Background: The objectives of this study were to assess the maintenance of effect of duloxetine 6... more Background: The objectives of this study were to assess the maintenance of effect of duloxetine 60 mg once-daily (QD) in Chinese patients with chronic pain due to osteoarthritis (OA) of the knee or hip and to provide additional long-term safety data. Methods: This was an open-label, extension phase of a randomized, double-blind, placebo-controlled clinical trial. Eligible patients were outpatients who met the American College of Rheumatology clinical and radiographic criteria for OA with a rating ≥4 on Brief Pain Inventory (BPI) 24-h average pain. After completing the 13-week placebocontrolled phase, patients originally assigned to placebo were titrated to duloxetine 60 mg QD (PLA_DLX), whereas patients originally assigned to duloxetine 60 mg QD remained on the same dose of duloxetine (DLX_DLX) for another 13 weeks. The maintenance effect of duloxetine 60 mg QD during the extension phase was evaluated by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase for patients who took duloxetine and reported ≥30% reduction in BPI average pain at the end of placebo-controlled phase (placebocontrolled phase duloxetine responders). Other BPI severity and interference items, as well as safety and tolerability, were assessed. Results: Of 342 patients entering the extension phase, 162 (97.6%) DLX_DLX-treated patients and 157 (89.2%) PLA_ DLX-treated patients completed this phase. Most patients (76.0%) were female. Mean age was 60.6 years. Mean BPI average pain was 5.5 at baseline of the placebo-controlled phase. Among 113 placebo-controlled phase duloxetine responders, mean change in BPI average pain during the extension phase was − 0.59 (from 2.47 to 1.88); the upper bound of the 1-sided 97.5% CI was − 0.31 and less than the pre-specified non-inferiority margin of a 1.5-point increase (p < 0.001). Significant within-group improvements in all BPI items were observed for both PLA_DLX and DLX_DLX groups during the extension phase (all p < 0.01). No deaths or suicide-related events occurred. Seven (4. 0%) PLA_DLX-treated patients and no DLX_DLX-treated patients discontinued due to an adverse event. Conclusion: The analgesic effect of duloxetine 60 mg QD among treatment responders was maintained for the entire duration of the extension phase. Duloxetine 60 mg QD was well tolerated during the extension phase. Trial registration: ClinicalTrials.gov identification number NCT01931475. Registered 29 August 2013.
The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once dail... more The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once daily (quaque die [everyday], QD) among Korean men with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in a real-world clinical setting. Materials and Methods: This was a single-country, prospective, observational cohort study in which patients newly prescribed tadalafil 5 mg QD for the treatment of BPH/LUTS were followed-up for 12±2 or 24±2 weeks, or to the last treatment, during post-marketing surveillance. Safety was evaluated in terms of the frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Effectiveness was assessed by changes in the International Prostate Symptom Score (IPSS) from baseline to each endpoint. Results: All patients receiving ≥1 dose of tadalafil 5 mg QD (N=637) were included in the safety population. Two percent of patients (n=13) experienced 15 TEAEs of mild (n=10; 66.7%) or moderate (n=5; 33.3%) severity. No severe TEAEs and no SAEs were reported. Effectiveness evaluations included all patients receiving tadalafil who had both baseline and endpoint observations (12-week, N=265; 24-week, N=44). Compared with baseline, the mean IPSS total score (±standard error) significantly improved by 4.7±0.3 and 6.4±0.7 points at the 12-and 24-week endpoints, respectively (p<0.0001), with significant improvements also observed on the storage, voiding, and quality of life subscores. In total, 69.1% of the patients had a clinically meaningful ≥3-point improvement in the IPSS total score. Conclusions: Tadalafil 5 mg QD was well tolerated and effective in Korean men with BPH/LUTS in a real-world clinical setting.
We assessed the efficacy and safety of duloxetine (60 mg, once daily), compared with placebo, dur... more We assessed the efficacy and safety of duloxetine (60 mg, once daily), compared with placebo, during a 13-week treatment period in Chinese patients with chronic pain due to osteoarthritis (OA). Patients were at least 40 years old (male or female) who met American College of Rheumatology clinical and radiographic criteria for the diagnosis of OA of the knee or hip. The primary efficacy measure in this phase 3, randomized, double-blind, placebo-controlled clinical trial was assessment of pain severity by the Brief Pain Inventory (BPI) 24-hour Average Pain rating. The clinical trial was conducted at 17 study centers. Statistical approaches included mixed-effects model repeated measures and analysis of covariance. A Fisher exact test was applied to categorical variables. Of 407 patients randomized (duloxetine: N=205; placebo: N=202), 166 (81.0%) patients from the duloxetine group and 176 (87.1%) patients from the placebo group completed the 13-week treatment phase. The majority (76.4%) ...
