Impact of the COVID-19 Pandemic on Patients Affected by Non-Communicable Diseases in Europe and in the USA.

An international online patient community, Carenity, conducted a patient study in two independent waves among adults affected by non-communicable diseases (NCDs) in Europe and in the United States of America (USA). The study aimed to assess the real time impact of the coronavirus disease 2019 (COVID-19) on the medical conditions of patients with NCDs, their access to health care, and their adaptation to daily life as well as to describe their sources of information on COVID-19 and their needs for specific information and support. During the pandemic, 50% of the patients reported a worsening of their medical condition, and 17% developed a new disease. Additionally, 26% of the respondents reported an impact of the pandemic on regular/long-term treatment intake. 54% of the patients felt very or completely socially isolated and reported a strong impact of the COVID-19 pandemic on their stress level and state of mind, with higher levels observed in the USA compared to Europe. 59% of the respondents wished to have received additional information regarding the risks associated to their medical condition during the pandemic. Television was the most used source of information, whereas physicians were the most trusted one. This study describes the substantial impact of the COVID-19 pandemic on NCD patients.

Clustering patients by depression symptoms to predict venlafaxine ER antidepressant efficacy: Individual patient data analysis.

OBJECTIVE: To identify clusters of patients with major depressive disorder (MDD) based on the baseline 17-item Hamilton Rating Scale for Depression (HAM-D17) items and to evaluate the efficacy of venlafaxine extended release (VEN) vs placebo, and the potential effect of dose on efficacy, in each cluster. METHODS: Cluster analysis was performed to identify clusters based on standardized HAM-D17 item scores of individual patient data at baseline from 9 double-blind, placebo-controlled studies of VEN for MDD. Change from baseline in HAM-D17 total score was analyzed using a mixed-effects model for repeated measures for each cluster; response and remission rates at week 8 were analyzed using logistic regression. Discontinuation rates were also evaluated in each cluster. RESULTS: In 2599 patients, 3 patient clusters were identified, characterized as High modified Core (mCore) Symptoms/High Anxiety (cluster 1), High mCore Symptoms/Medium Anxiety (cluster 2), and Medium mCore Symptoms/Medium Anxiety (cluster 3). Significant effects of VEN vs placebo were observed on change from baseline in HAM-D17 total score at week 8 for both clusters 1 and 2 (both P < 0.001), but not for cluster 3. In cluster 3, a significant treatment effect of VEN was observed at week 8 in the lower-dose subgroup but not in the higher-dose subgroup. All-cause discontinuation rates were significantly higher in placebo than VEN in each cluster. CONCLUSIONS: Three unique clusters of patients were identified differing in baseline mCore symptoms and anxiety. Cluster membership may predict efficacy outcomes and contribute to dose effects in patients treated with VEN. CLINICAL TRIALS REGISTRATION: NCT01441440; other studies included in this analysis were conducted before the requirement to register clinical studies took effect.

The potential long-term impact of the COVID-19 outbreak on patients with non-communicable diseases in Europe: consequences for healthy ageing.

The early stages of the COVID-19 pandemic have focused on containing SARS-CoV-2 infection and identifying treatment strategies. While controlling this communicable disease is of utmost importance, the long-term effect on individuals with non-communicable diseases (NCD) is significant. Although certain NCDs appear to increase the severity of COVID-19 and mortality risk, SARS-CoV-2 infection in survivors with NCDs may also affect the progression of their pre-existing clinical conditions. Infection containment measures will have substantial short- and long-term consequences; social distancing and quarantine restrictions will reduce physical activity and increase other unhealthy lifestyles, thus increasing NCD risk factors and worsening clinical symptoms. Vitamin D levels might decrease and there might be a rise in mental health disorders. Many countries have made changes to routine management of NCD patients, e.g., cancelling non-urgent outpatient visits, which will have important implications for NCD management, diagnosis of new-onset NCDs, medication adherence, and NCD progression. We may have opportunities to learn from this unprecedented crisis on how to leverage healthcare technologies and improve procedures to optimize healthcare service provision. This article discusses how the COVID-19 outbreak and related infection control measures could hit the most frail individuals, worsening the condition of NCD patients, while further jeopardizing the sustainability of the healthcare systems. We suggest ways to define an integrated strategy that could involve both public institutional entities and the private sector to safeguard frail individuals and mitigate the impact of the outbreak.

