Rallying All Resources: A Multidisciplinary Innovation to Plan for the Projected COVID-19 Inpatient Surge.

BACKGROUND: The COVID-19 pandemic resulted in the need for hospitals to plan for a potential "surge" of COVID-19 patients. PROBLEM: Prior to the onset of the COVID-19 pandemic, our hospital adult acute care capacity ranged 90% to 100%, and a potential hospital surge was projected for Oregon that would exceed existing capacity. APPROACH: A multidisciplinary team with stakeholders from nursing leadership, nursing units, nurse-led case management, and physicians from hospital medicine was convened to explore the conversion of an ambulatory surgical center to overflow patient acute care capacity. OUTCOMES: A protocol was rapidly created and implemented, ultimately transferring 12 patients to an ambulatory surgery unit. CONCLUSIONS: This project highlighted the ability for stakeholders and innovators to work together in an interprofessional, multidisciplinary way to rapidly create an overflow unit. While this innovation was designed to address COVID-19, the lessons learned can be applied to any other emerging infectious disease or acute care capacity crisis.

Management of Heparin-Resistant Patients with Benefits? Maximizing Biocompatibility in Cardiopulmonary Bypass: Combining ATryn® Recombinant Antithrombin III and Carmeda® Heparin-Bonded Perfusion Circuits: A Case Series.

As many as 25% of our cardiopulmonary bypass (CPB) patients have a diminished heparin response and fail to reach a therapeutic activated clotting time (ACT). We treat a majority of these patients with antithrombin III (ATryn®, recombinant antithrombin III [rhAT], rEVO Biologics). Our current CPB circuit uses Medtronic Carmeda® coating. We observed less post-operative bleeding in a number of patients treated with rhAT. We theorized that adding rhAT would allow patients with diminished heparin response to safely achieve a therapeutic ACT. On the basis of our postoperative bleeding observations, we wondered if using rhAT with a heparin-bonded CPB circuit enhanced its biocompatibility and perhaps improved patient outcomes. Data were collected on 15 patients undergoing CPB who received antithrombin III (AT) replacement therapy for diminished heparin response. We used patient data from 2012, prior to rhAT usage for comparison. All patients achieved therapeutic ACT after rhAT administration. We also observed decreased postoperative atrial fibrillation rates, improved platelet preservation, decreased intensive care unit and ventilator times in patients receiving rhAT compared to rates commonly observed at our center. Heparin-resistant patients can be treated with rhAT to achieve therapeutic ACTs. Our observations suggest that the use of rhAT in conjunction with Carmeda® heparin-bonded circuits may also have a positive benefit on some of the well-established negative clinical consequences of CPB and improve patient outcomes.

Randomized Trial of the Effect of Four Second-Generation Antipsychotics and One First-Generation Antipsychotic on Cigarette Smoking, Alcohol, and Drug Use in Chronic Schizophrenia.

No large-scale randomized trial has compared the effect of different second-generation antipsychotic drugs and any first-generation drug on alcohol, drug and nicotine use in patients with schizophrenia. The Clinical Antipsychotic Trial of Intervention Effectiveness study randomly assigned 1432 patients formally diagnosed with schizophrenia to four second-generation antipsychotic drugs (olanzapine, risperidone quetiapine, and ziprasidone) and one first-generation antipsychotic (perphenazine) and followed them for up to 18 months. Secondary outcome data documented cigarettes smoked in the past week and alcohol and drug use severity ratings. At baseline, 61% of patients smoked, 35% used alcohol, and 23% used illicit drugs. Although there were significant effects of time showing reduction in substance use over the 18 months (all p < 0.0001), this study found no evidence that any antipsychotic was robustly superior to any other in a secondary analysis of data on substance use outcomes from a large 18-month randomized schizophrenia trial.

Dopamine D2 receptor occupancy and cognition in schizophrenia: analysis of the CATIE data.

INTRODUCTION: Antipsychotic drugs exert antipsychotic effects by blocking dopamine D2 receptors in the treatment of schizophrenia. However, effects of D2 receptor blockade on neurocognitive function still remain to be elucidated. The objective of this analysis was to evaluate impacts of estimated dopamine D2 receptor occupancy with antipsychotic drugs on several domains of neurocognitive function in patients with schizophrenia in the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial. METHODS: The dataset from the CATIE trial was used in the present analysis. Data were extracted from 410 subjects who were treated with risperidone, olanzapine, or ziprasidone, received assessments for neurocognitive functions (verbal memory, vigilance, processing speed, reasoning, and working memory) and psychopathology, and provided plasma samples for the measurement of plasma antipsychotic concentrations. D2 receptor occupancy levels on the day of neurocognitive assessment were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our recently developed model. A multivariate general linear model was used to examine effects of clinical and demographic characteristics, including estimated D2 occupancy levels, on neurocognitive functions. RESULTS: D2 occupancy levels showed significant associations with the vigilance and the summary scores. Neurocognitive functions, including vigilance, were especially impaired in subjects who showed D2 receptor occupancy level of >77%. DISCUSSION: These findings suggest a nonlinear relationship between prescribed antipsychotic doses and overall neurocognitive function and vigilance. This study shows that D2 occupancy above approximately 80% not only increases the risk for extrapyramidal side effects as consistently reported in the literature but also increases the risk for cognitive impairment.

Factors associated with initiation on clozapine and on other antipsychotics among Medicaid enrollees.

OBJECTIVE: Demographic and clinical factors associated with starting clozapine and other antipsychotics were examined. METHODS: New York State Medicaid claims from 2008 to 2009 identified individuals with a schizophrenia spectrum disorder, continuous Medicaid eligibility during the study, and at least one clinic service and antipsychotic fill. The sample included individuals who initiated an antipsychotic without any fills for the same medication in the prior 90 days (N=7,035). RESULTS: Only 144 patients (2%) started on clozapine. They were more likely to be younger, white males who had received services in a state-operated facility, with more hospital admissions and higher total psychiatric costs. African Americans and Hispanics were less likely than whites to start on clozapine. Individuals with substance use disorders were less likely than those without them to start on clozapine. CONCLUSIONS: Clozapine was rarely prescribed, and problematic disparities were found. Quality improvement efforts are needed to ensure that patients are offered this effective treatment when appropriate.

Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial.

This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.

Genomewide association study of movement-related adverse antipsychotic effects.

BACKGROUND: Understanding individual differences in the development of extrapyramidal side effects (EPS) as a response to antipsychotic therapy is essential to individualize treatment. METHODS: We performed genomewide association studies to search for genetic susceptibility to EPS. Our sample consisted of 738 schizophrenia patients, genotyped for 492K single nucleotide polymorphisms (SNPs). We studied three quantitative measures of antipsychotic adverse drug reactions-the Simpson-Angus Scale (SAS) for Parkinsonism, the Barnes Akathisia Rating Scale, and the Abnormal Involuntary Movement Scale (AIMS)-as well as a clinical diagnosis of probable tardive dyskinesia. RESULTS: Two SNPs for SAS, rs17022444 and rs2126709 with p = 1.2 x 10(-10) and p = 3.8 x 10(-7), respectively, and one for AIMS, rs7669317 with p = 7.7 x 10(-8), reached genomewide significance (Q value < .1). rs17022444 and rs7669317 were located in intergenic regions and rs2126709 was located in ZNF202 on 11q24. Fourteen additional signals were potentially interesting (Q value < .5). The ZNF202 is a transcriptional repressor controlling, among other genes, PLP1, which is the major protein in myelin. Mutations in PLP1 cause Pelizaeus-Merzbacher disease, which has Parkinsonism as an occurring symptom. Altered mRNA expression of PLP1 is associated with schizophrenia. CONCLUSIONS: Although our findings require replication and validation, this study demonstrates the potential of genomewide association studies to discover genes and pathways that mediate adverse effects of antipsychotics.

Can a nonequivalent choice of dosing regimen bias the results of flexible dose double blind trials? The CATIE schizophrenia trial.

