Sleep is More Sensitive to High Doses of Caffeine in the Middle Years of Life

Many of us may be aware that caffeine can keep you up late into the night, but the power of caffeine to affect sleep may actually be stronger in middle-aged adults. This study examined the administration of high (400 mg) and low (200 mg) doses of caffeine and aspects of sleep in young (20-30 years old) and older (40-60 years old) adults. A double-blind cross-over design was used with stratified randomization including 22 participants in each category (young and old). Electroencephalographic electrodes measured sleep latency (essentially the time it takes to fall asleep), total sleep duration, time spent in each sleep stage, and sleep efficiency.

In general, the older adult group was more sensitive to the effects of the higher dose of caffeine compared to the younger group. The effects of the lower dose did not differ significantly between the age groups. Specifically, given the higher dose, the older group took more than twice as long to fall asleep, experienced shorter total sleep times (by about 1.5 hours), and experienced reduced sleep efficiency as well as reduced amounts of short wave sleep and rapid eye movement sleep. The younger group actually experienced enhanced stage 1 sleep when given the 400 mg dose. Despite the age groups having similar salivary caffeine concentrations across sampling times, they experienced different effects. This can be due to age-related changes in the adenosinergic system– such as reduced A1 binding of adenosine and increased binding of A2a receptors and increased adenosine-forming enzymes– that result in a complex interaction between age and dosing of caffeine. Caffeine expresses its wakeful effects via adenosine antagonism.

People aged 50-60 years old consume the most caffeine on average amongst the adult population. This same subset of adults also experiences vast changes in sleep independent of caffeine consumption. With these facts and the results of this study in mind, it seems that this population is vulnerable to poorer sleep. Also considering how important sleep is to overall health and well-being, it seems that middle-aged adults should exercise caution in consuming caffeine. For reference, four cups of coffee may have about the same amount of caffeine as the high dose group (assuming about 95 mg caffeine per cup of coffee). From my limited experience with patients at SilverScripts, I have already seen that some older patients consume that much caffeine on a daily basis. As student pharmacists, we can inform our patients that consuming a lot of caffeine may lead to negative effects, including sleep disturbances as well as others not discussed in this study.


Robillard R, Bouchard M, Cartier A, et al. Sleep is more sensitive to high doses of caffeine in the middle years of life. J Psychopharmacol. 2015; 29(6):688-97

The Efficacy of High-Dose vs. Standard-Dose Influenza Vaccinations for Older Adults

Older adults are known to suffer from more severe complications caused by the flu. 90% of deaths due to influenza are experienced by adults aged 65 and older. In 2009, the FDA licensed the high-dose influenza vaccination with 4 times more influenza haemagglutinin than the standard-dose. It was passed according to accelerated approval regulations. However, more research needs to be conducted to gather additional data beyond what was done prior to the high-dose vaccination’s approval to assess the effectiveness of the high-dose.

This article discusses a retrospective cohort analysis that studies the effectiveness of the high-dose versus the standard-dose influenza vaccinations in adults aged 65 and older. Influenza vaccination and infection rates were gathered from the US Medicare Program. The participants were thus enrolled in Medicare and had a Healthcare Common Procedure Coding System or Current Procedural Terminology code for either the high-dose or low-dose influenza vaccines between August 2012 and January 2013. The vaccinations were received in community pharmacy settings. If a participant had influenza before receiving the vaccination or received both the high-dose and standard-dose, he or she was excluded from the study.

Of the 12.5 million Medicare beneficiaries received influenza vaccinations within the set time frame, 19% received high-dose vaccinations and 81% received standard-dose vaccinations. The participants were said to be similar in age and medical condition. The high-dose vaccination was more effective in participants between the ages of 65 to 85 years old. There was a 22% reduction in influenza diagnosis in the group that received the high-dose vaccine. The high-dose vaccine was also more effective in preventing hospital and community setting influenza-related outcomes.



Lancet Infect Dis. 2015; 15(3): 293-300.


Because pharmacists have recently been given the responsibility of providing immunizations, the next step is to ensure that the most effective vaccines are being distributed to the population. At my Community Health site, almost all the older adults tell me that they have received their ‘flu shot’ at their community pharmacy. The results found in this study include evidence that can potentially lead to preventing the flu in these older adults who now come to the pharmacy for their influenza vaccination. Do you agree that pharmacists’ roles go beyond striving for positive health outcomes from medications to now including positive health outcomes from vaccinations?

