Nonrespons in first -line drug treatment of patients suffering from depression in psychiatric outpatient populations is a severe problem.

The non respons rate is up tot 30% and the non remission rate more than 50% in the first line of treatment with antidepressants in this population.

To devellop more rapid and efficious drug treatment strategies in depression.

During the last few years several strategies to improve outcome in depression have been under investigation. A few have proven to be valuable.

Medline search 2005–2010 into treatment resistent depression, combination therapy, augmentation therapy, drug therapy.

There is growing evidence for the value of the combination of antidepressants and of combining antidepressants with antipsychotics.

Treatment options as pindolol addition to antidepressants, substance P or folic acid addition do not seem of clinical significance yet.

The same is true for treatment methods who directly influence the glucocorticoid system such as glucocorticoid receptor antagonists.

NMDA antagonists look promising but more research into this option is needed.

There are two outstanding and much promising relatively new treatment options with: Combinations of antidepressants and with combinations of an antidepressant with an antipsychotic.