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Many depressed patients do not remit on antidepressant medication despite an adequate dosage and a sufficient duration of treatment.1 This has spawned endeavors to define treatment-resistant depression as a depressive episode that has shown insufficient response to 1 or more adequate trials of an antidepressant.1 What constitutes insufficient, inadequate, or partial response is still a matter of debate. Recently, an operational classification of degree of treatment resistance was proposed,2 with categorical distinctions defined by the percent symptom reduction from baseline as follows: nonresponse, < 25% reduction; partial response, 25%–49% reduction; and response without remission, ≥ 50% reduction but without achievement of remission.1 To determine the adequacy and outcome of treatment in a way that can be communicated among clinicians and researchers, it is crucial to employ a reliable and valid instrument. While historical rating of treatment is not as accurate as a prospective trial, there are many instances in which a decision is needed before the next trial is carried out. Several tools have been proposed, such as the Antidepressant Treatment History Form (ATHF),3 the Harvard Antidepressant Treatment History (HATH),4 and the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ).1,5 The ATHF and HATH have the advantage of integrating clinical judgment in the assessment of treatment resistance, but these questionnaires are quite burdensome.5 The ATRQ (Appendix 1) and accompanying questions are meant to provide clinicians with a user-friendly tool for assessment of prior treatment. It is often the case that a patient remembers whether a past treatment was somewhat helpful, although it is frequently difficult for him or her to remember exactly which antidepressant was taken, how long it was taken, and at what dose. However, it is important that the clinician explore past trials thoroughly using a systematic approach in order to characterize the adequacy of the trial and the degree of improvement. The clinician version of the ATRQ1,5 examines the adequacy of duration and dose of prior and current antidepressant treatments in a step-by-step procedure. It cannot be emphasized enough that, when assessing the duration and dose of clinical trials of antidepressants, clinicians must always inquire about adherence to each treatment trial. In addition, the ATRQ assesses the degree of improvement (in the most efficacious trial or in all trials during the current episode, depending on the version of the instrument) on a scale from 0% (not improved at all) to 100% (completely improved) (Table 1). The previous treatment may have been monotherapy, an augmentation trial, a trial of 2 antidepressants (combination therapy), or a switch to another antidepressant. Our group has adopted conventions to define resistance to each of these approaches. At the outset it is noted that the doses and durations required for adequate treatment are based on expert consensus1 rather than systematic research. We define an adequate monotherapy trial as a trial lasting at least 6 weeks at a minimum effective dose. In the context of this initial trial, the adequate duration for augmentation or combination treatment is at least 3 weeks. However, a combination trial from the onset (ie, starting with 2 drugs together) must be 6 weeks. Six weeks is also required for a switch to a different antidepressant. Each of these trials is considered a new trial. An increase in dose for at least 4 weeks represents optimization and is not considered a new or separate trial. However, if remission is later followed by relapse, a dose increase represents a new trial for the new episode. We recognize that the conventions used to define adequate dose and duration are not established and that other conventions, for example, a duration of 12 weeks, might be preferred. The ATRQ can be adapted to accommodate various definitions of dose and duration. Likewise, the threshold of resistance in terms of percent response may vary, depending on the questions being asked within a given clinical trial.

Assessing the Adequacy of Past Antidepressant Trials: A Clinician’s Guide to the Antidepressant Treatment Response Questionnaire