Definition
Treatment-resistant depression is difficult to define. The term embraces many variables that can influence response to treatment. Treatment-resistant depression must be differentiated from a chronic depressive illness (i.e., present for many years before the onset of treatment), and from a recurrent depression in which a single episode has resolved in a satisfactory manner, but recurrence or relapse has become the problem. Keller and associates have shown that more than 20% of patients with serious depression do not recover after 2 years of prospective follow up. Of those who do make an initial good recovery, more than 20% suffer a relapse 1 year later.
In defining a single episode of depression as treatment resistant (chronicity or relapse not being the problem), many variables must be considered. What is the definition of an adequate response? Is it a 50% or more reduction of symptoms, measured with an instrument such as the Hamilton Rating Scale, or should the patient be virtually symptom-free? How does one define adequate treatment? What dose of an anti-depressant can be considered optimal? Should serum levels be monitored? What is an adequate period for treatment (e.g., it has recendy been established that a tricyclic can take up to 12 weeks to produce a full response)? How many drug trials are necessary, and must electroconvulsive shock therapy (ECT) be used without a response, before treatment resistance is determined? What subtype of depression is being considered? For example, when an antidepressant is used alone, the response rate is only 20% in psychotic depression, but is much higher in nonpsychotic depression.
Most studies suggest that 60% to 70% of patients with serious depression respond to the first antidepressant drug that is administered. A further 10% to 15% respond after a course of ECT or a second antidepressant. About 15% of patients fail to recover and can be labeled treatment resistant.
This suggests that treatment resistance could be defined as the presence of significant symptoms after two adequate courses of antidepressants and a course of ECT The terms absolute and relative can be applied to TRD. Absolute TRD refers to patients who have been correctly diagnosed and adequately treated, but who fail to show an expected response. Relative TRD refers to patients who have not been correctly diagnosed or adequately treated.
Because treatment resistance is usually relative, a discussion of the many factors that can prevent a patient with depression from responding is essential. Guidelines for the various steps that can be taken if a particular treatment is unsuccessful are also important.