Economic burden associated with inadequate antidepressant medication management among patients with depression and known cardiovascular diseases: insights from a United States-based retrospective claims database analysis.

Aims: The current study examined the association between insufficient major depressive disorder (MDD) care and healthcare resource use (HCRU) and costs among patients with prior myocardial infarction (MI) or stroke.Methods: This was a retrospective study conducted using the MarketScan Claims Database (2010-2015). The date of the first MI/stroke diagnosis was defined as the cardiovascular disease (CVD) index date and the first date of a subsequent MDD diagnosis was the index MDD date. Adequacy of MDD care was assessed during the 90 days following the index MDD date (profiling period) using 2 measures: dosage adequacy (average fluoxetine equivalent dose of ≥20 mg/day for nonelderly and ≥10 mg/day for elderly patients) and duration adequacy (measured as the proportion of days covered of 80% or higher for all MDD drugs). Study outcomes included all-cause and CVD-related HCRU and costs which were determined from the end of the profiling period until the end of study follow-up. Propensity-score adjusted generalized linear models (GLMs) were used to compare patients receiving adequate versus inadequate MDD care in terms of study outcomes.Results: Of 1,568 CVD patients who were treated for MDD, 937 (59.8%) were categorized as receiving inadequate MDD care. Results from the GLMs suggested that patients receiving inadequate MDD care had 14% more all-cause hospitalizations, 4% more all-cause outpatient visits, 17% more CVD-related outpatient visits, 13% more CVD-related emergency room (ER) visits, higher per patient per year CVD-related hospitalization costs ($21,485 vs. $17,756), higher all-cause outpatient costs ($2,820 vs. $2,055), and higher CVD-related outpatient costs ($520 vs. $434) compared to patients receiving adequate MDD care.Limitations: Clinical information such as depression severity and frailty, which are potential predictors of adverse CVD outcomes, could not be ascertained using administrative claims data.Conclusions: Among post-MI and post-stroke patients, inadequate MDD care was associated with a significantly higher economic burden.

Healthcare resource use and cost associated with timing of pharmacological treatment for major depressive disorder in the United States: a real-world study.

Background: Guidelines recommend selective serotonin reuptake inhibitors (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) as first-line treatments for major depressive disorder (MDD) and emphasize the importance of early pharmacological treatment as key factors to treatment success.Objectives: To compare the MDD-related healthcare resource utilization (HCRU) and cost among patients (1) with early vs late pharmacological treatment initiation and (2) achieving minimum therapeutic dose (MTD) early vs late.Methods: The MarketScan database (2010-2015) was used. Adults who were newly-treated with SSRI/SNRI within 12 months after the initial MDD diagnosis (index) were included. Patients who initiated SSRI/SNRI within 2 weeks of the index date were defined as early initiators; those who reached MTD within 4 weeks of index date were defined as early MTD achievers. MDD-related HCRU and costs per year after the index date were compared between early and late initiators and between early and late achievers using propensity score matching and generalized linear models.Results: Of the 55,539 patients, 60% were early initiators and 61% were early MTD achievers. The mean number of MDD-related outpatient visits per year were significantly higher for late initiator (6.7 vs 4.2, p < .001) and late MTD achievers (6.5 vs 4.5, p < .001) vs their early counterparts. Mean annual MDD-related outpatient, drug, and total cost were significantly higher for late initiators and MTD achievers vs the early groups.Conclusions: There is an opportunity to improve outcomes by treating MDD patients with SSRI/SNRI within 2 weeks and at or above the MTD within 4 weeks of diagnosis or less.

Efficacy of venlafaxine extended release in major depressive disorder patients: effect of baseline anxiety symptom severity.

