Marc E. Agronin, MD

A new question must be added to the list that mental health clinicians ask their older patients while taking a history, regardless of age: “Have you used any cannabis products recently?”

I learned this lesson during a follow-up appointment with an 82-year-old man with Alzheimer disease. He reported some rather abrupt cognitive decline, and I asked him and his wife about recent medical changes without finding any clear precipitant. Finally, his wife sheepishly confessed that their son had sent them a grab bag of cannabis-derived products that the patient was taking. The family was desperate for anything to help his cognitive decline and they had heard that cannabis was a miracle cure for Alzheimer disease and many other conditions. Unfortunately, the patient received no benefit but did experience some mild, noticeable adverse effects. Without my probing, I never would have known. The next patient I asked explicitly about using cannabis products responded in an equally explicit manner: “No I haven’t,” he said, “but can you get me some?” It was clear that the age of cannabis had arrived.

Clinical Management of Cannabis Complications


Thomas R. Kosten, MD, and Christopher D. Verrico, PhD

The Age of Cannabis Has Arrived: Issues for Older Adults

Cannabis 2021: What Clinicians Need to Know

Cannabis and Psychosis: A Synthesis of Quantitative Reviews

How to Discuss Cannabis With Your Patients

You Spoke, We Listened. Psychiatry's Cannabis Survey

Figure. Percentage of Individuals 65 or Older Who Have Used Medical Marijuana

Older individuals with psychiatric disorders are increasingly using cannabis, largely in the form of prescribed medical marijuana and cannabidiol (CBD). This trend has been driven by several factors: reduced stigma, lifted restrictions on possession and sale by most states, and the enormous proliferation of articles and ads that tout supposed benefits of 

 for many conditions that afflict the elderly, including chronic pain, peripheral neuropathy, stress, anxiety, depression, insomnia, headaches, and the adverse effects of chemotherapy.

 As a result, medical marijuana use by individuals 65 or older has increased more than 8-fold in recent years, from less than 0.5% in 2006 to 4.2% in 2018

). In a survey of 345 adults in Colorado, 16% had used medical marijuana since legalization, with half the users being 75 or older.

 CBD has seen a particularly enormous surge in interest and availability after it was exempted from federal regulations in the 2018 US Farm Bill. Since then, it is estimated that 6.4% of adults aged 45 to 55 and 3.7% of those 55 or older have used CBD at least once.

Although the cannabis sativa plant contains hundreds of chemicals known as cannabinoids, the 2 main active chemicals are Δ-٩-tetrahydrocannabinol (THC) and CBD. THC has both psychotropic and euphoric properties and confers the high associated with marijuana, while CBD is noneuphoric because it does not activate the cannabinoid 1 receptor like THC does. The same plants that produce THC also produce CBD. Both THC and CBD come in a variety of forms; they can be smoked, vaped, eaten, ingested as liquids, used as oils, and applied via creams and cosmetics.

The psychotropic effects of both THC and CBD are mainly because of their interaction with endogenous cannabinoid receptors in the brain, as well as activation of a variety of other cannabinoid and noncannabinoid receptors (ie, serotonergic, glutaminergic, µ-opioid, and α1-adrenergic) in the central nervous system and on immunologic cells. Based on their known and theorized properties, marijuana and CBD have been proposed as remedies to modulate symptoms of stress, insomnia, pain, inflammation, and cognitive impairment, particularly in older individuals. As a result, there are many unsubstantiated claims that THC and/or CBD can treat Alzheimer disease, Parkinson disease, schizophrenia, and anxiety and mood disorders.

Several small case series have suggested a tentative basis for some of these claims. For example, a study looked at the use of an oral spray containing THC and CBD for peripheral nerve pain and found that it was well tolerated and showed a trend toward improvement in pain and sleep.

 Medical marijuana use has been associated with some improvement in both movements and neuropsychiatric symptoms in individuals with Parkinson disease.

 One small case series found improvement in behavioral and psychological symptoms of dementia from cannabis oil containing THC.

 A related randomized control trial of 50 individuals with dementia and associated neuropsychiatric symptoms did not see any benefit from THC, but did find it was well tolerated and with no appreciable effect on memory.

 Despite these limited data, agitation associated with dementia is a qualifying condition for medical marijuana in several states.

Gruber and colleagues studied a sample of middle-aged individuals using medical marijuana over 3 months and found improvements in 

 and reductions in depression, insomnia, and impulsivity.

 They also saw a reduction in the use of benzodiazepines and opioids as well as a normalization of brain activation waves to states seen in normal controls. It is not clear, however, if these neurocognitive results were the direct result of the medical marijuana or an indirect benefit of decreases in pain, anxiety, and 

Although there are many other in vivo, in vitro, and animal studies of THC and CBD, it is clear that evidence is limited, and there are few randomized controlled trials to support most of their theorized clinical benefits. In addition, these studies are based on a variety of cannabis products from multiple sources and with variable contents.

