Liang-Jen Wang

Adjunctive effects of aripiprazole on metabolic profiles: Comparison of patients treated with olanzapine to patients treated with other atypical antipsychotic drugs ☆

Metabolic abnormalities are serious adverse effects of atypical antipsychotic treatment. This study aims to determine the effects of adjunctive aripiprazole on metabolic profiles among patients receiving treatment with atypical antipsychotics, and to examine whether these effects are different from that of pre-existing atypical antipsychotics. In the 8-week open-label trial, aripiprazole was added to patients who were receiving treatment with atypical antipsychotics and had experienced weight gain or dyslipidemia. The dosage of pre-existing atypical antipsychotics was fixed, while the dosage of aripiprazole ranged from 5 to 20 mg/day during the study period. Metabolic profiles, including body weight, body mass index (BMI), plasma levels of fasting glucose, triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and adiponectin, were measured at baseline and week 8. As a result, 43 subjects (16 males and 27 females, mean age: 37.8±10.8 years) completed the study. The pre-existing antipsychotics were olanzapine (n=12), risperidone (n=19), quetiapine (n=6) and amisulpiride (n=6). The mean dosage of adjunctive aripiprazole was 9.9±3.2 mg/day. After the aripiprazole-augmented regimen for 8 weeks, patients treated with olanzapine had significant decreases in body weight, BMI and triglyceride levels, and had significant increases in adiponectin levels. For patients treated with other atypical antipsychotics, none of the metabolic parameters significantly changed after administering aripiprazole. In conclusion, aripiprazole-augmented treatment might be beneficial for the metabolic regulation of patients being treated with a stable dose of olanzapine, but not for those treated with other atypical antipsychotics. A long-term, randomized, double-blind controlled design is suggested to confirm these findings.

Long-term neurocognitive effects of methylphenidate in patients with attention deficit hyperactivity disorder, even at drug-free status

BackgroundMethylphenidate (MPH), a psycho-stimulant, is the most widely administered drug for the pharmacological management of patients with attention deficit hyperactivity disorder (ADHD). This study attempts to determine whether sustainable improvements occur in neurocognitive function among ADHD patients following 12-month treatment with MPH, at drug-free status. Whether age groups, gender or ADHD subtypes differ in neurocognitive performance during MPH treatment is also examined.MethodsStudy participants consisted of 103 ADHD patients (mean age: 9.1 ± 1.9 years old) who were drug naïve or drug free for at least 6 months. The patients were prescribed oral short-acting MPH at each dose range of 0.3–1.0 mg/kg daily. During 12 months of the study, the patients underwent the test of variables of attention (TOVA) at the baseline, month 6 and month12. Patients were instructed to not intake MPH for one week before the second and the third TOVA.ResultsSeventy five patients completed the study. Results of this study indicated that although commission errors and response sensitivity (d’) significantly improved during MPH treatment for 12 months, omission errors, response time, response time variability and ADHD score did not. While younger ADHD patients (<9 y/o) performed better in response time, response time variability, d’ and ADHD score than older ones (≥9 y/o), the latter more significantly improved in response time than the former during 12 months of treatment. Additionally, boys improved more than girls in omission error and d’. Moreover, although ADHD subtypes significantly differed in ADHD score during the treatment, MPH treatment and ADHD subtypes did not interact with each other for all TOVA indices.ConclusionsADHD patients significantly improved in impulsivity and perceptual sensitivity, determined as TOVA, during MPH treatment for 12 months. Age and gender, yet not ADHD subtypes, appear to influence the MPH treatment effects in some indices of TOVA. A future study containing a comparison group is suggested to confirm whether the neurocognitive improvements are attributed to long-term effects of MPH or natural maturation of patients.

Association of salivary dehydroepiandrosterone levels and symptoms in patients with attention deficit hyperactivity disorder during six months of treatment with methylphenidate

This prospective study aimed to determine whether salivary levels of dehydroepiandrosterone (DHEA) in patients with attention deficit hyperactivity disorder (ADHD) change significantly during 6 months of treatment with methylphenidate (MPH), and to investigate long-term relationship between these levels and ADHD symptoms. Fifty ADHD patients aged between 6 and 12 years, and 50 age- and gender-matched healthy subjects were recruited. ADHD patients were prescribed oral MPH with a dose range of 5-15 mg/day at the discretion of the psychiatrist. DHEA levels were determined from saliva samples collected from both ADHD patients and healthy subjects at pretreatment and 1, 3, and 6 months from pretreatment visit. ADHD symptoms were evaluated with the Swanson, Nolan, and Pelham, Version IV Scale for ADHD and the ADHD Rating Scale, and computerized Continuous Performance Test (CPT). The results showed that salivary DHEA levels significantly increased in ADHD patients during the 6-month course of methylphenidate treatment, but the DHEA levels did not significantly change in the untreated healthy group during the 6-month period of natural observation. For the longitudinal observation, among ADHD patients, the salivary DHEA levels were independently correlated with distraction and impulsivity performance in the CPT, but not correlated with inattention and hyperactivity in the clinical ADHD symptoms. Whether DHEA exerts effects on neurocognitive functions as mediators or independently of MPH warrants further investigation.

