The effectiveness of antipsychotic medications in patients who use or avoid illicit substances: results from the CATIE study

OBJECTIVE: This double-blind study compared a second generation (atypical) antipsychotic drugs compared to a representative older agent for patients with schizophrenia who use or avoid illicit substances. METHODS: Schizophrenic subjects were recruited at 57 U.S. sites and randomly assigned to olanzapine, perphenazine, quetiapine, risperidone or ziprasidone for up to 18 months. The primary aim of this analysis was to delineate differences between the overall effectiveness of these five treatments among patients who used or did not use illicit substances. RESULTS: There were no significant differences between treatment groups in time to all-cause treatment discontinuation among patients who use illicit drugs (median 3.3 to 6.8 months). Among non-users time to treatment discontinuation was significantly longer for patients treated with olanzapine (median 13.0 months) than perphenazine ( 5.9 months), risperidone (5.6 months), or quetiapine (5.0 months); time to discontinuation for ziprasidone (4.3 months) was even shorter, although the latter difference was not significant. The difference between risperidone and quetiapine, although small, was significant. All remaining differences were non-significant. Similar results were found for discontinuation due to inefficacy. There were no differences between illicit users and non-users in symptom reduction and global improvement, after adjustment for differential duration of treatment. Differences in discontinuation results were attenuated by non-compliance, but the trends persisted after controlling for treatment compliance. CONCLUSIONS: Among patients with chronic schizophrenia who avoid use of illicit drugs, olanzapine was more effective than other antipsychotics as reflected by longer time to all-cause discontinuation, but illicit substance abuse attenuated this advantage, reinforcing the need for concurrent substance abuse treatment.     

Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic

BACKGROUND: In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic. METHOD: Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason. RESULTS: The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168). CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.     

Comparative effectiveness of second-generation antipsychotic medications in early-onset schizophrenia

Scant information exists to guide pharmacological treatment of early-onset schizophrenia. We examine variation across commonly prescribed second-generation antipsychotic medications in medication discontinuation and psychiatric hospital admission among children and adolescents clinically diagnosed with schizophrenia. A 45-state Medicaid claims file (2001-2005) was analyzed focusing on outpatients, aged 6-17 years, diagnosed with schizophrenia or a related disorder prior to starting a new episode of antipsychotic monotherapy with risperidone (n = 805), olanzapine (n = 382), quetiapine (n = 260), aripiprazole (n = 173), or ziprasidone (n = 125). Cox proportional hazard regressions estimated adjusted hazard ratios of 180-day antipsychotic medication discontinuation and 180-day psychiatric hospitalization for patients treated with each medication. During the first 180 days following antipsychotic initiation, most youth treated with quetiapine (70.7%), ziprasidone (73.3%), olanzapine (73.7%), risperidone (74.7%), and aripirazole (76.5%) discontinued their medication (χ(2) = 1.69, df = 4, P = .79). Compared with risperidone, the adjusted hazards of antipsychotic discontinuation did not significantly differ for any of the 4-comparator medications. The percentages of youth receiving inpatient psychiatric treatment while receiving their initial antipsychotic medication ranged from 7.19% (aripiprazole) to 9.89% (quetiapine) (χ(2) = 0.79, df = 4, P = .94). As compared with risperidone, the adjusted hazard ratio of psychiatric hospital admission was 0.96 (95% CI: 0.57-1.61) for olanzapine, 1.03 (95% CI: 0.59-1.81) for quetiapine, 0.85 (95% CI: 0.43-1.70) for aripiprazole, and 1.22 (95% CI: 0.60-2.51) for ziprasidone. The results suggest that rapid antipsychotic medication discontinuation and psychiatric hospital admission are common in the community treatment of early-onset schizophrenia. No significant differences were detected in risk of either adverse outcome across 5 commonly prescribed second-generation antipsychotic medications.     

