Effect of galcanezumab in women with episodic migraine meeting criteria for menstrually related migraine: A post hoc analysis of EVOLVE-1 and EVOLVE-2.

BACKGROUND: We evaluated galcanezumab for migraine prevention in patients who met International Classification of Headache Disorders, 3rd edition criteria for menstrually related migraine (MRM). METHODS: Patients were identified post hoc from three double-blind, randomized, phase 3 clinical trials in patients with episodic migraine. Patients completed a 1-month prospective baseline period and up to 6 months (EVOLVE-1 and -2, studies pooled) of double-blind treatment with galcanezumab (120 mg/month) or placebo. Menses and headache information were recorded by electronic daily diary. Patients with a migraine attack starting during the 5-day perimenstrual interval (first day of bleeding ± 2 days) for ≥2 of their first three diary-recorded menstrual cycles were categorized as having MRM. The primary efficacy measure was mean change in monthly migraine headache days from baseline, averaged over Months 4 through 6. Response rates, change in monthly perimenstrual migraine headache days, monthly non-perimenstrual migraine headache days, and quality of life were also assessed. RESULTS: Post hoc MRM analysis criteria were met by 462/1133 women (41%). Mean (standard deviation) baseline monthly migraine headache days were 9.7 (±3.1; n = 146) for galcanezumab-treated patients and 9.6 (±2.8; n = 316) for placebo-treated patients. The mean change (standard error [SE]) in migraine headache days over Months 4 through 6 was -5.1 days (±0.39) for galcanezumab versus -3.2 (±0.35) for placebo (p < 0.001). The mean change (SE) in perimenstrual migraine headache days over Months 4 through 6 was -0.75 days (±0.08) for galcanezumab versus -0.49 (±0.07) for placebo (p = 0.004). For migraine headache days outside the perimenstrual period, the mean change in migraine headache days was -4.6 (±0.38) for galcanezumab and -2.8 (±0.33) for placebo (p < 0.001). Improvements in response rates and the Migraine-Specific Quality of Life Questionnaire were also observed over Months 4 through 6. CONCLUSION: Galcanezumab was effective for migraine prevention in women with MRM.

Relative efficacy of lasmiditan versus rimegepant and ubrogepant as acute treatments for migraine: network meta-analysis findings.

BACKGROUND: In the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to explore the relative efficacy of lasmiditan (serotonin [5-hydroxytryptamine] 1F receptor agonist) versus rimegepant and ubrogepant (calcitonin gene-related peptide antagonists) for the acute oral treatment of migraine through network meta-analysis (NMA). METHODS: Data included in the NMA were identified through a systematic literature search (conducted April 2018, updated May/December 2020) of phase II-IV, randomised controlled trials (RCTs) in adults with chronic/episodic migraine with/without aura. Treatments included: lasmiditan 50, 100, 200 mg; rimegepant 75 mg; ubrogepant 25, 50, 100 mg. Pairwise treatment comparisons from Bayesian fixed-effect/random-effects NMA, adjusted by baseline risk where appropriate, were conducted. Comparisons were reported as odds ratios with 95% credible intervals. Early-onset efficacy endpoints included: pain freedom at 2 hours and pain relief at 1 and 2 hours. Adverse drug reaction (ADR) profiles were summarised. Heterogeneity and inconsistency in the network were explored; sensitivity analyses investigated robustness of findings. RESULTS: Across 12 RCTs included in the base case, females represented >80% of included patients (mean age 37.9-45.7 years). Odds of achieving both pain freedom and pain relief at 2 hours were higher with lasmiditan 100 and 200 mg versus rimegepant 75 mg and ubrogepant 25 and 50 mg. Results for pain relief at 1 hour were consistent with those at 2 hours, but fewer comparisons were available. There were no statistically significant differences between lasmiditan 50 mg and ubrogepant or rimegepant for any outcome. Sensitivity analyses were in the same direction as base case analyses. Most commonly reported ADRs (incidence ≥2%) were: dizziness, fatigue, paraesthesia, sedation, nausea/vomiting and muscle weakness with lasmiditan; nausea with rimegepant; and nausea, somnolence and dry mouth with ubrogepant. CONCLUSIONS: The efficacy findings of this indirect comparison indicate that lasmiditan 100 mg or 200 mg might be an appropriate acute treatment option for patients with migraine seeking a fast onset of action. Differently from rimegepant and ubrogepant, lasmiditan use is associated with mainly neurological events, which are mostly mild or moderate in severity and self-limiting. 350/350 words.