 The 2 exceptions include a Food and Drug Administration (FDA)-approved form of synthetic THC known as dronabinol, which is used for treating appetite and weight loss resulting from AIDS as well as nausea and vomiting from chemotherapy, and a medication containing CBD for the treatment of 2 rare childhood seizure disorders. Dronabinol has also been studied in Alzheimer disease to treat anorexia and agitation and was found to be well tolerated with variable efficacy for both conditions.

, a CBD-THC combination, has been approved for the treatment of muscle spasms associated with multiple sclerosis.

The use of medical marijuana and CBD in older adults must be approached with caution because there are several potential adverse effects. It has been well established that heavy marijuana use in both young and middle-aged adults can cause mild functional and structural brain impairments affecting attention, 

, motor coordination, verbal memory, and executive function.

 Although these effects may be more variable with lighter use in older adults, they may be amplified by preexisting brain impairment as well as by underlying pulmonary and cardiovascular conditions, especially when medical marijuana is smoked or vaped.

 One review of 184 older patients (median age, 82) who were on medical marijuana for 6 months found that approximately 80% reported some benefit for the treated symptoms, but one-third reported adverse effects, including dizziness (12%) and sleepiness and fatigue (11.2%).

 Other reported adverse effects from a national epidemiologic survey included changes in mood and cognition, psychosis, increased heart rate and blood pressure, urinary retention, and blurred vision.

 In addition, THC has been associated with impaired driving in young adults, which could also be a problem in older drivers who may be impaired at baseline.

 of CBD use found that it is generally well tolerated with few adverse effects, the most common one being diarrhea.

 Other adverse effects associated with CBD include nausea, drowsiness, fatigue, dry mouth, and mood changes. Keep in mind that CBD is an inhibitor of several cytochrome P450 enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2D6, and CYP3A4. CBD can lead to drug-drug interactions with several commonly used medication groups in older patients, including blood thinners, antibiotics, anticonvulsants, antidepressants, and antipsychotics.

What To Ask Patients, and What To Tell Them

In this new era of medical marijuana and CBD, there are several important takeaways for clinicians working with older patients. Do not assume that because a patient is elderly and has physical or cognitive limitations that they do not fit the profile of a cannabis user. To the contrary: Every older patient along with their caregivers should be queried as to their use of cannabis, whether recreationally, from mail order or friends and family, or through a prescription. To this end, every clinical history should include questions about the use of cannabis products, including the stated reasons for use, the type of marijuana or CBD being used, and observed benefits and adverse effects. Concomitant medical conditions must be reviewed for potential vulnerabilities, such as an individual with hypertension using a product that increases blood pressure or heart rate, or an individual with chronic obstructive pulmonary disease using vaping oils. Potential 

 also need to be considered, with a focus on the categories of medications discussed in the article.

Patients and their caregivers need to understand that nearly all benefit claims are largely unsubstantiated, as they lack a rigorous scientific basis. Slick articles and ads generally exaggerate potential benefits, or they refer to in vitro or animal studies and anecdotal reports, making them sound as if they constitute direct evidence of clinical effects. They also need to understand the differences between THC and CBD, along with the fact that production is largely unregulated, so products can have many different ingredients and properties. Several studies have found wide discrepancies between labels for cannabis products and their actual contents, especially when it comes to the amount of THC or CBD.

 Thus, many products that claim only to have CBD actually have varying degrees of THC present. This lack of consistency often accounts for both inconsistent clinical effects as well as adverse effect issues, and these factors lead many older adults to discontinue use of cannabis products.

Finally, keep in mind that older patients with preexisting 

 such as in Alzheimer disease might be particularly vulnerable to adverse effects such as drowsiness, dizziness, fatigue, and mood changes, which in turn can account for significant and unpredictable fluctuations in cognition and behavior. Such unpredictability (in the amount of drug being ingested over time and the ensuing effects on brain and body) is exactly the sort of variability that can be hazardous in the older patient. Compounding these risks is the fact that many individuals will use products such as CBD oil without the knowledge and supervision of a knowledgeable clinician.

The bottom line is that more rigorous scientific study using randomized controlled trials is needed to substantiate the proposed benefits of cannabis and more fully understand the range and impact of common adverse effects.

is the chief medical officer at MIND Institute at Miami Jewish Health.

