This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.

Letter to the Editor

Drs Haq and Mickey Reply

Aazaz U. Haq, MD and Brian J. Mickey, MD, PhD

Published: July 27, 2016

See letter by DeQuardo and article by Mickey et al

This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.

Drs Haq and Mickey Reply

To the Editor: We thank Dr DeQuardo for his interest and for his thoughtful questions about our study. Most of the studies (9 of 11) in our meta-analysis defined medication failure as lack of response despite at least 1 adequate antidepressant medication trial in the current episode, operationalized as an Antidepressant Treatment History Form (ATHF) score ≥ 3. A score ≥ 3 indicates that the patient has received the medication at a minimally adequate daily dose (eg, nortriptyline ≥ 76 mg/d) for ≥ 4 weeks; for psychotic depression, coadministration of antipsychotic medication (chlorpromazine 400 mg/d or equivalent) for ≥ 3 weeks is also required.1

Dr DeQuardo expresses concern that this criterion may not be clinically relevant because "medication failure in today’s clinical environment is essentially a prerequisite to initiation of ECT." We disagree. Achieving an ATHF score ≥ 3 is not always easy in practice, given the requirements of adequate dosage, adequate duration, good adherence, and verification through medical records. Consequently, treating a patient with an ATHF score < 3 is not equivalent to using electroconvulsive therapy (ECT) as an initial treatment for an episode of depression. Furthermore, there are many clinical scenarios in which ECT is appropriate in the absence of a failed adequate medication trial. Besides catatonia, high suicide risk, patient preference, and prior ECT response, we would add severe functional impairment, psychosis, and medication intolerance as valid reasons. Indeed, lack of medication failure was not rare in the studies we reviewed: 402 out of 1,036 patients (39%) did not meet the criterion of an ATHF score ≥ 3 (9 studies).

On the other hand, we appreciate the perspective that the dichotomous "ATHF 3" criterion may not be relevant to many patients. We suspect that ECT response is actually predicted by the degree of medication resistance; that is, the fewer the failed trials, the greater the likelihood of ECT response. Although the available data are not compatible with meta-analysis, we found some evidence for this notion in the reviewed studies. Two studies that examined degree of medication resistance found a significant association with ECT response in the expected direction,2,3 2 studies found nonsignificant associations in the expected direction,4,5 and 1 study found no significant association and no obvious trend.6

Thus, we are confident that lack of an adequate medication trial in the current episode predicts a greater likelihood of ECT response. Greater degree of medication resistance may also predict a lesser likelihood of ECT response, but future work will be needed to rigorously test this idea.


1. Sackeim HA. The definition and meaning of treatment-resistant depression. J Clin Psychiatry. 2001;62(suppl 16):10-17. PubMed

2. Prudic J, Haskett RF, Mulsant B, et al. Resistance to antidepressant medications and short-term clinical response to ECT. Am J Psychiatry. 1996;153(8):985-992. PubMed doi:10.1176/ajp.153.8.985

3. Prudic J, Sackeim HA, Devanand DP. Medication resistance and clinical response to electroconvulsive therapy. Psychiatry Res. 1990;31(3):287-296. PubMed doi:10.1016/0165-1781(90)90098-P

4. Husain SS, Kevan IM, Linnell R, et al. Electroconvulsive therapy in depressive illness that has not responded to drug treatment. J Affect Disord. 2004;83(2-3):121-126. PubMed doi:10.1016/j.jad.2004.05.006

5. Rasmussen KG, Mueller M, Knapp RG, et al. Antidepressant medication treatment failure does not predict lower remission with ECT for major depressive disorder: a report from the consortium for research in electroconvulsive therapy. J Clin Psychiatry. 2007;68(11):1701-1706. PubMed doi:10.4088/JCP.v68n1109

6. Pluijms EM, Birkenhäger TK, Huijbrechts IP, et al. Influence of resistance to antidepressant pharmacotherapy on short-term response to electroconvulsive therapy. J Affect Disord. 2002;69(1-3):93-99. PubMed doi:10.1016/S0165-0327(00)00378-5

Aazaz U. Haq, MDa

Brian J. Mickey, MD, PhDb

aDepartment of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford, California.

bDepartment of Psychiatry, University of Utah School of Medicine, Salt Lake City

Potential conflicts of interest: None.

Funding/support: None.

J Clin Psychiatry 2016;77(7):e905

© Copyright 2016 Physicians Postgraduate Press, Inc.

Volume: 77

Quick Links: