Резистентные к лечению депрессии

Antidepressants can be grouped into 6 major categories: tricyclic antidepressants (TCAs), SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), serotonin neurotransmitter (5-HT2)-receptor antagonists (eg, nefazodone, trazodone), and novel agents (eg, mirtazapine, bupropion). If a patient fails to respond to one antidepressant class, it makes sense (at least conceptually) to switch to another, although most guidelines acknowledge that 2 failed trials of SSRIs may be justifiable before switching classes.
For example, in a study by Thase and colleagues,10 58 patients failed a trial of fluoxetine; however, there was a 76% response rate to citalopram among completers. Although this study was not blinded, it is interesting that citalopram (which is believed to be the most selective of the SSRIs) was effective when another SSRI was not.
Antidepressants that are associated with discontinuation symptoms (eg, paroxetine, venlafaxine, duloxetine) may produce discontinuation syndromes when stopped that can be erroneously attributed to adverse effects of the new drug, particularly if the new drug does not possess a significant degree of serotonin reuptake inhibition.
In a study by Zarate and colleagues,21 the onset of the antidepressant effect of ketamine occurred within 2 hours. Unfortunately, the drug must be given by intravenous infusion, but because the effect persisted for 7 days, ketamine treatment may be useful if given as a series.
Another NMDA-receptor antagonist now available in the United States is memantine (FDA-approved for Alzheimer disease). Memantine was shown to be effective in an open-label study in major depression. In a double-blind, randomized trial it showed comparable effects to escitalopram in patients with major depression and alcohol dependence.
Randomized controlled trials have supported the superior efficacy of a TCA/SSRI combination, as well as a mirtazapine/SSRI combination; open studies have done the same for TCA/MAOI and SSRI/bupropion combinations.
As with lithium, a recent review concluded that the trial data that support the efficacy of T3 augmentation are of better quality with TCAs than with SSRIs

Treatment-Resistant Depression