Héctor Dueñas - Academia.edu (original) (raw)

Papers by Héctor Dueñas

Research paper thumbnail of Assessment of functional outcomes by Sheehan Disability Scale in patients with major depressive disorder treated with duloxetine versus selective serotonin reuptake inhibitors

Human psychopharmacology, 2015

We compared functional impairment outcomes assessed with Sheehan Disability Scale (SDS) after tre... more We compared functional impairment outcomes assessed with Sheehan Disability Scale (SDS) after treatment with duloxetine versus selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder. Data were pooled from four randomized studies comparing treatment with duloxetine and SSRIs (three double blind and one open label). Analysis of covariance, with last-observation-carried-forward approach for missing data, explored treatment differences between duloxetine and SSRIs on SDS changes during 8 to 12 weeks of acute treatment for the intent-to-treat population. Logistic regression analysis examined the predictive capacity of baseline patient characteristics for remission in functional impairment (SDS total score ≤ 6 and SDS item scores ≤ 2) at endpoint. Included were 2193 patients (duloxetine n = 1029; SSRIs n = 835; placebo n = 329). Treatment with duloxetine and SSRIs resulted in significantly (p < 0.01) greater improvements in the SDS total score versus...

Research paper thumbnail of Nocebo Effects in the Treatment of Major Depression

The Journal of Clinical Psychiatry, 2015

The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is... more The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is a clinically salient yet seldom studied phenomenon that may be associated with poorer treatment outcomes, perceived adverse events, and treatment discontinuation. The covert presence of nocebo responders in clinical trials may contribute to outcome variance in both placebo and active treatment arms for important primary and secondary endpoints. Nocebo effects are thought to be driven by expectancy and conditioning. This study analyzed pooled clinical trial data in the placebo arms of controlled trials of antidepressant medications to investigate variables associated with the emergence of adverse outcomes in placebo-treated participants (N = 2,457). Specifically, we examined treatment-emergent adverse events (TEAEs) and discontinuation in placebo-treated individuals. Trials were commenced between 1993 and 2010 as studies of duloxetine versus active comparator and/or placebo. TEAEs were reported by 1,569 placebo-treated participants (63.9%), with 115 (4.7%) discontinuing from the studies due to TEAEs and 274 (11.2%) showing worsening of Hamilton Depression Rating Scale total score during placebo treatment. There was specifically no evidence to support the expectancy hypothesis, that reported TEAEs were influenced by adverse effects described in the clinical trials participant information and consent forms, or the conditioning hypothesis, that reported TEAEs would be influenced by adverse effect profiles of previous antidepressant medications used by these study participants. There was some evidence to suggest that people who had previously used complementary medications were more likely to report TEAEs. Variables specific to individual studies were the strongest predictors of TEAEs. In this study, TEAEs were very common among placebo-treated clinical trial participants. Unexpectedly, there was no evidence to associate TEAEs with adverse clinical outcomes, nor were the conditioning or expectancy hypotheses supported by these data. The nocebo effect is a common, covert, and poorly understood driver of clinical outcomes that requires further investigation.

Research paper thumbnail of Caregiving for patients with Alzheimer's disease or dementia and its association with psychiatric and clinical comorbidities and other health outcomes in Brazil

International journal of geriatric psychiatry, Jan 25, 2015

Individuals with dementia due to Alzheimer's disease often receive care from family members w... more Individuals with dementia due to Alzheimer's disease often receive care from family members who experience associated burden. This study provides the first broad, population-based account of caregiving-related health outcome burden in Brazil. Data were analyzed from the 2012 National Health and Wellness Survey in Brazil (n = 12 000), an Internet-based survey of adults (aged 18+ years), using stratified sampling by sex and age to ensure demographic representation of Brazil's adult population. Caregivers of individuals with Alzheimer's disease or dementia were compared with non-caregivers on comorbidities, productivity impairment, health-related quality of life, resource utilization, sociodemographic/health characteristics and behaviors, and Charlson comorbidity index scores. Regression models assessed outcomes associated with caregiving, adjusting for potential confounds. Among 10 853 respondents, caregivers' (n = 209) average age was 42.1 years, 53% were female, and ...

Research paper thumbnail of Should Unexplained Painful Physical Symptoms be Considered within the Spectrum of Depressive Symptoms?

Clinical Practice & Epidemiology in Mental Health, 2015

Objective: To examine whether painful physical symptoms (PPS) can be considered within the spectr... more Objective: To examine whether painful physical symptoms (PPS) can be considered within the spectrum of depressive symptoms. Methods: Data for this post-hoc analysis were taken from a 6-month observational study mostly conducted in East Asia, Mexico, and the Middle East of 1,549 depressed patients without sexual dysfunction at baseline. Both explanatory and confirmatory factor analyses (EFA and CFA) were performed on the combined items of the 16-item Quick Inventory of Depressive Symptomatology Self-Report and the Somatic Symptom Inventory (seven pain-related items only). An additional second-order CFA was also conducted to examine an association between retained factors and the overall "depressive symptoms" factor. In addition, Spearman's correlation was used to assess levels of correlation between retained factors and depression severity as well as quality of life. Results: Both EFA and CFA suggested and validated a four-factor solution, which included a pain factor. The other three factors identified were a mood/cognitive factor, a sleep disturbance factor, and an appetite/weight disturbance factor. All four factors were significantly associated with the overall factor of depression. They were also highly correlated to depression severity and quality of life (p<0.001 for all). The levels of correlations with the pain factor were generally greater than those with the appetite/weight factor and similar to those with the sleep factor. Conclusion: It may be reasonable to consider PPS within a broad spectrum of depressive symptoms. At least, they should be routinely assessed in patients with depression. Further research is warranted to validate these preliminary findings.

Research paper thumbnail of Real-world outcomes in patients with depression treated with duloxetine or a selective serotonin reuptake inhibitor in East Asia

Asia-Pacific psychiatry : official journal of the Pacific Rim College of Psychiatrists, Jan 24, 2015

This study compared treatment outcomes in patients with major depressive disorder treated with ei... more This study compared treatment outcomes in patients with major depressive disorder treated with either duloxetine with a daily dose of ≤60 mg or a selective serotonin reuptake inhibitor (SSRI) as monotherapy for up to 6 months in a naturalistic setting in East Asia. In addition, this study examined the impact of painful physical symptoms (PPS) on the effects of these treatments. This post-hoc analysis of data from a 6-month prospective observational study involving 1,549 major depressive disorder patients without sexual dysfunction focused on a subgroup of patients from East Asia (n = 587). Depression severity was measured using the Clinical Global Impression of Severity and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16 ), whereas quality of life (QoL) was measured using EuroQoL instruments. PPS were rated using the modified Somatic Symptom Inventory. Multiple regression analyses were performed to compare the treatment outcomes. Duloxetine-treated pa...

