Insight and Treatment Outcomes in Schizophrenia: Post-hoc Analysis of a Long-term, Double-blind Study Comparing Lurasidone and Quetiapine XR.

Objective: The objective of this post-hoc analysis was to evaluate the effect of lurasidone and quetiapine extended-release (XR) on insight and judgment and assess the longitudinal relationships between improvement in insight and cognitive performance, functional capacity, quality of well-being, and depressive symptoms in patients with schizophrenia. Design: Clinically unstable patients with schizophrenia (N=488) were randomized to once-daily, fixed-dose treatment with lurasidone 80mg, lurasidone 160mg, quetiapine XR 600mg, or placebo, followed by a long-term, double-blind, flexible-dose continuation study involving these agents. Results: Significantly greater improvement in insight and judgment (assessed by the Positive and Negative Syndrome Scale G12 item) for the lurasidone and quetiapine XR groups, compared to the placebo group, was observed at Week 6. Over a subsequent six-month continuation period, the flexible dose lurasidone group showed significantly greater improvement in insight from acute phase baseline compared to the flexible-dose quetiapine XR group (QXR-QXR) (p=0.032). Improvement in insight was significantly correlated with improvement in cognition (p=0.014), functional capacity (p=0.006, UPSA-B), quality of well-being (p=0.033, QWB), and depressive symptoms (p=0.05, Montgomery-Åsberg Depression Rating Scale [MADRS] score) across treatment groups and study periods. Conclusion: In this post-hoc analysis, flexibly dosed lurasidone 40 to 160mg/d was found to be associated with significantly greater improvement in insight compared to flexibly dosed quetiapine XR 200 to 800mg/d over long-term treatment in patients with schizophrenia. Across treatment groups, improvement in insight and judgment was significantly associated with improvement in cognition, functional capacity, quality of well-being, and depressive symptoms over time.

Change in daytime sleepiness and cognitive function in a 6-month, double-blind study of lurasidone and quetiapine XR in patients with schizophrenia.

Daytime sleepiness is a commonly reported adverse effect associated with psychotropic agents that may impair cognitive performance and functioning. The objective of this post-hoc analysis was to evaluate the long-term effects of lurasidone and quetiapine XR on daytime sleepiness and neurocognitive performance during a 6-month, double-blind continuation study, in subjects who completed an initial 6-week, randomized, placebo-controlled trial comparing these agents. Daytime sleepiness, cognitive performance, and health-related quality of life were assessed with the Epworth Sleepiness Scale (ESS), CogState computerized battery, and the Quality of Well-Being (QWB-SA) Scale, respectively. Treatment with flexible-dose lurasidone 40-160 mg/d, administered once daily in the evening, was associated with significantly reduced daytime sleepiness compared with flexibly dosed quetiapine XR 200-800 mg/d (p = 0.03, effect size = 0.36) at week 32 (month 6 of the continuation study endpoint). Incidence of markedly high sleepiness (ESS > 10) was significantly higher in the quetiapine XR (200-800 mg/d) group compared with the lurasidone (40-160 mg/day) group at both months 3 and 6 visits (p < 0.05). Lurasidone (40-160 mg/d) significantly improved neurocognitive performance compared to quetiapine XR (200-800 mg/d) before (effect size = 0.49) and after adjustment (effect size = 0.45) for sleepiness effect (p = 0.008 and 0.010, respectively). Increased daytime sleepiness was significantly associated with reduced neurocognitive performance (p = 0.019) and quality of well-being (p = 0.05). Our findings suggest that clinicians should actively monitor patients for the presence of daytime sleepiness due in part to its potential impact on neurocognitive performance and well-being.

Lurasidone for the treatment of depressive symptoms in schizophrenia: analysis of 4 pooled, 6-week, placebo-controlled studies.

