Role of cytokine changes in clozapine-induced fever: A cohort prospective study.

AIM: Clozapine-associated fever is common but the specific cytokine changes and treatment durations that may cause fever remain unknown. We investigated the association between inflammatory cytokine changes and clozapine-induced fever in patients who were treated with clozapine. METHODS: Forty-three patients with schizophrenia or schizoaffective disorder, diagnosed by using the Chinese Version of the Mini International Neuropsychiatric Interview, were treated with clozapine for the first time (first-time use group, n = 22) or for more than 6 months (long-term use group, n = 21). The Positive and Negative Syndrome Scale, tympanic temperature, and levels of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined at baseline and weeks 1, 2, 3, 4, and 6. A multiple linear regression with generalized estimating equation methods was used to analyze the association between the changes in the cytokine levels and clozapine-induced fever in the different groups. RESULTS: The IL-6 level changes were significantly different between the two groups (P = 0.04). In the first-time use group, the fever rate was increased (47.1%) compared with the long-term use group (5.6%, P = 0.005). Moreover, in these patients, the TNF-α, INF-γ, IL-2, and IL-6 levels were significantly (P < 0.001) different from patients who did not develop a fever. An interaction effect with the different treatment duration groups and fever development was only significant for IL-6 (P < 0.001). CONCLUSION: Patients who were treated with clozapine for the first time have an increased rate of developing a fever, and IL-6 might have a specific role in the interaction effect between treatment duration and fever development.

Comparison of outcomes after 3-month methadone maintenance treatment between heroin users with and without HIV infection: a 3-month follow-up study.

BACKGROUND: The aim of this study was to compare the changes in primary (heroin use-related) and secondary (depressive symptoms and quality of life, QOL) outcome indicators of 3-month methadone maintenance treatment (MMT) between heroin users with and without HIV infection. METHODS: A total of 242 intravenous heroin-dependent individuals (30 with and 212 without HIV infection) receiving MMT were recruited. Primary (severity of heroin dependence, harm caused by heroin use and current heroin use) and secondary (depressive symptoms and QOL) outcome indicators were determined before and after receiving 3-month MMT. Changes in primary and secondary outcome indicators between the two groups were compared using mixed-model analysis. RESULTS: Heroin users both with and without HIV infection showed significant improvement in three primary outcome indicators after 3-month MMT, and there was no difference in the changes of these primary outcome indicators between the two groups. However, improvements in depressive symptoms and the physical domain of QOL among HIV-infected heroin users were poorer than in those without HIV infection. CONCLUSIONS: The results of this study indicated that heroin users with HIV infection did improve in the primary but not the secondary outcomes after 3-month MMT.

Gender differences in heroin users receiving methadone maintenance therapy in Taiwan.

This study examined gender differences in heroin users who first received MMT. Compared with men, female heroin users were younger and more likely to be unemployed, to have family members using illicit substances, to initiate heroin use at a younger age, to begin MMT earlier after starting heroin use, to have methamphetamine use, to initiate methamphetamine use at a younger age, and to report a child-raising burden and a prior history of traumatic experiences. Men were more likely to have use of betel quid, and to initiate alcohol, nicotine and betel quid use at a younger age than women.

Predictors for dropping-out from methadone maintenance therapy programs among heroin users in southern Taiwan.

This study examined the methadone maintenance therapy (MMT) retention rates of heroin users in Taiwan and the predictors for dropout in the 18-month period after starting MMT. We consecutively recruited 368 intravenous heroin users receiving MMT in 2007-2008 and applied Cox proportional hazards regression analysis to determine the predictive effect of pre- and in-treatment variables on early discontinuation of MMT. The retention rate at 18 months was 32.3%. High heroin expenses, more severe harm caused by heroin use, perceived lower family support, and lower methadone dosage at 3 months after starting MMT increased the risk of dropout in the follow-up period.

Can heroin-dependent individuals benefit from a methadone maintenance treatment program before they drop out against medical advice? A 12-month follow-up study.

AIM: Little is known about whether heroin-dependent individuals receiving methadone maintenance treatment (MMT) who were discharged involuntarily and against medical advice (DAMA) get benefits before they left. The aims of this 12-month follow-up study were to examine whether the effects of MMT on depressive symptoms, heroin dependence and quality of life (QOL) are different among the non-DAMA group, the DAMA group, and the involuntarily discharged group, as well as the time effect of receiving MMT on changes in these three outcome indicators. METHOD: A total of 266 individuals receiving MMT were divided into the non-DAMA group, the DAMA group, and the involuntarily discharged group. Participants were interviewed at baseline and at 3, 6, 9, and 12 months of treatment for levels of depressive symptoms, heroin dependence and QOL. RESULTS: The levels of depressive symptoms, heroin dependence and QOL in all three groups improved after receiving MMT for 3 months and the improvement was maintained during the MMT period. There were no significant differences in the three outcome indicators among the three groups. CONCLUSION: The results support the concept that heroin-dependent individuals benefit from MMT, even if they do not want to stay in the program or drop out involuntarily.