What CATIE found: results from the schizophrenia trial

The authors provide an overview of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) sponsored by the National Institute of Mental Health. CATIE was designed to compare a proxy first-generation antipsychotic, perphenazine, to several newer drugs. In phase 1 of the trial, consenting patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone for up to 18 months on a double-blind basis. Patients with tardive dyskinesia were excluded from being randomly assigned to perphenazine and were assigned to one of the four second-generation antipsychotics in phase 1A. Clozapine was included in phase 2 of the study. Overall, olanzapine had the longest time to discontinuation in phase 1, but it was associated with significant weight and metabolic concerns. Perphenazine was not significantly different in overall effectiveness, compared with quetiapine, risperidone, and ziprasidone. Also, perphenazine was found to be the most cost-effective drug. Clozapine was confirmed as the most effective drug for individuals with a poor symptom response to previous antipsychotic drug trials, although clozapine was also associated with troublesome adverse effects. There were no differences in neurocognitive or psychosocial functioning in response to medications. Subsequent randomizations suggest that a poor response to an initial medication may mean that a different medication will be more effective or better tolerated. Although the CATIE results are controversial, they are broadly consistent with most previous antipsychotic drug trials and meta-analyses; however, the results may not generalize well to patients at high risk of tardive dyskinesia. Patient characteristics and clinical circumstances affected drug effectiveness; these patient factors are important in making treatment choices.     

Effectiveness of olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia after discontinuing perphenazine: a CATIE study

OBJECTIVE: The relative effectiveness of newly started antipsychotic drugs for individuals with schizophrenia may depend on multiple factors, including each patient's previous treatment response and the reason for a new medication trial. This randomized, double-blind study compared olanzapine, quetiapine, and risperidone in patients who had just discontinued the older antipsychotic perphenazine. METHOD: Subjects with schizophrenia (N=114) who had been randomly assigned to and then discontinued perphenazine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study were reassigned randomly to double-blinded treatment with olanzapine, 7.5-30.0 mg/day (N=38); quetiapine, 200-800 mg/day (N=38); or risperidone, 1.5-6.0 mg/day (N=38). The primary aim was to determine whether there were differences among these three treatments in effectiveness, as measured by time to treatment discontinuation for any reason. Secondary outcomes included reasons for treatment discontinuation and measures of drug tolerability. RESULTS: The time to treatment discontinuation was longer for patients treated with quetiapine (median, 9.9 months) and olanzapine (7.1 months) than with risperidone (3.6 months). There were no significant differences between treatments on discontinuation due to inefficacy, intolerability, or patient decision. CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued the older antipsychotic perphenazine, quetiapine and olanzapine were more effective than risperidone, as reflected by longer time to discontinuation for any reason. In the context of other results from the CATIE study, the effectiveness and acceptability of antipsychotic drugs appears to vary considerably according to clinical circumstances.     

The effects of antipsychotic medications on emotion perception in patients with chronic schizophrenia in the CATIE trial

Few pharmacological intervention studies have examined the impact of medication on social cognition, particularly emotion perception. The goal of this randomized, double-blind study is to compare the effects of several second generation antipsychotics and a first generation antipsychotic, perphenazine, on emotion perception in individuals with schizophrenia. Patients were assigned to receive treatment with olanzapine, queitapine fumarate, risperidone, ziprasidone or perphenazine for up to 18 months. Eight hundred and seventy three patients completed an emotion perception test immediately prior to randomization and after 2 months of treatment. We also examined baseline predictors of emotion perception change. Most treatments were associated with a small, non-statistically significant improvement in emotion perception at two months, although they did not differ from one another. Greater improvement in emotion perception at 2 months was significantly predicted by lower baseline emotion perception and higher baseline neurocognitive functioning, and marginally predicted by less time on an antipsychotic.     

What have we learned from CATIE about the pharmacologic treatment of schizophrenia?

