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In its early uptake and sweeping application of gender mainstreaming, the European Union (EU) sits in the vanguard. However, bringing a gender perspective to bear on policy has proven a stubborn challenge. Drawing on Bacchi's "What's the Problem Represented to Be?" approach and her conceptualization of policies as gendering practices, I critically interrogate how men have been implicated in the problem of gender inequality via policy discourse in the EU. I focus on violence against women/gender-based violence and gender inequalities in education. Analysis of these two issues serves to highlight some of the interpretive limits to the problem of gender inequality in the EU and likely beyond. The discursive elusiveness of men works to keep much of the workings of gender power obscured. Such discounting of "the man question" signals a significant misstep that undercuts gender mainstreaming's transformative prospects.
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INTRODUCTION: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific "ACKR1-null" ("Duffy null") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent. METHODS: We completed a multisite, 6-month, prospective, open-label clinical trial of clozapine treatment in people of African descent with schizophrenia spectrum disorders for whom clozapine was clinically indicated, with or without the ACKR1-null genotype. We examined clozapine safety and weekly ANC during clozapine treatment and evaluated ANC variability by ACKR1-null genotype, sex, study site, and clozapine dosing using repeated measures analysis of covariance. Genotype was assayed using TaqMan® technology. RESULTS: We enrolled 274 participants, of whom 227 (82.8 %) completed 6 months of clozapine treatment. There was one case of severe neutropenia (<500 cells/mm3) (0.36 %) over 1467.6 person-months of clozapine exposure. This participant recovered without sequelae after discontinuation of clozapine. Of the 249 participants with known genotypes, 199 (79.9 %) had the ACKR1-null genotype. Neutropenia (<1500 cells/mm3) occurred significantly more often in the ACKR1-null group (33 % [65/199]) than in those with the T allele (6 % (3/50); p < 0.001). Fourteen (5 %) patients discontinued due to adverse events. Rates of infection and fever were low and sialorrhea was the commonest side effect (N = 187, 68 %). CONCLUSION: To our knowledge, this is the largest prospective clozapine trial in people of African descent. Severe neutropenia was rare, despite the high prevalence (80 %) of the ACKR1-null genotype. Our findings suggest that clozapine can be used safely in Black patients including those with BEN.
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Schizophrenia is a severe mental disorder with various medical comorbidities and early mortality. Hyperprolactinemia is common in women and its impact on sexual function, galactorrhea and amenorrhea is well known. This paper evaluates the risk of 25-hydroxy vitamin D deficiency and other metabolic related laboratory abnormalities in women with schizophrenia having hyperprolactinemia (N = 43). The mean prolactin level in these women was 88.5 ± 56.0 ng/mL. We found that 100% of women were overweight of which 74% (32/43) of the women were obese, 56% (23/41) had abnormal total cholesterol levels and 30% (13/43) had high fasting blood glucose. Vitamin D levels were considered deficient or inadequate in 37% of women. We did not see significant correlations of prolactin with laboratory measures, however all female patients had elevated and high prolactin levels, leading to low variability in a small sample, which may have precluded seeing any direct relationships. Recognizing prolactin related side effects and understanding the role of other health measures seen in women with antipsychotic induced hyperprolactinemia in our female patients are critical steps toward better personalization of their care and recovery.
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Antipsicóticos , Hiperprolactinemia , Esquizofrenia , Antipsicóticos/efeitos adversos , Feminino , Humanos , Hiperprolactinemia/tratamento farmacológico , Gravidez , Prolactina , Vitamina D/análogos & derivadosRESUMO
BACKGROUND: A significant proportion of people with schizophrenia are characterized by impaired ability to socially engage with others. The development of effective interventions for social functioning remains a central therapeutic challenge. Cognitive-behavioral social skills training (CBSST) has been found to improve social functioning in schizophrenia, but with only medium effect sizes. Intranasal oxytocin also has prosocial effects, but also only with modest effect sizes. This study assessed whether the addition of intranasal oxytocin to CBSST can strengthen their impact on social function. METHODS: Participants (N = 62) with schizophrenia or schizoaffective disorder entered a 24-week, double-blind, placebo-controlled, randomized clinical trial with a 3-month follow-up evaluation at 2 sites: Maryland and San Diego. Participants were randomized to either intranasal oxytocin 36 IU (3 sprays) twice a day (n = 31) or intranasal placebo-oxytocin (3 sprays) twice a day (n = 31). All participants received CBSST plus a social cognition skills training module (48 total sessions). RESULTS: There were no significant treatment group differences in social functioning, positive symptoms, negative symptoms, defeatist beliefs, or asocial beliefs. The interpretation of treatment effects was complicated by site effects, whereby participants in San Diego began the trial with greater severity of impairments and subsequently showed greater improvements compared with participants in Maryland. CONCLUSIONS: The results did not support the utility of add-on intranasal oxytocin to psychosocial rehabilitation interventions like CBSST for improvement in social function (ClinicalTrials.gov trial number: NCT01752712).