OBJECTIVE: Depressive symptoms are common in schizophrenia and can worsen outcomes and increase suicide risk. Lurasidone is an atypical antipsychotic agent indicated for the treatment of schizophrenia and for the treatment of major depressive episodes associated with bipolar I disorder. This post hoc analysis evaluated the effect of lurasidone on depressive symptoms in patients with schizophrenia. METHODS: Patient-level data were pooled from 4 similarly designed, double-blind, placebo-controlled, 6-week registration studies of lurasidone (40-160 mg/d) in adult patients with an acute exacerbation of schizophrenia. Changes in depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), were analyzed for the overall sample and for subgroups of patients stratified by baseline MADRS scores. RESULTS: MADRS assessments at baseline and endpoint (day 42 or last observation carried forward [LOCF]) were available for 1330 patients. Patients receiving lurasidone experienced significantly greater decreases in MADRS score (-2.8, least-squares [LS] mean change, LOCF) compared with patients receiving placebo (-1.4, P < .001, effect size 0.24). Analysis of change in MADRS score (LOCF) by baseline symptom severity (MADRS score of ≥12, ≥14, ≥16, ≥18) showed significantly greater improvement for lurasidone-treated patients across all severity groups; effect sizes ranged from 0.25 to 0.34. Among patients with a baseline MADRS score of ≥12, depressive symptom remission (defined as MADRS score <10 at LOCF endpoint) was attained by 45.0% of lurasidone-treated patients and 36.3% of patients receiving placebo (P < .05). CONCLUSIONS: In a pooled analysis of short-term, placebo-controlled studies, lurasidone significantly improved depressive symptoms in patients with schizophrenia.

Daytime sleepiness associated with lurasidone and quetiapine XR: results from a randomized double-blind, placebo-controlled trial in patients with schizophrenia.

OBJECTIVE: The aim of this analysis was to compare the effects of 2 atypical antipsychotic agents, lurasidone (80 mg/d or 160 mg/d) and quetiapine XR (600 mg/d), on daytime alertness, and to evaluate the effects of daytime sleepiness on treatment outcomes in patients with an acute exacerbation of schizophrenia. METHODS: Patients who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria for schizophrenia were randomized to 6 weeks of double-blind treatment with fixed doses of lurasidone 80 mg/d (n = 125), lurasidone 160 mg/d (n = 121), quetiapine XR 600 mg/d (n = 119), or placebo (n = 121), all dosed once daily in the evening, with food. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). RESULTS: Daytime sleepiness improved in the lurasidone and placebo-treated groups but worsened in the quetiapine XR treatment group when compared to placebo (p = 0.001) and to either dose of lurasidone (both p < 0.01). Sedation associated with quetiapine XR treatment mediated an improvement in agitation [assessed by the Positive and Negative Syndrome Scale-Excitement (PANSS-EC) subscale] and a worsening in functional capacity [assessed by the University of California-San Diego (UCSD) Performance-Based Skills Assessment-Brief Version (UPSA-B) total score]; these mediating relationships were not observed for the lurasidone or placebo treatment groups. CONCLUSION: In this 6-week double-blind study, treatment with lurasidone 80 mg or 160 mg, administered once daily in the evening, was associated with a reduction in daytime sleepiness similar in magnitude to placebo, while quetiapine XR 600 mg/d was associated with a significant increase in daytime sleepiness, compared to both lurasidone dose groups and placebo. Daytime sleepiness was associated with improvement in agitation and worsening in functional capacity for quetiapine XR, but not lurasidone or placebo-treated patients.

Understanding the relationship between baseline BMI and subsequent weight change in antipsychotic trials: effect modification or regression to the mean?

The purpose of this study was to examine whether prior evidence of an inverse relationship between initial body weight and subsequent antipsychotic-induced weight change represents true effect modification or a statistical artifact, regression to the mean (RTM). We conducted a post-hoc analysis after pooling seven randomized, placebo- or active-controlled trials of ziprasidone and other antipsychotic agents. ANCOVA was applied to evaluate treatment-by-baseline body mass index (BMI) range interaction effect on weight change. Regression analysis was applied to estimate the potential bias due to RTM. Statistical interaction tests between baseline BMI ranges and treatment assignments (haloperidol, olanzapine, risperidone, or ziprasidone, versus placebo) were not significant within studies or across studies. Correlation between baseline and follow-up measurements of body weight in placebo-treated subjects was less than perfect (r=0.87, 6-month cohort), leading to RTM. Consistent with predictions based on RTM, the greatest weight change, on average, was observed in subgroups with baseline weights differing the most from the population mean. Our findings suggest that the previously observed correlation between baseline BMI and weight change subsequent to antipsychotic treatment reflects in part RTM, and not effect modification. This class of drugs appears to cause similar weight gain in both high and low baseline BMI groups.

