[Show abstract][Hide abstract] ABSTRACT: Duloxetine, a selective serotonin (5-hydroxytryptamine) and norepinephrine reuptake inhibitor, has been approved since 2004 for the treatment of adults with major depressive disorder (MDD). It is currently not approved for use in pediatric patients (aged <18 years) with MDD. The clinical development program for duloxetine in the pediatric MDD population, which consisted of three clinical studies, provided extensive data on the safety, tolerability, and pharmacokinetics of duloxetine across a wide dose range in pediatric patients of differing ages, sex, body weights, and sexual maturation.
[Show abstract][Hide abstract] ABSTRACT: Objective:
The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD).
Patients (n=337) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine (60-120 mg once daily [QD], n=117), fluoxetine (20-40 mg QD, n=117), or placebo (n=103). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS).
Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs (SAEs), total TEAEs, or discontinuation for AE during acute treatment. There were no completed suicides or deaths, and no clinically significant electrocardiogram (ECG) abnormalities observed during the study. One fluoxetine and one duloxetine patient experienced alanine aminotransferase (ALT) three or more times the upper limit of normal, which resolved during the study. A total of 8 (7.1%) duloxetine patients, 7 (6.8%) placebo patients, and 9 (8.0%) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 15/19 (79%) duloxetine, 19/19 (100%) placebo, and 16/19 (84%) fluoxetine had improvement in suicidal ideation at end-point during acute treatment. One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study.
Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number: NCT00849901.
Journal of child and adolescent psychopharmacology 05/2014; 24(4). DOI:10.1089/cap.2013.0146 · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
The purpose of this study was to evaluate the efficacy and safety of duloxetine fixed dose in the treatment of children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD).
Patients (n=463) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine 60 mg QD (n=108), duloxetine 30 mg QD (n=116), fluoxetine 20 mg QD (n=117, active control), or placebo (n=122). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS).
Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. Total TEAEs and discontinuation for AEs were significantly (p<0.05) higher only for the duloxetine 60 mg group versus the placebo group during acute treatment. No clinically significant electrocardiogram (ECG) or laboratory abnormalities were observed, and no completed suicides or deaths occurred during the study. A total of 7 (6.7%) duloxetine 60 mg, 6 (5.2%) duloxetine 30 mg, 9 (8.0%) fluoxetine, and 11 (9.4%) placebo patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 13/16 (81%) duloxetine 60 mg, 16/17 (94%) duloxetine 30 mg, 11/16 (69%) fluoxetine, and 13/15 (87%) placebo had improvement in suicidal ideation at end-point during acute treatment. One fluoxetine, one placebo, and six duloxetine patients had treatment-emergent suicidal behavior during the 36 week study.
Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number ( www.ClinicalTrials.gov ): NCT00849693.
Journal of child and adolescent psychopharmacology 05/2014; 24(4). DOI:10.1089/cap.2013.0096 · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess acute and longer-term safety of duloxetine in the treatment of children and adolescents with major depressive disorder (MDD), a pooled analysis of data from two completed randomized, double-blind, multicenter, phase 3, placebo- and active-controlled trials was undertaken. In these studies, neither duloxetine (investigational drug) nor fluoxetine (active control) demonstrated a statistically significant improvement compared with placebo on the primary efficacy measure.
Patients ages 7-17 years with MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) received duloxetine (n=341), fluoxetine (n=234), or placebo (n=225) for 10 week acute and 26 week extended (duloxetine or fluoxetine only) treatments. Safety measures included treatment-emergent adverse events (TEAEs), the Columbia-Suicide Severity Rating Scale, vital signs, electrocardiograms, laboratory samples, and growth (height and weight) assessments.
Significantly more patients discontinued because of adverse events during duloxetine (8.2%) treatment than during placebo (3.1%) treatment (p≤0.05). TEAEs in >10% of duloxetine-treated patients were headache and nausea. No completed suicides or deaths occurred. During acute treatment, 6.6% of duloxetine-, 8.0% of fluoxetine-, and 8.2% of placebo-treated patients had worsening suicidal ideation from baseline. Among patients initially randomized to duloxetine or fluoxetine who had suicidal ideation at study baseline, 81% of duloxetine- and 77% of fluoxetine-treated patients had improvements in suicidal ideation at end-point in the 36-week studies. Suicidal behavior occurred in two fluoxetine-treated patients and one placebo-treated patient during acute treatment, and in seven duloxetine-treated patients and one fluoxetine-treated patient during extended treatment. Duloxetine-treated patients had a mean pulse increase of ∼3 beats per minute, and mean blood pressure (both systolic and diastolic) increases of <2.0 mm Hg at week 36. Weight decrease (≥3.5%) during acute treatment occurred with statistically (p≤0.05) greater frequency for both the duloxetine (11.4%) and fluoxetine (11.5%) groups versus the placebo (5.5%) group; however, mean weight increase occurred for both duloxetine and fluoxetine groups during extended treatment.
