MAS SOBRE ANTIPSICOTICOS, ESQUIZOFRENIA, CATIE Y SUS CONTROVERSIAS
Artículos tomadas de la Red del colegio dominicano de Neuropsicofarmacología, magníficamente coordinado por el prof. dr. José angel saviñon.
THE EFFICACY-EFFECTIVENESS GAP IN SCHIZOPHRENIA
John J. Spollen III, MD
Introduction
Improved understanding of the illness of schizophrenia and advances in its treatment have significantly improved the quality of life for people with this most severe form of mental illness. However, these advances have also greatly complicated treatment. Whereas in years past, the knowledge of chlorpromazine equivalents and antiparkinsonian medications might have been enough to practice standard of care, today's psychiatrists need to be aware of an increasingly complicated pharmacologic armamentarium as well as an increasing number of proven psychosocial interventions. With the expansion of knowledge, it has become clear that there is an ever-growing gap between what we know and what we do and what we do and how well it works. The efficacy-effectiveness gap, or the difference between treatment provided in a structured research setting under very specific circumstances and that provided in routine clinical practice, has come under greater scrutiny as we realize that closing this gap is essential if people with schizophrenia are to benefit from these advances. The reasons for this gap are numerous, including a simple lack of knowledge (too many journals, not enough time), the fact that the various differences often seen between research and clinical work (patient population, artificial circumstances, resources available, staff knowledge, etc.) make translation very difficult, and because of a "prescribing-taking" gap (ie, nonadherence). During a symposium at this year's American Psychiatric Association (APA) annual meeting, experts in these areas discussed current research in various areas that may close the efficacy-evidence gap.
Realizing that most of us clinicians are not bright enough to remember every major article printed about schizophrenia in the last 10 years, there have been multiple attempts to provide treatment guidelines that summarize the literature. These guidelines are intended to be a synopsis of our knowledge about schizophrenia treatment and to provide an algorithm to help clinicians proceed through the various options in an organized and rational way. Some of the available guidelines for the treatment of schizophrenia include the APA's Practice Guidelines for the Treatment of Patients with Schizophrenia (1997), the Expert Consensus Guideline for the Treatment of Schizophrenia (1999), the schizophrenia treatment protocol from the Texas Medication Algorithm Project (1999), and the Schizophrenia Patient Outcomes Research Team (PORT; 1998),[1] which are currently being updated.
The PORT Study and ACT
Dr. Anthony Lehman,[2] Chair of the Department of Psychiatry at the University of Maryland and the principal investigator of the PORT study, reviewed the background of the PORT study and its main recommendations. The first recommendation was that patients with schizophrenia should be treated with antipsychotics. While most of us take this as obvious, Dr. Lehman shared with us that several people he spoke with, and others who felt strongly enough about the issue to email him, still thought that patients with schizophrenia should be allowed to "work through the psychotic process." Probably more controversial was that the recommendations did not specify that initial treatment should be with atypical antipsychotics or conventional agents, a point that could be argued either way. Probably not surprising in today's pharmacologically oriented psychiatry practice is that most studies show that appropriate pharmacotherapy is frequently, but certainly not always, provided.[3] The most apparent gap between knowledge and practice in the treatment of schizophrenia is in psychosocial modalities.[4] Although they are only rarely provided, there is strong evidence to support certain forms of case management, vocational rehabilitation, and specific forms of individual and family psychotherapy.
Assertive community treatment, known as ACT, is a model of intensive case management that is the most known and accepted psychosocial treatment program designed for schizophrenia. ACT grew out of the Program for Assertive Community Treatment, or PACT, model designed by Test and Stein as a response to the "revolving door" of repeated hospitalizations for patient with schizophrenia in the early 1970s. With much research over the next 2 decades, ACT has become the standard model for comprehensive treatment of people with schizophrenia and is available for the most severely ill people with schizophrenia in a number of states and in the Veterans Administration healthcare system. The basic tenets of ACT include high intensity community-based case management services with a low client-provider ratio, with various forms of direct assistance provided including medications, basic needs such as housing, food, and clothing, training in basic living skills, family and social support network psychoeducation, and vocational support. With the significant level of disability and functional impairment for many people with schizophrenia, the skills taught by ACT clinicians often start with such basic living skills as how to navigate public transportation, how to shop for and prepare food, and how to access emergency services. Even though ACT is proven and well known, there are still few patients with schizophrenia that have ACT available to them.
There are a number of randomized trials that show that a specific form of vocational rehabilitation, known as supported employment, is effective.[5] However, the model of supported employment is quite different from the traditional vocational rehabilitation model and also different from the "sheltered workshops" for people with disabilities many of us are familiar with. The older vocational rehabilitation model used a "train then place" model where people went to a training program that occurred at a vocational training center and then were told to go find a job. Supported employment uses a "place then train" model, where jobs are found and on-site job "coaches" provide on-the-job training. While several studies have shown that supported employment is significantly better than traditional models of vocational rehabilitation, it is only rarely provided.
