Pain can be a self-fulfilling prophecy: New brain imaging research shows that when we expect something to hurt it does, even if the stimulus isn't so painful -- ScienceDailyUnbeknownst to the subjects, heat intensity was not actually related to the preceding cue. The study found that when subjects expected more heat, brain regions involved in threat and fear were more activated as they waited. Regions involved in the generation of pain were more active when they received the stimulus. Participants reported more pain with high-pain cues, regardless of how much heat they actually got. "This suggests that expectations had a rather deep effect, influencing how the brain processes pain," said Jepma. Surprisingly, their expectations also highly influenced their ability to learn from experience. Many subjects demonstrated high "confirmation bias" -- the tendency to learn from things that reinforce our beliefs and discount those that don't. For instance, if they expected high pain and got it, they might expect even more pain the next time. But if they expected high pain and didn't get it, nothing changed.
What if the Placebo Effect Isn’t a Trick? - The New York TimesWill this work destroy the stuff that actually has to do with wisdom, preciousness, imagination, the things that are actually critical to who we are as human beings?” he asks. His answer: “I don’t know, but I have to believe there is an infinite reserve of wisdom and imagination that will resist being reduced to simple materialistic explanations.”
What if the Placebo Effect Isn’t a Trick? - The New York TimesThe subjects were randomly divided into four groups, following standard clinical-trial protocol, and received a daily dose of either vitamin E, aspirin, vitamin E with aspirin or a placebo. A subset also had their DNA sampled — which, Hall realized, offered her a vastly larger genetic database to plumb for markers correlated to placebo response. Analyzing the data amassed during the first 10 years of the study, Hall found that the women with the low-COMT gene variant had significantly higher rates of heart disease than women with the high-COMT variant, and that the risk was reduced for those low-COMT women who received the active treatments but not in those given placebos. Among high-COMT people, the results were the inverse: Women taking placebos had the lowest rates of disease; people in the treatment arms had an increased risk.
What if the Placebo Effect Isn’t a Trick? - The New York TimesA 2015 study published in the journal Pain analyzed 84 clinical trials of pain medication conducted between 1990 and 2013 and found that in some cases the efficacy of placebo had grown sharply, narrowing the gap with the drugs’ effect from 27 percent on average to just 9 percent. The only studies in which this increase was detected were conducted in the United States, which has spawned a variety of theories to explain the phenomenon: that patients in the United States, one of only two countries where medications are allowed to be marketed directly to consumers, have been conditioned to expect greater benefit from drugs; or that the larger and longer-duration trials more common in America have led to their often being farmed out to contract organizations whose nurses’ only job is to conduct the trial, perhaps fostering a more placebo-triggering therapeutic interaction.
What if the Placebo Effect Isn’t a Trick? - The New York TimesThe discovery of this genetic correlation to placebo response set Hall off on a continuing effort to identify the biochemical ensemble she calls the placebome — the term reflecting her belief that it will one day take its place among the other important “-omes” of medical science, from the genome to the microbiome. The rs4680 gene snippet is one of a group that governs the production of COMT, and COMT is one of a number of enzymes that determine levels of catecholamines, a group of brain chemicals that includes dopamine and epinephrine. (Low COMT tends to mean higher levels of dopamine, and vice versa.) Hall points out that the catecholamines are associated with stress, as well as with reward and good feeling, which bolsters the possibility that the placebome plays an important role in illness and health, especially in the chronic, stress-related conditions that are most susceptible to placebo effects.
What if the Placebo Effect Isn’t a Trick? - The New York TimesThe findings of the I.B.S. study were in keeping with a hypothesis Kaptchuk had formed over the years: that the placebo effect is a biological response to an act of caring; that somehow the encounter itself calls forth healing and that the more intense and focused it is, the more healing it evokes. He elaborated on this idea in a comparative study of conventional medicine, acupuncture and Navajo “chantway rituals,” in which healers lead storytelling ceremonies for the sick. He argued that all three approaches unfold in a space set aside for the purpose and proceed as if according to a script, with prescribed roles for every participant. Each modality, in other words, is its own kind of ritual, and Kaptchuk suggested that the ritual itself is part of what makes the procedure effective, as if the combined experiences of the healer and the patient, reinforced by the special-but-familiar surroundings, evoke a healing response that operates independently of the treatment’s specifics. “Rituals trigger specific neurobiological pathways that specifically modulate bodily sensations, symptoms and emotions,” he wrote. “It seems that if the mind can be persuaded, the body can sometimes act accordingly.”
