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OBJECTIVE Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses). METHODS Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates. RESULTS Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses. CONCLUSIONS Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.

AIM The change in psychiatric diagnoses in clinical practice is not an unusual phenomenon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders is a major clinical issue because of the differences in treatment regimens and long-term prognoses. In this study, we used a nationwide population-based sample to compare the diagnostic consistency and interchange rate between schizophrenic disorders and bipolar disorders. METHODS In total, 25 711 and 11 261 patients newly diagnosed as having schizophrenic disorder and bipolar disorder, respectively, were retrospectively enrolled from the Psychiatric Inpatient Medical Claims database between 2001 and 2005. We followed these two cohorts for 7 years to determine whether their diagnoses were consistent throughout subsequent hospitalizations. The interchange between the two diagnoses was analyzed. RESULTS In the schizophrenic disorder cohort, the overall diagnostic consistency rate was 87.3% and the rate of change to bipolar disorder was 3.0% during the 7-year follow-up. Additional analyses of subtypes revealed that the change rate from schizoaffective disorder to bipolar disorder was 12.0%. In the bipolar disorder cohort, the overall diagnostic consistency rate was 71.9% and the rate of change to schizophrenic disorder was 8.3%. CONCLUSION Changes in the diagnosis of a major psychosis are not uncommon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders might be attributed to the evolution of clinical symptoms and the observation of preserved social functions that contradict the original diagnosis. While making a psychotic diagnosis, clinicians should be aware of the possibility of the change in diagnosis in the future.

Substance abuse or addictive disorder is a global problem. A greater understanding of the associated changes in brain pathophysiology supports the notion that pharmacological treatments are part of the necessary treatment options. Craving is a core symptom of addictive disorder. It refers to a strong desire to use drugs again either to re-experience positive effects or to diminish negative experiences. Currently there are a number of medicines that are effective in the treatment of addictive disorders. These medications can either be for substitution (same pharmacological effect as the abused substance) or anticraving (decrease the craving of the abused substance). In this MEDLNE based review, specific compounds (naltrexone, acamprosate, topiramate, disulfiram, baclofen, N-acetylcysteine and bupropion) were selected that are known to diminish desire to use (anticraving effect) and that have been trialled for a number of different substance addictive disorders. Their therapeutic potential in clinical practice is discussed in light of their efficacy.

Aim Methamphetamine (METH) administration is associated with excessive oxidative stress. It is not known whether the systemic oxidative stress indices would alter during early abstinence in METH abusers with positive urine testing for recent METH exposure. Methods Sixty-four non-treatment-seeking METH abusers enrolled from a controlled environment and 60 healthy controls participated in the study. Fasting serum malondialdehyde (MDA) levels and anti-oxidant indices, including superoxide dismutase (SOD) and catalase (CAT) activity, and glutathione (GSH) levels, were measured at baseline and 2 weeks after the first measurement. We compared the differences of these oxidative stress indices between METH abusers and controls and examined the changes of the indices 2 weeks after baseline in the METH group. Results At baseline, the recently abstinent METH abusers had significantly higher MDA levels, lower SOD activity, and higher CAT activity and GSH levels compared to healthy controls. CAT and GSH values were positively correlated with MDA but negatively correlated with SOD. These oxidative stress indices did not significantly correlate with age, smoking amount, Alcohol Use Disorder Identification Test scores, or METH use variables. After 2 more weeks of abstinence, the indices did not alter nor normalize. Conclusion Compared to controls, we found that METH abusers have persistently higher systemic oxidative stress throughout early abstinence. The compromised SOD as well as elevated CAT activity and GSH levels may act together as a compensatory mechanism to counteract excessive oxidative stress induced by METH. Whether the oxidative stress could improve after a longer period of abstinence needs to be examined in future studies.

A 2-week, randomized, parallel-group open trial was designed to evaluate the safety and tolerability of a rapid initiation regimen with a higher dose of quetiapine (up to 800 mg/d by Day 4) than that used in the conventional initiation regimen of quetiapine (up to 400 mg/d by Day 5) in patients with schizophrenia or schizoaffective disorders. Forty patients were recruited and randomly (3:1) assigned to either the group with rapid initiation of quetiapine or the group with conventional initiation. At the end of the investigation, the difference between the groups in the incidence of adverse events was not significant; a significant drop in the Barnes Akathisia Rating Scale and Simpson-Angus Scale scores was observed only in the group with the rapid initiation regimen. The groups did not differ in terms of improvement on the Clinical Global Impression—Severity of Illness and Positive and Negative Syndrome Scale at the end of the study. The results of our 2-week study suggest that rapid initiation with a higher dose of quetiapine (up to 800 mg/d by Day 4) is well tolerated in patients with schizophrenia or schizoaffective disorders and does not compromise efficacy relative to the conventional initiation.