Persistence, use of resources and costs in patients under migraine preventive treatment: the PERSEC study.

BACKGROUND: Migraine represents a serious burden for national health systems. However, preventive treatment is not optimally applied to reduce the severity and frequency of headache attacks and the related expenses. Our aim was to assess the persistence to traditional migraine prophylaxis available in Spain and its relationship with the healthcare resource use (HRU) and costs. METHODS: Retrospective observational study with retrospective cohort design of individuals with migraine treated with oral preventive medication for the first time from 01/01/2016 to 30/06/2018. One-year follow-up information was retrieved from the Big-Pac™ database. According to their one-year persistence to oral prophylaxis, two study groups were created and describe regarding HRU and healthcare direct and indirect costs using 95% confidence intervals (CI). The analysis of covariance (ANCOVA) was performed as a sensitivity analysis. Patients were considered persistent if they continued on preventive treatment until the end of the study or switched medications within 60 days or less since the last prescription. Non-persistent were those who permanently discontinued or re-initiated a treatment after 60 days. RESULTS: Seven thousand eight hundred sixty-six patients started preventive treatment (mean age (SD) 48.2 (14.8) and 80.4% women), of whom 2,545 (32.4%) were persistent for 6 months and 2,390 (30.4%) for 12 months. Most used first-line preventive treatments were antidepressants (3,642; 46.3%) followed by antiepileptics (1,738; 22.1%) and beta-blockers (1,399; 17.8%). The acute treatments prescribed concomitantly with preventives were NSAIDs (4,530; 57.6%), followed by triptans (2,217; 28.2%). First-time preventive treatment prescribers were mostly primary care physicians (6,044; 76.8%) followed by neurologists (1,221; 15.5%). Non-persistent patients required a higher number of primary care visits (mean difference (95%CI): 3.0 (2.6;3.4)) and days of sick leave (2.7 (0.8;4.5)) than the persistent ones. The mean annual expenditure was €622 (415; 829) higher in patients who not persisted on migraine prophylactic treatment. CONCLUSIONS: In this study, we observed a high discontinuation rate for migraine prophylaxis which is related to an increase in HRU and costs for non-persistent patients. These results suggest that the treatment adherence implies not only a clinical benefit but also a reduction in HRU and costs.

Cluster-randomized, controlled 12-month trial to evaluate the effect of a parental psychoeducation program on medication persistence in children with attention-deficit/hyperactivity disorder.

BACKGROUND: This multicenter, cluster-randomized, nonblinded study evaluated the effect of parental psychoeducation on medication persistence among children and adolescents with newly diagnosed attention-deficit/hyperactivity disorder (ADHD). METHODS: Patients received standard medication alone or medication plus a parental psychoeducation program, and were followed for 12 months. The primary endpoint was time to withdrawal or termination of medication due to any cause. Secondary endpoints included change in ADHD symptom severity, functional outcome, program satisfaction, and safety. RESULTS: A total of 208 patients completed the study, which was terminated early because recruitment had ceased. At 12 months, there was no significant difference between the psychoeducation and control groups in the proportion of patients who discontinued pharmacologic treatment (13.2% versus 14.3%, respectively; size effect -0.3, P=0.34; hazard ratio 0.72, 95% confidence interval 0.36-1.43). Psychoeducation was associated with a significantly greater improvement in ADHD symptoms but not in functional outcome. Parental satisfaction with psychoeducation was high, and satisfaction with pharmacologic treatment was significantly greater in the psychoeducation group. There were no safety concerns. CONCLUSION: No significant advantage for parental psychoeducation plus medication over medication alone in terms of time to medication withdrawal was observed. Psychoeducation had inconsistent but interesting effects on other outcomes.

Residual symptoms and functioning in depression, does the type of residual symptom matter? A post-hoc analysis.

