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Antidepressant therapy with milnacipran and venlafaxine

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ABSTRACT

Specific serotonin norepinephrine reuptake inhibitors (SNRIs) have been described as “better tolerated tricyclic antidepressants” or as “boosted” selective serotonin reuptake inhibitors (SSRIs). Venlafaxine has become a therapeutic reference treatment for major depression. Although less widely studied, indirect comparisons with another SNRI, milnacipran, suggest an equivalent efficacy. This paper discusses these indirect comparisons and the recently published first double-blind, head-to-head comparison. Venlafaxine has potency at serotonin transporters which is about 30-fold greater than that at norepinephrine transporters while milnacipran has a similar potency at each transporter. Thus, at low doses, venlafaxine acts essentially as a SSRI, with significant noradrenergic activity only occurring at higher doses. To overcome the problem of the differing profile of venlafaxine at increasing doses, the first head-to-head study compared the therapeutic effects and tolerability of the two antidepressants when flexibly titrated to the high dose of 200 mg/day. The study showed that the two SNRIs have similar efficacy and safety profiles. Both drugs produced about 42% remissions at the end of the 20-week study. The most frequent adverse events in both groups were nausea, dizziness, headache, and sweating. Certain specific differences in tolerability are discussed.

No MeSH data available.


Principal adverse events experienced with milnacipran and venlafaxine during the study.Key: black columns = milnacipran; grey columns = venlafaxine. Notes: Only adverse events with a frequency ≥ 10% are shown.
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f3-ndt-6-017: Principal adverse events experienced with milnacipran and venlafaxine during the study.Key: black columns = milnacipran; grey columns = venlafaxine. Notes: Only adverse events with a frequency ≥ 10% are shown.

Mentions: During treatment, AEs were reported by 72% patients in the milnacipran group and 74% patients in the venlafaxine group. In both groups, the most common treatment-emergent AEs (occurring in ≥ 10% of patients) were nausea, headache, dizziness, constipation, hyperhidrosis, palpitations, and dry mouth (Figure 3). After the end of treatment during the down-titration, the incidence of AEs was greater in the venlafaxine group (14% versus 7% in the milnacipran group). In males, dysuria was experienced only in the milnacipran group (20%), while orgasmic disorders were only reported in the venlafaxine group (17%). Most of the AEs occurred during the first 3 weeks of treatment, and 85% of them were of mild or moderate severity. Five patients in the milnacipran group and seven patients in the venlafaxine group experienced at least one serious AE. Only three serious AEs (all in the venlafaxine group) were considered to be possibly related to the study treatment (one worsening depression, one anxiety related to an overdose of venlafaxine, and one biliary colic).


Antidepressant therapy with milnacipran and venlafaxine
Principal adverse events experienced with milnacipran and venlafaxine during the study.Key: black columns = milnacipran; grey columns = venlafaxine. Notes: Only adverse events with a frequency ≥ 10% are shown.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2819762&req=5

f3-ndt-6-017: Principal adverse events experienced with milnacipran and venlafaxine during the study.Key: black columns = milnacipran; grey columns = venlafaxine. Notes: Only adverse events with a frequency ≥ 10% are shown.
Mentions: During treatment, AEs were reported by 72% patients in the milnacipran group and 74% patients in the venlafaxine group. In both groups, the most common treatment-emergent AEs (occurring in ≥ 10% of patients) were nausea, headache, dizziness, constipation, hyperhidrosis, palpitations, and dry mouth (Figure 3). After the end of treatment during the down-titration, the incidence of AEs was greater in the venlafaxine group (14% versus 7% in the milnacipran group). In males, dysuria was experienced only in the milnacipran group (20%), while orgasmic disorders were only reported in the venlafaxine group (17%). Most of the AEs occurred during the first 3 weeks of treatment, and 85% of them were of mild or moderate severity. Five patients in the milnacipran group and seven patients in the venlafaxine group experienced at least one serious AE. Only three serious AEs (all in the venlafaxine group) were considered to be possibly related to the study treatment (one worsening depression, one anxiety related to an overdose of venlafaxine, and one biliary colic).

View Article: PubMed Central

ABSTRACT

Specific serotonin norepinephrine reuptake inhibitors (SNRIs) have been described as “better tolerated tricyclic antidepressants” or as “boosted” selective serotonin reuptake inhibitors (SSRIs). Venlafaxine has become a therapeutic reference treatment for major depression. Although less widely studied, indirect comparisons with another SNRI, milnacipran, suggest an equivalent efficacy. This paper discusses these indirect comparisons and the recently published first double-blind, head-to-head comparison. Venlafaxine has potency at serotonin transporters which is about 30-fold greater than that at norepinephrine transporters while milnacipran has a similar potency at each transporter. Thus, at low doses, venlafaxine acts essentially as a SSRI, with significant noradrenergic activity only occurring at higher doses. To overcome the problem of the differing profile of venlafaxine at increasing doses, the first head-to-head study compared the therapeutic effects and tolerability of the two antidepressants when flexibly titrated to the high dose of 200 mg/day. The study showed that the two SNRIs have similar efficacy and safety profiles. Both drugs produced about 42% remissions at the end of the 20-week study. The most frequent adverse events in both groups were nausea, dizziness, headache, and sweating. Certain specific differences in tolerability are discussed.

No MeSH data available.