1. Gruber SA, Sagar KA, Dahlgren MK, et al. 

Splendor in the grass? A pilot study assessing the impact of medical marijuana on executive function

2. Grinspoon P. Older adults and medical marijuana: reduced stigma and increased use. 

Updated April 6, 2020. Accessed February 1, 2020. 

https://www.health.harvard.edu/blog/older-adults-and-medical-marijuana-reduced-stigma-and-increased-use-2-2020040119321

3. Han BH, Palamar JJ. Trends in cannabis use among older adults in the United States, 2015-2018. 

4. Reynolds IR, Fixen DR, Parnes BL, et al. Characteristics and patterns of marijuana use in community-dwelling older adults.

5. Oberbarnscheidt T, Miller NS. The impact of cannabidiol on psychiatric and medical conditions. 

6. Russo EB. Cannabis therapeutics and the future of neurology. 

7. Serpell M, Ratcliffe S, Hovorka J, et al. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. 

8. Shelef A, Barak Y, Berger U, et al. Safety and efficacy of medical cannabis oil for behavioral and psychological symptoms of dementia: an-open label, add-on, pilot study. 

9. van den Elsen GA, Ahmed AI, Verkes RJ, et al. Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: a randomized controlled trial. 

10. Maust DT, Bonar EE, Ilgen MA, et al. Agitation in Alzheimer disease as a qualifying condition for medical marijuana in the United States. 

11. Gruber SA, Sagar KA, Dahlgren MK, et al. The grass might be greener: medical marijuana patients exhibit altered brain activity and improved executive function after 3 months of treatment. 

12. Britch SC, Babalonis S, Walsh SL. Cannabidiol: pharmacology and therapeutic targets. 

13. Antonsdottir IM, Makino KM, Porsteinsson AP. Dazed and confused: medical cannabis in Alzheimer disease. 

14. Crean RD, Crane NA, Mason BJ. An evidence-based review of acute and long-term effects of cannabis use on executive cognitive functions. 

15. Nader DA, Sanchez ZM. Effects of regular cannabis use on neurocognition, brain structure, and function: a systematic review of findings in adults. 

16. DeFilippis EM, Bajaj NS, Singh A, et al. Marijuana use in patients with cardiovascular disease: JACC review topic of the week. 

17. Abuhasira R, Ron A, Sikorin I, Novack V. Medical cannabis for older patients-treatment protocol and initial results. 

18. Benitez A, Lauzon S, Nietert PJ, et al. Self-reported cognition and marijuana use in older adults: Results from the national epidemiologic survey on alcohol and related conditions-III. 

19. Arkell TR, Vinckenbosch F, Kevin RC, et al. Effect of cannabidiol and Δ9-tetrahydrocannabinol on driving performance: a randomized clinical trial. 

20. Chesney E, Oliver D, Green A, et al. 

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials

Articles

Cannabis use has prompted symptoms such as dizziness, sleepiness, and fatigue in older patients. Are there any benevolent effects?

“Nursing home residents aren’t getting half of our resources or half of our attention, yet they account for roughly half the deaths.”

- David Grabowski, PhD, Harvard Medical School

Nursing homes and other long-term care settings provide an unfortunate perfect storm for pandemics. Most of the residents are old, ill, frail, often immunocompromised, and live in close quarters with roommates and others during congregate dining and activities.

 They are cared for by staff living in the community, many with young children, who then come into the facility and circulate among them every day, in addition to multiple family members who visit frequently. Combine this with unfortunate but inevitable slips in infection control, and a single infectious staff member or visitor can be like a spark to kindling. The rapid onset of the coronavirus disease 2019 (COVID-19) pandemic has highlighted all of these risk factors for infectious spread. There are hundreds of thousands of confirmed or suspected cases in United States nursing homes, and many deaths.

The COVID-19 pandemic has affected the mental health of residents in 2 fundamental ways; directly through infection, and indirectly, but more insidiously, through social isolation and other psychological stresses. In addition to its known pulmonary and other systemic effects, the coronavirus known as SARS-CoV-2 can infect the nervous system, with one pathway being directly through the olfactory bulb, and cause a variety of neurological and psychiatric symptoms in at least one-third to one-half of symptomatic individuals.

 Common acute neurological symptoms have been headache and loss of smell and taste, while more concerning symptoms include peripheral neuropathy, delirium, stroke, encephalitis, neurocognitive impairment, psychosis, and mood and anxiety disorders.

 These symptoms are seen acutely and can linger for weeks to months afterwards.

For any susceptible older individual in long-term care, key indicators of infection may include changes in energy, alertness, concentration, orientation, sleep, and appetite. COVID-19 testing is appropriate for any suspected situation with neuropsychiatric changes, regardless of whether there are respiratory symptoms or classic symptoms of fever and cough. Patients need early psychiatric consultation to ensure rapid identification and treatment of these symptoms, since acute changes can easily lead to long-lasting sequelae. Older individuals, especially those with frailty and dementia, need to be physically mobilized as soon as possible to reduce deconditioning, build confidence, and promote engagement with others.