Lurasidone: a new drug in development for schizophrenia.

BACKGROUND: Lurasidone is a novel psychotropic agent in development for the treatment of schizophrenia and bipolar disorder. OBJECTIVES: This paper describes the development of lurasidone, including its receptor binding affinities, pharmacokinetics, CNS activity in rodent models and results of early clinical efficacy and safety studies in humans. METHODS: The available literature on lurasidone was reviewed, including abstracts from medical congresses supplemented by data on file with the sponsor. RESULTS/CONCLUSIONS: Lurasidone has a high affinity for dopamine D(2) and serotonin 5-HT(2A) receptors as well as for receptors implicated in enhancement of cognitive function (e.g., 5-HT(7,) 5-HT(1A), alpha(2c)). Lurasidone has no affinity for muscarinic M(1) and histamine H(1) receptors and minimal affinity for alpha(1) adrenoceptors, dopamine D(1) and D(3) receptors, serotonin 5-HT(2C) receptors and alpha(2A) adrenoceptors. Phase II efficacy data indicate that lurasidone doses from 40 to 120 mg/day are effective in the treatment of schizophrenia, with positive symptom reduction exceeding that for negative symptoms, as seen with other antipsychotics. Preclinical data indicate that lurasidone reverses MK-801 induced learning and memory impairment in rodents, and active comparator data from a Phase Ib study of lurasidone 120 mg/day versus ziprasidone 160 mg/day also found a signal for effects on cognition. Phase II studies suggest that lurasidone has no significant QTc prolongation and a benign metabolic profile.

Long-term safety and efficacy of ziprasidone in subpopulations of patients with bipolar mania.

OBJECTIVE: To evaluate long-term safety and efficacy of ziprasidone. METHOD: Subjects completing a 21-day placebo-controlled trial of ziprasidone in DSM-IV acute bipolar mania (N = 65) were enrolled in a 52-week open-label extension of flexibly dosed ziprasidone 40 to 160 mg/day, administered b.i.d. Three subjects had missing evaluations (N = 62) but still provided demographic data. Subpopulations with manic (N = 43) or mixed (N = 19) episodes, and with (N = 37) or without (N = 25) psychotic symptoms, were identified. Safety evaluations included adverse event monitoring, electrocardiography, and standard laboratory assessments. Efficacy measures included change from initial study baseline in Mania Rating Scale (MRS) and Clinical Global Impressions-Severity of Illness scale (CGI-S) scores, as well as MRS responder rates (> or = 50% reduction from initial study baseline). The study was conducted from March 1998 to September 1999. RESULTS: Almost all adverse events (98%) were mild to moderate in severity. The mean +/- SD reduction in MRS score at week 55 (last observation carried forward [LOCF]) was -23.5 +/- 1.5 (p <.0001) from a baseline of 29.4. CGI-S score decreased by 2.32 +/- 0.25 at week 55 (LOCF, p <.0001) from a baseline of 5.0. MRS and CGI-S reductions were comparable across the subpopulations. The overall MRS responder rate was 86%; subpopulation responder rates were 88% (manic), 79% (mixed), 84% (psychotic), and 88% (nonpsychotic). Long-term improvement within subpopulations was comparable to the overall study population. CONCLUSION: Sustained and comparable improvements in symptoms were seen with up to 55 weeks of ziprasidone treatment for patients initially treated for bipolar mania, regardless of whether the baseline episode was manic or mixed or involved psychotic symptoms.

Remission in schizophrenia: 196-week, double-blind treatment with ziprasidone vs. haloperidol.