A Mind-Body Program for Older Adults With Chronic Low Back Pain

Approximately 100 million individuals in the United States suffer from chronic pain. Pain is prevalent in 52.9% of the older adult population ages 65 and older. Of the 52.9% experiencing pain, 30.3% were experiencing chronic back pain. Analgesics commonly cause severe adverse effects in older adults. Because of this prevalent drug therapy problem, nonpharmacologic treatments must often be utilized for effective management of chronic low back pain.

An experimental study was conducted among 282 patients with low chronic back pain 65 years or older. The goal of this study was to assess the effectiveness of a mind-body program at increasing function and reducing pain. The patients received an 8-week group program followed by 6 monthly sessions. The program was modeled on the Mindfulness-Based Stress Reduction program. This program took regular activities such as sitting, walking, and lying down and transformed then into meditation through breathing exercises and mindful awareness of thoughts and sensations. Compared with the control group, those receiving this mind-body treatment improved short-term function and long-term current and most severe pain.

The trial did not yield sustained results in treatment of lower chronic back pain, suggesting that future development of this intervention should focus on durability. This article was particularly of interest to me because it combined two of my interest in medicine with my interest in meditation. I often use meditation as a form of stress relief, and it is intriguing to see that meditation could also be used in pain management. Prescription pain medication is not the answer  for every patient and it is very often over-prescribed. I believe that is important for pharmacists to be aware of other pain management methods and share these methods with their patients. Although I do not believe that meditation alone is the answer, I think that a combination of medication therapy and meditation could be a very effective treatment for a lot of patients suffering from chronic pain.

JAMA Intern Med. Published online February 22, 2016.

Link to article

Barriers to Effective Management of Hypertension in Older Populations

The leading cause of preventible death, not only in our own country, but worldwide, is hypertension. There is substantial evidence from robust trials for management of hypertension in older adults. The prevalence of hypertension seems to  increase with age, and therefore management of hypertension among older individuals through pharmacotherapy is essential to reach optimal health care for older populations. I study was conducted through the Journal of Pharmaceutical Policy and Practice to determine how exactly the prevalence of hypertension changes with age. The study also explored evidence regarding current pharmacological management in older adults for hypertension. The evidence from this study was then used to identify barriers that prevent older adults from receiving the best quality of care in the management of their hypertension.

The study found that the number of individuals struggling with hypertension increases significantly with age. At the age of 65 years or younger, 30% of the population has hypertension. But the age of 80 and over, this percentage of individuals with hypertension increased to 70% of the population. With the increase of the prevalence of hypertension with age, there is good evidence for the use of a number of medications to control blood pressures in older population.  However, despite good evidence for pharmacological management of hypertension in older adults, the quality of care available for treatment of hypertension in older adults is suboptimal. System, physician, and patient related barriers prevented older adults from reaching optimal blood pressure control.

J of Pharm Policy and Pract Journal of Pharmaceutical Policy and Practice 8.1 (2015): n. pag. Web.

Link to article

This study showed me the importance of open dialogue between patients and pharmacists. A pharmacist could easily prevent the patient-related barrier to the optimal treatment of hypertension in older adults. A pharmacist must make sure that each of his or her patients knows exactly how to adhere to his or her medication regimen. A pharmacist must also be able to advocate for his or her patients by expressing any concerns that they may have to the physician. Communication and a strong patient-pharmacist relationship are key to fixing the under treatment of hypertension in the older population.

MTM intervention and reducing fall risk in older adults

A pilot study was done to look at medication therapy management intervention and fall risk-increasing drugs (FRIDs) in older adults. FRIDs can include both prescription and OTC medications and are often used by older adults despite being a factor associated with falling along with living environment and physical status. Falls for older adults are common and costly, but modifying medications that could increase risk of falling can help prevent this issue. Older adults use an average of 2.34 FRIDs, but MTM intervention by a pharmacist is an idea of how to curb this problem.