Introduction and Aims.Methamphetamine use leads to increased likelihood of premature death. The authors investigated the causes of death and risk of mortality in a large cohort of patients with methamphetamine dependence. Design and Methods.A cohort of 1254 subjects with methamphetamine dependence, admitted to a psychiatric centre in Taiwan from January 1990 to December 2007, was retrospectively studied. Diagnostic and sociodemographic data for each subject were extracted from the medical records based on a chart review process. Mortality data were obtained by linking to the National Death Certification System and standardised mortality ratios (SMRs) were estimated. The risk and protective factors for all-cause deaths were explored by means of survival analyses. Results.During the study period, 130 patients died. Of them, 63.1% died unnatural deaths, while the remaining 36.9% died natural deaths. The 1 year cumulative rates for unnatural and natural deaths were 0.018 and 0.006, respectively, and the 5 year rates were 0.046 and 0.023, respectively. The cohort had excessive mortality (SMR = 6.02), and women had a higher SMR for unnatural deaths than men (26.19 vs. 9.82, P = 0.001). For all-cause deaths, comorbidity with other substance use disorders was associated with increased risk of death, despite that being married was associated with a reduced risk. Discussion and Conclusions.A substantial proportion of the deceased died natural deaths, but most died unnatural deaths. The findings show significant evidence to provide valuable insight into premature deaths among methamphetamine-dependent users. This information is valuable for development of prevention and intervention programs.[Kuo C-J, Liao Y-T, Chen WJ, Tsai S-Y, Lin S-K, Chen C-C. Causes of death of patients with methamphetamine dependence: A record-linkage study. Drug Alcohol Rev 2010;30:621–628]

Long-term use of methamphetamine could induce psychosis, but consequences with regards to intelligence have seldom been investigated. Long-term use of alcohol could also result in intellectual deterioration.The IQ of 34 methamphetamine-induced psychosis (MIP) patients (age, 28.7 +/- 6.1 years) and 34 alcohol-dependent (AD) patients (age, 40.7 +/- 7.3 years) was compared using the Chinese version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III).The average full-scale IQ, verbal IQ, performance IQ, verbal comprehension index, working memory index, perceptual organization index, and processing speed index was 82.3 +/- 10.8, 84.3 +/- 11.9, 81.9 +/- 12.1, 85.5 +/- 11.9, 84.7 +/- 12.5, 85.4 +/- 13.6, and 78.5 +/- 12.7 in MIP patients and 90.5 +/- 12.0, 95.2 +/- 11.3, 86.0 +/- 13.7, 95.5 +/- 11.0, 87.1 +/- 14.5, 96.2 +/- 13.1, and 84.5 +/- 15.0 in AD patients, respectively. There were six MIP patients (17.6%) whose full-scale IQ was70 and 13 (38.2%) whose full-scale IQ was85 and70, while one AD patient had a full-scale IQ70 (2.9%) and 10 (22%) had full-scale IQ85 and70.Long-term use of methamphetamine can result not only in psychosis, but also in mentality deterioration. Intelligence deterioration is more severe in clinical MIP patients than AD patients. Assessment of the mentality of MIP patients is suggested to help with the implementation of rehabilitative programs for these patients.

