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Recent guidance from the National Institute for Health and Clinical Excellence (NICE) says that antidepressant drugs should be offered routinely to all patients with depression of at least moderate severity and recommends a selective serotonin reuptake inhibitor as first line treatment. 1 The NICE guidance goes on to state that "Patients started on antidepressants should be informed about the delay in onset of effect." This reflects conventional wisdom, but is it time to revisit this idea?
Speed of onset of the actions of antidepressants is clinically important for several reasons. Delayed onset means that depression, its associated disability, and for some patients the potential risk of suicide continue. Early onset of effects may improve future compliance and thus outcomes.
When tricyclic antidepressants were first introduced in the 1950s delays in antidepressant effects were not reported. Indeed, researchers on early tricyclic antidepressants asserted that they usually started to work within the first few days of treatment. 2 3 Later clinical experience suggested, however, that the drugs did not act immediately. The ensuing debate continued into the 1970s. By the mid-1970s, animal models suggested that the dissociation of acute biochemical changes induced by antidepressant treatment and the therapeutic action were due to the development of subsensitivity in the postsynaptic monoamine receptor. 4 5 In animal models, these changes became apparent only after dosing with antidepressants over a similar period to that taken for clinical efficacy to develop. In the 1980s, a series of pooled clinical studies seemed to confirm this delayed onset of action. 6...