Adherence to Typical Antipsychotics among Patients with Schizophrenia in Uganda: A Cross-Sectional Study.

Atypical Antipsychotics: Mechanism of Action

Consensus development conference on antipsychotic drugs and obesity and diabetes.

Due to the uncertainty whether atypical and typical antipsychotics have a stronger association with mortality among older people with schizophrenia, we examined the rates and causes of mortality in older adults with schizophrenia who take atypical or typical antipsychotics. In a 5-year prospective multicenter study of patients aged = 55 years with an ICD-10 diagnosis of schizophrenia, we used a multivariable logistic regression model to examine the association between atypical vs. typical antipsychotics and mortality, adjusting for sociodemographic and clinical characteristics. Of 313 older adults with schizophrenia, the 5-year all-cause mortality rates in patients who took atypical (n=192) and typical (n=167) antipsychotics were 36.4% and 24.3%, respectively. Following adjustment, no significant differences were found in all-cause mortality (AOR = 1.56; 95%CI 0.75-3.27; p = 0.24) or causes of mortality (all p > 0.05) between medication groups. Atypical antipsychotics were significantly associated with lower overall mortality in the subpopulation with baseline Mini Mental State Examination scores < 24 (AOR = 0.24; 95%CI 0.07-0.84; p = 0.025). Although atypical antipsychotics may not be associated with lower odds of overall mortality than typical antipsychotics in older people with schizophrenia, they might be associated with lower mortality among those with substantial cognitive impairment.

Typical antipsychotics are commonly used in combination with mood stabilizers for acute mania. Although typical antipsychotics are effective, they have undesirable side effects such as induction of depressive symptoms and tardive dyskinesia. Atypical antipsychotics have more favorable side effect profiles, and recent evidence shows their efficacy in treating mania. Apart from a previous small study that compared risperidone with typical neuroleptics as add-on therapy to mood stabilizers, no studies to date have directly compared atypical antipsychotics with typical antipsychotics as add-on therapy to mood stabilizers in a clinically relevant, naturalistic setting. This study is a chart review of all patients with DSM-IV-defined bipolar disorder, current episode mania (N = 204), admitted to the University of British Columbia Hospital during a 30-month period. Patients were separated into 3 groups according to the medications used: (1) mood stabilizer and typical antipsychotic, (2) mood stabilizer and atypical antipsychotic, and (3) combination: mood stabilizer plus a typical antipsychotic, then switched to mood stabilizer plus risperidone or olanzapine within I week. The atypical group was further subdivided into risperidone and olanzapine subgroups. Outcome was measured using Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) ratings generated by review of clinical information in the chart. Patients treated with typical antipsychotics were more severely ill at admission and at discharge than those treated with atypical antipsychotics. Patients in the atypical (p < .005) and combination (p < .05) groups showed significantly greater clinical improvement at discharge than patients treated with typical antipsychotics. This difference was also significant in the subset of patients with psychotic features (p < .03). Risperidone and olanzapine were associated with fewer extrapyramidal side effects than were typical antipsychotics (risperidone vs. typical antipsychotics, chi2 = 8.72, p < .01; olanzapine vs. typical antipsychotics, chi2 = 16.9, p < .001). Due to their superior effectiveness and side effect profile when compared with typical antipsychotics. atypical antipsychotics are an excellent choice as add-on therapy to mood stabilizers for the treatment of patients with mania.