To compare the remission rate and its time-course over 196 wk of double-blind treatment with an atypical antipsychotic, ziprasidone (80-160 mg/d given b.i.d., or 80-120 mg/d given q.d.), or a conventional antipsychotic, haloperidol (5-20 mg/d). Outcome assessments included attainment of remission (Andreasen criteria) by longitudinal analysis. Positive and Negative Syndrome Scale (PANSS) scores, Global Assessment of Functioning Scale (GAF) scores, and quality-of-life (QLS) were also assessed in the initial 40-wk study phase (n=599) and the 3-yr extension study (n=186). Discontinuation rates in the initial 40-wk core and follow-up extension studies were comparable between groups: 64% and 65% for the 80-160 mg/d ziprasidone group, 65% and 58% for the 80-120 mg/d ziprasidone group, and 60% and 66% for the 5-20 mg/d haloperidol group, respectively. Mean change scores from baseline to LOCF endpoint (week 40 or early termination) for PANSS negative and GAF (primary efficacy variables) were not statistically significantly different between ziprasidone and haloperidol. During the 3-yr extension study, ziprasidone-treated subjects (80-160 mg/d) were more likely to achieve remission (51%) than haloperidol-treated (40%) subjects (p=0.04), while there was a favourable trend associated with 80-120 mg/d ziprasidone (48%). Compared to the haloperidol group, subjects assigned to the 80-160 mg/d ziprasidone group showed a gradual and persistent improvement in remission (p=0.006) and quality-of-life (p=0.004) in the longitudinal analyses. Significant differences in the trajectory of PANSS total and GAF scores favouring the 80-160 mg/d ziprasidone group were also observed. In this long-term, double-blind study, ziprasidone treatment was more likely to result in remission than haloperidol treatment, and was associated with greater improvement in quality-of-life.

A randomized double-blind comparison of ziprasidone vs. clozapine for cognition in patients with schizophrenia selected for resistance or intolerance to previous treatment.

BACKGROUND: Recent data have suggested few differences in the cognitive effects of antipsychotic medications. However, assessment of such effects can be complex, due to a number of factors. Clozapine has previously shown greater clinical and lesser cognitive benefits than other atypicals. This study compared the cognitive benefits of clozapine and ziprasidone in schizophrenia patients (n=130) with a history of either failure to respond to or intolerance of previous adequate antipsychotic treatments. METHODS: Patients were randomized (double-blind) to either clozapine or ziprasidone in a single country (Italy), multi-site trial. The cognitive assessments examined episodic memory (RAVLT), executive functioning (Stroop test), and processing speed (Trail-making test (TMT) Parts A and B). RESULTS: Analyses found statistically significant within-group improvements for ziprasidone in learning and delayed recall on the RAVLT and on TMT Parts A and B. Clozapine-treated patients improved on the RAVLT, but not on the TMT. A composite cognitive score improved from baseline in both groups, but the improvements were significantly larger in the ziprasidone group (p=.029). IMPLICATIONS: These results indicated that cognitive functioning improved following treatment with ziprasidone in patients with a history of either treatment resistance or intolerance, and that the effects are comparable or greater than those observed with clozapine. One interpretation of these findings is that clozapine treatment interferes with the performance benefits associated with practice.

The factor structure of clinical symptoms in mixed and manic episodes prior to and after antipsychotic treatment.

BACKGROUND: While the factor structure of clinical symptoms in schizophrenia has been examined and provided crucial information about the illness, there is much less information available in bipolar disorder. This study examined the structure of symptoms of bipolar disorder at an unmedicated baseline assessment and after double-blind treatment with ziprasidone, haloperidol, or placebo. We hypothesized, consistent with recent studies of schizophrenia, that the factor structure after treatment would be similar to the structure of untreated symptoms at study baseline. METHODS: Hospitalized patients with manic (n = 363) or mixed (n = 71) bipolar episodes were rated with the Hamilton Depression Rating Scale (HAM-D) and the Mania Rating Scale [(MRS); derived from the Schedule for Affective Disorders and Schizophrenia - Change Bipolar Scale]. After 21 days of double-blind treatment, all patients were again rated with the MRS and HAM-D. RESULTS: Exploratory orthogonal factor analysis (varimax rotation) including both HAM-D total scores and the MRS items found different five-factor solutions for mixed and manic patients at the unmedicated baseline assessment. Confirmatory modeling indicated that these models, with some modifications, fit the data well. At the endpoint, however, a single-factor solution was found for mixed and manic groups. IMPLICATIONS: Symptomatology in bipolar disorder is multifactorial in an acute and unmedicated state, with slightly different factor structures for mixed and manic episodes. Following treatment, a single severity dimension is detected. These results suggest that symptom dimensions in mania may be different from those seen in schizophrenia, where different elements of symptoms have been proven to have different functional correlates and treatment response.