Sugar pills relieve pain for chronic pain patients: Placebo benefits can be predicted by brain anatomy and psychological traits -- ScienceDailyAbout 60 chronic back pain patients were randomized into two arms of the study. In one arm, subjects didn't know if they got the drug or the placebo. Researchers didn't study the people who got the real drug. The other study arm included people who came to the clinic but didn't get a placebo or drug. They were the control group. The individuals whose pain decreased as a result of the sugar pill had a similar brain anatomy and psychological traits. The right side of their emotional brain was larger than the left, and they had a larger cortical sensory area than people who were not responsive to the placebo. The chronic pain placebo responders also were emotionally self-aware, sensitive to painful situations and mindful of their environment. "Clinicians who are treating chronic pain patients should seriously consider that some will get as good a response to a sugar pill as any other drug," Apkarian said. "They should use it and see the outcome. This opens up a whole new field."
Visual illusion proves effective in relieving knee pain for people with osteoarthritis -- ScienceDailyUniSA researcher and NHMRC Career Development Fellow, Dr Tasha Stanton says the research combined visual illusions and touch, with participants reporting up to a 40 per cent decrease in pain when presented with an illusion of the knee and lower leg elongated. "We also found that the pain reduction was optimal when the illusion was repeated numerous times -- that is, its analgesic effect was cumulative," Dr Stanton says. The small study -- 12 participants -- focused on people over 50 years with knee pain, and a clinical diagnosis of osteoarthritis. Dr Stanton says the research provides "proof of concept" support that visual illusions can play a powerful role in reducing pain.
Lessons learned from placebo groups in antidepressant trialsThe analysis of ‘nocebo effects’, e.g. adverse effects in placebo groups of antidepressant trials also confirms the impact of expectations: nocebo symptoms reflected the typical side-effect patterns expected in the drug group, with higher symptoms rates in the placebo groups of tricyclic antidepressant trials compared with placebo groups of trials testing selective serotonin reuptake inhibitors.
Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial - EBioMedicineUsing truthful or deceiving verbal instructions, we tested how expectancies influence SSRI efficacy in social anxiety disorder. The number of responders was more than three times higher after open administration of escitalopram 20 mg compared to covert administration of the drug presented as “active placebo” in a cover story. Correct vs. incorrect information about the SSRI also yielded different neural changes in brain areas involved in emotion-cognition interactions.
Antidepressants and the Placebo EffectMany patients in clinical trials realize that they have been given the real drug, rather than the placebo, most likely because of the drug’s side effects. What effect is this likely to have in a clinical trial? We do not have to guess at the answer to this question. Bret Rutherford and his colleagues at Columbia University have provided the answer. They examined the response to antidepressants in studies that did not have a placebo group with those in studies where they did have a placebo group (Rutherford, Sneed, & Roose, 2009). The main difference between these studies is that in the first case, the patients were certain they were getting an active antidepressant, where as in the placebo-controlled trials, they knew that they might be given a placebo. Knowing for sure that they were getting an active drug boosted the effectiveness of the drug significantly. This supports the hypothesis that the relatively small difference between drug and placebo in antidepressant trials are at least in part due to “breaking blind” and discerning that one is in the drug group, because of the side effects produced by the drug.
Antidepressants and the Placebo EffectYet this 11% figure may overestimate the number of people who benefit from antidepressants. Antidepressants are also prescribed to people who do not qualify for the diagnosis of major depression. My neighbor’s pet dog died; his physician prescribed an antidepressant. A friend in the US was diagnosed with lumbar muscle spasms and was prescribed an antidepressant. I have lost count of the number of people who have told me they were prescribed antidepressants when complaining of insomnia – even though insomnia is a frequently reported side effect of antidepressants. About 20% of patients suffering from insomnia in the United States are given antidepressants as a treatment by their primary care physicians (Simon & VonKorff, 1997), despite the fact that “the popularity of antidepressants in the treatment of insomnia is not supported by a large amount of convincing data, but rather by opinions and beliefs of the prescribing physicians” (Wiegand, 2008, p. 2411).