Effects of baseline anxiety on the efficacy of venlafaxine extended release versus placebo were examined in a post hoc pooled subgroup analysis of 1573 patients enrolled in eight short-term studies of major depressive disorder. Anxiety subgroups were defined based on baseline 17-item Hamilton Rating Scale for Depression Item 10 score <3 (low) versus ≥3 (high). Change from baseline to final visit in Montgomery-Åsberg Depression Rating Scale total score and Montgomery-Åsberg Depression Rating Scale response and remission rates were analyzed. Change from baseline in Montgomery-Åsberg Depression Rating Scale total score and response and remission rates was significantly greater for venlafaxine extended release versus placebo in both low and high anxiety subgroups (all P < 0.0001). A statistically significant baseline anxiety by treatment interaction was observed for Montgomery-Åsberg Depression Rating Scale total score only (P = 0.0152). The adjusted mean change from baseline in Montgomery-Åsberg Depression Rating Scale total score was significantly greater in the high anxiety subgroup versus low anxiety subgroup for patients treated with venlafaxine extended release (-6.27 versus -3.89; P = 0.0440) but not placebo. These results support the efficacy of venlafaxine extended release for major depressive disorder treatment in patients with anxiety symptoms.

Cardiovascular hazards of insufficient treatment of depression among patients with known cardiovascular disease: a propensity score adjusted analysis.

Aims: The association between depression care adequacy and the risk of subsequent adverse cardiovascular disease (CVD) outcomes among patients with a previous diagnosis of myocardial infarction (MI) or stroke is not well defined. Methods and results: This retrospective cohort study used commercial claims data (2010-2015) and included adults with newly diagnosed and treated major depressive disorder (MDD) following an initial MI or stroke diagnosis. Depression care adequacy was assessed during the 3-month period following the MDD diagnosis index date using two measures: antidepressant dosage adequacy and duration adequacy. Cox models adjusted for the propensity of receiving adequate depression care were used to compare the risk of a composite CVD outcome (MI, stroke, congestive heart failure, and angina) as well as each individual CVD event between patients receiving adequate vs. inadequate depression care. A total of 1568 patients were included in the final cohort. Of these, 937 (59.8%) were categorized as receiving inadequate depression care based on at least one of the two treatment adequacy criteria. Propensity score adjusted Cox models showed that depression care inadequacy was associated with a significantly higher risk of the composite CVD endpoint [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39], stroke (HR 1.20, 95% CI 1.02-1.42), and angina (HR 1.95, 95% CI 1.21-3.16) with no significant interaction based on cohort included (MI vs. stroke) or the definition of inadequate depression (dose vs. duration inadequacy) (Pinteraction > 0.05). Conclusion: Inadequate MDD care was associated with a higher risk of adverse CVD events. These findings reveal a significant unmet clinical need in patients with post-MI or post-stroke MDD that may impact CVD outcomes.

Neuropathic pain responds better to increased doses of pregabalin: an in-depth analysis of flexible-dose clinical trials.

BACKGROUND: Pregabalin is an effective treatment option for many patients with neuropathic pain. Higher doses of pregabalin have been shown to be more effective in improving pain outcomes but, in practice, failing to appropriately increase the dose can leave patients under-treated. METHODS: This was a pooled analysis of 6 flexible-dose clinical trials of pregabalin in patients with neuropathic pain (diabetic peripheral neuropathy, peripheral herpetic neuralgia, posttraumatic pain, or postsurgical pain). Patients were divided into "dose pathway" groups based on their weekly pregabalin dose from the start of their trial to the first week of their maintenance phase. These were: 150 mg/day only; 150 to 300 mg/day; 150 to 300 to 450 mg/day; 150 to 300 to 450 to 600 mg/day; 150 to 300 to 600 mg/day; 300 to 600 mg/day. Pain outcomes assessed for each group at each new dose were proportion of 30% and 50% responders (≥30% or ≥50% reduction in mean pain score from baseline) and mean change in pain score. Percent change in mean pain score from baseline was assessed using a marginal structural model. RESULTS: Seven hundred and sixty-one patients treated with flexible-dose pregabalin were included in the analysis. For each dose pathway group, there was a notably greater proportion of 30% and 50% responders and change in pain score, at each escalating dose. As assessed by the marginal structural model, higher doses of pregabalin were estimated to result in a significantly greater change in mean pain score at each week. This dose response with flexible-dose pregabalin was consistent with that previously observed with fixed-dose pregabalin. CONCLUSION: Many patients who do not respond to lower doses of pregabalin will respond with notable improvements in pain outcomes when the dose is escalated. These data should encourage physicians treating patients with neuropathic pain to escalate pregabalin to the dose that delivers optimal analgesia and tolerable side effects.

Speed of Improvement in Symptoms of Depression With Desvenlafaxine 50 mg and 100 mg Compared With Placebo in Patients With Major Depressive Disorder.