Research paper thumbnail of Review of Efficacy and Safety of Duloxetine 40 to 60 mg Once Daily in Patients with Diabetic Peripheral Neuropathic Pain

Pain research and treatment, 2012

We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studie... more We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studies and 1 open-label, uncontrolled, 34-week maintenance-of-effect (MOE) study that examine duloxetine 40 and 60 mg once daily (QD) in patients with diabetic peripheral neuropathic pain (DPNP). In all placebo-controlled studies, duloxetine showed significantly (P ≤ .01) greater reduction in pain severity (weekly mean of 24-hour average pain severity ratings, primary outcome measure) compared with placebo. In all placebo-controlled studies, duloxetine showed significantly (P ≤ .05) greater improvement on brief pain inventory-Interference ratings. Patient global impression of improvement ratings were superior to placebo (P ≤ .01) for duloxetine patients in all placebo-controlled studies. Response rates (based on 30% pain reduction) ranged from 57% to 68% for duloxetine and from 35% to 47% for placebo and were statistically significantly different (P ≤ .01) between treatment groups in 3 out of...

Research paper thumbnail of Symtomatic Factors in Patients With Major Depressive Disorder (MDD): Results from an Observational Study

Research paper thumbnail of The Role of Descending Inhibitory Pathways on Chronic Pain Modulation and Clinical Implications

Pain Practice, 2013

The treatment and management of chronic pain is a major challenge for clinicians. Chronic pain is... more The treatment and management of chronic pain is a major challenge for clinicians. Chronic pain is often underdiagnosed and undertreated, and there is a lack of awareness of the pathophysiologic mechanisms that contribute to chronic pain. Chronic pain involves peripheral and central sensitization, as well as the alteration of the pain modulatory pathways. Imbalance between the descending facilitatory systems and the descending inhibitory systems is believed to be involved in chronic pain in pathological conditions. A pharmacological treatment that could restore the balance between these 2 pathways by diminishing the descending facilitatory pain pathways and enhancing the descending inhibitory pain pathways would be a valuable therapeutic option for patients with chronic pain. Due to the lack of evidence for pharmacological options that act on descending facilitation pathways, in this review we summarize the role of the descending inhibitory pain pathways in pain perception. This review will focus primarily on monoaminergic descending inhibitory pain pathways and their contribution to the mechanism of chronic pain and several pharmacological treatment options that enhance these pathways to reduce chronic pain. We describe anatomical structures and neurotransmitters of the descending inhibitory pain pathways that are activated in response to nociceptive pain and altered in response to sustained and persistent pain which leads to chronic pain in various pathological conditions. &

Research paper thumbnail of Predictors of remission in the treatment of major depressive disorder: real-world evidence from a 6-month prospective observational study

Neuropsychiatric Disease and Treatment, 2015

Research paper thumbnail of A Review of the Serotonin-Norepinephrine Reuptake Inhibitors: Pharmacologic Aspects and Clinical Implications for Treatment of Major Depressive Disorder and Associated Painful Physical Symptoms

Open Journal of Depression, 2013

Background: Depression is characterized by low mood, low self-esteem, and loss of interest or ple... more Background: Depression is characterized by low mood, low self-esteem, and loss of interest or pleasure. Painful physical symptoms (PPS) associated with depression have a negative impact on the probability of remission. Because both norepinephrine and serotonin are involved with the central regulation of pain, the serotonin-norepinephrine reuptake inhibitors (SNRIs) may have more success than the selective serotonin reuptake inhibitors (SSRIs) in impacting PPS as well as the core emotional symptoms of depression. Methods: Published preclinical and clinical data on the SNRIs (i.e., milnacipran, venlafaxine, and duloxetine) have been reviewed, paying special attention to the differentiation of the pharmacological aspects of the SNRIs. The efficacy and safety results on depression and associated PPS have also been summarized. Results: Each of the SNRIs has different profiles regarding the inhibition of binding to human serotonin and norepinephrine uptake transporters and clinical pharmacokinetics. All SNRIs have data for alleviating the core symptoms of depression; duloxetine and venlafaxine show efficacy for PPS associated with depression. There are also differences in tolerability and adverse events profiles. Conclusions: Although all SNRIs have the same dual mechanism of action for the treatment of depression, they have different pharmacologic profiles that may impact clinical outcomes.

Research paper thumbnail of Impact of Pretreatment With Antidepressants on the Efficacy of Duloxetine in Terms of Mood Symptoms and Functioning

The Primary Care Companion For CNS Disorders, 2014

Research paper thumbnail of Does Early Improvement in Anxiety Symptoms in Patients with Major Depressive Disorder Affect Remission Rates? A Post-Hoc Analysis of Pooled Duloxetine Clinic Trials

Open Journal of Depression, 2014

Objectives: Patients with major depressive disorder (MDD) and a comorbid anxiety disorder or sign... more Objectives: Patients with major depressive disorder (MDD) and a comorbid anxiety disorder or significant anxiety symptoms have decreased functioning, increased risk of suicidality, and worse post-treatment outcomes. This pooled analysis of 8 duloxetine MDD trials was designed to determine whether early improvement in anxiety symptoms predicts MDD remission. Methods: Eight trials were pooled. Patients with a baseline 17-item Hamilton Rating Scale for Depression (HA-MD17) anxiety/somatization factor score ≥7 were considered to have anxious depression. Early response on the HAMD17 total score was defined as a 20% reduction at weeks 2 or 4, a 30% reduction at weeks 2 or 4, or a 50% reduction at weeks 2 or 4 in the HAMD17 anxiety subscale. Each category was analyzed separately for all patients. MDD remission is a score of ≤7 on the HAMD17 total score at study endpoint. Results: The early responder group in each analysis showed greater numerical improvement at endpoint on the HAMD17 total score than the nonresponder group. Duloxetine showed statistically significantly greater improvement than placebo in most nonresponder and responder subgroups. There were no statistically significant interaction effects for the difference between duloxetine and placebo for any of the anxious categories. Conclusion: Although patients who responded in the various response categories had greater numerical improvement and greater remission rates than nonresponding patients, the response and nonresponse groups did not differ statistically regarding the treatment effect of duloxetine. Therefore, early improve-* Corresponding author.

