A randomized, double-blind, placebo-controlled study of flexible doses of levomilnacipran ER (40–120 mg/day) in patients with major depressive disorder

Figures & data

Table 1. Patient disposition.

	Placebo	Levomilnacipran ER 40–120 mg/day
Safety population, n	182	175
Intent-to-treat population, n	181	174
Completed study, % (safety population)	81.9	77.1
Reason for premature discontinuation
Adverse event	2.2	8.0*
Protocol violation	4.9	6.9
Withdrawal of consent	7.1	5.1
Lost to follow-up	2.7	2.3
Insufficient therapeutic response	0.5	0.6
Other	0.5	0

*p < 0.05.

ER, extended-release.

Table 2. Patient characteristics (safety population).

	Placebo (n = 182)	Levomilnacipran ER 40–120 mg/day (n = 175)
Demographic characteristics
Age, mean (SD), years	43.7 (13.3)	42.8 (12.9)
Sex, % women	63.7	56.6
Race, % white	81.9	76.0
BMI, mean (SD), kg/m^2	28.9 (5.7)	28.7 (5.4)
Major depressive disorder (MDD) disease characteristics
Age at onset, mean (SD), years	32.2 (14.2)	32.6 (13.6)
Recurrent MDD, n (%)	137 (75.3)	120 (68.6)
Duration of current episode,  mean (SD), months	15.1 (29.5)	20.2 (59.8)
Baseline MADRS score,  mean (SD)	35.5 (4.0)	35.9 (4.1)

BMI, body mass index; ER, extended-release; MADRS, Montgomery-Åsberg Depression Rating Scale.

Table 3. Efficacy and health outcomes results (ITT population).

Characteristics	Placebo (n = 181)	Levomilnacipran ER 40–120 mg/day (n = 174)
Secondary efficacy outcome (MMRM)
SDS total score
Baseline, mean (SEM)	20.8 (0.4)	21.7 (0.4)
LS mean change (SE)	−8.2 (0.7)	−8.8 (0.7)
Additional efficacy outcomes (MMRM)
HAMD17 total score
Baseline, mean (SEM)	24.4 (0.3)	24.9 (0.3)
LS mean change (SE)	−9.2 (0.6)	−9.9 (0.7)
CGI-I total score
Value at Week 8 (SE)	2.7 (0.1)	2.5 (0.1)
CGI-S total score
Baseline, mean (SEM)	4.7 (0.0)	4.8 (0.0)
LS mean change (SE)	−1.3 (0.1)	−1.5 (0.1)
Health outcomes (LOCF)
SF-36 PCS
Baseline, mean (SEM)	51.1 (0.8)	51.6 (0.8)
LS mean change (SE)	−1.2 (0.7)	0.2 (0.7)
SF-36 MCS
Baseline, mean (SEM)	19.1 (0.7)	18.3 (0.7)
LS mean change (SE)	14.9 (1.2)	15.7 (1.2)

CGI-I, Clinical Global Impression-Improvement; CGI-S, Clinical Global Impressions-Severity; ER, extended-release; HAMD, Hamilton Rating Scale for Depression; ITT, intent-to-treat; MCS, Mental Component Summary; PCS, Physical Component Summary; SDS, Sheehan Disability Score; SE, standard error; SEM, standard error of the mean; SF-36, Short-Form 36 Health Survey.

Figure 1. Change from baseline in MADRS total score (ITT population, MMRM).

Table 4. Most frequent (≥5% in any treatment group) double-blind treatment emergent adverse event (safety population).

Event	Placebo, % (n = 182)	Levomilnacipran ER 40–120 mg/day, % (n = 175)
Double-blind TEAEs
Nausea	3.3	17.1
Headache	12.1	16.0
Dry mouth	6.0	8.0
Hyperhidrosis	1.1	6.9
Insomnia	7.1	6.9
Dizziness	1.6	6.3
Vomiting	0.5	5.7
Heart rate increased	2.2	5.1
Upper respiratory tract infection	6.0	3.4
Ejaculation disorder^a	0	7.9
Erectile dysfunction^a	1.5	5.3

^aBased on the number of males in the safety population (placebo = 66, levomilnacipran ER = 76).

AE, adverse event; ER, extended-release; TEAE, treatment-emergent AE.

Table 5. Mean change in blood pressure and pulse rate (safety population).

Parameter, unit	Placebo (n = 182)		Levomilnacipran ER 40–120 mg/day (n = 175)
	n	Mean (SD)	n	Mean (SD)
Supine systolic blood pressure, mmHg
Baseline	181	119.5 (11.0)	174	118.7 (10.7)
Change at end of treatment	181	−0.6 (8.9)	174	2.8 (9.2)
Supine diastolic blood pressure, mmHg
Baseline	181	76.1 (7.4)	174	75.8 (8.2)
Change at end of treatment	181	−0.3 (7.6)	174	3.3 (8.4)
Supine pulse rate, bpm
Baseline	181	69.4 (7.7)	174	69.9 (9.0)
Change at end of treatment	181	−0.1 (8.2)	174	6.9 (9.7)

bpm, beats per minute; ER, extended-release.

Table 6. ASEX change in sexual dysfunction (safety population).

	Placebo			Levomilnacipran ER 40–120 mg/day
	n	n (%)	Mean (SD)	n	n (%)	Mean (SD)
Percentage of patients with sexual dysfunction^a
Women	109			94
Baseline sexual dysfunction		97 (89.0)			84 (89.4)
Endpoint sexual dysfunction		71 (65.1)			68 (72.3)
Men	65			71
Sexual dysfunction at baseline		40 (61.5)			50 (70.4)
Sexual dysfunction at endpoint		24 (36.9)			38 (53.5)
Change in sexual dysfunction: ASEX total score
Women
Baseline	104		21.8 (5.0)	87		23.0 (4.9)
Change at Week 8	94		−2.4 (5.3)	72		−2.3 (4.1)
Men
Baseline	61		18.6 (5.3)	67		18.8 (5.2)
Change at Week 8	54		−2.2 (4.3)	55		−1.1 (4.3)

^aCategorical sexual dysfunction reports the number (%) of patients with sexual dysfunction at baseline and endpoint; sexual dysfunction = total ASEX ≥19, or an individual item score ≥5, or a score ≥4 on three individual items44; endpoint = last available double-blind post-baseline assessment.

ASEX, Arizona Sexual Dysfunction Experience Scale; ER, extended-release.

McGahuey CA, Delgado PL, Gelenberg AJ. Assessment of sexual dysfunction using the Arizona Sexual Experiences Scale (ASEX) and implications for the treatment of depression. Psychiat Ann 1999;29:39-45

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