BackgroundThe role of antipsychotics in influencing mortality of patients with mental disorders is still unexplained.ObjectiveThe aim of this study was to determine mortality rates of patients treated with atypical and typical antipsychotics and to compare these data with the mortality rates for the general population.MethodsThe study was based on the 2008–2012 prescription drug reimbursement data from the Polish National Health Fund in Gdansk and mortality data from the death registry. Age-standardized death rates (SDRs) and 95 % confidence intervals (CIs) were calculated for individuals prescribed solely atypical or typical antipsychotics, patients prescribed both atypical and typical antipsychotics, and patients prescribed clozapine.ResultsBetween 2008 and 2012, typical and/or atypical antipsychotics and clozapine were prescribed to a total of 81,313 patients. The SDR for typical antipsychotic users (69.6 per 1000, 95 % CI 67.64–71.56) was higher than for those treated with both typical and atypical antipsychotics (53.25 per 1000, 95 % CI 50.8–55.69) or clozapine (65.11 per 1000, 95 % CI 58.63–71.58). The lowest mortality was documented in the case of patients treated exclusively with atypical antipsychotics (SDR = 48.38 per 1000, 95 % CI, 44.78–51.98). The SDRs for patients treated with antipsychotics were more than tenfold higher than the respective SDRs for the general population in 2008, but later in 2012, the differences dropped to threefold.ConclusionAlthough the study was based on administrative record linkage and therefore could not be adjusted for potential confounders, its results suggest that mortality in atypical antipsychotic users is lower than in typical antipsychotic users.

Objective: Bipolar disorder (BD) is a chronic psychiatric disorder which shows difficulties in the process of diagnosis and treatment. One of the biggest problems in BD maintenance therapy is to ensure medication compliance. Long-acting injectable (LAI) antipsychotic medications have important advantages in such cases. In this study we aimed to include both LAI atypical and typical antipsychotics and to compare the clinical status, number of hospitalization, and side effects of pre and post-treatment periods of one year separately. Methods: Our study sample was constituted of 802 BD patients whom are followed in Mood Disorders Unit of Gaziantep University. Among them 80 patients has been using typical or atypical LAI antipsychotics. In the context of the study criteria only 31 patients included in the study. Efficacy was assessed by the CGI, YMRS, HAMD scores of pre and post-treatment periods of one year (12 months ago, 6 months ago, treatment initiation time, 6 months later and 12 months later), by the rate of hospitalization, and by comparing the average number of mood episodes. Results: LAI antipsychotic usage rate was identified as 9.88% in the study sample. Both of the antipsychotics were shown to decrease the average number of episodes in one year, and effective in preventing manic episodes rather than depressive episodes. Atypical antipsychotics significantly decreased YMRS and CGI scores but a decrease in HAMD scores was not observed, whereas no significant changes were observed in all scale scores with typical antipsychotics. There were not any significant difference when typical and atypical LAI antipsychotics compared according to their side effects in pre and post-treatment periods. Discussion: To the best of our knowledge, this is the first study that atypical and typical LAI antipsychotics were both included. As a result, it was shown that LAI antipsychotics may be effective in the prevention of manic episodes and there were not any differences found in terms of pre and post-treatment side effects. The results of our study are needed to be repeated in new studies with increased number of patients.

To estimate the association between use of typical and atypical antipsychotics and all-cause mortality in a population of demented outpatients. The study cohort comprised all demented patients older than 65 years and registered in the Integrated Primary Care Information (IPCI) database, during 1996-2004. First, mortality rates were calculated during use of atypical and typical antipsychotics. Second, we assessed the association between use of atypical and typical antipsychotics and all-cause mortality through a nested case-control study in the cohort of demented patients. Each case was matched to all eligible controls at the date of death by age and duration of dementia. Odds ratios were estimated through conditional logistic regression analyses. The crude mortality rate was 30.1 (95%CI: 18.2-47.1) and 25.2 (21.0-29.8) per 100 person-years (PY) during use of atypical and typical antipsychotics, respectively. No significant difference in risk of death was observed between current users of atypical and typical antipsychotics (OR = 1.3; 95%CI: 0.7-2.4). Both types of antipsychotics were associated with a significantly increased risk of death as compared to non-users (OR = 2.2, 1.2-3.9 for atypical antipsychotics; OR=1.7, 1.3-2.2 for typical antipsychotics). Conventional antipsychotic drug should be included in the FDA's Public Health advisory, which currently warns only of the increased risk of death with the use of atypical antipsychotics in elderly demented persons.

