Use Of First-generation Antipsychotics Research Articles

Commentary: The Need to Guard Against Pharmaceutical Industry Influence

Back to table of contents Previous article Next article Brief ReportFull AccessCommentary: The Need to Guard Against Pharmaceutical Industry InfluenceRobert H. Howland M.D.Robert H. Howland M.D.Search for more papers by this authorPublished Online:1 May 2008AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Recently, an outpatient whom I have known a long time came for a routine medication visit. He has schizophrenia and has been clinically stable for many years on a well-tolerated dosage of fluphenazine. Unexpectedly, he asked me why I was giving him an "archaic" drug. He had just seen his primary care physician, Dr. R, for a routine medical visit. Dr. R had referred to fluphenazine as an "archaic 19th century drug" and thought that it was "time for a change." My patient did not understand what the problem was with his medication and was quite disturbed by these comments. We talked about his long-term experience with fluphenazine and discussed newer alternatives. Ultimately, we agreed that there was no need to make a change. In this issue of Psychiatric Services, Arbuckle and colleagues ( 1 ) report on a survey of psychiatrists regarding their opinion of second-generation antipsychotics. This topic is timely, given increasing concerns about the costs, efficacy, and safety of these agents compared with first-generation antipsychotics. The survey findings are predictable. Only 3% of respondents preferred first-generation agents. If psychiatrists do not prefer these drugs, and perhaps are not as familiar with them, why would they choose to use them or feel optimistic about their use? The vast majority (88%) was optimistic about the benefits of second-generation agents. If psychiatrists were not optimistic about these medications, would they still predict that they would be effective for patients who do not respond to first-generation antipsychotics? Moreover, why would a psychiatrist choose to not use a medication that he or she optimistically believes will offer an improvement? Even though less than a quarter of respondents (22%) cited drug representatives or advertisements as being an influential source of information, it is notable that having weekly visits from drug representatives was one of two factors significantly associated with optimism about second-generation antipsychotics (the other factor being familiarity with practice guidelines). This finding is not necessarily surprising. Would many psychiatrists admit to prescribing drugs on the basis of marketing influences rather than for strict clinical or scientific reasons? What occurs during these office visits? Brand-name drug samples are given. Branded pens, notepads, and educational materials are left behind. Copies of published studies about the product are presented, sometimes with published treatment guidelines if they are favorable or are not unfavorable to the product. By contrast, use of first-generation antipsychotics is not promoted through office visits, drug samples, educational materials, or other advertising efforts.The small number and narrow focus of the survey questions in this study, as well as the small unrepresentative sample of psychiatrists surveyed, limit the overall value and interpretation of the results. Despite these limitations, the authors know more about this group of psychiatrists than I know about Dr. R. I know nothing about Dr. R, except that he is not a psychiatrist and that he apparently believes that my prescribing fluphenazine is behind the times. Second-generation antipsychotics have been actively investigated for conditions other than schizophrenia, and some have gained approval for treatment of mood disorders. Consequently, they are being marketed more widely to the general public as well as to nonpsychiatrists. Although I do not know what sources of information influence Dr. R's opinion about antipsychotics for schizophrenia, it would surprise me if he, as a primary care physician, reads relevant research reports or practice guidelines. However, I think it is likely that drug representatives visit his office. If they do visit Dr. R, is he less likely to be optimistic toward the second-generation antipsychotics than the psychiatrists surveyed by Arbuckle and colleagues?With the advent of the second-generation agents, are patients with schizophrenia better off than they were 15 years ago? Schizophrenia is a devastating and difficult-to-treat illness, and it is always good to have treatment options. But the choice of drug treatment for an individual patient should be based as much as possible on the best unbiased clinical and scientific information available, together with sensitivity to practical cost considerations.Dr. Howland is affiliated with the Department of Psychiatry, Western Psychiatric Institute and Clinic, 3811 O'Hara St., Pittsburgh, PA 15213 (e-mail: [email protected]).Reference1. Arbuckle MR, Gameroff MJ, Marcus SC, et al: Psychiatric opinion and antipsychotic selection in the management of schizophrenia. Psychiatric Services 59:561–565, 2008Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 59Issue 5 May, 2008Pages 566-566PSYCHIATRIC SERVICES May 2008 Volume 59 Number 5 Metrics PDF download History Published online 1 May 2008 Published in print 1 May 2008

