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Milnacipran.
A review of its use in depression.
Spencer CM, Wilde MI.
Adis International Limited
Auckland, New Zealand.
demail@adis.co.nz
Abstract
Milnacipran is a cyclopropane derivative which acts by
inhibiting noradrenaline (norepinephrine) and serotonin
(5-hydroxytryptamine; 5-HT) reuptake at presynaptic sites; no postsynaptic
receptor activity has been demonstrated. It is most commonly administered
at a dosage of 50 mg twice daily for the treatment of major depressive
disorder. Improvement usually occurs within 2 weeks of treatment
initiation, but some patients do respond sooner. Most studies which
evaluated milnacipran were of short (4 to 8 weeks) duration and results
were not published in full with rigorous peer review. Nonetheless, the
drug is significantly more effective than placebo for the treatment of in-
or outpatients with moderate to severe major depressive disorder. Limited
data suggest that it may prevent relapse and be effective for long term
use, although this requires confirmation. Milnacipran 200 mg/day is
generally not significantly different from amitriptyline 150 mg/day in
terms of onset and efficacy. However, when doses are titrated (not a
requirement for milnacipran), milnacipran 50 or 100 mg/day has a slower
onset than the tricyclic antidepressant. At a dosage of 100 mg/day for 4
to 12 weeks, milnacipran generally has similar efficacy to imipramine and
clomipramine 150 mg/day, although milnacipran 50 to 150 mg/day had a
faster onset of activity than imipramine 50 to 150 mg/day in Japanese
patients. In a 6-month trial, milnacipran was less effective than
clomipramine. Milnacipran 50 or 100 mg twice daily was as effective as
fluoxetine 20 mg once daily or fluvoxamine 100 mg twice daily in 4- to
12-week studies. At a dosage of 50 then 100 mg daily it was also as
effective as mianserin 30 then 60 mg daily in a 4-week study. However,
when administered once daily (in the evening), milnacipran 100 mg/day was
not as effective as fluoxetine 20 mg/day after 6 weeks. The drug is
generally well tolerated, producing no more adverse events (including
anticholinergic events) than placebo, selective serotonin reuptake
inhibitors or mianserin and fewer adverse events than tricyclic
antidepressants in clinical trials. However, dysuria has been reported in
7% of male patients receiving milnacipran.
CONCLUSIONS: Data from
predominantly short term trials suggest that milnacipran generally has
similar efficacy to tricyclic antidepressants and SSRIs. Although further
published data are required to confirm its efficacy, good tolerability
profile and pharmacokinetic profile which suggests a low potential for
drug interactions, milnacipran should be considered a promising agent for
the treatment of patients with major depressive disorder.
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