Potential reasons for nonresponse to pharmacotherapy for major depressive disorders are inaccurate diagnosis, unaddressed co-occurring medical or psychiatric disorders, non-adherence to treatment, and complicating psychosocial and psychological factors according to the American Psychiatric Association (APA) treatment guidelines for major depressive disorders.
 Parker et al. proposed diagnostic paradigm errors such as failure to diagnose and manage bipolar disorder and psychotic depression, misdiagnosing secondary depression due to anxiety disorders and personality disorders, and failure to identify organic determinants.
 Based on our recent research, it takes an average of four years to finally diagnose bipolar disorder, and both patients and clinicians are responsible for this diagnostic lateness.
 Regarding adherence, it is known that more than half of outpatients with depression become non-adherent within 6 months after their initial consultation. The major reasons for non-adherence are thought to be lack of explanation about treatment duration, as well as lack of dependency on antidepressants, fewer side effects and treatment efficacy.
 Regarding pharmacotherapy, focusing on early response may predict good outcomes.
 It was clarified that even for treatment-refractory patients, almost 60% reach remission with social support and augmenting cognitive behavioral therapy. We should never give up on such patients.
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