It should be pointed out that in spite of being a hypertensive patient, her blood pressure, monitored daily, stayed within the normal range of 130 mmHg/70 mmHg. Biochemical parameters, creatinine, liver function laboratory

tests, TSH and EKG showed no changes with the combined treatment. Lithaemia was 0.66 mEq/L at the sixth week. No adverse effects were reported Inhibitors,research,lifescience,medical with the exception of dry mouth and moderate constipation, both well tolerated by the patient. Discussion The combination of high doses of both selleck compound clomipramine [Gervasoni et al. 2009] and mirtazapine achieved a high level of synergy, acting at pharmacodynamic level through triple serotoninergic enhancement (reuptake inhibition by clomipramine, alpha-2 and 5-HT2 antagonistic effects of mirtazapine) and dual noradrenergic enhancement

(reuptake inhibition by clomipramine and its active metabolite desmethylclomipramine, antagonistic alpha-2 effect of mirtazapine). In addition, blockage of the 5-HT2 and 5-HT3 receptors achieved Inhibitors,research,lifescience,medical with mirtazapine can help to reduce the serotoninergic sexual (5-HT2) and digestive (5-HT3) adverse effects of clomipramine. It is also known that sustained 5-HT2 blockage improves sleep and increases the gene expression of the 5-HT1A receptor (synergy between 5-HT2 antagonism and 5-HT1A stimulation) [Ruiz-Doblado Inhibitors,research,lifescience,medical et al. 2010]. In addition, both clomipramine and mirtazapine were considered two of the most effective antidepressant drugs in a recent review of the evidence [Montgomery et al. 2007]. Furthermore, lithium enhancement has a stabilizing effect on membranes and also Inhibitors,research,lifescience,medical on sodium cellular transportation, as well as the upregulation of gene expression associated with neurotransmission Inhibitors,research,lifescience,medical via second messengers (phosphatidylinositol). Finally, partial rapid eye movement sleep deprivation, during

the second half of the night, can enhance pharmacological effect. Although its efficacy is known at the empirical level, the mechanism of action of its antidepressant effect remains unclear. Nowadays there are ‘cleaner’ combinations in treatment algorithms for resistant melancholia, such as those associating venlafaxine or duloxetine (both dual 5-HT-NA Rolziracetam antidepressants) with a second antidepressant or mood regulator [Hannan et al. 2007; De la Gándara et al. 2008; Yazici, 2009], but some works have shown that the noradrenergic effect of these new drugs may be inferior to that of clomipramine, which achieves a powerful noradrenaline reuptake inhibition due to both the drug itself and its metabolite (clomipramine + desmethylclomipramine) [Gillman, 2007]. According to our current state of knowledge, this is the first documented case of response to this combination of drugs in resistant melancholia at these doses.