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study sponsored by the National Institute of Mental Health compared the effectiveness of four second-generation antipsychotics (olanzapine, risperidone, quetiapine, and ziprasidone), and one first-generation antipsychotic (perphenazine) in 1460 individuals with chronic schizophrenia. A hybrid of effectiveness and efficacy study design, the primary outcome was antipsychotic “effectiveness,” as measured by discontinuation of the assigned antipsychotic because of inadequate efficacy, inadequate tolerability, patient decision, or other reason. Most (64% to 82%) patients discontinued the phase-I antipsychotic before 18 months of treatment (approximately two-thirds subjects continued treatment with a different antipsychotic in phase 2). The five antipsychotics varied significantly in effectiveness, efficacy, and side-effect profiles. CATIE baseline results also find the general health of individuals with chronic schizophrenia to be poor, highlighting concerns about added risk from metabolic side effects of some antipsychotics. Analysis of comparative cost effectiveness, impact on cognition, rates of recovery, phase 2 results, and many other analyses are forthcoming, and the cumulative findings from the CATIE study will provide an evidence base for clinicians, health care administrators, patients and their families to make pharmacologic treatment choices.     

Cost-effectiveness of second-generation antipsychotics and perphenazine in a randomized trial of treatment for chronic schizophrenia

BACKGROUND: Second-generation antipsychotics have largely replaced first-generation antipsychotics for the treatment of schizophrenia, but a large-scale cost/effectiveness analysis has not been attempted. METHOD: Patients with schizophrenia (N=1,493) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of four second-generation drugs (olanzapine, quetia-pine, risperidone, or ziprasidone) and followed for up to 18 months. Patients with tardive dyskinesia were prohibited from assignment to perphenazine. Patients could be reassigned at any time to another second-generation drug, including clozapine, but not to perphenazine. The cost analysis included medications plus health services use. Quality-adjusted life year (QALY) ratings were assessed on the basis of Positive and Negative Syndrome Scale (PANSS) subscale scores and side effects. An intention-to-treat analysis included all available observations, classified by initial drug assignment, and costs of reassignment of most patients to another second-generation drug. The analysis was repeated considering only treatment on initially assigned medications. RESULTS: Although QALY ratings, PANSS scores, and other quality of life measures indicated modest improvement over 18 months, there were no significant differences between perphenazine and any second-generation medication. Average total monthly health care costs were 300 dollars-600 dollars (20%-30%) lower for perphenazine than for second-generation antipsychotics because of lower drug cost. Differences in costs remained when maximally discounted drug prices were used for all patients and when only observations during treatment with the first medication were included. CONCLUSIONS: Treatment with perphenazine was less costly than treatment with second-generation antipsychotics with no significant differences in measures of effectiveness. However, the trial was limited by a high dropout rate, and longer-term neurological and metabolic side effects require further study.     

Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment

OBJECTIVE: When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation. METHOD: Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]). RESULTS: Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation. CONCLUSIONS: For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.     

Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study

OBJECTIVE: This study examined the relative effects of the second-generation antipsychotic drugs and an older representative agent on psychosocial functioning in patients with chronic schizophrenia. METHOD: Consenting patients were enrolled in the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project. In phase 1, patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone for up to 18 months. Clozapine was included for patients who chose this pathway after discontinuing phase 1 due to inefficacy; all other patients received another second-generation antipsychotic. Psychosocial functioning was assessed using the Quality of Life Scale. RESULTS: Psychosocial functioning modestly improved for the one-third of phase 1 patients who reached the primary Quality of Life Scale analysis endpoint of 12 months (average effect size 0.19 SD units). Although for several of the drugs individually there were significant changes from baseline, overall there were no significant differences between the different agents. Results were similar at 6 and 18 months. There were no significant differences among the treatment groups in the amount of change in the Quality of Life Scale total score or subscale scores at 6, 12, or 18 months. Patients treated with clozapine in the efficacy pathway made comparable gains. Early treatment discontinuations, especially among patients most impaired at baseline, limited the ability to achieve more substantial functional gains. CONCLUSIONS: All antipsychotic treatment groups in all phases made modest improvements in psychosocial functioning. There were no differences among them after 6, 12, or 18 months. More substantial improvements would likely require more intensive adjunctive psychosocial rehabilitation interventions.     

