EFFICACY AND TOLERABILITY OF MILNACIPRAN - AN OVERVIEW

The relative benefits and risks of milnacipran, a novel antidepressant which selectively inhibits the reuptake of serotonin and noradrenalin e, have been evaluated in comparative trials against tricyclic antidep ressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs). A total of 2462 patients with major depressive disorders have been inves tigated. At the optimal dose (50 mg twice a day), the efficacy of miln acipran was equivalent to that of the TCAs, with response rates of app roximately 65% in both cases. Milnacipran was consistently effective a gainst all of the principal elements of depression (anxiety, cognitive function, sleep and psychomotor retardation), and did not produce sed ation or the emergence of suicidal thoughts. The Clinical Global Impre ssion (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 frequen cy of adverse events than milnacipran, particularly with respect to an ticholinergic-like effects; dysuria was the only adverse event occurri ng twice as frequently with milnacipran than with TCAs. Compared with TCAs, milnacipran was also associated with a lower incidence of cardio vascular adverse events. No haematological abnormalities occurred duri ng treatment with milnacipran, and the incidence of abnormal liver fun ction tests tended to be lower with milnacipran than with TCAs. In com parisons with SSRIs, milnacipran produced significantly higher respons e rates. The CGI-3 scores were significantly higher in milnacipran-tre ated 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 cl inical advantages over TCAs in terms of tolerability, and over SSRIs i n terms of efficacy. In particular, the lack of cardiovascular adverse events appears to offer advantages in cases of deliberate overdose. T o 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.