I want to draw your attention to two fairly recent studies. One of these is the BIND study. I love it when studies use easy-to-remember acronyms because it really helps to keep them straight. The BIND study found that “Many prolonged symptoms subsequent to benzodiazepine use and discontinuation … have been shown in a large survey of benzodiazepine users. Benzodiazepine-induced neurological dysfunction (BIND) has been proposed as a term to describe symptoms and associated diverse life consequences that may emerge during benzodiazepine use, tapering, and continue after benzodiazepine discontinuation. Not all people who take benzodiazepines will develop BIND, and risk factors for BIND remain to be evaluated.”
This analysis showed that more than seventeen identified symptoms persisted for more than one year after discontinuation of benzodiazepines. This was independent of the well-known benzodiazepine withdrawal syndrome, which can cause intractable seizures and be fatal. In studies going back as far as 1981, researchers Hallström and Lader found increased depression severity using the Hamilton scale in patients who were taken off benzodiazepines. Another study in 1987, carried out by researchers Smith and Wesson, my new favorite team, seemed to show that these symptoms resolved completely after six to twelve months. The new BIND study indicates otherwise. The persistent symptoms can include increased anxiety and depression, not unexpected, but also headache, dizziness, tinnitus, paresthesia, and even motor dysfunction. This would indicate that we should use extreme caution when prescribing these medications; is the risk of these potential long-term effects outweighed by the benefits to the patient’s quality of life? Then it got even more complicated.
There had been warning labels on benzodiazepines since the 1970s, finally saying: “WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS. Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.”
Deference had always been given to a physician’s judgment in the use of these medications, but that changed in 2017 when the U.S. Department of Justice found it needed an excuse to prosecute doctors targeted by their proprietary AI, nicknamed “The Beast.” Prosecutions of physicians for prescribing “dangerous medications in dangerous combinations” and for “ignoring the risk of addiction, overdose, and death” quickly became common. The prosecution of physicians for choosing to prescribe a combination of approved medications in approved dosages to patients who had been seen and evaluated was something new. In the past, physicians were understood to have the right to prescribe according to their education, training, and experience, but this was no more.
States and the DEA were grappling with an opioid crisis, and they were convinced that what was taken by physicians as a warning to be cautious was, in fact, an absolute prohibition on combination therapy with these two classes of medication: opiates and benzodiazepines specifically. These prosecutions were well-publicized, with the government repeating over and over again that these were “drug pushers in white coats” and that they had abrogated their oath to do no harm. Physicians got the message, and the heavily publicized prosecutions worked perfectly for what we in the U.S. Marine Corps used to call a Russian warning shot. Shoot the first few guys, and that warns the rest. There was a rapid rush to “deprescribe,” with physicians tapering patients who had been stable for decades on their medication.
Now, the FDA has always acknowledged that “Benzodiazepines are a class of medicines approved to treat generalized anxiety disorder, insomnia, seizures, social phobia, and panic disorder. Most benzodiazepines are recommended for periods of weeks or months to treat these disorders. However, the amount, frequency, and duration of treatment vary depending on the patient and the medical condition being treated.” And went on to say, “Benzodiazepines can be an important treatment option for treating disorders for which these drugs are indicated.”
It was also acknowledged that “No standard benzodiazepine tapering schedule is suitable for all patients; therefore, create a patient-specific plan to gradually reduce the dosage, and ensure ongoing monitoring and support as needed to avoid serious withdrawal symptoms or worsening of the patient’s medical conditions.” The problem is that you can’t bring the FDA into court with you; you can’t even bring a textbook unless you bring the authors too. Please note that it says if taken at recommended dosages, leaving open the interpretation that prescribing these medications within recommended dosages was wrong.
Also, no allowance was made for patients who had been on these medications for decades, with physicians having to either toe the party line and taper them or risk incarceration. Those of us taking further continuing medical education in pain and addiction treatment were aware that there was a serious risk associated with stopping these medications, and we used our professional judgment. I myself saw a patient whose physician had moved out of state, and he needed primary care. He had been on opiates and benzodiazepines for over a decade for a severe spinal injury that resulted from an industrial accident. He had suffered through seven failed back surgeries and experienced severe anxiety with panic attacks from the traumatic event. He had also suffered a new injury with a partial amputation. He came to me on three opiates and two benzodiazepines. I cut these back to two and one, respectively, and he was able to tolerate the change. Did I do the right thing? I believed, based on my own personal medical judgment, that I had. And a recent study supports my decision, finally answering the question, IF someone is already on opiates, is it safer to stop them or continue them?
The answer quantified what many of us already had gleaned from our studies. Discontinuing someone from benzodiazepines when they are also on opiates increases their risk of death by 1.6 times, over just continuing their current treatment. This study was published in JAMA. It evaluated a total of 353,576 patients, comparing a group of 213,011 patients with a mean age of 62, among whom about 64% were female with a racial mix of 60% White, 11% Hispanic, 9% Black, and 1.4% Asian all on benzodiazepines combined with opiates; with a group of 140,565 patients mean age 61, 79% White, 11% Black, 8.5% Hispanic, and 1% Asian who were on benzodiazepines only. The question was, when patients in the first group were discontinued on their benzodiazepine medications, such as to avoid concomitant use and thereby “protect” the patient, did they live longer? The answer was a resounding no.
Those who had been on long-term combined therapy whose benzodiazepines were stopped had a 1.6 times higher rate of mortality. The researchers went on to note, “These results suggest benzodiazepine discontinuation among patients prescribed for stable long-term treatment may be associated with unanticipated harms, and that efforts to promote discontinuation should carefully consider the potential risks of discontinuation relative to continuation.” So now what I believed to be true has been proven by a study involving a third of a million patients. I am happy to know that what I sincerely believed at the time, that I had made the best decision for the patient I described, has been proven right. But it will be cold comfort to my family as we await my sentencing for having written that first prescription.
L. Joseph Parker is a distinguished professional with a diverse and accomplished career spanning the fields of science, military service, and medical practice. He currently serves as the chief science officer and operations officer, Advanced Research Concepts LLC, a pioneering company dedicated to propelling humanity into the realms of space exploration. At Advanced Research Concepts LLC, Dr. Parker leads a team of experts committed to developing innovative solutions for the complex challenges of space travel, including space transportation, energy storage, radiation shielding, artificial gravity, and space-related medical issues.
He can be reached on LinkedIn and YouTube.