ABC was collected at baseline in adult out-patients with major depressive disorder (MDD) (n=528), bipolar disorder (n=395) and schizophrenia (n=447) in the Texas Medication Algorithm Project (TMAP). Psychometric properties of the ABC were assessed, and the association of ABC scores with treatment response at 3 months was evaluated. RESULTS: Evaluation of the ABC's internal consistency yielded Cronbach's alpha of 0.90-0.92 for patients across disorders. Factor analysis showed that the ABC was unidimensional for all patients and for patients with each disorder. For patients with MDD, lower anticipated benefits of treatment was associated with less symptom improvement and lower odds of treatment response [odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57-0.87, p=0.0011]. There was no association between ABC and symptom improvement or treatment response for patients with bipolar disorder or schizophrenia, possibly because these patients had modest benefits with treatment. CONCLUSIONS: The ABC is the first self-report that measures patient expectations about the benefits of treatment on everyday functioning, filling an important gap in available assessments of attitudes and expectations about treatment. The ABC is simple, easy to use, and has acceptable psychometric properties for use in research or clinical settings.

Cerebrospinal fluid monoamine metabolites and glucose metabolism in posttraumatic aggression.

BACKGROUND: This pilot study was conducted to determine if aggressive, post brain-injured patients have abnormal glucose metabolism or abnormal CSF monoamine metabolite concentrations as compared with non-aggressive, post brain-injured controls. METHODS: Subjects with a history of traumatic brain injury underwent a lumbar puncture and glucose tolerance test after a three-week medication wash-out period. Monoamine metabolite concentrations and glucose nadirs were compared between aggressive and control subjects. RESULTS: There were no statistical differences between the aggressive (n = 4) and control (n = 6) group with respect to age (28.5 +/- 15.7 versus 28.0 +/- 10.8), weight (72.5 kg +/- 14.1 versus 67.7 kg +/- 10.1) or number of months since brain injury (31.8 +/- 26.1 versus 33.3 +/- 23.3). There were no significant differences between the two groups in glucose nadirs following oral glucose challenge or in levels of CSF monoamine metabolite concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), or 3-methoxy-4-hydroxyphenylglycol (MHPG), although a trend toward significance was noted between the MHPG groups (higher MHPG within aggressive group). CONCLUSIONS: The preliminary data suggest that glucose metabolism and CSF monoamine metabolite concentrations do not differ significantly from aggressive subjects to controls in persons with brain injury. Follow-up prospective studies with larger sample sizes are needed to evaluate these preliminary findings.

Consensus guidelines in the treatment of major depressive disorder.

The number of available antidepressant medications has increased dramatically in the last 10 years. Furthermore, no single medication is a panacea for all depressed patients-a fact underscored by randomized, controlled trial evidence showing that when one medication fails, an alternative may succeed. Thus, a key issue in the treatment of depression is how to optimally orchestrate available medication options to maximally benefit the greatest number of patients most rapidly. One approach is the use of consensus guidelines or medication algorithms. This paper discusses the rationale for and critical issues in the development of medication algorithms, and the timely use of symptom measures to ensure proper implementation. Once developed, guidelines must be appropriately implemented by clinicians, adhered to by patients, and supported by administrators. These three stakeholder groups often need education, incentives, and ongoing support to implement such guidelines. Whether guidelines actually improve outcome is largely uninvestigated, although a recent study of depressed patients in primary care found that using guidelines did improve outcome but at an increased treatment cost. The clinical and economic impact of guideline-driven treatment for the severe and persistently depressed deserves study.

Mental health care from the public perspective: the Texas Medication Algorithm Project.

Medication treatment algorithms have been suggested as a strategy to provide uniform care at predictable costs. The Texas Medication Algorithm Project is a 3-phase study designed to provide solid data on the usefulness of medication algorithms. In phase 1, medication algorithms for the treatment of schizophrenia, major depressive disorder, and bipolar disorder were developed. Phase 2 was a feasibility study of these algorithms, and phase 3, now underway, compares the costs and outcome in 3 groups, one using a combination of an algorithm and patient/family education, a second using treatment as usual in a clinic that uses an algorithm for a different disorder, and a third using treatment as usual in a nonalgorithm clinic.

Texas Medication Algorithm Project: definitions, rationale, and methods to develop medication algorithms.

BACKGROUND: The Texas Medication Algorithm Project (TMAP), a public-academic collaborative effort, is a 3-phase project to develop, implement, and evaluate medication treatment algorithms for public sector patients with schizophrenia, major depressive disorders, or bipolar disorders. DISCUSSION: This paper, the first in a series describing the activities of the TMAP, focuses on the various definitions and reasons why guidelines have gained popularity. Also discussed are their strengths, the limitations of the various methods used to develop them, and potential barriers to their implementation.