Research paper thumbnail of PDB33 ECONOMIC EVALUATION OF THREE FIRST-LINE MEDICATIONS IN PAINFUL DIABETIC PERIPHERAL NEUROPHATY IN MEXICO

Value in Health, 2010

Abstracts fied the study population into groups by their oral hypoglycemic agents, and further an... more Abstracts fied the study population into groups by their oral hypoglycemic agents, and further analyzed the hazard ratio of myocardial infarction (MI) in different add-on medication and the survival of cardiovascular diseases between add-on TZDs group and non-TZD group. NMB regression model was used to estimate the cost-effectiveness difference on patients who used TZDs versus non-TZD users. RESULTS: The Cox proportional hazard model analysis demonstrated that sulfonylurea +rosiglitazone group had a higher risk of hospitalization for cardiovascular diseases comparing to add-on metformin group (HR 1.48, 95% CI: 1.21-1.80); As to the cost-effectiveness analysis: 1) Comparing to sulfonylurea+metformin group, the average annual medication cost (AAMC) per capita of sulfonylurea+rosiglitazone group increased NT$12,944, but the average days for hospitalization decreased 0.12 day; while the AAMC of sulfonylurea +pioglitazone group increased NT$10,329, but the average days for hospitalization decreased 0.22 day. 2) Comparing to metformin+sulfonylurea group, the AAMC of metformin+rosiglitazone group increased NT$11,486 dollars, but the average day for hospitalization decreased 0.09 day; while metformin+rosiglitazone group increased NT$11267, but the average days for hospitalization decreased 0.18 day. CONCLU-SIONS: Our results demonstrated that sulfonylurea + rosiglitazone group had a higher risk of hospitalization for cardiovascular diseases versus metformin group with TZD add-on treatment (HR 1.48, 95% CI: 1.21-1.80), and per capita AAMC was higher (NT$12944 increment) which was not justified in the decrease of 0.12 hospitalization days 0.12. As for other metformin add-on groups, the increased medication cost was also not justified. Research and Quality. The data sets provide information on the prescribed drug, demography, office-based visits, outpatients and inpatients for the years 2005 and 2006.The analysis is based on the Medicare payments for anti-diabetic drugs, without considering the drug forms and cost-efficiency as measured by the Medicare payment amounts for office-based visits, inpatients or outpatients. Statistics methods used include One-Way Frequencies, Summary Statistics, Box and Whisker Plots, Linear Multiple Regression and Spearman's rank correlation. SAS SQL and some SAS functions such as the MDY function and 0-1 indicator functions are utilized to preprocess the data. RESULTS: Results demonstrate that metformin users have fewer physician visits, lab tests and shorter length of stay in the hospital and it has a negative relationship with the former two factors. Insulin, metformin and its combination with glyburide are significant to predict the frequencies of doctor office visits, lab tests and length of stay. From the year 2005 to the year 2006, insulin and metformin users reduce their frequencies of physician visits and lab tests as well as days in the hospital. CONCLUSIONS: Among the diabetes medications in Medicare, metformin is the most cost-effective drug due to the fewest Medicare expenditures for office-based visits, inpatients and outpatients with spending one dollar on the drug. In 2006, with Medicare part D, metformin becomes more efficient, while insulin becomes more effective at the cost of an increased price .Therefore, it is recommended to prescribe metformin for the Medicare diabetic beneficiaries.

Research paper thumbnail of Improvement of psychic and somatic symptoms in adult patients with generalized anxiety disorder: examination from a duloxetine, venlafaxine extended-release and placebo-controlled trial

Psychological Medicine, 2009

Background. This study examined the efficacy and tolerability of duloxetine and venlafaxine exten... more Background. This study examined the efficacy and tolerability of duloxetine and venlafaxine extended-release (XR) treatment for generalized anxiety disorder (GAD), with a secondary focus on psychic and somatic symptoms within GAD.

Research paper thumbnail of Major depressive disorder in Latin America: The relationship between depression severity, painful somatic symptoms, and quality of life

Journal of Affective Disorders, 2005

Background: We report on two multi-center, prospective, observational studies (H6U-BC-LRAG and H6... more Background: We report on two multi-center, prospective, observational studies (H6U-BC-LRAG and H6U-BL-LRAH) to determine the clinical profile of Latin American outpatients with major depressive disorder (MDD) and the relationship between depression severity, painful somatic symptoms, and quality of life. Method: Patients (n=989) with MDD were classified according to the presence (SS+) or absence (SSÀ) of painful somatic symptoms using the Somatic Symptom Inventory (SSI). Visual Analogue Scale (VAS) quantified pain severity, HAMD 17 and CGI-S determined depression severity, while the Quality of Life in Depression Scale (QLDS) quantified subjective well-being. Results: At baseline, patients had an average CGI score of 4.5 (F0.8) and HAMD 17 score of 24.9 (F7.2). Of the patients studied, 72.6% reported painful somatic symptoms (95% CI: 69.8, 75.4), with women 2.7 times more likely to be SS+ than men ( pb0.0001). Adjusted mean HAMD 17 (26.79) and CGI-S (4.53) scores for SS+ patients were significantly ( pb0.0001) higher than for SSÀ patients (HAMD 17 : 22.87; CGI-S: 4.28). SS+ patients had greater severity of pain across all VAS measures ( pb0.0001). The presence of somatic symptoms had a significantly deleterious effect on quality of life ( pb0.0001). Conclusion: Greater severity of painful somatic symptoms was associated with increased depression severity and reduced quality of life. We concluded that both emotional and physical manifestations of MDD must be addressed for successful treatment. D

Research paper thumbnail of Effectiveness of antidepressants in the treatment of major depressive disorder in Latin America

International Journal of Psychiatry in Clinical Practice, 2007

Objective. Painful physical symptoms occur frequently in patients with major depressive disorder ... more Objective. Painful physical symptoms occur frequently in patients with major depressive disorder (MDD), and although numerous studies report the effect of antidepressants on emotional aspects of depression, few focus on their effect on physical symptoms. This observational study was conducted, in a clinical practice setting, to determine antidepressant treatment decisions and their outcome on the physical and emotional symptoms of MDD. Methods. Patients with a mean score ≥2 for pain-related items on the Somatic Symptom Inventory (SSI) were classified with painful physical symptoms (PPS +) and differentiated from the remaining patients (PPS -). Severity of depression and physical pain were determined using the 17-item Hamilton Depression Rating Scale (HAMD17) and Clinical Global Impressions of Severity Scale (CGI-S), and Visual Analog Scale (VAS), respectively. Results. At baseline, 72.6% of patients were PPS+. Compared to PPS- patients, PPS +patients were, on average, significantly more depressed at baseline (mean difference [95% CI]: HAMD17 4.6 [3.6, 5.5] and CGI-S 0.3 [0.2, 0.4]; all p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001), and remained more depressed and in greater pain at endpoint (HAMD17p=0.0074, CGI-S P =0.0151, and VAS P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). In addition, fewer PPS+ patients (65.8%) achieved remission (total HAMD17≤7) compared to PPS- patients (74.6%, P =0.0180). Conclusions. Painful physical symptoms are prevalent in MDD patients, highlighting the importance of addressing both the physical and emotional symptoms of depression.