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Terapia Cognitivo-Comportamental/métodos , Ocitocina/administração & dosagem , Transtornos Psicóticos/cirurgia , Esquizofrenia/terapia , Administração Intranasal , Adulto , Terapia Combinada , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/terapia , Habilidades Sociais , Resultado do TratamentoRESUMO
Prior studies examining the impact of oxytocin on negative symptoms in schizophrenia have yielded mixed results. The current study explored whether oxytocin can improve more proximal indicators of social affiliation as indicated by changes in behavior, language and subjective indices of social affiliation among individuals with schizophrenia spectrum disorders during a role-play designed to elicit affiliative responses. We tested the hypothesis that daily intranasal oxytocin administered for 6 weeks would improve social affiliation as manifested by increased social skill ratings, use of positive, affiliative, and social words, and subjective responses from a previously published randomized controlled trial. Forty outpatients with schizophrenia or schizoaffective disorder were randomized to the oxytocin, galantamine, or placebo group and completed affiliative role-plays and self-report questionnaires of affect, reactions to the affiliative confederate, and willingness to interact at baseline and post-treatment. Results demonstrated that oxytocin was not effective at improving behavioral or subjective indicators of social affiliation. This study adds to a growing literature that the prosocial effects of oxytocin in schizophrenia are limited or null.
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BACKGROUND: Despite adequate antipsychotic treatment, most people with schizophrenia continue to exhibit persistent positive and negative symptoms and cognitive impairments. The current study was designed to examine the efficacy and safety of adjunctive anti-inflammatory combination therapy for these illness manifestations. METHODS: Thirty-nine people with either Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, schizophrenia or schizoaffective disorder were entered into a 12-week double-blind, 2-arm, triple-dummy, placebo-controlled, randomized clinical trial: 19 were randomized to anti-inflammatory combination therapy and 20 were randomized to placebo. The Brief Psychiatric Rating Scale positive symptom item total score was used to assess positive symptom change, the Scale for the Assessment of Negative Symptoms total score was used to assess negative symptom change, the Calgary Depression Scale total score was used to assess depressive symptom change, and the MATRICS Consensus Cognitive Battery was used to assess neuropsychological test performance. RESULTS: There was a significant time effect for Brief Psychiatric Rating Scale positive symptom item score (t226 = -2.66, P = 0.008), but the treatment (t54=1.52, P = 0.13) and treatment × time (t223 = 0.47, P = 0.64) effects were not significant. There were no significant time (t144 = 0.53, P = 0.72), treatment (t58=0.48, P = 0.63), or treatment × time (t143 = -0.20, P = 0.84) effects for the Scale for the Assessment of Negative Symptoms total score; or for any of the other symptom measures. There were no significant group differences in the change in the MATRICS Consensus Cognitive Battery composite score over the course of the study (F1,26=2.20, P = 0.15). CONCLUSIONS: The study results suggest that there is no significant benefit of combined anti-inflammatory treatment for persistent positive symptoms or negative symptoms or cognitive impairments (clinicaltrials.gov trial number: NCT01514682).
