The early work of Professor Malcolm H. Lader and his colleagues documented the first indication of anatomical brain changes associated with benzodiazepines using computed axial tomography (CAT scan), which revealed abnormalities in at least half of the patients examined in the study, with two patients having definite cortical atrophy. The patients were either dependent on or experiencing a protracted withdrawal syndrome from, benzodiazepines. The results warranted further research as they were suggestive of brain damage.
Functional brain changes, such as those observed in organic brain syndrome (OBS) or organic brain disease (OBD) are documented in the literature to be associated by sedative-hypnotics and their respective withdrawal syndromes. OBS is a condition characterized by mental and/or cognitive function impairments that are physiological in nature – the symptoms occur without a psychiatric pathophysiology. Benzodiazepine physical dependence and withdrawal, alcoholism, and other centrally acting drugs are documented to be among its many possible causes.
Perceptual and sensory disturbances suggest a hyperexcitable central nervous system while recovering from benzodiazepine exposure and cessation. Problems with balance, hearing, tinnitus, and hypersensitivity to sound (hyperacusis) suggests possible vestibular involvement – the part of the brain that’s connected to the inner and middle ear. Hypersensitivity to touch, smell and light can also occur. To be understood, these phenomena require more research, but the documentation of their existence adds to the overwhelming amount of evidence that medication physical dependence and discontinuation (withdrawal) can significantly impact functional brain activity on a cellular level.
In 2011, Professor C. Heather Ashton made a public update to include supplemental information regarding brain damage to “Benzodiazepines: How They Work and How to Withdraw” which has been modified in 2012 and 2013. In the update, she wrote that any brain damage caused by benzodiazepines and/or their withdrawal syndrome is more of the functional variety than anatomical, involving the down-regulation of GABAA neuroreceptors in the central nervous system, where the receptor sites themselves become fewer and/or desensitized as a result of the presence of benzodiazepine continually occupying the receptor. It is hypothesized that the brain and central nervous system, in an attempt to reach a state of homeostasis and stability, will naturally oppose the constant presence of a drug in this way. These types of brain changes may be more apparently observed in more modern, more sophisticated functional brain activity studies such as fMRIs or qEEGs. It is unknown whether any potential brain and central nervous system changes induced by benzodiazepines can become permanent. Further research would be required to determine this.
There are other, non-benzodiazepine pharmaceutical medications that are well-known to cause functional brain and central nervous system damage. In particular, antipsychotics, antiemetics, treatments for Parkinson’s disease and dopaminergic pharmaceuticals are especially known to possibly cause movement disorders during or after their treatment. These movement disorders are known as Tardive Dyskinesia (TD), akathisia, dystonia among others – “tardive” meaning that the onset may occur long after cessation of the drug. TD is well-known to be potentially permanent in some cases. Atrophic brain changes have been observed after long-term treatment with antipsychotics, apparently worsening mental illness in some cases. Awareness of this risk became more heavily documented in the literature as more people were presenting with more visibly obvious signs and symptoms to neurologist’s offices. Movement disorder signs are readily recognizable, even in non-verbal patients, as they are so obvious and specific in their presentation. As such, highly dopaminergic drugs have fallen out of use even in psychiatry. High-profile celebrity cases of movement disorders such as Michael J. Fox, who suffers from Parkinson’s disease and struggled with his levodopa (dopaminergic drug) treatment, helped bring awareness to the problem of movement disorders associated with pharmaceuticals.