Association between antidepressants and venous thromboembolism in Taiwan.

OBJECTIVE: To investigate the association between venous thromboembolism (VTE) and antidepressant use in an Asian population. METHODS: The authors conducted a nested case-control study of 1888 patients with VTE and 11,222 matched controls enrolled in the National Health Insurance Research Database in Taiwan from 2001 to 2009. The antidepressant exposure status and potential confounding factors were measured and included in the analyses. Conditional logistic regressions were applied to determine the effect of antidepressant use on VTE. RESULTS: We found a significant association of current antidepressant use with VTE in the total study sample (adjusted odds ratio [aOR], 1.59; 95% confidence interval (CI), 1.27-2.00). With regard to antidepressant classes and potency, we found that tricyclic antidepressants (aOR, 1.56; 95% CI, 1.11-2.18), serotonin 5-HT2A receptor blockers (aOR, 2.03; 95% CI, 1.27-3.24), and antidepressants with a low potency of serotonin reuptake inhibition (aOR, 1.57; 95% CI, 1.18-2.08) were associated with a significantly increased risk of VTE. When further stratifying by age, sex, and comorbid conditions, the VTE risk with antidepressant use was elevated among young and middle-aged adults, but not among the elderly. In addition, an elevated risk of VTE was observed in women and subjects without severe comorbid conditions, but not in men and subjects with severe comorbid conditions. CONCLUSIONS: There was a small increase in VTE risk with antidepressant use. The prescription of antidepressant drugs should be cautious, and especially, should be based on clinical evaluations of benefits and risks. The underlying mechanisms of the interaction between antidepressants and VTE warrant further investigation.

Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study.

AIM: To examine comprehensively the relationship between exposure to four classes of psychotropic drugs including antipsychotics, antidepressants, benzodiazepines (BZDs) and Z-drugs, and motor vehicle accidents (MVAs). METHOD: The authors conducted a matched case-control study of 5183 subjects with MVAs and 31 093 matched controls, identified from the claims records of outpatient service visits during the period from 2000 to 2009. Inclusion criteria were defined as subjects aged equal to or more than 18 years and involved in MVAs. Conditional logistic regressions with covariates adjustment (including urbanity, psychiatric and non-psychiatric outpatient visits and Charlson comorbidity score) were applied to examine the effect of four classes of psychotropic drugs on MVAs. RESULTS: Significant increased risk of MVAs was found in subjects taking antidepressants within 1 month (adjusted odds ratio (AOR) 1.73, 95% confidence interval (CI) 1.34, 2.22), 1 week (AOR 1.71, 95% CI 1.29, 2.26), and 1 day (AOR 1.70, 95% CI 1.26, 2.29) before MVAs occurred. Similar results were observed in subjects taking benzodiazepines (BZDs) (AOR 1.56, 95% CI 1.38, 1.75 for 1 month; AOR 1.64, 95% CI 1.43, 1.88 for 1 week, and AOR 1.62, 95% CI 1.39, 1.88 for 1 day) and Z-drugs (AOR 1.42, 95% CI 1.14, 1.76 for 1 month, AOR 1.37, 95% CI 1.06, 1.75 for 1 week, AOR 1.34, 95% CI 1.03, 1.75 for 1 day), but not antipsychotics. Moreover, significant dose effects of antidepressants (equal to or more than 0.6-1.0 DDD), BZDs (equal to or more than 0.1-0.5 DDD) and Z-drugs (more than 1 DDD) were observed, respectively, on the risk of experiencing an MVA. CONCLUSION: Taken together, subjects taking antidepressants, BZDs and Z-drugs, separately, should be particularly cautioned for their increasing risk of MVAs.

Overlapping Prescriptions of Stimulants for Children and Adolescents With Attention-Deficit Hyperactivity Disorder.

OBJECTIVES: The study aimed to assess the occurrence of overlapping prescriptions for methylphenidate among children and adolescents with newly diagnosed attention-deficit hyperactivity disorder (ADHD) and to evaluate the extent to which physician-level and patient-level characteristics affected the risk of prescription overlap during a one-year treatment period. METHODS: The analytic sample comprised 3,081 incident cases of ADHD in 2002 involving children aged 17 years or younger from a retrospective cohort study in Taiwan. Medical and pharmacy claims data from 1999 to 2002 were retrieved from the National Health Insurance Program. All records of methylphenidate prescriptions within a year of treatment initiation were retrieved for each patient, and the number of overlapping days for any two successive prescriptions (new, renewal, or refill) was measured. Multilevel analyses were performed to identify predictors of methylphenidate prescription overlap. RESULTS: Within a year of treatment initiation, approximately 3% to 4% individuals with a new diagnosis of ADHD had experienced methylphenidate prescription overlap. Youngsters who resided in a rural region (adjusted odds ratio [AOR]=2.68) or who had ever changed prescribing doctors (AOR=3.04) were more likely to have visits with a methylphenidate prescription overlap. Receiving methylphenidate from physicians aged 46 or older was associated with 3.6-fold increased odds of prescription overlap. CONCLUSIONS: In an effort to improve the quality and safety of prescription of controlled substances in younger populations, interventions or policies should be devised to target both the service providers and the patients.