BACKGROUND: The degrees to which residual symptoms in major depressive disorder (MDD) adversely affect patient functioning is not known. This post-hoc analysis explored the association between different residual symptoms and patient functioning. METHODS: Patients with MDD who responded (≥50% on the 17-item Hamilton Rating Scale for Depression; HAMD-17) after 3 months of treatment (624/930) were included. Residual core mood-symptoms (HAMD-17 core symptom subscale ≥1), residual insomnia-symptoms (HAMD-17 sleep subscale ≥1), residual anxiety-symptoms (HAMD-17-anxiety subscale ≥1), residual somatic-symptoms (HAMD-17 Item 13 ≥1), pain (Visual Analogue Scale ≥30), and functioning were assessed after 3 months treatment. A stepwise logistic regression model with normal functioning (Social and Occupational Functioning Assessment Scale ≥80) as the dependent variable was used. RESULTS: After 3 months, 59.5% of patients (371/624) achieved normal functioning and 66.0% (412/624) were in remission. Residual symptom prevalence was: core mood symptoms 72%; insomnia 63%; anxiety 78%; and somatic symptoms 41%. Pain reported in 18%. Factors associated with normal functioning were absence of core mood symptoms (odds ratio [OR] 8.7; 95% confidence interval [CI], 4.6-16.7), absence of insomnia symptoms (OR 1.8; 95% CI, 1.2-2.7), episode length (4-24 weeks vs. ≥24 weeks [OR 2.0; 95% CI, 1.1-3.6]) and better baseline functioning (OR 1.0; 95% CI, 1.0-1.1). A significant interaction between residual anxiety symptoms and pain was found (p = 0.0080). CONCLUSIONS: Different residual symptoms are associated to different degrees with patient functioning. To achieve normal functioning, specific residual symptoms domains might be targeted for treatment.

Early response and remission as predictors of a good outcome of a major depressive episode at 12-month follow-up: a prospective, longitudinal, observational study.

OBJECTIVE: The goal of treating major depressive disorder (MDD) should be not only achieving remission in a particular episode but also avoiding relapses and attaining long-term recovery. The current study was designed to evaluate whether response and remission achieved within the first 6 weeks of antidepressant treatment are associated with a 12-month good outcome (achieving remission by 6 months and remaining in remission until the end of follow-up). METHOD: This prospective, longitudinal, multicenter study included adult outpatients who had a DSM-IV diagnosis of MDD, baseline scores ≥ 15 on the 17-item Hamilton Depression Rating Scale (HDRS(17)), Clinical Global Impressions-Severity of Illness scores ≥ 4, and a minimum remission period of 12 weeks between the index episode and the immediately prior episode (or who were in their first MDD episode). The primary efficacy measure was early response (a 50% decrease from baseline in HDRS(17) score by week 6). The secondary efficacy measure was early remission (HDRS(17) score ≤ 7 by week 6). RESULTS: Among the total of 930 patients included from December 2006 to June 2007, 38.2% showed early response, and 20.5% showed early remission. Of the early responders, 76.1% had a 12-month good outcome as compared to 81.1% of early remitters. Logistic regression showed that factors associated with a good outcome included early response (odds ratio [OR] = 4.14), being employed, and the absence of physical comorbidities. Early remission was also strongly associated with a good outcome (OR = 4.72). CONCLUSIONS: Either response or remission achieved by week 6 is the strongest prognostic factor for the 12-month good outcome of an episode of MDD.

Relapse and therapeutic interventions in a 1-year observational cohort study of nonadherent outpatients with schizophrenia.

OBJECTIVES: To evaluate the incidence rate of relapse, the clinical profiles, and the therapeutic interventions employed for patients with schizophrenia deemed as likely nonadherers to oral antipsychotic drugs. METHODS: A cohort of 597 outpatients whose therapy was modified because of a psychiatrist-perceived risk of nonadherence was followed for 12 months in an observational study. Baseline correlates of subsequent relapse were analyzed with Cox regression. RESULTS: At baseline, patients' mean (SD) age and time since diagnosis were 40.1 (11.1) and 15.2 (10.0) years, respectively; 63.7% were males. The Clinical Global Impression scale-Severity (CGI-S) score was ≥ 4 in 87.3% of the patients. Antipsychotic drugs were modified in 506 patients (84.8%); nonpharmacologic therapies were modified in 190 patients (31.8%). In both cases, the primary reason for the modifications was insufficient efficacy of current therapeutic regimen. The proportion of patients in oral antipsychotic monopharmacy decreased from 83.8% to 57.6%; 15.4% started long-acting (depot) formulations. Over the 12-month observation period, 90 patients (15.1%) relapsed. The hazard rate of relapse was higher in patients with substance use disorder or familial psychiatric antecedents and lower in patients who underwent modifications of nonpharmacological therapies or with negative attitude toward antipsychotic medication at baseline. CONCLUSIONS: Effective interventions to prevent relapse in patients with long-standing schizophrenia involving therapeutic challenges related to nonadherence are feasible. Rationale for the baseline correlates, and cues for clinical prevention of relapse in these patients are provided.