The Texas Medication Algorithm Project (TMAP) schizophrenia algorithms.

BACKGROUND: In the Texas Medication Algorithm Project (TMAP), detailed guidelines for medication management of schizophrenia and related disorders, bipolar disorders, and major depressive disorders have been developed and implemented. DISCUSSION: This article describes the algorithms developed for medication treatment of schizophrenia and related disorders. The guidelines recommend a sequence of medications and discuss dosing, duration, and switch-over tactics. They also specify response criteria at each stage of the algorithm for both positive and negative symptoms. The rationale and evidence for each aspect of the algorithms are presented.

The Texas Medication Algorithm Project Patient and Family Education Program: a consumer-guided initiative.

Educating patients with mental illness and their families about the illness and its treatment is essential to successful medication (disease) management. Specifically, education provides patients and families with the background they need to participate in treatment planning and implementation as full "partners" with clinicians. Thus, education increases the probability that appropriate and accurate treatment decisions will be made and that a treatment regimen will be followed. The Texas Medication Algorithm Project (TMAP) has incorporated these concepts into its philosophy of care and accordingly created a Patient and Family Education Program (PFEP) to complement the utilization of medication algorithms for the treatment of schizophrenic, bipolar, and major depressive disorders. This article describes how a team of mental health consumers, advocates, and professionals developed and implemented the PFEP. In keeping with the TMAP philosophy of care, consumers were true partners in the program's development and implementation. They not only created several components of the program and incorporated the consumer perspective, but they also served as program trainers and advocates. Initially, PFEP provides basic and subsequently more in-depth information about the illness and its treatment, including such topics as symptom monitoring and management and self-advocacy with one's treatment team. It includes written, pictorial, videotaped, and other media used in a phased manner by clinicians and consumer educators, in either individual or group formats.

Texas Medication Algorithm Project: development and feasibility testing of a treatment algorithm for patients with bipolar disorder.

BACKGROUND: Use of treatment guidelines for treatment of major psychiatric illnesses has increased in recent years. The Texas Medication Algorithm Project (TMAP) was developed to study the feasibility and process of developing and implementing guidelines for bipolar disorder, major depressive disorder, and schizophrenia in the public mental health system of Texas. This article describes the consensus process used to develop the first set of TMAP algorithms for the Bipolar Disorder Module (Phase 1) and the trial testing the feasibility of their implementation in inpatient and outpatient psychiatric settings across Texas (Phase 2). METHOD: The feasibility trial answered core questions regarding implementation of treatment guidelines for bipolar disorder. A total of 69 patients were treated with the original algorithms for bipolar disorder developed in Phase 1 of TMAP. RESULTS: Results support that physicians accepted the guidelines, followed recommendations to see patients at certain intervals, and utilized sequenced treatment steps differentially over the course of treatment. While improvements in clinical symptoms (24-item Brief Psychiatric Rating Scale) were observed over the course of enrollment in the trial, these conclusions are limited by the fact that physician volunteers were utilized for both treatment and ratings. and there was no control group. CONCLUSION: Results from Phases 1 and 2 indicate that it is possible to develop and implement a treatment guideline for patients with a history of mania in public mental health clinics in Texas. TMAP Phase 3, a recently completed larger and controlled trial assessing the clinical and economic impact of treatment guidelines and patient and family education in the public mental health system of Texas, improves upon this methodology.

The Texas Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Major Depressive Disorder.

BACKGROUND: This article describes the development of consensus medication algorithms for the treatment of patients with major depressive disorder in the Texas public mental health system. To the best of our knowledge, the Texas Medication Algorithm Project (TMAP) is the first attempt to develop and prospectively evaluate consensus-based medication algorithms for the treatment of individuals with severe and persistent mental illnesses. The goals of the algorithm project are to increase the consistency of appropriate treatment of major depressive disorder and to improve clinical outcomes of patients with the disorder. METHOD: A consensus conference composed of academic clinicians and researchers, practicing clinicians, administrators, consumers, and families was convened to develop evidence-based consensus algorithms for the pharmacotherapy of major depressive disorder in the Texas mental health system. After a series of presentations and panel discussions, the consensus panel met and drafted the algorithms. RESULTS: The panel consensually agreed on algorithms developed for both nonpsychotic and psychotic depression. The algorithms consist of systematic strategies to define appropriate treatment interventions and tactics to assure optimal implementation of the strategies. Subsequent to the consensus process, the algorithms were further modified and expanded iteratively to facilitate implementation on a local basis. CONCLUSION: These algorithms serve as the initial foundation for the development and implementation of medication treatment algorithms for patients treated in public mental health systems. Specific issues related to adaptation, implementation, feasibility testing, and evaluation of outcomes with the pharmacotherapeutic algorithms will be described in future articles.

