Duloxetine in the treatment of major depressive disorder: A placebo- and paroxetine-controlled trial
ABSTRACT Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder (MDD).
In this randomized, double-blind trial, patients age > or =18 meeting DSM-IV criteria for MDD were randomized to placebo (N=99), duloxetine 80 mg/day (N=93), duloxetine 120 mg/day (N=103), or paroxetine 20 mg/day (N=97). The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression (HAMD(17)) total score after 8 weeks of treatment; a number of secondary efficacy measures also were assessed. Safety and tolerability were assessed via collection and analysis of treatment-emergent adverse events (TEAEs), vital signs, and weight. The Arizona sexual experiences scale was used to assess sexual functioning. Patients who had a > or =30% reduction from baseline in the HAMD(17) total score at the end of the acute phase entered a 6-month continuation phase where they remained on the same treatment as they had taken during the acute phase; efficacy and safety/tolerability outcomes were assessed during continuation treatment.
More than 87% of patients completed the acute phase in each treatment group. Duloxetine-treated patients (both doses) showed significantly greater improvement (P<0.05) in the HAMD(17) total score at week 8 compared with placebo. Paroxetine was not significantly different from placebo (P=0.089) on mean change on the HAMD(17). Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures (six of nine) compared with placebo while duloxetine 80 mg/day (three of nine) and paroxetine (three of nine) were significantly superior to placebo on fewer secondary measures. HAMD(17) mean change data from this study and an identical sister study were pooled as defined a priori for the purposes of performing a non-inferiority test versus paroxetine. Both duloxetine doses met statistical criteria for non-inferiority to paroxetine. TEAE reporting rates were low in all treatment groups and no deaths occurred in the acute or continuation phases.
The efficacy of duloxetine at doses of 80 and 120 mg/day in the treatment of MDD was demonstrated. Tolerability, as measured by TEAEs, and safety were similar to paroxetine 20 mg/day and consistent with previous published data on duloxetine in the treatment of MDD.
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- "Similar to the publications noted above for continuous outcomes, this latter report is informative since the author had full access to the entire registration dossier for this pharmaceutical agent and so was able to summarize information on both positive and negative clinical trial results. For two of the more recently approved antidepressants , duloxetine and selegiline (transdermal patch), the sponsors' peer-reviewed primary data publications were utilized as these appeared to represent nearly exhaustive summaries of their respective development programs (Detke, 2002a, 2002b; Goldstein, 2002, 2004; Perahia, 2006; Feiger, 2006; Bodkin, 2002). The majority of the reference comparison datasets that we have used consist of studies performed in patients preferentially recruited based on the prior likelihood of response to treatment, i.e., patients "
ABSTRACT: Transcranial magnetic stimulation (TMS) is a novel treatment for patients with major depressive disorder. Although clearly safer and better tolerated than many other pharmacotherapeutic options or electroconvulsive therapy, questions have persisted about the magnitude of the efficacy of TMS in patients with pharmacoresistant depression, and the clinical significance of these outcomes. Previous studies have explored whether specific patient characteristics are associated with a greater likelihood of clinical benefit. In the largest such analysis conducted to date, the authors confirmed previous observations that the lower the number of prior failed antidepressant treatments, the better the clinical outcome of treatment with TMS. This relationship between prior treatment resistance and subsequent treatment outcome is consistent with previous evidence from antidepressant studies. The