Substance use disorders are familial, and genetic factors explain a substantial degree of their familial aggregation. Methamphetamine (MAP) abusers are commonly noted as having psychosis, depression and suicidal behavior. The goals of the present study were (i) to investigate relations of clinical correlates, such as gender, drug use behavior, psychiatric comorbidity and psychiatry family history, with suicidal behavior among Chinese MAP abusers; and (ii) to investigate whether there is an association between a polymorphism in the promotor region of the serotonin transporter gene (5-HTTLPR) and suicidal behavior among Chinese MAP abusers. A total of 439 MAP abusers from a hospital and detention center in Taipei were interviewed with the Diagnostic Interview for Genetic Study and the Family Interview for Genetic Study. The 5-HTTLPR polymorphism was compared between 94 MAP abusers with suicide attempts and 294 MAP abusers without suicide attempts, for whom DNA data were available. The results of the present study indicate that among MAP abusers in Taiwan, suicide attempts were significantly related to female gender, history of MAP-induced psychotic disorder, history of MAP-induced depressive disorder, and family history of psychotic disorders. Among suicide attempters, the attempters with moderate to severe lethality used higher MAP doses than those with minimal to mild lethality. In the present sample the triallelic 5-HTTLPR polymorphism (S, LG, LA) was not associated with MAP-induced depressive disorder, MAP-induced psychotic disorder or suicidal behavior, but studies with larger sample sizes are warranted before excluding the role of the 5-HTTLPR polymorphisms in suicidal behavior among MAP abusers.

Illicit drug users are generally considered both patients and criminals in Taiwan. This study presents drug use behaviors and criminal recidivism of male subjects incarcerated for illicit drug use in Taiwan after detoxification at a detention center. This study also examined the relationship between drug use behaviors and subsequent recidivism. Charts and crime records of 794 male patients from the acute detoxification unit in a detention center in northern Taiwan were reviewed. These subjects were incarcerated for methamphetamine or/and heroin use. The authors examined the relationship between the variables collected during detoxification and subsequent recidivism of illicit drug use in the following 5 years after detoxification. Of 794 subjects, 539 (67.9%) were repeat offenders during the following 5 years after detoxification. Their recidivism occurred primarily within the first 2 years after being released into the community. The recidivism rate for heroin users was significantly higher than that of methamphetamine users. Aged under 30 years, a previous criminal record, and a positive urine analyses test for illicit drugs upon entering the detoxification unit were significantly associated with recidivism. Recidivism rates of illicit drug users in Taiwan after detoxification in the detention center were substantially high. The efficacy of detoxification programs at detention centers in Taiwan needs to be re-evaluated.

Several lines of evidence have suggested that substance abuse is mediated by the dopaminergic rewarding system, primarily through the activity of the dopamine receptor D1 (DRD1). The purpose of the present study was to evaluate the association of DRD1 A-48G polymorphism with methamphetamine (MAP) abusers and MAP-induced psychosis patients. A total of 363 MAP abusers and 425 healthy normal controls were enrolled. The structural Diagnostic Interview for Genetic Study was used to evaluate all MAP abusers. The MAP abusers were classified into psychosis (n = 135) and non-psychosis (n = 228) groups. A-48G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism. The results show that male sex and a higher frequency of MAP abuse were the predisposing factors in the development of MAP psychosis. The DRD1 -48G allele frequency in the MAP psychosis group, non-psychosis group and the healthy normal controls was 0.14, 0.18 and 0.16, respectively. No association was found between DRD1 A-48G polymorphism and MAP abuse and MAP psychosis. However, the data provided additional evidence of ethnicity-related differences in the distribution of polymorphism in comparison to previous studies.

Methamphetamine (MAP) abuse has been common in Taiwan for the past decade. The purpose of the present study was to investigate MAP abuse in Taiwan, with specific attention to psychiatric comorbidity and gender differences. A total of 325 MAP abuse subjects (180 male, 145 female) from a detention center in Taipei were assessed with the Diagnostic Interview for Genetic Studies. The following were studied: drug use behavior, treatment-seeking behavior, lifetime prevalence of mood disorders, MAP psychosis, alcohol use disorders, pathological gambling and antisocial personality. The MAP-abuse subjects in Taiwan had high psychiatric morbidity and low access to mental health services. There also exist certain differences in the prevalence of psychiatric illnesses and treatment-seeking behavior between male and female subjects. Compared with their male counterparts, more female subjects reported experience of mental disturbance and experience of psychiatric treatment. The female subjects more commonly reported suicidal behaviors than the male subjects.