PURPOSE/BACKGROUND: This post hoc analysis examined the time point at which clinically significant improvement in major depressive disorder (MDD) symptoms occurs with desvenlafaxine versus placebo. METHODS: Data were pooled from 9 short-term, double-blind, placebo-controlled studies in adults with MDD randomly assigned to desvenlafaxine 50 mg/d, 100 mg/d, or placebo. A mixed-effects model for repeated-measures analysis of change from baseline score was used to determine the time point at which desvenlafaxine treatment groups separated from placebo on the 17-item Hamilton Rating Scale for Depression and psychosocial outcomes. The association between early improvement and week 8 outcomes was examined using logistic regression analyses. Time to remission for patients with early improvement versus without early improvement was assessed using Kaplan-Meier techniques. Comparisons between groups were performed with log-rank tests. RESULTS: In the intent-to-treat population (N = 4279 patients: desvenlafaxine 50 mg/d, n = 1714; desvenlafaxine 100 mg/d, n = 870; placebo, n = 1695), a statistically significant improvement on the 17-item Hamilton Rating Scale for Depression was observed with desvenlafaxine 50 mg/d at week 1 (P = 0.0129) and with desvenlafaxine 100 mg/d at week 2 (P = 0.0002) versus placebo. Early improvement was a significant predictor of later remission. Treatment assignment, baseline depression scale scores, and race were significantly associated with probability of early improvement. On several measures of depressive symptoms and function, desvenlafaxine 50 mg/d and 100 mg/d separated from placebo as early as week 1 and no later than week 4 in patients with MDD. IMPLICATIONS/CONCLUSIONS: These findings suggest that clinicians may be able to use depression rating scale scores early in treatment as a guide to inform treatment optimization.

Efficacy of Desvenlafaxine Compared With Placebo in Major Depressive Disorder Patients by Age Group and Severity of Depression at Baseline.

PURPOSE: This post hoc meta-analysis evaluated the efficacy and safety of desvenlafaxine 50 and 100 mg versus placebo across age groups and severity of depression at baseline in patients with major depressive disorder. METHODS: Data from placebo and desvenlafaxine 50-mg and 100-mg dose arms were pooled from 9 short-term, placebo-controlled, major depressive disorder studies (N = 4279). Effects of age (18-40 years, >40 to <55 years, 55-<65 years, and ≥65 years) and baseline depression severity (mild, 17-item Hamilton Rating Scale for Depression total score [HAM-D17] ≤18; moderate, HAM-D17 >18 to <25; severe, HAM-D17 ≥25) on desvenlafaxine efficacy were assessed using analysis of covariance for continuous end points and logistic regression for categorical end points. FINDINGS: Desvenlafaxine-treated (50 or 100 mg/d) patients had significantly (P < 0.05, 2-sided) greater improvement in most measures of depression and function compared with placebo for patients 18 to 40 years, older than 40 to younger than 55 years, and 55 to younger than 65 years, with no significant evidence of an effect of age. Desvenlafaxine significantly improved most measures of depression and function in moderately and severely depressed patients. There was a significant baseline severity by treatment interaction for HAM-D17 total score only (P = 0.027), with a larger treatment effect for the severely depressed group. IMPLICATIONS: Desvenlafaxine significantly improved depressive symptoms in patients younger than 65 years and in patients with moderate or severe baseline depression. Sample sizes were not adequate to assess desvenlafaxine efficacy in patients 65 years or older or with mild baseline depression.

Early improvement with pregabalin predicts endpoint response in patients with generalized anxiety disorder: an integrated and predictive data analysis.

Generalized anxiety disorder (GAD), a common mental disorder, has several treatment options including pregabalin. Not all patients respond to treatment; quickly determining which patients will respond is an important treatment goal. Patient-level data were pooled from nine phase II and III randomized, double-blind, short-term, placebo-controlled trials of pregabalin for the treatment of GAD. Efficacy outcomes included the change from baseline in the Hamilton Anxiety Scale (HAM-A) total score and psychic and somatic subscales. Predictive modelling assessed baseline characteristics and early clinical responses to determine those predictive of clinical improvement at endpoint. A total of 2155 patients were included in the analysis (1447 pregabalin, 708 placebo). Pregabalin significantly improved the HAM-A total score compared with the placebo at endpoint, treatment difference (95% confidence interval), -2.61 (-3.21 to -2.01), P<0.0001. Pregabalin significantly improved HAM-A psychic and somatic scores compared with placebo, -1.52 (-1.85 to -1.18), P<0.0001, and -1.10 (-1.41 to -0.80), P<0.0001, respectively. Response to pregabalin in the first 1-2 weeks (≥20 or ≥30% improvement in HAM-A total, psychic or somatic score) was predictive of an endpoint greater than or equal to 50% improvement in the HAM-A total score. Pregabalin is an effective treatment option for patients with GAD. Patients with early response to pregabalin are more likely to respond significantly at endpoint.

