PMC:546184 / 21712-24949 JSONTXT

{"project":"NEUROSES","denotations":[{"id":"T397","span":{"begin":11,"end":16},"obj":"PATO_0001516"},{"id":"T398","span":{"begin":129,"end":134},"obj":"PATO_0001516"},{"id":"T399","span":{"begin":219,"end":229},"obj":"CHEBI_36796"},{"id":"T400","span":{"begin":554,"end":564},"obj":"CHEBI_36796"},{"id":"T401","span":{"begin":836,"end":846},"obj":"CHEBI_36796"},{"id":"T402","span":{"begin":1925,"end":1935},"obj":"CHEBI_36796"},{"id":"T403","span":{"begin":2026,"end":2036},"obj":"CHEBI_36796"},{"id":"T404","span":{"begin":2867,"end":2877},"obj":"CHEBI_36796"},{"id":"T405","span":{"begin":3033,"end":3043},"obj":"CHEBI_36796"},{"id":"T406","span":{"begin":3105,"end":3115},"obj":"CHEBI_36796"},{"id":"T407","span":{"begin":493,"end":500},"obj":"PATO_0000467"},{"id":"T408","span":{"begin":794,"end":797},"obj":"CHEBI_26345"},{"id":"T409","span":{"begin":1894,"end":1898},"obj":"PATO_0001323"},{"id":"T410","span":{"begin":2390,"end":2400},"obj":"PATO_0000063"},{"id":"T545","span":{"begin":1549,"end":1559},"obj":"CHEBI_36796"},{"id":"T549","span":{"begin":1174,"end":1179},"obj":"PATO_0001516"},{"id":"T547","span":{"begin":2667,"end":2677},"obj":"CHEBI_36796"}],"text":"Efficacy – focus studies\nAnalyses of mean changes from baseline to Week 9 (MMRM mean change) for melancholic patients in the two focus studies (Studies 5 and 6) are summarized in Table 6. Melancholic patients receiving duloxetine had significantly greater improvement in mean HAMD17 total score and HAMD17 Maier subscale compared with those receiving placebo (p \u003c .001). Significant differences from placebo first occurred at Week 1 (Maier subscale, Figure 1) or Week 2 (total score) and were present at all subsequent visits. Significant advantages for duloxetine over placebo for mean changes to Week 9 among melancholic patients were also observed on the HAMD17 retardation and sleep subscales, but not for the anxiety subscale (p = .230). On both clinician-rated (CGI-S) and patient-rated (PGI-I) assessments of global improvement, duloxetine-treated melancholic patients had significantly greater mean improvements compared with melancholics receiving placebo (p \u003c .001). Robustness of the MMRM results was confirmed in that significant differences were also observed in LOCF mean change analyses.\nTable 6 Mean changes from baseline to week 9 in melancholic patients (focus studies) CGI = Clinical Global Impression; HAMD = Hamilton Rating Scale for Depression; PGI = Patient Global Impression\na. Values are mean change (percentage mean change), and p value is from main effect of treatment\nb. Mean score (SE). Lower mean score indicates greater improvement.\nFigure 1 Mean changes in HAMD17 Maier subscale for melancholic patients receiving duloxetine (60 mg QD) or placebo. ** p \u003c .005 vs. placebo. Mean changes from baseline (MMRM mean change) for VAS overall pain were also assessed. Figure 2 shows a visitwise plot of mean changes in VAS overall pain severity for melancholic patients. For the main effect of treatment (pooling results from all visits – interpreted similar to an area under the curve analysis) duloxetine-treated melancholic patients had significantly greater improvement compared with placebo. Duloxetine's advantage over placebo in treating the painful physical symptoms did not vary substantially between patients with and without melancholic features. However, the response profiles were somewhat different in that response to placebo was generally lower in patients with melancholic features compared with non-melancholic patients. For example, the mean percentage improvement in overall pain among non-melancholic patients receiving placebo was 15.6%, compared with a 0.5% worsening in overall pain among placebo-treated melancholic patients.\nFigure 2 Mean changes in VAS overall pain severity for melancholic patients receiving duloxetine (60 mg QD) or placebo. ** p \u003c .005 vs. placebo. Estimated probabilities (categorical MMRM analyses) of remission at Week 9 were significantly higher for melancholic patients treated with duloxetine (60 mg QD) compared with placebo (44.4% vs. 24.7%, respectively; p = .002). The estimated probability of response among melancholic patients was 74.7% for duloxetine compared with 42.2% for placebo (p \u003c .001). The advantage of duloxetine over placebo in remission and response rates was also significant in LOCF analyses (p = .032 and p = .002, respectively)."}