Running head: TRADITIONAL VERSUS ATYPICAL ANTIPSYCHOTICS 1 Traditional Versus Atypical Antipsychotics and Their Effect on Treating Schizophrenia Caitlin Hayden University of New Hampshire TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 2 Traditional Versus Atypical Antipsychotics and Their Effect on Treating Schizophrenia Issue In the past, traditional antipsychotic medications have been the standard in psychopharmacology for treating schizophrenia. Schizophrenia cannot be cured however, antipsychotic drugs can control the underlying psychotic symptoms associated with the disorder. One group of antipsychotic medications is the conventional, or traditional, drugs that are dopamine antagonists (D2 receptor agonists) (Varcarolis, Carson, & Shoemaker, 2006, pg. 404). The second group of antipsychotic medications is atypical drugs that are serotonin-dopamine antagonists (5-HT2A receptor antagonists). Traditional antipsychotics aim to control the positive symptoms of schizophrenia; the hallucinations, delusions, disordered thinking, and paranoia. However, they are becoming obsolete in the treatment of schizophrenia because of the troubling side effects. The blocking of the D2 receptor causes EPS and anticholinergic effects. (Varcarolis et al., 2006, p.407). For the record, this group of antipsychotic medications is much less expensive than atypical agents and come in depot form. In addition to relieving the positive symptoms of schizophrenia, atypical antipsychotics can also control the negative symptoms of schizophrenia (blunted affect, deficits in social interaction, and lack of motivation) in addition to the positive symptoms. This group of antipsychotics emerged 20 years ago starting with clozapine, also known as Clolzaril. Atypical antipsychotics are said to have fewer side effects and be better tolerated. Chosen as the first line antipsychotics, they encourage medication compliance and lessen rate of relapse, improve symptoms of depression and anxiety, and decrease suicidal behavior (Varcarolis et al., 2006, pg. 405). TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 3 . Side effects are minimal but serious including: weight gain, metabolic abnormalities (glucose dysregulation, hypercholesterolemia) that can increase the likelihood of cardiac conditions and diabetes. In spending an entire semester in a mental health clinical rotation, it is evident that numerous medications are used to treat schizophrenia. A medication regimen is specific to each individual patient and side effects are handled differently with each patient. Like all medications, physicians can favor certain ones or have had seen better results in certain ones when used by some of their patients. In my clinical practicum I have noticed this clinical issue. Information in textbooks make atypical antipsychotic medications appear to be the best option to treat schizophrenia but in my clinical practicum I have seen both groups of antipsychotic medications used and deemed successful. Traditional antipsychotics are stereotyped to have undesired side effects that steer patients away from them but the atypical group also have their respective side effects. I have worked with patients who have been prescribed atypical antipsychotics and others patients who have been prescribed traditional antipsychotics. I have actually seen more patients concerned with weight gain from the atypical agents than the EPSs from the traditional agents. During my clinical rotation I have seen certain psychiatrists push a certain group of medications on patients and I have always wondered if there was evidence to back up that one group of medications is more effective than other. I would expect that studies would show that atypical medications make for more medication compliance due to lessened EPSs. However, I would expect the research to mention that these atypical medications do cause weight gain, something that is undesired for all TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 4 patients. I would also expect mention of the fact that traditional medications are less expensive and more available in varying dosages. Clinical Bottom Line Evidence based research provides a basis of reasoning behind a current practice. It means that the practice has been initiated, attempted, and then either seen to success or failure. It is important to know if a current practice in place is supported by the best possible evidence based research because it gives us a stronger backing and support base for care. It is especially important when informing patients about treating schizophrenia and the medications that have been shown and tested to be effective. If current practices are not supported by the best possible evidence based research patients receiving the treatment may be more apt to question the use or reasoning behind the care. Yes, there are practices that do work and are not backed by evidence based research however they are not as widely accepted by patients. In the case of these antipsychotic medications where all patients have different reactions and results with different medications the reasoning behind giving certain medications takes more of a personalized approach. Research might be able to say that certain medications work better than others do because it was tested on a population of patients with schizophrenia but the results may not necessarily be applied to all schizophrenia patients. Even still, the research can surely be used as a reference tool and something to base the current practice on. Case and Clinical Question TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 5 My PICO question is: In treating Schizophrenia, what are the effects of atypical antipsychotic medications on symptoms and cognitive function compared with traditional antipsychotics as it relates to medication compliance and undesired side effects? I chose this as a question to research because while doing my mental health rotation I have come across a lot of medication discussion and was curious as to if there is evidence available to prove that one group of antipsychotic medications is better than the other. This question is interesting to me because medication is a serious part of treating mental illnesses. What the medications do and how they affect the patient are very important factors that are questioned by the patient and discussed with them. Antipsychotic medications in particular, that affect the brain and nervous system, for a patient with altered brain function can be difficult to advise patients to comply with. Search and Studies I utilized the University