Background: Duloxetine has been approved in the United States, European Union and some Asian coun... more Background: Duloxetine has been approved in the United States, European Union and some Asian countries for the treatment of diabetic peripheral neuropathic pain (DPNP). We assessed the efficacy and safety of duloxetine (60 mg once daily) compared with placebo in Chinese patients suffering from DPNP. Methods: This was a phase 3, multicenter, randomised, double-blind, parallel, placebo-controlled, 12-week trial of the treatment of DPNP with duloxetine. Subjects were male and female outpatients ≥ 18 years of age with DPNP, as assessed by the Michigan Neuropathy Screening Instrument, and had a rating of ≥ 4 on the Brief Pain Inventory-Modified Short Form-Severity weekly average pain item. The primary efficacy measure was the reduction in pain severity from baseline to 12 weeks, as measured by the weekly mean of 24-h average pain ratings recorded in the patient's diary. Mean changes from baseline in efficacy measures were analysed by a restricted maximum likelihood-based, mixed-effects model repeated measures approach and by analysis of covariance. Results: Of the 405 patients randomised, 203 patients were assigned to duloxetine 60 mg once daily and 202 patients were assigned to placebo. Duloxetine-treated patients showed significantly greater pain relief on 24-h average pain ratings compared with placebo-treated patients each week of the 12-week study period [week 12: least squares (LS) mean change duloxetine: À2.40, placebo: À1.97; LS mean change difference (95% confidence interval) = À0.43 (À0.82, À0.04), p = 0.030]. Compared with placebo, patients treated with duloxetine experienced higher rates of nausea (p = 0.010), somnolence (p < 0.001) and asthenia (p = 0.002). Conclusions: Duloxetine-treated patients showed significantly greater pain relief compared with placebo-treated patients over the 12-week study period. Duloxetine was shown in Chinese patients to have a safety profile similar to that found in previous duloxetine trials. What's known The efficacy of duloxetine for the treatment of diabetic peripheral neuropathic pain (DPNP) is welldocumented. This treatment has been approved in the United States, Europe and some Asian countries. What's new The present study is the first positive registration study of the use of duloxetine in the treatment of Chinese patients with DPNP. Patients treated with duloxetine had significantly greater reduction in weekly means of 24-h average pain, 24-h worst pain and 24-h night pain relative to placebo-treated patients. A greater proportion of patients treated with duloxetine experienced 30% and 50% reductions in weekly means of 24-h average pain, compared with the placebo group. More patients treated with duloxetine (compared with placebo) reported feeling 'much better.' The safety profile in Chinese patients was similar to that in other duloxetine studies.
Objectives: To conduct a systematic review of literature in on epidemiology and economic studies ... more Objectives: To conduct a systematic review of literature in on epidemiology and economic studies for patients diagnosed with Non-Psychotic Major Depressive Disorder (MDD). MethOds: The initial search strategy was developed in the PubMed/Medline database, and was then translated for the Cochrane and Embase database searches. Search strings for epidemiology and economics studies for MDD were constructed using varied approaches that included the use of MeSH terms, as well as keywords that would afford the best retrieval. Search statements were then combined to produce a final search set. Additional parameters were placed on the final search strategy to limit the retrieval to articles written in English, involving human subjects and published between 2000 and 2010. Results: Our search revealed 289 articles for epidemiology and 200 articles for economic studies on MDD from PubMed/Medline/Embase/Cochrane databases. After removing duplicates and non-relevant articles, 17 for epidemiology and 26 for economic studies were included in the final analysis. Fifteen studies on epidemiology were focused on MDD prevalence, one study was on cumulative incidence. Prevalence estimates were higher for lifetime than past year and ranged between 3.1% and 26.6% for lifetime prevalence and between 1.5% and 11.7% for past-year prevalence. Two studies examined burden of illness, one study budgetary impact of MDD, 14 studies examined cost effectiveness of MDD treatments, 3 studies examined cost utility analysis and 6 other studies examined retrospective claims analysis. cOnclusiOns: MDD prevalence was higher in the lifetime estimates, when compared to the estimates reflecting shorter time frames, although there appeared to be greater variability in the lifetime estimates. Overall, the cost of treating MDD varied with type of study, study time frame, study perspective, the year in which the costs were calculated, and the pharmacotherapy prescribed.
