High-dose tricyclics potentiation with mirtazapine, lithium and partial sleep-deprivation: why not tricyclics in combination strategies for resistant melancholia?

Abstract

In recent years, combination strategies (which involve adding additional antidepressants with a different neurochemical profile) and augmentation (with nonantidepressant drugs such as lithium, T3 and atypical antipsychotics) are being used more frequently to treat resistant unipolar melancholic depression [Yazici, 2009; Blier et al. 2010; Ruiz-Doblado et al. 2010]. The use of different combination and augmentation strategies in severe, resistant depression is based clinically and physiopathologically on the neurochemical complementarity of drugs, their synergies, on the improved tolerability and reduced undesirable effects when a second drug is associated, and also on the growing body of experience with combinations of antidepressants in naturalistic conditions of ‘real’ clinical practice [Rush et al. 2009]. However, the use of the strategy of combining several drugs in resistant diseases also presents a serious predicament in other areas of medicine (e.g. high-activity antiretroviral therapy [HAART], resistant hypertension, etc.). Given that the final objective of antidepressant treatment should be complete remission of the resistant melancholia and not just a simple response, different observations have endorsed that simultaneous administration of two antidepressants may produce neurochemical changes more quickly.