by Alan R. Gaby, M.D.

Elderly people are particularly susceptible to the adverse effects of medications. A meta-analysis of observational studies found that, of 7,533 hospitalizations among people aged 65 years or older, 1,251 (16.6%) were judged to be due to adverse drug reactions.[1] Despite these risks, the practice of putting old people on multiple prescription medications is widespread. A 2015 study found that the median number of prescription medicines used by elderly individuals was 4, and that 39% of old folks were taking 5 or more drugs.[2] According to one report, the average nursing home patient is taking 7 medications.

Drugs that act on the central nervous system (CNS) can be particularly problematic. These medications can impair cognitive function and may increase the risk of fall-related injury and death. Drugs that are considered CNS-active include antidepressants, antipsychotics, antiepileptics/anticonvulsants (e.g., gabapentin [Neurontin]), benzodiazepines, benzodiazepine receptor agonists (e.g., zolpidem [Ambien]), and opioids. The risks associated with CNS-active drugs may be even greater in elderly people with dementia, since these individuals already have impaired cognitive function.

A cross-sectional study was conducted on 1,159,968 community-dwelling elderly adults with dementia (median age, 83 years) who were insured by Medicare from 2015 to 2017. The primary outcome measure was the prevalence of CNS-active polypharmacy, defined as exposure to 3 or more medications for longer than 30 days consecutively from the drug classes listed above. Approximately 1 of every 7 subjects (13.9%) met the criterion for CNS-active polypharmacy. Of those with CNS-active polypharmacy, 57.8% were taking the drugs for longer than 180 days, and 29.4% were taking 5 or more medications. The most frequently used drugs were antidepressants (92% of polypharmacy days), antipsychotics (47.1% of polypharmacy days), benzodiazepines (40.7% of polypharmacy days), and gabapentin (33% of polypharmacy days).[3]

This epidemic of polypharmacy could become even worse in the future, now that the FDA has approved 2 new drugs (valbenazine [Ingrezza] and eutetrabenazine [Austedo]) for the treatment of tardive dyskinesia. Tardive dyskinesia is a movement disorder that occurs as a side effect of antipsychotic drugs and some antidepressants (drugs that are frequently prescribed for elderly demented patients). Ingrezza and Austedo are being heavily advertised to the general public, probably because the drug companies are charging around $7,000 per month for these drugs, and they figure that the money they can squeeze out of insurance companies will more than compensate for what they are spending on ads. These drugs can cause a wide range of side effects, including drowsiness, dizziness, gait disturbances, trouble with balance and coordination, and falls. Those side effects would be piled on top of all the other drug side effects that elderly patients are already experiencing.

There are often legitimate reasons for prescribing CNS-active medications for elderly individuals. However, the use of these drugs risks sending the patient on a downward spiral in which an additional drug is used to treat the side effects of a previously prescribed drug. Before you know it, the unfortunate patient is taking 3, 5, or even 7 medications and faring poorly; possibly at least in part because of all the drugs they are taking. All too often, doctors fail to consider the possibility that discontinuing a medication and trying a safer alternative is preferable to adding another drug.

An 85-year-old patient that I treated for many years once remarked that he was the only person among his circle of friends who was not taking any medications. Instead he was doing well on diet, nutritional supplements, exercise, and a good attitude. In contrast, all of his drug-taking friends were either dead or in wheelchairs. This anecdote does not prove anything, but it illustrates the point I am trying to make.

What alternatives do we have to the various medicines that are being given old folks? For the treatment of depression, there are lifestyle alternatives such as aerobic exercise and participating in more community activities. Biochemical treatments might include L-tryptophan, DHEA, magnesium, iron supplementation if iron deficiency is demonstrated, and an empirical trial of vitamin B₁₂ injections. In some cases, vitamin B₁₂ injections relieve not only depression in the elderly, but also anxiety and insomnia, which are other conditions for which CNS-active medications are prescribed. St. John’s wort may also be effective against depression, but because it interacts with so many medications, its use could be problematic.

Potentially effective treatments for anxiety and insomnia include discontinuing caffeine and taking L-tryptophan near bedtime. Magnesium is also effective for some people, particularly those on magnesium depleting drugs such as thiazide or loop diuretics or proton pump inhibitors.

For pain resulting from peripheral neuropathy, intramuscular administration of vitamin B₁₂ may be beneficial as a potential alternative to gabapentin.[4] Laboratory evaluation often does not predict whether a patient will have a positive response to vitamin B₁₂ therapy,⁴ so an empirical trial would be reasonable.

Antipsychotic drugs such as risperidone and aripiprazole are approved by the Food and Drug Administration for the treatment of schizophrenia and bipolar disorder. They are also frequently prescribed off-label as a sedative for elderly demented patients who exhibit aggressive or violent behavior. Research suggests that such behavior can sometimes be improved by training nursing home staff to help resolve specific issues that are bothering patients.

Dementia itself is difficult to treat effectively with natural medicine. However, there is evidence that some elderly demented individuals have a subnormal concentration of vitamin B₁₂ in their cerebrospinal fluid despite having normal serum levels of the vitamin.[5] In those patients, intramuscular administration of vitamin B₁₂ improved the dementia, whereas oral vitamin B₁₂ was not beneficial. Oral administration of other B vitamins may also improve dementia in some cases.[6] Magnesium may also be useful, particularly in patients taking magnesium-depleting medications. I saw an 83-year-old woman who had been diagnosed with Alzheimer’s disease, but who turned out to have furosemide-induced magnesium deficiency. Her mental status became essentially normal after she received a series of intravenous magnesium injections. Interestingly, her serum magnesium level was normal, which is not uncommon in patients with magnesium deficiency, since magnesium is primarily an intracellular ion.

If you have read this far, you probably have seen a pattern. Some elderly people may be able to substitute some of their CNS-active medications with treatments such as vitamin B₁₂ injections, other B vitamins, magnesium, iron (if deficient), and L-tryptophan. It may also be worthwhile to encourage lifestyle changes and to work on conflict resolution. It should be noted that L-tryptophan can increase the adverse effects of selective serotonin-reuptake inhibitors and some other medications, so it should be used with caution.

The treatment of health problems in the elderly can be difficult and complicated, especially when dementia is involved. However, we can probably do a better job by seeking safer alternatives to prescription medications and remembering to include “adverse drug reactions” in our differential diagnoses.

[1] Beijer HJ, de Blaey CJ. Hospitalisations caused by adverse drug reactions (ADR): a meta-analysis of observational studies. Pharm World Sci. 2002 Apr;24(2):46-54.

[2] Charlesworth CJ, et al. Polypharmacy among adults aged 65 years and older in the United States: 1988–2010. J Gerontol A Biol Sci Med Sci. 2015;70: 989-995.

[3] Maust DT, et al. Prevalence of central nervous system-active polypharmacy among older adults with dementia in the US. JAMA. 2021;325:952-961.

[4] Solomon LR. Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. Blood. 2005;105:978-85.

[5] van Tiggelen CJ, et al. Assessment of vitamin B12 status in CSF. Am J Psychiatry. 1984;141:136-137.

[6] Gaby AR. Dementia/cognitive decline. In Gaby AR. Nutritional Medicine, Second Edition. 2017, Concord NH. doctorgaby.com. Chapter 286.