Benzodiazepines Linked to Treatment Resistant Depression


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)

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Justin Karter
MIA Research News Editor: Justin M. Karter is the lead research news editor for Mad in America. He completed his doctorate in Counseling Psychology at the University of Massachusetts Boston. He also holds graduate degrees in both Journalism and Community Psychology from Point Park University. He brings a particular interest in examining and decoding cultural narratives of mental health and reimagining the institutions built on these assumptions.


  1. They should rename “Treatment Resistant Depression” as “Treatment Caused Depression,” which might be far more accurate terminology for what actually occurs for these people. The long term prescription and/or continuous changing up of SSRI’s is more likely the causative factor in not allowing the natural progression of a depressive episode to run its course.

    I hope Dr. Shipko reads and chimes in on this discussion. He has indicated in past blogs that benzodiazepines were necessary to prescribe to some of his patients who were involved in protracted withdrawal syndrome from SSRI’S. I’ve always thought that benzos would only provide more immediate reduction in anxiety but overall exacerbate a person’s problems and struggle with long term recovery. This study seems to bear this out.


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    • My thoughts exactly! The are blaming “depression” for their inability to do anything helpful, or even making things worse. Instead of saying “he has treatment-resistant depression,” what if they said, “We don’t have any idea how to help” or “our approach clearly didn’t work.” But such honesty appears to be anathema in the world of “mental health treatment.”

      What would we say if the mechanic said our car had a “repair-resistant engine?” We’d fire them and find someone who knew what he was doing!

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  2. I always thought it was common knowledge that benzos were addictive and it doesn’t seem surprising that a CNS depressant would lead to…depression. But, I’ve had umpteen co-occurring treatments and the warning was always that benzos are addictive. Never occurred to me that this wasn’t made clear outside of the D/A setting. I was that client who was not a victim of the benzo lie. I knew they were addictive, might cause God knows what, and didn’t care. I liked the feeling and didn’t want to deal with the issues they were numbing. Later in recovery, as a mental health “treatment” I found them to be a stay of execution. They just put off dealing with whatever unpleasant feeling I was experiencing and I didn’t find them to be a long term solution. But, as a medical treatment for detoxification from chronic alcohol dependence, I found them lifesaving, but was on a declining dose for less than a week.

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    • I was on them for a decade and my board certified psychiatrist insisted that it was perfectly safe. This kind of lie happens far more often than most people realize.

      Since withdrawing from them (on my own), I have not patronized another psychiatric death trap and never will if I can help it.

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  3. While it certainly may be one possible factor in what is being called treatment resistant depression that benzodiazepine use may directly cause more chronic symptoms, this study points to some other disturbing issues as well. As the researchers point out, benzodiazepines may lead to emotional numbing and less opportunity to deal with emotional issues. Yet all the people in the study group were then treated with various and often multiple antidepressants, which, as we all know, are major zombifiers. It would not be surprising that people who are inappropriately treated with medication, and deprived of the opportunity to actually get better would seem to be resistant to “treatment”. It is also not surprising that poorer people may not be given the opportunity to get therapy. The researchers also seem to partially define “treatment resistance” as those people who feel they haven’t improved on medication. So maybe we are talking about two different groups: those content to be zombies, and those who are trying to reject bad treatment.

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  4. I don’t think it’s only the benzodiazepines that cause Treatment Resistant Depression. Of course, how would I really know when we patients who are victimized by our psychiatrists, and our local Community Mental Healthcare facilities (yes, us on Medicaid) are given our typical cocktail of 4-7 or more psychotropic drugs inducing depressions so severe that suicide becomes very appealing to end our suffering. Psychiatrists seem blinded when they blatantly see patients experiencing Benzodiazepine Tolerance Withdrawal symptoms: heightened anxiety, chronic insomnia, escalating alcohol use, unexplained excruciating migraines, diarrhea, violence, chronic fatigue, crippling depression, panic attacks leading to full blown agoraphobia when we’ve never been diagnosed with, or experienced this before leading to total separation/isolation from friends, family, society, and then – yourself. This is a horrible state of mind to be in. Yet, hey call this ‘Treatment’. Instead we are given yet more psychiatric drugs inducing yet more acute depressions until we become a revolving door to the psychiatric hospitals, emergency rooms, intensive care units, or jail.

    Since I’ve been off all my psych drugs I haven’t returned, not once, to any of those places. And I thank God for that. But I feel for those still suffering and believing as I did for decades that I indeed did have a ‘chemical imbalance’ whereas they used countless drugs to fix it, when in fact, they were killing me.

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