Antidepressants and the Placebo EffectMore important, in both analyses, the mean difference between drug and placebo was less than two points on the HAM-D. The HAM-D is a 17-item scale on which people can score from 0 to 53 points, depending on how depressed they are. A six-point difference can be obtained just by changes in sleep patterns, with no change in any other symptom of depression. So the 1.8 difference that we found between drug and placebo was very small indeed – small enough to be clinically insignificant. But you don’t have to take my word for how small this difference is. The National Institute for Health and Care Excellence (NICE), which drafts treatment guidelines for the National Health Service in the United Kingdom, has established a three-point difference between drug and placebo on the HAM-D as a criterion of clinical significance (NICE, 2004). Thus, when published and unpublished data are combined, they fail to show a clinically significant advantage for antidepressant medication over inert placebo.
Even open-label placebos work, if they are explained -- ScienceDailyFor the first time, researchers from the University of Basel, along with colleagues from Harvard Medical School, have compared the effects of administering open-label and deceptive placebos. The team conducted an experimental study with 160 healthy volunteers who were exposed to increasing heat on their forearm via a heating plate. The participants were asked to manually stop the temperature rise as soon as they could no longer stand the heat. After that, they were given a cream to relieve the pain. Some of the participants were deceived during the experiment: they were told that they were given a pain relief cream with the active ingredient lidocaine, although it was actually a placebo. Other participants received a cream that was clearly labeled as a placebo; they were also given fifteen minutes of explanations about the placebo effect, its occurrence and its effect mechanisms. A third group received an open-label placebo without any further explanation. The subjects of the first two groups reported a significant decrease in pain intensity and unpleasantness after the experiment. "The previous assumption that placebos only work when they are administered by deception needs to be reconsidered," says Dr. Cosima Locher, a member of the University of Basel's Faculty of Psychology and first author of the study.
New study on the placebo effect and antidepressants in children and adolescents -- ScienceDailyThe results of the meta-analysis show that, although antidepressants work significantly better than placebos across the range of disorders, the difference is small and varies according to the type of mental disorder. However, the results also showed that the placebo effect played a significant role in the efficacy of antidepressants. The study also found that patients treated with antidepressants complained of greater side effects than those who received a placebo. The side effects included everything from mild symptoms such as headaches to suicidal behavior. Placebo effect stronger in cases of depression According to the study, the effects of antidepressants and placebos vary according to the type of mental disorder: antidepressants have a greater specific effect in the case of anxiety disorders than depressive disorders. On the other hand, placebos have a stronger effect in depressed patients than in those with an anxiety disorder. Lead authors Dr. Cosima Locher and Helen Koechlin from the Division of Clinical Psychology & Psychotherapy at the University of Basel's Faculty of Psychology see potential here for new treatment concepts. These would make use of factors contributing to the placebo effect, applying them specifically to the treatment of depression.
Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence | The BMJConclusions Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base.
With health care cuts looming, low-cost magnesium a welcome option for treating depression -- ScienceDailyThe researchers at the University of Vermont's Larner College of Medicine conducted an open-label, blocked, randomized cross-over trial involving 126 adults in outpatient primary care clinics. The study participants, who were currently experiencing mild-to-moderate depression, had a mean age of 52, with 38 percent of them male. Participants in the active arm of the study received 248 milligrams of elemental magnesium per day over six weeks, while those in the control arm received no treatment. Depression symptom assessments were conducted on all participants on a bi-weekly basis. The study team found that in 112 participants with analyzable data, consumption of magnesium chloride for six weeks resulted in a clinically significant improvement in measures of depression and anxiety symptoms. In addition, these positive effects were shown quickly, at two weeks, and the supplements were well tolerated and similarly effective regardless of age, sex, or use of antidepressants, among other factors.
Psychological and pharmacological interventions for social anxiety disorder in adults: a systematic review and network meta-analysis - The Lancet PsychiatryIndividual CBT compared with psychological placebo (SMD −0·56, 95% CrI −1·00 to −0·11), and SSRIs and SNRIs compared with pill placebo (−0·44, −0·67 to −0·22) were the only classes of interventions that had greater effects on outcomes than appropriate placebo. Individual CBT also had a greater effect than psychodynamic psychotherapy (SMD −0·56, 95% CrI −1·03 to −0·11) and interpersonal psychotherapy, mindfulness, and supportive therapy (−0·82, −1·41 to −0·24). Interpretation Individual CBT (which other studies have shown to have a lower risk of side-effects than pharmacotherapy) is associated with large effect sizes. Thus, it should be regarded as the best intervention for the initial treatment of social anxiety disorder. For individuals who decline psychological intervention, SSRIs show the most consistent evidence of benefit.