BACKGROUND: One of the major challenges in the design of double-blind flexible-dosing clinical trials comparing active drugs is the selection of dosing regimens that are equivalent across drugs. This study uses data from the CATIE schizophrenia trial to evaluate the hypothesis that drugs that were dosed somewhat higher in the trial than in typical practice would show greater efficacy and more side effects, especially at high capsule levels, than drugs that were dosed at lower relative strengths. METHODS: CATIE was a large (N=1460) randomized trial comparing 5 antipsychotics in patients with chronic schizophrenia. The blind was maintained in CATIE by prescribing identical-looking capsules of each medication. Dosing was flexible, such that PIs could prescribe from one to four capsules per day, and could modify the dose based on a patient's symptoms and side effects. Capsule strengths for olanzapine (7.5 mg) and quetiapine (200 mg) were relatively higher than for risperidone (1.5 mg), perphenazine (8 mg) or ziprasidone (40 mg). Proportional hazards models of time to all cause discontinuation and mixed regression models for continuous measures of symptoms, quality of life and side effects were used to test for interactions between randomly assigned drug and number of capsules prescribed per visit. We hypothesized that if a dosing bias was present, the flex-dosing design would result in a significant interaction such that drugs with higher relative dosing per capsule would be more effective and have more side effects than drugs with lower relative dosing and that this effect would be greatest at the largest prescribed dosing regimen (4 capsules). RESULTS: There were no significant interactions between drug assignment and number of capsules in the proportional hazards analyses of time to all cause discontinuation (p=.77, excluding ziprasidone and .74 in the ziprasidone cohort) or in the mixed model analysis of PANSS symptoms (p=.49), quality of life (p=.45); or measures of tardive dyskinesia (AIMS, p=.47). However a significant interaction was observed on the Barnes akathisia scale (p=.0005), on the Simpson Angus EPS scale (p=.10) and on the analysis of weight (p=0.014). Paired comparisons did not show the hypothesized pattern of relationships for akathisia or EPS, but such a pattern was suggested for olanzapine in the analysis of weight although it emerged at 2, 3 and 4 capsules indicating a general drug effect rather than a relative dosing difference. CONCLUSION: Dosing biases do not seem to have affected the results of the CATIE trial.

Does switching to a new antipsychotic improve outcomes? Data from the CATIE Trial.

PURPOSE: Previous analysis of data from CATIE showed that patients randomly assigned to switch to a new medication were more likely to discontinue study drug than those who stayed on the medication they had been taking prior to randomization. This study addresses additional outcomes measures evaluating symptoms, neurocognition, quality of life, neurological side effects, weight, and health costs. First, considering patients randomized to olanzapine or risperidone, outcomes among patients who had been on the drug to which they were randomized prior to CATIE (N=129 "stayers") were compared to outcomes of those who switched to either of these two drugs (N=269 "switchers"). A second set of analyses considered patients on baseline monotherapy with olanzapine (N=297); risperidone (N=252) or quetiapine (n=87) and compared those randomly assigned to stay on each of these medications with those assigned to switch to any of the other five phase 1 medications in CATIE. In mixed models of each outcome the independent variable of primary interest represented stay vs. switch, with multivariate adjustment for potential confounding factors. RESULTS: With one exception, there were no significant differences between stayers and switchers on any outcome measure in either set of analyses. The exception was that, in the second set of analyses, patients who stayed on olanzapine showed greater weight gain than those who switched from olanzapine to other drugs. CONCLUSION: Switching to a new medication yielded no advantage over staying on the previous medication. Staying on olanzapine was associated with greater weight gain.

Cross-sectional and longitudinal relationships between insight and attitudes toward medication and clinical outcomes in chronic schizophrenia.

