The efficacy and safety of 12 weeks of treatment with sertindole or olanzapine in patients with chronic schizophrenia who did not respond successfully to their previous treatments: a randomized, double-blind, parallel-group, flexible-dose study.

The aim of this study was to evaluate the efficacy, safety, and tolerability of sertindole in comparison with olanzapine in patients with chronic schizophrenia who did not respond successfully to their previous treatments. Patients with schizophrenia who were at least moderately ill and had failed to respond to previous antipsychotic treatment were randomized to double-blind sertindole or olanzapine treatment. A total of 389 patients were treated, 196 with sertindole (mean dose=17 mg/day) and 193 with olanzapine (mean dose=16 mg/day). Both drugs improved all the efficacy scale scores including the Positive and Negative Syndrome Scale total score. Although sertindole failed to prove noninferiority to olanzapine in terms of reduction in PANSS total score with the last-observation-carried-forward analysis, this can be attributed to the higher withdrawal rate in the sertindole group by day 16 by which sertindole was up-titrated to the effective dose. On excluding early withdrawals, the noninferiority criterion was fulfilled, as also in the observed-case analysis. They had similar safety profiles with respect to the total incidence of adverse events. The incidence of asymptomatic QT prolongation was higher in the sertindole group. Sertindole has an efficacy and safety profile that is comparable to that of olanzapine. The slow titration schedule and lack of sedating effect of sertindole should be considered when initiating treatment with this drug.

Risperidone maintenance treatment in schizophrenia: a randomized, controlled trial.

OBJECTIVE: Prevention of relapse is the crucial task in the maintenance treatment of schizophrenia. The investigators in this study sought to determine the duration of maintenance treatment needed with the initial therapeutic dose, in contrast to a reduced dose. METHOD: In a multicenter open-label, randomized, controlled study, patients with schizophrenia who were clinically stabilized following an acute episode were randomly assigned to a no-dose-reduction group (initial optimal therapeutic dose continued throughout the study), a 4-week group (initial optimal therapeutic dose continued for 4 weeks, followed by a 50% dose reduction that was maintained until the end of the study), or a 26-week group (initial optimal therapeutic dose continued for 26 weeks, followed by a 50% dose reduction until the end of the study). All patients continued until the last recruited patient completed the 1-year follow-up. RESULTS: Of the 404 patients who met the entry criteria and were randomly assigned, 374 completed the study. The estimated mean time from entry to relapse was 571 days in the 4-week group, 615 days in the 26-week group, and 683 days in the no-dose-reduction group, with estimated relapse rates of 30.5%, 19.5%, and 9.4%, respectively. Patients in the no-dose-reduction group experienced greater reduction in the severity of psychotic symptoms. CONCLUSIONS: Patients who continued to receive the full risperidone dose used for their acute episode had fewer relapses than those who had dose reductions after 4 weeks or 26 weeks during the maintenance period. There was negligible difference in side effects among the three groups.

Relationships of sleep duration with sleep disturbances, basic socio-demographic factors, and BMI in Chinese people.

OBJECTIVE: This study aimed at determining the mean total sleep time (TST) and the relationship between sleep duration and basic socio-demographic factors and BMI sleep problems in Chinese subjects. METHOD: A total of 5926 subjects were randomly selected and interviewed using standardized assessment tools. RESULTS: The reported mean TST was 7.76 h. Short sleepers were significantly older than medium and long sleepers. There were more urban residents who were short sleepers than medium and long sleepers. Short sleepers reported more sleep problems than medium and long sleepers. Short and long sleepers reported more psychiatric disorders than medium sleepers in both sexes, and short sleepers also had more major medical conditions in women. Short sleepers had a lower BMI than medium and long sleepers after controlling for the effects of age and psychiatric disorders in women. CONCLUSIONS: Nationwide epidemiologic surveys in China are needed to further explore the relationship between sleep duration and sleep problems.

Alcohol-related disorders in Beijing, China: prevalence, socio-demographic correlates, and unmet need for treatment.