Single dose of hallucinogenic drug psilocybin relieves anxiety and depression in patients with advanced cancer | EurekAlert! Science NewsPublished in the Journal of Psychopharmacology online Dec.1, the study showed that one-time treatment with the hallucinogenic drug psilocybin -- whose use required federal waivers because it is a banned substance -- quickly brought relief from distress that then lasted for more than six months in 80 percent of the 29 study subjects monitored, based on clinical evaluation scores for anxiety and depression. The NYU Langone-led study was published side by side with a similar study from Johns Hopkins. Study results were also endorsed in 11 accompanying editorials from leading experts in psychiatry, addiction, and palliative care. "Our results represent the strongest evidence to date of a clinical benefit from psilocybin therapy, with the potential to transform care for patients with cancer-related psychological distress," says study lead investigator Stephen Ross, MD, director of substance abuse services in the Department of Psychiatry at NYU Langone. "If larger clinical trials prove successful, then we could ultimately have available a safe, effective, and inexpensive medication -- dispensed under strict control -- to alleviate the distress that increases suicide rates among cancer patients," says Ross, also an associate professor of psychiatry at NYU School of Medicine. Study co-investigator Jeffrey Guss, MD, a clinical assistant professor of psychiatry at NYU Langone, notes that psilocybin has been studied for decades and has an established safety profile. Study participants, he says, experienced no serious negative effects, such as hospitalization or more serious mental health conditions. Although the neurological benefits of psilocybin are not completely understood, it has been proven to activate parts of the brain also impacted by the signaling chemical serotonin, which is known to control mood and anxiety. Serotonin imbalances have also been linked to depression. For the study, half of the participants were randomly assigned to receive a 0.3 milligrams per kilogram dose of psilocybin while the rest received a vitamin placebo (250 milligrams of niacin) known to produce a "rush" that mimics a hallucinogenic drug experience. Approximately half way through the study's monitoring period (after seven weeks), all participants switched treatments. Those who initially received psilocybin took a single dose of placebo, and those who first took niacin, then received psilocybin. Neither patients nor researchers knew who had first received psilocybin or placebo. Guss says, "The randomization, placebo control, and double-blind procedures maximized the validity of the study results." One of the key findings was that improvements in clinical evaluation scores for anxiety and depression lasted for the remainder of the study's extended monitoring period -- specifically, eight months for those who took psilocybin first.
Placebo sleep affects cognitive functioning. - PubMed - NCBI↓ Full text Placebo sleep affects cognitive functioning. Draganich C, et al. J Exp Psychol Learn Mem Cogn. 2014. Show full citation Abstract The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether perceived sleep quality affects cognitive functioning, 164 participants reported their previous night's sleep quality. They were then randomly assigned to 1 of 2 sleep quality conditions or 2 control conditions. Those in the "above average" sleep quality condition were informed that they had spent 28.7% of their total sleep time in REM, whereas those in the "below average" sleep quality condition were informed that they had only spent 16.2% of their time in REM sleep. Assigned sleep quality but not self-reported sleep quality significantly predicted participants' scores on the Paced Auditory Serial Addition Test and Controlled Oral Word Association Task. Assigned sleep quality did not predict participants' scores on the Digit Span task, as expected, nor did it predict scores on the Symbol Digit Modalities Test, which was unexpected. The control conditions showed that the findings were not due to demand characteristics from the experimental protocol. These findings supported the hypothesis that mindset can influence cognitive states in both positive and negative directions, suggesting a means of controlling one's health and cognition.
Tickling the brain can boost immunity: study"Feeding and sex expose one to bacteria," explained Rolls said. "It would give one an evolutionary advantage if -- when the reward system is activated -- immunity is also boosted."
In the Stroop task, which measures reaction time, improved accuracy was observed in subjects who believed they had ingested caffeinated coffee, even if they had only consumed decaf. Subjects who received caffeine and were told they were drinking decaf did not show an improved reaction time. Likewise, in a measure of reward motivation, the Card Arranging Reward Responsivity Objective Test, the participants who believed they had consumed caffeine sorted the cards more quickly than those who believed they’d consumed decaf.