An integrated analysis of the efficacy and safety of desvenlafaxine in the treatment of major depressive disorder.

The chronic course of major depressive disorder (MDD) often impedes the ability of patients to achieve full remission. Return of full functioning is a critical goal of antidepressant pharmacotherapy as the presence of residual depressive symptoms is associated with an increased risk of relapse. Treatment guidelines recommend selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, or atypical antidepressants as first-line treatment for moderate to severe MDD. Desvenlafaxine, administered as desvenlafaxine succinate, is an serotonin-norepinephrine reuptake inhibitor approved for the treatment of adults with MDD at the recommended dose of 50 mg/day. The aim of this integrated analysis was to assess the efficacy and safety of desvenlafaxine 50 and 100 mg/day compared with placebo in adult outpatients with MDD. The analysis used data from nine fixed-dose, short-term, placebo-controlled studies in adult outpatients diagnosed with MDD who had depressive symptoms for at least 30 days. Data from 4279 and 4317 patients were pooled for the efficacy and safety analyses, respectively. Statistically significant improvements were observed with desvenlafaxine 50 and 100 mg/day versus placebo for all efficacy endpoints assessed, including improvements in depressive symptoms, response and remission rates, as well as functional and cognitive outcomes. Treatment with desvenlafaxine 50 and 100 mg/day was generally safe and well tolerated. The findings of this integrated analysis of data from a large population of patients with MDD confirmed the antidepressant efficacy of both desvenlafaxine doses and add to previous evidence supporting the efficacy of desvenlafaxine.

How well do randomized controlled trial data generalize to 'real-world' clinical practice settings? A comparison of two generalized anxiety disorder studies.

The aim of this post-hoc comparison is to compare efficacy and tolerability results from two generalized anxiety disorder (GAD) studies: a placebo-controlled, randomized controlled trial (RCT) and a study conducted in the clinical practice setting, and to evaluate the extent to which results from RCTs in GAD patients can be generalized to clinical practice. In the clinical practice study, GAD outpatients (n=578) were treated with 4 weeks of pregabalin 150-600mg/day. In the double-blind placebo-controlled RCT, GAD outpatients (n=249) were randomized to 8 weeks of pregabalin (300-600mg/day), or placebo (only the first 4 weeks are included in the current analysis). Efficacy measures included the Hospital Anxiety and Depression Scale - Anxiety and Depression subscales (HADS-A; HADS-D), a visual analogue anxiety scale (VAS-Anxiety), and the Medical Outcomes Study Sleep Problems Index (MOS-SPI). Baseline HADS-A and HADS-D scores were both higher in the clinical practice study vs. the RCT. In the RCT, treatment with pregabalin resulted in significantly greater Week 4 change vs. placebo in the HADS-A (-5.3 vs. -3.9; P<0.005), VAS-Anxiety (-24.0 vs. -13.3; P<0.02), MOS-SPI (-19.1 vs. -9.5; P<0.01), and HADS-D (-2.7 vs. -1.4; P<0.05). The magnitude of Week 4 improvement on pregabalin in the clinical practice study was numerically larger on the HADS-A (-5.9), VAS-Anxiety (-36.0), MOS-SPI (-22.7), and HADS-D (-5.1), despite use of lower doses. These results suggest that clinical practice patients with GAD may achieve comparable efficacy on lower doses of pregabalin than tested in RCTs, despite having comparable levels of anxiety symptom severity at baseline. The current exploratory comparison also suggests that results from RCTs in patients with GAD may not be directly generalizable to clinical practice.

Pregabalin long-term treatment and assessment of discontinuation in patients with generalized anxiety disorder.

