New antidepressants or more of the same?

New antidepressants or more of the same? Effective antidepressant drugs have been available for half a century since the fi rst monoamine oxidase inhibitor (MAOI), isoniazid, and the prototype tricyclic antidepres-sant (TCA), imipramine, were introduced into therapy (Leonard and Spencer 1990). The use of MAOIs declined when reports appeared of hypertensive crises associated with ingestion of dietary tyramine, and the TCAs, despite their shortcomings in safety and tolerability, became the mainstays of treatment. A second generation of drugs of various classes was developed with diverse chemical structures and different mechanisms of action (Pinder and Wieringa 1993), of which the most widely prescribed have been the selective serotonin reuptake inhibitors (SSRIs). Although modern drug discovery technologies like combinatorial chemistry and high-throughput screening have made less likely the identifi cation of truly novel agents (Pinder 2001), new agents and biological targets continue to be investigated (Bosker et al 2004). Psychological treatments, including cognitive and interpersonal therapies, also have their place in the acute and maintenance treatment of depression (DeRubels et al 2005). Two of the new kids on the block have been reviewed in recent issues of Neuropsy-chiatric Disease and Treatment. One is a new formulation of an old irreversible MAOI, selegiline, and is the fi rst transdermal antidepressant to be introduced (Lee and Chen 2007), while the second, agomelatine, has a novel mechanism of action in being a melatonin receptor agonist and a serotonergic (5-HT 2c) antagonist (Kennedy and Eisfeld 2007). The selegiline transdermal system (STS) has already received US Food and Drug Administration (FDA)-approval, while agomelatine may be approved shortly by the European Agency for the Evaluation of Medicinal Products (EMEA). Do these newcomers represent major advances in therapy? For US physicians, the use of MAOIs has long been restricted to phenelzine, tranylcypromine, and isocarboxazid, with most prescriptions being written for phen-elzine. As the only MAOI available in the USA for the treatment of depression that does not require dietary restriction at clinically effective doses, STS is likely to fi nd a place in the antidepressant armamentarium particularly for the treatment of atypical depression, treatment-resistant patients, and those with accompanying anxiety disorders (Lee and Chen 2007). Outside the USA, physicians have long had access to the reversible MAOI moclobemide which also lacks dietary restrictions. If STS comes to Europe or to other parts of the world, it is likely to be the novelty factor that prompts physicians to prescribe a …