Antipsychotics and Mortality in Dementia

PsychiatryOnline | American Journal of Psychiatry | Antipsychotics and Mortality in Dementia
Commentary on Kales study Am J Psychiatry 2012;169:71-79

The study examined the relative risk of mortality associated with newly commenced prescriptions of olanzapine, quetiapine, and haloperidol, compared with risperidone as the reference compound, in a cohort of more than 30,000 veterans with dementia, ages 65 years and older.

Which antipsychotic has the highest and lowest risk of mortality?

Haloperidol was associated with significantly greater mortality than risperidone (relative risk=1.54).
Several studies have suggested that haloperidol confers a greater mortality risk than atypical antipsychotics (9), but the Kales et al. report is one of the few to have systematically compared mortality risk between different atypical antipsychotic agents.
Olanzapine and risperidone had similar mortality risk, while the risk for quetiapine was significantly lower (relative risk=0.73).
A key observation is that the highest increase in mortality risk was in the first 120 days, particularly in the first 30 days for haloperidol.

Which antipsychotic is best for aggression, agitation, or psychosis?

...three randomized controlled trials of quetiapine did not demonstrate any effectiveness in the treatment of aggression, agitation, or psychosis (4, 5).
The best evidence of efficacy is for risperidone, with consistent evidence of a modest but significant benefit over 12 weeks in the treatment of both aggression and psychosis.
There is also evidence of a similar level of benefit with aripiprazole, olanzapine, and haloperiodol, but only a few studies have examined other agents.
Through balancing the mortality data from this study and efficacy data from previous randomized controlled trials, risperidone and olanzapine emerge as the best evidence-based options.

What harms are associated with antipsychotic use?

...extrapyramidal symptoms, sedation, gait disturbances, and falls.
Many agents also lead to anticholinergic side effects, including delirium (4).
Tardive dyskinesia with atypical antipsychotics appears to occur less frequently than with typical antipsychotics, but QTc prolongation has been reported as a significant problem associated with several atypical antipsychotics.
A meta-analysis also identified a significant increase in respiratory and urinary tract infections as well as peripheral edema in people treated with risperidone, compared with placebo (4). These are likely to be class effects of atypical antipsychotics.
It has also become clear that other, more serious adverse outcomes, such as stroke and related cerebrovascular events, accelerated cognitive decline, and death, are significantly increased in people with dementia who are prescribed antipsychotics, compared with people with dementia not treated with these agents.
Deaths related to bronchopneumonia, thrombo-embolic events (including stroke and pulmonary embolism), and sudden cardiac arrhythmias are all significantly increased in people with dementia receiving antipsychotic treatment (6).
...meta-analyses of randomized controlled trials have reported significant incidence of sedation, chest-infection, and dehydration (4)

1.5- to 1.7-fold increase in mortality risk for people with Alzheimer's disease receiving antipsychotics

What can we do to reduce the harms associated with antipsychotic use?

...monitoring fluid intake and promoting vigilance for early detection and treatment of chest infections, may offer important potential opportunities to reduce excess mortality.
The potential role of ECG monitoring for prolonged QTc interval should perhaps also be considered

What about the use of non-psychotics like valproic acid?

The mortality risk for valproic acid and its derivatives, which were included as a nonantipsychotic comparison, was generally higher than the risk for quetiapine and similar to that for risperidone.

See guidelines below from UK Alzheimer's Society:

Optimising treatment and care for behavioural and psychological symptoms of dementia: A best practice guide

Obesity Counseling in Primary Care

Articles from NEJM

A Two-Year Randomized Trial of Obesity Treatment in Primary Care Practice 

by Wadden et al.

Practice Based Opportunities for WEight Reduction (POWER) Trial at Penn.
Enhanced weight-loss counseling (quarterly PCP visits combined with brief monthly sessions with lifestyle coaches who instructed participants about behavioral weight control PLUS meal replacements or weight-loss medication (orlistat or sibutramine)) helps about one third of obese patients achieve long-term, clinically meaningful weight loss.

Comparative Effectiveness of Weight-Loss Interventions in Clinical Practice

by Appel et al.