To assess and compare the levels of functioning in patients with major depressive disorder treate... more To assess and compare the levels of functioning 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. Patients and methods: Data for this post hoc analysis were taken from a 6-month prospective observational study involving 1,549 patients with major depressive disorder without sexual dysfunction. The present analysis focused on a subgroup of patients from East Asia (n=587). Functioning was measured using the Sheehan Disability Scale (SDS). Depression severity was assessed using the 16-item Quick Inventory of Depressive Symptomatology-Self Report. PPS were rated using the modified Somatic Symptom Inventory. A mixed model with repeated measures was fitted to compare the levels of functioning between duloxetine-treated (n=227) and SSRI-treated (n=225) patients, adjusting for baseline patient characteristics. Results: The mean SDS total score was similar between the two treatment cohorts (15.46 [standard deviation =6.11] in the duloxetine cohort and 16.36 [standard deviation =6.53] in the SSRI cohort, P=0.077) at baseline. Both descriptive and regression analyses confirmed improvement in functioning in both groups during follow-up, but duloxetine-treated patients achieved better functioning. At 24 weeks, the estimated mean SDS total score was 4.48 (standard error =0.80) in the duloxetine cohort, which was statistically significantly lower (ie, better functioning) than that of 6.76 (standard error =0.77) in the SSRI cohort (P,0.001). This treatment difference was more apparent in the subgroup of patients with PPS at baseline. Similar patterns were also observed for SDS subscores (work, social life, and family life). Conclusion: Depressed patients treated with duloxetine achieved better functioning compared to those treated with SSRIs. This treatment difference was mostly driven by patients with PPS at baseline.
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.
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...
fied the study population into groups by their oral hypoglycemic agents, and further analyzed the... more 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. CONCLUSIONS: 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.
BackgroundThis study examined the efficacy and tolerability of duloxetine and venlafaxine extende... more BackgroundThis 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.MethodThe design was a 10-week, multi-center, double-blind placebo-controlled study of duloxetine (20 mg or 60–120 mg once daily) and venlafaxine XR (75–225 mg once daily) treatment. Efficacy was measured using the Hamilton Anxiety Rating Scale (HAMA), which includes psychic and somatic factor scores. Tolerability was measured by occurrence of treatment-emergent adverse events (TEAEs) and discontinuation rates.ResultsAdult out-patients (mean age 42.8 years; 57.1% women) with DSM-IV-defined GAD were randomly assigned to placebo (n=170), duloxetine 20 mg (n=84), duloxetine 60–120 mg (n=158) or venlafaxine XR 75–225 mg (n=169) treatment. Each of the three active treatment groups had significantly greater improvements on HAMA total score from baseline to endpoint...
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NH... more This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
International Journal of Psychiatry in Clinical Practice, 2011
Background. In randomised controlled trials, the frequency of treatment-emergent sexual dysfuncti... more Background. 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. Methods. 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 fi rst 8 weeks in normal clinical practice. Results. Physician-assessed TESD frequency at week 8 was comparable with duloxetine and SSRI monotherapy (23.9 and 26.2%, respectively; P ϭ 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 signifi cantly greater with duloxetine than SSRI monotherapy (P Ͻ 0.001, 0.010, Ͻ 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: Յ 0.012). Several factors were signifi cantly (P Յ 0.05) associated with TESD at week 8 in this study. Conclusions. TESD rates with duloxetine and SSRIs at week 8 were comparable, however, signifi cant differences in effectiveness were observed in favour of duloxetine. Antidepressant tolerability with respect to TESD must be managed to maximize remission of depressed patients.