Medication treatment for the severely and persistently mentally ill: the Texas Medication Algorithm Project.

This article provides an overview of the issues involved in developing, using, and evaluating specific medication guidelines for patients with psychiatric disorders. The potential advantages and disadvantages, as well as the essential elements in the structure of algorithms, are illustrated by experience to date with the Texas Medication Algorithm Project, a public-academic collaboration. Phase 1 entailed assembling research findings on the efficacy of medications for schizophrenic, bipolar, and major depressive disorders. This knowledge was evaluated for its quality and relevance, integrated with expert clinical judgment as well as input by practicing clinicians, family advocates, and patients. Phase 1 (the design and development of the algorithms) was followed by a feasibility test (Phase 2). Phase 3 is an ongoing evaluation comparing the clinical and economic effects of using specific medication guidelines (algorithms) versus treatment as usual in public sector patients with severe and persistent mental illnesses.

The Texas Children's Medication Algorithm Project: Report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Attention-Deficit/Hyperactivity Disorder. Part I. Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES: Expert consensus methodology was used to develop evidence-based, consensually agreed-upon medication treatment algorithms for attention-deficit/hyperactivity disorder (ADHD) in the public mental health sector. Although treatment algorithms for adult mental disorders have been developed, this represents one of the first attempts to develop similar algorithms for childhood mental disorders. Although these algorithms were developed initially for the public sector, the goals of this approach are to increase the uniformity of treatment and improve the clinical outcomes of children and adolescents with ADHD in a variety of treatment settings. METHOD: A consensus conference of academic clinicians and researchers, practicing clinicians, administrators, consumers, and families was convened to develop evidence-based consensus algorithms for the pharmacotherapy of childhood ADHD. After a series of presentations of current research evidence and panel discussion, the consensus panel met and drafted the algorithms along with guidelines for implementation. RESULTS: The panel developed consensually agreed-upon algorithms for ADHD with and without specific comorbid disorders. The algorithms consist of systematic strategies for psychopharmacological interventions and tactics to ensure successful implementation of the strategies. While the algorithms focused on the medication management of ADHD, the conference emphasized that psychosocial treatments are often a critical component of the overall management of ADHD. CONCLUSIONS: Medication algorithms for ADHD can be developed with consensus. A companion article will discuss the implementation of these algorithms.

The Texas Children's Medication Algorithm Project: Report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Attention-Deficit/Hyperactivity Disorder. Part II: Tactics. Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES: Expert consensus methodology was used to develop a medication treatment algorithm for attention-deficit/hyperactivity disorder (ADHD). The algorithm broadly outlined the choice of medication for ADHD and some of its most common comorbid conditions. Specific tactical recommendations were developed with regard to medication dosage, assessment of drug response, management of side effects, and long-term medication management. METHOD: The consensus conference of academic clinicians and researchers, practicing clinicians, administrators, consumers, and families developed evidence-based tactics for the pharmacotherapy of childhood ADHD and its common comorbid disorders. The panel discussed specifics of treatment of ADHD and its comorbid conditions with stimulants, antidepressants, mood stabilizers, alpha-agonists, and (when appropriate) antipsychotics. RESULTS: Specific tactics for the use of each of the above agents are outlined. The tactics are designed to be practical for implementation in the public mental health sector, but they may have utility in many practice settings, including the private practice environment. CONCLUSIONS: Tactics for psychopharmacological management of ADHD can be developed with consensus.

The Texas Children's Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder.

OBJECTIVES: To develop consensus guidelines for medication treatment algorithms for childhood major depressive disorder (MDD) based on scientific evidence and clinical opinion when science is lacking. The ultimate goal of this approach is to synthesize research and clinical experience for the practitioner and to increase the uniformity of preferred treatment for childhood MDD. A final goal is to develop an approach that can be tested as to whether it improves clinical outcomes for children and adolescents with MDD. METHOD: A consensus conference was held. Participants included academic clinicians and researchers, practicing clinicians, administrators, consumers, and families. The focus was to review and use clinical evidence to recommend specific pharmacological approaches for treatment of MDD in children and adolescents. After a series of presentations of current research evidence and panel discussion, the consensus panel met, agreed on assumptions, and drafted the algorithms. The process initially addressed strategies of treatment and then tactics to implement the strategies. RESULTS: Consensually agreed-upon algorithms for major depressions (with and without psychosis) and comorbid attention deficit disorders were developed. Treatment strategies emphasized the use of selective serotonin reuptake inhibitors. The algorithm consists of systematic strategies for treatment interventions and recommended tactics for implementation of the strategies, including medication augmentation and medication combinations. Participants recommended prospective evaluation of the algorithms in various public sector settings, and many volunteered as sites for such an evaluation. CONCLUSIONS: Using scientific and clinical experience, consensus-derived algorithms for children and adolescents with MDD can be developed.

