Treatment-refractory depression: Definitions and characteristics

Abstract

Forty to 50% of depressed patients who are initially prescribed antidepressant medications or administered electroconvulsive therapy do not experience a timely remission. This group typifies treatment‐refractory depression (TRD), defined as a failure to demonstrate an “adequate” response to an “adequate” treatment trial (i.e., sufficient intensity of treatment for sufficient duration). The approach to the patient with TRD must be methodical. The clinician should examine potential factors contributing to apparent non‐response: trial adequacy, compliance, differential diagnosis, and treatable comorbid conditions. After addressing these variables, a patient who does not demonstrate a remission may be considered treatment resistant (relative or absolute). Although many of these patients will respond to a subsequent treatment regimen, there are no (or only nominally useful) predictors for the initial selection of that “subsequent” antidepressant treatment. Hence, the initial treatment is typically chosen on the basis of safety and convenience, not differential efficacy. The search for the clinical and biological correlates of long‐term or acute outcome presents a major nosologic conundrum: Who will respond to treatment? Which treatment? In this manner, TRD challenges the prognostic utility of our current phenomenologic‐based diagnostic system. Depression and Anxiety 5:154–164, 1997. © 1997 Wiley‐Liss, Inc.

Definition, Assessment, and Staging of Treatment—Resistant Refractory Major Depression: A Review of Current Concepts and Methods

“…In total, we retrieved 327 full electronic references, 16 of which met our selection criteria. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] …”

“…8,17 During the last decades, several authors developed different criteria for considering the categorical presence of TRD, including a failure to respond to adequate dosages of a single TCA (for example, amytriptilyne), an MAOI (for example, phenelzine) trial for a minimum of 4 weeks, a single adequate antidepressant treatment, 3 or more adequate trials of treatment (one of which must have been a TCA), 5 or more adequate treatments, at least one trial of electroconvulsive therapy, or a single trial of the newer heterocyclic antidepressants. 1,2,5,6,8,10 Unfortunately, none of these classifications have been systematically examined, verified for reliability, or validated for prospective predictive utility, and therefore, it is currently difficult to select criteria from among these different approaches to defining TRD. 10 Nevertheless, there is a general sense that a patient has clinically significant treatment resistance if a current episode of depression has not benefited from at least 2 adequate trials of different classes of antidepressants.…”

“…14 Relative resistance, on the other hand, was referred to as a failure to respond to a less than adequate (in terms of dosage and duration) antidepressant trial. 2,6 However, the latter definition is spurious because a patient's depression should be considered resistant or refractory to treatment only when an adequate intervention has been administered.…”

Multifunctional Pharmacotherapy: What Can We Learn from Study of Selective Serotonin Reuptake Inhibitor Augmentation of Antipsychotics in Negative-Symptom Schizophrenia?

“…[1][2][3] Development of new drugs over the last few decades has not produced dramatic improvement in response of schizophrenia, as highlighted recently by findings of large comparative studies. 4,5 Negative and cognitive symptoms of the illness have proved particularly resistant to treatment.…”

“…In clinical practice, this often results in the use of more than one drug and, over the years, many combinations of psychotropics have been tried in an attempt to improve response. There is evidence that some combinations do induce a favorable clinical response not achieved by each of the drugs given alone, in some patients, 2,3,6,7 but the choice of drug combinations and indications for their use are based on a trial-and-error paradigm guided by clinical experience and response.…”