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Anti-Inflamatórios/uso terapêutico , Antipsicóticos/uso terapêutico , Cognição/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Anti-Inflamatórios/efeitos adversos , Antipsicóticos/efeitos adversos , Baltimore , Biomarcadores/sangue , Citocinas/sangue , Ácidos Docosa-Hexaenoicos/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Ácido Eicosapentaenoico/uso terapêutico , Feminino , Fluvastatina/uso terapêutico , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Salicilatos/uso terapêutico , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE/BACKGROUND: Negative symptoms and cognitive impairments tend to co-occur in people with schizophrenia. If their association with each other is due, in part, to shared pathophysiology, then this suggests that a single drug could potentially be effective for both domains. The current study was designed to examine this hypothesis. METHODS/PROCEDURES: Fifty-eight participants with either Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision schizophrenia or schizoaffective disorder entered into a 6-week double-blind, placebo-controlled, double-dummy, randomized clinical trial of intranasal oxytocin and galantamine. Seventeen participants were randomized to intranasal oxytocin, 20 were randomized to galantamine, and 21 were randomized to placebo. The Scale for the Assessment of Negative Symptoms total score was used to assess change in negative symptoms (the primary outcome measure for oxytocin). The MATRICS Consensus Cognitive Battery composite score was used to assess cognition (the primary outcome measure for galantamine). FINDINGS/RESULTS: There were no significant group differences for negative symptoms (oxytocin vs placebo: F2,47.4 = 0.19, P = 0.83; galantamine vs placebo: F2,52.5 = 0.41, P = 0.67). There were no significant group differences for cognitive impairments (galantamine vs placebo: t40 = 0.71, P = 0.48; oxytocin vs placebo: t40 = 0.50, P = 0.62). There were also no significant group differences for the functional capacity or ancillary symptom measures. IMPLICATIONS/CONCLUSIONS: The lack of an efficacy signal for either compound precluded our ability to test whether pharmacological treatment pathways for negative symptoms and cognitive impairments overlap or are independent.
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Disfunção Cognitiva/tratamento farmacológico , Galantamina/administração & dosagem , Ocitocina/administração & dosagem , Pessimismo , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Administração Intranasal , Adulto , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nootrópicos/administração & dosagem , Ocitócicos/administração & dosagem , Pessimismo/psicologia , Esquizofrenia/epidemiologia , Resultado do TratamentoRESUMO
OBJECTIVE: Nicotine dependence is high in schizophrenia, and craving is known to impact relapse during quit attempts. METHODS: We compared tobacco craving in smokers with schizophrenia treated with different antipsychotics. RESULTS: Mean craving scores were lowest in participants receiving first-generation antipsychotics, although these differences were not statistically significant. Craving with clozapine was not lower than with other antipsychotics. CONCLUSIONS: Further research is needed to determine whether differences in craving exist between antipsychotic classes.
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Antipsicóticos/uso terapêutico , Fissura/efeitos dos fármacos , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Fumar/psicologia , Tabagismo/psicologia , Adulto , Benzodiazepinas/uso terapêutico , Clozapina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tabagismo/complicaçõesRESUMO
OBJECTIVE: The current study examined the efficacy and safety of rasagiline, a selective MAO-B inhibitor, for the treatment of persistent negative symptoms. METHODS: Sixty people with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder, who met a priori criteria for persistent negative symptoms, were randomized to receive rasagiline, 1mg/d (n = 31) or placebo (n = 29) in a 12-week, double-blind, placebo-controlled clinical trial. The Scale for the Assessment of Negative Symptoms (SANS) total score was used to assess change in negative symptoms. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), N-Back test, a probabilistic learning task, and a delayed discounting task were used to assess cognition. RESULTS: In a mixed model analysis of covariance (MM-ANCOVA), with time as a continuous variable, there was a significant treatment × time effect for SANS total score (F = 5.61(df = 1,40.3), P = .023). The treatment × time interaction effect was also significant for the SANS avolition subscale score (F(1,40.2) = 10.41, P = .002). In a post hoc MM-ANCOVA analyses, with time as a categorical variable, group differences were significant at week 12 for SANS total score (t(37.3) = 2.15; P = .04; d = -0.41) and SANS avolition subscale score (t(49.0) = 3.06; P = .004; d = -0.46). There was a significant difference in number of participants with a ≥20% reduction in SANS avolition score (χ(2)(1) = 10.94; P = .0009), but not in SANS total score (χ(2)(1) = 1.11; P = .29). There were no significant group differences on the RBANS, N-Back, probabilistic learning, or delayed discounting tasks. CONCLUSIONS: Study results support future studies of the utility of rasagiline for the treatment of negative symptoms, including avolition (clinicaltrials.gov trial number: NCT00492336).