Effectiveness of antipsychotic treatments for schizophrenia: interim 6-month analysis from a prospective observational study (IC-SOHO) comparing olanzapine, quetiapine, risperidone, and haloperidol

BACKGROUND: The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study was designed to provide information regarding use and outcome of antipsychotic treatments in a large, diverse population in real practice settings. METHOD: Outpatients with schizophrenia (ICD-10 or DSM-IV) who initiated or changed to a new antipsychotic entered this 3-year, naturalistic, prospective observational study. Four monotherapy treatment groups were defined according to the antipsychotic prescribed at baseline, namely olanzapine, risperidone, quetiapine, and haloperidol. Efficacy was assessed using the Clinical Global Impressions-Severity of Illness rating scale (CGI-S), inclusive of subscales for positive, negative, depressive, and cognitive symptoms. Tolerability was assessed by adverse event questionnaires and weight measurements. Six-month findings are described. RESULTS: At baseline, 5833 participants were prescribed monotherapy and the mean severity of illness was moderate to marked (CGI-S). At 6 months, olanzapine resulted in significantly greater improvements in overall, positive, negative, depressive, and cognitive symptoms compared with quetiapine, risperidone or haloperidol (p <.001). Improvements in overall, negative, and cognitive symptoms were significantly higher for risperidone compared with haloperidol (p <.001), whereas improvements across all symptoms were comparable for quetiapine and haloperidol. Extra-pyramidal symptoms and tardive dyskinesia decreased compared with baseline in the olanzapine, quetiapine, and risperidone groups but increased in the haloperidol group (p <.001, likelihood of extrapyramidal symptoms with haloperidol compared with olanzapine, quetiapine, or risperidone). Sexual function adverse events were most prominent in the haloperidol and risperidone treatment groups. Weight change was significantly greater for olanzapine compared with the other antipsychotics (p <.001). CONCLUSION: Our results support the previously reported positive impact of atypical antipsychotics, particularly olanzapine, in patients with schizophrenia.     

The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development

The National Institute of Mental Health initiated the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) program to evaluate the effectiveness of antipsychotic drugs in typical settings and populations so that the study results will be maximally useful in routine clinical situations. The CATIE schizophrenia trial blends features of efficacy studies and large, simple trials to create a pragmatic trial that will provide extensive information about antipsychotic drug effectiveness over at least 18 months. The protocol allows for subjects who receive a study drug that is not effective to receive subsequent treatments within the context of the study. Medication dosages are adjusted within a defined range according to clinical judgment. The primary outcome is all-cause treatment discontinuation because it represents an important clinical endpoint that reflects both clinician and patient judgments about efficacy and tolerability. Secondary outcomes include symptoms, side effects, neurocognitive functioning, and cost-effectiveness. Approximately 50 clinical sites across the United States are seeking to enroll a total of 1,500 persons with schizophrenia. Phase 1 is a double-blinded randomized clinical trial comparing treatment with the second generation antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone to perphenazine, a midpotency first generation antipsychotic. If the initially assigned medication is not effective, subjects may choose one of the following phase 2 trials: (1) randomization to open-label clozapine or a double-blinded second generation drug that was available but not assigned in phase 1; or (2) double-blinded randomization to ziprasidone or another second generation drug that was available but not assigned in phase 1. If the phase 2 study drug is discontinued, subjects may enter phase 3, in which clinicians help subjects select an open-label treatment based on individuals' experiences in phases 1 and 2.     