The Trend in Morning Levels of Salivary Cortisol in Children With ADHD During 6 Months of Methylphenidate Treatment

Objective: To determine the trend in cortisol levels in children with ADHD treated with methylphenidate (MPH) and nontreated healthy controls over a 6-month period. Method: The morning salivary cortisol levels of 50 patients with ADHD (40 boys and 10 girls, mean age = 7.6 years) and 50 age- and gender-matched healthy controls were measured at baseline and at 1, 3, and 6 months from baseline. The neuropsychological performance of the ADHD patients was measured via administration of the Continuous Performance Test. Results: The cortisol levels of ADHD patients increased significantly after 1 month of MPH treatment before decreasing to an intermediate level, but were significantly positively correlated with neuropsychological performance throughout the 6-month treatment period. The cortisol levels of the controls did not change significantly over the 6-month period. Conclusion: MPH administration appears to positively influence the functioning of the hypothalamic–pituitary–adrenal axis in ADHD patients.

Factors Associated With Drug-Related Psychiatric Disorders and Suicide Attempts Among Illicit Drug Users in Taiwan

Illicit drug users, entering a detention center and two psychiatric hospitals in Northern Taiwan, were interviewed for lifetime drug-use-related psychiatric disorders and suicide attempts. Among 197 participants, 17.3%, 16.8%, and 14.2% had a drug-induced psychotic disorder (DIP), a drug-induced mood disorder (DIM), and a history of suicide attempts, respectively. Continuous use of methamphetamine and joblessness were associated with DIP and DIM, accordingly. Polysubstance use was collectively correlated with DIP and DIM. Female gender and history of having any mood disorder were predictors of suicide. These results provide useful clues for detecting drug-related psychiatric disorders and suicide among illicit drug users. The studys limitations are noted.

Methods of suicide predict the risks and method-switching of subsequent suicide attempts: a community cohort study in Taiwan

Objective Suicide is a major public health concern. This study aimed to determine the predictors of repeated suicide attempts, focusing on whether lethality level of the suicidal method predicts the risk of subsequent suicide attempts. Methods All consecutive individuals (N=2,070) with an episode of nonfatal self-harm registered in a surveillance database provided by the Department of Health of Keelung City Government in Taiwan from January 1, 2006 to December 31, 2010 were enrolled and followed up until the end of 2011. The earliest attempt recorded in the database was defined as the index attempt. Subjects were classified according to suicide method into low-lethal and high-lethal groups. Data on time of and methods chosen for subsequent suicide attempts during the follow-up period were analyzed. Results Of the total people screened for the study, 18.1% made a repeated suicide attempt. Subjects in the high-lethal group were more likely to be male; aged 35–64 years; and single, divorced, or widowed. Compared to other time intervals, most subsequent suicide attempts occurred within 6 months from the index attempt. The independent predictors for repeated suicide attempts were the use of low-lethal methods in the index attempt and being 35–49 years old. Using high-lethal methods and being older than 50 years were associated with changing suicide method for the second attempt. Conclusion Lethality level of former suicidal method could predict repeated suicide attempts and changing of suicide methods. Further clarification is needed on whether a higher risk of repeat attempts is associated with higher rates of suicide mortality.

Validation of the Chinese version of Brief Assessment of Cognition in Schizophrenia

Objective A test battery that measures cognitive function impairment in patients with schizophrenia, the Brief Assessment of Cognition in Schizophrenia (BACS), has been translated into various languages and validated. This study aimed to test the reliability and validity of the Chinese version of the BACS in a Chinese-speaking population. Methods All participants in this study (66 patients with schizophrenia [mean age: 41.2 years, 57.6% male] and 66 age- and sex-matched healthy controls) were from Taiwan and assessed using the BACS and the University of California, San Diego (UCSD) Performance-Based Skills Assessment, Brief Version (UPSA-B). Thirty-eight of the 66 patients with schizophrenia received a reassessment using the BACS. Results The BACS had good test–retest reliability, and all BACS subtests had statistically insignificant practice effects. Principal components analysis demonstrated that a one-factor solution best fits our dataset (60.9% of the variance). In both patients and controls, the BACS composite scores were positively correlated with all BACS subscales (P<0.001) and UPSA-B scales (P<0.001). Furthermore, all BACS subtests (verbal memory, working memory, motor speed, verbal fluency, attention and processing speed, and executive function) significantly differentiated patients with schizophrenia from healthy controls (P<0.001), and the BACS composite score had the best discriminative validity (P<0.001). Conclusion The Chinese version of the BACS exhibits satisfactory psychometric properties, including high test–retest reliability, high internal consistency, acceptable concurrent validity, and good discriminant validity. We suggest that the BACS is a reliable and practical tool for assessing cognitive function in patients with schizophrenia.