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Transtornos Cognitivos/tratamento farmacológico , Indanos/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Adulto , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Indanos/administração & dosagem , Indanos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Monoaminoxidase/administração & dosagem , Inibidores da Monoaminoxidase/efeitos adversos , Testes Neuropsicológicos , Esquizofrenia/complicações , Esquizofrenia/fisiopatologiaRESUMO
OBJECTIVE: To clarify the efficacy and tolerability of bupropion sustained release (SR) for the treatment of cigarette smoking in people with schizophrenia. METHOD: The first study is a double-blind, placebo-controlled clinical trial with 32 outpatients from the Maryland Psychiatric Research Center. From May 2003 to July 2007, clinically stable people with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who smoked at least 10 cigarettes per day and who were interested in quitting smoking or cutting down were recruited for participation. All participated in a 9-week support group and were randomly assigned to receive 12 weeks of bupropion SR or placebo. The primary outcome measure was 4 weeks' sustained abstinence over the last 4 study weeks. Secondary outcome measures included decrease in smoking behavior and change in symptoms, neuropsychological performance, and side effects. In the second study, we performed an electronic literature search of MEDLINE in September 2008. Articles in English published between 2003 and 2008 were searched for the terms schizophrenia, bupropion SR, and smoking. Bibliographies of studies identified through the MEDLINE search were also examined. Case reports, open-label studies, crossover studies, and studies using nonstandard dosing of bupropion SR were excluded. In this way, 4 studies similar in methodology to the currently presented clinical trial were identified and the individual data combined in a meta-analysis. A random effects meta-analysis using Comprehensive Meta-Analysis software was used to obtain a pooled estimate of the odds ratio for 4-week smoking abstinence between bupropion SR and placebo. RESULTS: There were no significant results on the primary or secondary smoking measures for the clinical trial, although a numeric advantage favored the bupropion SR group. There were no significant findings for secondary symptom or side effect measures and no significant change in neuropsychological performance. For the meta-analysis totaling 226 subjects, there were significant findings in favor of bupropion SR. The pooled estimate of the odds ratio for 4-week abstinence was 2.7 (95% CI, 1.3 to 5.7; P = .009), and clinically significant greater smoking reduction in the bupropion SR group, with pooled difference estimates increasing over time between groups, became statistically significant by week 5 of study medication (P < .02). CONCLUSIONS: New clinical trial data and a meta-analysis strongly support the tolerability and efficacy of bupropion SR for the treatment of cigarette smoking in people with schizophrenia TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00176449.
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Bupropiona/uso terapêutico , Psicologia do Esquizofrênico , Grupos de Autoajuda/estatística & dados numéricos , Abandono do Hábito de Fumar/métodos , Fumar/tratamento farmacológico , Fumar/terapia , Antidepressivos de Segunda Geração/administração & dosagem , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/administração & dosagem , Bupropiona/efeitos adversos , Terapia Combinada/métodos , Terapia Combinada/psicologia , Terapia Combinada/estatística & dados numéricos , Preparações de Ação Retardada/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricosRESUMO
OBJECTIVE: The present study sought to better understand the relationships among smoking history, motivation to change, and smoking cessation outcomes in people with schizophrenia who smoke. METHOD: We examined smoking and quit history, negative consequences due to smoking, readiness to change, smoking temptation, and confidence to quit in a sample of people diagnosed with schizophrenia or schizoaffective disorder according to DSM-IV criteria who were participating in a larger randomized trial of bupropion SR and a psychoeducational intervention for smoking cessation. Data were collected from June 2003 to May 2005. RESULTS: At baseline, participants reported high levels of nicotine dependence and daily smoking, as well as multiple recent and lifetime quit attempts that were generally brief in nature. Participants were most concerned about the health effects of smoking and endorsed reasons for smoking related to coping with negative affect and boredom. Most participants reported wanting to quit smoking, but the sample generally reported low levels of confidence in their ability to quit. During the course of participation in the intervention, self-efficacy to quit increased while temptation to smoke decreased; however readiness to quit remained unchanged. CONCLUSION: Smoking cessation programs for people with schizophrenia should focus on teaching coping skills for negative affect, boredom, and specific "high risk situations" for smoking in addition to education, medication, or nicotine replacement therapy. Further, cessation efforts may benefit from directly addressing low self-efficacy for quitting, rather than readiness for change alone, among people with schizophrenia.
