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Benzodiazepines (BZs) are mostly prescribed for secondary symptom management when used in the treatment of post traumatic stress disorder. Most notably, they are given for insomnia and anxiety (in the form of hyperarousal). They work by enhancing the actions of the major calming neurotransmitter GABA which is estimated to be present in 40% of all synapses in the brain. They are estimated to be prescribed to 30%-74% of patients with PTSD within the United States.

After a few weeks of minimal use, however, there is evidence that their anxiolytic and hypnotic properties backfire; almost certainly eventually exacerbating initial baseline sleep and anxiety problems. This is also true for depression which is often comorbid in PTSD. Like alcohol, they are central nervous system depressants. The Committee of Medicines and the Royal College of Psychiatrists in the UK concluded in the late 1980’s and early 90’s that benzos should generally not be prescribed for longer than 2-4 weeks. Psychiatrist Heather Ashton,a leading expert on benzodiazepines who ran a withdrawal clinic for twelves years writes that the drugs “are no longer effective after a few weeks because of the development of tolerance. When tolerance develops “withdrawal” symptoms can appear even though the user continues to take the drug. Thus the symptoms suffered by many long-term users are a mixture of adverse effects of the drugs and “withdrawal” effects due to tolerance.” Indeed, several studies of BZs have demonstrated that symptoms are usually less severe after discontinuation than during treatment.

Tolerance withdrawal should be distinguished from dependence. Long-term prescribers, who although acknowledge dependence, seem to be oblivious to the overall negative trajectory the effects of the drugs can take which can be lower than initial baseline symptoms. It is important to underscore that tolerance withdrawal occurs at prescribed levels considered to be low and as a PRN (as needed). In a Xanax study conducted for the for the FDA, manufacturers Upjohn themselves, note that patients became addicted after eight weeks of use and that panic symptoms increased 350% upon withdrawal at that point. Tolerance is a problem in the treatment for PTSD because the majority of patients have symptoms which persist for longer than three months.

The psychobiology of post traumatic stress disorders are complex and it is difficult to try to define them without a whole background of interrelated, separate concepts. A Veteran’s Affairs guide for clinicians summarizes it thus: “the biological disturbance in PTSD can be conceptualized as a dysregulation of the hypothalamic-pituitary- adrenal (HPA) axis and the balance between excitatory and inhibitory brain neurocircuitry. There is a resultant dysregulation of adrenergic mechanisms that mediate the classical flight-fight or freeze response.”

Abnormal maladaptive responses (or another way of putting it: normal responses to abnormal stimuli) in the limbic structures of the hippocampus (memory oriented) and the amygdala (emotion oriented) within the central nervous system also occur in post traumatic stress disorders.

Benzodiazepines exert an effect on all of these structures. Several studies have measured specific hormone blunting, (namely of CRH, AVP and ACTH),  induced by the GABAergic inhibition from bentos.  This blunting suppresses the HPA axis. Also, benzos inhibit receptors in the hippocampus which in turn disrupt glucocorticoid feedback mechanisms that are involved in the regulation of the HPA axis.

This is to suggest that both post traumatic stress disorder and benzodiazepines have dysregulating consequences to the HPA axis. Benzos are not corrective or ‘balancing’ to post traumatic dysregulation; rather they are compounding. Long- term benzodiazepine use is not conducive to the homeostasis sought after in PTSD healing because it is so dysregulating in it of itself. Also according to the VA’s clinician’s guide “Both animal and human work suggests that BZs may interfere with the extinction of fear conditioning or potentiate the acquisition of fear responses, actually worsening recovery from trauma and interfering with one of our 1st- line recommended PTSD psychotherapies, prolonged exposure therapy.”

Interdose rebound tolerance problems aside, it is especially horrific to imagine those who have an underlying PTSD who are within the group of 15% of people whom Ashton reports develop a protracted withdrawal syndrome due to compensatory GABA downregulation which can last years after the drug is discontinued. This subgroup must overlay the traumatic physical with the traumatic psychological.  Consider the following statements about post traumatic stress disorder within the context of rebound and down regulation where excitation is even less mediated as a consequence of long term BZ use: “PTSD patients exhibit both reduced GABA plasma levels and reduced BZ receptor activity in the amygdala, prefrontal cortex and other brain areas. Since BZ receptors are a part of the GABAa receptor complex, these findings suggest that deficiencies in GABAergic mechanisms in the amygdala, PFC and elsewhere result in insufficient protection against the activating effects of norepinephrine and glutamate. It is possible that intrusive recollections, hyperarousal symptoms and disinhibited social and emotional behavior observed among patients with PTSD may be due to such deficient GABAergic function.”  Here are some phenomena that both PTSD and BZ use and withdrawal share in common: insomnia, anxiety, panic,nightmares, agoraphobia, depression, derealization, depersonalization, hallucinations and intrusive memories.

Essentially, PTSD is a dysregulation of physiology and BZs promote physiological dysregulation. People with the disorder need to be in a modulated state that is neither hyper nor hypo aroused in order to recover. Psychiatrist Daniel Siegel refers to this as “the therapeutic window of tolerance.” The hyperarousal of PTSD is akin to the excitatory state in BZ tolerance withdrawal and//or rebound and possible structural down regulation.