Change in quality of life and its predictors in heroin users receiving methadone maintenance treatment in Taiwan: an 18-month follow-up study.

BACKGROUND: A good quality of life (QOL) is associated with successful treatment in patients with opioid dependence. Therefore, it is of clinical benefit to examine what factors can predict a change in QOL among heroin users in the course of a methadone maintenance treatment (MMT) program. OBJECTIVES: This longitudinal study aimed to examine the patterns and predictors of change in QOL among heroin users during the period of an 18-month MMT program. METHODS: A total of 368 intravenous heroin users receiving MMT in southern Taiwan between 2007 and 2008 were interviewed using the Taiwan version of the Brief Version of the World Health Organization Quality of Life Instrument (WHOQOL-BREF) at baseline and after 3, 6, 9, 12, 15, and 18 months of treatment. Demographic and substance-use characteristics, severity of heroin use, HIV serostatus, criminal record, and family function data were collected during baseline interviews. Data on methadone dosage at each follow-up point and the duration of retention in the MMT program were also collected. RESULTS: Improvement in QOL was rapid during the first 3 months after initiation of MMT and slowed beyond the 3-month point. A higher dosage of methadone predicted a better QOL. In addition, longer retention in the program may be associated with a better QOL. CONCLUSIONS: The results supported the hypothesis that, regarding QOL, heroin users can benefit rapidly and continuously from a MMT. A higher dose of methadone and longer treatment may predict improvement in QOL. SCIENTIFIC SIGNIFICANCE: Efforts are needed to amend the modifiable factors related to poor QOL for heroin users in MMT programs.

Predictors of the severity of depressive symptoms among intravenous heroin users receiving methadone maintenance treatment in Taiwan: an 18-month follow-up study.

This 18-month follow-up study examined the predictors of the severity of depressive symptoms among intravenous heroin users receiving methadone maintenance treatment (MMT) in Taiwan. The severity of depressive symptoms in 368 intravenous heroin users receiving MMT in southern Taiwan was assessed using the Center for Epidemiological Studies Depression scale at baseline and at 3, 6, 9, 12, 15, and 18 months of treatment. Demographic and substance-using characteristics, severity of heroin use, HIV serostatus, criminal record, and family function were collected during baseline interviews. Data on methadone dosage at each follow-up interview and the duration of retention in the MMT program were also collected. A generalized estimating equation was used to determine independent predictors of depressive symptoms during the 18-month period of MMT. Female gender, lack of fixed employment, severe heroin use, concurrent methamphetamine use, low family function at baseline, heroin use during the MMT, low methadone dosage, and short duration of participation in MMT predicted more severe depressive symptoms during the 18-month MMT. This study found that sociodemographic and substance-using characteristics at baseline predicted the severity of depressive symptoms among heroin users receiving MMT. Methadone dosage and MMT duration were also predictive of depression severity. The predictors found in this study can be used to identify heroin users who are at risk for depressive symptoms in the MMT program.

Quality of life and its correlates among heroin users in Taiwan.

The aims of this study were to compare the quality of life (QOL) between subjects with and without heroin use and to examine the association of QOL with sociodemographic characteristics, characteristics of heroin use, family support, and depression among heroin users at entry to a methadone maintenance treatment program. A group of 123 heroin users who visited an outpatient addiction treatment clinic in southern Taiwan for methadone maintenance treatment were recruited into this study. We also recruited 106 subjects who had never used heroin as the control group. Their QOL status was assessed by the short form of the Taiwan Version of the World Health Organization Questionnaire on Quality of Life (the WHOQOL-BREF Taiwan version). The level of QOL between subjects with and without heroin use was compared, and the correlates of QOL among heroin users were examined. Heroin users had poorer QOL than nonusers in the physical, psychological, and social relationship domains but not the environment domain of the WHOQOL-BREF after controlling for the influences of other factors. In addition, heroin users with obvious depression had poorer QOL in all four domains than those without obvious depression. Also, heroin users who perceived higher family support had better QOL in the social relationship and environment domains. Heroin users had poorer QOL than nonusers in multiple domains. Relief of depressive symptoms and enhancement of family support should be important strategies to improve QOL in heroin users.