The impact of stress and social isolation

For the past 7 months, long-term care residents have been confined to their rooms without congregate dining, activities, and in-person family visits. They lack exercise, direct sunlight and fresh air, and a normal level of social interaction. At times, residents have had limited access to medical, mental health, and other therapeutic services. Because the majority of residents are not tech-savvy or even tech-capable, they have been fully and passively reliant on the time and availability of staff to facilitate video chats with family and other loved ones.

The psychological stress of social isolation can be particularly jarring for these individuals, even those already acclimated to some degree of pre-existing social isolation. They spend most of their time alone in their rooms, without in-person contact with family and other loved ones. They are surrounded by staff members rendered less familiar due to masks, gowns, and face shields. Hearing and visual loss can make effective communication very difficult through multiple layers of personal protective equipment (PPE). Residents may be confused and frightened seeing everyone wearing PPE.

Patients may be traumatized by the news on radio or TV, seeing other residents ill or dying, being ill themselves, and by experiencing the disruptions and losses brought on by COVID-19 spreading throughout the facility. Even under the best of circumstances, residents are often bored, lonely, anxious, sad, and confused. Trying to communicate with them can be limited by generational differences across residents and younger staff and family members, further complicating their ability to understand and cope with what is happening.

 These emotional disruptions can lead to new or recurrent mental health conditions, post-traumatic symptoms, and even life-threatening states due to failure to thrive, especially in those who survived infection.

Is there a solution to these challenges, other than the end of the COVID-19 scourge? Rigorous infection control, including the screening and regular testing of all employees, along with proper and consistent use of PPE, can reduce the risk of residents being infected. Equally important are efforts to attend to the minds and souls of staff and residents with dedication and creativity. Here are several suggestions to help reduce social isolation and improve engagement with residents:

Staff have to become like surrogate family members with frequent and more lengthy contacts, and wear photos and name tags on top of their PPE

Regular video chats with family members facilitated by social work and/or therapeutic programming staff are essential

Regular telehealth visits should be provided by doctors and other therapists

Celebratory, fun, and interesting snacks, treats, and programming (eg, music therapy) can be brought to the door, room, and bedside

Drive-thru family visits to the facility can be set up, using masks and social distancing

Activities can be brought to rooms via video and/or closed-circuit TV

At the same time, the enormous stress on staff from actual and feared exposure at work, financial loss if they miss extended work time when quarantined or sick, and the physical burden of wearing restrictive and hot PPE all day must be recognized and addressed. During previous pandemics, front-line staff have faced an increased risk for anxiety, panic attacks, depression, acute stress reactions, PTSD, and even suicide. Several ways to build up the “emotional PPE” for staff and support them include:

Provide multi-lingual staff education on stress identification and reduction 

Focus on deep breathing, hydration, taking breaks, and sleep hygiene

Hold daily staff huddles with safe social gathering to provide updates, reassurance, inspiration, education, and opportunities to vent and ask questions

Have a confidential mental health hotline

Provide on-site counseling and referrals to Employee Assistance Programs (EAP) or other professional mental health services

We must remember that these frontline caregivers are true heroes, facing daily stress that can be overwhelming. There are effective ways to support them over time, augmented by calling upon the many individuals in the community who want to help. Find them and engage them!

is a geriatric psychiatrist and senior vice president for Behavioral Health and the chief medical officer for MIND Institute at Miami Jewish Health. His discussed these issues during his “The Top Dos and Don’ts in the Psychopharmacologic Treatment of Geriatric Patients: Focus on Dementia and Late-Life Depression and Anxiety” presentation at Virtual Psych Congress 2020.

1. Godfrey E. ‘We’re Literally Killing Elders Now’ - Thousands of Americans in long-term-care facilities have died from COVID-19. My grandmother just became one of them. 

. April 29, 2020. Accessed September 18, 2020. 

https://www.theatlantic.com/politics/archive/2020/04/coronavirus-especially-deadly-nursing-homes/610855/

2. Paulin E. How to Track COVID-19 Nursing Home Cases and Deaths in Your State. American Association of Retired Persons. Updated June 11, 2020. Accessed September 18, 2020. 

https://www.aarp.org/caregiving/health/info-2020/coronavirus-nursing-home-cases-deaths.html

3. COVID-19 Nursing Home Data. Centers for Medicare and Medicaid Services. Updated September 6, 2020. Accessed September 18, 2020. 

4. Wu Y, Xu X, Chen Z, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. 

5. Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. 

