Why are people living with dementia prescribed mood stabilizers, antidepressants, and/or antipsychotics? I dive into these medications in this week’s blog post.

I’d like to share something personal. This week was rough. My dog, Amira, became very sick and was hospitalized.  I’m happy to say that she is much better. I must give a shout out to Steel City Vets in Hoover, Alabama, who took great care of her. But even with these awesome vets, vet techs, and veterinary nurses—I was a bundle of emotions. I was sad—what if I lose her? I really love the little turd muffin. I was worried—will she be ok? Is she scared? Does she think I abandoned her?

I basically stayed somewhat balanced and did not lose my shit because…

• I was able to cope using reason—I knew I made the most logical choice and I had used Steel City before when my cat, Pippin, got sick one weekend.
• I was able to cope using communication–I called the clinic and checked in on her.
• I was able to cope using social support--I had understanding friends and family who supported both of us—including my daughter Sara who wanted to know the visitation policy so she could stop by. Luckily, Amira was discharged in 24 hours so no need for that!

Let’s talk about people living with dementia. They also experience emotions, but their brain changes can make it very challenging for them to handle emotions and moods the way they did before the disease showed up. Plus, the isolation from the disease often takes away friends and family who, in the past, offer needed support. This sucks, but it is a sad reality.

People living with dementia experience brain changes. These brain changes can make it hard for them to handle common moods we all experience, like irritation, frustration, sadness, and anger. In some cases, you may notice that a person living with dementia “flies off the handle” when faced with minor, even petty, problems. There are non-drug ways to handle these moods and mood swings. However, there may be times when non-drug approaches do not totally work…or may not work at all. Here are some common medications that may be prescribed to help soften common moods and emotions experienced by people living with dementia.

Antidepresssants

People living with dementia likely have lower serotonin levels and other useful brain chemicals. Why? Brain cells—neurons—make brain chemicals. If you lose neurons—which you do with all of the dementias—you lose the ability to keep your brain chemicals at the correct levels. Some chemicals are needed for memory—like acetylcholine, which I talked about last week. Some chemicals keep us from feeling hopeless and depressed, even when going through rough times—like serotonin. Some chemicals help us from feeling overly anxious—like norepinephrine. These brain chemicals have other jobs in other parts of the body, but I’m going to focus just on the brain.

People living with dementia may experience new depression. Or, if they struggled with depression in the past, the depression may reappear with a vengeance. Here are some antidepressants that a provider (nurse practitioner, physician, physician’s assistant, psychiatrist) may use.

Selective Serotonin-Reuptake Inhibitors (SSRIs)

As I described in my blog about acetylcholine-esterase inhibitors, brain cells like to constantly keep brain chemicals fresh. There is a continuous process: make the chemical, slurp up the chemical (or break it down) to make fresh chemicals, release newly formed chemical. A similar process happens with serotonin.  If you are losing neurons, which happens with the dementias, then it makes sense that the brain’s ability to keep up necessary levels of serotonin drops as the disease gets worse.

There are several SSRIs which keep the levels of serotonin higher than usual in someone’s brain. Two that are commonly used with people living with dementia are sertraline (Zoloft) and citalopram (Celexa). These two are commonly used because of a systematic review completed by Seitz and others (I will put the references in the show notes).  One of the findings from the systematic review was that both sertraline and citalopram were associated with a decrease in agitation.[1]

A note about systematic reviews. When experts complete a systematic review, they compile all of studies that looked at all of these medications and rated the studies. They analyze the quality of the study design. Studies that involve larger and more diverse groups of people, and that use randomization (meaning people are picked at random to receive a drug, a placebo, or some type of treatment), are rated as having a higher quality than studies that involve small groups of similar people who get the same drug or treatment, and the researcher simply looks at “before and after” in the one group. Systematic reviews are helpful because one can decide which study results should affect clinical practice, and which study results may be problematic.

Serotonin Modulators

Another antidepressant commonly given to people living with dementia is trazodone (Oleptro). Trazodone belongs to a category of drug called “serotonin modulators.” Serotonin modulators do a couple of things. They act like SSRIs by blocking the re-uptake of serotonin AND they also act on several receptors that are part of the serotonin neurotransmitter system. Trazodone is often used “off-label” as a sleep aide and another systematic review notes that it works.[2] When using trazodone, you can get a boost of serotonin and help dealing with sleep difficulties.

Serotonin and Norepinephrine Reuptake Inhibitors

This category works by keeping levels of serotonin and another neurochemical, norepinephrine, higher than usual in someone’s brain. Norepinephrine helps with concentration and depression. Some common SNRIs include duloxetine (Cymbalta) and venlafaxine (Effexor). I was unable to locate any systematic reviews that examined the use of SNRIs in people living with dementia.