Metabolic Risk with Second-Generation Antipsychotic Treatment: A Double-Blind Randomized 8-Week Trial of Risperidone and Olanzapine

The second-generation antipsychotics are effective for treating psychotic disorders and incur fewer motor side effects than are commonly experienced with the use of first-generation antipsychotics. However, their use is commonly associated with weight gain and metabolic disturbances. This study examined weight and metabolic changes with two widely used antipsychotics, risperidone and olanzapine; addressing the issue of early monitoring for metabolic side effects. This 8-week double blind randomized trial included patients with schizophrenia or schizoaffective disorder (N = 377) randomly assigned to risperidone (2-6 mg/day) or olanzapine (5-20 mg/day). Weight, BMI, HbA1C, total cholesterol (TC), LDL-C, HDL-C and triglycerides (TG) were monitored. Mean BMI increases were higher in the olanzapine group as compared to risperidone (1.3 kg/m(2)(SD = 0.13) vs. 0.7 kg/m(2) (SD = 0.13)(p < 0.001). Increases in mean TC (13.5 mg/dl (SD 2.4), LDL-C (11.0 mg/dl (SD 2.2)) and TG (14.8 mg/dl (SD = 7.6)) occurred in the olanzapine group while significant changes in TC (-3.9 mg/dl (SD = 2.5)) and TG (-32.8 mg/dl (SD = 7.8)) were noted in the risperidone group. Men (not women) on olanzapine had higher than expected increases in lipids given the amount of weight gain. Baseline values and prior therapy did not contribute to the significant differences, however BMI increases (p = 0.0002) were linked to study discontinuation in both drug groups. The fact that significant metabolic changes occurred (both positive and negative) in eight weeks is important to clinical care. Monitoring for metabolic changes may be important within the first eight weeks of treatment, as changes can be determined very early in antipsychotic treatment.

A Case of Acute Dystonia after Single Dose of Aripiprazole in a Man with Cocaine Dependence

Cocaine users appear to have an elevated risk of acute dystonia related to the use of first-generation antipsychotics.1 The second generation of antipsychotics are generally less prone to causing a...

Trends in the Use of Psychotropic Drugs in Taiwan: A Population-Based National Health Insurance Study, 1997-2004

Trends in the Use of Psychotropic Drugs in Taiwan: A Population-Based National Health Insurance Study, 1997-2004

Persistence with polypharmacy and excessive dosing in patients with schizophrenia treated in four European countries

The purpose of this study was to calculate the proportion of patients with schizophrenia receiving persistent antipsychotic polypharmacy and excessive dosing in four European countries; to test the hypothesis that excessive dosing and/or antipsychotic polypharmacy is associated with higher levels of psychopathology; and to establish whether use of second-generation antipsychotics is a protective or a risk factor for polypharmacy and excessive dosing. Participants with schizophrenia were recruited from patients under the care of psychiatric services serving geographical catchment areas in Croydon (UK), Verona (Italy), Amsterdam (Netherlands), and Leipzig (Germany). We defined patients persistently receiving high antipsychotic dose (i.e. excessive dosing) as those with a prescribed daily dose/defined daily dose ratio of >1.5 both at initial assessment and after 1 year of follow-up. Similarly, we defined patients persistently receiving polypharmacy as those being prescribed two or more antipsychotic drugs both at baseline and at follow-up. A sample of 375 participants with schizophrenia was analyzed. A proportion of 28% of patients persistently received high-dose antipsychotic drugs, and a proportion of 13% of patients persistently received antipsychotic polypharmacy. In the multivariate analysis, psychopathology was not a predictor of persistent polypharmacy and excessive dosing; similarly, use of second-generation antipsychotics was not associated with polypharmacy and excessive dosing; however, persistence with high antipsychotic doses was predicted by baseline use of first-generation antipsychotics and second-generation antipsychotics concurrently. Antipsychotic drug use for patients with schizophrenia is only sometimes satisfactory and offers the opportunity of improvement. Clinicians should consider that dose reduction strategies have been shown to be a feasible intervention in patients with schizophrenia.