Research paper thumbnail of Frequency of treatment-emergent sexual dysfunction and treatment effectiveness during SSRI or duloxetine therapy: 8-week data from a 6-month observational study

International Journal of Psychiatry in Clinical Practice, 2011

In randomised controlled trials, the frequency of treatment-emergent sexual dysfunction (TESD) in... more In randomised controlled trials, the frequency of treatment-emergent sexual dysfunction (TESD) in patients with major depressive disorder (MDD) at week 8 was lower with duloxetine than selective serotonin reuptake inhibitor (SSRI) therapy. This 6-month, prospective, observational study compared the frequency of TESD (using the Arizona Sexual Experience [ASEX] scale) in MDD patients treated with duloxetine or SSRI monotherapy in the first 8 weeks in normal clinical practice. Physician-assessed TESD frequency at week 8 was comparable with duloxetine and SSRI monotherapy (23.9 and 26.2%, respectively; P = 0.545). Improvements in Clinical Global Impressions of Severity (CGI-S), 16-item Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR(16)), Integral Inventory for Depression (IID) total scores and remission rates were statistically significantly greater with duloxetine than SSRI monotherapy (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001, 0.010, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, and 0.002, respectively), but TESD attenuated improvements in quality of life measures (EuroQoL questionnaire-5 dimensions [EQ-5D] and Sheehan Disability Scale [SDS] scores: ≤0.012). Several factors were significantly (P ≤ 0.05) associated with TESD at week 8 in this study. TESD rates with duloxetine and SSRIs at week 8 were comparable, however, significant differences in effectiveness were observed in favour of duloxetine. Antidepressant tolerability with respect to TESD must be managed to maximize remission of depressed patients.

Research paper thumbnail of Treatment-emergent sexual dysfunction with SSRIs and duloxetine: Effectiveness and functional outcomes over a 6-month observational period

International Journal of Psychiatry in Clinical Practice, 2011

Objective . To evaluate frequencies of treatment-emergent sexual dysfunction (TESD) in patients w... more Objective . To evaluate frequencies of treatment-emergent sexual dysfunction (TESD) in patients with major depressive disorder (MDD) treated with duloxetine or selective serotonin reuptake inhibitor (SSRI) monotherapy for up to 6 months in a prospective, observational study. Methods . Sexually active MDD patients without sexual dysfunction at entry were enrolled from twelve countries ( N ϭ 1,647). TESD was assessed over the study period using the Arizona sexual experience (ASEX) scale. A priori -specifi ed secondary 6-month clinical endpoints were also examined. Results . The frequency of TESD at 6 months with duloxetine was comparable to that with SSRI monotherapy (23.4 and 28.7%, respectively; P ϭ 0.087). Improvements in Clinical Global Impressions of Severity (CGI-S), 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR 16 ), Integral Inventory for Depression (IID) total scores, remission and sustained remission rates were statistically signifi cantly greater with duloxetine than SSRI monotherapy at 6 months ( P Ͻ 0.001 for each), but TESD attenuated improvements in quality of life measures. Four factors were consistently signifi cantly ( P Յ 0.05) associated with TESD at week 8 and 6 months. Conclusions . Six-month TESD rates were comparable between duloxetine and SSRIs, with greater MDD effectiveness in favour of duloxetine. Improved recognition and management of TESD may improve quality of life for MDD patients in usual clinical practice. ABSTRACT Objectives: Previous research has been inconclusive whether attention-deficit/hyperactivity disorder (ADHD), when comorbid with disruptive disorders (oppositional defiant disorder [ODD] or conduct disorder [CD]), with the internalizing disorders (anxiety and/or depression), or with both, should constitute separate clinical entities. Determination of the clinical significance of potential ADHD + internalizing disorder or ADHD + ODD/CD syndromes could yield better diagnostic decision-making, treatment planning, and treatment outcomes. Method: Drawing upon cross-sectional and longitudinal information from 579 children (aged 7-9.9 years) with ADHD participating in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA), investigators applied validational criteria to compare ADHD subjects with and without comorbid internalizing disorders and ODD/CD. Results: Substantial evidence of main effects of internalizing and externalizing comorbid disorders was found. Moderate evidence of interactions of parent-reported anxiety and

Research paper thumbnail of Major depressive disorder severity and the frequency of painful physical symptoms: a pooled analysis of observational studies

Current Medical Research and Opinion, 2012

This retrospective post-hoc analysis of observational studies assesses the frequency of painful p... more This retrospective post-hoc analysis of observational studies assesses the frequency of painful physical symptoms (PPS) in patients with major depressive disorder (MDD) of varied severity as may be seen in clinical practice. Observational studies of MDD that collected a clinician-reported measure of depression severity and included assessment of PPS were screened for this individual patient-level analysis. Six observational studies were included that enrolled outpatients with a diagnosis of MDD (assessed using the 17-item Hamilton depression scale, Hospital Anxiety and Depression Scale-Depression, or Inventory of Depressive Symptomatology). Measures of PPS were based on the original study assessment (modified Somatic Symptom Inventory [SSI] and Visual Analogue Scale [VAS]). Patients were divided into analysis cohorts based on the presence or absence of PPS. To model PPS status, odds ratios were calculated from logistic regression for cross-sectional analysis (main analysis) and generalized linear mixed models for longitudinal models (exploratory longitudinal analysis). For the main analysis, four studies (N = 2943, 71.6% female, mean age 45.3 years) were identified. Of 2901 eligible patients, 61.7% were classified as having painful physical symptoms (PPS+). At study entry, 73.1% (957/1309) of patients in the severe category of depression, 56.8% (537/945) of those with moderate depression, and 45.6% (295/647) of those with mild depression were PPS+. The exploratory longitudinal analysis was performed using a subset (N = 2430) from the studies used in the main analysis plus two others (an additional 7984 patients, 6742 of which were modeled). The likelihood of patients that were PPS- at baseline later developing PPS was 5% to 13% greater for patients with increased depression severity (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and the likelihood of PPS+ patients later not having PPS was 9% to 17% less for patients with increased depression severity (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Since this is a retrospective aggregate analysis of several observational studies, and due to missing data, care should be taken in the interpretation of these results. Despite the use of adjustment techniques, selection bias and unmeasured confounding may still be an issue for comparative analysis as not all variables were collected for all studies. For patients treated in typical care settings, PPS were associated with depression severity. However, patients with mild and moderate depression also exhibited PPS. Clinicians should be aware that PPS are present, and may warrant treatment, across depression severities.

Research paper thumbnail of Use of antidepressants in the treatment of depression in Asia: Guidelines, clinical evidence, and experience revisited

Major depressive disorder is prevalent worldwide, and only about half of those affected will expe... more Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients.

