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Everyday Problems in Treating Depression: Focus on SNRIs

  • Siegfried Kasper


Most effective antidepressants directly or indirectly increase the synaptic concentrations of serotonin (5-HT) and/or norepinephrine (NE) by blocking the reuptake of one or both of the neurotransmitters. This property was initially discovered with the tricyclic antidepressants (TCAs). Their various additional interactions at different receptors and ion channels are not required for antidepressant action, but are responsible for the poor tolerability and toxicity in overdose of the early antidepressants.

The selective serotonin reuptake inhibitors are effective and well tolerated. Selective norepinephrine reuptake inhibitors, such as reboxetine, also have proven antidepressant activity. A selective action on one or the other of the principal monoamines thus appears to be sufficient for antidepressant activity. The idea that a dual action on both neurotransmitters might produce greater efficacy in certain patients led to the development of the serotonin norepinephrine reuptake inhibitor (SNRI) antidepressants, which block the reuptake of both 5-HT and NE without the nonspecific, side-effect–inducing interactions of the TCAs. The three SNRIs—venlafaxine, milnacipran, and duloxetine—constitute a new class of antidepressants.

Antidepressant response rates rarely exceed 60% to 70% and remission rates are usually <50%. Although SNRIs clearly provide superior efficacy in certain populations, their use has not dramatically changed antidepressant therapy. The search for agents that are more effective, rapidly acting, and better tolerated continues. However, clinicians must find ways to better use the antidepressants that are available today. This supplement, based on a symposium held at the International Forum on Affective Disorders in Budapest in December 2007, discusses several everyday problems in the treatment of depression, with a focus on SNRIs.


Corresponding author

Department of Psychiatry and Psychotherapy, Medical University of Vienna (MUV), Währinger Gürtel 18–20, A - 1090 Vienna, Austria ; Tel: 43-1-40400-3568; Fax:, 43-1-40400-3099 ; E-mail:,


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2. Papakostas, GI, Thase, ME, Fava, M, Nelson, JC, RC, Shelton. Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents. Biol Psychiatry. 2007;62:12171227.
3. SA, Montgomery, DS, Baldwin, Blier, P, et al. Which antidepressants have demonstrated superior efficacy? A review of the evidence. Int Clin Psychopharmacol. 2007;22:323329.


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