Discontinuation effects following cessation of 12 and 24 wk of pregabalin treatment for generalized anxiety disorder (GAD) were evaluated in a placebo- and lorazepam-controlled, randomized, double-blind, multicentre trial conducted in 16 countries. The study design consisted of two 12-wk treatment periods (periods 1 and 2), each followed by a 1-wk taper and two post-discontinuation assessments, one immediately following the taper and one 1-wk post-taper. Patients were assigned to receive an initially flexible dose of pregabalin 450-600 mg/d, pregabalin 150-300 mg/d, or lorazepam 3-4 mg/d for 6 wk; responders continued fixed-dose therapy for 6 additional weeks. Patients entering period 2 continued on the same fixed dose or switched to placebo. Discontinuation effects were evaluated with the Physician Withdrawal Checklist (PWC) and reported discontinuation-emergent signs and symptoms. Rebound anxiety was measured with the Hamilton Anxiety Rating Scale. GAD symptoms improved with all treatments and improvements were maintained over 12 and 24 wk. Low levels of discontinuation symptoms were evident in all treatment groups. For patients who received active treatment during both periods, mean (95% confidence interval) increases on the PWC from last visit on active treatment to the second post-discontinuation assessment were: pregabalin 450-600 mg/d: 2.8 (1.6-3.9), pregabalin 150-300 mg/d: 1.7 (0.7-2.8), lorazepam 3-4 mg/d: 2.2 (1.0-3.5). Rates of rebound anxiety were also low at both 12 and 24 wk (0-6%). This suggests that risk of discontinuation symptoms and rebound anxiety are low for pregabalin after 12 and 24 wk of treatment.

Long-term treatment of anxiety disorders with pregabalin: a 1 year open-label study of safety and tolerability.

OBJECTIVE: Short-term clinical trials have demonstrated the efficacy and safety of pregabalin in the treatment of generalized anxiety disorder (GAD). This study examined long-term safety and tolerability of pregabalin in patients with GAD, social anxiety disorder (SAD), or panic disorder (PD). RESEARCH DESIGN AND METHODS: Patients (n = 528) completing one of four randomized, double-blind, placebo-controlled trials of pregabalin for GAD, SAD, or PD were treated, open label, with flexible-dose pregabalin (150-600 mg/day) for 1 year. CLINICAL TRIAL REGISTRATION: NCT00150449. MAIN OUTCOME MEASURES: The primary outcomes were safety and tolerability. Illness severity was assessed at baseline and Weeks 27/52 using the Clinical Global Impression of Severity (CGI-S) scale. Patients were characterized as 'responders' or 'non-responders' based on CGI-S scores ≤2 and >2, respectively. Analyses were performed on the total anxiety (GAD, SAD and PD) and GAD groups. RESULTS: During 1 year of treatment with pregabalin, dizziness (12.5%) was the only treatment-related adverse event (AE) occurring ≥10%. Somnolence, weight gain, headache and insomnia occurred at 7.6%, 5.5%, 5.3% and 4.7%, respectively. Few treatment-related AEs were rated as severe in the total anxiety (5.1%) or GAD (3.6%) groups. Discontinuation rates due to AEs were similar (9.7% and 10.6%, respectively). No clinically significant laboratory, electrocardiogram, or other treatment-related safety findings were noted, except for treatment-related weight gain, which occurred in both the total (24.4%) and GAD (19.4%) groups. Mean CGI-S scores were similar at baseline in the total (n = 528; score, 3.4) and GAD groups (n = 330; score, 3.6), and CGI-S responder rates were similar at last-observation-carried-forward endpoint (51.3% and 48.1%, respectively). CONCLUSIONS: Pregabalin was generally well tolerated in the long-term treatment of anxiety disorders. Improvement in illness severity was maintained over time. The key limitations of this study were that it was not randomized and neither placebo- nor active-comparator-controlled.

Effects of pregabalin on sleep in generalized anxiety disorder.

