CGPR: When do you start benzodiazepines in older adults?

Dr. Aiken: The best evidence for benzodiazepines in the elderly is in panic disorder, followed by phobias, social anxiety disorder, and generalized anxiety disorder. Benzodiazepines are also the mainstay of treating catatonia, rapid eye movement sleep behavior disorder, and alcohol withdrawal. However, benzodiazepines often remain the last resort in older adults. All benzodiazepines are listed on the Beers Criteria for potentially inappropriate medication use in older adults (2019 American Geriatrics Society Beers Criteria® Update Expert Panel, J Am Geriatr Soc 2019;67(4):674–694).

CGPR: Which benzodiazepines do you prefer to use in older adults?

Dr. Aiken: Lorazepam (Ativan). It doesn’t linger or build up metabolites. It also has a low risk of abuse or accidental overdose. Oxazepam (Serax) is even safer—it has the lowest abuse and overdose risk among the benzos and an even shorter half-life than lorazepam (Buckley NA et al, BMJ 1995;310(6974):219–221). However, it’s harder to dose—you can’t break it in half—and some patients don’t respond to it because it can take up to an hour (instead of 30 minutes) to take effect. When it comes to panic disorder, only alprazolam (Xanax) and clonazepam (Klonopin) are FDA approved. I tend to avoid clonazepam in older adults because of its longer half-life and tendency to build up metabolites, and I tend to avoid alprazolam because it can lead to a more severe withdrawal syndrome (it also has a higher abuse potential).

CGPR: Which benzodiazepines are you least likely to prescribe in older adults?

Dr. Aiken: I shy away from benzodiazepines that build up metabolites or that have a long half-life. Quazepam (Doral), diazepam (Valium), clorazepate (Tranxene), chlordiazepoxide (Librium), and flurazepam (Dalmane) are the worst offenders. Some of them have short half-lives but produce active metabolites that linger for days or weeks.

CGPR: In which other populations are you reluctant to start a benzodiazepine?

Dr. Aiken: People with a history of addiction (especially opioid use disorders), people at elevated fall risk, and people with sleep apnea. I also think twice before prescribing to patients with chronic nonspecific anxiety, such as anxiety in a person with borderline personality disorder. There’s some evidence, though not well controlled, that problem-solving skills decline with long-term benzodiazepine use (Crowe SF and Stranks EK, Arch Clin Neuropsychol 2018;33(7):901–911).

CGPR: What are the risks of prescribing benzodiazepines in older adults?

Dr. Aiken: Benzodiazepines increase the risk of motor vehicle accidents two- to four-fold in the elderly, and raise the fall risk 1.5-fold (Donnelly K et al, PLoS One 2017;12(4):e0174730; Bartlett G et al, BMC Fam Pract 2009;10:1). They suppress respiration, which may be a problem for those with pulmonary disorders like chronic obstructive pulmonary disease (COPD). In older adults, they can cause delirium or disinhibition. And then there’s the opioid problem.

CGPR: How do they interact with opioids?

Dr. Aiken: I view benzos as a different drug when they’re combined with opioids. It’s extremely rare to die from benzodiazepine overdose (unlike barbiturate overdose), but benzodiazepines present a high risk of accidental overdose when taken with opioids (Buckley NA and McManus PR, Drug Saf 2004;27(2):135–141). Benzodiazepines are involved in about 80% of opioid-related deaths and raise the risk of opioid overdose deaths two- to four-fold. Both suppress breathing in different ways. It’s like a stereo. When you unplug one wire, the music still plays and the person still breathes, but when you unplug both, death can happen. Most of these are accidental overdoses.

CGPR: Many older patients have chronic pain conditions and are prescribed low-dose opioids on a daily basis. Are you saying that these patients should not use benzodiazepines for anxiety?