Report weight change baseline up to 12-15 months in duloxetine-treated patients during clinical t... more Report weight change baseline up to 12-15 months in duloxetine-treated patients during clinical trials of chronic painful conditions of diabetic peripheral neuropathic pain (DPNP), fibromyalgia, chronic low back pain (CLBP) and chronic knee pain as a result of osteoarthritis. Methods: Weight change data from 16 duloxetine studies in chronic painful conditions were pooled by pain condition and duration, creating 10 datasets. Datasets included placebo-controlled, open-label and routine-care-controlled designs. Assessments included mean weight change from baseline, baseline body mass index category, potentially clinically significant (PCS) weight change and weight-related treatment-emergent adverse events. Results: Total number of patients was 5111 with mean baseline weight ranging from 70 to 97 kg. All duloxetine groups had significant mean weight loss compared with placebo at acute phase completion (p £ 0.001). In studies > 3 months, patients from fibromyalgia and CLBP studies had overall mean weight increase (up to 1.1 kg), whereas patients in DPNP studies had overall mean weight loss ()0.33 to)1.7 kg) at end-point. Overall, the percentage of patients with PCS weight gain was 0.4-16% and PCS weight loss was 2.5-9.9%. Discussion: Weight change data in clinical trials of patients with fibromyalgia or CLBP treated with duloxetine for up to 15 months were consistent with data reported in 10 clinical trials of patients with major depressive disorder (MDD) using duloxetine up to 52 weeks. Patients with DPNP had weight loss at end-point. Conclusion: Mean weight changes and percentages of patients with PCS weight loss and weight gain observed in DPNP, fibromyalgia and CLBP with long-term duloxetine treatment were consistent with those reported previously for MDD studies. What's known A prior publication reported weight changes with long-term use (up to 52 weeks) of duloxetine in patients with major depressive disorder. What's new This manuscript extends those observations to report weight change with duloxetine use in clinical trials lasting up to 15 months in patients with chronic painful conditions.
... 1237 Soundings Down and out in Italy George Dunea; Drunk in charge Ian Robertson 1238 Medicin... more ... 1237 Soundings Down and out in Italy George Dunea; Drunk in charge Ian Robertson 1238 Medicine and the Media The longestday Melanie D'Souza; None so deafasthosethatwillnothearTina Beaconsfield 1239 PersonalView Their simple sorrows Peter Hettiaratchy ...
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;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;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.
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;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.
Page 1. Salud Mental, Vol. 30, No. 2, marzo-abril 2007 25 SUMMARY Background Major Depressive Dis... more Page 1. Salud Mental, Vol. 30, No. 2, marzo-abril 2007 25 SUMMARY Background Major Depressive Disorder (MDD) is a disease associated to emo-tional, vegetative and physical symptoms, including for the latter those pain-related symptoms. ...
Background: The objectives of this study were to assess the maintenance of effect of duloxetine 6... more Background: The objectives of this study were to assess the maintenance of effect of duloxetine 60 mg once-daily (QD) in Chinese patients with chronic pain due to osteoarthritis (OA) of the knee or hip and to provide additional long-term safety data. Methods: This was an open-label, extension phase of a randomized, double-blind, placebo-controlled clinical trial. Eligible patients were outpatients who met the American College of Rheumatology clinical and radiographic criteria for OA with a rating ≥4 on Brief Pain Inventory (BPI) 24-h average pain. After completing the 13-week placebocontrolled phase, patients originally assigned to placebo were titrated to duloxetine 60 mg QD (PLA_DLX), whereas patients originally assigned to duloxetine 60 mg QD remained on the same dose of duloxetine (DLX_DLX) for another 13 weeks. The maintenance effect of duloxetine 60 mg QD during the extension phase was evaluated by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase for patients who took duloxetine and reported ≥30% reduction in BPI average pain at the end of placebo-controlled phase (placebocontrolled phase duloxetine responders). Other BPI severity and interference items, as well as safety and tolerability, were assessed. Results: Of 342 patients entering the extension phase, 162 (97.6%) DLX_DLX-treated patients and 157 (89.2%) PLA_ DLX-treated patients completed this phase. Most patients (76.0%) were female. Mean age was 60.6 years. Mean BPI average pain was 5.5 at baseline of the placebo-controlled phase. Among 113 placebo-controlled phase duloxetine responders, mean change in BPI average pain during the extension phase was − 0.59 (from 2.47 to 1.88); the upper bound of the 1-sided 97.5% CI was − 0.31 and less than the pre-specified non-inferiority margin of a 1.5-point increase (p < 0.001). Significant within-group improvements in all BPI items were observed for both PLA_DLX and DLX_DLX groups during the extension phase (all p < 0.01). No deaths or suicide-related events occurred. Seven (4. 0%) PLA_DLX-treated patients and no DLX_DLX-treated patients discontinued due to an adverse event. Conclusion: The analgesic effect of duloxetine 60 mg QD among treatment responders was maintained for the entire duration of the extension phase. Duloxetine 60 mg QD was well tolerated during the extension phase. Trial registration: ClinicalTrials.gov identification number NCT01931475. Registered 29 August 2013.
