All sorts of medications are prescribed for anxiety in older adults. Today, we look at when and how to discontinue them.

Publication Date: 03/25/2024

Duration: 22 minutes, 47 seconds

Transcript: 

KELLIE NEWSOME: From benzos to antipsychotics, all sorts of medications are prescribed for anxiety. Today, we look at when and how to deprescribe them in older adults.

CHRIS AIKEN: Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report.

KELLIE NEWSOME: And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.

We’re continuing our countdown of the most-read articles from 2023. This one is from our geropsychiatry journal, and its place at #2 on the list speaks to how important this topic is for all of us: Deprescribing Anti-anxiety Medications in Older Adults, by Rachel Meyen. You can read all of the top 15 articles free online through the link in the show notes or just Google “Top 15 Carlat Psychiatry Articles of 2023.”  Dr. Meyen is an outpatient geriatric psychiatrist at the Sacramento VA Medical Center and has no conflicts related to this article.

CHRIS AIKEN: When we see an older adult who is stable and not misusing medications, our inclination is usually not to “not rock the boat.” But when it comes to anti-anxiety medications, tapering is often a good idea, especially considering the risks of falls, sedation, and accidents. These risks increase with age, and while some patients are cautious and concerned about those risks many others are in denial about it. 

I think of an older man I treated who was on long-term lorazepam and had had a recent fall. He was adamant that the fall had nothing to do with the benzo, blaming it on his housecleaner who had used a new floor wax that day. Most older adults have a seemingly valid reason for falling – and the reason is probably true. The thing to keep in mind is that we all face crooked step-stones, uneven carpet, and waxy floors – but we don’t all fall under these irregularities. When we do, it’s usually an early sign of vestibular decline. In other words, the early falls have a seemingly good reason, but as things progress people start falling without any external cause.

KELLIE NEWSOME: What did you do for that patient?

CHRIS AIKEN: So if an older adult falls on a benzo, I have a pretty strict policy about tapering it off, which I did. The patient was not happy, but when I followed up a month later I heard a different tune. He said “For two years I’ve felt like I was walking on a boat dock – I even went to ENT and neurology to find out the cause – and ever since I came off that benzo the problem has gone away. I feel steady.”

KELLIE NEWSOME: I wish all our desprescribing cases ended that way. Let’s get back to Dr. Meyen’s text. Indeed, the first medication she recommends deprescribing is a benzo. 

In older adults, benzodiazepines raise the risk of falls, altered cognition, oversedation, and drug-drug interactions. And in patients on opioids, they raise the risk of potentially fatal respiratory depression. Benzodiazepines can also cause or aggravate delirium, worsening outcomes in patients with acute medical issues. In short, benzodiazepines are not recommended for older adults. But stopping the benzo is not so simple. When benzodiazepines are abruptly discontinued, withdrawal can include seizure or death, so a slow taper is best.

Next are the z-hypnotics, which also act on the benzo receptor but are activate the sleep part not the anti-anxiety part: zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). These are not much safer than benzos and also increase the risk of falls. Patients can have abnormal sleep-related behaviors on them, like cooking or driving. 

CHRIS AIKEN: Antidepressants don’t raise as much alarm as benzos in the elderly, but they have risks as well. SSRIs increase the risk of postural sway, falls, fractures, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and bleeding, while SNRIs can cause constipation and lead to a modest increase in blood pressure (van Poelgeest EP et al, Eur Geriatr Med 2021;12(3):585–596). Both SSRIs and SNRIs have been linked to osteoporosis after age 50 – and there’s a known biological mechanism behind this risk. 

KELLIE NEWSOME: Trazodone is often thought of as the safer sleep medication – and if lack of DEA regulation is the mark of safety it does look good. But a closer look reveals problems in the elderly. In one large study in nursing homes, trazodone was more likely to cause falls than Ambien, and almost as risky as the benzodiazepines. Trazodone also causes daytime sedation, and geriatric psychiatrists worry about reduced food intake, decreased quality of life, and diminished ability to participate in care on it.

    Another class that lacks addictive properties but causes problems in older adults is the antihistamines. Hydroxyzine and diphenhydramine are often used for anxiety and insomnia, but they can cause oversedation, and they have anticholinergic effects including cognitive impairment.