Antipsychotic use in the treatment of outpatients with schizophrenia in the VA from fiscal years 1999 to 2006

OBJECTIVE: This study examined changes in prescribing patterns of antipsychotic medications to treat schizophrenia. METHODS: Pharmacy records for patients with schizophrenia were obtained from Department of Veterans Affairs databases. The proportion of patients prescribed specific second-generation antipsychotics or any first-generation antipsychotic was calculated per year. RESULTS: In fiscal year (FY) 2006, 78,849 veterans with schizophrenia were prescribed antipsychotic medication. For FY 1999 to FY 2006 the percentage of patients with schizophrenia who received first-generation antipsychotics decreased from 40.8% to 15.9%, but the percentage receiving olanzapine, after peaking at 32.0% in FY 2001, decreased to 19.0%. The percentage of patients given quetiapine increased from 2.5% to 18.8%; risperidone, from 25.5% to 29.7%. However, clozapine usage remained flat, at 2.0%-3.0%. Use of then-new ziprasidone and aripiprazole rose from 5.0% to 9.0%. CONCLUSIONS: Use of each antipsychotic newly marketed over eight years increased while use of risperidone was unchanged and use of olanzapine and the first-generation antipsychotics declined.     

Treatment adherence among patients with bipolar or manic disorder taking atypical and typical antipsychotics

OBJECTIVE: This retrospective claims-based study evaluated treatment adherence among patients with bipolar or manic disorder treated with atypical and typical antipsychotics. METHOD: Claims data for 18,158 antipsychotic treatment episodes in 15,224 commercially insured patients with bipolar or manic disorder (ICD-9-CM criteria), from January 1999 through August 2003, were evaluated. Overall adherence was measured by adherence intensity (medication possession ratio) and treatment duration (length of treatment episodes). Treatment-related factors that may affect medication adherence were also investigated. Pairwise comparisons of the individual atypicals and a combined group of leading typical antipsychotics were undertaken using multiple regression analysis adjusting for differing patient characteristics. RESULTS: Adherence intensity with quetiapine was 3% greater than with the typicals combined (p=.002) and was greater than with risperidone or olanzapine by 4% (p<.001) and 2% (p=.001), respectively. Olanzapine (2%, p<.001) and ziprasidone (3%, p=.001) showed significantly greater adherence intensity than risperidone. Risperidone (p=.002), olanzapine (p=.055), and the typicals (p=.021) demonstrated negative associations between dose and adherence intensity, while quetiapine showed a nonsignificant trend for a positive association (p=.074). Quetiapine and risperidone had significantly longer treatment durations than the typicals combined (1.05 and 1.00 months, respectively, p<.001) and longer treatment durations than olanzapine (0.75 and 0.79 months, respectively, p<.001) or ziprasidone (0.78 months, p=.002 and 0.69 months, p=.003, respectively). Shorter treatment durations were associated with switching to other antipsychotics or remaining on or switching to other psychotropics (e.g., traditional mood stabilizers) only. All of the atypicals except ziprasidone were associated with a significantly lower likelihood of switching compared with the typicals (p<.05). CONCLUSIONS: The claims-based findings of this study suggest that, for bipolar or manic disorder, quetiapine therapy may be associated with better treatment adherence than typical or some atypical antipsychotics. Estimated differences, however, were relatively small, particularly for adherence intensity.     

Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: a randomized, double-blind 52-week comparison

OBJECTIVE: The authors sought to compare the effects of olanzapine, quetiapine, and risperidone on neurocognitive function in patients with early psychosis. METHOD: In a 52-week double-blind, multicenter study, 400 patients early in the course of psychotic illness (<5 years) were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day). The mean modal daily dose was 11.7 mg (SD=5.3) for olanzapine, 506 mg (SD=215) for quetiapine, and 2.4 mg (SD=1.0) for risperidone. A total of 224 patients completed neurocognitive assessments at baseline and at 12 weeks, and 81 patients also completed them at 52 weeks. Neurocognitive composite scores were calculated from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and from the Brief Assessment of Cognition in Schizophrenia. RESULTS: At week 12, there was significant improvement in neurocognition for each treatment (p<0.01), but no significant overall difference between treatments. Composite z score improvements on the CATIE neurocognitive battery were 0.17 for olanzapine, 0.33 for quetiapine, and 0.32 for risperidone. Composite z score improvements on the Brief Assessment of Cognition in Schizophrenia were 0.19 for olanzapine, 0.34 for quetiapine, and 0.22 for risperidone. Statistically significant relationships between improvements in neurocognition and functional outcome were observed at weeks 12 and 52. CONCLUSIONS: Olanzapine, quetiapine, and risperidone all produced significant improvements in neurocognition in early-psychosis patients. Although cognitive improvements were modest, their clinical importance was suggested by relationships with improvements in functional outcome.     

