Efficacy and tolerability of milnacipran

Montgomery, S.A.; Prost, J. F.; Solles, A.; Briley, Mike

doi:10.1097/00004850-199609004-00007

Cited by 67 publications

(32 citation statements)

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“…On the basis of doubleblind trials versus placebo, tricyclic antidepressants (TCAs), or SSRIs, [21][22][23][24][25][26] twice-daily milnacipran has shown efficacy in major depressive episodes and is approved for the treatment of depression in many countries outside the United States. Milnacipran studies in depression were conducted outside the United States a decade ago; as such, no valid comparison between levomilnacipran SR and milnacipran data can be made.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Levomilnacipran Sustained Release 40 mg, 80 mg, or 120 mg in Major Depressive Disorder

Asnis¹,

Bose²,

Gommoll³

et al. 2013

J. Clin. Psychiatry

125

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Objective: This phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and tolerability of fixed-dose levomilnacipran sustained release (SR) compared with placebo in patients with major depressive disorder (MDD); the study was conducted from September 2009-May 2011.Method: Outpatients met DSM-IV-TR criteria for MDD with an ongoing major depressive episode ≥ 8 weeks' duration. After a 1-week placebo lead-in, patients were randomly assigned to receive placebo (n = 179) or levomilnacipran SR 40 mg (n = 181), 80 mg (n = 181), or 120 mg (n = 183) once daily for 8 weeks of double-blind treatment, followed by a 2-week double-blind down-taper. The primary efficacy parameter was change from baseline on the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) total score. The prespecified secondary efficacy parameter was change from baseline in Sheehan Disability Scale (SDS) total score. Additional efficacy measures included the 17-item Hamilton Depression Rating Scale (HDRS 17 ) and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I). Safety and tolerability were also evaluated. Results:The least squares mean difference (LSMD) for change from baseline in MADRS total score was significantly superior to placebo for all dose groups: −3.23 (P = .0186), −3.99 (P = .0038), and −4.86 (P = .0005) for levomilnacipran SR 40, 80, and 120 mg, respectively. The LSMD was significantly different for levomilnacipran SR 80 mg and 120 mg versus placebo on the SDS (−2.51 and −2.57, respectively, P < .05 for both doses), HDRS 17 (−2.09 and −2.34, respectively, P < .05 for both doses), CGI-S (−0.43 [P < .01] and −0.35 [P < .05], respectively), and CGI-I (−0.34 and −0.32, respectively, P < .05 for both doses) assessments. The most common treatmentemergent adverse events (≥ 10% of any treatment group) were headache, nausea, constipation, dry mouth, increased heart rate, and hyperhidrosis.Conclusions: Levomilnacipran SR demonstrated significant improvement in depressive symptoms and functioning relative to placebo. In this study, levomilnacipran SR was generally well tolerated. September 28, 2012; accepted January 28, 2013 (doi:10.4088/JCP.12m08197 T he complex nature of major depressive disorder (MDD) suggests that recovery may be most appropriately judged by multiple factors. Even when patients achieve symptom improvement, impaired social and occupational functioning may persist and interfere with well-being. As such, it has been suggested that return to wellness in patients with MDD may be better defined by evaluating a combination of symptoms, functional status, and pathophysiologic changes. Submitted:1 The development of effective and safe new medications that address all aspects of MDD treatment is essential.Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin-norepinephrine reuptake inhibitor (SNRI) in late-stage clinical development for treatment of MDD in adults. A sustained release (SR) formulation of levomilnacipran was developed to al...

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Levomilnacipran Sustained Release 40 mg, 80 mg, or 120 mg in Major Depressive Disorder

Asnis¹,

Bose²,

Gommoll³

et al. 2013

J. Clin. Psychiatry

125

View full text Add to dashboard Cite

show abstract

“…On the basis of double-blind trials versus placebo, tricyclic antidepressants, or SSRIs, [24][25][26][27][28][29] twice-daily milnacipran has shown efficacy in major depressive episodes and is approved for the treatment of depression in several European countries. Milnacipran studies in depression were conducted a decade ago, and no …”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Levomilnacipran Sustained Release in Moderate to Severe Major Depressive Disorder