of New Hampshire’s Dimond Library to access my research articles. Under the “Health/Medicine/Sports” category I searched the following electronic databases: CINAHL, MEDLINE, PsycINFO, and PubMed. I began by using keywords including “schizophrenia medications”, “antipsychotics”, “atypical antipsychotics”, and “traditional antipsychotics”. For each search I found numerous articles with the key words in the title but upon further examination only a handful of accessible articles were relevant to my PICO question. I came across many informational articles regarding atypical and traditional antipsychotic medications; I chose to disregard them for the analysis portion due to the fact that they did not involve or discuss any clinical trials that could provide statistical results proving or disproving a hypothesis of TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 6 one group of antipsychotic medications being more effective than the other. One of the articles that I decided not to use was, “Healthy Promotion in Persons with Schizophrenia: Atypical Medications”. It went into great detail about the effects of atypical medications and specific medications and their actions. It touched based on traditional antipsychotics but was stated in a bias way which is not conducive to my PICO question and the clinical issue. I came across some difficulty in finding articles pertinent to my topic because many of the articles were focused solely on atypical antipsychotics or solely on traditional antipsychotics without mention of the other group of medications. Without studies which compare the effects of both groups of antipsychotics there is no research to provide evidence that one group is more superior. I also contribute the difficulty of my search process to the lack of research surrounding this comparison. However, I did manage to find the following articles which related directly to my PICO question, “Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study”, “Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia”, and “Antipsychotic Effects on Cognition in Schizophrenia: A Meta-Analysis of Randomised Controlled Trials”. Evidence The first pertinent article that I found was, “Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study”. It was a multi-site, double blind study done in the spring of 2006 by a TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 7 number of doctors, nurse practioners, and nurses. The objective of the study was clearly stated at the beginning of the article: to compare the safety and efficacy of olazapine and risperidone (atypical) and molindone (traditional). 116 patients, between the ages of 8 and 19 years old, diagnosed with early onset schizophrenia (EOS) or schizoaffective disorder were involved. The participants were randomly assigned olazapine, risperidone, or molindone daily for eight weeks. On the Levels of Evidence Pyramid, a random control trial is second from the top, making this research study a strong piece of evidence (University of Illinois, 2009). The entire article is very easy to comprehend and follow as it is divided into method, results, discussion, and conclusion. Each division is elaborated upon and provides detailed information regarding the study setting and design, participants, interventions, outcomes, and statistical analyses. The major limitation of the study was identified as the small sample size which inhibited the ability to identify predictors of response or adverse effects and only allowed for the identification of large differences. I identified this as a weakness of the evidence. A small sample signs means that the results cannot be generalized to a larger population. However, in the conclusion, recommendations for further study and analysis on this topic are stated. Overall, I would consider this research article to be a good base for evidence practice, although it should be used to accompany other research articles. It was well written, and had a well designed and well organized study that was completed thoroughly. From the study results the authors were able to state that, “risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder” and, “the results question the nearly exclusive use of second-generation TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 8 antipsychotics to treat early-onset schizophrenia and schizoaffective disorder”(Sikich et al., 2008). Another article that I located was “Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia”. It was a CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study. Initiated by the National Institute of Mental Health, this study was aimed at comparing perphenazine, a first generation (traditional) antipsychotic, to newer (atypical) drugs. In the abstract, a purpose was not clearly identified, although it stated that, “the relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly” (Lieberman et al.,2005). In this double-blind, randomized control trial, 1483 patients were assigned to receive olanzapine, perphenazine, quetiapine, or risperidone and then followed for up to 18 months or until treatment was discontinued. One strength of this research article that relates to reliability is the fact that it was stated that the study was approved by the institutional review board at and informed consent was obtained from the patients or legal/guardians. A hypothesis of significant differences in the overall effectiveness of olanzapine, perphenazine, quetiapine, risperidone, and ziprasidone in treating schizophrenia reflecting variations in efficacy and tolerability, was tested using patient characteristics and symptoms. These factors were measured using the PANSS (Positive and Negative Syndrome Scale) and the Clinical Global Impressions (CGI) Scale. The study design, participants, interventions, objectives and outcomes, and statistical analysis were all included and discussed thoroughly in the research article. Charts and tables were included to show the results. The article had a TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 9 very professional tone that was organized and well written. The authors recognized that dosage may have been a factor in effecting the results. Although the dose range was approved by the FDA, all participants of the study reacted differently. Results showed that 74 percent of the patients discontinued their assigned medications prior to the eighteenth month due to intolerable side effects. Olanzapine (an atypical antipsychotic) had the lowest discontinuation rate and it was concluded that, “patients with chronic schizophrenia in this study discontinued