Mayor Depression affects 340 millions of people in the world 16.2% of risk of life prevalence, 2/3 are women. A refractary depression is the one that does not respond to a well found treatment in a period of time (usually around 8 weeks). It is associated to a higher rate of suicide, 15% higher rate of suicidal thoughts and actions, 33%, which means a worse prognosis. Higher costs; they visit the doctor three times as much as people who are not depressed.

we have analysed the main therapeutic reports on refractary depression.

ECT, may be effective if it is administrated acutely, but results tend to be poor if it is used for a long period of time. The STAR D report (Rush, 2006) showed that 25% of the patients improved as they were given a different antidepressant

The potentation of citalopram with bupropion or buspirone may also be useful (Madhulkar, 2006); combinations of antidepressants with some atypical antipsychotics have given good results (Nemeroff, 2004).

Fluoxetina, olanzapina or a combination of both were effective on a 60% of patients with a refractary depression (Shelton, 2001). Bolder I and II reports showed the effectiveness of using quetiapina. We introduce here the potential mechanisms of action of some atypical antipsychotics in refractary depression (improvement on the serotoninergic transmission, a blockade of the 5HT2 postsinaptic receptors, a release of dopamine in the prefrontal cortex).

The polyfarmacy is common. It is unknown which treatment or combination is better.