Impact of pretreatment with antidepressants on the efficacy of duloxetine in terms of mood symptoms and functioning: an analysis of 15 pooled major depressive disorder studies.

OBJECTIVE: This post hoc analysis aimed to determine whether patients with major depressive disorder (MDD) in duloxetine trials who were antidepressant naive or who were previously exposed to antidepressants exhibited differences in efficacy and functioning. METHOD: Data were pooled from 15 double-blind, placebo- and/or active-controlled duloxetine trials of adult patients with MDD conducted by Eli Lilly and Company. The individual studies took place between March 2000 and November 2009. Data were analyzed using 4 pretreatment subgroups: first-episode never treated, multiple-episode never treated, treated previously only with selective serotonin reuptake inhibitors (SSRIs), and previously treated with antidepressants other than just SSRIs. Measures included the 17-item Hamilton Depression Rating Scale (HDRS-17) total and somatic symptom subscale scores, Montgomery-Asberg Depression Rating Scale (MADRS) total score, and Sheehan Disability Scale total score. Response rates (50% and 30%) were based on the HDRS-17 total score and remission rates on either the HDRS-17 or MADRS total score. RESULTS: Response and remission rates were significantly greater (P < .05 in 11 of 12 comparisons) for duloxetine versus placebo in the 4 subgroups. A trend of greater response and remission occurred for first-episode versus multiple-episode patients; both groups were generally higher than the antidepressant-treated groups. Mean changes in efficacy measures were mostly significantly greater (P < .05 in 13 of 16 comparisons) for duloxetine versus placebo within each pretreatment subgroup, with some (P < .05 in 2 of 24 comparisons) significant interaction effects between subgroups on HDRS-17 total and somatic symptoms scores. CONCLUSIONS: Duloxetine was generally superior to placebo on response and remission rates and in mean change on efficacy measures. Response and remission rates were numerically greater for first-episode versus multiple-episode and drug-treated patients. Mean change differences on efficacy measures among the 4 subgroups were inconsistent. Duloxetine showed a similar therapeutic effect independent of episode frequency and antidepressant pretreatment.

A systematic review of combination therapy with stimulants and atomoxetine for attention-deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability.

OBJECTIVE: The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability. METHODS: Literature databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms. RESULTS: Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events. CONCLUSIONS: Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success.

Effectiveness of antidepressants in the treatment of major depressive disorder in Latin America.

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<0.0001), and remained more depressed and in greater pain at endpoint (HAMD17p=0.0074, CGI-S P =0.0151, and VAS P <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.

Major depressive disorder in Latin America: the relationship between depression severity, painful somatic symptoms, and quality of life.

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 (SS-) of painful somatic symptoms using the Somatic Symptom Inventory (SSI). Visual Analogue Scale (VAS) quantified pain severity, HAMD17 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 (+/- 0.8) and HAMD17 score of 24.9 (+/- 7.2). 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 (p < 0.0001). Adjusted mean HAMD17 (26.79) and CGI-S (4.53) scores for SS+ patients were significantly (p < 0.0001) higher than for SS- patients (HAMD(17): 22.87; CGI-S: 4.28). SS+ patients had greater severity of pain across all VAS measures (p < 0.0001). The presence of somatic symptoms had a significantly deleterious effect on quality of life (p < 0.0001). 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.