Efficacy and tolerability of milnacipran: an overview.
Montgomery SA, Prost JF, Solles A, Briley M.
St Mary's Hospital Medical School, London, UK.
Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:47-51
Abstract
The relative benefits and risks of milnacipran, a novel
antidepressant which selectively inhibits the reuptake of serotonin and
noradrenaline, have been evaluated in comparative trials against
tricyclic antidepressants (TCAs) or selective serotonin reuptake
inhibitors (SSRIs). A total of 2462 patients with major depressive
disorders have been investigated. At the optimal dose (50 mg twice a
day), the efficacy of milnacipran was equivalent to that of the TCAs,
with response rates of approximately 65% in both cases. Milnacipran was
consistently effective against all of the principal elements of
depression (anxiety, cognitive function, sleep and psychomotor
retardation), and did not produce sedation or the emergence of suicidal
thoughts. The Clinical Global Impression (CGI-3) score, a measure of the
overall therapeutic impact of a treatment, was significantly higher with
milnacipran than with TCAs (1.98 versus 1.84, p < 0.05). TCAs were
associated with a higher frequency of adverse events than milnacipran,
particularly with respect to anticholinergic-like effects; dysuria was
the only adverse event occurring twice as frequently with milnacipran
than with TCAs. Compared with TCAs, milnacipran was also associated with
a lower incidence of cardiovascular adverse events. No haematological
abnormalities occurred during treatment with milnacipran, and the
incidence of abnormal liver function tests tended to be lower with
milnacipran than with TCAs. In comparisons with SSRIs, milnacipran
produced significantly higher response rates. The CGI-3 scores were
significantly higher in milnacipran-treated patients (2.64 versus 2.32,
p < 0.05). The adverse event profiles of the two treatments were
similar, as was the incidence of abnormal liver function tests. These
studies suggest that milnacipran offers clinical advantages over TCAs in
terms of tolerability, and over SSRIs in terms of efficacy. In
particular, the lack of cardiovascular adverse events appears to offer
advantages in cases of deliberate overdose. To date, 15 such overdoses
have occurred; none was fatal and each had a favourable outcome. The
reproducible pharmacokinetic characteristics of milnacipran present
further advantages over both groups of agents, due to lack of drug
accumulation and a low risk of drug interactions.
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