Experience of VA Psychiatrists With Pharmaceutical Detailing of Antipsychotic Medications

Side effect profiles of atypical antipsychotics, typical antipsychotics, or no psychotropic medications in persons with mental retardation

Extrapyramidal symptoms (EPS) are seen in 50–75% of patients treated with typical antipsychotics and are a cause of treatment failure in at least 30% of the patients. Using atypical antipsychotics, the EPS incidence is lower, but a low-dosage strategy using typical antipsychotics is also known to cause fewer EPS. What conclusions can be drawn for the daily clinical practice? A naturalistic study including all schizophrenic inpatients in a psychiatric ward (n=123) analysed the effects of treatment concerning positive/negative symptoms, EPS, number of days to re-hospitalization and inpatient-days in the year after baseline admittance, using atypical and typical antipsychotics as recommended by the Danish Society of Psychiatry. The incidence of EPS was significantly higher in patients who were treated with typical antipsychotics in relation to atypical antipsychotics (46% vs. 12%, P<0.001). Patients with EPS had significantly more negative symptoms and a poorer level of function at discharge. Nevertheless, no difference regarding re-hospitalization and inpatient-days was found, whether the patient was treated with typical or atypical antipsychotics. However, it is important to underline that patients treated with atypical oral antipsychotic do as well as patients on typical depot antipsychotics.

The authors tested the hypothesis that the use of an atypical drug, clozapine, for patients with schizophrenia is related to less impairment in information processing deficits (assessed by prepulse inhibition of the startle response) than is the use of typical antipsychotics. Two groups of schizophrenic patients--receiving either clozapine or a range of typical antipsychotics--were tested for prepulse inhibition (a reduction in response to a starting stimulus, if preceded briefly by a weak, nonstartling stimulus; measured at prepulse-to-pulse intervals of 30 msec, 60 msec, and 120 msec) of the acoustic startle response and compared with a group of healthy volunteers. Patients receiving typical antipsychotics showed less prepulse inhibition with 30-msec and 60-msec prepulse trials than did comparison subjects. Clozapine-treated patients showed normal levels of prepulse inhibition. Clozapine is superior to typical antipsychotics in normalizing prepulse inhibition, presumably because of its pharmacological effects on prefrontal regions of the brain or its effects on a broader range of neuroreceptors.