The study was a randomized, controlled trial with 80 older adults (average age 74.9 and 76.3 years) split into a control group or an MTM intervention group. The outcomes of the study that were used to measure were the discontinuation of FRIDs, and the number of falls, as well as the acceptance of recommendations of the pharmacist by the patients and the prescribers. 77% of the intervention group had their FRID use discontinued while only 28% of the control group had their FRID use discontinued (outside of pharmacist intervention). 28% of the intervention group fell post intervention while 24% of the control group fell. There was a 75% acceptance rate of the pharmacist recommendations by patients and prescribers. Overall, pharmacists providing MTM intervention focusing on FRID use in older adults was effective in modifying the use and supports that pharmacists can play a role in modifying FRID use in older adults. In the future, it could be useful to study the relationship between reducing FRID use by pharmacists and the rate of falls more closely.

J Am Pharm Assoc. 2016; 56(1): 22-28

Quetiapine safety in older adults: a systematic literature review

Quetiapine (Seroquel) is a second-generation antipsychotic that is used for many indications including schizophrenia and bipolar disorder. Off label indications include behavioral and psychological symptoms of dementia (BPSD). There are no systematic reviews on quetiapine in older adults, and the goal of this literature review was to review the safety profile and study adverse effects in this vulnerable population.

A systematic literature review was done using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases that were searched were CINAHL, PubMed, Medline, PsycInfo and Cochrane Library.

The most commonly found adverse effects were somnolence (25-39%), dizziness, headache, postural hypotension, and weight gain. Quetiapine was found to have significantly more cognitive impairment when compared to placebo, as well as higher rates of falls and increased mortality in patients with Parkinson’s disease. Controversially, it was found that quetiapine did not have any adverse effects in patients with dementia. Quetiapine was then compared to risperidone (quetiapine is metabolized to the active metabolite of risperidone so they are very similar drugs however they are metabolized differently in the body) and it was found that quetiapine had an increased rate for falls and injury, however less risk for mortality and reduced cardiovascular events compared to risperidone.

These findings show that consideration should be given to prescribing quetiapine in older adults. The percentage of somnolence and falls/injuries reported are very large and this is a huge concern for the older population. Pharmacists and doctors must anticipate and weigh these adverse effects against the therapeutic benefits when putting an older patient on quetiapine.

El-Saifi, N., Moyle, W., Jones, C. and Tuffaha, H. (2016), Quetiapine safety in older adults: a systematic literature review. Journal of Clinical Pharmacy and Therapeutics, 41: 7–18. doi: 10.1111/jcpt.12357

Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study

A study investigated the use of benzodiazepines the risk of it causing dementia or rapid cognitive decline. Benzodiazepines are used among 9-12% of older adults in the United States to treat anxiety and insomnia. Drugs that fall into this class are not recommended for long term use in older adults due to the associated increased risk of falls and delirium. Single dose studies found that benzodiazepines impair memory and attention span, but its effect in long term use is still uncertain. One problem with determining if long term benzodiazepine use increases the risk of dementia is that dementia is often preceded by anxiety and insomnia: symptoms often treated with benzodiazepines. Two out of three known studies that considered early dementia symptoms and potential for reverse causation reported an increased risk of dementia with benzodiazepine use.

The investigators hypothesized that cumulative, heavier benzodiazepine exposure over a long period of time was the most likely mechanism to cause an increased risk of dementia. The study was conducted within an integrated healthcare delivery system in the North West US. There were 3434 randomly selected participants in the study aged 65 or older who did not have dementia at the start of the study. Every two years, the cognitive abilities screening instrument (CASI) was administered to test for dementia. It was also used to assess cognitive trajectory. Computerized pharmacy data was use to define benzodiazepine exposure associated with risk of dementia. This consisted of the total standardized daily doses (TSDDs) over a 10 year period. The date of onset dementia was made the midpoint between the visit triggering the dementia evaluation and the visit before that.

While the study found a slightly higher risk of dementia associated with the lowest use of benzodiazepine, it did not find an increased risk in those using the highest level. Therefore, the findings do not support the theory that cumulative use of benzodiazepines at levels used in our population has a causal relationship to increased risk of cognitive decline or dementia. However, the study did not investigate acute adverse cognitive effects that can occur upon starting benzodiazepine treatment in older adults. Healthcare providers should still avoid benzodiazepine use in older adults to prevent other important adverse effects. Considering that other studies did report a causal relationship, it seems that this is a topic that still requires more investigation.

Gray GL, Dublin S, Yu O, et al. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. BMJ. 2016;352:90.