In two behavioral interventions, one delivered with in-person support and the other delivered remotely, without face-to-face contact between participants and weight-loss coaches, obese patients achieved and sustained clinically significant weight loss over a period of 24 months.

Obesity Treatment in Primary Care — Are We There Yet?

Editorial by Dr. Yanovski

Wadden study: "Although weight loss in the brief-lifestyle-counseling group (2.9 kg) and the usual-care group (1.7 kg) did not differ significantly at 2 years, participants in the enhanced-lifestyle-counseling group lost significantly more weight (4.6 kg) than did those in either of the other two groups and were more likely to lose at least 5% of their initial body weight (35% in the enhanced-lifestyle-counseling group, vs. 26% in the brief-lifestyle-counseling group and 22% in the usual-care group)."

Appel study: "Weight loss at 2 years was similar in the groups that received in-person support (5.1 kg) and remote support (4.5 kg) and was significantly greater than the weight loss in the control group (0.8 kg). Participants assigned to either the in-person or the remote lifestyle intervention were twice as likely as those assigned to the control group to have lost 5% or more of their initial body weight at 2 years (41% for the in-person group and 38% for the remote group, vs. 19% for the control group)."

"A well-recognized issue that affects the sustainability of behavioral interventions is that attendance at face-to-face counseling sessions decreases substantially over time."

"Given that remotely delivered coaching resulted in weight-loss outcomes similar to those of in-person visits, the use of mobile technologies to deliver behavioral weight-loss treatment in primary care appears to be promising. Such interventions may present fewer barriers to adherence than interventions delivered in person, since they allow for greater scheduling flexibility, decreased travel time, and lower transportation costs. In addition, a telephone-based coaching program has the potential for widespread implementation in multiple practice settings, including geographically isolated areas."

"Determining the costs and cost-effectiveness of these and other treatments in primary care settings is crucial. In addition, these two studies were not powered to detect differences in cardiovascular risk reduction, and there were no consistent between-group differences with respect to lipid levels, glucose levels, or blood pressure at 2 years."

MEDICARE COVERS SCREENING AND COUNSELING FOR OBESITY

The services will be free to beneficiaries — the Medicare deductible and co-pay will not apply.

(From Medscape) Medicare patients are eligible for "intensive behavioral therapy for obesity" from primary care providers — nonphysicians included — in a primary care setting if their body mass index (BMI) is 30 kg/m2 or more. They are entitled to 1 face-to-face counseling visit each week for a month, followed by a face-to-face session every other week for an additional 5 months.

If a patient has lost at least 6.6 pounds during the first 6 months of counseling, he or she is entitled to an additional visit every month for another 6 months. For patients who fail to lose the required weight, "a reassessment of their readiness to change and BMI is appropriate after an additional 6-month period," according to CMS.

Specific services reimbursable under Medicare include an obesity screening, an assessment of the patient's diet, and behavioral counseling and therapy to promote sustained weight loss through diet and exercise. This course of treatment does not include medications for losing weight. CMS noted that the US Preventive Services Task Force had omitted medication from its recommendation for obesity screening and therapy for adults because of concerns about adverse drug events and lack of evidence about patients maintaining their weight after they stop taking such medications.

It remains to be seen what Medicare will pay for obesity counseling. In a "decision memo" published online, CMS stated that it is in the process of establishing payment codes.

The Rain Stick

This insightful and truthful poem + commentary was shared with me by a medical student.

The Rain Stick (from Academic Medicine)

Upend the rain stick and what happens next

Is a music that you never would have known

To listen for. In a cactus stalk

Downpour, sluice-rush, spillage and backwash

Come flowing through. You stand there like a pipe

Being played by water, you shake it again lightly

And diminuendo runs through all its scales

Like a gutter stopping trickling. And now here comes

A sprinkle of drops out of the freshened leaves,

Then subtle little wets off grass and daisies;

Then glitter-drizzle, almost-breaths of air.

Upend the stick again. What happens next

Is undiminished for having happened once,

Twice, ten, a thousand time before.

Who cares if all the music that transpires

Is the fall of grit or dry seeds through a cactus?

You are like a rich man entering heaven

Through the ear of a raindrop. Listen now again.