BACKGROUND: The study aimed to determine the prevalence of alcohol use, episodic heavy drinking, and alcohol dependence and their socio-demographic correlates in Beijing, China. methods: A total of 5,926 subjects were randomly selected in Beijing and interviewed using the Composite International Diagnostic Interview (CIDI 1.0). Data on basic socio-demographic and current major medical conditions were also collected. RESULTS: The 12-month prevalence of alcohol use and episodic heavy drinking were 32.5 and 13.8%, respectively. The 12-month and lifetime prevalence of alcohol dependence were 1.7 and 4.3%, respectively. Age above 24 years, male sex, being married and employed, low education level (junior high school, primary school or illiterate), rural residence, and having comorbid psychiatric disorders were all significantly associated with a higher likelihood of alcohol-related disorders. Only 2.4% of the subjects with alcohol dependence were receiving treatment, and a mere 1.4% had sought treatment from mental health professionals. CONCLUSIONS: Nationwide surveys are urgently needed to further explore the prevalence of alcohol-related disorders in China.

Generalized anxiety disorder in China: prevalence, sociodemographic correlates, comorbidity, and suicide attempts.

PURPOSE: This study aims to determine the 12-month and lifetime prevalence of generalized anxiety disorder (GAD) and its sociodemographic correlates. DESIGN AND METHODS: A total of 5,926 subjects were randomly selected and interviewed. FINDINGS: The overall 12-month and lifetime prevalence of GAD was 0.8%, and 1.2%, respectively. Being older than 25 years and female, lower education level, unemployed status, and lower (RMB2000/month) monthly income were associated with increased risk of GAD. PRACTICE IMPLICATIONS: The low percentage of subjects treated for GAD indicates a major public health problem that should be addressed.

Lifetime prevalence of suicidal ideation, suicide plans and attempts in rural and urban regions of Beijing, China.

OBJECTIVE: There has been no large-scale survey of suicide-related behaviours including suicidal ideations, plans and attempts in China involving both rural and urban areas and using standardized assessment tools. The aim of the present study was to determine the lifetime prevalence of suicide-related behaviour and its relationship with sociodemographic factors and psychiatric disorders in the rural and urban regions of Beijing, China. METHODS: A total of 5926 subjects were randomly selected in Beijing and interviewed using the Composite International Diagnostic Interview. Basic sociodemographic and clinical data and data on suicide-related behaviour were also collected. RESULTS: The overall lifetime prevalence estimates of suicidal ideation, plans and attempts were 2.3%, 1.4%, and 1.0%, respectively; the corresponding figures were 2.8%, 1.6%, and 1.3% in the rural sample, and 1.8%, 1.3%, and 0.9% in the urban sample. Age (>25 years), female sex, unmarried status, lower education level, lower (RMB2000 month(-1)) monthly income and presence of major medical disorders were significantly associated with increased risk of suicide-related behaviour. 36.2% of subjects with suicide-related behavior consulted a medical practitioner and 20.7% consulted a psychiatrist. CONCLUSIONS: The prevalence of lifetime suicide-related behaviour in Beijing is lower than in Western countries, but the low percentage of subjects treated for suicide-related behaviour indicates a major public health problem that should be addressed. National surveys are needed to further explore the prevalence of suicide-related behaviour in China.

Smoking and psychiatric disorders in the rural and urban regions of Beijing, China: a community-based survey.