Functional impairment related to painful physical symptoms in patients with generalized anxiety disorder with or without comorbid major depressive disorder: post hoc analysis of a cross-sectional study.

BACKGROUND: Generalized anxiety disorder (GAD) is the most frequent anxiety disorder in primary care patients. It is known that painful physical symptoms (PPS) are associated with GAD, regardless the presence of comorbid major depressive disorder (MDD). However the specific role of such symptoms in patients' functional impairment is not well understood. The objective of the present study is to assess functional impairment related to the presence of PPS in patients with GAD. METHODS: This is a post hoc analysis of a cross-sectional study. Functioning, in the presence (overall pain score >30; Visual Analog Scale) or absence of PPS, was assessed using the Sheehan Disability Scale (SDS) in three groups of patients; 1) GAD and comorbid MDD (GAD+MDD+), 2) GAD without comorbid MDD (GAD+MDD-), 3) controls (GAD-MDD-). ANCOVA models were used. RESULTS: Of those patients with GAD+MDD+ (n = 559), 436 (78.0%) had PPS, compared with GAD+MDD- (249 of 422, 59%) and controls (95 of 336, 28.3%). Functioning worsened in both GAD groups in presence of PPS (SDS least squares mean total score: 16.1 vs. 9.8, p < 0.0001, GAD+MDD+; 14.3 vs. 8.2, p < 0.0001, GAD+MDD-). The presence of PPS was significantly associated with less productivity. CONCLUSIONS: Functional impairment related to the presence of PPS was relevant. Clinical implications should be considered.

Optimal cutoff point of the Hamilton Rating Scale for Depression according to normal levels of social and occupational functioning.

The main goal in the treatment of major depressive disorder (MDD) is to achieve remission, defined as the resolution of symptoms and the return to normal levels of functionality. However, the clinical assessment of remission is usually merely based on scores of symptomatic rating scales. One of the most widely used scales to measure remission is the HAM-D(17), in which remission is defined as a score ≤ 7. Nevertheless, several studies have shown that this cutoff could be too high when also functioning is considered. This is a post-hoc analysis of a 6-month prospective study, performed over a sample of 292 Spanish patients with MDD, in order to find the optimal cutoff in the HAM-D(17) scale, considering normal levels of functionality, evaluated by the SOFAS; by means of plotting Receiver Operating Characteristics (ROC) curves. Our results show that a score of ≤ 5 maximized both sensitivity and specificity for identifying normal levels of functionality with respect to other scores, and thus agree with previous works, which suggest that a cutoff ≤ 7 might be too high to consider remission in patients with MDD, when normal levels of functioning are taken into account.

Treatment patterns and health care resource utilization in a 1-year observational cohort study of outpatients with schizophrenia at risk of nonadherence treated with long-acting injectable antipsychotics.

PURPOSE: To describe (1) the clinical profiles and the patterns of use of long-acting injectable (LAI) antipsychotics in patients with schizophrenia at risk of nonadherence with oral antipsychotics, and in those who started treatment with LAI antipsychotics, (2) health care resource utilization and associated costs. PATIENTS AND METHODS: A total of 597 outpatients with schizophrenia at risk of nonadherence, according to the psychiatrist's clinical judgment, were recruited at 59 centers in a noninterventional prospective observational study of 1-year follow-up when their treatment was modified. In a post hoc analysis, the profiles of patients starting LAI or continuing with oral antipsychotics were described, and descriptive analyses of treatments, health resource utilization, and direct costs were performed in those who started an LAI antipsychotic. RESULTS: Therapy modifications involved the antipsychotic medications in 84.8% of patients, mostly because of insufficient efficacy of prior regimen. Ninety-two (15.4%) patients started an LAI antipsychotic at recruitment. Of these, only 13 (14.1%) were prescribed with first-generation antipsychotics. During 1 year, 16.3% of patients who started and 14.9% of patients who did not start an LAI antipsychotic at recruitment relapsed, contrasting with the 20.9% who had been hospitalized only within the prior 6 months. After 1 year, 74.3% of patients who started an LAI antipsychotic continued concomitant treatment with oral antipsychotics. The mean (median) total direct health care cost per patient per month during the study year among the patients starting any LAI antipsychotic at baseline was €1,407 (€897.7). Medication costs (including oral and LAI antipsychotics and concomitant medication) represented almost 44%, whereas nonmedication costs accounted for more than 55% of the mean total direct health care costs. CONCLUSION: LAI antipsychotics were infrequently prescribed in spite of a psychiatrist-perceived risk of nonadherence to oral antipsychotics. Mean medication costs were lower than nonmedication costs.