Anxiety, for example, can be a consequence of hyperexcitation/hyperarousal. Interestingly, the word kindling is both a term in psychology and biology respectively referring to the exponentially adverse reexperiencing of trauma in the mind and adverse rexperiencing of detox in the body. The CNS hypoarousal features of numbing, neurovegetative depression, memory problems and derealization/depersonalization, are associated with both PTSD and BZ use.

Indeed, the data supports that PTSD and sustained BZ use are at pharmacodynamic odds. A 2015 systematic review and meta-analysis published by Guina M.D et al in The Journal of Psychiatric Practice examined 18 studies with over 5,200 trauma surviving participants which suggested that “benzodiazepines were associated with no improvement in PTSD-related outcomes, and that using BZs in patients with recent trauma actually increased PTSD risk.” They write “those studies providing sufficient data suggest that the risk of developing PTSD is two to five times higher in groups receiving benzodiazepines than in control groups.”

In addition to the aforementioned compounded biological problems of treating PTSD with benzos, the application can carry additional practical problems specific to different forms of trauma. For example, complex trauma occurs overtime from chronically stressful situations. Healing from C-PTSD  itself can be a lengthy process and benzodiazepine use can delay it’s spontaneous recovery. In Judith Herman’s second phase of C-PTSD recovery, for instance, the sufferer must emotionally process the trauma (often times incorporating grief). As previously mentioned, BZs are not conducive to this; either blunting emotions through hypoarousal or creating a reactionary overly intense, hyperaroused- excitatory state. Now the patient has three problems: the original trauma, an oscillating dysregulated physiology to contend with and whatever new additional problems develop from and in the delayed healing, medicated posttraumatic period. Benzodiazepine  use is  therefore also particularly ill suited for developmental C- PTSD.

Both PTSD and C-PTSD are commonly caused by military trauma. Unfortunately, despite a 2010 recommendation by the VA and DoD not to administer benzos for PTSD, over 30% of U.S. veterans are prescribed the class of drug.  This is also a population already high in traumatic brain injury (TBI)  and substance use disorders (SUD). BZs are contraindicated in SUD because of the risk of abuse and death taken in combination with other substances. It is estimated that there is a 50% comorbidity rate of PTSD and SUD among veterans.

Benzos induce anxiety in a roundabout way over time even though they are “anxiolytics”, ironically however they are more readily recognized for promoting results that resemble a core symptom cluster in PTSD: avoidance. Even at low doses BZs blunt emotions. To reiterate again, as the study for the FDA illustrates (to name one), the overwhelming majority of prescribing professionals seriously underestimate the physiological impact of these drugs even at prescribed levels they consider to be “small” or safe. Users might not be overtly “escaping” through ‘passing out’ as with opiates or causing less insidious, feeling- changing brain damage like with alcohol abuse, nevertheless however, psychic pain is avoided as distress tolerance is lowered in the ‘body-mind connection’. It is like an antonym to cognitive behavioral therapy where one tries to obtain mastery over their brain/bodily initiated thoughts with their mind. How benzodiazepines affect trauma speaks to ideas put forth that traumatic memories are stored in the body/cells (Janet, Ogden, Rothschild, Van der Kolk).

As Herman and many others suggest, traumatized people need to emotionally process their trauma to progress in their healing process to a place where traumatic incidents are less overwhelming and less of a factor in their present life. There is good reason to contend that benzodiazepines  stunt this process. Guina et al. write “for fear extinction to occur, patients must emotionally and cognitively process the experience of anxiety, but BZDs allow distraction patients to avoid this processes. Some patients with PTSD use distraction techniques to avoid internal reminders of trauma, some rarely leave places of comfort to avoid external reminders, and others engage in reckless behaviors to “escape”. BZDs may provide another form of avoidance, an attempt to self-medicate hyperarousal, numb feelings, suppress memories, and escape thoughts. Overcoming avoidance behaviors is essential for successful treatment, but it is often the patient’s largest obstacle for recovery (as Herman explains that avoidant coping style is a poor prognostic factor for trauma-related disorders).”

Emotions have an intimate relationship with maturity and living a full, robust life. BZs don’t just discriminate on what has happened in the past; they can constrict the emotional present day life of those who take them. Emotional stunting and blunting  is a common theme in substance abuse recovery. Tian Dayton and Stephanie Brown,for example, are several people  who have explored the topic of emotional anesthesia in it of itself and also the role that it plays in trauma.

Dissociation is a form of peritrauma avoidance but can also occur post trauma as well. BZs resemble this traumatic reaction in that both the defense mechanism and the drug disrupt the normal flow of conscious experience (both in sensation and in memory).   Benzos create anterograde amnesia, that is they disrupt the assimilation of present experience into the brain/body/psyche. Perhaps anterograde amnesia partly accounts for why some people even without PTSD can experience intrusive memories upon cessation. Only in 2013 in DSM 5 was PTSD reclassified from an anxiety disorder. The 2015 meta analysis review reads “Shavel et al. speculated that these structures [the amygdala and hippocampus implicated in PTSD] may be less responsive to to BZDs than the locus ceruleus [implicated in panic disorder]. In addition, rather than targeting specific implicated structures BZDs indiscriminately depress global brain function (including structures such as the prefrontal cortex that are already hypoactive in PTSD and which, when functioning adequately, allow for various cognitive processes and modulation of the amygdala)”.

It is clear that benzodiazepine use, rebound and withdrawal exacerbate both secondary and core symptoms in post traumatic stress disorder.

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