BackgroundCultural views of Attention-Deficit/Hyperactivity Disorder (ADHD), differing healthcare... more BackgroundCultural views of Attention-Deficit/Hyperactivity Disorder (ADHD), differing healthcare systems and funding mechanisms, and the availability of mental health services can greatly influence the perceptions, diagnosis, and treatment of ADHD. There is, however, lack of information about treatment practice and the treatment decision-making process for ADHD, particularly in non-Western countries. Our study compared characteristics of paediatric patients newly diagnosed with ADHD symptoms who did and who did not initiate treatment, and also examined whether any differences varied by region in Central Europe and East Asia.MethodsData were taken from a 1-year prospective, observational study that included 1,068 paediatric patients newly diagnosed with ADHD symptoms. Clinical severity was measured using the Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) scale and the Child Symptom Inventory-4 (CSI-4) checklist. Logistic regression was used to explore patient characteristics ...
The aim of the present study was to investigate clinical and economic consequences of medication ... more The aim of the present study was to investigate clinical and economic consequences of medication nonadherence during 21-month follow-up in the treatment of bipolar disorder following a manic or mixed episode. Data were taken from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM), which was a prospective, observational study on patient outcomes with a manic/mixed episode in Europe. Physician-rated adherence was dichotomized as adherence/non-adherence at each assessment. Cox proportional hazards models were employed to investigate the impact of non-adherence on remission, recovery, relapse, recurrence, hospitalization and suicide attempts. Costs of medication and resource use in adherent and non-adherent patients during follow-up were estimated with multivariate analyses. Of the 1341 patients analysed, 23.6% were rated non-adherent over 21 months. Non-adherence was significantly associated with decreased likelihood of achieving remission and recovery as well as increased risk of relapse and recurrence as well as hospitalization and suicide attempts. In addition, costs incurred by non-adherent patients during this period were significantly higher than those of adherent patients (£10231 vs £7379, p b 0.05). This disparity mainly resulted from differences in inpatient costs (£4796 vs £2150, p b 0.05). In conclusion, non-adherence in bipolar patients was associated with poorer long term clinical outcomes that have economic implications for health-care providers.
To compare health care utilization of duloxetine initiators and pregabalin initiators among fibro... more To compare health care utilization of duloxetine initiators and pregabalin initiators among fibromyalgia patients in a real-world setting. Methods: A retrospective cohort study was conducted based on a US national commercial health claims database (2006-2009). Fibromyalgia patients who initiated duloxetine or pregabalin in 2008, aged 18-64 years, and who maintained continuous health insurance coverage 1 year before and 1 year after initiation were assigned to duloxetine or pregabalin cohorts on the basis of their initiated agent. Patients who had pill coverage of the agents over the course of 90 days preceding the initiation were excluded. The two comparative cohorts were constructed using propensity score greedy match methods. Descriptive analysis and paired t-test were performed to compare health care utilization rates in the postinitiation year and the changes of these rates from the preinitiation year to the postinitiation year. Results: Both matched cohorts (n=1,265 pairs) had a similar mean initiation age (49-50 years), percentage of women (87%-88%), and prevalence of baseline comorbid conditions (neuropathic pain other than diabetic peripheral neuropathic pain, low back pain, cardiovascular disease, hypertension, headache or migraine, and osteoarthritis). In the preinitiation year, both cohorts had similar inpatient, outpatient, and medication utilization rates (inpatient, 15.7%-16.1%; outpatient, 100.0%; medication, 97.9%-98.7%). The utilization rates diverged in the postinitiation year, with the pregabalin cohort using more fibromyalgia-related inpatient care (3.2% versus 2.2%; P,0.05), any inpatient care (19.3% versus 16.8%; P,0.05), and fibromyalgiarelated outpatient care (62.1% versus 51.8%; P,0.05). From the preinitiation period to the postinitiation period, the duloxetine cohort experienced decreases in certain utilization rates, whereas the pregabalin cohort had increases (percentage of patients with a fibromyalgia-related admission, −1.2% versus 0.4% [P,0.01]; number of fibromyalgia-related outpatient claims, −1.7 versus 4.7 [P,0.01]). Conclusion: Fibromyalgia patients initiating pregabalin tended to consume more fibromyalgiarelated inpatient and outpatient care in the first postinitiation year, whereas fibromyalgia patients initiating duloxetine tended to have lower utilization rates of fibromyalgia-related inpatient care in the postinitiation year than in the preinitiation year.
To assess the impact of pain severity and time to diagnosis of depression on health care costs fo... more To assess the impact of pain severity and time to diagnosis of depression on health care costs for primary care patients with pre-existing unexplained pain symptoms who subsequently received a diagnosis of depression. Patients and methods: This retrospective cohort study analyzed 4000 adults with unexplained pain (defined as painful physical symptoms [PPS] without any probable organic cause) and a subsequent diagnosis of depression, identified from the UK General Practice Research Database using diagnostic codes. Patients were categorized into four groups based on pain severity (milder or more severe; based on number of pain-relief medications and use of opioids) and time to diagnosis of depression (#1 year or .1 year from PPS index date). Annual health care costs were calculated (2009 values) and included general practitioner (GP) consultations, secondary care referrals, and prescriptions for pain-relief medications for the 12 months before depression diagnosis and in the subsequent 2 years. Multivariate models of cost included time period as a main independent variable, and adjusted for age, gender, and comorbidities. Results: Total annual health care costs before and after depression diagnosis for the four patient groups were higher for the groups with more severe pain (£819-£988 versus £565-£628; P , 0.001 for all pairwise comparisons) and highest for the group with more severe pain and longer time to depression diagnosis in the subsequent 2 years (P , 0.05). Total GP costs were highest in the group with more severe pain and longer time to depression diagnosis both before and after depression diagnosis (P , 0.05). In the second year following depression diagnosis, this group also had the highest secondary care referral costs (P , 0.01). The highest drug costs were in the groups with more severe pain (P , 0.001), although costs within each group were similar before and after depression diagnosis. Conclusion: Among patients with unexplained pain symptoms, significant pain in combination with longer time from pain symptoms to depression diagnosis contribute to higher costs for the UK health care system.