BACKGROUND: In China, there is limited information on smoking and its socio-demographic correlates in general, and in psychiatric patients in particular. The aim of this study was to determine the prevalence of lifetime, current mild, and heavy smoking, the socio-demographic correlates of current smoking, and its relationship with psychiatric disorders in the Beijing municipality, China. METHODS: A total of 5926 subjects who met the study's entry criteria were randomly selected from the urban and rural areas of Beijing and interviewed using standardized assessment tools, including the collection of basic socio-demographic and clinical data. All subjects fully cooperated in the interviews and readily disclosed all of the information. RESULTS: The prevalence of lifetime smoking was 35.9%; the rates for current mild and heavy smoking were 21.8% and 10.8%, respectively. An age of 24 years or above, male sex, married, divorced, separated or widowed marital status, relatively low level of education (less than college level), being employed, a relatively high monthly income (more than RMB500), rural abode, and having a psychiatric disorder were risk factors of current smoking. Both current mild and heavy smoking were significantly associated with alcohol dependence, and current heavy smoking was also associated with a history of a major depressive episode. CONCLUSIONS: The prevalence of smoking in the rural and urban areas of Beijing is unacceptably high. In addition to certain socio-demographic factors, smoking was associated with common psychiatric disorders. Nationwide surveys are warranted to further explore the prevalence of smoking in China. Effective strategies to reduce the high rate of smoking are also needed.

Prevalence and socio-demographic correlates of major depressive episode in rural and urban areas of Beijing, China.

OBJECTIVE: This study aimed to determine the 12-month and lifetime prevalence of major depressive episode (MDE) and their socio-demographic correlates in both the urban and rural areas of Beijing, China. METHODS: A total of 4767 adults were randomly selected and interviewed in Beijing using the Composite International Diagnostic Interview (CIDI 1.0). Basic socio-demographic and clinical data were collected during the interviews. RESULTS: The overall 12-month prevalence of MDE was 3.2%; 2.8% and 3.8% for men and women, respectively. The overall lifetime prevalence of MDE was 5.3%; 4.4% and 6.3% for men and women, respectively. Being older than 25 years of age was independently associated with increased risk of MDE. Sixteen point three percent of the subjects with lifetime MDE attempted suicide while the rate of suicide attempts was only 0.2% in subjects without MDE. The percentage of subjects with MDE who received any type of treatment from medical practitioners was 33.1%; of them, only 5.4% sought help from mental health professionals. CONCLUSIONS: National epidemiologic surveys are needed to further explore the prevalence of MDE in China. The low percentage of subjects treated for MDE constitutes a major public health problem that should be urgently addressed.

The prevalence of insomnia, its sociodemographic and clinical correlates, and treatment in rural and urban regions of Beijing, China: a general population-based survey.

STUDY OBJECTIVES: To determine the prevalence of insomnia, its sociodemographic and clinical correlates, and treatment patterns in Chinese people. DESIGN: A total of 5,926 subjects were randomly selected in the urban and rural areas of Beijing and interviewed using standardized assessment tools. Basic sociodemographic and clinical data were also collected. SETTING: Urban and rural regions of Beijing municipality, China. Patients or Participants Adult residents older than 15 years. Interventions N/A. MEASUREMENTS AND RESULTS: The prevalence of at least one type of insomnia was 9.2%; the rates of difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA) were 7.0%, 8.0%, and 4.9%, respectively. Increased age (age >44 and 24 years in the urban and rural samples, respectively), female sex, married, divorced, separated, or widowed marital status; having a major medical condition; and suffering from a psychiatric disorder were risk factors for all types of insomnia in both the urban and rural samples. A low level of education (primary school or illiteracy) was significantly associated with a higher likelihood of all types of insomnia in the urban sample. Current smokers and current drinkers were less likely to report any type of insomnia in the rural sample. Unemployment was associated with DMS in the urban sample, while it was associated with DIS and DMS in the rural sample. Only 5.4% of the participants with any type of insomnia reported their symptoms to medical practitioners. In contrast, nearly one-third of the subjects with insomnia reported taking benzodiazepines as sleep-enhancing drugs. CONCLUSIONS: Nationwide epidemiologic surveys are needed to further explore the prevalence of insomnia in China. The low percentage of subjects treated for insomnia indicates a major public health problem that should be addressed. Strict controls on use of benzodiazepines are warranted.

Prevalence and socio-demographic correlates of schizophrenia in Beijing, China.