Montgomery

Mansuy²,

Ruth³

et al. 2013

J. Clin. Psychiatry

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Objective:To investigate the efficacy and safety of levomilnacipran sustained release (SR), an antidepressant candidate in late-stage development, in major depressive disorder (MDD).Method: Between December 2006 and October 2007, a 10-week, randomized, double-blind, placebocontrolled, parallel-group, multicenter, flexible-dose trial assessed once-daily levomilnacipran SR (75 mg or 100 mg) in outpatients (18-70 years) meeting DSM-IV criteria for a major depressive episode (duration ≥ 1 month) with a 17-item Hamilton Depression Rating Scale (HDRS 17 ) score > 22 and Sheehan Disability Scale (SDS) score ≥ 10. Levomilnacipran SR dose was increased to 100 mg/d over 12 days. The primary efficacy measure was Montgomery Asberg Depression Rating Scale (MADRS) score change from baseline to week 10; secondary efficacy measures were the HDRS 17 , SDS, Clinical Global Impressions-Improvement scale, and MADRS response (≥ 50% decrease from baseline) and remission (score ≤ 10). Safety was evaluated according to adverse events, laboratory investigations, and vital signs/physical findings. Results: Efficacy analyses included 276 levomilnacipran SR-treated patients and 277 placebo-treated patients. Levomilnacipran SR was significantly superior to placebo on MADRS total score change from baseline to week 10 (least squares mean difference [LSMD] = −4.2 [95% CI, −5.7 to −2.6]; P < .0001). Statistical significance in favor of levomilnacipran SR was demonstrated on change from baseline to week 10 in HDRS 17 total score (LSMD = −3.4 [95% CI, −4.7 to −2.2]; P < .0001) and SDS total score (LSMD = −3.4 [95% CI, −4.6 to −2.2]; P < .0001) and subscales. Significantly more levomilnacipran SR patients versus placebo patients achieved MADRS response (59.1% vs 42.2%; P < .0001) and remission (46.4% vs 26.0%; P < .0001). Levomilnacipran SR was generally safe and well tolerated; more levomilnacipran SR patients (9.4%) versus placebo patients (6.5%) discontinued due to adverse events, but more placebo patients versus levomilnacipran SR patients discontinued overall (24.9% vs 20.2% Submitted: August 29, 2012; accepted February 1, 2013 (doi:10.4088/JCP.12m08141 Major depressive disorder (MDD) is a common, potentially dangerous, and disabling disorder. It has a chronic recurrent course and is recognized as the most common cause of disability during the course of a working life.1 Effective treatment of MDD is a public health priority.Levomilnacipran (1S, 2R-milnacipran), a potent and selective serotonin-norepinephrine reuptake inhibitor (SNRI) with greater potency for inhibition of norepinephrine (NE) relative to serotonin (5-HT) reuptake, is in clinical development for the treatment of adult MDD. In animal models of depression, it shows a potent antidepressantlike effect 2 suggesting that it may offer therapeutic effects similar to older tricyclic antidepressants without the accompanying safety and tolerability issues. The sustained release (SR) formulation was developed to allow for once-daily dosing.Potency for inhibition of 5-HT reuptake...

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“…Further speci®cally designed studies are, however, required to con®rm unequivocally the potential rapid onset of action of venlafaxine. Despite initial results (Serre et al, 1986) suggesting a rapid onset of action for milnacipran, a meta-analysis of the major comparative studies has not con®rmed any dierence in onset of action of milnacipran compared with TCAs or SSRIs (Montgomery et al, 1996).…”

Section: Onset Of Actionmentioning

confidence: 94%

“…A placebo-controlled dose-ranging study (reviewed by Lecrubier et al, 1996) demonstrated, however, that the ecacy with milnacipran 200 mg/day was not superior to that obtained with 100 mg/day, whereas the higher dose was associated with an increased frequency of sideeects (Montgomery et al, 1996). One hundred mg/day (administered as 50 mg twice daily) has thus been de®ned as the optimal and recommended dose (Lecrubier et al, 1996).…”

Section: Antidepressant Ecacymentioning

confidence: 99%

Efficacy and tolerability of milnacipran

Cited by 67 publications

References 0 publications

Efficacy and Safety of Levomilnacipran Sustained Release 40 mg, 80 mg, or 120 mg in Major Depressive Disorder

Efficacy and Safety of Levomilnacipran Sustained Release 40 mg, 80 mg, or 120 mg in Major Depressive Disorder

Efficacy and Safety of Levomilnacipran Sustained Release in Moderate to Severe Major Depressive Disorder

Specific serotonin and noradrenaline reuptake inhibitors (SNRIs). A review of their pharmacology, clinical efficacy and tolerability

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