Purpose: Medication nonadherence is common in the treatment of patients with severe mental illnes... more Purpose: Medication nonadherence is common in the treatment of patients with severe mental illness and is a frequent cause of relapse. Different formulations have been developed in an effort to improve medication adherence. The aim of this study was to explore whether there are differential clinical outcomes between two different formulations of olanzapine (orodispersible tablets [ODTs] vs standard oral tablets [SOT]) for the treatment of nonadherent patients with schizophrenia or bipolar disorder. Methods: Data for this analysis were from an observational study conducted in Europe (N=903). Adult schizophrenia and bipolar disorder patients in outpatient settings who initiated or changed to either olanzapine ODT or SOT according to physician decision within the last 45 days were eligible for enrollment. The follow-up period was 1 year. Of the 903 participants, 266 nonadherent patients (Medication Adherence Rating Scale score 0-4 at baseline) were included in the analysis. Clinical outcomes of interest were: 1) hospitalization and 2) relapse identified by the participating psychiatrist or hospitalization. An adjusted logistic regression model was fitted. Results: Patients taking ODT had more severe illness at baseline (P,0.001) as assessed with the Clinical Global Impression with mean (standard deviation [SD]) scores of ODT 4.63 (1.03) and SOT 4 (1.16). In the regression models adjusted for potential confounders, patients taking ODT had significantly lower odds for hospitalization (odds ratio =0.355; 95% confidence interval =0.13-0.974) and relapse or hospitalization (odds ratio =0.368; 95% confidence interval =0.183-0.739), respectively. Conclusion: Nonadherent patients with schizophrenia or bipolar disorder treated with the orodispersible formulation were less likely to be hospitalized or suffer relapse compared to those patients taking the standard oral coated tablets.
Objectius: Els objectius generals d'aquesta tesi son descriure l'evolucio dels pacients a... more Objectius: Els objectius generals d'aquesta tesi son descriure l'evolucio dels pacients amb esquizofrenia durant tres anys de seguiment i analitzar les diferencies entre regions del mon amb diferents nivells de desenvolupament. Els objectius especifics son: • Descriure la frequencia de resposta al tractament en pacients ambulatoris amb esquizofrenia en diferents regions del mon. • Analitzar les caracteristiques demografiques (edat, sexe, estat civil) i els factors clinics (edat d'inici, temps d'evolucio, gravetat de la malaltia, funcionament) associades a la resposta clinica. • Descriure la frequencia de la remissio clinica i funcional en pacients ambulatoris amb esquizofrenia en diferents regions del mon. • Analitzar les caracteristiques demografiques (edat, sexe, estat civil) i els factors clinics (edat d'inici, temps d'evolucio, gravetat de la malaltia, funcionament) associats a la remissio clinica i funcional. Metodes: La base de dades de l'estudi Wor...
Background: Hospitalization is a costly and distressing event associated with relapse during schi... more Background: Hospitalization is a costly and distressing event associated with relapse during schizophrenia treatment. No information is available on the predictors of hospitalization during maintenance treatment with olanzapine long-acting injection (olanzapine-LAI) or how the risk of hospitalization differs between olanzapine-LAI and oral olanzapine. This study aimed to identify the predictors of psychiatric hospitalization during maintenance treatment with olanzapine-LAI and assess ed four parameters: hospitalization prevalence, incidence rate, duration, and the time to first hospitalization. Olanzapine-LAI was also compared with a sub-therapeutic dose of olanzapine-LAI and with oral olanzapine. Methods: This was a post hoc exploratory analysis of data from a randomized, doubleblind study comparing the safety and efficacy of olanzapine-LAI (pooled act ive depot groups: 405 mg/4 weeks, 300 mg/2 weeks, and 150 mg/2 weeks) with oral olanzapine and sub-therapeutic olanzapine-LAI (45 m...
To investigate the impact of anxiety symptoms on depression outcomes in Asian patients with major... more To investigate the impact of anxiety symptoms on depression outcomes in Asian patients with major depressive disorder (MDD) (n=714). The 17-item Hamilton Depression Scale (HAMD-17), overall severity, somatic symptoms, and quality of life (QOL) (EuroQOL Questionnaire-5 Dimensions [EQ-5D]) were assessed at baseline and 3 months. Anxiety was measured using items 10 and 11 from the HAMD-17. Linear, tobit, and logistic multiple regression models analyzed the impact of anxiety symptoms on outcomes. Baseline anxiety was related to age and the presence of pain symptoms at baseline. Regression models showed that a higher level of anxiety was associated with a lower frequency of remission and lower QOL at 3 months. Patients with lower baseline anxiety symptoms had higher remission rates (odds ratio for each point of anxiety symptoms, 0.829 [95% confidence interval [CI]: 0.723-0.951]). Patients with higher levels of baseline anxiety had a lower QOL at 3 months (a decrease in EQ-5D tariff score...
Many patients with schizophrenia and bipolar disorder have impaired insight and low medication ad... more Many patients with schizophrenia and bipolar disorder have impaired insight and low medication adherence. The aim of this post hoc analysis was to explore the relationship between insight and medication adherence. We included 903 patients with schizophrenia or bipolar disorder who participated in an observational study conducted in Europe on the outcomes of patients treated with two oral formulations of olanzapine over a 1-year period. Evaluations included Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), insight (Scale to Assess Unawareness of Mental Disorder, SUMD) medication adherence (Medication Adherence Rating Scale, MARS), and therapeutic alliance (Working Alliance Inventory, WAI). Medication adherence was higher in bipolar patients (mean MARS score (SD) 6.5 (2.8) versus 5.8 (2.7) in schizophrenia; p < 0.001). Patients with schizophrenia had lower insight (i.e., SUMD item 1, unawareness of mental disorder, mean (SD) of 2.5 (1.3) in schizophrenia ver...