OBJECTIVE: There has been no large-scale survey of schizophrenia in China involving both rural and urban areas using standardized assessment tools and diagnostic criteria. This study aimed to determine the lifetime prevalence of schizophrenia and its socio-demographic correlates in Beijing, China. METHODS: A total of 5926 subjects were randomly selected in Beijing and interviewed using the Composite International Diagnostic Interview (CIDI 1.0). Basic socio-demographic and clinical data were collected during the interviews. RESULTS: The lifetime prevalence of schizophrenia was 0.49%, and 0.44% and 0.55% for men and women, respectively. Unmarried status, lower monthly income, urban abode and positive family history were associated with an increased risk of schizophrenia; 9.7% of the subjects with lifetime schizophrenia reported a history of suicide attempts. The percentage of subjects with schizophrenia who were receiving treatment and their preference to seek treatment from mental health professionals were 58% and 29%, respectively. CONCLUSIONS: National surveys are urgently needed to further explore the prevalence of schizophrenia in China. The low percentage of subjects treated for schizophrenia is a serious public health issue that should be addressed in the near future.

Effects of risperidone on glucose metabolism in Chinese patients with schizophrenia: a prospective study.

BACKGROUND: While most of the second generation antipsychotic agents are associated with abnormal glucose metabolism, previous studies have shown that risperidone has relatively little effect upon blood glucose levels. This study aimed to explore the effect of risperidone on the glucose-regulating mechanism of patients with schizophrenia by using the oral glucose tolerance test (OGTT), measuring insulin and C-peptide levels. METHODS: Thirty inpatients with schizophrenia taking risperidone were studied. All the patients were given a simplified OGTT at baseline and six weeks after treatment. Plasma glucose, insulin, and C-peptide concentrations were measured at fasting, then 1 and 2h after OGTT respectively. Other data, including demographic characteristics and plasma drug concentrations, were also recorded. RESULTS: (1) There was no significant increase in the proportion of patients demonstrating abnormal plasma glucose levels compared with baseline (p=1.000, McNemar test); (2) risperidone was associated with elevated insulin concentrations (p=0.013), C-peptide levels (p=0.020), insulin/glucose ratio (p=0.020) and BMI (p<0.01); (3) no sex differences in glucose-related measures were observed. CONCLUSION: Risperidone treatment may be associated with alterations in glucose-regulating mechanisms in patients with schizophrenia.

Socio-demographic and clinical characteristics of 3129 heroin users in the first methadone maintenance treatment clinic in China.

BACKGROUND: This study aimed to determine the characteristics of heroin users in the first methadone maintenance treatment (MMT) clinic in China. METHODS: In a retrospective chart review, the notes of 3127 heroin users who received both detoxification and MMT at the clinic were analyzed. Their socio-demographic and clinical data were collected, and the frequency of human immunodeficiency virus (HIV), Hepatitis C virus (HCV), and syphilis infections was investigated. RESULTS: The main findings are as follows: (1) 66.5% of the patients were younger than 35 years; (2) 55.1% were married at admission; (3) 32% were non-local residents; (4) the majority had high school level education, a history of smoking and alcohol consumption prior to the initial heroin use, and did not have stable jobs; (5) 28.4% were self-employed; (6) 5.4% of the sample had total hearing loss coupled with loss of speech; (7) 83.4% sniffed heroin or injected it intravenously at the time of admission, but 87.2% had smoked the drug when they first began abusing it; (8) a significant proportion of the patients were infected with HIV, HCV, and syphilis. CONCLUSIONS: Some of the above findings are not consistent with the results of previous studies conducted in Western countries and China. The unique socio-cultural and clinical characteristics of heroin abusers in different regions of China should be considered when MMT services are planned.

Escitalopram in major depressive disorder: a multicenter, randomized, double-blind, fixed-dose, parallel trial in a Chinese population.

