Refractory Major Depressive Disorder

Refractory Major Depressive Disorder

A staging system for treatment-resistant depression (TRD) has been proposed and ranges from failure to respond to a single agent (Stage 1) to failure of multiple treatments and electroconvulsive therapy (Stage 5; Thase and Rush, 1995), and is presented in Ta-ble 46.5. The term refractory depression has been proposed to de-scribe patients who have Stage 5 treatment-resistant depression.

Refractory MDD or Stage 5 in Table 46.5 is estimated to occur in up to 20% of patients. A larger percentage of patients with MDD, up to 30%, may show only partial improvement. The concept of treatment-resistant depression or refractory depres-sion describes this lack of response to a number of clinical trials using optimal dosing and duration of antidepressant medication. One must typically offer the patient a rational series of treatment trials using optimal dosing and duration of each antidepres-sant. Many individuals consider a patient refractory if a course of three, four, or five treatments is offered without substantial clinical response. The standard approach to the management of refractory depression includes increasing the antidepressant dose and monitoring for a full 8 to 12 week course augmenting the treatment with several augmentation strategies using an adequate combination of antidepressant drug treatment and psychotherapy and switching to alternative somatic treatments including ECT when indicated.

Refractory MDD is ameliorated in the context of a caring and collaborative treatment relationship based on a favorable ther- apeutic alliance. Patients sometimes will undermine treatment through their own persistent use of substances such as alcohol or lack of adherence to specific pharmacotherapy recommenda-tions. In this context the attention to the therapeutic alliance is particularly critical. In assessing an individual with refractory symptoms, pharmacologic factors including pharmacokinetic considerations, drug–drug interactions and extreme sensitivity to antidepressant drugs must be considered.

Despite many alternative strategies, substantial morbidity and occasional mortality are associated with refractory MDD. In addition, careful attention to psychosocial factors associated with refractoriness is critical. These psychosocial factors include early childhood adversity and abuse, early family dysfunction, increased neuroticism and marked disruption in the development of a stable sense of self.