Long-term effectiveness of aripiprazole in adolescents and young adults with bipolar disorder: A naturalistic study

Abstract Objective. The purpose of this study was to investigate the long-term effectiveness of aripiprazole in Taiwanese samples of adolescents and young adults with bipolar disorders. Methods. This investigation comprises a 24-week, observational, prospective study. A total of 28 patients with bipolar I disorder, diagnosed using the Mini International Neuropsychiatric Interview, were administered aripiprazole. Effectiveness was assessed by the change from the baseline in Clinical Global Impression Scale (CGI), Brief Psychiatric Rating Scale (BPRS) and The World Health Organization Quality of Life questionnaire (WHOQOL). Results. The sample comprised 19 males and nine females with a mean (SD) age of 18.5 (3.3) years. The diagnosis was bipolar I disorder with manic (n = 8), depressive (n = 6) and mixed (n = 14) episodes. Eighteen patients (64.3%) discontinued aripiprazole prematurely. The CGI severity, BPRS total score improved significantly from the baseline to the endpoint. Conclusion. Aripiprazole led to clinically meaningful improvement of global symptoms in adolescents and young adults with bipolar disorder. However, discontinuation of medication within 6 months was high. Whether aripiparzole benefits patients with manic episodes more than those with depressive or mixed episodes warrants further investigation.

Differences in Clinical Features of Methamphetamine Users with Persistent Psychosis and Patients with Schizophrenia

Background: Methamphetamine exerts neurotoxic effects and elicits psychotic symptoms. This study attempted to compare clinical differences between methamphetamine users with persistent psychosis (MAP) and patients with schizophrenia. In addition, we examined the discrimination validity by using symptom clusters to differentiate between MAP and schizophrenia. Methods: We enrolled 53 MAP patients and 53 patients with schizophrenia. The psychopathology of participants was assessed using the Chinese version of the Diagnostic Interview for Genetic Studies and the 18-item Brief Psychiatric Rating Scale. Logistic regression was used to examine the predicted probability scores of different symptom combinations on discriminating between MAP and schizophrenia. The receiver operating characteristic (ROC) analyses and area under the curve (AUC) were further applied to examine the discrimination validity of the predicted probability scores on differentiating between MAP and schizophrenia. Results: We found that MAP and schizophrenia demonstrated similar patterns of delusions. Compared to patients with schizophrenia, MAP experienced significantly higher proportions of visual hallucinations and of somatic or tactile hallucinations. However, MAP exhibited significantly lower severity in conceptual disorganization, mannerism/posturing, blunted affect, emotional withdrawal, and motor retardation compared to patients with schizophrenia. The ROC analysis showed that a predicted probability score combining the aforementioned 7 items of symptoms could significantly differentiate between MAP and schizophrenia (AUC = 0.77). Conclusion: Findings in the current study suggest that nuanced differences might exist in the clinical presentation of secondary psychosis (MAP) and primary psychosis (schizophrenia). Combining the symptoms as a whole may help with differential diagnosis for MAP and schizophrenia.

Salivary Neurosteroid Levels and Behavioural Profiles of Children with Attention-Deficit/Hyperactivity Disorder During Six Months of Methylphenidate Treatment

OBJECTIVE This prospective study aimed to investigate the relationships between salivary levels of neurosteroids, including dehydroepiandrosterone (DHEA), cortisol, and DHEA/cortisol ratios, and behavioral symptoms in patients with attention-deficit/hyperactivity disorder (ADHD) during treatment with methylphenidate (MPH). METHODS Fifty-eight ADHD patients (48 boys and 10 girls) were included in the study initially. Forty patients (mean age: 7.77±1.64 years; 32 boys and 8 girls) who completed the study received treatment with oral MPH with a dose range of 5-15 mg/day (mean dose: 12.47±7.74 mg/day.) for 6 months at the discretion of the psychiatrist. DHEA and cortisol levels were determined from saliva samples collected at 0800 h at baseline and 6 months from baseline. ADHD symptoms were evaluated with the Child Behavior Checklist (CBCL). RESULTS Salivary DHEA levels (mean difference=9.05 pg/mL, p=0.027) and DHEA/cortisol ratios (mean difference=32.42, p=0.007) in ADHD patients were significantly increased, but the cortisol levels did not change significantly. During a 6 month follow-up, all behavioral problems assessed using the CBCL improved significantly. Changes in salivary DHEA levels were positively correlated with changes in salivary cortisol levels (r=0.44, p=0.004); however, changes in salivary levels of DHEA, cortisol, and the DHEA/cortisol ratio were not significantly correlated with change in any subscales of the CBCL. Mean doses of MPH were not significantly correlated with changes in neurosteroid levels and behavioral symptoms. CONCLUSIONS These findings provide evidence that MPH administration might affect DHEA levels and DHEA/cortisol ratios. Whether levels of neurosteroids are directly associated with brain function or behavioral problems in ADHD patients warrants further investigation.