By Seamus Heaney


Commentary by Dr. Connelly

"The Rain Stick contains secrets for all who want to, try to, and long to heal and care for others. The opening lines direct the reader toward a mystery that is not often acknowledged in medicine, the mystery of not-knowing. "

"True understanding requires the physician to follow the narrative thread, ask questions to clarify asides, and listen on many levels. Learning from The Rain Stick interested physicians could ask:

If I engage this patient from a perspective of not-knowing, how might I be surprised? If I am open, interested, curious about the patient, what might I understand about him or her or even myself?"

"The impression that patients are static objects is flawed. ... Heaney reminds us that no experience is routine or everyday. Each patient no matter how routine the symptom, as seen by the physician, holds a unique experience within."

"Who cares if all the music that transpires/Is the fall of grit or dry seeds through a cactus?

As judgments precede interactions, physicians become closed, not interested, not curious, not receptive, not caring. And in this diminished state, they do not see or hear the truth arising in the experience with the other."

"... many physicians fear being open and vulnerable with patients. Yet, a closer look at the fear may reveal a deep and personal misunderstanding. Fear does not require abandonment of self. This discomfort can easily be diminished by direct and real human contact as demonstrated by true listening such that the other feels heard and understood."

"Ultimately physicians may be able to share interpersonal lessons and kindness as well as nurturing the potential for personal growth, change, even transformation, if they are willing to-listen now again."

Discussing Overall Prognosis with the Very Elderly — NEJM

Discussing Overall Prognosis with the Very Elderly — NEJM

Perspective article.

"offering to discuss overall prognosis with very elderly patients should be the norm, not the exception."

"We would suggest that clinicians should routinely offer to discuss the overall prognosis for elderly patients with a life expectancy of less than 10 years, or at least by the time a patient reaches 85 years of age. By that age, the average remaining life expectancy in the United States is 6 years; 85-year-old Americans have a 75% chance of living 3 more years and a 25% chance of living 10 more years"

"For patients with a life expectancy of more than 10 years, cancer screening, intensive blood-pressure management, and tight control of glycated hemoglobin levels will have high priority, whereas for patients with a shorter life expectancy, priority might be given to reducing the pill burden and engaging in advance care planning."

"Avoiding burdensome and potentially risky interventions of limited benefit may improve a patient's functional abilities and quality of life."

"a majority of elderly patients (65%) might want to discuss prognosis, whereas a substantial minority might not. Clinicians should therefore offer to discuss overall prognosis with very elderly patients — but respect those who decline."

See Table: Common Medical Decisions and Life Choices That Offer Opportunities to Discuss Overall Prognosis with Very Elderly Patients.

"To make care more patient-centered, we need to start helping our very elderly patients set goals of care that take their overall prognosis into account. We should do so in the ordinary course of clinical practice, letting our patients be our guides."

Neurology - Dementia Article | Vitamin D-Mentia: Randomized Clinical Trials Should Be the Next Step

Neurology - Dementia Article | Vitamin D-Mentia: Randomized Clinical Trials Should Be the Next Step

Annweiler C et al. – Hypovitaminosis D is highly prevalent in the elderly. Its possible role in the pathogenesis of Alzheimer’s disease (AD) is particularly important, as AD remains a public health concern with no current efficient treatment. Vitamin D administration could be a multitarget stabilizing treatment for AD since vitamin D simultaneously targets several factors leading to neurodegeneration through immunoregulatory, antioxidant and anti-ischemic actions, as well as the regulation of neurotrophic factors, acetylcholine neurotransmitter and clearance of amyloid beta peptide, and the avoidance of hyperparathyroidism.

Neuroepidemiology , 12/08/2011 Clinical Article

Cholecalciferol (vitamin D3) reduces mortality in adults; other forms of vitamin D do not

ACPJC article.
Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults.
Cochrane Database Syst Rev. 2011;(7):CD007470.

In meta-analysis, cholecalciferol (vitamin D3) reduced all cause mortality by 6% (NNT 161).

Systematic pain management reduced agitation in nursing home residents with dementia

ACPJC article.
Husebo BS, Ballard C, Sandvik R, Nilsen OB, Aarsland D. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial.
BMJ. 2011;343:d4065.