To carry-out a cost-effectiveness analysis (CEA) of the effect of Pregabalin (PGB) versus usual c... more To carry-out a cost-effectiveness analysis (CEA) of the effect of Pregabalin (PGB) versus usual care in refractory outpatients with Generalized Anxiety Disorder (GAD) treated according with usual medical practice in Mental Health Centers in Spain. METHODS: CEA was carried-out by means of a nested case-control design which used secondary data extracted at random from a 6-month cohort prospective observational study (the ADAN study) conducted to ascertain cost-of-illness in GAD (DSM-IV criteria). Refractory subjects were those who claimed of persistent symptoms of anxiety and showed suboptimal response (HAM-Anxiety scale 16) after a course of standard doses of any anti-anxiety drug, alone or in combination, for 6 months. At baseline, patients could switch to PGB (monotherapy or add-on) or to usual care, alone or in combination, which were considered cases and controls respectively. Health outcomes included quality-adjusted life years (QALYs) gain by EQ-5D. A 3 rd-payer perspective was chosen for the CEA analysis in year 2009. Sensitivity analysis was performed by bootstrapping techniques (10000 re-samples were obtained) in order to obtain a cost-effectiveness acceptability curve. RESULTS: A total of 858 refractory subjects (mean baseline HAM-A; score 25.7) were identified; 429 in each of the PGB and UC group. Compared with UC, PGB was associated with significant higher QALY gain after 6 months of treatment; 0.1225 0.0995 vs 0.1009 0.0938 (p 0.001), but significantly increased health care costs; a1,240.6 1,407.4 vs a931.4 940.2 (p 0.0001). The deterministic ICER ratio was a14,287 per QALY gained with a re-sampling ICER of a15,804 (95 CI: 15,064-16,545). The 90% of re-samples fold below a25,052 threshold and 95% a30,000. CONCLUSIONS: Despite the design of the primary study, this evaluation could suggest that pregabalin may be cost-effective in comparison with usual care in refractory outpatients with Generalized Anxiety Disorders managed in Mental Health Centers under usual medical practice in Spain.
To provide information on functional outcomes for patients with schizophrenia manifesting negativ... more To provide information on functional outcomes for patients with schizophrenia manifesting negative symptoms across five European countries. METHODS: Physicians in France, Germany, Italy, Spain, and the UK who prescribed antipsychotics for at least 15 patients with schizophrenia within the preceding 3 months were invited to complete a questionnaire concerning their patients' clinical status and functional performance. RESULTS: Data were obtained from 704 physicians treating a total of 6569 patients from France (n = 1492), Germany (n = 1439), Italy (n = 1002), Spain (n = 1310), and the UK (n = 1326). Physicians rated patient symptoms on a 5-point scale as either predominated by or with a high level of positive symptoms (38%), predominated by or with a high level of negative symptoms (32%), or not dominated by either type of symptom (22%). Physicians did not rate 8% of patients using this scale. Patients with a predominance of negative symptoms were rated as having significantly greater functional impairment than those with predominant positive symptoms as measured by physician ratings on the Global Assessment of Functioning scale (P < 0.01) and on 5-point global numerical ratings of overall function, cognitive function, and patients' overall ability to meet their own needs (P < 0.01). In addition, 57% of patients in whom negative symptoms predominated required a caregiver, compared with 49%-50% of patients in other symptom categories. CONCLUSIONS: In this large, multinational, cross-sectional physician survey, patients with schizophrenia in whom negative symptoms predominated had levels of functional impairment at least as great as, if not greater than, those for patients in whom positive symptoms predominated. These results suggest that additional attention should be given to effectively treating the persistent negative symptoms present in many patients with schizophrenia.
Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Centra... more Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime."
Purpose: To describe pharmacological treatment patterns in Asian patients with major depressive d... more Purpose: To describe pharmacological treatment patterns in Asian patients with major depressive disorder (MDD), including duration of treatment, reasons for medication discontinuation, rate of medication nonadherence, factors associated with medication nonadherence, and impact of medication nonadherence on depression outcomes. Patients and methods: Data were from a prospective, observational 3-month study of East Asian MDD inpatients from 40 sites in six East Asian countries who initiated antidepressant treatment at baseline (n=569). Assessments included the Clinical Global Impression-Severity scale (CGI-S), 17-item Hamilton Depression Rating Scale (HAMD-17), painful physical symptoms, response and remission, employment status, quality of life (QoL) (EuroQOL Questionnaire-5 Dimensions [EQ-5D]) and health state using the visual analog scale, adherence by clinician opinion, and patient self-report. Cox proportional hazards modeling, Kaplan-Meier survival analysis, and regression modeling were employed. Results: Median time to discontinuation for any reason was 70 days (95% confidence interval: 47; 95). Reasons for discontinuation were inadequate response in 64.1%, nonadherence in 6.2%, and adverse events in 4.1%; 25.6% who discontinued experienced an adequate response to treatment. In those patients who had an adequate response, age and country were significantly associated with time to medication discontinuation. Patient-reported nonadherence was 57.5% and clinician-reported nonadherence was 14.6% (62/426). At 3 months, nonadherent patients had significantly higher disease severity (CGI-S, P=0.0001; HAMD-17, P0.0001), lower QoL ratings (EQ-5D tariff, P=0.0007; EQ-5D visual analog scale, P=0.0024), and lower response and remission rates (both P0.0001) compared with adherent patients. The odds of response and remission were greater among adherent patients. Conclusion: Early discontinuation of antidepressants among Asian MDD patients was high. A total of 25.6% who discontinued prematurely were experiencing an adequate response to treatment. Nonadherent patients had significantly higher disease severity, lower QoL ratings, and lower response and remission rates compared with adherent patients.