Escitalopram, the S-enantiomer of citalopram and the most selective of the selective serotonin reuptake inhibitor (SSRI) has been shown to be efficacious in the treatment of major depression in white populations. Our aim in this study was to investigate the efficacy and tolerability of escitalopram in Chinese patients with moderate to severe major depression. Patients who met DSM-IV criteria for a major depressive episode were enrolled in this multicenter, randomized, double-blind, fixed-dose comparison trial. Patients were given escitalopram 10 mg/day or fluoxetine 20 mg/day for 8 weeks. All patients were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D-17) and the Montgomery-Asberg Depression Rating Scale (MADRS). Tolerability was assessed on the basis of adverse effects (measured with a locally developed checklist), regular biochemical tests, and electrocardiograph (ECG) assessments. Two hundred forty patients were enrolled and randomized to escitalopram (123 patients) or fluoxetine (117 patients). The HAM-D-17 total scores of both groups decreased significantly from baseline, but there was no significant difference at week 8 between the two groups (15.8 for escitalopram and 14.7 for fluoxetine; P >.05). There were no significant differences in response rates at all visits after treatment based on either HAM-D-17 or MADRS. A post hoc analysis indicated that escitalopram was superior to fluoxetine on two items of the HAM-D-17: "depressed mood" (P =.023) and "work and interest" (P =.024). The adverse events reported in the escitalopram and fluoxetine groups were comparable, and most were mild to moderate. Both drugs showed good compliance profiles. Escitalopram 10 mg/day is at least as efficacious as fluoxetine 20 mg/day and well tolerated in Chinese patients with major depression, with possible superiority in some core symptoms such as "depressed mood" and "work and interest."

Hemoperfusion in the treatment of acute clozapine intoxication in China.

BACKGROUND AND AIMS: No systematic study has focused on the characteristics and outcome of acute clozapine intoxication, although clozapine is the most widely used antipsychotic agent in China. The study reported herein examined the features of clozapine intoxication and the therapeutic effect of hemoperfusion (HP). METHODS: In a retrospective chart review, the notes of 47 patients who attempted suicide by ingesting large amounts of clozapine and were treated at the only psychiatric emergency service in Beijing were analyzed. Of the 20 unconscious patients with plasma clozapine concentrations of more than 2000 ng/mL, 14 received a combination of HP and symptomatic treatment, whereas the other 6 and the remaining 27 patients received only symptomatic treatment. Patients' psychiatric conditions and both plasma clozapine and norclozapine concentrations were closely monitored and registered. RESULTS: One patient died of pulmonary edema and subsequent heart failure, but the rest of the patients recovered without any sequelae. Patients who received HP regained consciousness significantly faster than their counterparts with the same level of clozapine plasma concentration (>2000 ng/mL) who did not receive HP. CONCLUSIONS: A combination of HP and symptomatic treatment is the best therapeutic option when plasma clozapine concentration is high.

Gender differences in 542 Chinese inpatients with schizophrenia.

OBJECTIVE: To investigate gender differences in the onset and other clinical features of Han Chinese inpatients with schizophrenia. METHODS: Five-hundred-and-forty-two Han Chinese inpatients with DSM-IV schizophrenia were assessed with the Positive and Negative Symptoms Scale (PANSS), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Function scale (GAF) and locally-developed standardized data collection forms. Comparisons were made between male and female patients. RESULTS: This is the largest study of gender differences in schizophrenia to be conducted in a Chinese population. In our sample, we found that schizophrenia onset occurred at a significantly earlier age in male patients compared to female patients and that late-onset schizophrenia (as defined by onset> or =45 years) was significantly more common in female patients. The paranoid subtype of schizophrenia was less common in male patients, males received higher daily doses of antipsychotics and demonstrated a different pattern of antipsychotic usage, being less likely to be treated with SGAs. Further, cigarette smoking was more common in male patients and male patients were more likely to be single or never married. By contrast, female patients showed a different pattern of ongoing symptoms and severity, being more likely to have persistent positive symptoms, more severe positive and affective symptoms, and a greater number of suicide attempts whereas male patients were more likely to show severe deterioration over time. CONCLUSIONS: There are notable gender differences in the age at onset, treatment and a range of other clinical features in Han Chinese patients with schizophrenia. Such differences were largely consistent with those reported in Western studies. These gender differences need to be considered in the assessment and management of Chinese patients with schizophrenia.

Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia.

AIM: To study the relationship between age, gender, cigarette smoking and plasma concentrations of clozapine (CLZ) and its metabolite, norclozapine (NCLZ) in Chinese patients with schizophrenia. METHODS: Data from a therapeutic drug monitoring programme were analysed retrospectively. One hundred and ninety-three Chinese inpatients with schizophrenia were assessed using clinical data forms. Steady-state plasma concentrations of CLZ and NCLZ were assayed using high-performance liquid chromatography. Comparisons of dosage and plasma CLZ concentrations were undertaken between males (n = 116) and females (n = 77), younger (40 years, n = 111) and current male smokers (n = 50) and nonsmokers (n = 66). RESULTS: (i) Plasma CLZ concentrations demonstrated large interindividual variability, up to eightfold at a given dose; (ii) there were significant effects of gender on plasma CLZ concentrations (relative to dose per kg of body weight) with female patients having significantly higher concentrations than males (30.09 +/- 24.86 vs. 19.87 +/- 3.55 ng ml(-1) mg(-1) day(-1) kg(-1); P < 0.001); (iii) there were no significant differences in plasma CLZ concentrations between those patients 40 years; and (iv) there were no significant differences in plasma CLZ concentrations between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher. CONCLUSIONS: Plasma CLZ concentrations vary up to eightfold in Chinese patients. Among the patient-related factors investigated, only gender was significant in affecting CLZ concentrations in Chinese patients with schizophrenia, with female patients having higher levels.

Cigarette smoking in Chinese male inpatients with schizophrenia: a cross-sectional analysis.

Given the high rates of cigarette smoking in schizophrenia in many published studies from around the world, we studied the relationship between smoking status and clinical characteristics in male Chinese schizophrenic inpatients. Two hundred seventy-nine schizophrenic inpatients were assessed using clinical data forms to ascertain historical, demographic and treatment variables and collateral information was also collected from case records and interviews with patients and family members. Current smokers (N=112) were compared with non-smokers (N=167) on clinical variables by independent sample t-tests and chi(2) tests, with adjustment for confounding variables using ANCOVA and binary logistic regression analysis. Compared to non-smokers, current smokers were significantly more likely to be divorced, have lower educational attainment, a more episodic course, have a greater number of previous psychotic relapses and more likely to be treated with clozapine. There was no correlation, however, between smoking consumption and schizophrenic psychopathology. Accordingly, cigarette smoking may be associated with certain clinical features in schizophrenic patients, and should be carefully screened for when making treatment and rehabilitation plans.

Antipsychotic drug use in 503 Chinese inpatients with schizophrenia.

Objective. To determine current patterns of antipsychotic medication use and metabolic complications among hospitalized Chinese patients with schizophrenia. Method. A total of 503 inpatients who met ICD-10 diagnostic criteria for schizophrenia were enrolled. Demographic features and records of current treatment (medication, dose, duration of treatment) were collected through cross-sectional chart review along with biophysical parameters (body mass index and laboratory findings). Results. (1) Most patients (457/503, 90.9%) were found to receive antipsychotic monotherapy; (2) clozapine was the most common medication used (152/507, 30.2%); (3) the subset of patients treated within the course of a first episode psychosis, or with less than 5 years of illness, were more likely to be treated with second-generation antipsychotics (SGAs) than with conventional antipsychotic medications or clozapine; (4) patients treated with clozapine or conventional antipsychotics were more likely to manifest metabolism-related physical conditions than those receiving SGAs. Conclusion. Conventional antipsychotics and clozapine constitute the current mainstream of schizophrenia treatment in China where a lower percentage of patients receive SGAs other than clozapine than in developed countries. The high incidence of treatment-related metabolic complications in this population suggests that these issues are under-appreciated based on current patterns of medication use.