Medical services utilization and charge comparisons between elderly patients with and without Alzheimer's disease in a managed care organization.

OBJECTIVES: The purposes of this study were to describe the health service utilization patterns and the associated charges for elderly patients (aged > or = 65 years) diagnosed with Alzheimer's disease (AD) enrolled in a managed care organization (MCO), and to compare these patterns and charges with those of elderly enrollees not diagnosed with AD (non-AD). METHODS: We analyzed medical claims data over a 12-month period for the population of elderly patients with a diagnosis of AD or AD-related dementia, and for all other elderly patients enrolled in an integrated MCO. Comparisons were made at the level of service location (eg, inpatient hospital, outpatient hospital, physician's office). RESULTS: For a total of 250 patients diagnosed with AD (66.0% female, 34.0% male; mean age. 80.5 years), health care charges were 1.6 times higher per patient per year than the corresponding charges for 13,553 non-AD patients (58.6% female, 41.4% male; mean age, 73.3 years). AD patients received 1.7 times more health care services per patient per year than their non-AD counterparts. CONCLUSIONS: Despite the lack of nursing home and prescription drug data, our results show that AD patients in this MCO used more health care services and had higher annual medical care charges than non-AD patients. If MCOs conduct similar analyses of elderly AD patients' patterns of care and compare these with the patterns of elderly non-AD patients, they may be able to pinpoint areas of disparity in medical care and improve service delivery for AD patients.

Pharmacokinetics and drug interactions of cholinesterase inhibitors administered in Alzheimer's disease.

Cholinesterase inhibitors are the first agents to be successfully developed specifically for the treatment of cognitive decline associated with Alzheimer's disease. Basic knowledge of their pharmacokinetics is important to their appropriate administration. Their pharmacokinetics help determine the magnitude and duration of their pharmacologic effects, and also the manner in which they affect the degree of cholinesterase inhibition and recovery. The clinical utility of measuring these values in daily practice awaits further research. Drug interactions with cholinesterase inhibitors may occur by pharmacokinetic or pharmacodynamic mechanisms. For the most part, interactions that are mediated by the hepatic cytochrome P-450 system have been inadequately evaluated.

Pharmacotherapy of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a potentially devastating illness, both to the patient and family members. Its etiology is unclear, but some evidence points toward dysfunction in an orbitofrontal striatal-limbic neuronal loop. Although many agents have been used, clomipramine, a tricyclic antidepressant, appears to be the most promising therapy. Clomipramine was approved by the Food and Drug Administration and released for general use in early 1990 under the brand name Anafranil. Clomipramine's adverse effect profile is similar to that of currently marketed tricyclic antidepressants; however, it is associated with a higher frequency of seizures, estimated to be 0.7%. Although other serotonergic agents such as fluoxetine have shown promise in OCD, they have been studied only in a limited number of patients. Other agents, with the possible exception of monoamine oxidase inhibitors, either have resulted in inconsistent improvement or have been reported in an anecdotal fashion.

Antipsychotic agents in patients with dementia.

We conducted a MEDLINE search to obtain data on various antipsychotics administered to patients with dementia and psychosis or behavioral symptoms. Additional unpublished data from conference proceedings and unpublished clinical trials were provided by Janssen Pharmaceutica, Eli Lilly and Company, and Zeneca Pharmaceuticals. All clinical trials that evaluated traditional typical or atypical antipsychotics in patients with dementia were reviewed for efficacy and safety data. Consensus guidelines published in 1994 or later were considered. After reviewing clinical trials and expert opinions, we devised an algorithm for optimal treatment of these patients. Although data are limited and do not conclusively show superiority of one agent over another, based on clinical experience and side effect profiles, risperidone is considered to be the drug of choice for treating patients with dementia and psychosis. Alternative treatment options in an algorithmic format also are recommended.

Fluoxetine: a serotonin-specific, second-generation antidepressant.