Results from this pooled analysis of two studies were consistent with the known safety and tolerability profile of duloxetine. Clinical Trial Registry Numbers: NCT00849901 and NCT00849693.
59th Meeting of American Academy of Child and Adolescent Psychiatry; 10/2012
[Show abstract][Hide abstract] ABSTRACT: This preliminary, 32-week study assessed the safety, tolerability, and pharmacokinetics of duloxetine in pediatric patients (aged 7-17 years) with major depressive disorder.
Patients received flexible duloxetine doses of 20-120 mg once daily, with dose changes made based on clinical improvement and tolerability. Pharmacokinetic samples were collected across all duloxetine doses, and data were analyzed using population modeling. Primary outcome measures included treatment-emergent adverse events (TEAEs), vital signs, and Columbia-Suicide Severity Rating Scale (C-SSRS).
Of the 72 enrolled patients, 48 (66.7%) completed acute treatment (18 weeks) and 42 (58.3%) completed extended treatment. Most patients (55/72; 76%) required doses ≥ 60 mg once daily to optimize efficacy based on investigator judgment and Clinical Global Impressions-Severity score. Body weight and age did not significantly affect duloxetine pharmacokinetic parameters. Typical duloxetine clearance in pediatric patients was ≈ 42%-60% higher than that in adults. Four patients (5.6%) discontinued due to TEAEs. Many (36/72, 50%) patients experienced potentially clinically significant (PCS) elevations in blood pressure, with most cases (21/36, 58%) being transient. As assessed via C-SSRS, one nonfatal suicidal attempt occurred, two patients (2.8%) experienced worsening of suicidal ideation, and among the 19 patients reporting suicidal ideation at baseline, 17 (90%) reported improvement in suicidal ideation.
Results suggested that pediatric patients generally tolerated duloxetine doses of 30 to 120 mg once daily, although transient PCS elevations in blood pressure were observed in many patients. Pharmacokinetic results suggested that adjustment of total daily dose based on body weight or age is not warranted for pediatric patients and different total daily doses may not be warranted for pediatric patients relative to adults.
Journal of child and adolescent psychopharmacology 02/2012; 22(1):48-55. DOI:10.1089/cap.2011.0072 · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Relatively little research has focused on the relationship between functional remission and symptomatic remission in mood and anxiety disorders. This study investigates the relationship and synchrony between symptomatic and functional remission in outpatients with major depressive disorder (MDD) and generalized anxiety disorder (GAD). Using data from three MDD (N=1419) and four GAD (N=1847) randomized, placebo-controlled duloxetine studies, we calculated the percentages of patients meeting symptomatic, functional, and combined functional-symptomatic remission criteria for each disorder. We also calculated mean depression [17-item Hamilton depression rating scale (HAMD₁₇), Montgomery-Asberg depression rating scale] scores and mean anxiety (Hamilton anxiety rating scale) scores for patients meeting Sheehan disability scale (SDS) functional remission and the mean SDS scores for patients with symptomatic remission. Among the patients with MDD, 38% achieved symptomatic remission (HAMD₁₇ ≤ 7), 32% achieved functional remission (SDS ≤ 6), and 23% achieved combined functional-symptomatic remission. Mean HAMD₁₇ and Montgomery-Asberg depression rating scale scores for patients with functional remission were approximately 6. Mean SDS total scores for patients with symptomatic remission were 7.1 (patients with HAMD₁₇ ≤ 7) and 8.6 (patients with Montgomery-Asberg depression rating scale ≤ 10). Among the patients with GAD, 30% achieved symptomatic remission (Hamilton anxiety rating scale ≤ 7), 45% achieved functional remission (SDS ≤ 6), and 25% achieved combined symptomatic-functional remission. The mean Hamilton anxiety rating scale score in GAD was approximately 8 for patients with functional remission and the mean SDS total score was approximately 4 in patients with symptomatic remission. The study shows that functional remission does not always move in tandem with symptom remission and provides useful anchor points or rules of thumb for evaluating symptomatic and functional remission in MDD and GAD.
