Do we need new antidepressants?

Tolerability and efficacy are important factors determining the choice of an antidepressant. Older tricyclic antidepressants (TCAs) are associated with significant behavioural toxicity, notably psychomotor and cognitive impairment and sedation. These effects are not seen with newer TCAs and selective serotonin reuptake inhibitors (SSRIs). Furthermore, TCAs are associated with a variety of somatic adverse events resulting from binding to muscarinic, al-adrenergic and HI-histaminergic receptors, including dry mouth, visual disturbances and tremor. SSRIs are largely devoid of these effects, but gastrointestinal disturbances such as nausea end dyspepsia are common with these agents. Although the two classes of agent are broadly comparable in efficacy, there is some evidence that SSRIs may be less effective than TCAs in severely depressed patients. Hence, an antidepressant that is effective irrespective of the severity of depression and has a good tolerability profile, should offer important therapeutic advantages. Clinical experience with milnacipran, a new serotonin and noradrenaline reuptake inhibitor, indicates that this agent meets these criteria. (C) 1997 John Wiley & Sons, Ltd.