Fluoxetine is a bicyclic antidepressant that is a specific and potent inhibitor of the presynaptic reuptake of serotonin. It has essentially no effect on the reuptake of norepinephrine or other neurotransmitters. Similarly, it has negligible binding affinity for neurotransmitter receptor sites. It is well absorbed after oral administration, with absolute bioavailability in dogs of approximately 72 +/- 27.6%. The mean Tmax is between 4 and 8 hours, and it is approximately 94% protein bound. After a single dose, the elimination half-life is 1-3 days. After long-term administration, the elimination half-life averages 4 days. Its pharmacokinetics appear nonlinear. It is metabolized to an active metabolite norfluoxetine, which is also specific for the inhibition of serotonin reuptake. Norfluoxetine's elimination half-life averaged 7 days after long-term administration. Little is known about potential drug interactions; however, fluoxetine appears to have minimal clinically relevant interactions. Fluoxetine is indicated in the treatment of major depression. Its efficacy is comparable to the tricyclics and it has a similar onset of action. Although doses as high as 80 mg/day have been used, the optimal dosage range appears to be 20-40 mg once daily. Fluoxetine has been used with success in obsessive-compulsive disorder and intention myoclonus, however, its use in these disorders remains investigational. The frequency of side effects is low and dose related; the most common effects are nausea, anxiety, insomnia, anorexia, diarrhea, nervousness, and headache. Eight reports of intentional overdose with fluoxetine alone resulted in no deaths and mild adverse effects. It will be marketed as 20-mg capsules under the brand name of Prozac. Although fluoxetine should be added to formularies, its use should be reserved for treatment of those who do not respond to or do not tolerate tricyclic agents.

Postinduction carbamazepine clearance in an adult psychiatric population.

The objective of this study was to describe the postinduction clearance of carbamazepine (CBZ) in adult psychiatric patients by population pharmacokinetic analysis using the NONMEM program. Specifically, an estimate of CBZ clearance and insight into the effect of common patient characteristics on clearance were sought. Steady-state trough CBZ serum concentrations, CBZ dosing history, concomitant drug administration, and other data from 45 patients were collected retrospectively. A one-compartment model with first-order absorption and first-order elimination was used, with absorption rate, bioavailability, and volume of distribution fixed to literature values. No evidence was found that race, sex, age, ethanol use, smoking, and concomitant lithium significantly affected CBZ clearance. In the final model, clearance was based on lean body weight. The coefficient of variation for clearance estimates was 16.5%. Residual variability was modest. Estimates for volume of distribution, rates of absorption and elimination, and bioavailability could not be pursued rigorously. Although these results may assist in understanding CBZ disposition in this population, their general clinical application should be approached with caution.

CYP2D6 mutations and therapeutic outcome in schizophrenic patients.

STUDY OBJECTIVE: To investigate whether a relationship exists between the most common known cytochrome P450 (CYP) isozyme 2D6 mutations and schizophrenia. Because most antipsychotic and antidepressant agents interact with CYP2D6, we also investigated clinical outcomes in schizophrenic poor metabolizers (PMs) and extensive metabolizers (EMs). DESIGN: Prospective, observational study. SETTING: Two psychiatric hospitals and a university-affiliated nonpsychiatric hospital. SUBJECTS: Thirty-nine consecutive schizophrenic patients (POP 1), 89 schizophrenics of French Canadian origin (POP 2), and 384 healthy French Canadians (POP 3). INTERVENTION: All study subjects were genotyped for CYP2D6 mutant alleles. POP 1 patients were evaluated before and after 21 or more days of treatment with antipsychotic drugs metabolized at least in part by CYP2D6. MEASUREMENTS AND MAIN RESULTS: Whole blood was collected to determine CYP2D6 alleles *1, *3, *4, *5, *6, and *7 using standard restriction fragment length polymorphisms and polymerase chain reaction techniques. In comparison, CYP2D6 genotypes were determined in POP 2 and POP 3. Twenty-three (59.0%) of 39 patients in POP 1 were genotypically EM homozygotes, 15 (38.4%) were EM heterozygotes, and 1 (2.6%) was a PM. Similar genotype distributions were determined in POP 2 and in POP 3. Genotype distributions for all three populations were in Hardy-Weinberg equilibrium (p>0.05), and there was no significant difference among them (p=0.857). In POP 1, no differences were seen among genotypes in disease symptom severity, number and severity of adverse drug effects, or attitudes toward drug treatment at baseline and at the end of the study. In fact, all patients improved significantly during their hospital stay (all p<0.05), although independent of the CYP2D6 genotype. CONCLUSION: Common CYP2D6 mutant alleles were not associated with schizophrenia or with disease symptoms, antipsychotic-related adverse effects, or attitudes toward treatment.