Research paper thumbnail of Assessment of functional outcomes by Sheehan Disability Scale in patients with major depressive disorder treated with duloxetine versus selective serotonin reuptake inhibitors

Human psychopharmacology, 2015

We compared functional impairment outcomes assessed with Sheehan Disability Scale (SDS) after tre... more We compared functional impairment outcomes assessed with Sheehan Disability Scale (SDS) after treatment with duloxetine versus selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder. Data were pooled from four randomized studies comparing treatment with duloxetine and SSRIs (three double blind and one open label). Analysis of covariance, with last-observation-carried-forward approach for missing data, explored treatment differences between duloxetine and SSRIs on SDS changes during 8 to 12 weeks of acute treatment for the intent-to-treat population. Logistic regression analysis examined the predictive capacity of baseline patient characteristics for remission in functional impairment (SDS total score ≤ 6 and SDS item scores ≤ 2) at endpoint. Included were 2193 patients (duloxetine n = 1029; SSRIs n = 835; placebo n = 329). Treatment with duloxetine and SSRIs resulted in significantly (p < 0.01) greater improvements in the SDS total score versus...

Research paper thumbnail of Nocebo Effects in the Treatment of Major Depression

The Journal of Clinical Psychiatry, 2015

The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is... more The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is a clinically salient yet seldom studied phenomenon that may be associated with poorer treatment outcomes, perceived adverse events, and treatment discontinuation. The covert presence of nocebo responders in clinical trials may contribute to outcome variance in both placebo and active treatment arms for important primary and secondary endpoints. Nocebo effects are thought to be driven by expectancy and conditioning. This study analyzed pooled clinical trial data in the placebo arms of controlled trials of antidepressant medications to investigate variables associated with the emergence of adverse outcomes in placebo-treated participants (N = 2,457). Specifically, we examined treatment-emergent adverse events (TEAEs) and discontinuation in placebo-treated individuals. Trials were commenced between 1993 and 2010 as studies of duloxetine versus active comparator and/or placebo. TEAEs were reported by 1,569 placebo-treated participants (63.9%), with 115 (4.7%) discontinuing from the studies due to TEAEs and 274 (11.2%) showing worsening of Hamilton Depression Rating Scale total score during placebo treatment. There was specifically no evidence to support the expectancy hypothesis, that reported TEAEs were influenced by adverse effects described in the clinical trials participant information and consent forms, or the conditioning hypothesis, that reported TEAEs would be influenced by adverse effect profiles of previous antidepressant medications used by these study participants. There was some evidence to suggest that people who had previously used complementary medications were more likely to report TEAEs. Variables specific to individual studies were the strongest predictors of TEAEs. In this study, TEAEs were very common among placebo-treated clinical trial participants. Unexpectedly, there was no evidence to associate TEAEs with adverse clinical outcomes, nor were the conditioning or expectancy hypotheses supported by these data. The nocebo effect is a common, covert, and poorly understood driver of clinical outcomes that requires further investigation.

Research paper thumbnail of Caregiving for patients with Alzheimer's disease or dementia and its association with psychiatric and clinical comorbidities and other health outcomes in Brazil

International journal of geriatric psychiatry, Jan 25, 2015

Individuals with dementia due to Alzheimer's disease often receive care from family members w... more Individuals with dementia due to Alzheimer's disease often receive care from family members who experience associated burden. This study provides the first broad, population-based account of caregiving-related health outcome burden in Brazil. Data were analyzed from the 2012 National Health and Wellness Survey in Brazil (n = 12 000), an Internet-based survey of adults (aged 18+ years), using stratified sampling by sex and age to ensure demographic representation of Brazil's adult population. Caregivers of individuals with Alzheimer's disease or dementia were compared with non-caregivers on comorbidities, productivity impairment, health-related quality of life, resource utilization, sociodemographic/health characteristics and behaviors, and Charlson comorbidity index scores. Regression models assessed outcomes associated with caregiving, adjusting for potential confounds. Among 10 853 respondents, caregivers' (n = 209) average age was 42.1 years, 53% were female, and ...

Research paper thumbnail of Should Unexplained Painful Physical Symptoms be Considered within the Spectrum of Depressive Symptoms?

Clinical Practice & Epidemiology in Mental Health, 2015

Objective: To examine whether painful physical symptoms (PPS) can be considered within the spectr... more Objective: To examine whether painful physical symptoms (PPS) can be considered within the spectrum of depressive symptoms. Methods: Data for this post-hoc analysis were taken from a 6-month observational study mostly conducted in East Asia, Mexico, and the Middle East of 1,549 depressed patients without sexual dysfunction at baseline. Both explanatory and confirmatory factor analyses (EFA and CFA) were performed on the combined items of the 16-item Quick Inventory of Depressive Symptomatology Self-Report and the Somatic Symptom Inventory (seven pain-related items only). An additional second-order CFA was also conducted to examine an association between retained factors and the overall "depressive symptoms" factor. In addition, Spearman's correlation was used to assess levels of correlation between retained factors and depression severity as well as quality of life. Results: Both EFA and CFA suggested and validated a four-factor solution, which included a pain factor. The other three factors identified were a mood/cognitive factor, a sleep disturbance factor, and an appetite/weight disturbance factor. All four factors were significantly associated with the overall factor of depression. They were also highly correlated to depression severity and quality of life (p<0.001 for all). The levels of correlations with the pain factor were generally greater than those with the appetite/weight factor and similar to those with the sleep factor. Conclusion: It may be reasonable to consider PPS within a broad spectrum of depressive symptoms. At least, they should be routinely assessed in patients with depression. Further research is warranted to validate these preliminary findings.

Research paper thumbnail of Real-world outcomes in patients with depression treated with duloxetine or a selective serotonin reuptake inhibitor in East Asia

Asia-Pacific psychiatry : official journal of the Pacific Rim College of Psychiatrists, Jan 24, 2015

This study compared treatment outcomes in patients with major depressive disorder treated with ei... more This study compared treatment outcomes in patients with major depressive disorder treated with either duloxetine with a daily dose of ≤60 mg or a selective serotonin reuptake inhibitor (SSRI) as monotherapy for up to 6 months in a naturalistic setting in East Asia. In addition, this study examined the impact of painful physical symptoms (PPS) on the effects of these treatments. This post-hoc analysis of data from a 6-month prospective observational study involving 1,549 major depressive disorder patients without sexual dysfunction focused on a subgroup of patients from East Asia (n = 587). Depression severity was measured using the Clinical Global Impression of Severity and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16 ), whereas quality of life (QoL) was measured using EuroQoL instruments. PPS were rated using the modified Somatic Symptom Inventory. Multiple regression analyses were performed to compare the treatment outcomes. Duloxetine-treated pa...

