Study: Thinking migraine drugs will help will boost the positive effects

According to a study, simply thinking a drug will help the effects of migraine headaches make the drug more effective and boosts the positive effects of the drug.

A new study of migraine sufferers is the latest to demonstrate the remarkable power of the placebo effect, finding that what a doctor tells you when prescribing medicine can influence your body’s response to it. The study, published Wednesday in the journal Science Translational Medicine, compared the effects of the common migraine drug Maxalt (rizatriptan) to an inactive placebo (sugar pill) in 66 sufferers of chronic migraine headaches, a condition whose symptoms include throbbing headaches, nausea, vomiting and sensitivity to light and sound.

The researchers from Harvard Medical School and Beth Israel Deaconess Medical Center (BIDMC) in Boston found that study participants reported relief from the placebos even when they knew they were taking them.

Interestingly, the researchers also found a ‘reverse-placebo’ effect, whereby patients who believed they were getting the placebo found that the real drug did not work as well as it should have.

The so-called ‘placebo effect‘ is a powerful, effective medical treatment and has been found to help treat or reduce the symptoms of a wide variety of conditions such as irritable bowel syndrome (IBS), depression, anxiety, ADHD, restless leg syndrome and others.

However, the current study is the first to quantify how much pain relief is attributed to a drug’s pharmacological effect, and how much to a placebo effect, and demonstrates that a positive message and a powerful medication are both important for effective clinical care.

The study uncovered three key findings: 1) the benefits of Maxalt increased when patients were told they were receiving an effective drug for the treatment of acute migraine; 2) when the identities of Maxalt tablets and placebo pills were switched, patients reported similar reductions in pain from placebo pills labeled as Maxalt as from Maxalt tablets labeled as placebo; and 3) study participants reported pain relief even when they knew the pill they were receiving was a placebo, compared with no treatment at all.

“One of the many implications of our findings is that when doctors set patients’ expectations high, Maxalt [or, potentially, other migraine drugs] becomes more effective,” said Rami Burstein, PhD, the study’s senior author and Director of Pain Research in the Department of Anesthesia, Critical Care and Pain Medicine at BIDMC.

“Increased effectiveness means shorter migraine attacks and shorter migraine attacks mean that less medication is needed,” he said.

“This study untangled and reassembled the clinical effects of placebo and medication in a unique manner,” said the study’s other senior author, Ted Kaptchuk, Director of the Program in Placebo Studies and Therapeutic Encounter (PiPS) at BIDMC and Harvard Medical School.

“Very few, if any, experiments have compared the effectiveness of medication under different degrees of information in a naturally recurring disease. Our discovery showing that subjects’ reports of pain were nearly identical when they were told that an active drug was a placebo as when they were told that a placebo was an active drug demonstrates that the placebo effect is an unacknowledged partner for powerful medications,” Kaptchuk said.

The researchers studied over 450 attacks in the 66 participants. After an initial “no treatment” episode in which patients documented their headache pain and accompanying symptoms 30 minutes after headache onset, and again two hours later (2.5 hours after onset), the participants were provided with six envelopes containing pills to be taken for each of their next six migraine attacks.

Of the six treatments, two were made with positive expectations (envelopes labeled “Maxalt”), two were made with negative expectations (envelopes labeled “placebo”), and two were made with neutral expectations (envelopes labeled “Maxalt or placebo”). In each of the three situations – positive, negative or neutral – one of the two envelopes contained a Maxalt tablet while the other contained a placebo, no matter what the label actually indicated. The patients then documented their pain experiences in the same manner as they had initially in the no-treatment session.

The results consistently showed that giving the pills accompanied by positive information incrementally boosted the efficacy of both the active migraine medication and the inert placebo.

“When patients received Maxalt labeled as placebo, they were being treated by the medication – but without any positive expectation,” Burstein said.

“This was an attempt to isolate the pharmaceutical effect of Maxalt from any placebo effect.”

Conversely, the inert placebo labeled as Maxalt was an attempt to isolate the impact of the placebo effect from pharmaceutical effect.

“Even though Maxalt was superior to the placebo in terms of alleviating pain, we found that under each of the three messages, the placebo effect accounted for at least 50 percent of the subjects’ overall pain relief. When, for example, Maxalt was labeled ‘Maxalt,’ the subjects’ reports of pain relief more than doubled compared to when Maxalt was labeled ‘placebo.’ This tells us that the effectiveness of a good pharmaceutical may be doubled by enhancing the placebo effect,” said Kaptchuk.

The researchers were surprised to find that even when subjects were given a clearly labeled placebo, they reported pain relief when compared with no treatment.

“Contrary to conventional wisdom that patients respond to a placebo because they think they’re getting an active drug, our findings reinforce the idea that open label placebo treatment may have a therapeutic benefit,” wrote the study’s authors.

The researchers said the study’s findings suggest that placebos may someday provide a therapeutic boost to drug treatments, although further research is needed to explore how this is best applied in clinical care settings.

Read more here

Study: No proof that medications ease migraines in children

A recent study showed that many medications that adults use to ease migraines may not have any effect on children with migraines. In fact, the placebos seemed just as effective as the medications in children.

Medicines to prevent or treat migraines in adults aren’t effective in stopping the headaches in children, according to two studies that suggest doctors may want to re-evaluate the use of the drugs in pediatric patients.