Just because I could not locate a systematic review or meta-analysis does not mean there are problems with these medications. It just means the research has not caught up to clinical practice. The take-home message is that everyone reacts differently to medications. If medications from one category do not work, clinicians will try medications from another category. Until we have better genetic testing available to see how people potentially metabolize medications—and whether one type of medication would be more beneficial than another medication–prescribing will remain trial and error.

Benzodiazepines

This category includes medications for anxiety, such as lorazepam (Ativan) and Alprazolam (Serax), and medications for sleep, such as temazepam (Restoril) and triazolam (Halcion). While some of these medications may have a place for short-term use for acute anxiety attacks and panic attacks, or the psychiatric management of psychotic behavior, they are not good for long-term use in people living with dementia (or anyone). All of these benzodiazepines are associated with impaired memory, judgment, and coordination—so why prescribe them for someone who is already struggling with memory issues? These medications are also linked with increased falls in older adults.

Ironically, even thought benzodiazepines are widely prescribed for anxiety and sleep in older adults for dementia, there have been no randomized clinical trials testing the risks, benefits, and alternatives to benzodiazepines.²

Mood Stabilizers

A group of medications used for seizures are often prescribed to persons living with dementia who are showing physical aggression and agitation. Valproate products include: sodium valproate (Depakote), valproic acid (Depakene), divalproex sodium (Depakote sprinkles), and others. Even though it is often used, and many families report that the medication is useful, a 2018 meta-analysis did not find evidence of benefit.[3] This finding may be due to how the studies were conducted or how the results were reported.

Antipsychotics

Antipsychotics are commonly prescribed to people living with dementia. There are two main categories of antipsychotics: first generation and second generation. The second generation are also called “atypicals.”

First-Generation Antipsychotics

These drugs block dopamine receptors, specifically the D2 receptors. There are several types of dopamine receptors, by the way, and each type has a particular job. The first generation antipsychotics were developed to treat schizophrenia, which was thought to be caused by hyperactive D2 receptors. Stimulation of the D2 receptors may cause delusions, hallucinations, and other behaviors IN SCHIZOPHRENIA, NOT NECESSARILY DEMENTIA. However, D2 receptors are also important for movement. This is why first-generation antipsychotics are not a good idea for people living with dementia—there is a very high risk of movement disorders, like akathisia (can’t stay still), acute dystonic reactions (involuntary, repeated twisting movements that can be painful) and tardive dyskinesia (involuntary, repeated movements like grimacing, lip smacking, tongue protrusion, and eye movements). Examples of first-generation antipsychotics include haloperidol (Haldol), thiothixene (Navane), trifluoperazine (Stelazine), and chlorpromazine (Thorazine). Risk of movement disorders is increased in people living with Lewy Body dementia or Parkinson’s Disease Dementia. Another problem with first-generation antipsychotics is their anticholinergic effect (which means these drugs lower acetylcholine levels), which is problematic with Alzheimer’s dementia and can make memory problems worse.

Second-Generation Antipsychotics

These medications target multiple receptors, including the D2 ones. Unlike first-generation antipsychotics, the second-generation antipsychotics target multiple receptors and quickly “get off” of the D2 receptors. Therefore, the second-generation antipsychotics help with psychiatric conditions—like the first-generation ones—but with less movement disorders. These second-generation antipsychotics include quetiapine (Seroquel), risperidone (Risperdal), aripiprazole (Abilify), and olanzapine (Zyprexa). Of

all of these medications, risperidone is the most likely to cause movement disorders (even though there is less risk compared to the first-generation meds, the risk remains). There is not enough evidence today to identify which antipsychotic medication is both safest and most beneficial for people living with dementia. It is a decision that should be made by a knowledgeable clinician with an understanding of the diagnosis, other clinical conditions, and current medications.

Bottom Line

Antidepressant medication makes sense when you think about what is going on in the brain of a person living with dementia. In fact, some of the studies I referenced found that antidepressants alone, and antidepressants combined with meds like donepezil, were more effective than antipsychotics in controlling difficult behaviors like agitation. On the other hand, antipsychotic medications were developed to address behaviors (like hallucinations and delusions) in people diagnosed with schizophrenia. These medications are not to be used lightly. This is why I promote non-drug approaches to behavior as much as possible.

[3] Baillon SF, Narayana U, Luxenberg JS, Clifton AV. Valproate preparations for agitation in dementia. Cochrane Database Syst Rev. 2018;10:CD003945.

• [2] McCleery J, Cohen DA, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev. 2016;11:CD009178.

• [1] Seitz DP, Adunuri N, Gill SS, Gruneir A, Herrmann N, Rochon P. Antidepressants for agitation and psychosis in dementia. Cochrane Database of Systematic Reviews. 2011(2).

Categories: Dementia

Tagged as: antidepressants medications

Dr. Rita Jablonski

Rita Jablonski, PhD, CRNP, FAAN, FGSA is a nurse practitioner, researcher, tenured professor, and former family caregiver. Her research and practice involve all aspects of dementia management; she is best known for non-drug strategies to address dementia-related behaviors.