Chronic and treatment resistant depression: diagnosis and stepwise therapy

Abstract

Background: The 12-month prevalence of depression in Europe is approximately 7%; depression becomes chronic in 15-25% of sufferers. One-third to one-half do not respond to an initial trial of drug therapy lasting several weeks.

Methods: Selective literature review, including consideration of the German National Disease Management Guideline Unipolar Depression.

Results: At the end of an initial trial of treatment with an antidepressant drug, usually lasting four weeks, its efficacy should be evaluated systematically. In case of non-response, the following options have been found useful: measurement of the serum drug level, dose escalation (but not for selective serotonin reuptake inhibitors [SSRIs]), lithium augmentation, the addition of a second-generation antipsychotic (atypical neuroleptic), and any one of several defined combinations of antidepressants. There is no empirical evidence for switching to another antidepressant. Electroconvulsive therapy is the most effective treatment for refractory depression. Cognitive behavioral therapy, interpersonal psychotherapy, psychoanalysis and psychodynamic psychotherapy have also been found useful. The cognitive behavioral analysis system of psychotherapy (CBASP) was developed specifically for the treatment of chronic depression.

Conclusion: The structured application of treatments of documented efficacy, in a stepwise treatment algorithm that gives equal weight to drugs and psychotherapy, is the best way to prevent or overcome treatment resistance and chronification.

Figures

Figure 1

Steps in an algorithm for the diagnostic evaluation of depression. The recommended tests serve to rule out somatic disease; they do not include prerequisite tests fo particular treatment options (e.g., ECG before treatment with serotonin reuptake inhibitors or tricyclic antidepressants). Any of the tests listed may be omitted if it is clear, in the individual patient, that a pathological finding on that test is not to be expected. CBC, complete blood count CRP, c-reactive protein CT, computed tomography MRI, magnetic resonance imaging TSH, thyroid-stimulating hormone EEG, electroencephalography TPHA, treponema pallidum hemagglutination assay

Figure 2

Time course of treatment with an antidepressant (first step in treatment algorithm)

Figure 3

Algorithm: drug treatment for refractory depression. From: German S3 Guideline / National Disease Management Guideline Unipolar Depression (6). Each treatment step should be applied for four weeks (six weeks in older patients). The color of each box indicates how well the efficacy of each treatment strategy has been documented in controlled trials. TCA, tricyclic antidepressant; SSRI, serotonin reuptake inhibitor