An analysis of 21 trials published in JAMA Pediatrics showed that Johnson and Johnson’s seizure medicine Topamax and the antidepressant trazodone “have limited evidence” to support use in children’s migraines occurring fewer than 15 times a month. Other drugs, including some medicines for hypertension are no better than a placebo, the research found.

About 8 million kids, or 1 of 20 in the U.S., get migraines, according to Jacksonville, Florida-based Nemours, a nonprofit children’s health organization. The results show that more studies are needed to look at the use of adult migraine medicines in kids and what role placebos have in helping children and adolescents, researchers said

“Pediatric clinical trials are different than trials conducted in adults for many reasons,” William Rodriguez, Pediatric Science Director of the Food and Drug Administration Office of Pediatric Therapeutics, said in an e-mail. “One of the issues is that a failed pediatric trial seldom motivates a sponsor to conduct additional pediatric trials. This is in contrast to what happens with failed adult trials. It has to do with the fact the sponsor is usually much more interested in the adult market as the pediatric populations with diseases are small.”

FDA Analysis

Rodriguez was an author on a second analysis by the FDA of trials of children given a commonly used class of migraine drugs called triptans. It found that many children got better without the medication.

In the first study from the Medical College of Wisconsin in Milwaukee, the researchers analyzed 21 trials of migraine medicines that included children and adolescents. Of those, 13 included a group that received a placebo rather than study drug.

They found that Topamax and trazodone reduced episodic migraines more than placebo, less than one headache a month when compared to placebo, while clonidine, for high blood pressure; flunarizine, a calcium channel blocker; pizotifen, a migraine drug; propranolol, for high blood pressure; and valproate, an anticonvulsant, were no more effective than placebo.

The analysis also showed that children taking a placebo, rather than the study drugs, reduced their migraines by an average of about three headaches a month. The high placebo response suggests more studies of pediatric headaches should include a placebo group, the authors said.

Few Studies

“There were surprisingly few studies on treating headaches in children, particularly compared to the hundreds that have been done in adults,” said Jeffrey Jackson, a study author and professor of medicine at the Medical College of Wisconsin, in a Jan. 28 e-mail. “Most of the drugs that are effective in adults do not have evidence of effectiveness in children.”

The FDA analysis found that high placebo response rates were consistent across the migraine trials studied and pose a challenge to those who design the research. When putting together clinical trials, researchers need to take into account those children who feel better after taking a placebo.

“These studies clearly demonstrate why we cannot assume what works in adults will work in kids and why children need their own studies,” Rodriguez said. “There are many -- over 50 percent in most studies -- of children who do not need a drug for the migraine to resolve in a couple of hours. Drug therapy appears to be effective in a certain subset of children with migraine.”

Read more here

Study: Sleeping Pills Owe Half Their Benefits to Placebo Effect

A new study claims that half of the benefit people see from using sleeping pills is due to the placebo affect.

Half of the benefit of taking sleeping pills comes from the placebo effect, according to a major new study published in theBritish Medical Journal.

Researchers re-analysed results from more than a dozen clinical trials of the most common type of sleeping tablets, known as Z-drugs (non-benzodiazepine hypnotics).

These drugs are frequently used in the UK and USA as a short-term treatment for insomnia with almost £25m worth of prescriptions handed out in Britain each year. However, some health experts have questioned whether the benefits of Z-drugs justify their side effects, which can include memory loss, fatigue and impaired balance.

Questions have also been raised about the validity of published research into the effects of these drugs based on trials sponsored by pharmaceutical companies themselves.

Academics from the University of Lincoln, Harvard Medical School and University of Connecticut conducted a meta-analysis of data from clinical trials of Z-drugs comparing drug effects with placebo effects. This type of comparison enables researchers to determine how much of the drug effect comes from the constituents of the drug itself, and how much is due to other factors (like the placebo response or regression to the mean).

They used data submitted by pharmaceutical companies to the US Food and Drug Administration (FDA) for approval of new products. This included 13 clinical trials containing 65 different comparisons and more than 4,300 participants.

The FDA collates results from both published and unpublished studies, enabling researchers to avoid common types of bias (such as reporting bias) which can undermine other research based on sponsored trials.

Their findings, published in this week's British Medical Journal(17th December 2012), indicate that once the placebo effect is discounted, the drug effect is of 'questionable clinical importance'.

Lead author Professor Niroshan Siriwardena, from the School of Health and Social Care at the University of Lincoln, said: "Our analysis showed that Z-drugs did reduce the length of time it took for subjects to fall asleep, both subjectively and as measured in a sleep lab, but around half of the effect of the drug was a placebo response.

"There was not enough evidence from the trials to show other benefits that might be important to people with sleep problems, such as sleep quality or daytime functioning.

"We know from other studies that around a fifth of people experience side effects from sleeping tablets and one in one hundred older people will have a fall, fracture or road traffic accident after using them.

"Psychological treatments for insomnia can work as effectively as sleeping tablets in the short-term and better in the long-term, so we should pay more attention to increasing access to these treatments for patients who might benefit."

He said future studies of sleeping tablets should investigate a broader range of outcomes, not just time taken to fall asleep, and that pharmaceutical companies should be more transparent in disclosing results from their studies so that researchers can independently analyse their results.

Read more here