We analyzed two polymorphisms in genes encoding proteins of the dopamine system, the Val158Met polymorphism in the catechol-O-methyltransferase gene and the 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene for association with methamphetamine abuse. We used a case/control design with 416 methamphetamine abusing subjects and 435 normal controls. All subjects were Han Chinese from Taiwan. We found an excess of the high activity Val158 allele in the methamphetamine abuser group, consistent with several previous reports of association of this allele with drug abuse. The 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene itself did not show significant association with methamphetamine abuse. However, analysis of the 120-bp VNTR polymorphism and the exon 3 VNTR in the dopamine D4 receptor as a haplotype showed significant association with methamphetamine abuse, which gave an empirical P value 0.0034 for a heterogeneity model. Moreover, there were significant interactive effects between polymorphisms in the catechol-O-methyltransferase and dopamine D4 genes. The evidence of interaction between COMT 158 Val/Met and DRD4 48-bp VNTR polymorphisms (P = 0.0003, OR = 1.45, 95% CI: 1.148-1.77), and between COMT 158 Val/Met and DRD4 120 bp promoter polymorphisms (P = 0.01, OR = 1.10, 95% CI: 1.10-1.18) were significant but the latter was weak. We conclude that genetic variation in the dopamine system may encode an additive effect on risk of becoming a methamphetamine abuser.

Forty refractory schizophrenic patients (21 females and 19 males) participated in a fixed-dose study with clozapine. After a 6-week trial of haloperidol and a 1-week washout time period, non-responding patients were placed on clozapine and the dosage titrated up to 400 mg/day for the next 5 weeks. Plasma clozapine levels and its two metabolites desmethylclozapine (DCLOZ) and clozapine N-oxide (CNO) were measured at weeks 2, 4 and 6. Blood samples were obtained 10–12 h post-evening dose and prior to the morning dose. Clozapine and its metabolites were assayed by HPLC with UV detection. Patients were assessed for clinical response with the Brief Psychiatric Rating Scale (BPRS) at baseline and at weeks 2, 4 and 6. BPRS scores were also divided into positive (+) and negative (−) symptoms subscales. Plasma clozapine and DCLOZ levels were significantly lower in males. Plasma CNO levels were slightly lower in males but it was not statistically significant. Decreased total BPRS, (+) and (−) symptoms subscale scores occurred during the study for both gender groups. A greater magnitude of change for the (−) symptom subscale score was observed in the male group. Gender was not a significant factor in the incidence or severity of side-effects. © 1997 John Wiley & Sons, Ltd.

The pharmacokinetic interaction between buspirone and haloperidol was evaluated in schizophrenic patients in two different groups. In both groups, haloperidol doses (10-40 mg/day) remained constant for 6 weeks before the addition of buspirone 10 mg three times daily. Serial blood samples were obtained from the 11 patients in group I at baseline (before addition of buspirone) and after administration for 24 hours. The pharmacokinetic parameters of haloperidol were determined alone and with coadministration of buspirone. In group II, buspirone 10 mg three times daily was added to treatment with haloperidol in 27 patients. Blood samples were obtained before addition of buspirone and at weeks 2 and 6 of treatment with buspirone. Samples were obtained 10 to 12 hours after administration of the evening dose and before the morning dose. Haloperidol and its metabolite, reduced haloperidol (RH), were assayed by means of high-performance liquid chromatography with electrochemical detection. Significant changes in the pharmacokinetic parameters of haloperidol were not found in group I; a mean increase in the half-life (t1/2) of haloperidol from 21.5 to 28.1 hours was observed, but this finding was not statistically significant. Under steady-state conditions, plasma levels of haloperidol in the patients in group II did not change significantly from baseline to week 6. Plasma concentrations of RH remained unaltered in both groups. The results indicate that coadministration of buspirone does not markedly affect the pharmacokinetics or plasma concentrations of haloperidol.

A single dose of haloperidol decanoate 100 mg was administered to 15 schizophrenic patients. Blood samples were obtained prior to injection, 1 h, 3 h, 6 h, 8 h, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, one week, two weeks, three weeks and four weeks post-injection. Haloperidol and its reduced metabolite, reduced haloperidol, plasma levels were assayed by HPLC with electrochemical detection. The pharmacokinetic parameters of haloperidol were determined. The mean time of maximal (Tmax) plasma levels for haloperidol was 5·73 ± 0·80 days. The haloperidol plasma levels showed a biexponential decline with an elimination half-life of 15·78 ± 5·90 days. Reduced haloperidol was rapidly formed from the haloperidol. The Tmax of reduced haloperidol was 7·00 ± 2·35 days. The mean ratio reduced haloperidol/haloperidol was 0·155 ± 0·111. Since the Tmax occurs at approximately six days, a weekly loading dose of haloperidol decanoate is feasible during the transition from oral to depot therapy.