Sleep disturbance is a cardinal symptom in both DSM-IV and ICD-10 criteria for generalized anxiety disorder (GAD). This review summarizes the results of clinical trials and pooled analyses that provide data on pregabalin's effect on sleep disturbance in patients diagnosed with GAD. The hypothesized mechanism of action of pregabalin is distinctly different from other anxiolytics. Pregabalin binds to a membrane α2δ subunit protein to inhibit release in excited central nervous system neurons of neurotransmitters implicated in pathological anxiety. Treatment with pregabalin has been found to be associated with significant improvement in GAD-related sleep disturbance across seven placebo-controlled clinical trials. Treatment with pregabalin is associated with improvement in all forms of insomnia and improvement in sleep has been found to be correlated with reduction in functional impairment and improvement in quality of life on subjective global measures. Results of a mediational analysis suggest that 53% of the effect of pregabalin on sleep disturbance was due to a direct effect and 47% was due to an indirect effect, mediated through prior reduction in anxiety symptom severity. In patients with GAD, improvement in sleep has been found to be associated with a reduction in daytime sleepiness. However, dose-related sedation is reported, typically in the first 2 wk of treatment, in approximately 10-30% of patients, depending on the dose used and the speed of titration. Insomnia is a common component of the clinical presentation of GAD and pregabalin appears to be an efficacious treatment for this often chronic and disabling symptom.

Quality of life in depressed women over 40 years old.

OBJECTIVES: This study aims to determine quality of life and satisfaction in depressed Spanish women over 40 years old in the outpatient psychiatry setting. Secondarily, the association between several characteristics of depressed patients and quality of life was assessed. MATERIAL AND METHODS: Cross-sectional, descriptive study, carried out in the Spanish psychiatry setting in 2008. A total of 365 Spanish psychiatrists participated. 1069 patients older than 18 years old signed the informed consent. Depressive symptoms were assessed using the 17 Item Hamilton for Depression Rating Scale (HAM-D17). The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scale assessed the patient's satisfaction and life enjoyment. RESULTS: Were included a total of 942 patients with the following characteristics: mean age of 52.46 years, medical comorbidity in 62.9%, and a history of psychiatric disorders in 79.6%. HAM-D17 mean score of 21.39. According to the Q-LES-Q questionnaire, Global satisfaction mean score was of 35.2%, the highest mean scores were achieved in the treatment satisfaction and the lowest mean scores in free time activities. The quality of life was influenced by the intensity of depressive symptoms and physical comorbidity. CONCLUSION: The study results show an impairment of quality of life in depressed women attending outpatient psychiatric centers. This decrease in the quality of life is associated with depressive symptoms and medical comorbidity.

Calidad de vida en mujeres deprimidas mayores de 40 años / Quality of life in depressed women older than 40 years old

Introducción. El objetivo de este estudio fue evaluar la calidad de vida relacionada con la salud en una muestra amplia de mujeres deprimidas, mayores de 40 años, que recibían atención psiquiátrica ambulatoria en España. Secundariamente se estudió la influencia de las características clínicas y sociodemográficas en la calidad de vida de las pacientes. Material y métodos. Estudio descriptivo, trasversal, realizado en el año 2008. Participaron 365 psiquiatras de centros de atención psiquiátrica ambulatoria de todo el territorio español. Se incluyeron 1.069 mujeres mayores de 40 años diagnosticadas de depresión según el juicio del investigador utilizando criterios DSM-IV. La intensidad de la sintomatología depresiva se evaluó mediante la escala de Hamilton de la depresión de 17 ítems (HAM-D17). Para evaluar la satisfacción y el disfrute del paciente con su vida cotidiana se administró la escala Q-LES-Q. Resultados. Se incluyeron en el análisis 942 pacientes cuyas características más relevantes fueron: edad media de 52,46 años; comorbilidad médica en el 62,9% y antecedentes de de trastornos psiquiátricos en el 79,6%. La puntuación media en la escala de Hamilton Depresión (HAM-D17) fue de 21,39 puntos. En la el cuestionario Q-LES-Q: el grado de satisfacción global fue de 35,2%.; la puntuación más alta se obtuvo en el área de satisfacción con la medicación y la más baja en actividades de tiempo libre. La intensidad de los síntomas depresivos y la presencia de comorbilidad física influyeron en la calidad de vida. Conclusión. La calidad de vida en mujeres mayores de 40 años tratadas ambulatoriamente por un trastorno depresivos mayor se encuentra reducida. Esta disminución se ve influida principalmente por: la intensidad de los síntomas depresivos y la presencia de enfermedad física (AU)