The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once dail... more The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once daily (quaque die [everyday], QD) among Korean men with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in a real-world clinical setting. Materials and Methods: This was a single-country, prospective, observational cohort study in which patients newly prescribed tadalafil 5 mg QD for the treatment of BPH/LUTS were followed-up for 12±2 or 24±2 weeks, or to the last treatment, during post-marketing surveillance. Safety was evaluated in terms of the frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Effectiveness was assessed by changes in the International Prostate Symptom Score (IPSS) from baseline to each endpoint. Results: All patients receiving ≥1 dose of tadalafil 5 mg QD (N=637) were included in the safety population. Two percent of patients (n=13) experienced 15 TEAEs of mild (n=10; 66.7%) or moderate (n=5; 33.3%) severity. No severe TEAEs and no SAEs were reported. Effectiveness evaluations included all patients receiving tadalafil who had both baseline and endpoint observations (12-week, N=265; 24-week, N=44). Compared with baseline, the mean IPSS total score (±standard error) significantly improved by 4.7±0.3 and 6.4±0.7 points at the 12-and 24-week endpoints, respectively (p<0.0001), with significant improvements also observed on the storage, voiding, and quality of life subscores. In total, 69.1% of the patients had a clinically meaningful ≥3-point improvement in the IPSS total score. Conclusions: Tadalafil 5 mg QD was well tolerated and effective in Korean men with BPH/LUTS in a real-world clinical setting.
We assessed the efficacy and safety of duloxetine (60 mg, once daily), compared with placebo, dur... more We assessed the efficacy and safety of duloxetine (60 mg, once daily), compared with placebo, during a 13-week treatment period in Chinese patients with chronic pain due to osteoarthritis (OA). Patients were at least 40 years old (male or female) who met American College of Rheumatology clinical and radiographic criteria for the diagnosis of OA of the knee or hip. The primary efficacy measure in this phase 3, randomized, double-blind, placebo-controlled clinical trial was assessment of pain severity by the Brief Pain Inventory (BPI) 24-hour Average Pain rating. The clinical trial was conducted at 17 study centers. Statistical approaches included mixed-effects model repeated measures and analysis of covariance. A Fisher exact test was applied to categorical variables. Of 407 patients randomized (duloxetine: N=205; placebo: N=202), 166 (81.0%) patients from the duloxetine group and 176 (87.1%) patients from the placebo group completed the 13-week treatment phase. The majority (76.4%) ...
Background: Duloxetine has been approved in the United States, European Union and some Asian coun... more Background: Duloxetine has been approved in the United States, European Union and some Asian countries for the treatment of diabetic peripheral neuropathic pain (DPNP). We assessed the efficacy and safety of duloxetine (60 mg once daily) compared with placebo in Chinese patients suffering from DPNP. Methods: This was a phase 3, multicenter, randomised, double-blind, parallel, placebo-controlled, 12-week trial of the treatment of DPNP with duloxetine. Subjects were male and female outpatients ≥ 18 years of age with DPNP, as assessed by the Michigan Neuropathy Screening Instrument, and had a rating of ≥ 4 on the Brief Pain Inventory-Modified Short Form-Severity weekly average pain item. The primary efficacy measure was the reduction in pain severity from baseline to 12 weeks, as measured by the weekly mean of 24-h average pain ratings recorded in the patient's diary. Mean changes from baseline in efficacy measures were analysed by a restricted maximum likelihood-based, mixed-effects model repeated measures approach and by analysis of covariance. Results: Of the 405 patients randomised, 203 patients were assigned to duloxetine 60 mg once daily and 202 patients were assigned to placebo. Duloxetine-treated patients showed significantly greater pain relief on 24-h average pain ratings compared with placebo-treated patients each week of the 12-week study period [week 12: least squares (LS) mean change duloxetine: À2.40, placebo: À1.97; LS mean change difference (95% confidence interval) = À0.43 (À0.82, À0.04), p = 0.030]. Compared with placebo, patients treated with duloxetine experienced higher rates of nausea (p = 0.010), somnolence (p < 0.001) and asthenia (p = 0.002). Conclusions: Duloxetine-treated patients showed significantly greater pain relief compared with placebo-treated patients over the 12-week study period. Duloxetine was shown in Chinese patients to have a safety profile similar to that found in previous duloxetine trials. What's known The efficacy of duloxetine for the treatment of diabetic peripheral neuropathic pain (DPNP) is welldocumented. This treatment has been approved in the United States, Europe and some Asian countries. What's new The present study is the first positive registration study of the use of duloxetine in the treatment of Chinese patients with DPNP. Patients treated with duloxetine had significantly greater reduction in weekly means of 24-h average pain, 24-h worst pain and 24-h night pain relative to placebo-treated patients. A greater proportion of patients treated with duloxetine experienced 30% and 50% reductions in weekly means of 24-h average pain, compared with the placebo group. More patients treated with duloxetine (compared with placebo) reported feeling 'much better.' The safety profile in Chinese patients was similar to that in other duloxetine studies.