KELLIE NEWSOME: Let’s pause for a preview of the CME quiz for this episode

1. Which medication can cause temperature imbalance?

A. Benzodiazepines

B. Trazodone

C. Risperidone

D. Valproic acid

The next class to think about is the anticonvulsants. Other than gabapentin, which is generally well tolerated in the elderly, anticonvulsants increase the risk of drug-drug interactions and toxicity (McGeeney BE, J Pain Symptom Manage 2009;38(2 Suppl):S15–S27). Valproic acid (Depakote) can induce thrombocytopenia or hyperammonemia. Symptoms of elevated ammonia include irritability, headache, vomiting, and gait abnormalities – in severe cases it can cause seizures, encephalopathy, or coma. 

CHRIS AIKEN: Antipsychotics are high on the list to deprescribe in older adults, especially when they are not being used for a psychotic disorder. These medications increase the risk of movement disorders, sedation, muscle stiffness, restlessness, tardive dyskinesia, weight gain, falls, metabolic disturbances, cardiac arrhythmias, and difficulty swallowing (which can lead to aspiration pneumonia). 

Many of those risks are higher in the elderly – for example, the risk of tardive dyskinesia is about double in older adults. Anticholinergic problems are much more likely in older adults – we’re talking dry mouth – and all the dental problems that go along with it, constipation, blurry vision – which can lead to accidents, urinary retention – with its accompanying UTIs, and cognitive confusion. Anticholinergic effects also make it hard to regulate body temperature – something we are already seeing deaths from as the climate warms. Here are the antipsychotics with the lowest anticholinergic burden:

Brexpiprazole (Rexulti)

Lumateperone (Caplyta)

Lurasidone (Latuda)

The typical antipsychotic thiothixene

Ziprasidone (Geodon)

Another warning with antipsychotics is in dementia. Here we worry about several things. First, there’s little evidence that they work for psychosis in dementia. There’s also a black box warning of an increased risk of death and cerebrovascular events in dementia-related psychosis. Finally, antipsychotics and other psych meds with anticholinergic effects can interfere with the therapeutic effects of certain dementia medications – the acetylcholinesterase inhibitors like donepezil, galantamine, and rivastigmine. This is a pharmacodynamics interaction in the brain – the anticholinergic med is directly blocking the therapeutic action of the acetylcholinesterase inhibitor. The combination of an antipsychotic and an acetylcholinesterase inhibitor can in theory disrupt the balance of dopamine and acetylcholine in ways that increase the risk of Parkinsonina side effects. 

KELLIE NEWSOME: Here’s how to taper in practice. Before making a decision to taper, take a careful history to determine the patient’s underlying diagnosis, history of medication trials, current symptoms, remission status, and functioning. You need to find out how helpful – or not – that medication has been to them. Let them know about the specific risks with the medication, as you open up the conversation about coming off it. 

When done well, this kind of education can motivate change. For example, in the EMPOWER trial, primary care physicians mailed a letter about the risks of long-term benzo use and instructions on safe tapering protocols to patients on benzos – it was a randomized trial so only half got the letter. Of the 148 patients who received the brochure, 27% completely self-tapered off of benzodiazepines and another 11% reduced their dose. The ones who didn’t get that letter had a much lower rate – only 5% discontinued use (Tannenbaum C et al, JAMA Intern Med 2014;174(6):890–898). 

While it’s important to talk about risks, don’t forget to accentuate the positive. Talk about the potential positive psychological outcomes of coming off the medication. In one study, patients had greater mental clarity and more self-confidence after coming off a benzo. I’ve seen lots of older adults who are more lively – energetic and active – off them – it’s real enough you can see it in their movements on the mental status exam. Give patients a voice. You may decide that you can’t prescribe that benzo any more, but you can allow patients to have a say in the length of the taper.

CHRIS AIKEN: The online edition of the article has a useful table for tapering medications. Here are some tips. For benzodiazepines, decrease the dose by 5%–25% every two to four weeks. Some patients will require a slower taper, especially if they have taken benzodiazepines for decades. Alternatively, you can convert to an equivalent dose of the longer-acting diazepam prior to tapering. However, due to its long half-life and buildup of metabolites, this strategy is less appealing in older adults. 

KELLIE NEWSOME: Here’s a pearl: There are 3 benzodiazepines that don’t produce active metabolites and are not affected by CYP drug interactions in the liver: lorazepam, oxazepam, and temazepam. Of those 3, lorazepam’s profile makes it the easiest to taper. 