Research paper thumbnail of Review of Efficacy and Safety of Duloxetine 40 to 60 mg Once Daily in Patients with Diabetic Peripheral Neuropathic Pain

Pain research and treatment, 2012

We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studie... more We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studies and 1 open-label, uncontrolled, 34-week maintenance-of-effect (MOE) study that examine duloxetine 40 and 60 mg once daily (QD) in patients with diabetic peripheral neuropathic pain (DPNP). In all placebo-controlled studies, duloxetine showed significantly (P ≤ .01) greater reduction in pain severity (weekly mean of 24-hour average pain severity ratings, primary outcome measure) compared with placebo. In all placebo-controlled studies, duloxetine showed significantly (P ≤ .05) greater improvement on brief pain inventory-Interference ratings. Patient global impression of improvement ratings were superior to placebo (P ≤ .01) for duloxetine patients in all placebo-controlled studies. Response rates (based on 30% pain reduction) ranged from 57% to 68% for duloxetine and from 35% to 47% for placebo and were statistically significantly different (P ≤ .01) between treatment groups in 3 out of...

Research paper thumbnail of Symtomatic Factors in Patients With Major Depressive Disorder (MDD): Results from an Observational Study

Research paper thumbnail of The Role of Descending Inhibitory Pathways on Chronic Pain Modulation and Clinical Implications

Pain Practice, 2013

The treatment and management of chronic pain is a major challenge for clinicians. Chronic pain is... more The treatment and management of chronic pain is a major challenge for clinicians. Chronic pain is often underdiagnosed and undertreated, and there is a lack of awareness of the pathophysiologic mechanisms that contribute to chronic pain. Chronic pain involves peripheral and central sensitization, as well as the alteration of the pain modulatory pathways. Imbalance between the descending facilitatory systems and the descending inhibitory systems is believed to be involved in chronic pain in pathological conditions. A pharmacological treatment that could restore the balance between these 2 pathways by diminishing the descending facilitatory pain pathways and enhancing the descending inhibitory pain pathways would be a valuable therapeutic option for patients with chronic pain. Due to the lack of evidence for pharmacological options that act on descending facilitation pathways, in this review we summarize the role of the descending inhibitory pain pathways in pain perception. This review will focus primarily on monoaminergic descending inhibitory pain pathways and their contribution to the mechanism of chronic pain and several pharmacological treatment options that enhance these pathways to reduce chronic pain. We describe anatomical structures and neurotransmitters of the descending inhibitory pain pathways that are activated in response to nociceptive pain and altered in response to sustained and persistent pain which leads to chronic pain in various pathological conditions. &

Research paper thumbnail of Predictors of remission in the treatment of major depressive disorder: real-world evidence from a 6-month prospective observational study

Neuropsychiatric Disease and Treatment, 2015

Research paper thumbnail of A Review of the Serotonin-Norepinephrine Reuptake Inhibitors: Pharmacologic Aspects and Clinical Implications for Treatment of Major Depressive Disorder and Associated Painful Physical Symptoms

Open Journal of Depression, 2013

Background: Depression is characterized by low mood, low self-esteem, and loss of interest or ple... more Background: Depression is characterized by low mood, low self-esteem, and loss of interest or pleasure. Painful physical symptoms (PPS) associated with depression have a negative impact on the probability of remission. Because both norepinephrine and serotonin are involved with the central regulation of pain, the serotonin-norepinephrine reuptake inhibitors (SNRIs) may have more success than the selective serotonin reuptake inhibitors (SSRIs) in impacting PPS as well as the core emotional symptoms of depression. Methods: Published preclinical and clinical data on the SNRIs (i.e., milnacipran, venlafaxine, and duloxetine) have been reviewed, paying special attention to the differentiation of the pharmacological aspects of the SNRIs. The efficacy and safety results on depression and associated PPS have also been summarized. Results: Each of the SNRIs has different profiles regarding the inhibition of binding to human serotonin and norepinephrine uptake transporters and clinical pharmacokinetics. All SNRIs have data for alleviating the core symptoms of depression; duloxetine and venlafaxine show efficacy for PPS associated with depression. There are also differences in tolerability and adverse events profiles. Conclusions: Although all SNRIs have the same dual mechanism of action for the treatment of depression, they have different pharmacologic profiles that may impact clinical outcomes.

Research paper thumbnail of Impact of Pretreatment With Antidepressants on the Efficacy of Duloxetine in Terms of Mood Symptoms and Functioning

The Primary Care Companion For CNS Disorders, 2014

Research paper thumbnail of Does Early Improvement in Anxiety Symptoms in Patients with Major Depressive Disorder Affect Remission Rates? A Post-Hoc Analysis of Pooled Duloxetine Clinic Trials

Open Journal of Depression, 2014

Objectives: Patients with major depressive disorder (MDD) and a comorbid anxiety disorder or sign... more Objectives: Patients with major depressive disorder (MDD) and a comorbid anxiety disorder or significant anxiety symptoms have decreased functioning, increased risk of suicidality, and worse post-treatment outcomes. This pooled analysis of 8 duloxetine MDD trials was designed to determine whether early improvement in anxiety symptoms predicts MDD remission. Methods: Eight trials were pooled. Patients with a baseline 17-item Hamilton Rating Scale for Depression (HA-MD17) anxiety/somatization factor score ≥7 were considered to have anxious depression. Early response on the HAMD17 total score was defined as a 20% reduction at weeks 2 or 4, a 30% reduction at weeks 2 or 4, or a 50% reduction at weeks 2 or 4 in the HAMD17 anxiety subscale. Each category was analyzed separately for all patients. MDD remission is a score of ≤7 on the HAMD17 total score at study endpoint. Results: The early responder group in each analysis showed greater numerical improvement at endpoint on the HAMD17 total score than the nonresponder group. Duloxetine showed statistically significantly greater improvement than placebo in most nonresponder and responder subgroups. There were no statistically significant interaction effects for the difference between duloxetine and placebo for any of the anxious categories. Conclusion: Although patients who responded in the various response categories had greater numerical improvement and greater remission rates than nonresponding patients, the response and nonresponse groups did not differ statistically regarding the treatment effect of duloxetine. Therefore, early improve-* Corresponding author.

