Benzodiazepine-Induced or Increased Symptoms
Many of the side effects are related to their neuropharmacology. Benzodiazepines and Z-drugs achieve their desired effects by increasing the availability of the calming neurotransmitter GABA to the neurons of the central nervous system (CNS). But the CNS has evolved to preserve homeostasis by counteracting any perturbation. Over time, the CNS reduces the calming effects of the benzodiazepine or Z-drug by producing more of the excitatory neurotransmitter glutamate, by reducing the effectivity or number of GABA receptors, or by other mechanisms. As this natural rebalancing happens, it can have several effects.
(1) New benzodiazepine-related symptoms can appear. Regardless of why a patient was prescribed benzodiazepines, they can begin to exhibit the whole range of symptoms associated with benzodiazepine withdrawal syndrome. For example, a patient who was prescribed Xanax for anxiety can begin to experience muscle pain or insomnia.
(2) The original symptoms can increase in intensity. The change in the balance of neurotransmitters can increase the neural sensitivity of the patient. This can result in an increase in the severity of the original symptoms beyond the level of the complaint for which the benzodiazepine was originally prescribed.
(3) Central sensitization can occur. A normally-functioning CNS responds at appropriate levels to stressors, and then quickly returns to a balanced state. When the CNS is repeatedly subjected to the destabilizing influence of a benzodiazepine, it can paradoxically increase the sensitivity of the CNS to stimuli that would normally not cause a CNS reaction. This is called “central sensitization” of the CNS. When this occurs, it is as if the CNS only partially balances each of the stimuli to which an affected individual is subjected. In addition, neuroadaptation of the CNS can result in a highly exaggerated response to normal external stimuli. Symptoms, in fact, can be present even in the absence of stimuli, similar to what is seen for pain in fibromyalgia. Kindling is a related phenomenon in which episodic exposure to benzodiazepines results in sensitization. A residual amount of stimulus remains, which then gets added to subsequent stimuli. The result can be that simple inputs, like the background noise of a restaurant or the sound and pressure changes of wind, can be perceived by the patient as overwhelming or even painful.
There are thousands of anecdotes of these types of changes occurring in patients prescribed a benzodiazepine, seen especially during withdrawal from the drugs. Many examples can be found in on-line forums such as Benzo Buddies. Most patients do not experience these induced or increased symptoms until they have been using the drugs for months or they attempt to discontinue the drugs after prolonged use. Discontinuance studies are not typically required for drug approval by the FDA. Lacking economic or legal motivation, no formal studies have been done on these phenomena. Please see the page on our programs to see how the Alliance for Benzodiazepine Best Practices is helping translate the compelling stories of benzodiazepine withdrawal syndrome sufferers into the hard evidence that prescribers and regulators need to change benzodiazepine prescriptive practices.