Although many people doubt that traditional psychodynamic psychotherapy is tremendously beneficial for patients with schizophrenia, there are specific forms of psychotherapy that have been proven effective in this population.[6] Cognitive-behavioral psychotherapy (CBT) has been shown to decrease symptomatology and increase insight.[7] A cognitive-behavioral family intervention reduced relapse and caregiver stress.[8] Many other examples of these exist.[1] Although there are indications that a number of patients with schizophrenia are provided with individual "counseling," it is doubtful that many of these therapists are using research-proven models. Even family therapy, with the long-standing knowledge of how "expressed emotion" in families can adversely affect patients, is rarely provided. One potentially positive move in this area is that the National Alliance for the Mentally Ill is spearheading a family psychoeducational program, entitled "Family to Family," which could dramatically increase the availability of family interventions for schizophrenia in the United States, and studies to measure its effectiveness are ongoing. Given the relative complexity, increased resources needed, difficulties with reimbursement, not to mention the fact that no one is making a billion dollars from selling CBT, it is understandable why psychosocial therapies would be behind pharmacologic therapies in their utilization. Unfortunately, it is precisely these types of treatments that may make life enjoyable for people with schizophrenia when medications are insufficient (which is much more often than not).
While pharmacologic treatments are extensively studied, most experts agree that even in this heavily studied area, there is much to be learned in the everyday use of these treatments. Most of the data we have is from phase 3 clinical trials, which are designed to prove the drug is safe and effective and often provide little knowledge of how a drug should be used in routine clinical practice. There are multiple reasons for this. The study population of patients is usually not representative of routine clinical samples because they are medically healthy and have few, if any, common comorbid conditions like substance abuse. In addition, study durations are usually 12 weeks or less, and routine treatment is usually indefinite. Also, the comparators in the studies, either placebo or high-dose haloperidol, are not representative of current clinical options (let's hope not, anyway). It is because of reasons such as these that this type of research tells us about efficacy and not effectiveness. A more fundamental problem with current data is that such studies only get a measure of "central tendencies" (whether the treatment works for a group of similar people) but gives little to no information about individual variability and its effect on treatment. Although the last issue is difficult to solve, the others are solvable using methods that test effectiveness rather than simply efficacy. The NIMH-funded Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study, led by Dr. Jeff Lieberman at the University of North Carolina, is exactly this type of study and will provide a wealth of information about how to use antipsychotics in the real world.
Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) Study
Dr. Scott Stroup,[9] also of the University of North Carolina and a coinvestigator on the CATIE, reviewed the study's methodology and complex design. A total of 1400 patients will be in the study. The only main exclusions are for first episode and treatment resistant patients; therefore, patients who are medically ill and/or substance abusers will be enrolled. In the first phase, patients will be randomized in a double-blind fashion to flexible dosing of perphenazine, risperidone, olanzapine, or quetiapine. Phase 2 will be for patients who do not respond to or cannot tolerate the medications given in phase 1 and will include ziprasidone and clozapine as options. Because clozapine will be recommended to all patients who fail an atypical antipsychotic in phase 1 because of lack of efficacy, there should be a large amount of data available to answer whether clozapine should be an earlier option than it typically is now. One very interesting point about the CATIE study is that the main outcome variable is "all cause discontinuation." While most psychiatrists are used to efficacy measurements, like a change in the PANSS rating scale, there is a good argument that this is a very narrow and "clinician-centered" outcome. By using "all cause discontinuation" as the main outcome variable, important information about tolerability and patient choice, in addition to efficacy, is included. Even though "all cause discontinuation" is the main outcome measure, there will of course be a wealth of data on other variables, including efficacy, safety/tolerability, cognition, adherence, violence, substance use, and cost-effectiveness.
An interesting sidebar to the study that is very important to future research in schizophrenia is that the CATIE will also investigate the patient's decision-making capacity by use of the MacArthur competency assessment. This will help learn what predicts decision-making capacity and whether capacity changes over time. With the increasing scrutiny by research-governing institutions, like Institutional Review Boards and the US Food and Drug Administration, on decision-making capacity in cognitively impaired patients, the findings are likely to change how consent is given for research in schizophrenia. The last patient is likely to be enrolled next month and the first data are expected to be available by early 2005. It is probably safe to say that the CATIE trial will provide the most clinically useful data for the use of antipsychotic medications in schizophrenia we have ever seen.
Even the best-prescribed treatments are only successful if the patient agrees to take it. Noncompliance to, or nonadherence with, prescribed treatment is a major reason for reduced effectiveness of treatments in clinical practice. It should be noted that adherence is much more than just "taking the pills" and includes a myriad of activities including coming to appointments, pursuing recommended lifestyle changes such as stopping smoking and increasing exercise, as well as practicing skills learned in various forms of psychoeducation and psychotherapy. However, the vast amount of research in nonadherence is related to pharmacotherapy, and the following descriptions of nonadherence all refer to medications.