Impact of antipsychotic treatment on nonfasting triglycerides in the CATIE Schizophrenia Trial phase 1

BACKGROUND: Recent literature documents a stronger association between nonfasting triglycerides (TG) and cardiovascular risk compared to fasting TG. Given concerns over antipsychotic effects on serum TG, this analysis explored changes in nonfasting TG in phase 1 of the CATIE Schizophrenia Trial. METHODS: Change in nonfasting TG, adjusted for baseline value, was compared between antipsychotic treatment groups using subjects with nonfasting laboratory assessments at baseline and 3 months. RESULTS: Among the 246 subjects there were significant treatment differences in 3-month change from baseline (p=0.009). The greatest increases in median and adjusted mean nonfasting TG levels were seen among those randomized to quetiapine (mean+54.7 mg/dl, median+26 mg/dl) and olanzapine (mean+23.4 mg/dl, median+26.5 mg/dl), while ziprasidone was neutral (mean+0.0 mg/dl, median+8 mg/dl), and decreases were seen with risperidone (mean -18.4 mg/dl, median -6.5 mg/dl) and perphenazine (mean -1.3 mg/dl, median -22 mg/dl). Pairwise comparisons indicated a significant between-group difference for perphenazine vs. olanzapine (p=0.002) and a trend for perphenazine vs. quetiapine (p=0.006). CONCLUSIONS: This analysis provides further evidence for differential antipsychotic metabolic liabilities, and confirms signals for the effects of olanzapine and quetiapine on serum TG seen in earlier CATIE analyses. Future consensus recommendations will clarify the role of nonfasting TG monitoring in routine clinical practice.     

The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors

Background

How long an antipsychotic is effective in maintaining response is important in choosing the correct treatment for people with schizophrenia. This post-hoc analysis describes maintenance of response over 24 or 28 weeks in people treated for schizophrenia with olanzapine, risperidone, quetiapine, ziprasidone, or aripiprazole.

Methods

This was a post-hoc analysis using data from 5 double-blind, randomized, comparative trials of 24 or 28 weeks duration in which olanzapine was compared to risperidone (1 study; N = 339), quetiapine (1 study; N = 346), ziprasidone (2 studies; N = 548 and 394) or aripiprazole (1 study; N = 566) for treatment of schizophrenia. For each study, time to loss of response in patients who met criteria for response at Week 8 and the proportion of patients who lost response following Week 8 were compared by treatment group. The number needed to treat (NNT) with olanzapine rather than comparator to avoid loss of one additional responder over 24 or 28 weeks of treatment was calculated for each study.

Results

Time maintained in response was significantly longer (p < .05) for olanzapine compared to risperidone, quetiapine, and ziprasidone. Olanzapine did not significantly differ from aripiprazole. The proportion of patients who lost response was significantly lower for olanzapine versus risperidone, quetiapine, and ziprasidone (p < .05). NNTs to avoid one additional patient with loss of response with olanzapine versus risperidone, quetiapine and ziprasidone were favourable, ranging from 5 to 9.

Conclusion

During 24 and 28 weeks of treatment, the antipsychotics studied differed in the time that treated patients with schizophrenia remained in response and the proportion of patients who lost response. Olanzapine treatment resulted in a consistent and statistically significant advantage in maintenance of response compared to treatment with risperidone, quetiapine and ziprasidone; but not compared to treatment with aripiprazole.     