International clinical psychopharmacology 03/2011; 26(2):75-83. DOI:10.1097/YIC.0b013e328341bb5f · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Data on 1,700 patients pooled from 5 randomized, placebo-controlled duloxetine studies (3 in diabetic peripheral neuropathic pain and 2 in fibromyalgia) were analyzed to determine clinically important differences (CIDs) in the 0 to 10 Numeric Rating Scale-Pain Intensity (NRS-PI) for patient-reported "worst" and "least" pain intensity while validating the previously published level for "average" pain. The correspondence between the baseline-to-endpoint raw and percentage change in the NRS-PI for the worst, least, and average pain were compared to patients' perceived improvements at endpoint as measured by the 7-point Patient Global Impression of Improvement (PGI-I) scales. Stratification by baseline pain separated the raw but not the percent change scores. The PGI-I category of "much better" or above was our a priori definition of a CID. Cutoff points for the NRS-PI change scores were determined using a receiver operator curve analysis. A consistent relationship between the worst and average NRS-PI percent change and the PGI-I was demonstrated regardless of the study, pain type, age, sex, or treatment group with a reduction of approximately 34%. The least pain item CID was slightly higher at 41%. Raw change CID cutoff points were approximately -2, -2.5 and -3 for least, average, and worst pain respectively. PERSPECTIVE: We determined an anchor-based value for the change in the worst, least, and average pain intensity items of the Brief Pain Inventory that best represents a clinically important difference. Our findings support a standard definition of a clinically important difference in clinical trials of chronic-pain therapies.
The journal of pain: official journal of the American Pain Society 09/2009; 11(2):109-18. DOI:10.1016/j.jpain.2009.06.007 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate whether comorbid major depressive disorder (MDD) influenced the efficacy and safety of duloxetine in treating fibromyalgia (FM).
This was a post-hoc analysis using pooled data from 4 double-blind, placebo-controlled studies of patients with American College of Rheumatology-defined primary FM with or without MDD. Patients were randomized to duloxetine [60 or 120 mg/d (N=797)] or placebo (N=535) for approximately 3 months. Efficacy measures included the Brief Pain Inventory average pain score, 17-item Hamilton Depression Rating Scale, Fibromyalgia Impact Questionnaire, and Patient's/Clinician's Global Impressions of Improvement/Severity scales.
At baseline, 26% of patients met diagnostic criteria for MDD. At endpoint (3 mo or last observation), duloxetine showed significantly (P<0.05) greater improvement versus placebo on the Brief Pain Inventory, Fibromyalgia Impact Questionnaire, Patient's Global Impressions of Improvement scale, and Clinician's Global Impressions of Severity scale in patients with and without comorbid MDD. The effect of duloxetine on these efficacy measures was consistent across FM patients with or without MDD (P>0.1 for treatment-by-strata interaction). On the 17-item Hamilton Depression Rating Scale, duloxetine showed significantly (P<0.05) greater improvement versus placebo in patients with comorbid MDD. The safety profile of duloxetine versus placebo with respect to serious adverse events and discontinuation owing to adverse events was similar for FM patients with versus without MDD (P>0.1 treatment-by-strata interaction).
Duloxetine was effective in reducing pain and other symptoms in FM patients with and without MDD and demonstrated a similar safety profile for both groups.
The Clinical journal of pain 07/2009; 25(6):461-8. DOI:10.1097/AJP.0b013e318197d4e4 · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated hypothesized early symptom changes as differential predictors of long-term remission for duloxetine and escitalopram.
This was a post-hoc analysis from a placebo-controlled, randomized, double-blind study of patients with major depressive disorder treated for 8 weeks with duloxetine 60 mg/day (N = 273) or escitalopram 10 mg/day (N = 274), and for another 6 months with duloxetine up to 120 mg/day or escitalopram up to 20 mg/day. Odds ratios (ORs) for successful treatment (sustained remission), defined as a 17-item Hamilton Depression Rating Scale (HAMD-17) score </= 7 over 8 months, were determined for improvement in HAMD-17 depressed mood, retardation, and anxiety symptom factor subscales (20% decrease), along with associated positive predictive values (PPVs) and negative predictive values (NPVs).
