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Safety and tolerability of levomilnacipran ER in major depressive disorder: results from an open-label, 48-week extension study.

Mago R, Forero G, Greenberg WM, Gommoll C, Chen C - Clin Drug Investig (2013)

Bottom Line: The objective of this study was to evaluate the longer-term safety and tolerability of levomilnacipran extended-release (ER).No clinically meaningful changes occurred in mean liver enzyme, metabolic, hematologic, urinalysis, or serum values; potentially clinically significant high AST or ALT values (≥3 × upper limit of normal) occurred in five patients.No new or inconsistent safety/tolerability findings were discovered during longer-term evaluation.

View Article: PubMed Central - PubMed

Affiliation: Mood Disorders Program, Department of Psychiatry and Human Behavior, Thomas Jefferson University, 833 Chestnut St., Suite 210 E, Philadelphia, PA, 19107, USA, rajnish.mago@jefferson.edu.

ABSTRACT

Background: Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin (5-HT) and norepinephrine (noradrenaline) reuptake inhibitor approved for the treatment of major depressive disorder in adults.

Objective: The objective of this study was to evaluate the longer-term safety and tolerability of levomilnacipran extended-release (ER).

Methods: Patients who completed double-blind treatment/down-taper in one of three lead-in levomilnacipran ER studies were eligible for this 48-week open-label extension. Safety evaluations included assessment of treatment-emergent adverse events (TEAEs), physical examinations, laboratory and vital sign measures, and suicidality, summarized using descriptive statistics for the safety population.

Results: The completion rate was 47 %; median treatment duration was 280 days. The most frequent reasons for discontinuation were withdrawal of consent (14 %) and adverse events (AEs; 13 %). TEAEs were reported by 712 (86 %) patients; most were mild/moderate and occurred early in treatment. The most common TEAEs were headache (22 %) and nausea (16 %); 36 (4 %) patients had ≥1 serious AEs. No clinically meaningful changes occurred in mean liver enzyme, metabolic, hematologic, urinalysis, or serum values; potentially clinically significant high AST or ALT values (≥3 × upper limit of normal) occurred in five patients. Vital sign changes occurred early and remained relatively stable. Mean increases for pulse rate (9.1 beats per minute [bpm]), and supine systolic (3.9 mmHg) and diastolic (3.3 mmHg) blood pressure were noted. The increase in the mean QT interval corrected using the Bazett formula (10.9 ms) was consistent with heart rate increase (12.8 bpm); there was no meaningful change in mean QT interval corrected using the Fridericia formula (-1.3 ms). Other than tachycardia and heart rate increases, ECG-related TEAEs were low (<0.5 %).

Conclusion: No new or inconsistent safety/tolerability findings were discovered during longer-term evaluation.

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Related in: MedlinePlus

Study design. ER extended-release
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Related In: Results  -  Collection


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Fig1: Study design. ER extended-release

Mentions: This extension study was 52 weeks in duration and consisted of a 48-week open-label treatment period followed by a down-taper period of up to 4 weeks (Fig. 1); week 0/visit 1 refers to the last visit of the double-blind down-taper, which was also the first week of the open-label study. There were 18 scheduled clinic visits during the open-label treatment (weeks 0–48) and down-taper (weeks 48–52) periods; visits occurred weekly for the first 4 weeks and every 4 weeks thereafter. Additionally, 11 interim telephone contacts were conducted at 2-week intervals between site visits to evaluate adverse events (AEs) and concomitant medications.Fig. 1


Safety and tolerability of levomilnacipran ER in major depressive disorder: results from an open-label, 48-week extension study.

Mago R, Forero G, Greenberg WM, Gommoll C, Chen C - Clin Drug Investig (2013)

Study design. ER extended-release
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3775192&req=5

Fig1: Study design. ER extended-release
Mentions: This extension study was 52 weeks in duration and consisted of a 48-week open-label treatment period followed by a down-taper period of up to 4 weeks (Fig. 1); week 0/visit 1 refers to the last visit of the double-blind down-taper, which was also the first week of the open-label study. There were 18 scheduled clinic visits during the open-label treatment (weeks 0–48) and down-taper (weeks 48–52) periods; visits occurred weekly for the first 4 weeks and every 4 weeks thereafter. Additionally, 11 interim telephone contacts were conducted at 2-week intervals between site visits to evaluate adverse events (AEs) and concomitant medications.Fig. 1

Bottom Line: The objective of this study was to evaluate the longer-term safety and tolerability of levomilnacipran extended-release (ER).No clinically meaningful changes occurred in mean liver enzyme, metabolic, hematologic, urinalysis, or serum values; potentially clinically significant high AST or ALT values (≥3 × upper limit of normal) occurred in five patients.No new or inconsistent safety/tolerability findings were discovered during longer-term evaluation.

View Article: PubMed Central - PubMed

Affiliation: Mood Disorders Program, Department of Psychiatry and Human Behavior, Thomas Jefferson University, 833 Chestnut St., Suite 210 E, Philadelphia, PA, 19107, USA, rajnish.mago@jefferson.edu.

ABSTRACT

Background: Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin (5-HT) and norepinephrine (noradrenaline) reuptake inhibitor approved for the treatment of major depressive disorder in adults.

Objective: The objective of this study was to evaluate the longer-term safety and tolerability of levomilnacipran extended-release (ER).

Methods: Patients who completed double-blind treatment/down-taper in one of three lead-in levomilnacipran ER studies were eligible for this 48-week open-label extension. Safety evaluations included assessment of treatment-emergent adverse events (TEAEs), physical examinations, laboratory and vital sign measures, and suicidality, summarized using descriptive statistics for the safety population.

Results: The completion rate was 47 %; median treatment duration was 280 days. The most frequent reasons for discontinuation were withdrawal of consent (14 %) and adverse events (AEs; 13 %). TEAEs were reported by 712 (86 %) patients; most were mild/moderate and occurred early in treatment. The most common TEAEs were headache (22 %) and nausea (16 %); 36 (4 %) patients had ≥1 serious AEs. No clinically meaningful changes occurred in mean liver enzyme, metabolic, hematologic, urinalysis, or serum values; potentially clinically significant high AST or ALT values (≥3 × upper limit of normal) occurred in five patients. Vital sign changes occurred early and remained relatively stable. Mean increases for pulse rate (9.1 beats per minute [bpm]), and supine systolic (3.9 mmHg) and diastolic (3.3 mmHg) blood pressure were noted. The increase in the mean QT interval corrected using the Bazett formula (10.9 ms) was consistent with heart rate increase (12.8 bpm); there was no meaningful change in mean QT interval corrected using the Fridericia formula (-1.3 ms). Other than tachycardia and heart rate increases, ECG-related TEAEs were low (<0.5 %).

Conclusion: No new or inconsistent safety/tolerability findings were discovered during longer-term evaluation.

Show MeSH
Related in: MedlinePlus