long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanz... more long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection Background: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI), and whether observed changes differ from those seen with oral olanzapine. Methods: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264) with daily oral olanzapine (10 mg/day; n=260). Levels of functioning were assessed with the Heinrichs-Carpenter Quality of Life Scale. Functional status was also classified as "good", "moderate", or "poor", using a previous data-driven approach. Changes in functional levels were assessed with McNemar's test and comparisons between olanzapine-LAI and oral olanzapine employed the Student's t-test. Results: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score) from 64.0-70.8 (P0.001). Patients on oral olanzapine also increased their level of functioning from 62.1-70.1 (P0.001). At baseline, 19.2% of the olanzapine-LAI-treated patients had a "good" level of functioning, which increased to 27.5% (P0.05). The figures for oral olanzapine were 14.2% and 24.5%, respectively (P0.001). Results did not significantly differ between olanzapine-LAI and oral olanzapine. Conclusion: In this 2-year, open-label, randomized study of olanzapine-LAI, outpatients with schizophrenia maintained or improved their favorable baseline level of functioning over time. Results did not significantly differ between olanzapine-LAI and oral olanzapine.
Background: Bipolar disorder (BD) is characterized by episodes of mania and depression. The debil... more Background: Bipolar disorder (BD) is characterized by episodes of mania and depression. The debilitating symptoms during an acute episode require intensive treatment, frequently leading to inpatient psychiatric care, which places significant demands on health and social care systems and incurs substantial costs. However, no study to date has estimated the economic impact of relapse. Objectives: To estimate the direct costs associated with relapse in the treatment of BD following an acute manic or mixed episode over a 21-month follow-up period in routine clinical practice in Europe, using data from a large, prospective, observational study. Methods: EMBLEM was a prospective, observational study on the outcomes of patients with a manic/mixed episode of BD conducted in 14 European countries. Patients eligible for analysis were those enrolled in the 21-month maintenance phase of the study, following the 3-month acute phase. Relapse was defined as achieving any one of the following criteria: (i) at least a onepoint increase in Clinical Global Impression-Bipolar Disorder (CGI-BP) overall score from the previous visit, with a final rating of ‡4; (ii) inpatient admission for an acute episode of BD; or (iii) psychiatrists' confirmation of relapse. Data on healthcare resource use were recorded retrospectively for the four respective periods (3-6, 6-12, 12-18 and 18-24 month visits). Multivariate analyses were performed to compare the cost of resource use (inpatient stay, day care, psychiatrist visits and medication) for those who relapsed during the 21-month maintenance phase and those who never relapsed. A sensitivity analysis was also conducted to examine the 6-month costs during relapse. The analyses were adjusted for patient characteristics and took account of non-Normality of the cost data by using a log link
ical trials registries, and EMA reports. We extracted data for depression severity (mean differen... more ical trials registries, and EMA reports. We extracted data for depression severity (mean differences or related statistics) on the primary comparisons of 1) agomelatine 25 mg/day versus placebo, and 2) agomelatine 25 mg/day versus any SSRI. We calculated Hedges' g effect size for each trial and combined them by the inverse variance method assuming a random effects model. Two meta-analyses were conducted: one with the results of published and unpublished trials and the other only with results of published trials. RESULTS: Ten trials (5 unpublished) gave data on the efficacy of agomelatine versus placebo. Overall, the results were homogeneous (I 2 ϭ 9.2%), and showed agomelatine was better than placebo for reducing the severity of depression at 8 weeks (g ϭ-0.18; 95% CI ϭ-0.25 to-0.10; p Ͻ0.0001). However when the analysis was restricted to published trials the effect size was 45% overestimated (g ϭ-0.26; 95% CI ϭ-0.36 to-0.15; p Ͻ 0.0001; I 2 ϭ 3.4%). 7 trials (4 unpublished) gave data on the comparison of agomelatine versus any SSRI. There was no difference in efficacy with all trials combined (g ϭ 0.01; 95% CI ϭ-0.16 to 0.18; p ϭ 0.87), but agomelatine significantly outperformed SSRIs in the subset of published trials (g ϭ-0.17; 95%
Atypical antipsychotic agents are considered the first-line treatment of schizophrenia. Aim of pr... more Atypical antipsychotic agents are considered the first-line treatment of schizophrenia. Aim of present study was to identify factors affecting the cost of schizophrenia treatment with atypical antipsychotic agents. METHODS: A retrospective database study was conducted in three public hospitals in Hong Kong. Patients initiated on atypical antipsychotic agents (amisulpride, olanzapine, quetiapine and risperidone) between March 2003 and September 2003 for treatment of schizophrenia for at least three months was recruited. Patient medical records were reviewed for up to 12 months before and after initiation date of the antipsychotic agents to retrieve baseline demographic and clinical factors and health care resource utilization for schizophrenia. A multiple regression model was used to identify demographic, clinical factors and choice of atypical antipsychotic agents with significant association to health care resource utilization. RESULTS: Eighty-two patients were included in the analysis. Thirty-four (41%) patients were male and mean age was 43 ± 14 years. The mean cost per patient per month was USD 431 ± 914 (1USD = 7.8HKD). Three factors were associated with direct medical cost of health care resource utilized: 1). History of drug abuse (RR = 1.26; 95% CI = 1.05-1.52); 2). prior use of depot antipsychotic (RR = 1.22; 95% CI = 1.05-1.42); and 3). previous duration of hospitalization before initiation of atypical antipsychotic therapy (RR = 1.00; 95% CI = 1.00-1.01). CONCLUSION: History of drug abuse, prior use of depot antipsychotic, previous duration of hospitalization appeared to be influential to direct medical cost of atypical antipsychotic treatment. The choice of antipsychotic agents did not appear to affect the cost of treatment.