For both drugs, 2-week HAMD-17 improvement on all symptom subscales (except sleep for duloxetine) significantly predicted remission with ORs > 2.0. In a follow-up analysis, specific subscale items for psychological anxiety, motor retardation, and suicidality significantly predicted remission for duloxetine, and psychological and somatic anxiety for escitalopram. Notably, high NPVs on the Maier subscale indicated that a lack of 20% improvement on the "core" depression factor by Week 2 was highly predictive of unsuccessful treatment outcome over 8 months.
In accord with hypotheses, early symptom changes were specific to treatment, with early response in the core depression factor (Maier subscale), anxiety, and motor activity for duloxetine, and core factor and anxiety for escitalopram. Lack of early response in depression symptom subscales was highly predictive of lack of sustained remission.
[Show abstract][Hide abstract] ABSTRACT: Diabetic patients are predisposed to cardiovascular (CV) disease and other chronic medical conditions. We compared the safety of duloxetine in patients with (CV-positive) and without (CV-negative) historical/comorbid cardiovascular conditions at study entry.
Data were pooled from three double-blind studies in which patients (age > or =18 years) with diabetic peripheral neuropathic pain (DPNP) were randomized to 12 weeks of duloxetine (DLX) 60 mg qd (n=344), 60 mg bid (n=341), or placebo (PBO, n=339). Safety assessments included discontinuation rates, spontaneously reported treatment-emergent adverse events (TEAEs), changes in vital signs, and changes in lab analytes.
Mean age of CV-positive patients (n=762) vs. CV-negative patients (n=262) was 61.1 vs. 56.1 years. The most common historical or comorbid CV conditions were hypertension, coronary artery disease, and myocardial infarction. Discontinuation due to adverse events was higher for DLX than for PBO in both CV-positive and CV-negative patients (13.5% DLX, 6.0% PBO, and 14.3% DLX, 3.4% PBO, respectively). Rates of CV-related TEAEs in CV-positive (8.4% DLX; 9.9% PBO) and CV-negative (8.6% DLX; 5.7% PBO) patients were similar (P>.1). Mean changes in blood pressure for each DLX dose vs. PBO between CV-positive and CV-negative patients were not statistically significant (P>.1), nor were sustained hypertension rates between CV-positive (2.4% DLX; 2.8% PBO) and CV-negative (2.9% DLX; 4.7% PBO) patients.
In this analysis, the safety of duloxetine in patients with DPNP was not found to be significantly different between patients with and without historical or comorbid CV conditions.
Journal of diabetes and its complications 09/2008; 23(5):349-59. DOI:10.1016/j.jdiacomp.2008.07.004 · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the relationship between global functional impairment and the treatment of anxious symptoms and painful somatic symptoms (PSS) in patients with generalized anxiety disorder (GAD).
Data from two double-blind, placebo-controlled trials in adult outpatients meeting DSM-IV criteria for GAD were pooled. In the first trial (9-week, fixed-dose treatment period), patients were randomized to duloxetine 60 mg QD (n=168), duloxetine 120 mg QD (n=170), or placebo (n=175). In the second trial (10-week, flexible-dose treatment period), patients were randomized to 60-120 mg QD of duloxetine (n=168) or placebo (n=159). Path analysis was used to assess the relative contributions of changes in psychic and somatic anxiety and PSS on improved functional outcomes. Clinical trial registration information: Study 1: NCT00122824; Study 2: study completed before registration required.
Sheehan Disability Scale (SDS), Hamilton Anxiety Rating Scale (HAMA), and Visual Analog Scale for overall pain (VAS).
There was a moderate correlation (0.45, p<0.05) at endpoint between changes in global functional impairment and changes in psychic anxiety (controlling for somatic anxiety and PSS); whereas the correlation between changes in global functional impairment and changes in somatic anxiety (controlling for psychic anxiety and PSS) was weak (0.09, p<0.05). The correlation between changes in global functional impairment and changes in PSS (controlling for psychic and somatic anxiety) was weak (0.27, p<0.05). Path analysis revealed that 37% of the total improvement in functional impairment (Sheehan Disability Scale total score) due to duloxetine treatment was independent of improvement in the Hamilton Anxiety Rating Scale (HAMA) psychic and somatic anxiety subscale scores or Visual Analog Scale for overall pain (VAS) score. Improvement in psychic anxiety accounted for 47% of the total treatment effect on improvement of functional impairment, whereas 7% and 9% of the improvement in functional impairment was accounted for by improvements in somatic anxiety and overall pain, respectively.