Long-term changes in weight and plasma lipids during maintenance treatment with ziprasidone.

To measure the long-term changes in weight and plasma lipids after switching antipsychotic treatment to ziprasidone, three 52-week, open-label extension studies of ziprasidone in outpatients (N=185) with schizophrenia or schizoaffective disorder successfully completing one of three, 6-week switch studies were carried out. Pre-switch treatment consisted of risperidone (n=43), olanzapine (n=71), or conventional antipsychotic agents (n=71). The maximum length of exposure to ziprasidone was 58 weeks. Nonfasting total cholesterol and triglyceride levels were obtained at baseline and at weeks 6, 19, 32, 45, and 58. Weight was measured at baseline and during each follow-up visit; height was recorded at baseline for the purpose of body mass index (BMI) calculation. Efficacy measures included the Positive and Negative Syndrome Scale and Clinical Global Impression-Severity scale which were obtained at baseline and major follow-up points. Clinically significant sustained improvements in weight, BMI, total cholesterol, and triglyceride levels were observed among patients switched to ziprasidone from risperidone or olanzapine. Switching from conventional antipsychotics was not associated with significant changes in weight and lipid parameters. Mean reductions in weight from baseline to study endpoint were 9.8 kg (p<0.001) and 6.9 kg (p<0.005) for patients previously treated with olanzapine and risperidone, respectively. These findings demonstrate that switching from risperidone or olanzapine to ziprasidone is associated with sustained, clinically significant improvements in weight and plasma lipids.

Risk of discontinuation of atypical antipsychotic agents in the treatment of schizophrenia.

OBJECTIVES: To compare discontinuation rates of atypical antipsychotic agents in patients with schizophrenia. METHOD: Adult Maryland Medicaid patients with schizophrenia were categorized based on initial atypical antipsychotic drug received: aripiprazole (n=446); olanzapine (n=1705); quetiapine (n=1467); risperidone (n=1580); and ziprasidone (n=700). Discontinuation was measured using refill patterns, allowing 14-day gaps between refill dates. Using olanzapine as the reference drug, the hazard of discontinuation within the first year of follow-up was compared across atypicals using Cox proportional hazard models adjusted for demographic and clinical covariates. Sensitivity analysis tested the robustness of results by using different definitions of the index date. RESULTS: At one-year follow-up, most patients discontinued their antipsychotic medication (90.4% adjusted mean discontinuation). The hazard ratio (HR) for discontinuing therapy in patients starting treatment on aripiprazole, risperidone, or ziprasidone was not significantly different from olanzapine [HR 1.047, 0.973 and 0.990, respectively]. Quetiapine was associated with significantly higher hazard of discontinuation [HR 1.130] than olanzapine. Covariates associated with significantly lower discontinuation were being male [HR 0.899], older age [HR 0.997] and being on concurrent medication when initiating therapy [HR 0.225]; having a previous hospitalization was associated with significantly higher discontinuation hazard [HR 1.276]. Results were robust in the sensitivity analysis. CONCLUSIONS: Discontinuation rates were high at one-year follow-up and did not differ significantly for patients on aripiprazole, olanzapine, risperidone, or ziprasidone. The higher hazard of discontinuation associated with quetiapine when compared to olanzapine is consistent with that observed in Phase I of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).

Ziprasidone in treatment-resistant schizophrenia: a 52-week, open-label continuation study.