6. Varatharaj A, Thomas N, Elllul MA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. 

7. Agronin M. Why It’s So Hard to Talk to Your Parents About the Coronavirus (and Vice Versa). 

https://www.wsj.com/articles/why-its-so-hard-to-talk-to-your-parents-about-the-coronavirus-and-vice-versa-11587236112

The COVID-19 pandemic has affected the mental health of residents in 2 fundamental ways; directly through infection, and indirectly, but more insidiously, through social isolation and other psychological stresses.

The Impact of COVID-19 on Mental Health in Long-Term Care Settings

When working with older individuals with psychiatric symptoms, most clinicians are familiar with the adage “start low and go slow” to guide their prescribing. This refrain has often been augmented with the phrase “but do go” to emphasize the importance of not stopping too early in the titration process. What are the roots of this approach? And, how should it unfold when applied to 3 common psychiatric disorders seen in later life: neurocognitive disorders, depression, and anxiety?

The first principle of prescribing any medication in later life is to appreciate important changes in drug metabolism due to aging organ systems. In terms of pharmacokinetics (ie, what the body does to the drug), absorption time is generally stable since decreases in intestinal absorption are offset by increased transit time; distribution varies by type of drug since increased body fat and decreased body water lead to increased volume of distribution for lipophilic drugs and decreased for hydrophilic drugs; bioavailability is increased for many drugs since there is upwards of a 30% reduction in initial hepatic metabolism; and half-lives are often lengthened since renal excretion is slowed by up to 50%.1 In terms of pharmacodynamics (ie, what the drug does to the body), drug response is less predictable due to alterations in receptor sensitivity, neuronal loss, and changes in key cholinergic and serotonergic pathways. In addition, older individuals tend to be more sensitiveto drug effects and may require lower doses, especially with opioids, anesthetics, and benzodiazepines. Some of the most concerning side effects are due to anticholinergic, antihistaminic, extrapyramidal, and sedating properties of medications.

One major guideline for safe prescribing in later life is The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, also called the Beers List, which was first developed in 1991 by geriatrician Mark Beers, MD. The list highlights medications that pose undue risk for negative outcomes, including falls, injuries, and even death.2 Since 2011, the American Geriatric Society have been revising and updating the list based on both consensus and evidence-based approaches. With these considerations in mind, we can explore several psychiatric conditions frequently seen in older individuals who have multiple comorbid conditions and polypharmacy.

There are no cures nor disease-modifying treatments for Alzheimer disease, aside from several experimental agents. Instead, there are 2 categories of medications that are US Food and Drug Administration-approved to improve its symptoms. These include 3 acetylcholinesterase inhibitors (AChEIs) that are indicated for mild-to-severe Alzheimer such as donepezil, rivastigmine, and galantamine; and 1 NMDA (glutamate) receptor antagonist called memantine for moderate-to-severe Alzheimer. There is also evidence that these agents can improve symptoms in Lewy body dementia and vascular dementia.

Here are several key do’s and don’ts to keep in mind when prescribing these medications:

keep expectations modest; the goal is symptomatic improvement and not curing the disease.

promise disease slowing, but educate patients and caregivers about realistic expectations and side effects.

start with the lowest dose and titrate slowly, per guidelines.

combine multiple acetylcholinesterase inhibitors.

combine acetylcholinesterase inhibitors with memantine as the disease progresses into moderate and advanced stages.

monitor closely for important side effects of AChEIs such as nausea, vomiting, diarrhea, nightmares, or slowed heart rate; and sedation, dizziness or confusion with memantine use.

start early. The later in the disease course you initiate use of cognitive enhancers, the less benefit you may see. Remember that studies have shown significant symptomatic benefit even in moderate-to-severe disease states.

Treating older individuals with depression poses unique challenges and considerations. Various forms of late-life depression affect 9% to 18% of individuals older than 55, and these rates increase significantly after the age of 85, especially for individuals in nursing homes and hospitals. On the other hand, the more serious and specific diagnosis of major depressive disorder is less prevalent than in younger individuals, with rates of 2% versus 6% to 7%.

Depression can have significant impacts on our bodies by accelerating brain aging and increasing the risk for medical conditions such as diabetes mellitus, cancer, neurocognitive disorders, and both cardiovascular and cerebrovascular disease and events. Risk factors associated with late-life depression include female gender, chronic medical illness, neurocognitive impairment, functional impairment, social isolation, and major life stresses. In many older individuals, depression may present with less mood-related symptoms and more physical or functional complaints and social issues, including fatigue, weight loss, pain, social isolation, resistance, agitation, self-neglect, and substance use. Up to 30% of older individuals with depression may have impairment in executive dysfunction, often due to vascular damage to frontolimbic white matter tracts. This “depression executive dysfunction syndrome,”as described by George S. Alexopoulos, MD, is notable for a poorer response to antidepressants and cognitive-behavioral therapy, earlier relapse, and a greater risk for recurrence.