Current Medical Research and Opinion 08/2008; 24(9):2457-66. DOI:10.1185/03007990802293643 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Various analytical strategies for addressing missing data in clinical trials are utilised in reporting study results. The most commonly used analytical methods include the last observation carried forward (LOCF), observed case (OC) and the mixed model for repeated measures (MMRM). Each method requires certain assumptions regarding the characteristics of the missing data. If the assumptions for any particular method are not valid, results from that method can be biased. Results based on these different analytical methods can, therefore, be inconsistent, thereby making interpretation of clinical study results confusing. In this investigation, we compare results from MMRM, LOCF and OC in order to illustrate the potential biases and problems in interpretation.
Data from an 8-month, double-blind, randomised, placebo-controlled (placebo; n = 137), outpatient depression clinical trial comparing a serotonin-noradrenalin reuptake inhibitor (SNRI; n = 273) with a selective serotonin reuptake inhibitor (SSRI; n = 274) were used. The study visit schedule included efficacy and safety assessments weekly to week 4, bi-weekly to week 8, and then monthly. Visitwise mean changes for the 17-item Hamilton Depression Rating Scale (HAMD(17)) Maier subscale (primary efficacy outcome), blood pressure, and body weight were analysed using LOCF, MMRM and OC.
Last observation carried forward consistently underestimated within-group mean changes in efficacy (benefit) and safety (risk) for both drugs compared with MMRM, whereas OC tended to overestimate within-group changes.
Inferences are based on between-group comparisons. Therefore, whether or not underestimating (overestimating) within-group changes was conservative or anticonservative depended on the relative magnitude of the bias in each treatment and on whether within-group changes represented improvement or worsening. Preference should be given in analytic plans to methods whose assumptions are more likely to be valid rather than relying on a method based on the hope that its results, if biased, will be conservative.
International Journal of Clinical Practice 07/2008; 62(8):1147-58. DOI:10.1111/j.1742-1241.2008.01808.x · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Assessing antidepressant onset efficacy presents substantial methodological challenges. Most assessments of onset efficacy are based on post hoc analyses. This article presents a case study of a prospectively designed trial to compare antidepressant onset efficacy.
The current study design was compared with previously published criteria for an ideal onset of action study. Prospectively defined sensitivity analyses were used to assess whether results of the present study were influenced by the assumptions and decisions necessary to implement this study.
The study achieved its primary objective of establishing noninferiority between SNRI and SSRI. Sensitivity analyses suggested that results from the primary analysis were not influenced by patient population, outcome measure, cut-off for defining clinically meaningful sustained improvement, or analytical method. Although not all limitations could be addressed, appropriate conclusions could be drawn. For example, the study tested only one fixed dose of each drug; hence, conclusions are limited to those dosages and cannot be extrapolated across the entire dose ranges, as would be possible in the ideal study.
This article illustrates that prospectively designed studies (as opposed to retrospective comparisons) can be implemented and sensitivity analyses can be used to address concerns regarding assumptions and arbitrary decisions.
[Show abstract][Hide abstract] ABSTRACT: To test the hypothesis that in patients with major depressive disorder (MDD), the response for specific Hamilton Depression Rating Scale items will differ for duloxetine compared with selective serotonin reuptake inhibitors (SSRIs) and that patterns of response will differ based on symptom severity at baseline.
Data were pooled from all Lilly-sponsored clinical trials where duloxetine was compared with placebo and an SSRI in patients with MDD: 7 randomized, double-blind, fixed-dose, 8-week studies of duloxetine (n = 1,133) versus SSRI (n = 689) versus placebo (n = 641). Duloxetine doses were 40, 60, 80 and 120 mg/day. SSRI doses were 10 mg/day (escitalopram) and 20 mg/day (fluoxetine and paroxetine).
Compared to SSRI-treated patients, duloxetine-treated patients had a significantly greater (p < or = 0.05) reduction in the 17-item Hamilton Depression Rating Scale (HAMD17) total score and HAMD17 items of work and activities, psychomotor retardation, genital symptoms and hypochondriasis. Differences favoring the SSRIs approached significance for middle insomnia (p = 0.057) and late insomnia (p = 0.06), with effect sizes at least twice the magnitude of the corresponding effect sizes for duloxetine. Similarly, the advantage for duloxetine versus the SSRIs approached significance for general somatic symptoms (p = 0.056), with an effect size twice that observed for the SSRIs. The HAMD17 total score difference was driven mostly by patients with lower baseline MDD severity (HAMD17 total score < or = 19), where the HAMD17 effect size advantage for duloxetine over combined SSRIs was statistically significant (p = 0.031).