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of long-term ziprasidone therapy in treatment-resistant schizophrenia. METHOD: This prospective, 1-year, open-label study of ziprasidone (40-160 mg/day) was conducted in subjects who had participated in a previous randomized 12-week comparison of ziprasi-done and chlorpromazine in treatment-resistant schizophrenia (DSM-III-R criteria). The clinical response of 62 subjects was evaluated (32 subjects had been on ziprasidone treatment and 30 had been on chlorpromazine treatment prior to enrollment in the continuation study). Assessments included the Positive and Negative Syndrome Scale total and subscale scores, movement disorder scales, body weight, and laboratory measures. This study was conducted from May 2000 to April 2002. RESULTS: Thirty-three subjects (53%) completed 1 year of open-label ziprasidone therapy. Ziprasidone maintained clinical improvement (no significant symptom exacerbation) in 30 of 41 subjects (73%) who responded to the initial 12-week double-blind treatment with either ziprasidone or chlorpromazine. Ziprasidone did not increase body weight and was associated with a favorable metabolic profile during the continuation study period. There were no significant changes in standard movement disorder measures from the core study baseline during long-term ziprasidone treatment. CONCLUSION: Ziprasidone was effective and well tolerated in the long-term therapy of patients with treatment-resistant schizophrenia.

Effect of initial ziprasidone dose on length of therapy in schizophrenia.

OBJECTIVE: To examine the effects of initial ziprasidone dose on discontinuation rates, using retrospective integrated medical and pharmacy claims data. METHODS: Patients > or = 18 years with a diagnosis of schizophrenia or schizoaffective disorder and a ziprasidone claim between March 2001 and February 2003 who were continuously enrolled for at least six months before and three months after initiation of ziprasidone were included. They were stratified by initial daily dose (> or = 40 and < 80 mg [low] vs. > or = 80 and < 120 mg [medium] vs. 120-160 mg [high]). The six-month risk of discontinuation was examined using Cox proportional hazards models controlling for gender, psychiatric comorbidities, and pre-ziprasidone utilization of antipsychotics (atypical, conventional, none). RESULTS: The mean age of the sample (n=1058) was 38 years; 42% were male. The six-month risk of discontinuation was significantly lower in patients in the high-dose group as compared to the low-dose group (HR=0.737 for high-dose vs. low-dose, 95% CI=0.581, 0.935; P=0.012) and trended towards significance when comparing high-dose and medium-dose groups (HR=0.857 for high-dose vs. medium-dose, 95% CI=0.694, 1.059; P=0.153). CONCLUSIONS: Patients initiating ziprasidone therapy with an initial dose of at least 120 mg/day had better medication adherence compared to those initiating at lower doses. These findings confirm results seen in clinical trials suggesting improved efficacy and tolerability at higher ziprasidone doses.

Change in framingham risk score in patients with schizophrenia: a post hoc analysis of a randomized, double-blind, 6-week trial of ziprasidone and olanzapine.

OBJECTIVE: To examine the change in Framingham risk score (FRS) arising from short-term treatment with ziprasidone or olanzapine. METHOD: Hospitalized adults with a primary DSM-IV diagnosis of schizophrenia or schizo-affective disorder were randomly assigned to 6 weeks of double-blind treatment with ziprasidone or olanzapine from November 21, 1998 to September 28, 2000. Data on fasting lipid levels were collected at screening and endpoint, and blood pressure was measured at screening and baseline and weekly until week 6 of treatment (or last visit). FRS for patients aged ≥30 years was calculated using an algorithm derived from the Framingham Heart Study. Baseline-to-endpoint least-squares mean changes in age-adjusted FRS by gender were compared using analysis of covariance (baseline adjusted). RESULTS: Men who received olanzapine demonstrated a mean increase in their total cholesterol levels (+18.5 mg/dL; N = 53) and low-density lipoprotein cholesterol levels (+13.0 mg/dL; N = 45), whereas men who received ziprasidone demonstrated a mean decrease in their total cholesterol levels (-8.5 mg/dL; N = 44) and low-density lipoprotein cholesterol levels (-7.2 mg/dL; N = 40) (p = .0006 and p = .004, respectively). Additionally, men who received olanzapine showed an increase in baseline FRS (+7.69%; N = 53), whereas men who received ziprasidone showed a decrease in baseline FRS (-11.06%; N = 42) (p = .09). In women, treatment differences in FSR numerically favored ziprasidone but were not statistically significant. Neither treatment had a significant effect on blood pressure. CONCLUSION: In short-term treatment, olanza-pine was associated with a significant worsening of lipid profile compared with ziprasidone, with a consequent increase in FRS versus ziprasidone. These findings, coupled with the significant weight gain in patients treated with olanzapine versus ziprasidone, warrant investigation in longer-term trials.