Objectives: To conduct a systematic review of literature in on epidemiology and economic studies ... more Objectives: To conduct a systematic review of literature in on epidemiology and economic studies for patients diagnosed with Non-Psychotic Major Depressive Disorder (MDD). MethOds: The initial search strategy was developed in the PubMed/Medline database, and was then translated for the Cochrane and Embase database searches. Search strings for epidemiology and economics studies for MDD were constructed using varied approaches that included the use of MeSH terms, as well as keywords that would afford the best retrieval. Search statements were then combined to produce a final search set. Additional parameters were placed on the final search strategy to limit the retrieval to articles written in English, involving human subjects and published between 2000 and 2010. Results: Our search revealed 289 articles for epidemiology and 200 articles for economic studies on MDD from PubMed/Medline/Embase/Cochrane databases. After removing duplicates and non-relevant articles, 17 for epidemiology and 26 for economic studies were included in the final analysis. Fifteen studies on epidemiology were focused on MDD prevalence, one study was on cumulative incidence. Prevalence estimates were higher for lifetime than past year and ranged between 3.1% and 26.6% for lifetime prevalence and between 1.5% and 11.7% for past-year prevalence. Two studies examined burden of illness, one study budgetary impact of MDD, 14 studies examined cost effectiveness of MDD treatments, 3 studies examined cost utility analysis and 6 other studies examined retrospective claims analysis. cOnclusiOns: MDD prevalence was higher in the lifetime estimates, when compared to the estimates reflecting shorter time frames, although there appeared to be greater variability in the lifetime estimates. Overall, the cost of treating MDD varied with type of study, study time frame, study perspective, the year in which the costs were calculated, and the pharmacotherapy prescribed.
To assess and compare the levels of functioning in patients with major depressive disorder treate... more To assess and compare the levels of functioning 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. Patients and methods: Data for this post hoc analysis were taken from a 6-month prospective observational study involving 1,549 patients with major depressive disorder without sexual dysfunction. The present analysis focused on a subgroup of patients from East Asia (n=587). Functioning was measured using the Sheehan Disability Scale (SDS). Depression severity was assessed using the 16-item Quick Inventory of Depressive Symptomatology-Self Report. PPS were rated using the modified Somatic Symptom Inventory. A mixed model with repeated measures was fitted to compare the levels of functioning between duloxetine-treated (n=227) and SSRI-treated (n=225) patients, adjusting for baseline patient characteristics. Results: The mean SDS total score was similar between the two treatment cohorts (15.46 [standard deviation =6.11] in the duloxetine cohort and 16.36 [standard deviation =6.53] in the SSRI cohort, P=0.077) at baseline. Both descriptive and regression analyses confirmed improvement in functioning in both groups during follow-up, but duloxetine-treated patients achieved better functioning. At 24 weeks, the estimated mean SDS total score was 4.48 (standard error =0.80) in the duloxetine cohort, which was statistically significantly lower (ie, better functioning) than that of 6.76 (standard error =0.77) in the SSRI cohort (P,0.001). This treatment difference was more apparent in the subgroup of patients with PPS at baseline. Similar patterns were also observed for SDS subscores (work, social life, and family life). Conclusion: Depressed patients treated with duloxetine achieved better functioning compared to those treated with SSRIs. This treatment difference was mostly driven by patients with PPS at baseline.
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.
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...
fied the study population into groups by their oral hypoglycemic agents, and further analyzed the... more 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. CONCLUSIONS: 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.