Potentially important differences in symptom response patterns were found between duloxetine and the combined SSRIs depending on symptom severity, and different HAMD17 items responded differently to duloxetine compared with SSRIs. Understanding these differences may be useful in tailoring antidepressant therapy for individual patients.
[Show abstract][Hide abstract] ABSTRACT: This was a post hoc analysis to determine whether baseline severity of depression influenced the efficacy of duloxetine in treating major depressive disorder (MDD) and to better characterise the symptom response profile for duloxetine in patients with mild, moderate or more severe depression.
Data were pooled from four double-blind, placebo-controlled studies in which outpatients with MDD were randomised to duloxetine (60 mg/day) or placebo for 8-9 weeks. Patients were retrospectively stratified according to baseline 17-item Hamilton Depression Rating scale (HAMD17) total scores: mild=total score<or=19 (duloxetine, n=246; placebo, n=184); moderate=20-24 (duloxetine, n=333; placebo, n=217); severe=25+ (duloxetine, n=127; placebo, n=87).
Duloxetine produced significantly greater baseline-to-end-point improvement vs. placebo (p<0.05) on the HAMD17 total score, Maier and retardation subscales, HAMD17 items 1 (depressed mood), 7 (work and activities) and 10 (psychic anxiety) in all three patient cohorts. The largest effect sizes were observed in assessments of core emotional depressive symptoms. A significant improvement for duloxetine vs. placebo was not observed for sleep-related symptoms at end-point or genital symptoms at any time point during acute treatment. With respect to the time course of depressive symptom improvement, the data show that regardless of baseline severity, the most rapid and consistent improvement for duloxetine compared with placebo was observed in the core symptoms of MDD (measured by the Maier subscale).
Regardless of baseline MDD severity, duloxetine at one dose (60 mg/day) produced a significant improvement compared with placebo on the core emotional symptoms of MDD.
International Journal of Clinical Practice 09/2007; 61(8):1337-48. DOI:10.1111/j.1742-1241.2007.01444.x · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Depression and antidepressant therapy have been associated with sexual dysfunction in short-term and point-prevalence trials.
This report describes effects of duloxetine and escitalopram on sexual functioning during acute and long-term treatment of major depressive disorder (MDD).
In this 8-month, double-blind, placebo-controlled study, adult outpatients with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)-defined MDD were randomized to duloxetine 60 mg/day (N = 273; 173 female), escitalopram 10 mg/day (N = 274; 186 female), or placebo (N = 137; 87 female). After the first 8 weeks of treatment, dose increases were permitted to optimize treatment.
The 14-item Changes in Sexual Functioning Questionnaire (CSFQ) was used to assess sexual functioning.
Of the 114 patients who did not meet total CSFQ score criteria for global sexual dysfunction at baseline (duloxetine, N = 51; escitalopram, N = 39; placebo, N = 24), the incidence of treatment-emergent sexual dysfunction was significantly higher for escitalopram compared with placebo at 4 and 8 weeks, and significantly higher compared with duloxetine at 4 weeks. At 8 weeks, the incidence of treatment-emergent sexual dysfunction was 17/51 (33.3%) for duloxetine-treated patients; 19/39 (48.7%) for escitalopram-treated patients; and 4/24 (16.7%) for placebo-treated patients (P = 0.01 escitalopram vs. placebo; P = 0.13 duloxetine vs. placebo). After 12 weeks, no significant differences were observed between active drugs. At 8 months, the incidence of treatment-emergent sexual dysfunction was 33.3% for duloxetine, 43.6% for escitalopram, and 25.0% for placebo. Regardless of treatment, patients who achieved remission of MDD showed improvement in global sexual functioning, whereas worsening was observed for patients who did not achieve remission (P < 0.001). Discontinuation rates for sexual side effects did not differ between duloxetine (N = 2) and escitalopram (N = 7) (P = 0.07).
Short-term treatment demonstrated a higher incidence of treatment-emergent sexual dysfunction with escitalopram compared with duloxetine and placebo. After 12 weeks, there were no statistically significant differences between drugs; however, MDD outcome (regardless of treatment) had a significant impact on improvement in global sexual functioning.
Journal of Sexual Medicine 08/2007; 4(4 Pt 1):917-29. DOI:10.1111/j.1743-6109.2007.00520.x · 3.15 Impact Factor