Dr. Aiken: Being in treatment for pain doesn’t reduce the overdose risk. These deaths are not just happening to people who abuse or misuse their medications. Adding a benzodiazepine could cause fatal respiratory depression if they have pulmonary disease and are taking high doses of an opioid, like oxycodone 80 mg/day. If I have any concerns, I’ll usually require that the pain doctor be in charge of both the benzo and the opioid. It’s easier to spot problems when one person is handling both scripts, and overdoses are more likely when the treatment is split (Chua KP et al, JAMA Netw Open 2021;4(8):e2120353).

CGPR: What is the relationship between benzodiazepine use and the risk for dementia?

Dr. Aiken: This is an unanswered question because we don’t have controlled trials to tease apart the variables. There are about half a dozen associational studies showing increased risk of dementia with benzodiazepines, but keep in mind that dementia often presents with anxiety or depression (Penninkilampi R and Eslick GD, CNS Drugs 2018;32(6):485-497). One study found the same risk with antidepressants as with benzodiazepines, which suggests these drugs are just a marker for something else, like a psychiatric disorder (Baek YH et al, J Am Med Dir Assoc 2020;21(2):201–211.e2). One of our best studies tried to skip ahead—they removed all the patients who converted to dementia in the first few years of starting a benzo, thinking that these might be cases that were misdiagnosed as ­anxiety. That study also found no association (Osler M and Jørgensen MB, Am J Psychiatry 2020;177(6):497–505). Finally, a recent study found the opposite—patients on higher-dose benzodiazepines had a lower risk of dementia (Gray SL et al, BMJ 2016;352:i90).

CGPR: Which cognitive domains are impaired with benzodiazepine use?

Dr. Aiken: Benzodiazepines decrease cognitive functioning with long-term use. Although cognitive function often improves with discontinuation of the benzodiazepine, some deficits may remain. Benzodiazepines affect memory, visuospatial abilities, concentration, and psychomotor speed. This happens gradually over many years, so patients don’t complain even though their lives could be going downhill. Benzodiazepines also decrease problem solving abilities, which may be related to suicide risk. I believe that suicide is the last resort of problem solving. I saw a study that benzodiazepines reduced people’s ability to recognize negative emotions like anger in others (Garcez H et al, Psychopharmacology (Berl) 2020;237(1):1–9). There’s a problem-solving skill right there—reading faces is important to solving social problems.

CGPR: How do you approach the discussion about benzodiazepine risks and benefits with a patient?

Dr. Aiken: It depends on the patient. Some patients feel bad about being on benzos even though their use is appropriate and they are unable to taper off. I’ll remind them that a daily benzodiazepine is safer than daily alcohol and that there are risks to untreated anxiety. But when I’m planning on short-term use, I’ll emphasize the risks of benzodiazepines more. “Just because I’m a doctor, it doesn’t mean that everything I prescribe is good for you. This medication will get you through the crisis, but don’t plan on using it long term because…” and then I’ll emphasize the risks I’ve mentioned in this interview, including tolerance and dependence.

CGPR: How do you approach patients already taking benzodiazepines when they are willing to tolerate the risks?

Dr. Aiken: I want to understand their values—which may differ from mine—and make sure they understand the risks. Our job is not to reduce risks to zero, so I might be comfortable continuing the benzos in these patients. But let’s say they had a recent fall or car accident and were on a high dose. In that case I’d start by depersonalizing any conflict that might arise. I’d communicate that I am on their side, but that I also have to stay within the lanes when prescribing controlled substances. Then I would begin a taper.

CGPR: How do you approach the taper in older adults who have taken benzodiazepines for decades? Do you follow taper schedules?

Dr. Aiken: The technical part is easy. Lower every two to four weeks, and lower by smaller increments toward the end of the taper. Most patients can be safely tapered off over one to three months. The psychological management is more difficult. The patient has to trust me, and they have to be ready. I don’t want the taper to be a failure because then they’ll feel burned, and our next attempt will be harder. I also give them something to look forward to—I mention that one study found people were more confident and had a greater sense of mental clarity after successfully tapering off.

CGPR: The Ashton manual, which provides benzodiazepine taper schedules to minimize withdrawal symptoms after long-term use, recommends switching to diazepam for a smoother taper. What are your thoughts about this strategy in older adults?

