ABSTRACT
The definition of treatment-resistant depression remains debatable, although there is at least some agreement that it indicates a failure to respond to at least two ADs given in reasonable doses for a reasonable period of time. Nevertheless, the term cannot be found in the DSM-5, despite the massive number of studies aimed at its treatment. Instead, we now have persistent depressive disorder, accompanied by a specifier labeled persistent major depressive episode. This chapter will review the basic data on the frequency of treatment-resistant depression and will examine the many possibilities of treatment, including various drug combinations, augmentation strategies, and the use of antipsychotics, anti-inflammatories, hyperthermia, and antidiabetic drugs. We will also review the move to neurotherapeutics, including vagus nerve stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, theta-burst stimulation, deep brain stimulation, and various neurosurgical procedures such as cingulotomy. The risks and benefits of each will be reviewed, as well as their methodological problems and adverse events. In the following chapter, the use of hallucinogenic and psychogenic drugs, including ketamine and psilocybin, will be explored.