Research paper thumbnail of PDB33 ECONOMIC EVALUATION OF THREE FIRST-LINE MEDICATIONS IN PAINFUL DIABETIC PERIPHERAL NEUROPHATY IN MEXICO

Value in Health, 2010

Abstracts fied the study population into groups by their oral hypoglycemic agents, and further an... more Abstracts fied the study population into groups by their oral hypoglycemic agents, and further analyzed the hazard ratio of myocardial infarction (MI) in different add-on medication and the survival of cardiovascular diseases between add-on TZDs group and non-TZD group. NMB regression model was used to estimate the cost-effectiveness difference on patients who used TZDs versus non-TZD users. RESULTS: The Cox proportional hazard model analysis demonstrated that sulfonylurea +rosiglitazone group had a higher risk of hospitalization for cardiovascular diseases comparing to add-on metformin group (HR 1.48, 95% CI: 1.21-1.80); As to the cost-effectiveness analysis: 1) Comparing to sulfonylurea+metformin group, the average annual medication cost (AAMC) per capita of sulfonylurea+rosiglitazone group increased NT$12,944, but the average days for hospitalization decreased 0.12 day; while the AAMC of sulfonylurea +pioglitazone group increased NT$10,329, but the average days for hospitalization decreased 0.22 day. 2) Comparing to metformin+sulfonylurea group, the AAMC of metformin+rosiglitazone group increased NT$11,486 dollars, but the average day for hospitalization decreased 0.09 day; while metformin+rosiglitazone group increased NT$11267, but the average days for hospitalization decreased 0.18 day. CONCLU-SIONS: Our results demonstrated that sulfonylurea + rosiglitazone group had a higher risk of hospitalization for cardiovascular diseases versus metformin group with TZD add-on treatment (HR 1.48, 95% CI: 1.21-1.80), and per capita AAMC was higher (NT$12944 increment) which was not justified in the decrease of 0.12 hospitalization days 0.12. As for other metformin add-on groups, the increased medication cost was also not justified. Research and Quality. The data sets provide information on the prescribed drug, demography, office-based visits, outpatients and inpatients for the years 2005 and 2006.The analysis is based on the Medicare payments for anti-diabetic drugs, without considering the drug forms and cost-efficiency as measured by the Medicare payment amounts for office-based visits, inpatients or outpatients. Statistics methods used include One-Way Frequencies, Summary Statistics, Box and Whisker Plots, Linear Multiple Regression and Spearman's rank correlation. SAS SQL and some SAS functions such as the MDY function and 0-1 indicator functions are utilized to preprocess the data. RESULTS: Results demonstrate that metformin users have fewer physician visits, lab tests and shorter length of stay in the hospital and it has a negative relationship with the former two factors. Insulin, metformin and its combination with glyburide are significant to predict the frequencies of doctor office visits, lab tests and length of stay. From the year 2005 to the year 2006, insulin and metformin users reduce their frequencies of physician visits and lab tests as well as days in the hospital. CONCLUSIONS: Among the diabetes medications in Medicare, metformin is the most cost-effective drug due to the fewest Medicare expenditures for office-based visits, inpatients and outpatients with spending one dollar on the drug. In 2006, with Medicare part D, metformin becomes more efficient, while insulin becomes more effective at the cost of an increased price .Therefore, it is recommended to prescribe metformin for the Medicare diabetic beneficiaries.

Research paper thumbnail of Improvement of psychic and somatic symptoms in adult patients with generalized anxiety disorder: examination from a duloxetine, venlafaxine extended-release and placebo-controlled trial

Psychological Medicine, 2009

Background. This study examined the efficacy and tolerability of duloxetine and venlafaxine exten... more Background. This study examined the efficacy and tolerability of duloxetine and venlafaxine extended-release (XR) treatment for generalized anxiety disorder (GAD), with a secondary focus on psychic and somatic symptoms within GAD.

Research paper thumbnail of Major depressive disorder in Latin America: The relationship between depression severity, painful somatic symptoms, and quality of life

Journal of Affective Disorders, 2005

Background: We report on two multi-center, prospective, observational studies (H6U-BC-LRAG and H6... more Background: We report on two multi-center, prospective, observational studies (H6U-BC-LRAG and H6U-BL-LRAH) to determine the clinical profile of Latin American outpatients with major depressive disorder (MDD) and the relationship between depression severity, painful somatic symptoms, and quality of life. Method: Patients (n=989) with MDD were classified according to the presence (SS+) or absence (SSÀ) of painful somatic symptoms using the Somatic Symptom Inventory (SSI). Visual Analogue Scale (VAS) quantified pain severity, HAMD 17 and CGI-S determined depression severity, while the Quality of Life in Depression Scale (QLDS) quantified subjective well-being. Results: At baseline, patients had an average CGI score of 4.5 (F0.8) and HAMD 17 score of 24.9 (F7.2). Of the patients studied, 72.6% reported painful somatic symptoms (95% CI: 69.8, 75.4), with women 2.7 times more likely to be SS+ than men ( pb0.0001). Adjusted mean HAMD 17 (26.79) and CGI-S (4.53) scores for SS+ patients were significantly ( pb0.0001) higher than for SSÀ patients (HAMD 17 : 22.87; CGI-S: 4.28). SS+ patients had greater severity of pain across all VAS measures ( pb0.0001). The presence of somatic symptoms had a significantly deleterious effect on quality of life ( pb0.0001). Conclusion: Greater severity of painful somatic symptoms was associated with increased depression severity and reduced quality of life. We concluded that both emotional and physical manifestations of MDD must be addressed for successful treatment. D

Research paper thumbnail of Effectiveness of antidepressants in the treatment of major depressive disorder in Latin America

International Journal of Psychiatry in Clinical Practice, 2007

Objective. Painful physical symptoms occur frequently in patients with major depressive disorder ... more Objective. Painful physical symptoms occur frequently in patients with major depressive disorder (MDD), and although numerous studies report the effect of antidepressants on emotional aspects of depression, few focus on their effect on physical symptoms. This observational study was conducted, in a clinical practice setting, to determine antidepressant treatment decisions and their outcome on the physical and emotional symptoms of MDD. Methods. Patients with a mean score ≥2 for pain-related items on the Somatic Symptom Inventory (SSI) were classified with painful physical symptoms (PPS +) and differentiated from the remaining patients (PPS -). Severity of depression and physical pain were determined using the 17-item Hamilton Depression Rating Scale (HAMD17) and Clinical Global Impressions of Severity Scale (CGI-S), and Visual Analog Scale (VAS), respectively. Results. At baseline, 72.6% of patients were PPS+. Compared to PPS- patients, PPS +patients were, on average, significantly more depressed at baseline (mean difference [95% CI]: HAMD17 4.6 [3.6, 5.5] and CGI-S 0.3 [0.2, 0.4]; all p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001), and remained more depressed and in greater pain at endpoint (HAMD17p=0.0074, CGI-S P =0.0151, and VAS P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). In addition, fewer PPS+ patients (65.8%) achieved remission (total HAMD17≤7) compared to PPS- patients (74.6%, P =0.0180). Conclusions. Painful physical symptoms are prevalent in MDD patients, highlighting the importance of addressing both the physical and emotional symptoms of depression.

