Prior use of benzodiazepines, such as Xanax, Librium, or Ativan, may increase the risk of treatment-resistant depression (TRD), according to a new study published in The Journal of Nervous and Mental Disease. The study, which aimed to examine the determinants of TRD, found that the “regular use of benzodiazepines was a particularly strong correlate of TRD.”

The researchers, Gordon Parker and Rebecca Graham from the University of New South Wales, report that no previous research has been done on the association between benzodiazepine use and treatment-resistant depression.

There is not yet a consensus among researchers as to what constitutes treatment-resistant depression (TRD), which is also referred to as “refractory depression,” “chronic depression,” and “difficult-to-treat depression.” Approximately 60% of patients do not respond to antidepressants and, in some definitions, this would qualify all of these people as “treatment resistant.” The currently accepted definition requires a failure to respond to two different antidepressants.

Using antidepressants as the standard for treatment-resistance is problematic, however. The researchers point out that “if causal factors are largely psychosocial and require differing treatment strategies (such as psychotherapy), any non-response to an antidepressant treatment might not be unexpected.” They argue that under these conditions, “treatment-resistance” might be better characterized as a diagnostic “paradigm failure.”

While other studies have attempted to identify biological explanations for TRD, this latest study attempts to determine psychosocial variables. To do this, the researchers recruited 922 patients diagnosed with major depressive disorder between 2008 and 2013. All of the patients were then extensively interviewed for their socioeconomic, personality, and medical history using the computerized MAP tool.

After analyzing the data, the researchers identified some variables that appeared to contribute to treatment-resistant depression, including more medical problems, a decreased likelihood of full-time employment, and a greater use of benzodiazepines.

Benzodiazepines are mainly prescribed for the treatment of symptoms that have been classified as mood and anxiety disorders, but their use has been challenged due to the drugs side-effects and addictiveness.

The researchers speculate that the effects of the drug itself might explain the worsening of depression. “Benzodiazepines, by their very action, suppress feelings, and this may worsen depression and the effectiveness of any treatment,” they write.

In addition, the drugs may promote avoidance of feelings and cognitive inhibition while leading to a greater detachment from others. These effects also make it more difficult for a patient to benefit from psychotherapy.

The researchers also add that long-term use of benzodiazepines in linked to impaired cognitive functioning, which may provide another possible explanation for the increased likelihood of TRD.

*

Parker, G. B., & Graham, R. K. (2015). Determinants of Treatment-Resistant Depression: The Salience of Benzodiazepines. The Journal of nervous and mental disease, 203(9), 659-663. (Abstract)