BACKGROUND: We evaluated the cross-sectional and longitudinal association of measures of both insight and attitudes toward medication to outcomes that included psychopathology and community functioning. METHODS: Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) was a large 18-month follow-up study pharmacotherapy of people with schizophrenia. Insight was measured using the Insight and Treatment Attitudes Questionnaire and attitudes toward medication by the Drug Attitude Inventory. Widely known scales were used to assess symptoms of schizophrenia and depression and community functioning. Medication adherence was globally assessed by the treating psychiatrist using several sources of information. Bivariate correlations and mixed model regression analyses were used to test the relationship of insight and medication attitudes to outcomes at baseline and during the follow-up period. Regression models were used to evaluate the relationship between change in insight and medication attitudes and changes outcomes. RESULTS: There was a significant relationship at baseline between insight and drug attitudes and symptoms of schizophrenia and depression, as well as with community functioning. Higher levels of insight at baseline were significantly associated with lower levels of schizophrenia symptoms at follow-up while more positive medication attitudes were significantly associated with both lower symptom levels and better community functioning. Change in insight scores over time was associated with declining schizophrenia symptoms but increasing levels of depression. Change toward more positive medication attitudes was associated, independently of changes in insight, with significant decreases in psychopathology, improvement in community functioning, and greater medication compliance. CONCLUSION: Greater patient understanding of their illness and more positive attitudes toward medication may improve outcomes. Educational interventions that affect these attitudes may be an important part of psychosocial rehabilitation and/or recovery-oriented services.

Relationship of cognition and psychopathology to functional impairment in schizophrenia.

OBJECTIVE: This study evaluated the association of neurocognition and symptoms with measures of social and occupational functioning in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). METHOD: CATIE was an 18-month study of individuals with schizophrenia. Symptoms of 1,386 patients were measured with the positive syndrome scale of the Positive and Negative Syndrome Scale (PANSS) and a PANSS negative symptom scale that eliminated items that most overlap with measures of community functioning or neurocognition. The Heinrichs-Carpenter Quality of Life Scale, which a rater completes on the basis of the patient's self-report, and recent employment were used to assess community functioning. Hierarchical regression analyses and mixed models tested the association of neurocognition and symptoms with social/occupational functioning as well as changes in these measures during treatment. RESULTS: Both symptoms and neurocognition were associated with quality of life in bivariate correlation analyses. Symptoms contributed more to the incremental explained variance in quality of life than did neurocognitive functioning, but both kinds of measures were significantly related to quality of life. In an analysis including only the positive syndrome scale, the increased explained variance in quality of life was about equal to that associated with neurocognition. Neurocognition and both symptom measures were independently associated with quality of life in the cross-sectional mixed-model analysis. Changes in neurocognition and both symptom measures during treatment were also significantly associated with change in the quality of life. CONCLUSIONS: Both psychotic symptoms and neurocognitive deficits appear to contribute independently to decreased quality of life in schizophrenia.

Science and recovery in schizophrenia.

Mental health advocates and policy makers are increasingly attuned to the importance of the recovery concept, and psychiatrists and neuroscientists increasingly emphasize the medical model and neurobiological mechanisms in relation to schizophrenia. Studies have shown that people with schizophrenia are tremendously heterogeneous in each domain of recovery, and the various domains of recovery are themselves relatively independent from one another. Studies have also shown that current interventions are effective for specific dimensions of the illness and functions, are usually ameliorative rather than curative, and are effective only for a proportion of patients. Hence, the authors suggest defining recovery in terms of improvements in specific domains rather than globally -- for example, "recovery of cognitive functioning" or "recovery of vocational functioning" -- to signify improvements in specific areas. This definition realistically emphasizes states of relative and partial recovery that patients can achieve in response to treatment. The emphasis on a range of improvements in specific areas should allow clinicians to communicate more clearly regarding the current findings and goals of treatment. The article also examines current research on various aspects of recovery, including the effects of treatment on pathophysiology, symptoms, cognitive impairments, quality of life, and self-agency. An operational definition of recovery allows for bridging hope and recovery with important advances in the science of the brain. Future clinical and neuroscience research and service development should emphasize measures of recovery as outcomes for people with schizophrenia.

Use of Antipsychotics Pre- and Post-Dissemination of CATIE Data.