BackgroundCultural views of Attention-Deficit/Hyperactivity Disorder (ADHD), differing healthcare... more BackgroundCultural views of Attention-Deficit/Hyperactivity Disorder (ADHD), differing healthcare systems and funding mechanisms, and the availability of mental health services can greatly influence the perceptions, diagnosis, and treatment of ADHD. There is, however, lack of information about treatment practice and the treatment decision-making process for ADHD, particularly in non-Western countries. Our study compared characteristics of paediatric patients newly diagnosed with ADHD symptoms who did and who did not initiate treatment, and also examined whether any differences varied by region in Central Europe and East Asia.MethodsData were taken from a 1-year prospective, observational study that included 1,068 paediatric patients newly diagnosed with ADHD symptoms. Clinical severity was measured using the Clinical Global Impression-ADHD-Severity (CGI-ADHD-S) scale and the Child Symptom Inventory-4 (CSI-4) checklist. Logistic regression was used to explore patient characteristics ...
The aim of the present study was to investigate clinical and economic consequences of medication ... more The aim of the present study was to investigate clinical and economic consequences of medication nonadherence during 21-month follow-up in the treatment of bipolar disorder following a manic or mixed episode. Data were taken from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM), which was a prospective, observational study on patient outcomes with a manic/mixed episode in Europe. Physician-rated adherence was dichotomized as adherence/non-adherence at each assessment. Cox proportional hazards models were employed to investigate the impact of non-adherence on remission, recovery, relapse, recurrence, hospitalization and suicide attempts. Costs of medication and resource use in adherent and non-adherent patients during follow-up were estimated with multivariate analyses. Of the 1341 patients analysed, 23.6% were rated non-adherent over 21 months. Non-adherence was significantly associated with decreased likelihood of achieving remission and recovery as well as increased risk of relapse and recurrence as well as hospitalization and suicide attempts. In addition, costs incurred by non-adherent patients during this period were significantly higher than those of adherent patients (£10231 vs £7379, p b 0.05). This disparity mainly resulted from differences in inpatient costs (£4796 vs £2150, p b 0.05). In conclusion, non-adherence in bipolar patients was associated with poorer long term clinical outcomes that have economic implications for health-care providers.
To compare health care utilization of duloxetine initiators and pregabalin initiators among fibro... more To compare health care utilization of duloxetine initiators and pregabalin initiators among fibromyalgia patients in a real-world setting. Methods: A retrospective cohort study was conducted based on a US national commercial health claims database (2006-2009). Fibromyalgia patients who initiated duloxetine or pregabalin in 2008, aged 18-64 years, and who maintained continuous health insurance coverage 1 year before and 1 year after initiation were assigned to duloxetine or pregabalin cohorts on the basis of their initiated agent. Patients who had pill coverage of the agents over the course of 90 days preceding the initiation were excluded. The two comparative cohorts were constructed using propensity score greedy match methods. Descriptive analysis and paired t-test were performed to compare health care utilization rates in the postinitiation year and the changes of these rates from the preinitiation year to the postinitiation year. Results: Both matched cohorts (n=1,265 pairs) had a similar mean initiation age (49-50 years), percentage of women (87%-88%), and prevalence of baseline comorbid conditions (neuropathic pain other than diabetic peripheral neuropathic pain, low back pain, cardiovascular disease, hypertension, headache or migraine, and osteoarthritis). In the preinitiation year, both cohorts had similar inpatient, outpatient, and medication utilization rates (inpatient, 15.7%-16.1%; outpatient, 100.0%; medication, 97.9%-98.7%). The utilization rates diverged in the postinitiation year, with the pregabalin cohort using more fibromyalgia-related inpatient care (3.2% versus 2.2%; P,0.05), any inpatient care (19.3% versus 16.8%; P,0.05), and fibromyalgiarelated outpatient care (62.1% versus 51.8%; P,0.05). From the preinitiation period to the postinitiation period, the duloxetine cohort experienced decreases in certain utilization rates, whereas the pregabalin cohort had increases (percentage of patients with a fibromyalgia-related admission, −1.2% versus 0.4% [P,0.01]; number of fibromyalgia-related outpatient claims, −1.7 versus 4.7 [P,0.01]). Conclusion: Fibromyalgia patients initiating pregabalin tended to consume more fibromyalgiarelated inpatient and outpatient care in the first postinitiation year, whereas fibromyalgia patients initiating duloxetine tended to have lower utilization rates of fibromyalgia-related inpatient care in the postinitiation year than in the preinitiation year.
To assess the impact of pain severity and time to diagnosis of depression on health care costs fo... more To assess the impact of pain severity and time to diagnosis of depression on health care costs for primary care patients with pre-existing unexplained pain symptoms who subsequently received a diagnosis of depression. Patients and methods: This retrospective cohort study analyzed 4000 adults with unexplained pain (defined as painful physical symptoms [PPS] without any probable organic cause) and a subsequent diagnosis of depression, identified from the UK General Practice Research Database using diagnostic codes. Patients were categorized into four groups based on pain severity (milder or more severe; based on number of pain-relief medications and use of opioids) and time to diagnosis of depression (#1 year or .1 year from PPS index date). Annual health care costs were calculated (2009 values) and included general practitioner (GP) consultations, secondary care referrals, and prescriptions for pain-relief medications for the 12 months before depression diagnosis and in the subsequent 2 years. Multivariate models of cost included time period as a main independent variable, and adjusted for age, gender, and comorbidities. Results: Total annual health care costs before and after depression diagnosis for the four patient groups were higher for the groups with more severe pain (£819-£988 versus £565-£628; P , 0.001 for all pairwise comparisons) and highest for the group with more severe pain and longer time to depression diagnosis in the subsequent 2 years (P , 0.05). Total GP costs were highest in the group with more severe pain and longer time to depression diagnosis both before and after depression diagnosis (P , 0.05). In the second year following depression diagnosis, this group also had the highest secondary care referral costs (P , 0.01). The highest drug costs were in the groups with more severe pain (P , 0.001), although costs within each group were similar before and after depression diagnosis. Conclusion: Among patients with unexplained pain symptoms, significant pain in combination with longer time from pain symptoms to depression diagnosis contribute to higher costs for the UK health care system.