Generalized anxiety disorder, with or without co-morbid major depressive disorder, in primary care: prevalence of painful somatic symptoms, functioning and health status.

BACKGROUND: Painful physical symptoms (PPS) have received little attention in patients with generalized anxiety disorder (GAD). The objective of the present study was to assess the prevalence of PPS in patients with GAD vs patients with GAD and co-morbid major depressive disorder (MDD) and a control group (patients neither with GAD nor MDD). METHODS: This is a cross-sectional, multi-center, epidemiological study, in primary care. Patients were screened for GAD (HADS-A), followed by a diagnosis confirmation (MINI). Patients were considered to have PPS when VAS overall pain score >30. Functioning and health status was assessed (SDS, EUROQoL-5D). Relationships between the presence of PPS and functioning and health status was analyzed (ANCOVA models). Results were adjusted for confounding factors. RESULTS: Of 7152 patients, 1546 (22%) screened positive for GAD, 981 (14%) had confirmed GAD diagnosis, of whom 559 (8%) had GAD with co-morbid MDD and 422 (6%) had GAD alone. Of the 5292 (74%) patients screened negative for GAD, 336 (5%) were confirmed as controls. PPS in patients with GAD were twice as prevalent as in the control group: 59.0% vs. 28.3%; p<0.001. The presence of co-morbid MDD was associated with a significantly higher prevalence of PPS: 78.0% vs. 59.0%; p<0.001. PPS were significantly associated with functioning and health status impairment (p<0.001) both in GAD alone and in GAD and co-morbid MDD compared with controls. LIMITATIONS: Results do not prove causal relationships. CONCLUSIONS: Our results support the clinical relevance of PPS in patients suffering from GAD; therefore they need to be considered when evaluating the patient.

Clinical evaluation of combined therapy for type 2 diabetes.

OBJECTIVE: Therapeutic guidelines recommend the combination of drugs as necessary to control type 2 diabetes (T2D). This research assessed the effectiveness of pioglitazone (Pio), metformin (Met) and sulfonylurea (SU) combinations in the routine clinical practice. RESEARCH DESIGN AND METHODS: A nationwide, 12-month prospective, observational cohort study was performed in 2294 patients with T2D (50.3% females, mean age: 61.1 years, mean body mass index: 30.2 kg/m(2), mean time since diagnosis: 8.5 years) who started, at the discretion of treating physician, oral antihyperglycaemic treatment with either Pio + SU, Pio + Met or SU + Met because of inadequate control with previous therapy. Fasting plasma glucose (FPG), glycohaemoglobin (HbA1c), lipids, blood pressure, and anthropometric parameters were measured, and 10-year cardiovascular risk was estimated. RESULTS: FPG, HbA1c and total cholesterol at baseline had mean values (184.6 mg/dl, 8.5% and 246.0 mg/dl, respectively) associated with an excess of micro- and macrovascular risk. The mean changes from baseline in the Pio + SU, Pio + Met and SU + Met cohorts were, respectively, -37.9, -32.7 and -25.8 mg/dl for FPG; -1.1, -1.0 and -0.7% for HbA1c; -30.7, -38.7 and -17.1 mg/dl for triglycerides; and +2.3, +2.5 and +0.6 mg/dl for HDL cholesterol. In consequence, the estimated 10-year cardiovascular risk decreased more in the Pio cohorts, particularly with Pio + Met (1.7% versus 1.4% Pio + SU and 1.0% SU + Met -Framingham equation- and 0.6% versus 0.4% SU + Met - Systematic Coronary Risk Evaluation model-). Related adverse events were significantly (p = 0.016) more frequent in Pio cohorts (4.7% with Pio + SU, 5.1% with Pio + Met) than in the SU + Met cohort (2.4%). CONCLUSIONS: In patients with T2D failing therapy, mostly SU or Met monotherapy, pioglitazone add-on treatment was associated with a significant improvement of micro- and macrovascular risk estimations. These results from real-life clinical conditions support the findings of prior randomised trials, although they should be interpreted with caution because of the observational, nonrandomised design.