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Motivação , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Abandono do Hábito de Fumar/métodos , Fumar/psicologia , Fumar/terapia , Adulto , Monóxido de Carbono/metabolismo , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Psicometria , Abandono do Hábito de Fumar/psicologiaRESUMO
The large numbers of partial clozapine responders represent a major therapeutic challenge. Unfortunately, there are no clear data to support how best to treat these patients. This study examines the efficacy and safety of adjunctive risperidone in a well-defined treatment-resistant population optimally treated with clozapine. A total of 69 inpatients and outpatients with DSM-IV schizophrenia or schizoaffective disorder entered a 16-week double-blind, placebo-controlled, randomized clinical trial. Of them, 33 participants were randomized to risperidone and 36 were randomized to placebo. There was no significant group difference in the predefined response criteria. There were modest group differences for Brief Psychiatric Rating Scale (BPRS) positive symptoms, which were significant in the completer analysis (F=5.70; df=1, 70.3; p=0.02; ES=0.27) but not the intent-to-treat (ITT) analyses (F=3.01; df=1, 77.5; p=0.09; ES=0.19). A similar pattern was found for the BPRS total score, with the completer analysis showing a significant improvement in the risperidone group (F=5.21; df=1, 64.9; p=0.03; ES=0.27), whereas the ITT analysis was not significant (F=3.52; df=1, 71.3; p=0.06; ES=0.22). In addition, there was a small, but significant, group difference for negative symptoms, as measured by the SANS total score, which favored the risperidone group (F=5.67; df=1, 78.7; p=0.02; ES=0.24). There were no significant group differences on safety measures, including neuropsychological test and extrapyramidal symptom scores. A significant elevation of prolactin in the risperidone group was observed. The study results suggest that adjunctive risperidone may have a modest benefit for treatment-resistant clozapine patients. The study results are discussed in the context of previous double-blind studies of adjunctive risperidone. (clinicaltrials.gov, trial number: NCT00056498).
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Clozapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Esquizofrenia/fisiopatologia , Resultado do TratamentoRESUMO
Cigarette smoking is in schizophrenia is prevalent and may be due to self-medicating attempts to improve cognitive deficits related to alpha7 and alpha4beta2 nicotinic receptor dysregulation. Galantamine is an acetylcholinesterase inhibitor that acts as a positive allosteric modulator of nicotine acetylcholine receptors including both the alpha4beta2 and alpha7 subunits. In a double-blind randomized clinical trial galantamine was compared to placebo for its effects on cognitive functioning in people with schizophrenia. This manuscript reports findings for galantamine's effect on smoking behavior in people from this 12-week trial who were smokers (18 galantamine, 25 placebo). Expired CO was measured every 2 weeks and the Fagerström Test for Nicotine Dependence (FTND) was administered at baseline and endpoint. Expired CO measures in galantamine subjects were 23.0+/-9.7 ppm and 21.1+/-10.3 ppm at baseline and Week 12, respectively, compared to 20.1+/-8.5 ppm and 21.0+/-10.3 ppm at baseline and Week 12 in placebo subjects. The mean tau-b correlation between expired CO level and visit was -0.05+/-0.41 in the galantamine group and 0.13+/-0.42 in the placebo group (F=0.73, df=1,38, p=0.40), suggesting that there were no trends toward increased or decreased smoking in either group. Mean FTND scores in the galantamine group were 4.9+/-2.5 at baseline and 5.2+/-2.2 at Week 12, compared to 4.1+/-2.6 at baseline and 3.7+/-2.6 at Week 12 in the placebo group (Mantel-Haenszel chi2=5.53, df=1, p=0.019), for an effect size of 0.4. These results suggest that galantamine has no effect on cigarette smoking and that during galantamine treatment nicotine dependency scores worsen.
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Galantamina/uso terapêutico , Nootrópicos/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Abandono do Hábito de Fumar , Adulto , Antipsicóticos/uso terapêutico , Testes Respiratórios , Monóxido de Carbono/análise , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Receptores Nicotínicos/efeitos dos fármacos , Esquizofrenia/diagnóstico , Automedicação , Receptor Nicotínico de Acetilcolina alfa7RESUMO
OBJECTIVE: Olanzapine has been hypothesized to have superior efficacy in patients with treatment-resistant schizophrenia. The authors examined the comparative efficacy and safety of olanzapine and haloperidol in outpatients with partially responsive schizophrenia. METHOD: Sixty-three outpatients with schizophrenia who met retrospective and prospective criteria for either residual positive or residual negative symptoms entered a 16-week double-blind, parallel-groups comparison of olanzapine and haloperidol. RESULTS: There were no significant differences between the two drugs in their effect on positive or negative symptoms. There were no significant differences between the two treatment groups on measures of social and functional outcome. Olanzapine-treated patients had a significant reduction in extrapyramidal symptoms and subjective measures of stiffness and dry mouth, but the increases in systolic blood pressure and weight in olanzapine-treated patients were significantly greater than they were in haloperidol-treated patients. CONCLUSIONS: Olanzapine has limited differential benefit for either positive or negative symptoms in patients with treatment-resistant schizophrenia. Although olanzapine is associated with fewer extrapyramidal symptoms, other side effects may offset this benefit.