Antipsychotic effects on estimated 10-year coronary heart disease risk in the CATIE schizophrenia study

OBJECTIVE: Persons with schizophrenia die earlier than the general population, in large part due to cardiovascular disease. The study objective was to examine effects of different antipsychotic treatments on estimates of 10-year coronary heart disease (CHD) risk calculated by the Framingham Heart Study formula. METHOD: Change in 10-year risk for CHD was compared between treatment groups in 1125 patients followed for 18 months or until treatment discontinuation in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial. RESULTS: The covariate-adjusted mean change in 10-year CHD risk differed significantly between treatments. Olanzapine was associated with a 0.5% (SE 0.3) increase and quetiapine, a 0.3% (SE 0.3) increase; whereas risk decreased in patients treated with perphenazine, -0.5% (SE 0.3), risperidone, -0.6% (SE 0.3), and ziprasidone -0.6% (SE 0.4). The difference in 10-year CHD risk between olanzapine and risperidone was statistically significant (p=0.004). Differences in estimated 10-year CHD risk between drugs were most marked in the tertile of subjects with a baseline CHD risk of at least 10%. Among individual CHD risk factors used in the Framingham formula, only total and HDL cholesterol levels differed between treatments. CONCLUSIONS: These results indicate that the impact on 10-year CHD risk differs significantly between antipsychotic agents, with olanzapine producing the largest elevation in CHD risk of the agents studied in CATIE.     

The CATIE schizophrenia trial: results, impact, controversy

The CATIE (Clinical Antipsychotic Trials for Intervention Effectiveness) Schizophrenia Trial was designed to examine fundamental issues about second-generation antipsychotic (SGA) medications (olanzapine, risperidone, quetiapine, and ziprasidone) - their relative effectiveness and their effectiveness compared to a first-generation antipsychotic (FGA), perphenazine. This article reviews these and other findings from this important trial and offers a perspective regarding their meaning for practice and their significance for the advancement of research in psychiatry. The primary outcome measure, time to discontinuation, served as an index of effectiveness and was remarkably short; only 26% of subjects completed the 18-month trial on the medicine to which they were initially randomized. Subjects receiving olanzapine experienced a slightly longer time to discontinuation. Based on this single criterion, olanzapine showed greater effectiveness than the other agents despite its association with significant metabolic disturbance, especially weight gain. Perphenazine unexpectedly showed comparable levels of effectiveness and produced no more extrapyramidal side effects than the other agents. Despite modest prolactin elevation, risperidone was the best-tolerated medication. Ziprasidone was associated with weight loss and with positive impact on lipids and blood glucose. In Phase 2, clozapine demonstrated better effectiveness compared to other SGAs for subjects who discontinued their Phase 1 medication because of efficacy. Olanzapine and risperidone showed greater effectiveness in the tolerability pathway. CATIE secondary outcomes are currently being examined. Improvements in cognition were modest among all the agents in Phase 1, and perphenazine was no less effective in improving cognitive performance than the SGAs. Cost-effectiveness analysis revealed a significant advantage for perphenazine, due to the impact of the high-priced, brand-name SGAs on overall health care costs.     

Effectiveness of antipsychotic maintenance therapy with quetiapine in comparison with risperidone and olanzapine in routine schizophrenia treatment: results of a prospective observational trial

Objective of this observational trial is to examine the effects of quetiapine in comparison with olanzapine and risperidone on clinical outcomes and quality of life in patients with schizophrenia and schizoaffective disorder in routine care. 374 adult persons with schizophrenia or schizoaffective disorder prescribed antipsychotic maintenance therapy with quetiapine, olanzapine, or risperidone at discharge from inpatient treatment were included. Clinical and psychosocial outcomes were assessed before discharge and at 6, 12, 18, and 24?months. Statistical analyses were conducted by mixed-effects regression models for longitudinal data. The propensity score method was used to control for selection bias. Patients discharged on olanzapine had significantly lower hospital readmissions than those receiving quetiapine or risperidone. The average chlorpromazine equivalent dose of quetiapine was higher than in patients treated with olanzapine or risperidone. No further significant differences between treatment groups were found. Quetiapine and risperidone are less effective in preventing the need for psychiatric inpatient care than olanzapine, and higher chlorpromazine equivalent doses of quetiapine are needed to obtain clinical effects similar to those of olanzapine and risperidone.