In terms of selecting an antidepressant for older individuals, there is no favored agent based on multiple studies and meta-analyses, but they all work better than placebo.

 In general, individuals older than 55 years have slightly lower response rates and higher relapse rates compared to younger individuals.

Augmentation strategies that have shown efficacy for late-life depression include the use of antipsychotics, lithium, and methylphenidate. The addition of acetylcholinesterase inhibitors may help improve cognitive deficits, but they have not been shown to be helpful for depressive symptoms. Although antidepressants can improve depression and quality of life associated with medical illnesses, they do not clearly improve the medical conditions themselves. The exception of this is post-myocardial infarct depression, for which they may reduce the risk of recurrent cardiac events, procedures, and overall mortality.

Anxiety disorders are very common conditions in late life, affecting 1.2% to 28% of older patients depending on the subtype of disorder; generalized anxiety disorder and phobias are the most common. Higher rates are seen in chronic obstructive pulmonary disease, diabetes, depression, Alzheimer disease, and Parkinson disease. Antidepressants are first-line treatments, with both selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors most commonly used.

Benzodiazepine use in older patients is often necessary but must be managed carefully. On the one hand, they work quickly and effectively, and at low doses there is little risk of dose escalation or addiction. In general, there is a low risk of drug-drug interactions except with alcohol or other sedative-hypnotics. The purported risk of dementia associated with benzodiazepine use has limited evidence; even if true, it is less of a priority when working with older adults suffering from acute anxiety, especially when they may already have neurocognitive impairment.

 There is good reason for caution, however, given their concerning risk-to-benefit ratio, especially when prescribed by non-specialists. In older patients, benzodiazepine use is associated with an increased risk of falls with fractures, excess sedation, cognitive deficits, and motor vehicle accidents, and an overall elevated mortality rate.

Here are several important suggestions for safer benzodiazepine use:

use in individuals who have a history of unsteady gait, falls, or who are already on multiple medications affecting the central nervous system.

combine with other benzodiazepines or sedative-hypnotics.

 use when there is active alcohol or other substance abuse.

long-term use, escalate doses unnecessarily, or abruptly withdraw the medication.

use antidepressants as the pharmacologic base for anxiety disorders, with benzodiazepines as short-term options for severe symptoms.

use cognitive behavioral therapy, sleep hygiene, and other forms of psychotherapy.

remember that lorazepam and temazepam have no active metabolites since they are metabolized by conjugation only.

Benzodiazepines can be helpful in the short run for acute anxiety and panic while waiting for the more enduring antidepressant to take effect. Thereafter, they are best used only on an as-needed basis and always with close supervision. Individuals with Alzheimer disease and other neurocognitive disorders will be especially vulnerable to side effects of confusion and sedation. In some circumstances, low dose antipsychotics and trazodone can substitute for benzodiazepines, but only under the careful management of a geriatric psychiatrist or other specialist.

1. Shi S, Klotz U. Age-related changes in pharmacokinetics. 

2. American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. 

3. Kok RM, Reynolds CF. Management of depression in older adults: a review. 

4. Alexopoulos GS. Mechanisms and treatment of late-life depression. 

5. Cipriani A, Furukawa TA, Salantiet G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. 

6. Tedeschini E, Levkovitz Y, Lovieno N, et al. Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials. 

7. Kim JM, Stewart R, Yong-Seong L, et al. Effect of escitalopram vs placebo treatment for depression on long-term cardiac outcomes in patients with acute coronary syndrome: a randomized clinical trial. 

8. Crocco EA, Jaramillo S, Cruz-Ortiz C, Camfield K. Pharmacological management of anxiety disorders in the elderly. 

9. Salzman C, Shader RI. Benzodiazepine use and risk for Alzheimer disease.

10. Markota M, Rummans TA, Bostwick JM, Lapid MI. Benzodiazepine use in older adults: dangers, management, and alternative therapies. 

When working with older individuals with psychiatric symptoms, most clinicians are familiar with the adage “start low and go slow.” But what other tips should you consider when prescribing psychopharmacology? 

Do’s and Don’ts of Psychopharmacology in Late Life: Key Challenges and Opportunities

The COVID-19 pandemic has hit particularly hard on older individuals, who are more susceptible to serious illness as a result of underlying comorbid conditions. We see a similar phenomenon in many natural disasters, in which age is often a liability in terms of physical injury and death. Not surprising, we end up defining aging in terms of decline, disease and death, and viewing older individuals solely as potential victims. This attitude limits the way in which we can communicate with and learn from the elders in our lives—and it leads us, in turn, to denigrate our own aging selves.

