When Tapering Benzodiazepines, Plan for the Long Game

Daniela Rakocevic, M.D., M.Sc., chief of addiction psychiatry, assistant professor of psychiatry, and program director, addiction psychiatry fellowship, at Feinberg School of Medicine at Northwestern University, discussed the differences between chronic prescription benzodiazepine use and sedative, hypnotic, or anxiolytic (SHA) use disorder.

“In chronic benzodiazepine use, the patient may have increased tolerance and physiological dependence, but they’re using their medications as prescribed,” Rakocevic said. “They may be attached to their medications and worry about coming off them, but … there aren’t any of the red flags we see in SHA use disorder, like multiple prescriptions and prescribers, asking for a specific benzodiazepine, using benzodiazepines from friends and family, or obtaining non-prescription benzodiazepines from the street or dark web.”

Rakocevic said that the goal of deprescribing is to reduce medication burden while improving the patient’s quality of life. “Set the stage for deprescribing, because it’s difficult for our patients,” she said. “It a lot of work and emotional fortitude, and you’ll be more successful if you first talk about the pros and cons of staying on benzodiazepines or getting off them.”

According to Rakocevic, one way to develop rapport is to use shared decision-making to set up a gradual and flexible tapering plan. “Ask the patient to make decisions, such as when they want to focus on tapering, morning, afternoon, or night,” she said.

“Prepare for the long game—three months, six months, 18 months, two years,” Rakocevic said. “We want the patient to be comfortable and improve functioning, but we have to do all of this safely.”

Rakocevic added that some patients may not be able to taper off benzodiazepines completely. “A more suitable goal may be to reduce or maintain the current dose,” she said.

Christopher Blazes, M.D., an associate professor and fellowship director in addiction psychiatry at Oregon Health and Science University, discussed benzodiazepine use and withdrawal management in the residential treatment setting. He challenged common practices such as using benzodiazepines to manage alcohol withdrawal.

“We have been habituated to believe that benzodiazepines are the standard of treatment for alcohol withdrawal,” he said. “But they’re only better than placebo for preventing withdrawal seizures, and not better than other agents.”

Blazes explained that withdrawal from alcohol and benzodiazepines are similar in that N-methyl-D-aspartate receptors become hyperactive and produce symptoms such as insomnia, irritability, and anxiety. Therefore, some of the treatment options overlap, including alpha-2 agonists such as clonidine, guanfacine, dexmedetomidine, lofexidine, and tizanidine.

“These drugs … more closely address the underlying pathophysiology that underlies withdrawal symptoms than do benzodiazepines,” he said. “Clonidine is easy because it comes in a patch that allows slow distribution over time, and you can combine it with oral medications.”

Antiepileptics such as gabapentin, oxcarbazepine, and phenobarbital are also options, Blazes added. However, health professionals are often skittish about using phenobarbital, in part because of its long half-life.

“After a patient takes it for about three or four days, it’s in their system for a week,” Blazes said. “If someone leaves against medical advice during that time, it’s still in their body and can interact with opioids and other substances and be dangerous.”

Alëna Balasanova, M.D., a member of APA’s Council on Addiction Psychiatry and director of addiction psychiatry education at the University of Nebraska Medical Center, is a champion of incorporating phenobarbital into treatment at her institution. She and her colleagues developed and studied a four-day phenobarbital protocol for patients in the intensive care unit with severe alcohol withdrawal syndrome (SAWS). The protocol involves one day of loading doses, followed by a taper over the next three days.

The team studied the clinical impact of phenobarbital versus benzodiazepines on SAWS and published their findings the January 2024 Annals of Pharmacotherapy. “The phenobarbital group had a shorter length of stay in the hospital [compared with the benzodiazepine group], 2.8 days versus 4.7 days,” Balasanova said. “The phenobarbital group also had less time in [intensive care] and progressive care, a lower incidence of dexmedetomidine rescue, and lower rates of antipsychotic initiation.” ■