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Milnacipran and selective serotonin
reuptake inhibitors in major depression.
Lopez-Ibor J, Guelfi
JD, Pletan Y, Tournoux A, Prost JF.
Neuva Zelanda 44
Madrid, Spain.
Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:41-6.
Abstract
In drug development the move from
tricyclic antidepressants (TCAs) to selective serotonin reuptake
inhibitors (SSRIs) involved not only the loss of the direct receptor
interactions responsible for the adverse side effects of TCAs, but also
the ability to inhibit the reuptake of noradrenaline. Selectivity for the
single neurotransmitter, serotonin, may explain why SSRIs tend to be less
efficacious than the TCAs, especially in more serious forms of depression.
The advent of selective serotonin and noradrenaline reuptake inhibitors
(SNRIs) has tended to confirm the idea that an action on both monoamine
systems is important for maximal antidepressant efficacy. This paper
reviews clinical trials comparing the new SNRI milnacipran with the SSRIs
fluoxetine and fluvoxamine. A meta-analysis of the principal trials shows
greater response rates (the proportion of patients with a decrease in
symptom scores of 50% or more) with milnacipran (50 mg twice a day) than
with fluoxetine (20 mg once a day), or fluvoxamine (100 mg twice a day)
(milnacipran: 64%; SSRIs: 50%). Remission rates (the proportion of
patients with Hamilton Depression Rating Scores of 7 or below) were also
higher with milnacipran than with SSRIs (39 versus 28%). In one study, in
which 100 mg milnacipran was given once a day in the evening, the higher
response rate obtained with fluoxetine appears to be largely attributable
to an inappropriate milnacipran dosage regimen. Data from a
pharmacovigilance database including all patients participating in
clinical trials with milnacipran (n = 5732) showed that, compared with the
SSRIs, milnacipran produced fewer gastrointestinal side effects, such as
nausea, and less anxiety. Milnacipran was, however, associated with a
higher incidence of headache, dry mouth and dysuria. The results of these
studies suggest that milnacipran is superior in efficacy to SSRIs and is
equally well tolerated. Milnacipran, therefore, appears to offer a
therapeutic advantage over the SSRIs.
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