Mirtazapine selective serotonin reuptake inhibitors with

Clinical reports, prescription databases, and a few trials support the use of selective serotonin reuptake inhibitors in combination with the older tricyclics, especially desipramine with bupropion and, most recently, with mirtazapine in patients who do not show an adequate response to a single agent. 

When compared with the selective serotonin reuptake inhibitors (SSRIs), mirtazapine may show an earlier onset of action (although data are currently not well established). Mirtazapine has also been found to be efficacious in the treatment of elderly patients with depression. Mirtazapine has been shown to be effective in the treatment of panic disorder, social phobia, and post-traumatic stress disorder. In one study, mirtazapine combined with citalopram in obsessive-compulsive patients induced an earlier response when compared with citalopram plus placebo. It was suggested that antagonism of presynaptic a2-adrenergic receptors does not enhance serotonin neurotransmission directly, but rather disinhibits the norepinephrine activation of serotonergic neurons and thereby increases serotonergic neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. 

Most prominent among the psychotropics that enhance serotonergic transmission are the selective serotonin reuptake inhibitors (SSRIs), which may induce sexual dysfunction in as many as 50-75% of patients, in part by activation of central 5-HT2 receptors. Antidepressants that antagonize the 5-HT2 receptor, such as mirtazapine and trazodone, cause fewer sexual side-effects compared with the SSRIs. Stimulation of the 5-HTia receptor facilitates sexual functioning, while activation of the 5-HTib,id and 5-HTic receptors inhibits... 

Ozmenler NK, Karlidere T, Bozkurt A, Yetkin S, Doruk A, Sutcigil L. Mirtazapine augmentation in depressed patients with sexual dysfunction due to selective serotonin reuptake inhibitors. Hum Psychopharmacol 2008 23(4) 321-6. 

With this caveat in mind, each side of the debate has evidence to support its position. The evidence is first summarized supporting the position that SSRIs are less effective than are some other antidepressants (particularly those with dual effects on both serotonin and NE CNS systems) in patients with more severe depression or who are hospitalized. Danish investigators in two double-blind, active-controlled studies found that clomipramine produced a superior response with either paroxetine or citalopram in the treatment of patients hospitalized for major depression (116, 117). Two double-blind studies also have shown that venlafaxine and mirtazapine were more effective than fluoxetine in patients hospitalized with depression ( 114,118). Finally, there are studies showing that the addition of desipramine (one of the most selective NE reuptake inhibitors) to an SSRI can convert nonresponders or pamal responders to full response ( 119, 119a, 120). 

---