Adherence
Dr. Mark Olfson,[10] of the Department Psychiatry at Columbia University, provided an overview of research about nonadherence in the treatment of schizophrenia. The news was not good. Approximately 7% of patients become nonadherent each month after discharge from the hospital. More importantly, the relapse rate for patients who are nonadherent is 11% per month, compared with a relapse rate of only 3% for patients on depot neuroleptics. The silver lining to this cloud is that there are effective interventions for medication nonadherence available. The proven interventions require a cognitive and/or behavioral approach. The frequently used method of telling patients "how bad it is for you to not take your medications" is almost certainly not very effective. One recommended strategy was to try motivational interviewing, a technique that first gained favor in treatment of substance abuse but is fast becoming a form of therapy for any type of therapeutic change. To provide a brief if not comprehensive explanation of motivational interviewing, it is where a discussion is held with a patient about their perspective about the positives and negatives about taking medications (or any other type of behavior) and, without arguing for change, the clinician helps the patient form an argument for change. The trick is that it must be the patient who eventually makes the argument for change. The patient's plan for change then becomes a self-fulfilling prophecy. One thing that was plain, though, was that educational alone, which is the current standard of care, does practically nothing to improve adherence rates. Given the importance of adherence for both pharmacologic therapy as well as psychosocial therapies, future research in this area is greatly needed. A recent request for proposals from the NIMH in this area guarantees that this literature will be strengthened in a few years.
Although our knowledge base about the treatment of schizophrenia has greatly increased over the last 20 years, much of that knowledge is not benefiting patients. For a multitude of reasons, the routine clinical care of schizophrenia is far behind the current evidence. The efficacy-effectiveness gap is a significant impediment to improving the lives of people with schizophrenia. Given the various reasons for the gap, various strategies are required to close it. We need better implementation of currently available treatment modalities for schizophrenia, especially in the psychosocial treatments. Improved availability and higher utilization of services such as assertive community treatment and supported employment are needed. We need data that go far beyond the industry-supported data on atypical antipsychotics. The CATIE will provide a wealth of clinically useful information. We need improved adherence, as effective interventions are ineffective when patients will not adhere to them. Some interventions to improve adherence are already available, but more research in this area is on the way. With this and other effectiveness research, the efficacy-effectiveness gap may grow smaller and the lives of people with schizophrenia will be thereby improved.
References
Lehman AF, Steinwachs DM. Translating research into practice: The Schizophrenia Patient Outcomes Research Team (PORT) treatment recommendations. Schizophr Bull. 1998;24:1-10.
Lehman AF. Overview of best practices: current treatment guidelines and protocols for schizophrenia. Program and abstracts of the American Psychiatric Association 156th Annual Meeting; May 17-22, 2003; San Francisco, California. Abstract S28A.
Buchanan RW, Kreyenbuhl J, Zito JM, Lehman A. The schizophrenia PORT pharmacological treatment recommendations: conformance and implications for symptoms and functional outcome. Schizophr Bull. 2002;28:63-74.
Lehman AF, Steinwachs DM. Evidence-based psychosocial treatment practices in schizophrenia: lessons from the Patient Outcomes Research Team (PORT) project. 2003;31:141-154.
Bond GR, Becker DR, Drake RE, et al. Implementing supported employment as an evidence-based practice. Psychiatr Serv. 2001;52:313-322.
Pilling S, Bebbington P, Kuipers E, et al. Psychological treatments in schizophrenia: I. meta-analysis of family intervention and cognitive behaviour therapy. Psychol Med. 2002;32:763-782.
Turkington D, Kingdon D, Turner T. Effectiveness of a brief cognitive-behavioural therapy intervention in the treatment of schizophrenia. Br J Psychiatry. 2002;180:523-527.
Sellwood W, Barrowclough C, Tarrier N, Quinn J, Mainwaring J, Lewis S. Needs-based cognitive-behavioural family intervention for careers of patients suffering from schizophrenia: 12-month follow-up. Acta Psychiatr Scand. 2001;104:346-355. Lieberman JA, Stroup S. Research gaps and current research initiatives to improve the treatment of schizophrenia. Program and abstracts of the American Psychiatric Association 156th Annual Meeting; May 17-22, 2003; San Francisco, California. Abstract S28B.
Olfson M, West JC, Wilk JE, Marcus S. Factors affecting the effectiveness of clinical decisions in treating schizophrenia. Program and abstracts of the American Psychiatric Association 156th Annual Meeting; May 17-22, 2003; San Francisco, California. Abstract S28C.
Discusión ampliada para miembros de AAPB
¿Estás de acuerdo conque es imposible mantenerse al día con la información medica?
¿Que criterios usas para creer o no lo que lees?
¿Si un trabajo fue sponsoreado por laboratorios de la industria farmacéutica se convierte en menos serio? ¿Reconocidos científicos que trabajan para laboratorios deben abstenerse de continuar opinando , si lo hacen imparcialmente?
¿Crees que el tratamiento psicosocial y las técnicas de las cuales habla el PORT (por ejemplo empleo obligatorio) son imprescindibles para el tratamiento de la esquizofrenia?
¿La tasa de discontinuación es suficiente para determinar efectividad?
¿Los criterios de adherencia son válidos para psicóticos?
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