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Determinants of Treatment-Resistant Depression

The Salience of Benzodiazepines

Parker, Gordon B. MD, PhD, FRANZCP*†; Graham, Rebecca K. BA (Psych hons), PhD*†

The Journal of Nervous and Mental Disease: September 2015 - Volume 203 - Issue 9 - p 659–663
doi: 10.1097/NMD.0000000000000348
Original Articles

Treatment-resistant depression (TRD) lacks consensus regarding its definition, despite being common in clinical practice. This study was designed to identify factors contributing to TRD in patients diagnosed with a major depressive disorder. Patients were grouped into “low,” “medium,” and “high” treatment-resistant (TR) groups based on the number of medications that had been prescribed for their depression. We identified a number of factors linked to TRD. The high TR group was generally older, had a longer depressive episode duration, a higher number of comorbid medical and anxiety disorders, a lower education, and were less likely to be in full-time employment. They also reported less trait irritability and were more likely to view medication as being a contributor to their current depression. Some differences between non-melancholic and melancholic subsets were evident and point to the benefits in research on TRD analyzing the two diagnostic groups separately. The most striking finding was benzodiazepine use, which was significantly more common in the high TR group and within both the melancholic and non-melancholic subsets. Some potential explanations for this finding are offered.

*School of Psychiatry, University of New South Wales; and †Black Dog Institute, Sydney, Australia.

Send reprint requests to Gordon B. Parker, MD, PhD, FRANZCP, Black Dog Institute, Hospital Road, Prince of Wales Hospital, Randwick, Sydney 2031, Australia. E-mail:

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