Here is a counterpoint to this approach: aging brings key strengths that enable us to make better decisions, cope better, and even thrive during adversity: 

1. Wisdom
2. Resilience
3. Purpose
4. Creativity

Wisdom is one key strength, based upon not only all of the skills, experiences and knowledge that we accumulate with age, but also on ways in which our brains and minds draw upon and integrate different parts and perspectives better.

Research tells us that aging minds are more positive, practical and less emotionally reactive and impulsive. This wisdom make us more psychologically resilient as we age, enabling us to cope better with adversity. We can couple these strengths with a sense of purpose that often grows and deepens with age, conferring all sorts of benefits including improved wellness, fewer cardiovascular events, and even longer lives.

Another emergent strength is creativity, enabling us to express ourselves through art, relationships, volunteer work and other endeavors that can transcend the many physical and cognitive changes that may otherwise bog us down with age. Put together, the clear lesson here is to learn from and be inspired and guided by both aging and the elders around us. We need to celebrate the strengths that only aging can confer.

Videos

We need to celebrate the strengths that only aging can confer.

4 Components of Positive Aging

How can psychiatrists help caregivers deal with behavioral disturbances at home, without the possibility of having an in-person doctor’s appointment? Marc E. Agronin, MD, offers tips for helping patients in this special population, as well as their caregivers, during and after the pandemic.

Dr Agronin is a geriatric psychiatrist and Senior Vice President for Behavioral Health and the Chief Medical Officer for MIND Institute at Miami Jewish Health.

How can psychiatrists help caregivers deal with behavioral disturbances at home, without the possibility of an in-person doctor’s appointment? In this video, Marc E. Agronin, MD, offers tips for helping patients with Alzheimer disease and other dementias.

Caring for Patients With Neurocognitive Disorders During the Pandemic

During this unprecedented time, many individuals with Alzheimer disease (AD) are homebound with their caregivers. How can clinicians help caregivers deal with common dilemmas under stay-at-home orders? We spoke with Marc Agronin, MD, a geriatric psychiatrist and Senior Vice President for Behavioral Health and the Chief Medical Officer for 

Psychiatric Times: How can clinicians advise caregivers to help them and their loved ones get through this time?

In one word-routine. Remind caregivers it is important to have a set routine each day that is predictable, stimulating, and involves regular exercise, fresh air and sunlight, whether in one’s yard, on a balcony or within a safe perimeter around the home. They should have a set time to wake up, have meals, listen to music, play games, and have social contact with others, either by phone, video chat, or at a safe social distance.

Everyone in the home should get dressed each morning in daily clothes and attend to one’s hygiene as if it is a regular day. They should make certain to get adequate hydration and healthy meals with fruits and vegetables and enforce a regular bedtime. It is also important to avoid excess time watching the news.

Psychiatric Times: How can psychiatrists help caregivers deal with behavioral disturbances at home, without the possibility of having an in-person doctor’s appointment?

This is a challenge. When any behavioral disturbances occur, query the caregiver to generate several ideas on what may be the underlying causes: Boredom? Anxiety from watching news about the pandemic on TV? Lack of physical or social stimulation? Underlying pain or discomfort? Discordant interactions with other people in the home? Having some idea of what may be triggering the behaviors can provide immediate solutions.

Caregivers should be counseled to provide a set daily routine as described in the first question. They should be advised to reach out to their internist if they suspect a physical cause, and to you or your office (perhaps with a telehealth option) if they have 

 or questions about behavioral changes or psychotropic medications. There are simple de-escalation strategies (eg, deep breathing, distractions) and PRN medication options that can be provided. Finally, help them to feel calm, engaged with the affected person, and hopeful that things will improve.

Psychiatric Times: What approaches can help to relieve anxiety among caregivers and individuals with neurocognitive impairment?

Anxiety is a common problem during the pandemic, with people worrying about getting ill, obtaining necessary goods, losing income, or being isolated from other people and activities. Anxiety may present in many ways in someone with cognitive impairment, including mood changes (nervousness, sadness, irritability), sleep and appetite disturbances, physical symptoms (eg, headache, indigestion, muscle aches, or even minor shortness of breath or chest pressure that they misinterpret as coronavirus symptoms) and social isolation. It is important to recognize these symptoms as anxiety and rule out anything more serious. Providing the opportunity for people to describe how they are feeling and vent about their concerns will help, and this can be done over the phone or on a video chat.

Educate caregivers about several simple approaches to relieve anxiety in themselves and the cognitively impaired person, including deep breathing/relaxation techniques, stretching and exercise, fresh air and sunlight, and fun and stimulating activities to distract one’s mind. Some individuals may have more serious symptoms of anxiety or even panic, and will need pharmacologic intervention, especially if there is a history of anxiety or mood disorders or psychosis. Tailor the medication to the symptoms using established regimens, being careful to avoid side effects that can be more difficult to manage over the phone.