[Prevalence of metabolic syndrome and consistency in its diagnosis in type 2 diabetic patients in Spain]. / Prevalencia del síndrome metabólico y grado de concordancia en su diagnóstico en pacientes con diabetes mellitus tipo 2 en España.

OBJECTIVE: To determine the prevalence of metabolic syndrome, the degree of consistency among World Health Organization (WHO), The Third Report National Cholesterol Education Program (NCEP-ATP III) and the International Diabetes Federation (IDF) diagnostic criteria and the relationship with cardiovascular risk in a Spanish population of patients with type 2 diabetes. MATERIAL AND METHODS: This descriptive, epidemiologic, multicenter and cross-sectional study included 1259 patients with type 2 diabetes. The primary variable was diagnosis of metabolic syndrome according to WHO, NCEP-ATP III and IDF criteria. RESULTS: The prevalence of metabolic syndrome was 71.5% (WHO), 78.2% (NCEP-ATP III), and 89.5% (IDF). The prevalence of metabolic syndrome was higher in sedentary diabetic patients (WHO=79.3%, NCEP-ATP III=86.2%, and IDF=93.9) than in those who exercised moderately (WHO=61.4%, NCEP-ATP III=73.2%, and IDF=85.5%, [p<0.001]). The percentage of patients with metabolic syndrome and moderate/high cardiovascular risk was 38.9% (WHO), 33.6% (NCEP-ATP III), and 30.1%, (IDF). Consistency among WHO, NCEP-ATP III and IDF criteria was low. Only comparison of WHO vs NCEP-ATP III criteria was acceptable (k=0.52 [0.46-0.58]). CONCLUSIONS: The prevalence of metabolic syndrome in patients with type 2 diabetes in Spain is high, even when the low consistency among WHO, NCEP-ATP III and IDF criteria is considered. A standard definition of metabolic syndrome, according to routine clinical practice, is needed. Cardiovascular risk is greater when OMS and NCEP-ATP III criteria are used for the diagnosis of metabolic syndrome compared with IDF criteria.

Recovery from schizophrenia: results from a 1-year follow-up observational study of patients in symptomatic remission.

OBJECTIVES: This report presents the results of an observational empirical clinical investigation about the prevalence and correlates of a proposed definition of recovery from schizophrenia in outpatients in Spain. METHODS: Of 1010 outpatients with schizophrenia (DSM-IV-TR), a subgroup of 452 patients in symptomatic remission (SR) was followed for 1 year. SR was defined according to Andreasen's severity criteria based on the Scales for the Assessment of Positive (SAPS) and Negative (SANS) Symptoms. A Global Assessment of Functioning scale score of >80 was considered to be indicative of adequate functioning (AF). Correlates of recovery were identified by logistic regression. RESULTS: At baseline, 103 (22.8%; N=452) patients fulfilled the recovery definition (SR + AF). After 1 year, 338 patients (89.9%; N=376) maintained SR. Among these, the proportion of patients in recovery increased to 27.1% (102 out of 376). Better premorbid adjustment (PA) and improved social cognition correlated with recovery at baseline. After 1 year, PA, duration of untreated psychosis (DUP), type of pharmacotherapy, attitudes toward medication, and variation of depressive symptoms and social cognition determined the likelihood of recovery. CONCLUSIONS: The proportion of patients in recovery increased among those fulfilling SR criteria. After 1 year, in addition to known factors like shorter DUP and better PA, social cognitive abilities and depressive symptoms were found to correlate with recovery.