Impact of atypical antipsychotics on outcomes of care in schizophrenia.

OBJECTIVE: To compare persistence, compliance, and psychiatric treatment costs in patients who were initiated on atypical antipsychotics. METHODS: Medical and pharmacy claims data were used to compare persistence (days of therapy between first and last prescriptions, allowing therapy gaps < 90 days); compliance (ratio of days of medication supplied to total days on therapy); treatment costs in adults with schizophrenia having claims for atypical antipsychotics from March 2001 to August 2003; and enrollment for > or =6 months before and > or =12 months after therapy initiation. Psychiatric treatment costs for 1 year were examined before and after therapy initiation. Differences in costs were tested by univariate analyses. RESULTS: Persistence was approximately 30 days longer for patients receiving ziprasidone (n = 217; 228 days) than risperidone (n = 831; 193 days) or olanzapine (n = 762; 201 days). Compliance was significantly (P<.05) higher among patients receiving ziprasidone (87%) compared with other treatments (78%-80%). Ziprasidone patients had significantly larger decreases (- USD 6866) in mean annual psychiatric-related costs following therapy initiation than those on risperidone (- USD 3353; P = .0116) or olanzapine (- USD 4764; P = .0021). The primary driver of cost savings was reduced hospitalization after treatment initiation. CONCLUSION: Patients initiated on ziprasidone had longer persistence, better compliance, and greater decreases in psychiatric-related costs than those initiated on other atypicals.

The Atypical Antipsychotic Therapy and Metabolic Issues National Survey: practice patterns and knowledge of psychiatrists.

A nationwide survey in 2003 of 300 randomly selected psychiatrists who routinely treat schizophrenia with atypical antipsychotic therapy was conducted to ascertain practice patterns and attitudes regarding metabolic disturbances during atypical antipsychotic therapy with an emphasis on how these perceptions impact therapeutic decision making. Psychiatrists generally believe that some atypical antipsychotic drugs are associated with metabolic disturbances and that atypical antipsychotics differ in their risk for metabolic disturbances. A majority of respondents (82%) believed that patients with schizophrenia-even those not receiving atypical antipsychotic therapy-are at greater risk for metabolic abnormalities than the general population. A majority of respondents recognized weight gain and diabetes mellitus (59% and 51%, respectively) as potential metabolic complications of atypical antipsychotic therapy, while only some recognized dyslipidemia and certain acute metabolic decompensations like diabetic ketoacidosis (22% and 2%, respectively). Large minorities of respondents (48% and 43%) indicated a willingness to risk weight gain and/or diabetes for the benefits of atypical antipsychotics, possibly because metabolic issues were regarded as long-term issues. However, large majorities also stated that they considered metabolic issues when selecting atypical antipsychotic therapy for some or all of their patients (90%), and that emergence of metabolic dysfunction prompted them to change atypical antipsychotic treatment regimens (85%). Additional efforts at continuing education and communication regarding metabolic outcomes associated with atypical antipsychotic therapy, as well as critical reviews in this area, may help clarify atypical antipsychotic treatment risks and benefits. The results from the survey indicate that psychiatrists are aware of and concerned about metabolic risks and how they differ across the atypical antipsychotic class. The impact of additional data and educational efforts in this area, such as a recently published consensus statement from the American Diabetes Association and other organizations, remains to be assessed.