Adherence patterns with first- versus second-generation antipsychotics for newly diagnosed schizophrenia in Taiwan.

OBJECTIVE: The aim of this study was to compare the early adherence patterns for first-generation antipsychotics and second-generation antipsychotics during the first month of treatment for patients newly diagnosed as having schizophrenia. METHODS: With a random sample from the Taiwan national health insurance database, persons with a schizophrenia diagnosis (ICD-9-CM code 295.X) and a concurrent initial antipsychotic prescription from 1998 to 2006 were defined as being newly treated for schizophrenia. Adherence patterns within one month of diagnosis were categorized into four independent groups: refill, switch, admission, and discontinuation. RESULTS: Treatment initiated with first-generation or second-generation antipsychotics resulted in similar rates of refill (57% versus 59%). However, patients who started with first-generation antipsychotics were significantly less likely to switch (9% versus 14%) but more likely to discontinue (34% versus 26%) medications than those whose treatment was initiated with second-generation antipsychotics. CONCLUSIONS: The data substantiated previous observations of the magnitude of adherence problems in Asian populations and highlight the importance of developing new strategies for intervention.

Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population-based study.

BACKGROUND: The association between autoimmune diseases and schizophrenia has rarely been systematically investigated. AIMS: To investigate the association between schizophrenia and a variety of autoimmune diseases and to explore possible gender variation in any such association. METHOD: Taiwan's National Health Insurance Research Database was used to identify 10 811 hospital in-patients with schizophrenia and 108 110 age-matched controls. Univariate and multiple logistic regression analyses were performed, separately, to evaluate the association between autoimmune diseases and schizophrenia. We applied the false discovery rate to correct for multiple testing. RESULTS: When compared with the control group, the in-patients with schizophrenia had an increased risk of Graves' disease (odds ratio (OR) = 1.32, 95% CI 1.04-1.67), psoriasis (OR = 1.48, 95% CI 1.07-2.04), pernicious anaemia (OR = 1.71, 95% CI 1.04-2.80), celiac disease (OR = 2.43, 95% CI 1.12-5.27) and hypersensitivity vasculitis (OR = 5.00, 95% CI 1.64-15.26), whereas a reverse association with rheumatoid arthritis (OR = 0.52, 95% CI 0.35-0.76) was also observed. Gender-specific variation was found for Sjögren syndrome, hereditary haemolytic anaemia, myasthenia gravis, polymyalgia rheumatica and dermatomyositis. CONCLUSIONS: Schizophrenia was associated with a greater variety of autoimmune diseases than was anticipated. Further investigation is needed to gain a better understanding of the aetiology of schizophrenia and autoimmune diseases.

Five-year trajectories of long-term benzodiazepine use by adolescents: patient, provider, and medication factors.

OBJECTIVES: This study sought to understand the stability of and change in benzodiazepine use among incident long-term benzodiazepine users over a five-year period and to investigate predictors of variation in use patterns from adolescence into adulthood. METHODS: Long-term use was defined as receipt of benzodiazepine prescriptions for 31 or more cumulative days in a calendar year. Data for 1999-2005 were obtained from the National Health Insurance Research Database in Taiwan. Two age groups of incident long-term users in 2000 were identified--1,758 aged 12-15 and 5,265 aged 16-19-and their benzodiazepine prescription records from 2001 to 2005 were retrieved. Group-based trajectory analyses and polytomous logistic regression were performed to evaluate differential risk of benzodiazepine use over time. RESULTS: From 3% to 5% of the incident benzodiazepine users were long-term users. Four distinct groups of users emerged from the five years of study data: occasional, decelerating, accelerating, and chronic users. Overall, one-quarter were accelerating or chronic users. A history of psychosis or epilepsy, prescription by providers from multiple specialties, and receipt of benzodiazepines with a long half-life or mixed indications significantly increased one's risk of becoming a chronic or accelerating user (range of adjusted odds ratios from 2 to 6). CONCLUSIONS: Patient characteristics and attributes of service providers and pharmacological agents played significant roles in benzodiazepine use patterns. Prescribers can reduce the risk of long-term use by assessing whether pediatric patients have received benzodiazepines from multiple doctors for various medical conditions.

Differential effects of predictors on methylphenidate initiation and discontinuation among young people with newly diagnosed attention-deficit/hyperactivity disorder.

