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Several placebo-controlled trials have shown that milnacipran, 100 mg/day in two doses, is an effective antidepressant in both the ambulatory and hospital settings. Comparative trials against tricyclic antidepressants (imipramine and clomipramine) failed to show that milnacipran was any more effective. Milnacipran has not been compared with specific or non specific MAOI antidepressants. As regards non tricyclic-non MAOI antidepressants, milnacipran has been compared only to two specific serotonin reuptake inhibitors, fluvoxamine and fluoxetine. The trials cannot convince us of a difference in efficacy between the two types of treatment. The claimed superiority of milnacipran over serotonin reuptake inhibitors is not based on firm evidence of better efficacy or fewer adverse effects. The overall tolerability of milnacipran is similar to that of fluoxetine and fluvoxamine. Relative to the tricyclic antidepressants, milnacipran has fewer atropinic effects (sedation and sweating). In contrast, it cause more dysuria, and cannot, therefore, replace tricyclics in elderly men with prostate disorders. Tricyclics remain the preferred first-line antidepressant drugs. When they are contraindicated or poorly tolerated, many other antidepressants with well-documented risk-benefit ratios are available.

People from different ethnic or environmental backgrounds may respond differently to psychotropic drugs. The underlying psychogenic or biochemical cause of mental illness may vary in different cultures and cause differences in the presenting symptomatology. The psychotropic effect of drugs may then differ or be interpreted differently. Also, the pharmacokinetics of drugs, particularly rates of metabolism, may differ on account of genetic and/or environmental factors. The relevance of such differences to general clinical treatment will depend on the type of drug. If the margin of safety of a particular compound is small, then variation due to ethnic origin may be an important factor. For relatively safe drugs this is not so crucial but, in psychiatry particularly, unpleasant drug-induced side effects are common and it is desirable to find the preparation most acceptable to the individual. Clinical findings should not be extrapolated from one culture to another without examination of the relevant ethnic groups.