Evaluation of patients' and parents' quality of life in a randomized placebo-controlled atomoxetine study in attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of this study was to demonstrate the superior efficacy of atomoxetine with respect to placebo and to compare parent and child perceptions of health-related quality of life (HRQoL). METHOD: This randomized, placebo-controlled, 12-week parallel clinical trial included 151 untreated children/adolescents with newly diagnosed attention-deficit/hyperactivity disorder (ADHD). Parents' and patients' reports of HRQoL were obtained separately using the Child Health and Illness Profile and compared using analysis of covariance. RESULTS: The ADHD Rating Scale baseline mean score was 39.21. Baseline HRQoL was perceived as considerably compromised by parents, especially in the risk avoidance and achievement domains (mean t-scores, 32.47 and 33.16, respectively), but less by children, and restricted to the achievement domain (mean t-score, 41.54). Atomoxetine improved HRQoL with respect to placebo in these two domains as assessed by parents (difference between adjusted mean changes and 95% confidence interval, 8.53, 4.05-13.00 and 3.39, 0.13-6.65) and in the risk avoidance domain by patients (3.56, 1.04-6.07). A modest correlation of clinical severity with HRQoL was found in this clinical population. CONCLUSIONS: This study confirms prior reports the impact of ADHD on the HRQoL of patients as assessed by their parents. The patients' perspective is of a lesser impact. Atomoxetine improved HRQoL as assessed by both parents and patients.

Remission in schizophrenia: results from a 1-year follow-up observational study.

OBJECTIVES: This study used the Remission in Schizophrenia Working Group operational-severity criteria to, a) provide descriptive data on prevalence and stability of symptomatic remission, b) attempt a criterion (concurrent) validation of this measure of remission, and c) explore correlates of remission stability. METHODS: From an unselected sample of 1010 stable outpatients with schizophrenia (DSM-IV-TR), a subgroup of 452 (44.8%) in symptomatic remission was followed for 1 year. Of these, 376 were re-evaluated in a research diagnostic assessment. In addition to relevant sociodemographic and clinical data, measures included symptoms, depression, functioning, social cognition, attitudes towards medication, and quality of life. Estimates of point prevalence are provided. Correlates of remission were identified by logistic regression. RESULTS: Symptomatic remission at baseline correlated with better premorbid adjustment, better social cognition, good treatment compliance, younger age, the absence of comorbid substance abuse, current or past participation in psychotherapy, and a lack of past participation in rehabilitation. After 1 year, 338 out of the 376 (89.9%) patients re-evaluated were found again in remission. In this assessment, better premorbid adjustment, good treatment compliance, and improvement of depressive symptoms and social cognition during follow-up again correlated with remission. CONCLUSIONS: The results of this study suggest that symptomatic remission (as defined above) has considerable criterion validity and is a realistic goal in the treatment of schizophrenia. Attaining and sustaining remission may warrant better clinical and functional outcomes for patients.

[Six-month effectiveness and tolerability of pioglitazone in combination with sulfonylureas or metformin for the treatment of type 2 diabetes mellitus]. / Efectividad y tolerabilidad a 6 meses de la pioglitazona en combinación con sulfonilureas o metformina en el tratamiento de la diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: Pioglitazone has been reported to improve common cardiovascular risk factors in addition to glycemic control in patients with type 2 diabetes mellitus (T2DM). The changes in cardiovascular risk profile were evaluated comparatively in large cohorts either treated or not with pioglitazone-containing combinations in the current clinical setting within Spain. PATIENTS AND METHOD: A nationwide prospective, controlled, observational cohort clinical study was performed in 2294 patients with T2DM who started, at the criterion of the treating physician, oral antihyperglycemic treatment with either pioglitazone plus a sulfonylurea (Pio+SU; n=851), pioglitazone plus metformin (Pio+Met; n=723) or a sulfonylurea plus metformin (SU+Met; n=720) due to inadequate control with previous therapy. Serum cholesterol, blood glucose, hemoglobin A1C, blood pressure and certain anthropometric parameters were measured at baseline and after 6 months of treatment. RESULTS: Serum high density lipoprotein-cholesterol increased in average (mg/dl) 2.08 with Pio+SU, 2.06 with Pio+Met and 0.67 with SU+Met; while triglycerides decreased (mg/dl) 26.6, 30.6 and 17.6 in the same cohorts. Inter-group differences were significant (p<0.001 in both parameters). Total cholesterol decreased significantly more with SU+Met than in the pioglitazone cohorts. Mean fasting plasma glucose and hemoglobin A1C reductions were significantly greater in the pioglitazone cohorts than in the SU+Met cohort: 27.74, 28.94 and 23.46 mg/dl (p=0.012); and 0.80, 0.87 and 0.71% (p=0.016) with Pio+SU, Pio+Met and SU+Met, respectively. Slight, but significant variations of body weight were also registered in the Pio+SU (+1.4 kg) and SU+Met (-0.7 kg) groups. CONCLUSIONS: Treatment with pioglitazone was associated with significant improvements of lipid and glycemic parameters that are linked to insulin resistance and cardiovascular risk in patients with T2DM in their routine clinical care. The non-randomised allocation of patients to treatments, inherent to its observational design, is an important limitation of the present study.