We investigated the share of branded and generic antipsychotics before and after the publication of the CATIE results in September, 2005. According to our data, the publication of the CATIE results has had very little impact on new patient starts. To determine the impact of CATIE on use of olanzapine (Zyprexa((R))) subsequent to first line therapy, we also examined product share for switch/add patients. We found that since the publication of the CATIE results, the use of olanzapine has stabilized, following a decline subsequent to first line therapy, and may potentially be growing very slowly. An expert commentary is provided on the data.

Barriers to employment for people with schizophrenia.

OBJECTIVE: There is growing interest in identifying and surmounting barriers to employment for people with schizophrenia. The authors examined factors associated with participation in competitive employment or other vocational activities in a large group of patients with schizophrenia who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, a multisite clinical trial comparing the effects of first- and second-generation antipsychotics. METHOD: Baseline data on more than 1,400 patients with a diagnosis of schizophrenia were collected before their entry into the CATIE study. Multinomial logistic regression was used to examine the relationship between participation in either competitive employment or other vocational activities and sociodemographic characteristics, schizophrenia symptoms, neurocognitive functioning, intrapsychic functioning, availability of psychosocial rehabilitation services, and local unemployment rates. RESULTS: Altogether, 14.5% of the patients reported participating in competitive employment in the month before the baseline assessment, 12.6% reported other (noncompetitive) employment activity, and 72.9% reported no employment activity. Participation in either competitive or noncompetitive employment was associated with having less severe symptoms, better neurocognitive functioning, and higher scores on a measure of intrapsychic functioning that encompassed motivation, empathy, and other psychological characteristics. Competitive employment, in contrast to other employment or no employment, was negatively associated with receipt of disability payments as well as with being black. Greater access to rehabilitation services was associated with greater participation in both competitive and noncompetitive employment. CONCLUSIONS: Overall employment of persons with schizophrenia seems to be impeded by clinical problems, including symptoms of schizophrenia and poorer neurocognitive and intrapsychic functioning. However, participation in competitive employment may be specifically impeded by the potentially adverse incentives of disability payments and by race and may be promoted by the availability of rehabilitation services.

Measuring outcome priorities and preferences in people with schizophrenia.

BACKGROUND: Measures have not taken account of the relative importance patients place on various outcomes. AIMS: To construct and evaluate a multidimensional, preference-weighted mental health index. METHOD: Each of over 1200 patients identified the relative importance of improvement in six domains: social life, energy, work, symptoms, confusion and side-effects. A mental health index was created in which measures of well-being in these six domains were weighted for their personal importance. RESULTS: The strongest preference was placed on reducing confusion and the least on reducing side-effects. There was no significant difference between the unweighted and preference-weighted mental health status measures and they had similar correlations with global health status measures. Patients with greater preference for functional activities such as work had less preference for medical model goals such as reducing symptoms and had less symptoms. CONCLUSIONS: A preference-weighted mental health index demonstrated no advantage over an unweighted index.

Decision-making capacity for research participation among individuals in the CATIE schizophrenia trial.

OBJECTIVE: Uncertainty regarding the degree to which persons with schizophrenia may lack decision-making capacity, and what the predictors of capacity may be led us to examine the relationship between psychopathology, neurocognitive functioning, and decision-making capacity in a large sample of persons with schizophrenia at entry into a clinical trial. METHOD: In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial, a clinical trial sponsored by the National Institute of Mental Health designed to compare the effectiveness of antipsychotic drugs, subjects were administered the MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) and had to demonstrate adequate decision-making capacity before randomization. The MacCAT-CR, the Positive and Negative Syndrome Scale (PANSS), and an extensive neurocognitive battery were completed for 1447 study participants. RESULTS: The neurocognitive composite score and all 5 neurocognitive subscores (verbal memory, vigilance, processing speed, reasoning, and working memory) were positive correlates of the MacCAT-CR understanding, appreciation, and reasoning scales at baseline. Higher levels of negative symptoms, but not positive symptoms, were inversely correlated with these three MacCAT-CR scales. Linear regression models of all three MacCAT-CR scales identified working memory as a predictor; negative symptoms made a small contribution to the understanding and appreciation scores. CONCLUSIONS: Negative symptoms and aspects of neurocognitive functioning were correlated with decision-making capacity in this large sample of moderately ill subjects with schizophrenia. In multiple regression models predicting performance on the MacCAT-CR scales, working memory was the only consistent predictor of the components of decision-making capacity. Individuals with schizophrenia who have prominent cognitive dysfunction, especially memory impairment, may warrant particular attention when participating in research.