CHRIS AIKEN: However, if you do switch to diazepam, think about 14 mg/day as a cut-off point for the taper. If the total daily diazepam dose is over 14 mg per day, decrease in 2 mg increments every one to two weeks. If it’s below 14 mg per day, decrease in 1 mg increments every one to two weeks. You may need to go even slower in the last 25% of the taper.

KELLIE NEWSOME: For z-hypnotics, taper slowly to avoid rebound insomnia. One study reported that a “stepped approach” was effective, starting with a written letter to the patient from their physician recommending discontinuation of zolpidem, followed by a structured taper combined with cognitive behavioral therapy for insomnia (Bélanger L et al, Sleep Med Clin 2009;4(4):583–592). If your patient is taking sustained-release zolpidem, it’s best to switch to the immediate-release version before tapering, because the latter formulation lets you decrease in smaller increments. The instant release is also associated with a lower risk of falls. Once on the instant release, you can lower zolpidem by 2.5 mg each week.

CHRIS AIKEN: For antidepressants, we worry about discontinuation syndrome with SSRIs and SNRIs, particularly with paroxetine and venlafaxine, but it can happen with all of them. The classic symptom is flu-like feelings, vertigo, and brain “zaps”, but the potential discontinuation symptoms are many and include worsening of mood/anxiety symptoms (which may be misinterpreted as relapse). 

If discontinuation symptoms occur, return to the previous dose at which your patient did not experience symptoms and/or slow the taper. Examples include decreasing sertraline by 25–50 mg every two to six weeks or decreasing venlafaxine by 37.5 mg every two to six weeks. For trazodone, reduce by 25 mg weekly as tolerated.

KELLIE NEWSOME: For anticonvulsants, we recommend tapering off lamotrigine, carbamazepine, and valproic acid if inappropriately prescribed for anxiety, but you should probably keep them on if they are used for bipolar disorder. Discontinuation syndromes in anticonvulsants is uncommon, but a taper is recommended to avoid problems. Decrease lamotrigine daily dose by 25–50 mg every five to seven days, carbamazepine daily dose by 200 mg weekly, and valproic acid daily dose by 250 mg weekly. Other medications may require adjustment due to enzyme induction and drug-drug interactions of anticonvulsants.

CHRIS AIKEN: Antipsychotics are also best tapered gradually – there are rare cases of withdrawal psychosis and withdrawal movement disorders occurring in people who had no earlier history of psychosis. Generally I would taper them over 2-4 weeks, but the duration depends on the patient. 

KELLIE NEWSOME: Antihistamines can be stopped without a taper. The risk of discontinuation symptoms from stopping “cold turkey” is low. 

CHRIS AIKEN: Tapering will reduce the risk, but it won’t treat the underlying anxiety disorder that may crop up. Dr. Meyen recommends psychotherapy and – if medications are needed – possibly pregabalin (Lyrica) – which is backed by large trials in anxiety disorders and has regulatory approval in other countries. The usual dose is 300-600mg per day, though lower doses may be needed in older adults. Gabapentin 100 mg can be given as needed one to three times daily to treat anxiety, and it can be used at night to promote sleep. The evidence is not very robust for gabapentin, but it is usually better tolerated than pregabalin. Remember that gabapentin is renally cleared, so check creatinine clearance before ­prescribing.

Buspirone is very well tolerated in the elderly and can be an effective adjuvant to SSRIs for anxiety. Start at 5 mg twice daily and increase by 5 mg/day every few days. The maximum daily dose is 60 mg daily, although many older adults experience benefit at 15–30 mg daily.

Mirtazapine helps with anxiety and sleep. Tolerability is good in older adults, and the side effect of appetite stimulation can be a “two-fer” in patients with anxiety and poor oral intake. Start at 7.5 mg at bedtime and increase in 7.5 mg increments every few days to one week. Mirtazapine 7.5–15 mg primarily targets sleep, and a 15–30 mg dose is usually sufficient to control anxiety in older adults.

KELLIE NEWSOME: We’ve also had success with Silexan – a branded extract of Lavender that has regulatory approval for generalized anxiety disorder in a dozen European countries. The pharmaceutical company that manufacturers Silexan in Germany also produces an over the counter version that they sell as CalmAid in the US. Silexan is safe and well tolerated in older adults, and has a large effect size in anxiety. To learn how to use it, google Carlat Silexan. 

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Check out the online article which has a tapering schedules for deprescribing in the elderly. Join us next week for the #1 most read article: Viibryd Goes Generic.

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