BackgroundThis study examined the efficacy and tolerability of duloxetine and venlafaxine extende... more BackgroundThis 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.MethodThe design was a 10-week, multi-center, double-blind placebo-controlled study of duloxetine (20 mg or 60–120 mg once daily) and venlafaxine XR (75–225 mg once daily) treatment. Efficacy was measured using the Hamilton Anxiety Rating Scale (HAMA), which includes psychic and somatic factor scores. Tolerability was measured by occurrence of treatment-emergent adverse events (TEAEs) and discontinuation rates.ResultsAdult out-patients (mean age 42.8 years; 57.1% women) with DSM-IV-defined GAD were randomly assigned to placebo (n=170), duloxetine 20 mg (n=84), duloxetine 60–120 mg (n=158) or venlafaxine XR 75–225 mg (n=169) treatment. Each of the three active treatment groups had significantly greater improvements on HAMA total score from baseline to endpoint...
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NH... more This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
International Journal of Psychiatry in Clinical Practice, 2011
Background. In randomised controlled trials, the frequency of treatment-emergent sexual dysfuncti... more Background. 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. Methods. 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 fi rst 8 weeks in normal clinical practice. Results. Physician-assessed TESD frequency at week 8 was comparable with duloxetine and SSRI monotherapy (23.9 and 26.2%, respectively; P ϭ 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 signifi cantly greater with duloxetine than SSRI monotherapy (P Ͻ 0.001, 0.010, Ͻ 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: Յ 0.012). Several factors were signifi cantly (P Յ 0.05) associated with TESD at week 8 in this study. Conclusions. TESD rates with duloxetine and SSRIs at week 8 were comparable, however, signifi cant differences in effectiveness were observed in favour of duloxetine. Antidepressant tolerability with respect to TESD must be managed to maximize remission of depressed patients.
Report weight change baseline up to 12-15 months in duloxetine-treated patients during clinical t... more Report weight change baseline up to 12-15 months in duloxetine-treated patients during clinical trials of chronic painful conditions of diabetic peripheral neuropathic pain (DPNP), fibromyalgia, chronic low back pain (CLBP) and chronic knee pain as a result of osteoarthritis. Methods: Weight change data from 16 duloxetine studies in chronic painful conditions were pooled by pain condition and duration, creating 10 datasets. Datasets included placebo-controlled, open-label and routine-care-controlled designs. Assessments included mean weight change from baseline, baseline body mass index category, potentially clinically significant (PCS) weight change and weight-related treatment-emergent adverse events. Results: Total number of patients was 5111 with mean baseline weight ranging from 70 to 97 kg. All duloxetine groups had significant mean weight loss compared with placebo at acute phase completion (p £ 0.001). In studies > 3 months, patients from fibromyalgia and CLBP studies had overall mean weight increase (up to 1.1 kg), whereas patients in DPNP studies had overall mean weight loss ()0.33 to)1.7 kg) at end-point. Overall, the percentage of patients with PCS weight gain was 0.4-16% and PCS weight loss was 2.5-9.9%. Discussion: Weight change data in clinical trials of patients with fibromyalgia or CLBP treated with duloxetine for up to 15 months were consistent with data reported in 10 clinical trials of patients with major depressive disorder (MDD) using duloxetine up to 52 weeks. Patients with DPNP had weight loss at end-point. Conclusion: Mean weight changes and percentages of patients with PCS weight loss and weight gain observed in DPNP, fibromyalgia and CLBP with long-term duloxetine treatment were consistent with those reported previously for MDD studies. What's known A prior publication reported weight changes with long-term use (up to 52 weeks) of duloxetine in patients with major depressive disorder. What's new This manuscript extends those observations to report weight change with duloxetine use in clinical trials lasting up to 15 months in patients with chronic painful conditions.
... 1237 Soundings Down and out in Italy George Dunea; Drunk in charge Ian Robertson 1238 Medicin... more ... 1237 Soundings Down and out in Italy George Dunea; Drunk in charge Ian Robertson 1238 Medicine and the Media The longestday Melanie D'Souza; None so deafasthosethatwillnothearTina Beaconsfield 1239 PersonalView Their simple sorrows Peter Hettiaratchy ...
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;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;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.
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;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.
Page 1. Salud Mental, Vol. 30, No. 2, marzo-abril 2007 25 SUMMARY Background Major Depressive Dis... more Page 1. Salud Mental, Vol. 30, No. 2, marzo-abril 2007 25 SUMMARY Background Major Depressive Disorder (MDD) is a disease associated to emo-tional, vegetative and physical symptoms, including for the latter those pain-related symptoms. ...
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