Dr. Aiken: It’s helpful for patients to have clarity in the schedule, and the Ashton manual is one way to provide that. I’m also firm that although patients can negotiate the duration of the taper (stay on the new dose for longer), they can’t go back to the old dose. Ashton recommends switching to diazepam, but I don’t always follow this strategy in elderly patients because of its long half-life. Also, as alprazolam has unique properties, other benzodiazepines may be ineffective in preventing withdrawal symptoms. Some patients will therefore need to stay with alprazolam to treat its own withdrawal (Ait-Daoud N et al, J Addict Med 2018;12(1):4–10).

CGPR: What other medications do you use to help with the tolerability of a benzodiazepine taper?

Dr. Aiken: Randomized controlled trials have shown some evidence for propranolol (60–120 mg/day), pregabalin (200–400 mg/night), trazodone (75–400 mg/day), valproate (1000–2500 mg/day), and carbamazepine (200–800 mg/day), but these medications have their own side effects in older adults (Fluyau D et al, Ther Adv Psychopharmacol 2018;8(5):147–168). Eszopiclone (Lunesta) is a good choice for stabilizing sleep because it produces a metabolite with benzodiazepine-like effects on anxiety. Outside of that published evidence, I’ve had success with Silexan (160 mg/night), which is a lavender oil available over the counter through the brand CalmAid.

CGPR: How does Silexan work?

Dr. Aiken: It might help by treating the underlying anxiety disorder. Silexan has a large effect size in several generalized anxiety disorder trials (0.87)—including a large, head-to-head trial with paroxetine—while most other medications have small effect sizes of 0.2–0.3 (Generoso MB et al, J Clin Psychopharmacol 2017;37(1):115–117). I’ve found that many patients spontaneously taper down their benzodiazepine after starting Silexan.

CGPR: Which nonpharmacological interventions can be helpful in managing a benzodiazepine taper?

Dr. Aiken: A specific form of cognitive behavioral therapy (CBT) has good evidence to improve benzodiazepine withdrawal. It’s similar to CBT for panic disorder, as it incorporates physical stress reduction techniques like deep breathing, muscle relaxation, and cognitive skills to tolerate physical symptoms of anxiety. One of the developers, Michael Otto, has a book on the technique that I recommend to patients (Otto MW, Pollack MH. Stopping Anxiety Medication: Workbook. Oxford, UK: Oxford University Press; 2009).

CGPR: What are some better alternatives to benzodiazepines in older adults when prescribed for insomnia?

Dr. Aiken: CBT for insomnia (CBT-I) is my first-line option, but it only works if the patient is motivated. I teach it in person and guide technologically savvy patients to use an app at home, like CBT-I Coach (free) or the FDA-cleared Somryst ($120). Older adults may prefer benzos and z-hypnotics because they do more than initiate sleep. They are amnestic agents with rewarding and anxiolytic qualities, and they help patients turn off ruminative thoughts. However, they come with an increased risk of falls and driving impairment. A few hypnotics are not listed on the Beers Criteria in this population but are almost as effective as the benzos and z-hypnotics when we look at the raw numbers, like time to sleep onset and duration of sleep. These are ramelteon (8 mg/night), suvorexant (10–20 mg/night), lemborexant (5–10 mg/night), low-dose doxepin (3–6 mg/night, available as generic), and melatonin (1–3 mg/night). The first three in that list have extensive studies in the elderly. One lemborexant study enrolled people up to age 93! To assess the safety of lemborexant, researchers woke participants up in the middle of the night, had them stand up, and shook them—and they didn’t fall.

CGPR: Are you comfortable prescribing these hypnotics for longer than a month or two in older adults?

Dr. Aiken: Sure. Most of my patients have chronic insomnia because they have a chronic mood disorder, so I will need to treat insomnia over the long term. Ramelteon is my go-to because it’s generic, and in some studies, it worked better the longer patients took it. The scientific rationale is that it entrains the circadian system, which is a nice thing to tell patients because it gives them reassurance.

CGPR: Thank you for your time, Dr. Aiken.