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Medical News & Perspectives
March 25, 2020

Matters of the Mind—Sleep Medications and Dementia Risk, Depression and Weight Gain, Opioids and Mental Disorders

JAMA. Published online March 25, 2020. doi:10.1001/jama.2020.1836

Recent studies have assessed the relationship between sedentary behavior and depressive symptoms in adolescents, whether benzodiazepines or z-hypnotics increase dementia risk, and how opioid prescribing rates differ among people with certain psychiatric illnesses compared with the general public.

Less Physically Active Teens Might Have Higher Depression Risk

Younger adolescents who stay physically active during their teens might help lower their risk of depressive symptoms at age 18 years, a recent study in The Lancet Psychiatry suggests.

Depression appears to be increasing among adolescents, the authors wrote. They cited a US study that showed that the 12-month prevalence of major depressive episodes in teens rose from 8.7% in 2005 to 11.3% in 2014.

London researchers distributed hip-worn accelerometers to measure how physically active a population-based cohort of UK adolescents were at ages 12, 14, and 16 years and compared those findings with results from a standardized mental health assessment when they were 18 years old. The scientists had accelerometer data for 1220 teens at all 3 age points and for 2486 at 1 or more time points.

To the best of their knowledge, the authors wrote, theirs was the first study to use repeated objective measures instead of self-reported data to examine whether physical activity levels and sedentary behavior were associated with depressive symptoms in adolescents. Self-reported information about physical activity is subject to biases, such as recall and mood, the authors noted.

The accelerometer data showed that total physical activity decreased as the adolescents got older, driven by a decline in light physical activity and an increase in sedentary behavior.

Depression scores at age 18 years were 8% to 11% lower for every additional 60 minutes per day of light activity at ages 12, 14, and 16 years. Depression scores were 8% to 11% higher for every additional hour of sedentary behavior per day.

However, total physical activity and moderate to vigorous physical activity weren’t consistently associated with depressive symptoms, possibly because the study was underpowered to detect that, the authors wrote. Only 50 participants at baseline got at least 60 minutes of moderate to vigorous physical activity per day, as recommended by UK national guidelines.

Light activity could include standing during some classes, having to walk distances between classes, or engaging in hobbies such as playing a musical instrument or painting, the authors wrote. They noted that a variety of psychosocial and biological mechanisms could explain why physical activity might influence depressive symptoms. They include stimulating neuroplasticity in brain regions connected to depression, reducing inflammation, or promoting self-esteem.

Sleep Medications Linked to Higher Dementia Risk

Using benzodiazepines (BZDs) or z-hypnotics may increase the risk of developing dementia, scientists in Taiwan recently reported in Neurotherapeutics.

The researchers identified 260 502 people aged 65 years or older in Taiwan’s National Health Insurance Research Database who were newly prescribed oral BZDs or z-hypnotics between 2003 and 2012.

Z-hypnotics are nonbenzodiazepines with similar clinical effects. They include zaleplon (Sonata), zolpidem (Ambien, Intermezzo), and zopiclone. (Zopiclone is not approved in the United States, but eszopiclone, a stereoisomer of zopiclone, is sold under the brand name Lunesta, among others.)

Compared with nonusers, older people who used BZDs or z-hypnotics for more than 28 days during each quarter of the year had a greater risk of dementia during the follow-up period. The risk was even more pronounced in patients who took both types of drugs at the same time. Paradoxically, short-acting BZDs were associated with a greater risk of dementia than long-acting BZDs. People who used a combination of short-acting and long-acting BZDs as well as a z-hypnotic were nearly 5 times more likely to be diagnosed with dementia than people who didn’t use any of the drugs.

One limitation of their study, the authors noted, was that their data set did not include some factors related to cognitive decline, such as education, smoking, alcohol consumption, family history, apolipoprotein E4 status, and baseline cognitive function.

Still, in an accompanying editorial, 2 University of Florida cognition scientists called the study’s finding “alarming” and deserving of “additional scrutiny of prescribing habits and susceptibility to neurodegenerative changes.”

Opioid Dispensing Among Patients With Serious Mental Illness

People with serious mental illness, who are most at risk of developing opioid-related problems, are also more likely to be prescribed opioids than individuals without mental illness, a recent study in BMC Psychiatry concluded.

The study’s authors noted that people with mental illness may also have particularly high rates of chronic noncancer pain. More frequent complaints of pain, higher pain intensity, and the more chronic nature of pain reported in some people with mental health disorders can make them much more likely to be prescribed an opioid than people without mental health problems, although evidence of the drugs’ effectiveness over the long-term is lacking, the researchers wrote. To date, however, the authors said, little is known about opioid prescribing rates among people with mental illness.

For the BMC Psychiatry study, the researchers, who were from Georgia State University in Atlanta and several Kaiser Permanente locations, analyzed electronic medical record data from the 13 sites that make up the Mental Health Research Network, funded by the National Institute of Mental Health.

They identified 65 750 people diagnosed with major depressive disorder (MDD), 38 117 with bipolar disorder, and 12 916 with schizophrenia or schizoaffective disorder and matched them on age, sex, and Medicare status to controls with no documented mental illness. All were aged 18 to 70 years and had insurance.

The scientists examined data about chronic non–cancer pain diagnoses and prescription opioid medication dispensing. After accounting for age, sex, race, income, medical comorbidities, and health care utilization, they found that having an MDD or bipolar disorder diagnosis increased the odds of being diagnosed with chronic noncancer pain by nearly 2-fold. Conversely, having a schizophrenia diagnosis was linked with a 14% lower chance of having the pain diagnosis.

What’s more, patients with a bipolar disorder or MDD diagnosis were, respectively, 2 and 2 ½ times more likely to receive an opioid prescription, even after accounting for potential confounders as well as a chronic pain diagnosis.

The relationship between depressive symptoms and opioid use is likely bidirectional, the authors wrote. Although people with MDD or bipolar disorder might present with more severe pain that results in an opioid prescription than people without either condition, prior research suggests that chronic opioid use can increase the risk of depression.

Having a schizophrenia diagnosis was not associated with receiving opioids. One possible explanation is that people with schizophrenia might have reduced sensitivity to pain compared with individuals without psychiatric illness. And research has shown that antipsychotics have analgesic qualities. On the other hand, the authors wrote, people with schizophrenia might experience as much pain as those with other mental illnesses, but they might be less likely to express it.

The authors noted that their study had some limitations: Data about opioid prescriptions might not necessarily represent patients’ actual medication use. Plus, patients with 2 or more mental health diagnoses were classified as having only the one the researchers ranked as most serious, with schizophrenia first, bipolar disorder second, and mood disorder third. And, because all the patients in their sample had health care coverage, the findings might not be generalizable to uninsured populations.

Some have called for mental health clinicians to help manage pain in patients with psychiatric disorders, the authors noted, but added that more research is needed to evaluate the effectiveness of doing so.

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