authors examined the clinical significance of the treatment effects seen with TMS in pharmacoresistant major depression in their recently completed studies by comparing these outcomes with the results reported in several large, comprehensive published reference datasets of antidepressant medications studied in both treatment-responsive and treatment-resistant patient populations. The efficacy of TMS demonstrated in randomized controlled trials was comparable to that of pharmaceutical antidepressants studied in similarly designed registration trials and to the adjunctive use of atypical antipsychotic medications in controlled trials of antidepressant non-responders. These data may be helpful in treatment-planning decisions when using TMS in clinical practice.Psychopharmacology bulletin 02/2009; 42(2):5-38. · 0.50 Impact Factor
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- "With regard to the most recent antidepressants, escitalopram appears as well tolerated as other SSRIs (possibly better than paroxetine) and better tolerated than venlafaxine (Baldwin, et al., 2007). Studies with duloxetine have reported both equal and poorer tolerability compared with SSRIs (Hudson, et al., 2005; Perahia, et al., 2006; Khan, et al., 2007; Wade, et al., 2007; Lee, et al., 2007) but fewer sexual side effects than paroxetine (Delgado, et al., 2005). In pooled data from two studies against venlafaxine more patients on duloxetine discontinued overall, and due to side effects, (NNH about 20) (Perahia, et al., 2007) RCTs are probably not the best way to assess the impact of tolerability in practice. "
ABSTRACT: A revision of the 2000 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in May 2006. Key areas in treating depression were reviewed, and the strength of evidence and clinical implications were considered. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is provided, which identifies the quality of evidence to inform the recommendations, the strength of which are based on the level of evidence. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse, and stopping treatment.Journal of Psychopharmacology 07/2008; 22(4):343-96. DOI:10.1177/0269881107088441 · 2.81 Impact Factor
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- "87 12 weeks Fluoxetine 20-40 Venlafaxine 75- 150 51 vs. 56 Higher rates of dizziness (10 vs. 2), nausea (33 vs. 28), and vomiting (15 vs. 2) with venlafaxine Higher rate of insomnia (11 vs. 5) with fluoxetine No differences Fair Bielski et al., 2004  198 8 weeks Escitalopram 20 Venlafaxine 225 68 vs. 85 Higher rates of nausea (24 vs. 6) and somnolence (17 vs. 9) with venlafaxine Higher rate of ejaculation disorder (23 vs. 7) with venlafaxine; mean changes in vital signs significantly higher with venlafaxine Fair Montgomery et al., 2004  293 8 weeks Escitalopram 10- 20 Venlafaxine 75- 150 67 vs. 71 Higher rate of nausea with venlafaxine (data NR) No differences Fair Hong et al., 2003  133 6 weeks Fluoxetine 20-40 Mirtazapine 15-45 58 vs. 71 Higher rates of dizziness (20 vs. 14) and weight gain (8 vs. 3) with mirtazapine Higher rate of nausea (12.1 vs. 0) with fluoxetine No differences Fair Versiani et al., 2005  297 8 weeks Fluoxetine 20-40 Mirtazapine 15-60 45 vs. 50 Higher rate of weight gain (7 vs. 1) with mirtazapine Higher rate of nausea (24 vs. 16) with fluoxetine No differences Fair Wheatley et al., 1998  133 6 weeks Fluoxetine 20-40 Mirtazapine 15-60 NR Higher rates of somnolence (18 vs. 13) and weight gain (12 vs. 0) with mirtazapine Higher rates of headache (18 vs. 9) and nausea (10 vs. 3) with fluoxetine No differences Fair Costa e Silva et al., 1998  382 8 weeks Fluoxetine 20-40 Venlafaxine 75- 225 65 vs. 69 Higher rates of nausea (29 vs. 19), dizziness (8 vs. 3), and somnolence (8 vs. 2) with venlafaxine No differences Fair De Nayer et al., 2002  146 12 weeks Fluoxetine 20-40 Venlafaxine 75- 150 67 vs. 56 Higher rate of nausea (29 vs. 21) for venlafaxine No differences Fair Dierick et al., 1996  314 8 weeks Fluoxetine 20 Venlafaxine 75- 150 56 vs. 63 Higher rates of nausea (28 vs. 14) with venlafaxine No differences Fair Tylee et al., 1997  341 12 weeks Fluoxetine 20 Venlafaxine 75 72 vs. 81 Higher rates of nausea (35 vs. 18) and vomiting (13 vs. 5) with venlafaxine Higher rate of headache (17 vs. 11) with fluoxetine No differences Fair Nemeroff et al., 2005  308 6 weeks Fluoxetine 20-60 Venlafaxine 75- 225 NR Higher rates of nausea (40 vs. 22), headache (36 vs. 24), insomnia (22 vs. 15), dizziness (13 vs. 8), and vomiting (11 vs. 5) with venlafaxine No differences Fair Rudolph et al., 1999  301 8 weeks Fluoxetine 20-60 Venlafaxine 75- 225 NR Higher rates of nausea (36 vs. 20), dizziness (26 vs. 6), and infection (13 vs. 5) with venlafaxine Higher rate of diarrhea (19 vs. 14) with fluoxetine No differences Fair Schatzberg et al. 2006  300 8 weeks Fluoxetine 20-60 Venlafaxine 37,5- 225 94 vs. 92 Higher rates of nausea (45 vs. 23)and headache (26 vs. 18) with venlafaxine No differences Fair Silverstone et al., 1999  368 12 weeks Fluoxetine 20-60 Venlafaxine 75- 225 NR Higher rates of dizziness (38 vs. 18), nausea (41 vs. 32), and insomnia (32 vs. 25) with venlafaxine No differences Fair Tzanakaki et al., 2000  109 6 weeks Fluoxetine 60 Venlafaxine 225 46 vs. 49 Higher rates of dizziness (6 vs. 0) and insomnia (13 vs. 2) with venlafaxine Higher rates of nausea (15 vs. 6) and vomiting (6 vs. 0) with No differences Fair fluoxetine Detke et al., 2004  367 8 weeks Paroxetine 20 Duloxetine 80 Duloxetine 120 NR Higher rate of nausea (23.6 vs. 11.6 vs. 5.4) with duloxetine 80 and paroxetine Higher rates of somnolence (7.5 vs. 5.8 vs. 2.1) with duloxetine 120 and paroxetine No differences Fair Perahia et al., 2006  392 8 weeks Paroxetine 20 Duloxetine 80 Duloxetine 120 NR No differences No differences Fair Benkert et al., 2003   275 6 weeks Paroxetine 20-40 Mirtazapine 15-45 63 vs. 68 Higher rate of weight gain (15 vs. 4) with mirtazapine Higher rate of nausea (11 vs. 4) with paroxetine Higher rate of orgasmic dysfunction (14 vs. 3) with paroxetine Fair Schatzberg et al., 2002  "
ABSTRACT: Evidence indicates that only minor differences in efficacy exist among second-generation antidepressants for the treatment of major depressive disorder (MDD). However, a comprehensive assessment of both benefits and harms is crucial to evaluate the net benefit. To review systematically the comparative harms of second-generation antidepressants for the treatment of MDD in adults by including both experimental and observational evidence. We searched MEDLINE, EMBASE, PsychLit, The Cochrane Library and the International Pharmaceutical Abstracts from 1980 to April 2007. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database to identify unpublished research. Eligible study designs were trials and observational studies comparing one drug of interest with another. Two persons independently reviewed abstracts and full-text articles. One investigator extracted relevant data. A senior reviewer checked data for completeness and accuracy. We included 104 experimental and observational studies. If data were sufficient, we conducted meta-analyses of randomized controlled trials on the relative risk of specific adverse events. Findings indicate that the spectrum of adverse events is similar. The frequency of specific adverse events, however, differed across drugs. Venlafaxine was associated with a significantly higher rate of nausea and vomiting than selective serotonin reuptake inhibitors. Compared with other drugs, paroxetine frequently led to more sexual adverse effects and bupropion to fewer such effects; mirtazapine and paroxetine was associated with more weight gain and sertraline with a higher rate of diarrhoea. Overall, however, these differences did not lead to different discontinuation rates. The evidence is insufficient to draw conclusions about rare but severe adverse events. Adverse event profiles are similar among second-generation antidepressants. However, different frequencies of specific adverse events might be clinically relevant and influence the choice of a treatment.Drug Safety 02/2008; 31(10):851-65. DOI:10.2165/00002018-200831100-00004 · 2.62 Impact Factor