Purpose: Medication nonadherence is common in the treatment of patients with severe mental illnes... more Purpose: Medication nonadherence is common in the treatment of patients with severe mental illness and is a frequent cause of relapse. Different formulations have been developed in an effort to improve medication adherence. The aim of this study was to explore whether there are differential clinical outcomes between two different formulations of olanzapine (orodispersible tablets [ODTs] vs standard oral tablets [SOT]) for the treatment of nonadherent patients with schizophrenia or bipolar disorder. Methods: Data for this analysis were from an observational study conducted in Europe (N=903). Adult schizophrenia and bipolar disorder patients in outpatient settings who initiated or changed to either olanzapine ODT or SOT according to physician decision within the last 45 days were eligible for enrollment. The follow-up period was 1 year. Of the 903 participants, 266 nonadherent patients (Medication Adherence Rating Scale score 0-4 at baseline) were included in the analysis. Clinical outcomes of interest were: 1) hospitalization and 2) relapse identified by the participating psychiatrist or hospitalization. An adjusted logistic regression model was fitted. Results: Patients taking ODT had more severe illness at baseline (P,0.001) as assessed with the Clinical Global Impression with mean (standard deviation [SD]) scores of ODT 4.63 (1.03) and SOT 4 (1.16). In the regression models adjusted for potential confounders, patients taking ODT had significantly lower odds for hospitalization (odds ratio =0.355; 95% confidence interval =0.13-0.974) and relapse or hospitalization (odds ratio =0.368; 95% confidence interval =0.183-0.739), respectively. Conclusion: Nonadherent patients with schizophrenia or bipolar disorder treated with the orodispersible formulation were less likely to be hospitalized or suffer relapse compared to those patients taking the standard oral coated tablets.
Objectius: Els objectius generals d'aquesta tesi son descriure l'evolucio dels pacients a... more Objectius: Els objectius generals d'aquesta tesi son descriure l'evolucio dels pacients amb esquizofrenia durant tres anys de seguiment i analitzar les diferencies entre regions del mon amb diferents nivells de desenvolupament. Els objectius especifics son: • Descriure la frequencia de resposta al tractament en pacients ambulatoris amb esquizofrenia en diferents regions del mon. • Analitzar les caracteristiques demografiques (edat, sexe, estat civil) i els factors clinics (edat d'inici, temps d'evolucio, gravetat de la malaltia, funcionament) associades a la resposta clinica. • Descriure la frequencia de la remissio clinica i funcional en pacients ambulatoris amb esquizofrenia en diferents regions del mon. • Analitzar les caracteristiques demografiques (edat, sexe, estat civil) i els factors clinics (edat d'inici, temps d'evolucio, gravetat de la malaltia, funcionament) associats a la remissio clinica i funcional. Metodes: La base de dades de l'estudi Wor...
Background: Hospitalization is a costly and distressing event associated with relapse during schi... more Background: Hospitalization is a costly and distressing event associated with relapse during schizophrenia treatment. No information is available on the predictors of hospitalization during maintenance treatment with olanzapine long-acting injection (olanzapine-LAI) or how the risk of hospitalization differs between olanzapine-LAI and oral olanzapine. This study aimed to identify the predictors of psychiatric hospitalization during maintenance treatment with olanzapine-LAI and assess ed four parameters: hospitalization prevalence, incidence rate, duration, and the time to first hospitalization. Olanzapine-LAI was also compared with a sub-therapeutic dose of olanzapine-LAI and with oral olanzapine. Methods: This was a post hoc exploratory analysis of data from a randomized, doubleblind study comparing the safety and efficacy of olanzapine-LAI (pooled act ive depot groups: 405 mg/4 weeks, 300 mg/2 weeks, and 150 mg/2 weeks) with oral olanzapine and sub-therapeutic olanzapine-LAI (45 m...
To investigate the impact of anxiety symptoms on depression outcomes in Asian patients with major... more To investigate the impact of anxiety symptoms on depression outcomes in Asian patients with major depressive disorder (MDD) (n=714). The 17-item Hamilton Depression Scale (HAMD-17), overall severity, somatic symptoms, and quality of life (QOL) (EuroQOL Questionnaire-5 Dimensions [EQ-5D]) were assessed at baseline and 3 months. Anxiety was measured using items 10 and 11 from the HAMD-17. Linear, tobit, and logistic multiple regression models analyzed the impact of anxiety symptoms on outcomes. Baseline anxiety was related to age and the presence of pain symptoms at baseline. Regression models showed that a higher level of anxiety was associated with a lower frequency of remission and lower QOL at 3 months. Patients with lower baseline anxiety symptoms had higher remission rates (odds ratio for each point of anxiety symptoms, 0.829 [95% confidence interval [CI]: 0.723-0.951]). Patients with higher levels of baseline anxiety had a lower QOL at 3 months (a decrease in EQ-5D tariff score...
Many patients with schizophrenia and bipolar disorder have impaired insight and low medication ad... more Many patients with schizophrenia and bipolar disorder have impaired insight and low medication adherence. The aim of this post hoc analysis was to explore the relationship between insight and medication adherence. We included 903 patients with schizophrenia or bipolar disorder who participated in an observational study conducted in Europe on the outcomes of patients treated with two oral formulations of olanzapine over a 1-year period. Evaluations included Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), insight (Scale to Assess Unawareness of Mental Disorder, SUMD) medication adherence (Medication Adherence Rating Scale, MARS), and therapeutic alliance (Working Alliance Inventory, WAI). Medication adherence was higher in bipolar patients (mean MARS score (SD) 6.5 (2.8) versus 5.8 (2.7) in schizophrenia; p < 0.001). Patients with schizophrenia had lower insight (i.e., SUMD item 1, unawareness of mental disorder, mean (SD) of 2.5 (1.3) in schizophrenia ver...