Research paper thumbnail of Frequency of treatment-emergent sexual dysfunction and treatment effectiveness during SSRI or duloxetine therapy: 8-week data from a 6-month observational study

International Journal of Psychiatry in Clinical Practice, 2011

In randomised controlled trials, the frequency of treatment-emergent sexual dysfunction (TESD) in... more In randomised controlled trials, the frequency of treatment-emergent sexual dysfunction (TESD) in patients with major depressive disorder (MDD) at week 8 was lower with duloxetine than selective serotonin reuptake inhibitor (SSRI) therapy. This 6-month, prospective, observational study compared the frequency of TESD (using the Arizona Sexual Experience [ASEX] scale) in MDD patients treated with duloxetine or SSRI monotherapy in the first 8 weeks in normal clinical practice. Physician-assessed TESD frequency at week 8 was comparable with duloxetine and SSRI monotherapy (23.9 and 26.2%, respectively; P = 0.545). Improvements in Clinical Global Impressions of Severity (CGI-S), 16-item Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR(16)), Integral Inventory for Depression (IID) total scores and remission rates were statistically significantly greater with duloxetine than SSRI monotherapy (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001, 0.010, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, and 0.002, respectively), but TESD attenuated improvements in quality of life measures (EuroQoL questionnaire-5 dimensions [EQ-5D] and Sheehan Disability Scale [SDS] scores: ≤0.012). Several factors were significantly (P ≤ 0.05) associated with TESD at week 8 in this study. TESD rates with duloxetine and SSRIs at week 8 were comparable, however, significant differences in effectiveness were observed in favour of duloxetine. Antidepressant tolerability with respect to TESD must be managed to maximize remission of depressed patients.

Research paper thumbnail of Treatment-emergent sexual dysfunction with SSRIs and duloxetine: Effectiveness and functional outcomes over a 6-month observational period

International Journal of Psychiatry in Clinical Practice, 2011

Objective . To evaluate frequencies of treatment-emergent sexual dysfunction (TESD) in patients w... more Objective . To evaluate frequencies of treatment-emergent sexual dysfunction (TESD) in patients with major depressive disorder (MDD) treated with duloxetine or selective serotonin reuptake inhibitor (SSRI) monotherapy for up to 6 months in a prospective, observational study. Methods . Sexually active MDD patients without sexual dysfunction at entry were enrolled from twelve countries ( N ϭ 1,647). TESD was assessed over the study period using the Arizona sexual experience (ASEX) scale. A priori -specifi ed secondary 6-month clinical endpoints were also examined. Results . The frequency of TESD at 6 months with duloxetine was comparable to that with SSRI monotherapy (23.4 and 28.7%, respectively; P ϭ 0.087). Improvements in Clinical Global Impressions of Severity (CGI-S), 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR 16 ), Integral Inventory for Depression (IID) total scores, remission and sustained remission rates were statistically signifi cantly greater with duloxetine than SSRI monotherapy at 6 months ( P Ͻ 0.001 for each), but TESD attenuated improvements in quality of life measures. Four factors were consistently signifi cantly ( P Յ 0.05) associated with TESD at week 8 and 6 months. Conclusions . Six-month TESD rates were comparable between duloxetine and SSRIs, with greater MDD effectiveness in favour of duloxetine. Improved recognition and management of TESD may improve quality of life for MDD patients in usual clinical practice. ABSTRACT Objectives: Previous research has been inconclusive whether attention-deficit/hyperactivity disorder (ADHD), when comorbid with disruptive disorders (oppositional defiant disorder [ODD] or conduct disorder [CD]), with the internalizing disorders (anxiety and/or depression), or with both, should constitute separate clinical entities. Determination of the clinical significance of potential ADHD + internalizing disorder or ADHD + ODD/CD syndromes could yield better diagnostic decision-making, treatment planning, and treatment outcomes. Method: Drawing upon cross-sectional and longitudinal information from 579 children (aged 7-9.9 years) with ADHD participating in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA), investigators applied validational criteria to compare ADHD subjects with and without comorbid internalizing disorders and ODD/CD. Results: Substantial evidence of main effects of internalizing and externalizing comorbid disorders was found. Moderate evidence of interactions of parent-reported anxiety and

Research paper thumbnail of Major depressive disorder severity and the frequency of painful physical symptoms: a pooled analysis of observational studies

Current Medical Research and Opinion, 2012

This retrospective post-hoc analysis of observational studies assesses the frequency of painful p... more This retrospective post-hoc analysis of observational studies assesses the frequency of painful physical symptoms (PPS) in patients with major depressive disorder (MDD) of varied severity as may be seen in clinical practice. Observational studies of MDD that collected a clinician-reported measure of depression severity and included assessment of PPS were screened for this individual patient-level analysis. Six observational studies were included that enrolled outpatients with a diagnosis of MDD (assessed using the 17-item Hamilton depression scale, Hospital Anxiety and Depression Scale-Depression, or Inventory of Depressive Symptomatology). Measures of PPS were based on the original study assessment (modified Somatic Symptom Inventory [SSI] and Visual Analogue Scale [VAS]). Patients were divided into analysis cohorts based on the presence or absence of PPS. To model PPS status, odds ratios were calculated from logistic regression for cross-sectional analysis (main analysis) and generalized linear mixed models for longitudinal models (exploratory longitudinal analysis). For the main analysis, four studies (N = 2943, 71.6% female, mean age 45.3 years) were identified. Of 2901 eligible patients, 61.7% were classified as having painful physical symptoms (PPS+). At study entry, 73.1% (957/1309) of patients in the severe category of depression, 56.8% (537/945) of those with moderate depression, and 45.6% (295/647) of those with mild depression were PPS+. The exploratory longitudinal analysis was performed using a subset (N = 2430) from the studies used in the main analysis plus two others (an additional 7984 patients, 6742 of which were modeled). The likelihood of patients that were PPS- at baseline later developing PPS was 5% to 13% greater for patients with increased depression severity (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and the likelihood of PPS+ patients later not having PPS was 9% to 17% less for patients with increased depression severity (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Since this is a retrospective aggregate analysis of several observational studies, and due to missing data, care should be taken in the interpretation of these results. Despite the use of adjustment techniques, selection bias and unmeasured confounding may still be an issue for comparative analysis as not all variables were collected for all studies. For patients treated in typical care settings, PPS were associated with depression severity. However, patients with mild and moderate depression also exhibited PPS. Clinicians should be aware that PPS are present, and may warrant treatment, across depression severities.

Research paper thumbnail of Use of antidepressants in the treatment of depression in Asia: Guidelines, clinical evidence, and experience revisited

Major depressive disorder is prevalent worldwide, and only about half of those affected will expe... more Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients.