Efficacy and safety of multiple doses of levomilnacipran extended-release for the treatment of major depressive disorder

Abstract

ObjectiveThe aim of this meta-analysis was to evaluate the efficacy and safety of levomilnacipran extended-release (ER) in the treatment of major depressive disorder (MDD).MethodsRandomized controlled trials were searched by electronic databases. Unpublished data were also searched by the relevant websites. Weighted mean difference (WMD) and risk ratio (RR) with 95% confidence interval (CI) were calculated and pooled using fixed-effects model or random-effects model.ResultsFive randomized placebo-controlled trials including 2,637 patients were analyzed. Compared with placebo, levomilnacipran ER had a greater reduction in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score and Sheehan Disability Scale (SDS) total score (MADRS: WMD −3.49 [95% CI −4.28, −2.70; P<0.00001]; SDS: WMD −2.41 [95% CI −3.05, −1.77; P<0.00001]). Significantly more patients in levomilnacipran ER achieved MADRS response rate (RR 1.35 [95% CI 1.23, 1.47; P<0.00001]) and MADRS remission rate (RR 1.30 [95% CI 1.06, 1.59; P=0.01]). In terms of safety, more patients discontinued due to adverse events (AEs) in levomilnacipran ER compared with placebo (RR 3.15 [95% CI 2.26, 4.39; P<0.00001]), but it was generally well tolerated in each eligible trial. The most common AEs were nausea, delay in ejaculation, erectile dysfunction, tachycardia, headache and increase in heart rate.ConclusionLevomilnacipran ER is a safe and effective short-term treatment for MDD (≤10 weeks). Long-term and head-to-head trials comparing levomilnacipran ER with other antidepressants are needed to confirm the conclusion.

Antidepressant Drugs Effects on Blood Pressure

“…Milnacipran and levomilnacipran are contraindicated in end-stage kidney disease and chronic liver disease and patients with previous cardiovascular disease. Milnacipran and levomilnacipran can induce an increase in both systolic and diastolic BP (+3 and +3.2 mmHg in systolic and diastolic BP, respectively, for levomilnacipran, and + 3 mmHg for both in systolic and diastolic BP with milnacipran) ( 132 – 137 ) as observed during office and ambulatory BP monitoring ( 138 – 140 ). Takotsubo cardiomyopathy has been described at both therapeutic doses and in overdoses of milnacipran; high doses of this drug show negative inotropic, chronotropic, and dromotropic effects ( 67 , 141 ).…”

Association of 5-HT1A Receptors with Affective Disorders

“…Similarly, treatment with levomilnacipran (40-120 mg) in patients aged 18-80 diagnosed with some depression disorder, significantly reduced symptoms after 8-10 weeks of treatment [90]. These data show that the effect of SNRIs in treating major depression disorders depends on the characteristics of patients and the dosage schedule.…”

“…Venlafaxine MDD, AD, syndrome of chronic pain, BDD [85,86] Desvenlafaxine MDD in adult patients [89] Duloxetine MDD, DPNP, fibromyalgia [96,104,107] Atomoxetine ADHD in adults and pediatric patients under 6 years old [103,108] Sibutramine Treatment of obesity [106] Milnacipran MDD, fibromyalgia [85,105] Levomilnacipran MDD, AD in adult patients [90] Abbreviations: MDD, major depression disorder; BDD, bipolar depression disorder; AD, anxiety disorder; DPNP, diabetic peripheral neuropathy pain; ADHD, attention deficit hyperactivity disorder. Indeed, in some cases they work better than classic antidepressant drugs (e.g., SSRIs and tricyclic drugs) in certain groups of patients.…”

The Cardiovascular Effects of Newer Antidepressants in Older Adults and Those With or At High Risk for Cardiovascular Diseases

“…In clinical trials with medically healthy adults, levomilnacipran increased systolic and diastolic blood pressure, pulse, and the QTc interval by a small but statistically significant degree. However, the increase in QTc in this population was not deemed clinically significant 61 . There are no studies of the cardiovascular effects of levomilnacipran in older adults, adults with cardiovascular disease, or adults who have been medically hospitalized.…”