Objectives: This study aims to determine quality of life and satisfaction in depressed Spanish women over 40 years old in the outpatient psychiatry setting. Secondarily, the association between several characteristics of depressed patients and quality of life was assessed. Material and Methods: Cross-sectional, descriptive study, carried out in the Spanish psychiatry setting in 2008. A total of 365 Spanish psychiatrists participated. 1069 patients older than 18 years old signed the informed consent. Depressive symptoms were assessed using the 17 Item Hamilton for Depression Rating Scale (HAM-D17). The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scale assessed the patient’s satisfaction and life enjoyment. Results: Were included a total of 942 patients with the following characteristics: mean age of 52.46 years, medical comorbidity in 62.9%, and a history of psychiatric disorders in 79.6%. HAM-D17 mean score of 21.39. According to the Q-LES-Q questionnaire, Global satisfaction mean score was of 35.2%, the highest mean scores were achieved in the treatment satisfaction and the lowest mean scores in free time activities. The quality of life was influenced by the intensity of depressive symptoms and physical comorbidity. Conclusion: The study results show an impairment of quality of life in depressed women attending outpatient psychiatric centers. This decrease in the quality of life is associated with depressive symptoms and medical comorbidity (AU)

Elucidating the mechanism of action of pregabalin: α(2)δ as a therapeutic target in anxiety.

This review provides a brief summary of what is known about the anxiolytic mechanism of action of pregabalin, a highly selective, high-affinity ligand of the P/Q type of voltage-gated calcium channel (CaV). Evidence from in vivo models of neuronal hyperexcitability suggests that pregabalin reduces synaptic release of neurotransmitters in selected CNS regions including the cortex, olfactory bulb, hypothalamus, amygdala, hippocampus, cerebellum and dorsal horn of the spinal cord. Release of neurotransmitters from the synaptic vesicle, and propagation of neurotransmission, requires the vesicle to fuse with the presynaptic membrane. Pregabalin binding to the α(2)δ type 1 protein of the P/Q type CaV reduces the availability of Ca2+ required for membrane fusion and exocytosis of neurotransmitters. Evidence that the anxiolytic mechanism of action of pregabalin is mediated by binding to the α(2)δ type 1 protein comes from animal models, which have demonstrated a structure-activity relationship between the affinity of ligands for the α(2)δ type 1 protein and their potency in models of anxiety such as the Vogel conflict test. Furthermore, the anxiolytic activity of pregabalin is lost in transgenic mice with specific point mutations in the CaV α(2)δ type 1 protein. Pregabalin-mediated reduction in calcium currents has also been shown to result in a significant inhibition of the release of neurotransmitters implicated in pathological anxiety such as glutamate and monoamine neurotransmitters. However, further research is needed to confirm that these effects contribute to the anxiolytic mechanism of action of pregabalin. Finally, pregabalin may also act by inhibiting synaptogenesis of excitatory neurons formed in response to chronic stress or anxiety, or more acutely inhibit the trafficking of CaV to the plasma membrane.

[Mental disorders in psychiatric outpatients in Spain]. / Trastornos mentales en pacientes de atención especializada en el ámbito extrahospitalario español.

OBJECTIVES: The aim of data presented is to increase knowledge about the morbidity and impact of mental disorders in Spanish psychiatry. The objective is to describe, based on real practice conditions, the most prevalent mental disorders in a sample of Spanish patients treated in outpatient Psychiatry centers. MATERIAL AND METHOD: Epidemiological, naturalistic, prospective, cross-sectional study, carried out in the outpatient psychiatry setting in Spain in 2006. Mental disorders were assessed using the International Neuropsychiatric Interview (MINI). RESULTS: A total of 1,436 patients, 72% of whom were women, mean age of 49.2 ± 13.3 years, were included. According to the MINI assessment, 90.3 % of the patients were diagnosed of at least one mental disorder. The most prevalent mental disorders were: recurrent major depressive episode (27.2%, 353 patients); only current major depressive episode (2 weeks) (25.9%, 336 patients); current dysthymic disorder (last 2 years) (25.9%, 336 patients); current major depressive episode with melancholy symptoms (18.7%, 243 patients); current generalized anxiety disorder (16.6 %, 215 patients). CONCLUSIONS: The study results show the prevalence of mental disorders in a sample representative of the Spanish population, treated in outpatient specialized Psychiatry centers. Mood and generalized anxiety disorders were the most prevalent disorders.