their antipsychotic study medications at a high rate, indicating substantial limitations in the effectiveness of the drugs” (Lieberman et al.,2005). The final article that I found was a meta-analysis of 18 randomized control trials testing the effects of antipsychotic medications, both atypical and traditional. “Antipsychotic effects on cognition in schizophrenia: A meta-analysis of randomised controlled trials” was completed in November of 2008 by using the Medline database to find studies that had the same aim: seeing if the use of atypical agents provided better results than traditional agents in treating patients with schizophrenia. The Medline search was “a) limited to randomised controlled trials which examined adult patients, aged between 16 and 65, diagnosed with schizophrenia, or a schizoaffective or schizophreniform disorder; b) used at least one standardised neuropsychological test that appears in the Lezak manual, and c) present the necessary data to estimate an effect size (i.e., means and standard deviations on neuropsychological measures, or t, F, or p values)” (Guilera, Pino, Gómez-Benito & Rojo, 2009). The antipsychotic medications used in the studies included olanzapine, risperidone, haldolperidol, clozapine, and quetiapine. TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 10 A meta-analysis is a specific type of systematic review and at the top of the Levels of Evidence Pyramid (University of Illinois, 2009). Because it compares and summarizes numerous studies it is considered the strongest level of evidence. As with most meta-analyses, the summary of all research studies comes with limitations. For this particular meta-analysis the limitations were recognized as study design, pharmacological method used, and neuropsychological tests administered. The 18 studies examined consisted of both double blinded and non blinded designs which may indicate that the results of the non blinded studies are biased. Also, there was no consistency regarding dosage of the medications used. The variability of the neuropsychological tests affects the results as they relate to efficacy. The authors of the meta-analysis categorized cognitive function into 11 domains and listed all of the tests that are associated with each. This allowed the 18 studies to be divided and assessed based on the cognitive domain they tested. The authors then translated the cognitive testing to measurements on the global cognitive index. In reviewing the 18 independent studies, atypical agents showed slight improvements in the global cognitive index (Guilera et al., 2009). However, due to the limitations mentioned, conclusions regarding atypical agents improving neurological status more so than traditional agents can not be made. The authors recommended that more research be done around atypical agents versus traditional agents. Overall, this research article was well written, well organized and very thorough; the authors made sure to include every little detail about the strengths and weaknesses of the meta-analysis. Comments and Conclusion TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 11 After analyzing the research articles that I found relating to my PICO question (In treating Schizophrenia, what are is the effect of atypical antipsychotic medications on symptoms and cognitive function compared with traditional antipsychotics as it relates to medication compliance and undesired side effects?) I was able to sense a common theme. The results of the meta-analysis and the two other studies can not provide statistical significance stating that atypical antipsychotics are more effective in treating schizophrenia than traditional antipsychotics. From this information I am without any best evidence supporting or refuting my PICO question. Based on what I have learned from my research and search process, the research in this area of nursing is incomplete. All of the studies stated that further research must be completed to appropriately address the topic. I agree that more research needs to be done. Using evidence based practice is becoming more and more popular and desired in all nursing and healthcare fields and mental health is no exception. In order for current practices to be considered the best practices they must be backed by evidence. Future research studies must be tightly controlled and well designed to ensure that there is consistency in the methods and results. Of course, larger samples sizes will enable the results of the studies to be generalized to a population of schizophrenia patients. I have gained an ample amount of information regarding atypical and traditional antipsychotic medications in regards to their actions, side effects, patient reactions, and medication compliance. And in the event that I endure the mental health route I will continue to follow research regarding this topic. With this knowledge nurses (myself included) can better aid and educate their patients about such medications. On a more TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 12 general note this research has made me more aware of current practices backed by evidence based research and sparked my curiosity regarding other nursing topics. TRADITIONAL VS ATYPICAL ANTPSYCHOTICS 13 References Beebe, L. (2003). Health promotion in persons with schizophrenia: atypical medications. Journal of the American Psychiatric Nurses Association, 9(4), 115-122. Retrieved from CINAHL Plus with Full Text database. Guilera, G., Pino, O., Gómez-Benito, J., & Rojo, J. (2009). Antipsychotic effects on cognition in schizophrenia: A meta-analysis of randomised controlled trials. The European Journal of Psychiatry, 23(2), 77-89. Retrieved from PsycINFO database. Lieberman JA, Stroup TS, McEvoy JP, et al. (2005) Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia. New England Journal of Medicine; 353 (12): 1209-1223. Sikich, L., Frazier, J., McClellan, J., Findling, R., Vitiello, B., Ritz, L., et al. (2008). Double-blind comparison of first- and second-generation antipsychotics in early- onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study. American Journal of Psychiatry, 165(11), 1420-1431. Retrieved from CINAHL Plus with Full Text database. University of Illinois-Chicago (2009). Evidence-based practice in the health sciences: Evidence-based nursing tutorial. Retrieved from http://ebp.lib.uic.edu/nursing/?q=node/12 Varcarolis, E.M, Carson, V.B., & Shoemaker, N.C. (2006). Foundations of psychiatric mental health nursing: a clinical approach. St. Louis, Missouri: Elsevier.
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