Psychiatric Times: What should you say to participants in a research study which has been suspended?

Nearly every study for AD in the country has had to be either suspended or delayed because of stay-at-home orders, closed sites, or the inadvisability of conducting in-person visits. It may be months before study procedures can be up and running again. This is unfortunate, but necessary, and will require significant alterations in study procedures.

is aware of these gaps and have provided guidance to study sponsors. If you are a principal investigator, you will have already been informed by each study sponsor about its status and what to communicate with subjects. If you have a patient who is in a study, encourage them to stay in touch with the study coordinator and/or principal investigator to find out what to do about study medications, and whether any study procedures can be conducted by phone or video.

What should you advise caregivers for individuals with neurocognitive impairment who have difficulty understanding and cooperating with social distancing?

First of all, it is important to remind all caregivers to follow stay-at-home orders and not make any trips to stores or anywhere else with someone who does not understand or follow the rules of social distancing, as that will put them and others at an unacceptable risk of exposure to the 

. A cognitively impaired patient who resists wearing a mask properly or approaches others too closely may cause unpleasant social interactions.

This issue will become even more important when rules are relaxed but most people will be out in public wearing masks and still social distancing from one another. If the 

 person cannot understand or follow the rules, you will need to counsel the caregiver to keep them at home. If the person can understand the rules, you can advise the caregiver to remind them before and during each outing and provide them with a comfortable facemask that will not cause them to unnecessarily touch their face to adjust it.

During this time, many individuals with Alzheimer disease are homebound with their caregivers. Here's how clinicians can help caregivers deal with common dilemmas under stay-at-home orders.

Alzheimer Disease and COVID-19

is Sir Arthur Conan Doyle, but he was actually Dr Arthur Conan Doyle before he became a writer. He used the medical approach at the time-and that was to be a good detective. This is the type of model we need to think about when we are working with patients who have an underlying major neurocognitive order such as Alzheimer disease with associated agitation. You have to be a good 

 to look at all the different potential causes, so I would like to focus specifically on what causes agitation and few tips on how you can get at that.

Keep in mind that by virtue of the fact that someone is suffering from a neurocognitive disorder, they have a brain that is which is damaged. If you look at it on the level of neurocircuitry, a person’s ability to regulate their affect is impaired, their executive function is impaired, and so this in of itself is sufficient to explain why a lot of people end up having exaggerated or inappropriate or disorganized responses to stress given those changes. In addition, we see that some of the key brain nuclei that are involved in the regulation of cognition or mood or behavior such as the serotonergic and dopaminergic systems are also impaired. Again, this also provides a setting for why we see agitated behaviors.

Clinicians look for several different categories of 

. One would certainly be medical factors, some either acute or underlying disease state that is impairing brain function. One of the most common causes would be infection, and related to that, delirium. We also look for psychiatric illness. There might be an underlying depression; there could be anxiety, panic attacks, and psychosis which are driving the agitation. We have to look at different psychological factors. Someone may be feeling very stressed out in their environment. There might be an unmet need: are they hungry, thirsty, over-stimulated?

It may be that the caregiver is not competent or is overwhelmed or burned out and so they are not providing the right amount of care or the care they are providing is stimulating agitation in the patient. Finally, we have to look at medication-related issues. Certainly, many different medications (ie, narcotics, steroids), as well as sedating medications (which we think might be helping to treat pain or even relax the person), can actually worsen brain function and could also be associated with agitation.

Dr Agronin is a geriatric psychiatrist and currently serves as the Senior Vice President for Behavioral Health and the Chief Medical office at MIND Institute at Miami Jewish Health in Miami, FL. He is the author of 

The Dementia Caregiver: A Guide to Caring for Someone with Alzheimer’s Disease and Other Neurocognitive Disorders

In this video, Marc E. Agronin, MD, discusses several factors that may play a role in agitation. One would be underlying medical causes. It could be an acute disease state impairing brain function. And the list goes on.

Detecting Agitation in Patients With Dementia and Alzheimer Disease

Every clinician who works with individuals who have dementia-what we now refer to as major neurocognitive disorders-encounters states of agitation that can worsen function, pose safety concerns, and increase caregiver stress. It can be both confusing and frustrating to understand and manage these behaviors, but there are several approaches that can make all the difference.

 by the International Psychogeriatric Association as involving excessive motor activity or verbal or physical aggression that causes emotional distress and excess disability for the affected person, and impairs relationships, social functioning, and activities of daily living.

 These behaviors are commonly part of a larger 

Agitation can worsen function, pose safety concerns, and increase caregiver stress. It can be both confusing and frustrating to understand and manage these behaviors, but there are several approaches that can make all the difference.