Serum concentrations of clozapine and norclozapine in the prediction of relapse of patients with schizophrenia.

Schizophrenic outpatients (n=102) whose condition had stabilized with clozapine (CLZ) therapy and were being maintained on CLZ were followed for 1 year. Clinical status and concentrations of serum clozapine (CLZ) and its metabolite norclozapine (NCLZ) were evaluated periodically or when relapse occurred. Relapse was defined as a significant exacerbation of psychotic symptoms or hospitalization. Thirty-three patients relapsed and 69 did not. Relapse patients displayed significantly lower serum concentrations of CLZ and a sum of CLZ and NCLZ at endpoint than non-relapses (CLZ: 162 ng/ml vs. 237 ng/ml, p<0.001; CLZ+NCLZ: 225 ng/ml vs. 301 ng/ml, p<0.001). When all subjects were pooled together, a significant inverse correlation was observed between percent increase in the total score on the Brief Psychiatric Rating Scale (BPRS) from baseline and serum levels of CLZ alone (r=0.404, p<0.001) and the sum of CLZ and NCLZ (r=0.364, p<0.001). Relapses and non-relapses were well separated by a threshold CLZ serum concentration of 200 ng/ml with a sensitivity of 73% and a specificity of 80%. The threshold value represented about a 40% lower serum CLZ level than concentration achieved in acute treatment. Survival analysis showed a similarity of the relapse risk over time defined by the CLZ serum threshold and by symptomatic criteria. These results suggest that effective relapse prevention may require maintenance of patients at CLZ serum concentrations above 200 ng/ml and above 60% of the acute-phase level during long-term maintenance treatment of schizophrenia.

The differential effects of steady-state fluvoxamine on the pharmacokinetics of olanzapine and clozapine in healthy volunteers.

The combination of atypical antipsychotics and selective serotonin reuptake inhibitors is an effective strategy in the treatment of certain psychiatric disorders. However, pharmacokinetic interactions between the two classes of drugs remain to be explored. The present study was designed to determine whether there were different effects of steady-state fluvoxamine on the pharmacokinetics of a single dose of olanzapine and clozapine in healthy male volunteers. One single dose of 10 mg olanzapine (n = 12) or clozapine (n = 9) was administered orally. Following a drug washout of at least 4 weeks, all subjects received fluvoxamine (100 mg/day) for 9 days, and one single dose of 10 mg olanzapine or clozapine was added on day 4. Plasma concentrations of olanzapine, clozapine, and N-desmethylclozapine were assayed at serial time points after the antipsychotics were given alone and when added to fluvoxamine. No bioequivalence was found in olanzapine alone and cotreatment with fluvoxamine for the mean peak plasma concentration (C(max)), the area under the concentration-time curve from time 0 to last sampling time point (AUC(0-t)), and from time 0 to infinity (AUC(0- infinity )). Under the cotreatment, C(max) of olanzapine was significantly elevated by 49%, with a 32% reduced time (t(max)) to C(max), whereas the C(max) and t(max) of clozapine were unaltered. The cotreatment increased the AUC(0-t) and AUC(0- infinity ) of olanzapine by 68% and 76%, respectively, greater than those of clozapine (40% and 41%). The presence of fluvoxamine also prolonged the elimination half-life (t(1/2)) of olanzapine by 40% and, to a much greater extent, clozapine by 370% but reduced the total body clearance (CL/F) of clozapine (78%) more significantly than it did for olanzapine (42%). The apparent volume of distribution (V(d)) was suppressed by 31% in olanzapine combined with fluvoxamine but was unaltered in the clozapine regimen. A significant reduction in the N-desmethylclozapine to clozapine ratio was present in the clozapine with fluvoxamine regimen. The effects of fluvoxamine on different aspects of pharmacokinetics of the two antipsychotics may have implications for clinical therapeutics.