To carry-out a cost-effectiveness analysis (CEA) of the effect of Pregabalin (PGB) versus usual c... more To carry-out a cost-effectiveness analysis (CEA) of the effect of Pregabalin (PGB) versus usual care in refractory outpatients with Generalized Anxiety Disorder (GAD) treated according with usual medical practice in Mental Health Centers in Spain. METHODS: CEA was carried-out by means of a nested case-control design which used secondary data extracted at random from a 6-month cohort prospective observational study (the ADAN study) conducted to ascertain cost-of-illness in GAD (DSM-IV criteria). Refractory subjects were those who claimed of persistent symptoms of anxiety and showed suboptimal response (HAM-Anxiety scale 16) after a course of standard doses of any anti-anxiety drug, alone or in combination, for 6 months. At baseline, patients could switch to PGB (monotherapy or add-on) or to usual care, alone or in combination, which were considered cases and controls respectively. Health outcomes included quality-adjusted life years (QALYs) gain by EQ-5D. A 3 rd-payer perspective was chosen for the CEA analysis in year 2009. Sensitivity analysis was performed by bootstrapping techniques (10000 re-samples were obtained) in order to obtain a cost-effectiveness acceptability curve. RESULTS: A total of 858 refractory subjects (mean baseline HAM-A; score 25.7) were identified; 429 in each of the PGB and UC group. Compared with UC, PGB was associated with significant higher QALY gain after 6 months of treatment; 0.1225 0.0995 vs 0.1009 0.0938 (p 0.001), but significantly increased health care costs; a1,240.6 1,407.4 vs a931.4 940.2 (p 0.0001). The deterministic ICER ratio was a14,287 per QALY gained with a re-sampling ICER of a15,804 (95 CI: 15,064-16,545). The 90% of re-samples fold below a25,052 threshold and 95% a30,000. CONCLUSIONS: Despite the design of the primary study, this evaluation could suggest that pregabalin may be cost-effective in comparison with usual care in refractory outpatients with Generalized Anxiety Disorders managed in Mental Health Centers under usual medical practice in Spain.
To provide information on functional outcomes for patients with schizophrenia manifesting negativ... more To provide information on functional outcomes for patients with schizophrenia manifesting negative symptoms across five European countries. METHODS: Physicians in France, Germany, Italy, Spain, and the UK who prescribed antipsychotics for at least 15 patients with schizophrenia within the preceding 3 months were invited to complete a questionnaire concerning their patients' clinical status and functional performance. RESULTS: Data were obtained from 704 physicians treating a total of 6569 patients from France (n = 1492), Germany (n = 1439), Italy (n = 1002), Spain (n = 1310), and the UK (n = 1326). Physicians rated patient symptoms on a 5-point scale as either predominated by or with a high level of positive symptoms (38%), predominated by or with a high level of negative symptoms (32%), or not dominated by either type of symptom (22%). Physicians did not rate 8% of patients using this scale. Patients with a predominance of negative symptoms were rated as having significantly greater functional impairment than those with predominant positive symptoms as measured by physician ratings on the Global Assessment of Functioning scale (P < 0.01) and on 5-point global numerical ratings of overall function, cognitive function, and patients' overall ability to meet their own needs (P < 0.01). In addition, 57% of patients in whom negative symptoms predominated required a caregiver, compared with 49%-50% of patients in other symptom categories. CONCLUSIONS: In this large, multinational, cross-sectional physician survey, patients with schizophrenia in whom negative symptoms predominated had levels of functional impairment at least as great as, if not greater than, those for patients in whom positive symptoms predominated. These results suggest that additional attention should be given to effectively treating the persistent negative symptoms present in many patients with schizophrenia.
Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Centra... more Publish with Bio Med Central and every scientist can read your work free of charge "BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime."
Purpose: To describe pharmacological treatment patterns in Asian patients with major depressive d... more Purpose: To describe pharmacological treatment patterns in Asian patients with major depressive disorder (MDD), including duration of treatment, reasons for medication discontinuation, rate of medication nonadherence, factors associated with medication nonadherence, and impact of medication nonadherence on depression outcomes. Patients and methods: Data were from a prospective, observational 3-month study of East Asian MDD inpatients from 40 sites in six East Asian countries who initiated antidepressant treatment at baseline (n=569). Assessments included the Clinical Global Impression-Severity scale (CGI-S), 17-item Hamilton Depression Rating Scale (HAMD-17), painful physical symptoms, response and remission, employment status, quality of life (QoL) (EuroQOL Questionnaire-5 Dimensions [EQ-5D]) and health state using the visual analog scale, adherence by clinician opinion, and patient self-report. Cox proportional hazards modeling, Kaplan-Meier survival analysis, and regression modeling were employed. Results: Median time to discontinuation for any reason was 70 days (95% confidence interval: 47; 95). Reasons for discontinuation were inadequate response in 64.1%, nonadherence in 6.2%, and adverse events in 4.1%; 25.6% who discontinued experienced an adequate response to treatment. In those patients who had an adequate response, age and country were significantly associated with time to medication discontinuation. Patient-reported nonadherence was 57.5% and clinician-reported nonadherence was 14.6% (62/426). At 3 months, nonadherent patients had significantly higher disease severity (CGI-S, P=0.0001; HAMD-17, P0.0001), lower QoL ratings (EQ-5D tariff, P=0.0007; EQ-5D visual analog scale, P=0.0024), and lower response and remission rates (both P0.0001) compared with adherent patients. The odds of response and remission were greater among adherent patients. Conclusion: Early discontinuation of antidepressants among Asian MDD patients was high. A total of 25.6% who discontinued prematurely were experiencing an adequate response to treatment. Nonadherent patients had significantly higher disease severity, lower QoL ratings, and lower response and remission rates compared with adherent patients.