Pharmacogenetics of antipsychotic therapy: pivotal research issues and the prospects for clinical implementation

The core hypothesis underlying pharmacogenetics is that genetic factors play a significant role in the well-recognized differences between individuals in response to medication and susceptibility to adverse effects. If these genetic factors can be identified and understood, they may serve as predictors to guide clinicians in tailoring medication to the individual patient. Recent developments in the field of antipsychotic drug treatment suggest that pharmacogenetics could play an important role, permitting the use of first-generation antipsychotics (FGAs) for patients in whom the use of second-generation antipsychotics (SGAs) is limited by efficacy considerations or adverse effects. In this paper, key issues that need to be taken into consideration in designing and interpreting pharmacogenetic studies of antipsychotic drugs are discussed against the background of data emanating from studies on the genetics of tardive dyskinesia (TD), an important adverse effect of FGAs. The issues considered include the advantages and potential pitfalls of case-control association studies of pharmacogenetic traits, the role of demographic factors such as age and gender, additive effects of genes, and gene-gene and gene-environment interaction. The prospects for implementation of pharmacogenetic testing in the clinic are considered in the context of a preliminary model that has been tested for prediction of susceptibility to TD.

Impact of second-generation antipsychotics on the use of antiparkinson agents in nursing homes and assisted-living facilities

Background: It is not known whether the reduced risk of motor adverse effects with second-generation antipsychotics (SGAPs) translates into less use of antiparkinson drugs (APDs). Objective: This study sought to estimate national rates of concomitant prescribing of APDs and antipsychotic drugs among elderly Medicare beneficiaries without Parkinson's disease (PD) who were residing in institutional settings from 1997 to 2000, a period during which the use of SGAPs increased greatly. Methods: This was a retrospective, cross-sectional, descriptive analysis using the Medicare Current Beneficiary Survey database. The population of interest was residents of nursing homes (NHs) and assisted-living facilities (ALFs) who received concomitant antipsychotic drugs and APDs but did not have PD. The primary objective of the study was to estimate the prevalence of concomitant APD and antipsychotic drug use for each study year, by use of first-generation antipsychotics (FGAPs) and SGAPs in each setting. A secondary objective was to compare concomitant use of APDs and individual antipsychotic agents (ie, clozapine, risperidone, olanzapine, quetiapine, ziprasidone, haloperidol, and thioridazine). We computed population-level annual prevalence rates for APD use and tested for statistically significant differences in APD use between FGAPs and SGAPs at the 5% significance level. Results: In NH residents, concomitant use of APDs and antipsychotics decreased from 20.7% in 1997 to 9.0% in 2000 ( P < 0.005). APD use in NH residents declined similarly among users of FGAPs (from 23.2% in 1997 to 13.3% in 2000; P < 0.005) and SGAPs (from 18.4% in 1997 to 8.1% in 2000; P < 0.005). In ALF residents, concomitant use of APDs and antipsychotics decreased from 24.5% in 1997 to 21.1% in 2000 ( P < 0.005). ADP use in ALF residents receiving FGAPs decreased from 26.9% in 1997 to 24.2% in 2000 ( P < 0.005); there was no significant change in ADP use among ALF residents receiving SGAPs (from 21.0% in 1997 to 21.7% in 2000). Conclusions: These results provide the first nationally representative estimate of the concomitant use of APDs and antipsychotic drugs among older individuals in long-term care settings. The decrease in concomitant use of APDs and antipsychotics when SGAPs were used in NHs suggests an association between the use of SGAPs and a reduction in the prescribing cascade, in which one drug is used to treat the adverse effects of another. The results also suggest that some Medicare beneficiaries in ALFs may be continued on APDs despite changes in the prescribing of antipsychotic agents, implying a need for better medication-management practices in these institutions.

Epidemiology of First- and Second-generation Antipsychotic Agents in Lombardy, Italy

This study investigated the age and gender distribution of antipsychotic prescribing in Lombardy, a region of nine million inhabitants in northern Italy. From the Regional Administrative Database of Lombardy, all ambulatory prescriptions of antipsychotics dispensed during 2001 were extracted and prevalence data were calculated by dividing users by the total number of male and female residents in each age group. During the study period 86,187 subjects were dispensed antipsychotic agents, yielding a prevalence of use of 0.87 (95 % CI: 0.86, 0.88) per 100 males and 1.01 (95 % CI: 1.00, 1.02) per 100 females. The prevalence of use progressively rose with age in both sexes, with the highest rates in old and very old subjects. The prevalence of use of first-generation antipsychotics progressively increased with age and dramatically increased in old and very old subjects; in contrast, the prevalence of use of second-generation antipsychotics remained substantially stable or slightly decreased up to 65 years of age and increased thereafter. Antipsychotic agents are prescribed widely in the general population, and very high rates were observed in those aged 80 years or more.