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessStudy Questions Superiority Of Newer AntipsychoticsJim RosackJim RosackSearch for more papers by this authorPublished Online:3 Nov 2006https://doi.org/10.1176/pn.41.21.0023Research funded by the United Kingdom's National Health Service suggests that when patients with schizophrenia need to change their medication, either because of ineffectiveness or intolerable side effects, the newer, nonclozapine second-generation antipsychotics (SGAs) do not appear to offer significant benefits over the first-generation antipsychotics (FGAs).The study's findings, reported in the October Archives of General Psychiatry, have generated significant discussion (see article below).The study, known as the Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1), is the second over the last year to challenge the widely held perception that SGAs are safer and more effective in treating patients with schizophrenia than are the FGAs. In April, results from the National Institute of Mental Health's CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study indicated that in general patients were likely to do as well on the FGA perphenazine as on newer SGAs (Psychiatric News, April 21).For nearly 50 years, patients taking the older medications would often relapse or develop severe side effects, including sedation and involuntary muscle movements. The development of SGAs was thought to be a major advance primarily because the medications reduced the risk of extrapyramidal symptoms and the potential for development of tardive dyskinesia over the long term. Claims that the SGAs are more effective than the FGAs resulted in significant shifting of prescribing patterns away from the older drugs, even though research comparing the old and the new has produced mixed results.In the Archives report, Peter Jones, M.D., Ph.D., a professor of psychiatry at the University of Cambridge and Cambridgeshire and Peterborough Mental Health NHS Trust, and colleagues studied 227 people with schizophrenia aged 18 to 65 from 14 community psychiatric services in the English National Health Service.“The key question was whether the additional acquisition costs of second-generation antipsychotics over first-generation antipsychotics would be offset by improvements in health-related quality of life or savings in the use of other health and social care services in people with schizophrenia for whom a change in drug treatment was being considered for clinical reasons, most commonly suboptimal efficacy or adverse effects,” Jones and his coauthors wrote.The participants were randomly assigned to receive one class of drug or the other. (Clozapine was not included in the study; see Original article: box) However, their treating physicians determined which of the first- or second-generation medications would be best for them. In the FGA group, 49.15 percent of the patients were started on sulpiride, which is not available in the United States. In the SGA group, 46 percent were started on olanzapine.Participants were assessed at baseline and at 12, 26, and 52 weeks after the change in treatment with the Quality of Life Scale, where higher scores reflect a better quality of life.The researchers hypothesized that the SGAs would produce a five-point improvement in quality-of-life scores compared with the FGAs. Symptoms, side effects, treatment costs, and satisfaction with the drug also were measured.The researchers expressed surprise in finding their hypothesis was not validated (see chart).“Participants in the first-generation antipsychotic arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores,” the authors noted. “Participants reported no clear preference for either drug group; and lastly, costs were similar.”Over the course of the 52 weeks of the trial, mean total costs per patient in the FGA arm were $34,750, compared with $37,185 per patient in the SGA arm. Antipsychotic drug costs accounted for only a small portion of the total costs encountered (2.1 percent for FGAs, and 3.8 percent for SGAs). There was a greater difference in hospitalization costs: inpatient admissions accounted for 93.2 percent of total costs in the FGA arm and 81.5 percent in the SGA arm. Overall the authors concluded that costs were similar between the FGA and SGA arms though they noted that there was a trend toward greater costs in the SGA arm.“All the data suggest that careful prescribing of first-generation antipsychotics, at least in the context of a trial, is not associated with poorer efficacy or a greater adverse-effect burden, both of which would translate into lower quality of life in the medium term,” Jones and his coauthors concluded. “This suggests that despite recent policy statements and prescribing patterns, further randomized and other evaluations of second-generation antipsychotics would still be useful in establishing their role in the long-term management of schizophrenia and, likewise, the continued role of older drugs.”An abstract of “Randomized Controlled Trial of the Effect on Quality of Life of Second- vs. First-Generation Antipsychotic Drugs in Schizophrenia” is posted at<http://archpsyc.ama-assn.org/cgi/content/full/63/10/1079>.▪ ISSUES NewArchived

EPA-0048 - Relationships between serum total antioxidant capacity and typical/atypical antipsychotic treatment in acute paranoid schizophrenia

Treatment Costs Related to Bipolar Disorder and Comorbid Conditions Among Medicaid Patients With Bipolar Disorder

To report the outcomes of a retrospective database analysis to compare the effectiveness of atypical and typical antipsychotic drugs. Medical records of patients admitted to the psychiatry outpatient clinic between January 1998 and October 2005 were retrospectively reviewed. Data obtained from patient records were noted on a special form assessing four aspects of the treatment history: socio-demographic features, disease characteristics, initial treatment at the time of admission, and course of treatment. Patient groups (typical/atypical and Risperidone/Haloperidol/Olanzapine) were compared for time to all-cause medication discontinuation and rate of discontinuation. There was no statistically significant difference in the duration of treatment between patients using atypical (n = 150) and typical (n = 124) antipsychotics. The duration of treatment was significantly longer in patients on Haloperidol (n = 91) compared with those on Risperidone (n = 63). Rates of discontinuation over 18 months were 59.3% for patients on atypical antipsychotics and 57.3% for those on typical antipsychotics, and 68.3% for patients on Risperidone, 51.6% for patients on Haloperidol and 54.3% for patients on Olanzapine. Despite our hypothesis patients with chronic schizophrenia discontinued their atypical and typical antipsychotics, at a high rate with no significant difference indicating substantial limitations in the effectiveness of these drugs.