Prevalence, characteristics, and attribution of somatic symptoms in Spanish patients with major depressive disorder seeking primary health care.

BACKGROUND: Somatic symptoms (SS) tend to dominate clinical symptomatology in patients with depression in primary care. OBJECTIVE: The authors performed a cross-sectional nationwide epidemiological study on 1,150 primary-care patients with major depression and evaluated the prevalence of SS and physicians' attribution of their origin. METHOD: Patients were administered the Structured Polyvalent Psychiatric Interview. RESULTS: Ninety-three percent of patients had at least one SS fully or partially attributed to depression, and 45% of patients had four to nine. Painful symptoms, despite being the most frequent, were the least often attributed to depression (fewer than 25% of patients with pain) and significantly more often attributed to a combined origin. CONCLUSION: Results suggest that primary-care physicians tend to associate pain with depression to a significantly lesser extent than any other somatic symptom (e.g., cardiopulmonary or gastrointestinal). Therefore, special attention should be given to painful symptoms in order to ensure efficient management of depression in primary care.

Clinical characteristics of agitated psychotic patients treated with an oral antipsychotics attended in the emergency room setting: NATURA study.

Purpose. Prospective observational study to describe the clinical characteristics of patients with acute psychosis and agitation who receive oral psychopharmacological treatment at psychiatric emergency services (PES). Methods. A total of 278 patients with acute psychosis and agitation were admitted to PES and received oral psychopharmacological treatment. Diagnosis at admission, agitation level at entry and discharge, use of mechanical restraints, pharmacological and time to reintervention were prospectively explored. Severity of the disease was evaluated according to the Positive and Negative Syndrome Scale-Excitement Component (PANSS-EC), Agitation Calmness Evaluation Scale (ACES) and Clinical Global Impression-Severity (CGI-S) at admission, before first reintervention (if any) and at discharge from PES. Results. Most prevalent diagnoses were schizophrenia (77%) and bipolar disorder (12.2%). Mean (SD) scores in rating scales at baseline and at discharge were, respectively: PANSS-EC, 20.38(5.3) and 13.04 (5.5); CGI-S, 3.86(1.1) and 2.17(0.9); and ACES, 2.35(0.6) and 3.60(1.1). A total of 21.6% (60/278) of the patients required mechanical restraints and 38.1% (106/278) reintervention. From the emergency room, 20.5% patients went home while 71.2% were transferred to inpatient units. Conclusion. Clinical characteristics of psychotic agitated patients may help in deciding which type of treatment should be used and may be useful for the design of future prospective trials to explore treatment of agitation.

Worse quality of life for children with newly diagnosed attention-deficit/hyperactivity disorder, compared with asthmatic and healthy children.

OBJECTIVE: To evaluate the quality of life (QOL) of untreated children with newly diagnosed attention-deficit/hyperactivity disorder (ADHD), compared with asthmatic and healthy children. METHODS: This prospective, case-control study included a group of 120 children, 6 to 12 years of age, with newly diagnosed ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Subjects were matched according to age, gender, and health care area with 2 control groups, ie, 93 asthmatic children and 120 healthy children. Sociodemographic characteristics and Child Health Questionnaire scores were collected. RESULTS: The QOL of children with ADHD was rated worse than that of asthmatic or healthy children for most Child Health Questionnaire domains. The greatest differences were found in behavior, social limitations attributable to physical problems, emotional impact on parents, and family activities. Almost every psychosocial domain was more affected in comparison with asthmatic children and both psychosocial and physical domains in comparison with healthy children. CONCLUSIONS: ADHD interferes with the daily lives of children, parents, and families even more than asthma, primarily in areas related to psychosocial functioning, although evidence of impaired physical functioning also emerged. Delays in recognition, assessment, and management of ADHD may affect negatively the QOL of those children.