Dummy pills and pain relief; the connection between hostility and heart attacks in women with diabetes; and insomnia is not simply an adverse effect of depression

Matters of the Mind: Honest Placebos, Hostility and Heart Attacks, and Sleepless Nights. Rita Rubin. JAMA, October 3, 2019. doi:10.1001/jama.2019.15983

Dummy pills and pain relief, the connection between hostility and heart attacks in women with diabetes, and the notion that insomnia is not simply an adverse effect of depression have been the focus of recent studies.


“Honest” Placebos Might Help Relieve Back Pain

Until recently, the conventional wisdom was that placebo treatments worked only if patients who received them didn’t know they were placebos.

But not telling patients that sugar pills or saline injections are placebos raises ethical and legal questions related to informed consent.

Researchers have started to investigate the effectiveness of prescribing placebos with patients’ full knowledge, an approach called open-label placebo (OLP).

It turns out that the placebo effect can survive disclosure to patients, at least in those with chronic back pain, according to a German study recently published in Pain.

The researchers randomly assigned 127 people aged 19 years or older who had chronic back pain (persisting for at least 12 weeks) to usual care or usual care plus placebo. As part of the informed consent procedure before randomization, participants were shown a video produced by CBS New York that had been translated into German. The video contained information about the placebo effect in general and recent research findings about the potential benefits of OLPs.

Participants randomized to the placebo received capsules made by Zeebo Effect, a Vermont company that markets them as “honest placebos.” They’re not actually sugar pills—they contain microcrystalline cellulose, refined wood pulp commonly used as a food additive. Patients in the placebo group were told the capsules were placebos that they should take twice a day for 21 days.

The combination of OLP with treatment as usual significantly reduced patient-reported pain, disability, and depressive symptoms but not stress or anxiety, the study found. In addition, OLP treatment showed a trend toward reduced demand for analgesic rescue medication to help relieve back pain. However, OLP had no effect on objective measures of spine mobility, such as range of motion. This suggests that the approach wouldn’t work for conditions with primarily objective treatment outcomes, such as cardiovascular or immunological diseases, according to the authors.


Hostility and the Heart in Women With Diabetes

A growing body of evidence suggests that hostility is bad for the heart.

Recent findings reported in Menopause suggest this holds true for postmenopausal women with type 2 diabetes. Researchers tracked 15 029 women aged 50 to 79 years at enrollment, all of whom were participants in the Women’s Health Initiative (WHI), for 10 years on average. All of the women reported being treated for diabetes, either at the beginning of the study or during the follow-up period. None had been diagnosed with cardiovascular disease before entering the study.

At baseline, the researchers administered questionnaires to the women to assess a variety of personality traits.

During follow-up, 1118 cases of nonfatal or fatal myocardial infarction and 710 cases of stroke occurred. After accounting for confounders such as age, race and ethnicity, education, high cholesterol, and family history of myocardial infarction, women in the highest quartile of hostility had a 22% higher risk of a heart attack than women in the lowest quartile. No other personality traits were associated with coronary heart disease (CHD) risk, and there was no statistically significant association between hostility—or any other personality trait—and stroke risk.

In a stratified analysis, though, a higher level of hostility and CHD risk were significantly associated only in women diagnosed with diabetes during the course of the study, not those with the disease at baseline. The researchers speculated that among women with higher hostility, those who weren’t yet diagnosed with diabetes at the beginning of the study might have lived longer with impaired glucose homeostasis, in part because they might be less likely to engage in healthy behaviors such as seeing a physician regularly.

Previous research has found that higher levels of hostility in people with type 2 diabetes raised susceptibility to stress-induced inflammation, a possible explanation for the increased risk of a heart attack. However, another study also based on WHI participants, but not specifically those with diabetes, found that greater hostility was not associated with a higher risk of CHD, while greater optimism was linked to a lower risk.

Personality traits are not easily changed, the authors point out. But, at least, identifying patients with diabetes who have high hostility could lead to the testing of interventions that would help minimize their risk for adverse outcomes.

Sorting Out the Relationship Between Depression and Insomnia

Nearly 90% of people with major depressive disorder (MDD) report disturbed sleep, but a recent study in the Journal of Affective Disorders suggests that MDD and insomnia are comorbid yet separate disorders.

The study involved patients enrolled in the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study, a prospective, randomized clinical trial funded by the National Institutes of Health (NIH) that assessed the efficacy of several antidepressants and cognitive therapy for people with treatment-resistant depression.

The 7-year study enrolled 4041 outpatients aged 18 to 75 years with MDD and tested 4 different medications or medication combinations. The insomnia study assessed the first level of STAR*D, which tested citalopram for 12 or 14 weeks, depending on whether patients responded early or late.

The insomnia study excluded participants who had no postbaseline assessments as well as those who reported sleeping more than average, not less, bringing the total included in the analysis to 2788 people.

At baseline and 5 or 6 times during treatment with citalopram, researchers administered the Quick Inventory of Depressive Symptomology–Clinician Rated (QIDS-C) to assess symptom severity for the previous week. Three of the 16 items on the QIDS-C deal with insomnia, and the researchers combined them to arrive at a global insomnia score. Each QIDS-C item has a maximum score of 3, so the maximum global insomnia score, signifying the most severe insomnia, was 9.

Participants’ global insomnia scores improved over the course of the study. After accounting for age, hypnotic medication use by a quarter of participants, medication dose, and general medical comorbidity, global insomnia scores dropped on average from 6.2 at baseline to 3.7 by week 9 before increasing to 4.4 at the end of the citalopram treatment phase. This further validates the sedative effects of citalopram, the authors wrote.

Patients with more severe depression symptoms at baseline were less likely to achieve MDD remission by the end of the study. Patients with more severe insomnia at baseline were also less likely to achieve MDD remission, which was not explained by the severity of their depression. On the other hand, improved sleep was independent of MDD remission.

These findings support the notion that insomnia is not simply a symptom of MDD but a separate, co-occurring disease process, which, if true, should shift how clinicians conceptualize and treat insomnia and MDD, according to the researchers. For example, they wrote, instead of lumping together excessive sleep and insomnia as a single biological dysfunction when assessing patients with MDD, it might be better to evaluate and treat those sleep disturbances independently with targeted therapies.