Physical health monitoring of patients with schizophrenia.

OBJECTIVE: Schizophrenia is associated with several chronic physical illnesses and a shorter life expectancy, compared with life expectancy in the general population. One approach to improving the health of patients with schizophrenia is to improve the monitoring of physical health that occurs in psychiatric settings. The authors discuss a consensus panel's recommendations for improving the physical health monitoring of patients with schizophrenia who are treated in outpatient settings. METHOD: A consensus meeting including psychiatric and other medical experts assembled on October 17-18, 2002, to evaluate the existing literature and to develop recommendations for physical health monitoring of patients with schizophrenia. Conference participants reviewed the literature in the following areas: 1) weight gain and obesity; 2) diabetes; 3) hyperlipidemia; 4) prolongation of the QT interval on the ECG; 5) prolactin elevation and related sexual side effects; 6) extrapyramidal side effects, akathisia, and tardive dyskinesia; 7) cataracts; and 8) myocarditis. Experts for each topic area formulated monitoring recommendations that were discussed by all of the participants until a consensus was reached. RESULTS: Consensus recommendations included regular monitoring of body mass index, plasma glucose level, lipid profiles, and signs of prolactin elevation or sexual dysfunction. Information from monitoring should guide the selection of antipsychotic agents. Specific recommendations were made for cardiac monitoring of patients who receive medications associated with QT interval prolongation, including thioridazine, mesoridazine, and ziprasidone, and for monitoring for signs of myocarditis in patients treated with clozapine. Patients who receive both first- and second-generation antipsychotic medications should be examined for extrapyramidal symptoms and tardive dyskinesia. Patients with schizophrenia should receive regular visual examinations. CONCLUSIONS: The conference participants recommended that mental health care providers perform physical health monitoring that typically occurs in primary care settings for their patients who do not receive physical health monitoring in those settings. This change in usual practice is recommended on the basis of the conference participants' belief that this additional monitoring will result in the earlier detection of common, serious risk factors that could, without detection and intervention, contribute to impaired health of patients with schizophrenia.

The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2003 update.

BACKGROUND: The Texas Medication Algorithm Project (TMAP) has been a public-academic collaboration in which guidelines for medication treatment of schizophrenia, bipolar disorder, and major depressive disorder were used in selected public outpatient clinics in Texas. Subsequently, these algorithms were implemented throughout Texas and are being used in other states. Guidelines require updating when significant new evidence emerges; the antipsychotic algorithm for schizophrenia was last updated in 1999. This article reports the recommendations developed in 2002 and 2003 by a group of experts, clinicians, and administrators. METHOD: A conference in January 2002 began the update process. Before the conference, experts in the pharmacologic treatment of schizophrenia, clinicians, and administrators reviewed literature topics and prepared presentations. Topics included ziprasidone's inclusion in the algorithm, the number of antipsychotics tried before clozapine, and the role of first generation antipsychotics. Data were rated according to Agency for Healthcare Research and Quality criteria. After discussing the presentations, conference attendees arrived at consensus recommendations. Consideration of aripiprazole's inclusion was subsequently handled by electronic communications. RESULTS: The antipsychotic algorithm for schizophrenia was updated to include ziprasidone and aripiprazole among the first-line agents. Relative to the prior algorithm, the number of stages before clozapine was reduced. First generation antipsychotics were included but not as first-line choices. For patients refusing or not responding to clozapine and clozapine augmentation, preference was given to trying monotherapy with another antipsychotic before resorting to antipsychotic combinations. CONCLUSION: Consensus on algorithm revisions was achieved, but only further well-controlled research will answer many key questions about sequence and type of medication treatments of schizophrenia.