OBJECTIVE: Previous population-based studies have identified factors accounting for differential utilization of psychotropic medications among young patients with attention-deficit/hyperactivity disorders (ADHDs); yet, few analyses have addressed changes in such factors that can occur in the help-seeking process. The aim of this study was to examine patient- and service provider-level predictors for methylphenidate (MPH) initiation and discontinuation. METHOD: This cohort study included 10,153 newly diagnosed ADHD patients under 18 years of age in 2000, identified from the National Health Insurance Research Database. The risk association was estimated by time-dependent survival analyses, as indexed by hazard ratio. RESULTS: Approximately 30% of young people received MPH treatment within the year of their ADHD diagnosis, and virtually none remained in treatment beyond 12 months. Regardless of co-morbidity status, the following were significantly associated with earlier initiation of MPH treatment: older age (e.g., adjusted hazard ratio [aHR] for age 12-17 = 4.5-7.6), lower socioeconomic status (aHR = 1.2-1.4), southern residence (aHR = 1.4-1.6), receiving the diagnosis while school was in session (aHR = 1.3-1.4), receiving the diagnosis from a physician specializing in pediatrics or psychiatry (aHR = 7.3-16.8), and receiving the diagnosis in a district hospital/clinic (aHR = 1.3-1.7). However, once treatment started, older ages appeared to increase the risk of early discontinuation by 15%, and the corresponding estimates for receiving initial MPH in a regional hospital or district hospital/clinic were 27% and 32%, respectively. Change in treatment location upon subsequent visit was associated with a 58% reduction in early discontinuation. CONCLUSIONS: This information about time-varying predictors for MPH utilization throughout treatment may provide insight into the delivery of pediatric mental health services and has important implications for the design of clinical treatment programs.

Multidimensional assessments of impulsivity in subjects with history of suicidal attempts.

OBJECTIVE: This study aimed to examine whether subjects with history of suicidal attempts had higher impulsivity as measured by neurocognitive tests and self-report questionnaires. The interrelationships among different impulsivity measures were also explored. METHODS: Fifty-four nonpsychotic psychiatric inpatients, including 24 subjects with previous history of suicidal attempts and 30 comparison subjects without previous suicidal attempts, completed the self-report Barratt Impulsiveness Scale-11-Chinese version (BIS-11-CH) and 2 neuropsychologic tests of impulsivity: the immediate memory task/delayed memory task (IMT/DMT) and the single key impulsivity paradigm (SKIP). RESULTS: The results indicated that subjects with previous suicidal attempts exhibited higher BIS-11-CH factor 2 (lack of self-control/attentional impulsivity) subscore (P = .02) and more commission errors in IMT (P = .03). However, BIS-11-CH scores and performance indices of IMT/DMT and of SKIP did not correlate with each other. CONCLUSIONS: Our findings supported that subjects with previous suicidal attempts had higher impulsivity, which could be revealed by both self-report and neurocognitive measures. However, there is no correlation among self-report, IMT/DMT, and SKIP measures, indicating that they might be measuring different dimensions of impulsivity.

Predictors of the incidence and discontinuation of long-term use of benzodiazepines: a population-based study.

Long-term use of benzodiazepines (BZDs) has been linked with an array of negative health consequences and increased medical costs and social burden. In this study, we sought to investigate the factors accounting for differential risks in the process from incident BZD use to long-term use and discontinuation in the general population. On the basis of a random sample of 187,413 people enrolled in Taiwan's National Health Insurance program on January 1, 2000, data of 2000-2002 healthcare and pharmacological services utilization were retrieved. Long-term use (LTU) was defined by having received BZD prescriptions for 180 or more days within any given calendar year. Multivariate logistic regression analyses were carried out to assess the strength of associations while adjusting for the effects of individual sociodemographics, service providers, and pharmacological agents simultaneously. Results indicated that males, elderly, and those with physical or mental disorders were more likely to become long-term users of BZDs. Having received BZD prescriptions in multiple pharmacological agents, short-acting or mixed-type agents, and hypnotic indication were associated with a roughly 2- to 5-fold increased risk of BZD LTU soon after prescription initiation. With respect to discontinuation, the effects of pharmacological characteristics seem more salient as compared to those of individual and service-provider factors. Future strategies targeting individual factors and modifying service-provider prescription behaviors may be considered to reduce possible negative consequences of BZD LTU.

Benzodiazepine and risk of hip fractures in older people: a nested case-control study in Taiwan.

OBJECTIVE: To examine the characteristics of benzodiazepines usage and their associations with hip fractures. METHOD: All subjects were aged 65 and older and enrolled in the National Health Insurance program in Taiwan, 2001-2004. Cases (N = 217) were elderly patients who were identified with hip fractures for the first time in their outpatient claims. They were individually matched to 1,214 comparison patients based on age, gender, and index year. Benzodiazepine usage (doses, duration, half-life) and the other covariates including comorbidities, health care utilization, and psychotropic medications used in the 180 days before index events were constructed. RESULTS: Using nonusers as reference group, use of benzodiazepines was significantly associated with hip fractures (adjusted odds ratio [AOR] = 1.7, 95% confidence interval [CI] = 1.2-2.5). Such risks appear to be particularly high during the first month (AOR = 5.6, 95% CI = 2.7-11.8) of exposure, doses higher than 3.0 mg/day in diazepam equivalents (AOR = 1.8, 95% CI = 1.1-3.1), and using short-acting benzodiazepines (AOR = 1.8, 95% CI = 1.3-2.7). CONCLUSIONS: Benzodiazepine exposure in the elderly increases the risk of hip fractures. This is true even with modest dosage, short-acting agents and short-term exposures. Clinicians should prescribe benzodiazepines judiciously with the elderly to minimize drug-related hip fractures.