long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanz... more long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection Background: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI), and whether observed changes differ from those seen with oral olanzapine. Methods: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264) with daily oral olanzapine (10 mg/day; n=260). Levels of functioning were assessed with the Heinrichs-Carpenter Quality of Life Scale. Functional status was also classified as "good", "moderate", or "poor", using a previous data-driven approach. Changes in functional levels were assessed with McNemar's test and comparisons between olanzapine-LAI and oral olanzapine employed the Student's t-test. Results: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score) from 64.0-70.8 (P0.001). Patients on oral olanzapine also increased their level of functioning from 62.1-70.1 (P0.001). At baseline, 19.2% of the olanzapine-LAI-treated patients had a "good" level of functioning, which increased to 27.5% (P0.05). The figures for oral olanzapine were 14.2% and 24.5%, respectively (P0.001). Results did not significantly differ between olanzapine-LAI and oral olanzapine. Conclusion: In this 2-year, open-label, randomized study of olanzapine-LAI, outpatients with schizophrenia maintained or improved their favorable baseline level of functioning over time. Results did not significantly differ between olanzapine-LAI and oral olanzapine.
Background: Bipolar disorder (BD) is characterized by episodes of mania and depression. The debil... more Background: Bipolar disorder (BD) is characterized by episodes of mania and depression. The debilitating symptoms during an acute episode require intensive treatment, frequently leading to inpatient psychiatric care, which places significant demands on health and social care systems and incurs substantial costs. However, no study to date has estimated the economic impact of relapse. Objectives: To estimate the direct costs associated with relapse in the treatment of BD following an acute manic or mixed episode over a 21-month follow-up period in routine clinical practice in Europe, using data from a large, prospective, observational study. Methods: EMBLEM was a prospective, observational study on the outcomes of patients with a manic/mixed episode of BD conducted in 14 European countries. Patients eligible for analysis were those enrolled in the 21-month maintenance phase of the study, following the 3-month acute phase. Relapse was defined as achieving any one of the following criteria: (i) at least a onepoint increase in Clinical Global Impression-Bipolar Disorder (CGI-BP) overall score from the previous visit, with a final rating of ‡4; (ii) inpatient admission for an acute episode of BD; or (iii) psychiatrists' confirmation of relapse. Data on healthcare resource use were recorded retrospectively for the four respective periods (3-6, 6-12, 12-18 and 18-24 month visits). Multivariate analyses were performed to compare the cost of resource use (inpatient stay, day care, psychiatrist visits and medication) for those who relapsed during the 21-month maintenance phase and those who never relapsed. A sensitivity analysis was also conducted to examine the 6-month costs during relapse. The analyses were adjusted for patient characteristics and took account of non-Normality of the cost data by using a log link
ical trials registries, and EMA reports. We extracted data for depression severity (mean differen... more ical trials registries, and EMA reports. We extracted data for depression severity (mean differences or related statistics) on the primary comparisons of 1) agomelatine 25 mg/day versus placebo, and 2) agomelatine 25 mg/day versus any SSRI. We calculated Hedges' g effect size for each trial and combined them by the inverse variance method assuming a random effects model. Two meta-analyses were conducted: one with the results of published and unpublished trials and the other only with results of published trials. RESULTS: Ten trials (5 unpublished) gave data on the efficacy of agomelatine versus placebo. Overall, the results were homogeneous (I 2 ϭ 9.2%), and showed agomelatine was better than placebo for reducing the severity of depression at 8 weeks (g ϭ-0.18; 95% CI ϭ-0.25 to-0.10; p Ͻ0.0001). However when the analysis was restricted to published trials the effect size was 45% overestimated (g ϭ-0.26; 95% CI ϭ-0.36 to-0.15; p Ͻ 0.0001; I 2 ϭ 3.4%). 7 trials (4 unpublished) gave data on the comparison of agomelatine versus any SSRI. There was no difference in efficacy with all trials combined (g ϭ 0.01; 95% CI ϭ-0.16 to 0.18; p ϭ 0.87), but agomelatine significantly outperformed SSRIs in the subset of published trials (g ϭ-0.17; 95%
Atypical antipsychotic agents are considered the first-line treatment of schizophrenia. Aim of pr... more Atypical antipsychotic agents are considered the first-line treatment of schizophrenia. Aim of present study was to identify factors affecting the cost of schizophrenia treatment with atypical antipsychotic agents. METHODS: A retrospective database study was conducted in three public hospitals in Hong Kong. Patients initiated on atypical antipsychotic agents (amisulpride, olanzapine, quetiapine and risperidone) between March 2003 and September 2003 for treatment of schizophrenia for at least three months was recruited. Patient medical records were reviewed for up to 12 months before and after initiation date of the antipsychotic agents to retrieve baseline demographic and clinical factors and health care resource utilization for schizophrenia. A multiple regression model was used to identify demographic, clinical factors and choice of atypical antipsychotic agents with significant association to health care resource utilization. RESULTS: Eighty-two patients were included in the analysis. Thirty-four (41%) patients were male and mean age was 43 ± 14 years. The mean cost per patient per month was USD 431 ± 914 (1USD = 7.8HKD). Three factors were associated with direct medical cost of health care resource utilized: 1). History of drug abuse (RR = 1.26; 95% CI = 1.05-1.52); 2). prior use of depot antipsychotic (RR = 1.22; 95% CI = 1.05-1.42); and 3). previous duration of hospitalization before initiation of atypical antipsychotic therapy (RR = 1.00; 95% CI = 1.00-1.01). CONCLUSION: History of drug abuse, prior use of depot antipsychotic, previous duration of hospitalization appeared to be influential to direct medical cost of atypical antipsychotic treatment. The choice of antipsychotic agents did not appear to affect the cost of treatment.
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